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Sample records for major loxl1 risk

  1. Prevalence of high-risk alleles in the LOXL1 gene and its association with pseudoexfoliation syndrome and exfoliation glaucoma in a Latin American population.

    Science.gov (United States)

    Jaimes, Martha; Rivera-Parra, David; Miranda-Duarte, Antonio; Valdés, Gerardo; Zenteno, Juan Carlos

    2012-03-01

    Pseudoexfoliation syndrome (XFS) is a major risk factor for exfoliation glaucoma (XFG). A significant association exists between XFG and several SNPs in the lysyl oxidase-like 1 (LOXL1) gene. The purpose of this study was to report the results of the first association study between LOXL1 polymorphisms and XFS and/or XFG in a Latin American population. Genotypes of three high-risk SNPs of LOXL1 (rs1048661, rs3825942, and rs2165241) were analyzed by direct sequencing. A case-control study was conducted with 102 unrelated XFS/XFG Mexican patients (42 XFS/60 XFG) as well as 97 control subjects. Allele frequencies, Hardy-Weinberg equilibrium, and haplotype association analysis were assessed with the Haplo View software. The T allele of the intronic SNP rs2165241 was more frequent in XFS/XFG patients than in controls (OR [95% CI] = 2.41 [1.59-3.64]; p = 0.00001). The G allele of rs3825942 was found in a higher frequency in XFS/XFG than in controls (100% vs 95% respectively, p = 0.0019). No significant association between XFS and the rs1048661 (R141L) SNP was observed. The TGT haplotype was observed in a higher frequency in patients than in controls (p = 0.025), and produced the highest risk in our study (OR [95% CI] = 3.20 [1.09-9.39]; p = 0.025). This is the first study associating LOXL1 gene polymorphism and XFS/XFG in Latin America. LOXL1 variants are associated with an elevated risk for XFS/XFG in the Mexican population. A higher risk was conferred by the T allele of the intronic rs2165241 SNP rather than by the worldwide "high-risk" G allele of rs3825942.

  2. Common sequence variants in the LOXL1 gene in pigment dispersion syndrome and pigmentary glaucoma.

    Science.gov (United States)

    Giardina, Emiliano; Oddone, Francesco; Lepre, Tiziana; Centofanti, Marco; Peconi, Cristina; Tanga, Lucia; Quaranta, Luciano; Frezzotti, Paolo; Novelli, Giuseppe; Manni, Gianluca

    2014-04-16

    Single nucleotide polymorphisms (SNPs) within the LOXL1 gene are associated with pseudoesfoliation syndrome and pseudoesfoliation glaucoma. The aim of our study is to investigate a potential involvement of LOXL1 gene in the pathogenesis of pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG). A cohort of Caucasian origin of 84 unrelated and clinically well-characterised patients with PDS/PG and 200 control subjects were included in the study. Genomic DNA from whole blood was extracted and the coding and regulatory regions of LOXL1 gene were risequenced in both patients and controls to identify unknown sequence variations. Genotype and haplotype analysis were performed with UNPHASED software. The expression levels of LOXL1 were determined on c-DNA from peripheral blood lymphocytes by quantitative real-time RT-PCR. A significant allele association was detected for SNP rs2304722 within the fifth intron of LOXL1 (Odds ratio (OR = 2.43, p-value = 3,05e-2). Haplotype analysis revealed the existence of risk and protective haplotypes associated with PG-PDS (OR = 3.35; p-value = 1.00e-5 and OR = 3.35; p-value = 1.00e-4, respectively). Expression analysis suggests that associated haplotypes can regulate the expression level LOXL1. Haplotypes of LOXL1 are associated with PG-PDS independently from rs1048661, leading to a differential expression of the transcript.

  3. Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci.

    Science.gov (United States)

    Aung, Tin; Ozaki, Mineo; Lee, Mei Chin; Schlötzer-Schrehardt, Ursula; Thorleifsson, Gudmar; Mizoguchi, Takanori; Igo, Robert P; Haripriya, Aravind; Williams, Susan E; Astakhov, Yury S; Orr, Andrew C; Burdon, Kathryn P; Nakano, Satoko; Mori, Kazuhiko; Abu-Amero, Khaled; Hauser, Michael; Li, Zheng; Prakadeeswari, Gopalakrishnan; Bailey, Jessica N Cooke; Cherecheanu, Alina Popa; Kang, Jae H; Nelson, Sarah; Hayashi, Ken; Manabe, Shin-Ichi; Kazama, Shigeyasu; Zarnowski, Tomasz; Inoue, Kenji; Irkec, Murat; Coca-Prados, Miguel; Sugiyama, Kazuhisa; Järvelä, Irma; Schlottmann, Patricio; Lerner, S Fabian; Lamari, Hasnaa; Nilgün, Yildirim; Bikbov, Mukharram; Park, Ki Ho; Cha, Soon Cheol; Yamashiro, Kenji; Zenteno, Juan C; Jonas, Jost B; Kumar, Rajesh S; Perera, Shamira A; Chan, Anita S Y; Kobakhidze, Nino; George, Ronnie; Vijaya, Lingam; Do, Tan; Edward, Deepak P; de Juan Marcos, Lourdes; Pakravan, Mohammad; Moghimi, Sasan; Ideta, Ryuichi; Bach-Holm, Daniella; Kappelgaard, Per; Wirostko, Barbara; Thomas, Samuel; Gaston, Daniel; Bedard, Karen; Greer, Wenda L; Yang, Zhenglin; Chen, Xueyi; Huang, Lulin; Sang, Jinghong; Jia, Hongyan; Jia, Liyun; Qiao, Chunyan; Zhang, Hui; Liu, Xuyang; Zhao, Bowen; Wang, Ya-Xing; Xu, Liang; Leruez, Stéphanie; Reynier, Pascal; Chichua, George; Tabagari, Sergo; Uebe, Steffen; Zenkel, Matthias; Berner, Daniel; Mossböck, Georg; Weisschuh, Nicole; Hoja, Ursula; Welge-Luessen, Ulrich-Christoph; Mardin, Christian; Founti, Panayiota; Chatzikyriakidou, Anthi; Pappas, Theofanis; Anastasopoulos, Eleftherios; Lambropoulos, Alexandros; Ghosh, Arkasubhra; Shetty, Rohit; Porporato, Natalia; Saravanan, Vijayan; Venkatesh, Rengaraj; Shivkumar, Chandrashekaran; Kalpana, Narendran; Sarangapani, Sripriya; Kanavi, Mozhgan R; Beni, Afsaneh Naderi; Yazdani, Shahin; Lashay, Alireza; Naderifar, Homa; Khatibi, Nassim; Fea, Antonio; Lavia, Carlo; Dallorto, Laura; Rolle, Teresa; Frezzotti, Paolo; Paoli, Daniela; Salvi, Erika; Manunta, Paolo; Mori, Yosai; Miyata, Kazunori; Higashide, Tomomi; Chihara, Etsuo; Ishiko, Satoshi; Yoshida, Akitoshi; Yanagi, Masahide; Kiuchi, Yoshiaki; Ohashi, Tsutomu; Sakurai, Toshiya; Sugimoto, Takako; Chuman, Hideki; Aihara, Makoto; Inatani, Masaru; Miyake, Masahiro; Gotoh, Norimoto; Matsuda, Fumihiko; Yoshimura, Nagahisa; Ikeda, Yoko; Ueno, Morio; Sotozono, Chie; Jeoung, Jin Wook; Sagong, Min; Park, Kyu Hyung; Ahn, Jeeyun; Cruz-Aguilar, Marisa; Ezzouhairi, Sidi M; Rafei, Abderrahman; Chong, Yaan Fun; Ng, Xiao Yu; Goh, Shuang Ru; Chen, Yueming; Yong, Victor H K; Khan, Muhammad Imran; Olawoye, Olusola O; Ashaye, Adeyinka O; Ugbede, Idakwo; Onakoya, Adeola; Kizor-Akaraiwe, Nkiru; Teekhasaenee, Chaiwat; Suwan, Yanin; Supakontanasan, Wasu; Okeke, Suhanya; Uche, Nkechi J; Asimadu, Ifeoma; Ayub, Humaira; Akhtar, Farah; Kosior-Jarecka, Ewa; Lukasik, Urszula; Lischinsky, Ignacio; Castro, Vania; Grossmann, Rodolfo Perez; Sunaric Megevand, Gordana; Roy, Sylvain; Dervan, Edward; Silke, Eoin; Rao, Aparna; Sahay, Priti; Fornero, Pablo; Cuello, Osvaldo; Sivori, Delia; Zompa, Tamara; Mills, Richard A; Souzeau, Emmanuelle; Mitchell, Paul; Wang, Jie Jin; Hewitt, Alex W; Coote, Michael; Crowston, Jonathan G; Astakhov, Sergei Y; Akopov, Eugeny L; Emelyanov, Anton; Vysochinskaya, Vera; Kazakbaeva, Gyulli; Fayzrakhmanov, Rinat; Al-Obeidan, Saleh A; Owaidhah, Ohoud; Aljasim, Leyla Ali; Chowbay, Balram; Foo, Jia Nee; Soh, Raphael Q; Sim, Kar Seng; Xie, Zhicheng; Cheong, Augustine W O; Mok, Shi Qi; Soo, Hui Meng; Chen, Xiao Yin; Peh, Su Qin; Heng, Khai Koon; Husain, Rahat; Ho, Su-Ling; Hillmer, Axel M; Cheng, Ching-Yu; Escudero-Domínguez, Francisco A; González-Sarmiento, Rogelio; Martinon-Torres, Frederico; Salas, Antonio; Pathanapitoon, Kessara; Hansapinyo, Linda; Wanichwecharugruang, Boonsong; Kitnarong, Naris; Sakuntabhai, Anavaj; Nguyn, Hip X; Nguyn, Giang T T; Nguyn, Trình V; Zenz, Werner; Binder, Alexander; Klobassa, Daniela S; Hibberd, Martin L; Davila, Sonia; Herms, Stefan; Nöthen, Markus M; Moebus, Susanne; Rautenbach, Robyn M; Ziskind, Ari; Carmichael, Trevor R; Ramsay, Michele; Álvarez, Lydia; García, Montserrat; González-Iglesias, Héctor; Rodríguez-Calvo, Pedro P; Fernández-Vega Cueto, Luis; Oguz, Çilingir; Tamcelik, Nevbahar; Atalay, Eray; Batu, Bilge; Aktas, Dilek; Kasım, Burcu; Wilson, M Roy; Coleman, Anne L; Liu, Yutao; Challa, Pratap; Herndon, Leon; Kuchtey, Rachel W; Kuchtey, John; Curtin, Karen; Chaya, Craig J; Crandall, Alan; Zangwill, Linda M; Wong, Tien Yin; Nakano, Masakazu; Kinoshita, Shigeru; den Hollander, Anneke I; Vesti, Eija; Fingert, John H; Lee, Richard K; Sit, Arthur J; Shingleton, Bradford J; Wang, Ningli; Cusi, Daniele; Qamar, Raheel; Kraft, Peter; Pericak-Vance, Margaret A; Raychaudhuri, Soumya; Heegaard, Steffen; Kivelä, Tero; Reis, André; Kruse, Friedrich E; Weinreb, Robert N; Pasquale, Louis R; Haines, Jonathan L; Thorsteinsdottir, Unnur; Jonasson, Fridbert; Allingham, R Rand; Milea, Dan; Ritch, Robert; Kubota, Toshiaki; Tashiro, Kei; Vithana, Eranga N; Micheal, Shazia; Topouzis, Fotis; Craig, Jamie E; Dubina, Michael; Sundaresan, Periasamy; Stefansson, Kari; Wiggs, Janey L; Pasutto, Francesca; Khor, Chiea Chuen

    2017-07-01

    Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 × 10 -14 ) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10 -8 ). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.

  4. Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci

    DEFF Research Database (Denmark)

    Aung, Tin; Ozaki, Mineo; Lee, Mei Chin

    2017-01-01

    Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS c...

  5. DNA sequence variants in the LOXL1 gene are associated with pseudoexfoliation glaucoma in a U.S. clinic-based population with broad ethnic diversity

    Directory of Open Access Journals (Sweden)

    Miller Joan W

    2008-02-01

    Full Text Available Abstract Background Pseudoexfoliation syndrome is a major risk factor for glaucoma in many populations throughout the world. Using a U.S. clinic-based case control sample with broad ethnic diversity, we show that three common SNPs in LOXL1 previously associated with pseudoexfoliation in Nordic populations are significantly associated with pseudoexfoliation syndrome and pseudoexfoliation glaucoma. Methods Three LOXL1 SNPs were genotyped in a patient sample (206 pseudoexfoliation, 331 primary open angle glaucoma, and 88 controls from the Glaucoma Consultation Service at the Massachusetts Eye and Ear Infirmary. The SNPs were evaluation for association with pseudeoexfoliation syndrome, pseudoexfoliation glaucoma, and primary open angle glaucoma. Results The strongest association was found for the G allele of marker rs3825942 (G153D with a frequency of 99% in pseudoexfoliation patients (with and without glaucoma compared with 79% in controls (p = 1.6 × 10-15; OR = 20.93, 95%CI: 8.06, 54.39. The homozygous GG genotype is also associated with pseudoexfoliation when compared to controls (p = 1.2 × 10-12; OR = 23.57, 95%CI: 7.95, 69.85. None of the SNPs were significantly associated with primary open angle glaucoma. Conclusion The pseudoexfoliation syndrome is a common cause of glaucoma. These results indicate that the G153D LOXL1 variant is significantly associated with an increased risk of pseudoexfoliation and pseudoexfoliation glaucoma in an ethnically diverse patient population from the Northeastern United States. Given the high prevalence of pseudooexfoliation in this geographic region, these results also indicate that the G153D LOXL1 variant is a significant risk factor for adult-onset glaucoma in this clinic based population.

  6. Correlation of Aqueous Humor Lysyl Oxidase Activity with TGF-ß Levels and LOXL1 Genotype in Pseudoexfoliation.

    Science.gov (United States)

    Gayathri, Ramakrishnan; Coral, Karunakaran; Sharmila, Ferdinamarie; Sripriya, Sarangapani; Sripriya, Krishnamoorthy; Manish, Panday; Shantha, B; Ronnie, George; Vijaya, Lingam; Narayanasamy, Angayarkanni

    2016-10-01

    Pseudoexfoliation (PXF) is a microfibrillopathy involving disordered elastogenesis. Abnormal extracellular matrix (ECM) production underlies the pathophysiology of PXF. The enzyme Lysyl oxidase (LOX) and its isoforms are known to cross-link the elastin and collagen. Though the etiopathogensis of PXF is not well understood, studies report on the genetic risk involving LOXL1 gene. This study aims to screen LOXL1 coding variants rs1048661 and rs3825942 in the South Indian population and the implication of the single nucleotide polymorphism (SNP) with LOX activity. The levels of transforming growth factor β (TGF-β) in aqueous humor and its correlation with the LOX activity were also examined. Blood, plasma, and aqueous aspirates were prospectively collected from PXF cases with and without glaucoma and cataract cases as controls. DNA was extracted from 48 PXF cases without glaucoma, 12 PXF cases with glaucoma, and 40 age-matched cataract-alone controls without PXF/glaucoma for analyzing LOX SNPs. LOX activity was measured in aqueous humor and plasma of 30 PXF cases without glaucoma, 24 age-matched cataract-alone controls without PXF/glaucoma, and 14 PXF cases with glaucoma. Protein levels of LOX, LOXL1, LOXL2, and total TGF-β were estimated in plasma and aqueous humor by ELISA. The specific activity of LOX in aqueous humor was found to be significantly lowered in PXF cases compared with cataract-alone controls (p = 0.014). This decrease in LOX activity in PXF cases was associated with high-risk GG haplotype. However, this was not statistically significant and a larger sample size is warranted. TGF-β1 and TGF-β2 negatively correlated with LOX activity in aqueous humor (p = 0.028; p = 0.046, respectively). The LOXL1 SNPs, rs1048661 and rs3825942, are associated with PXF in the South Indian population correlating with lowered LOX activity in the aqueous humor. The increased level of total TGF-β in the aqueous humor of PXF cases is possibly associated with LOX

  7. Exfoliation syndrome and exfoliation glaucoma-associated LOXL1 variations are not involved in pigment dispersion syndrome and pigmentary glaucoma.

    Science.gov (United States)

    Rao, Kollu Nageswara; Ritch, Robert; Dorairaj, Syril K; Kaur, Inderjeet; Liebmann, Jeffrey M; Thomas, Ravi; Chakrabarti, Subhabrata

    2008-07-09

    Single nucleotide polymorphisms (SNPs) in the LOXL1 gene have been implicated in exfoliation syndrome (XFS) and exfoliation glaucoma (XFG). We have shown that these SNPs are not associated with the primary glaucomas such as primary open-angle (POAG) glaucoma and primary angle-closure glaucoma (PACG). To further establish the specificity of LOXL1 SNPs for XFS and XFG, we determined whether these SNPs were involved in pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG). Three SNPs of LOXL1 (rs1048661, rs3825942, and rs2165241) were screened in a cohort of 78 unrelated and clinically well characterized glaucoma cases comprising of PG (n=44) and PDS (n=34) patients as well as 108 ethnically matched normal controls of Caucasian origin. The criteria for diagnosis of PDS/PG were Krukenberg spindle, hyperpigmentation of the trabecular meshwork, and wide open angle. Transillumination defects were detected by infrared pupillography, and the presence of a Zentmayer ring was considered as a confirmatory sign. All three SNPs were genotyped in cases and controls by resequencing the genomic region of LOXL1 harboring these variants and were further confirmed by polymerase chain reaction (PCR)-based restriction digestions. Haplotypes were generated from the genotype data, and the linkage disequilibrium (LD) and haplotype analysis were done with Haploview software that uses the expectation maximization (EM) algorithm. The LOXL1 SNPs showed no significant association with PDS or PG. There was no significant difference in the frequencies of the risk alleles of rs1048661 ('G' allele; p=0.309), rs3825942 ('G' allele' p=0.461), and rs2165241 ('T' allele; p=0.432) between PG/PDS cases and controls. Similarly, there was no involvement of the XFS/XFG-associated haplotypes, 'G-G' (p=0.643; [OR=1.08, 95%CI, 0.59-1.97]) and 'T-G' (p=0.266; [OR=1.35, 95%CI, 0.70-2.60]), with the PDS/PG phenotypes. The risk haplotype 'G-G' was observed in ~55% of the normal controls. There was no

  8. A single nucleotide polymorphism in the promoter of the LOXL1 gene and its relationship to pelvic organ prolapse and preterm premature rupture of membranes.

    Science.gov (United States)

    Ferrell, Georgia; Lu, Minyan; Stoddard, Paul; Sammel, Mary D; Romero, Roberto; Strauss, Jerome F; Matthews, Catherine A

    2009-05-01

    Pelvic organ prolapse and preterm premature rupture of membranes, the 2 conditions which have in common weakening of the tensile strength of tissues, are thought to be caused, in part, by abnormal extracellular matrix synthesis and/or catabolism. We identified a new single nucleotide polymorphism (NT_010194(LOXL1):g.45008784A>C) in the promoter of the LOXL1 gene, which is essential for elastin synthesis. Promoter studies showed that the minor "C'' allele had significantly greater activity than the major "A'' allele. Case-control studies examined the association of the alleles of this single nucleotide polymorphism with pelvic organ prolapse and preterm premature rupture of membranes. When comparing allele frequencies and genotypes in pelvic organ prolapse cases versus controls, no significant associations were found. A case-control study conducted in African American neonates also found no significant associations between the promoter alleles and preterm premature rupture of membranes. We conclude that a functional single nucleotide polymorphism exists in the promoter region of the LOXL1 gene. Association studies suggest that the promoter single nucleotide polymorphism does not contribute significantly to risk of pelvic organ prolapse or preterm premature rupture of membranes.

  9. Tumor-secreted LOXL2 activates fibroblasts through FAK signaling

    DEFF Research Database (Denmark)

    Barker, Holly E; Bird, Demelza; Lang, Georgina

    2013-01-01

    models. Here, we discovered that tumor-derived LOXL2 directly activated stromal fibroblasts in the tumor microenvironment. Genetic manipulation or antibody inhibition of LOXL2 in orthotopically grown mammary tumors reduced the expression of α-smooth muscle actin (α-SMA). Using a marker for reticular....... Importantly, in vitro assays revealed that tumor-derived LOXL2 and a recombinant LOXL2 protein induced fibroblast branching on collagen matrices, as well as increased fibroblast-mediated collagen contraction and invasion of fibroblasts through extracellular matrix. Moreover, LOXL2 induced the expression of α...

  10. LOXL2 induces aberrant acinar morphogenesis via ErbB2 signaling

    DEFF Research Database (Denmark)

    Chang, Joan; Nicolau, Monica; Cox, Thomas R

    2013-01-01

    Lysyl oxidase-like 2 (LOXL2) is a matrix remodeling enzyme that has been shown to play a key role in invasion and metastasis of breast carcinoma cells. However, very little is known about its role in normal tissue homeostasis. Here, we investigate the effects of LOXL2 expression in normal mammary...... epithelial cells in order to gain insight into how LOXL2 mediates cancer progression....

  11. Pre-clinical evaluation of small molecule LOXL2 inhibitors in breast cancer

    DEFF Research Database (Denmark)

    Chang, Joan; Lucas, Morghan C; Leonte, Lidia Elena

    2017-01-01

    inhibitor in the MDA-MB-231 human model of breast cancer. We confirmed a functional role for LOXL2 activity in the progression of primary breast cancer. Inhibition of LOXL2 activity inhibited the growth of primary tumors and reduced primary tumor angiogenesis. Dual inhibition of LOXL2 and LOX showed...... a greater effect and also led to a lower overall metastatic burden in the lung and liver. Our data provides the first evidence to support a role for LOXL2 specific small molecule inhibitors as a potential therapy in breast cancer....

  12. Matrix stiffness-upregulated LOXL2 promotes fibronectin production, MMP9 and CXCL12 expression and BMDCs recruitment to assist pre-metastatic niche formation.

    Science.gov (United States)

    Wu, Sifan; Zheng, Qiongdan; Xing, Xiaoxia; Dong, Yinying; Wang, Yaohui; You, Yang; Chen, Rongxin; Hu, Chao; Chen, Jie; Gao, Dongmei; Zhao, Yan; Wang, Zhiming; Xue, Tongchun; Ren, Zhenggang; Cui, Jiefeng

    2018-05-04

    Higher matrix stiffness affects biological behavior of tumor cells, regulates tumor-associated gene/miRNA expression and stemness characteristic, and contributes to tumor invasion and metastasis. However, the linkage between higher matrix stiffness and pre-metastatic niche in hepatocellular carcinoma (HCC) is still largely unknown. We comparatively analyzed the expressions of LOX family members in HCC cells grown on different stiffness substrates, and speculated that the secreted LOXL2 may mediate the linkage between higher matrix stiffness and pre-metastatic niche. Subsequently, we investigated the underlying molecular mechanism by which matrix stiffness induced LOXL2 expression in HCC cells, and explored the effects of LOXL2 on pre-metastatic niche formation, such as BMCs recruitment, fibronectin production, MMPs and CXCL12 expression, cell adhesion, etc. RESULTS: Higher matrix stiffness significantly upregulated LOXL2 expression in HCC cells, and activated JNK/c-JUN signaling pathway. Knockdown of integrin β1 and α5 suppressed LOXL2 expression and reversed the activation of above signaling pathway. Additionally, JNK inhibitor attenuated the expressions of p-JNK, p-c-JUN, c-JUN and LOXL2, and shRNA-c-JUN also decreased LOXL2 expression. CM-LV-LOXL2-OE and rhLOXL2 upregulated MMP9 expression and fibronectin production obviously in lung fibroblasts. Moreover, activation of Akt pathway contributed to LOXL2-induced fibronectin upregulation. LOXL2 in CM as chemoattractant increased motility and invasion of BMCs, implicating a significant role of LOXL2 in BMCs recruitment. Except that, CM-LV-LOXL2-OE as chemoattractant also increased the number of migrated HCC cells, and improved chemokine CXCL12 expression in lung fibroblasts. The number of HCC cells adhered to surface of lung fibroblasts treated with CM-LV-LOXL2-OE was remarkably higher than that of the control cells. These results indicated that the secreted LOXL2 facilitated the motility of HCC cells and

  13. LOXL4 knockdown enhances tumor growth and lung metastasis through collagen-dependent extracellular matrix changes in triple-negative breast cancer.

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    Choi, Sul Ki; Kim, Hoe Suk; Jin, Tiefeng; Moon, Woo Kyung

    2017-02-14

    Lysyl oxidase (LOX) family genes catalyze collagen cross-link formation. To determine the effects of lysyl oxidase-like 4 (LOXL4) expression on breast tumor formation and metastasis, we evaluated primary tumor growth and lung metastasis in mice injected with LOXL4-knockdown MDA-MB-231 triple-negative human breast cancer cells. In addition, we analyzed overall survival in breast cancer patients based on LOXL4 expression using a public online database. In the mouse xenograft model, LOXL4 knockdown increased primary tumor growth and lung colonization as well as collagen I and IV, lysine hydroxylase 1 and 2, and prolyl 4-hydroxylase subunit alpha 1 and 2 levels. Second harmonic generation imaging revealed that LOXL4 knockdown resulted in the thickening of collagen bundles within tumors. In addition, weak LOXL4 expression was associated with poor overall survival in breast cancer patients from the BreastMark dataset, and this association was strongest in triple-negative breast cancer patients. These results demonstrate that weak LOXL4 expression leads to remodeling of the extracellular matrix through induction of collagen synthesis, deposition, and structural changes. These alterations in turn promote tumor growth and metastasis and are associated with poor clinical outcomes in triple-negative breast cancer.

  14. ZEB1 induces LOXL2-mediated collagen stabilization and deposition in the extracellular matrix to drive lung cancer invasion and metastasis.

    Science.gov (United States)

    Peng, D H; Ungewiss, C; Tong, P; Byers, L A; Wang, J; Canales, J R; Villalobos, P A; Uraoka, N; Mino, B; Behrens, C; Wistuba, I I; Han, R I; Wanna, C A; Fahrenholtz, M; Grande-Allen, K J; Creighton, C J; Gibbons, D L

    2017-04-06

    Lung cancer is the leading cause of cancer-related deaths, primarily due to distant metastatic disease. Metastatic lung cancer cells can undergo an epithelial-to-mesenchymal transition (EMT) regulated by various transcription factors, including a double-negative feedback loop between the microRNA-200 (miR-200) family and ZEB1, but the precise mechanisms by which ZEB1-dependent EMT promotes malignancy remain largely undefined. Although the cell-intrinsic effects of EMT are important for tumor progression, the reciprocal dynamic crosstalk between mesenchymal cancer cells and the extracellular matrix (ECM) is equally critical in regulating invasion and metastasis. Investigating the collaborative effect of EMT and ECM in the metastatic process reveals increased collagen deposition in metastatic tumor tissues as a direct consequence of amplified collagen gene expression in ZEB1-activated mesenchymal lung cancer cells. In addition, collagen fibers in metastatic lung tumors exhibit greater linearity and organization as a result of collagen crosslinking by the lysyl oxidase (LOX) family of enzymes. Expression of the LOX and LOXL2 isoforms is directly regulated by miR-200 and ZEB1, respectively, and their upregulation in metastatic tumors and mesenchymal cell lines is coordinated to that of collagen. Functionally, LOXL2, as opposed to LOX, is the principal isoform that crosslinks and stabilizes insoluble collagen deposition in tumor tissues. In turn, focal adhesion formation and FAK/SRC signaling is activated in mesenchymal tumor cells by crosslinked collagen in the ECM. Our study is the first to validate direct regulation of LOX and LOXL2 by the miR-200/ZEB1 axis, defines a novel mechanism driving tumor metastasis, delineates collagen as a prognostic marker, and identifies LOXL2 as a potential therapeutic target against tumor progression.

  15. Circulating LOXL2 Levels Reflect Severity of Intestinal Fibrosis and GALT CD4+ T Lymphocyte Depletion in Treated HIV Infection

    Directory of Open Access Journals (Sweden)

    Sophie Seang

    2017-06-01

    Conclusions: Circulating LOXL2 levels may be a noninvasive measure of intestinal fibrosis and GALT CD4+T lymphocyte depletion in treated HIV infection. LOXL2 crosslinks elastin and collagen, and elevated LOXL2 levels occur in pathologic states, making LOXL2 inhibition a potential interventional target for intestinal fibrosis and its sequelae.

  16. Escin Ia suppresses the metastasis of triple-negative breast cancer by inhibiting epithelial-mesenchymal transition via down-regulating LOXL2 expression.

    Science.gov (United States)

    Wang, Yuhui; Xu, Xiaotian; Zhao, Peng; Tong, Bei; Wei, Zhifeng; Dai, Yue

    2016-04-26

    The saponin fraction of Aesculus chinensis Bunge fruits (SFAC) could inhibit the invasion and migration of MDA-MB-231 cells. Among which, escin Ia showed more potent inhibition of the invasion than other five main saponin constituents. It selectively reduced the expression of LOXL2 mRNA and promoted the expression of E-cadherin mRNA, and prevented the EMT process of MDA-MB-231 cells and TNF-α/TGF-β-stimulated MCF-7 cells. Moreover, it reduced the LOXL2 level in MDA-MB-231 cells but not in MCF-7 cells. When MCF-7 cells were stimulated with TNF-α/TGF-β, transfected with LOXL2 or treated with hypoxia, escin Ia down-regulated the level of LOXL2 in MCF-7 cells. Meanwhile, escin Ia suppressed the EMT process in LOXL2-transfected or hypoxia-treated MCF-7 cells. Of interest, escin Ia did not alter the level of HIF-1α in hypoxia-induced MCF-7 cells. In TNBC xenograft mice, the metastasis and EMT of MDA-MB-231 cells were suppressed by escin Ia. In conclusion, escin Ia was the main active ingredient of SFAC for the anti-TNBC metastasis activity, and its action mechanisms involved inhibition of EMT process by down-regulating LOXL2 expression.

  17. Crystal structure of human lysyl oxidase-like 2 (hLOXL2) in a precursor state.

    Science.gov (United States)

    Zhang, Xi; Wang, Qifan; Wu, Jianping; Wang, Jiawei; Shi, Yigong; Liu, Minhao

    2018-04-10

    Lysyl oxidases (LOXs), a type of copper- and lysyl tyrosylquinone (LTQ) -dependent amine oxidase, catalyze the oxidative deamination of lysine residues of extracellular matrix (ECM) proteins such as elastins and collagens and generate aldehyde groups. The oxidative deamination of lysine represents the foundational step for the cross-linking of elastin and collagen and thus is crucial for ECM modeling. Despite their physiological significance, the structure of this important family of enzymes remains elusive. Here we report the crystal structure of human lysyl oxidase-like 2 (hLOXL2) at 2.4-Å resolution. Unexpectedly, the copper-binding site of hLOXL2 is occupied by zinc, which blocks LTQ generation and the enzymatic activity of hLOXL2 in our in vitro assay. Biochemical analysis confirms that copper loading robustly activates hLOXL2 and supports LTQ formation. Furthermore, the LTQ precursor residues in the structure are distanced by 16.6 Å, corroborating the notion that the present structure may represent a precursor state and that pronounced conformational rearrangements would be required for protein activation. The structure presented here establishes an important foundation for understanding the structure-function relationship of LOX proteins and will facilitate LOX-targeting drug discovery. Copyright © 2018 the Author(s). Published by PNAS.

  18. Lysyl Oxidase-Like 1 Protein Deficiency Protects Mice from Adenoviral Transforming Growth Factor-β1-induced Pulmonary Fibrosis.

    Science.gov (United States)

    Bellaye, Pierre-Simon; Shimbori, Chiko; Upagupta, Chandak; Sato, Seidai; Shi, Wei; Gauldie, Jack; Ask, Kjetil; Kolb, Martin

    2018-04-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by excessive deposition of extracellular matrix (ECM) in the lung parenchyma. The abnormal ECM deposition slowly overtakes normal lung tissue, disturbing gas exchange and leading to respiratory failure and death. ECM cross-linking and subsequent stiffening is thought to be a major contributor of disease progression and also promotes the activation of transforming growth factor (TGF)-β1, one of the main profibrotic growth factors. Lysyl oxidase-like (LOXL) 1 belongs to the cross-linking enzyme family and has been shown to be up-regulated in active fibrotic regions of bleomycin-treated mice and patients with IPF. We demonstrate in this study that LOXL1-deficient mice are protected from experimental lung fibrosis induced by overexpression of TGF-β1 using adenoviral (Ad) gene transfer (AdTGF-β1). The lack of LOXL1 prevented accumulation of insoluble cross-linked collagen in the lungs, and therefore limited lung stiffness after AdTGF-β1. In addition, we applied mechanical stretch to lung slices from LOXL1 +/+ and LOXL1 -/- mice treated with AdTGF-β1. Lung stiffness (Young's modulus) of LOXL1 -/- lung slices was significantly lower compared with LOXL1 +/+ lung slices. Moreover, the release of activated TGF-β1 after mechanical stretch was significantly lower in LOXL1 -/- mice compared with LOXL1 +/+ mice after AdTGF-β1. These data support the concept that cross-linking enzyme inhibition represents an interesting therapeutic target for drug development in IPF.

  19. Trans-suppression of host CDH3 and LOXL4 genes during Cryptosporidium parvum infection involves nuclear delivery of parasite Cdg7_FLc_1000 RNA.

    Science.gov (United States)

    Ming, Zhenping; Gong, Ai-Yu; Wang, Yang; Zhang, Xin-Tian; Li, Min; Li, Yao; Pang, Jing; Dong, Stephanie; Strauss-Soukup, Juliane K; Chen, Xian-Ming

    2018-05-01

    Intestinal infection by Cryptosporidium parvum causes significant alterations in the gene expression profile in host epithelial cells. Previous studies demonstrate that a panel of parasite RNA transcripts of low protein-coding potential are delivered into infected host cells and may modulate host gene transcription. Using in vitro models of human intestinal cryptosporidiosis, we report here that trans-suppression of the cadherin 3 (CDH3) and lysyl oxidase like 4 (LOXL4) genes in human intestinal epithelial cells following C. parvum infection involves host delivery of the Cdg7_FLc_1000 RNA, a C. parvum RNA that has been previously demonstrated to be delivered into the nuclei of infected host cells. Downregulation of CDH3 and LOXL4 genes was detected in host epithelial cells following C. parvum infection or in cells expressing the parasite Cdg7_FLc_1000 RNA. Knockdown of Cdg7_FLc_1000 attenuated the trans-suppression of CDH3 and LOXL4 genes in host cells induced by infection. Interestingly, Cdg7_FLc_1000 was detected to be recruited to the promoter regions of both CDH3 and LOXL4 gene loci in host cells following C. parvum infection. Host delivery of Cdg7_FLc_1000 promoted the PH domain zinc finger protein 1 (PRDM1)-mediated H3K9 methylation associated with trans-suppression in the CDH3 gene locus, but not the LOXL4 gene. Therefore, our data suggest that host delivery of Cdg7_FLc_1000 causes CDH3 trans-suppression in human intestinal epithelial cells following C. parvum infection through PRDM1-mediated H3K9 methylation in the CDH3 gene locus, whereas Cdg7_FLc_1000 induces trans-suppression of the host LOXL4 gene through H3K9/H3K27 methylation-independent mechanisms. Copyright © 2018 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

  20. Comparative analysis of lysyl oxidase (like) family members in pulmonary fibrosis.

    Science.gov (United States)

    Aumiller, Verena; Strobel, Benjamin; Romeike, Merrit; Schuler, Michael; Stierstorfer, Birgit E; Kreuz, Sebastian

    2017-03-10

    Extracellular matrix (ECM) composition and stiffness are major driving forces for the development and persistence of fibrotic diseases. Lysyl oxidase (LOX) and LOX-like (LOXL) proteins play crucial roles in ECM remodeling due to their collagen crosslinking and intracellular functions. Here, we systematically investigated LOX/L expression in primary fibroblasts and epithelial cells under fibrotic conditions, Bleomycin (BLM) induced lung fibrosis and in human IPF tissue. Basal expression of all LOX/L family members was detected in epithelial cells and at higher levels in fibroblasts. Various pro-fibrotic stimuli broadly induced LOX/L expression in fibroblasts, whereas specific induction of LOXL2 and partially LOX was observed in epithelial cells. Immunohistochemical analysis of lung tissue from 14 IPF patients and healthy donors revealed strong induction of LOX and LOXL2 in bronchial and alveolar epithelium as well as fibroblastic foci. Using siRNA experiments we observed that LOXL2 and LOXL3 were crucial for fibroblast-to-myofibroblast transition (FMT). As FMT could only be reconstituted with an enzymatically active LOXL2 variant, we conclude that LOXL2 enzymatic function is crucial for fibroblast transdifferentiation. In summary, our study provides a comprehensive analysis of the LOX/L family in fibrotic lung disease and indicates prominent roles for LOXL2/3 in fibroblast activation and LOX/LOXL2 in IPF.

  1. Major life events and risk of Parkinson's disease

    DEFF Research Database (Denmark)

    Rod, Naja Hulvej; Hansen, Johnni; Schernhammer, Eva

    2010-01-01

    major life events are risk factors for Parkinson's disease. Between 1986 and 2006, we identified 13,695 patients with a (PD) primary diagnosis of PD in the Danish National Hospital Register. Each case was frequency matched by age and gender to five population controls. Information on major life events...... before onset of PD was ascertained from national registries. Among men, number of life events was associated with risk of Parkinson's disease in an inverse dose-response manner (P ....34-0.99). Life events were not associated with PD in women. In contrast, a higher risk of PD was observed among women who had never been married (1.16; 1.04-1.29) and among men (1.47; 1.18-1.82) and women (1.30; 1.05-1.61) who have never been employees. The lower risk of Parkinson's disease among men who had...

  2. The copper dependent-lysyl oxidases contribute to the pathogenesis of pulmonary emphysema in chronic obstructive pulmonary disease patients.

    Science.gov (United States)

    Besiktepe, Neziha; Kayalar, Ozgecan; Ersen, Ezel; Oztay, Fusun

    2017-12-01

    Abnormalities in the elastic fiber biology are seen in pulmonary emphysema (PE). The copper-dependent lysyl oxidases regulate the production and accumulation of elastic fibers in the connective tissue. This study focused on the relationship between lysyl oxidase (LOX), LOX-like protein 1 (LOXL1), and LOXL2 and PE pathogenesis. Lung samples with or without PE from patients with chronic obstructive lung disease (n=35) were used. Protein levels of elastin, LOX, LOXL1, LOXL2, hypoxia inducible factor 1-alpha (HIF-1α), copper metabolism domain containing-1 (COMMD1), and phosphatase and tensin homolog (PTEN) were assayed using microscopic and biochemical methods The emphysematous areas were characterized by enlargement of the alveoli, destruction of the alveolar structure, accumulation of macrophages in the alveolar lumens, and showed increased HIF-1α immunoreactivity. Additionally, the emphysematous areas had significantly lower elastin, LOX, LOXL1, LOXL2, HIF-1α, COMMD1, and PTEN protein levels than the non-emphysematous areas. We suppose that the reductions in the HIF-1α levels led to decreases in the protein levels of active LOX, LOXL1, and LOXL2. These decreases might cause abnormalities in the elastic fiber biology. HIF-1α activation induced by decreased COMMD1 and protease activation induced by decreased PTEN might contribute to the development of PE. Finally, methods aimed at increasing the protein levels of LOXs, COMMD1 and PTEN might be effective for treating PE. Copyright © 2017 Elsevier GmbH. All rights reserved.

  3. Risk of major congenital malformations in relation to maternal overweight and obesity severity: cohort study of 1.2 million singletons.

    Science.gov (United States)

    Persson, Martina; Cnattingius, Sven; Villamor, Eduardo; Söderling, Jonas; Pasternak, Björn; Stephansson, Olof; Neovius, Martin

    2017-06-14

    Objective  To estimate the risks of major congenital malformations in the offspring of mothers who are underweight (body mass index (BMI) malformation, and subgroups of organ specific malformations diagnosed during the first year of life. Risk ratios were estimated using generalised linear models adjusted for maternal factors, sex of offspring, and birth year. Results  A total of 43 550 (3.5%) offspring had any major congenital malformation, and the most common subgroup was for congenital heart defects (n=20 074; 1.6%). Compared with offspring of normal weight mothers (risk of malformations 3.4%), the proportions and adjusted risk ratios of any major congenital malformation among the offspring of mothers with higher BMI were: overweight, 3.5% and 1.05 (95% confidence interval 1.02 to 1.07); obesity class I, 3.8% and 1.12 (1.08 to 1.15), obesity class II, 4.2% and 1.23 (1.17 to 1.30), and obesity class III, 4.7% and 1.37 (1.26 to 1.49). The risks of congenital heart defects, malformations of the nervous system, and limb defects also progressively increased with BMI from overweight to obesity class III. The largest organ specific relative risks related to maternal overweight and increasing obesity were observed for malformations of the nervous system. Malformations of the genital and digestive systems were also increased in offspring of obese mothers. Conclusions  Risks of any major congenital malformation and several subgroups of organ specific malformations progressively increased with maternal overweight and increasing severity of obesity. For women who are planning pregnancy, efforts should be encouraged to reduce adiposity in those with a BMI above the normal range. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  4. Risk Factors to Growth Retardation in Major Thalassemia

    Directory of Open Access Journals (Sweden)

    Riva Uda

    2011-03-01

    Full Text Available The increasing in the life span of patients with major thalassemia should be followed by increased quality of life. There are factors which can affect growth retardation in these patients. The aim of this study was to find out the risk factors for growth retardation in patients with major thalassemia. An analytical study with cross-sectional design was conducted at Pediatric Thalassemia Clinics of Dr.Hasan Sadikin Hospital, Bandung, in June to July 2006. The subjects of this study were patients with major thalassemia. Inclusion criteria’s were age under 14 years old, had no chronic diseases like tuberculosis, cerebral palsy with complete medical records. Risk factors were the timing of diagnosis, initial and dose of deferoxamine, volume of transfused blood, mean pretransfusion hemoglobin level, family income, and age. Antropometric measurement indices were used to assess the growth which expressed in Z score. Growth evaluated based on height/age (H/A and growth retardation if H/A <-2 SD. Risk factors for growth retardation were analyzed separately using chi-square test and odds ratio (OR with 95% confidence interval (CI. Then they were analyzed simultaneously with logistic regression method. Subjects consisted of 152 patients with major thalassemia. Seventy three thalassemia patients were stunted. Analysis showed that age (OR: 5.42, 95% CI:2.32–12.65, p <0.001, dosage of deferoxamine (OR: 4.0, 95% CI: 1.29–12.41, p: 0.016, and family income (OR: 2.32, 95% CI: 1.06–5.06, p: 0.036 were risks factors for growth retardation. Conclusion, risk factors for growth retardation in major thalassemia are age, dosage of deferoxamine, and family income.

  5. Global risk of radioactive fallout after major nuclear reactor accidents

    International Nuclear Information System (INIS)

    Lelieveld, J.; Kunkel, D.; Lawrence, M.G.

    2012-01-01

    Major reactor accidents of nuclear power plants are rare, yet the consequences are catastrophic. But what is meant by ''rare''? And what can be learned from the Chernobyl and Fukushima incidents? Here we assess the cumulative, global risk of exposure to radioactivity due to atmospheric dispersion of gases and particles following severe nuclear accidents (the most severe ones on the International Nuclear Event Scale, INES 7), using particulate "1"3"7Cs and gaseous "1"3"1I as proxies for the fallout. Our results indicate that previously the occurrence of INES 7 major accidents and the risks of radioactive contamination have been underestimated. Using a global model of the atmosphere we compute that on average, in the event of a major reactor accident of any nuclear power plant worldwide, more than 90% of emitted "1"3"7Cs would be transported beyond 50 km and about 50% beyond 1000 km distance before being deposited. This corroborates that such accidents have large-scale and trans-boundary impacts. Although the emission strengths and atmospheric removal processes of "1"3"7Cs and "1"3"1I are quite different, the radioactive contamination patterns over land and the human exposure due to deposition are computed to be similar. High human exposure risks occur around reactors in densely populated regions, notably in West Europe and South Asia, where a major reactor accident can subject around 30 million people to radioactive contamination. The recent decision by Germany to phase out its nuclear reactors will reduce the national risk, though a large risk will still remain from the reactors in neighbouring countries.

  6. Genome-wide association study identifies HLA 8.1 ancestral haplotype alleles as major genetic risk factors for myositis phenotypes.

    Science.gov (United States)

    Miller, F W; Chen, W; O'Hanlon, T P; Cooper, R G; Vencovsky, J; Rider, L G; Danko, K; Wedderburn, L R; Lundberg, I E; Pachman, L M; Reed, A M; Ytterberg, S R; Padyukov, L; Selva-O'Callaghan, A; Radstake, T R; Isenberg, D A; Chinoy, H; Ollier, W E R; Scheet, P; Peng, B; Lee, A; Byun, J; Lamb, J A; Gregersen, P K; Amos, C I

    2015-10-01

    Autoimmune muscle diseases (myositis) comprise a group of complex phenotypes influenced by genetic and environmental factors. To identify genetic risk factors in patients of European ancestry, we conducted a genome-wide association study (GWAS) of the major myositis phenotypes in a total of 1710 cases, which included 705 adult dermatomyositis, 473 juvenile dermatomyositis, 532 polymyositis and 202 adult dermatomyositis, juvenile dermatomyositis or polymyositis patients with anti-histidyl-tRNA synthetase (anti-Jo-1) autoantibodies, and compared them with 4724 controls. Single-nucleotide polymorphisms showing strong associations (Pmyositis phenotypes together, as well as for the four clinical and autoantibody phenotypes studied separately. Imputation and regression analyses found that alleles comprising the human leukocyte antigen (HLA) 8.1 ancestral haplotype (AH8.1) defined essentially all the genetic risk in the phenotypes studied. Although the HLA DRB1*03:01 allele showed slightly stronger associations with adult and juvenile dermatomyositis, and HLA B*08:01 with polymyositis and anti-Jo-1 autoantibody-positive myositis, multiple alleles of AH8.1 were required for the full risk effects. Our findings establish that alleles of the AH8.1 comprise the primary genetic risk factors associated with the major myositis phenotypes in geographically diverse Caucasian populations.

  7. Living Near Major Traffic Roads and Risk of Deep Vein Thrombosis

    Science.gov (United States)

    Baccarelli, Andrea; Martinelli, Ida; Pegoraro, Valeria; Melly, Steven; Grillo, Paolo; Zanobetti, Antonella; Hou, Lifang; Bertazzi, Pier Alberto; Mannucci, Pier Mannuccio; Schwartz, Joel

    2010-01-01

    Background Particulate air pollution has been consistently linked to increased risk of arterial cardiovascular disease. Few data on air pollution exposure and risk of venous thrombosis are available. We investigated whether living near major traffic roads increases the risk of deep vein thrombosis (DVT), using distance from roads as a proxy for traffic exposure. Methods and Results Between 1995-2005, we examined 663 patients with DVT of the lower limbs and 859 age-matched controls from cities with population>15,000 inhabitants in Lombardia Region, Italy. We assessed distance from residential addresses to the nearest major traffic road using geographic information system methodology. The risk of DVT was estimated from logistic regression models adjusting for multiple clinical and environmental covariates. The risk of DVT was increased (Odds Ratio [OR]=1.33; 95% CI 1.03-1.71; p=0.03 in age-adjusted models; OR=1.47; 95%CI 1.10-1.96; p=0.008 in models adjusted for multiple covariates) for subjects living near a major traffic road (3 meters, 10th centile of the distance distribution) compared to those living farther away (reference distance of 245 meters, 90th centile). The increase in DVT risk was approximately linear over the observed distance range (from 718 to 0 meters), and was not modified after adjusting for background levels of particulate matter (OR=1.47; 95%CI 1.11-1.96; p=0.008 for 10th vs. 90th distance centile in models adjusting for area levels of particulate matter roads is associated with increased risk of DVT. PMID:19506111

  8. Major life events and risk of alcohol use disorders

    DEFF Research Database (Denmark)

    Just-Østergaard, Emilie; Mortensen, Erik L.; Flensborg-Madsen, Trine

    2018-01-01

    , household income, cohabitation status and psychiatric comorbidity. Findings: Serious family conflicts in childhood [hazard ratio (HR) = 1.35; 95% confidence interval (CI) = 1.00, 1.83] and serious economic problems in adult life (HR = 2.22; 95% CI = 1.64, 3.01) were associated significantly with increased......Aims: To estimate associations of individual major life events as well as accumulated major life events in childhood, adult private life and adult work life with risk of alcohol use disorders (AUD). Design: Prospective cohort study with baseline examination in 1991–93 and linkage to national...

  9. First-Trimester Pregnancy Exposure to Venlafaxine or Duloxetine and Risk of Major Congenital Malformations

    DEFF Research Database (Denmark)

    Lassen, Dorte; Ennis, Zandra Nymand; Damkier, Per

    2016-01-01

    and noradrenaline reuptake inhibitors, SNRIs, significantly less data are available. Following the PRISMA guideline for systematic reviews, we performed a systematic search on the risk of major congenital malformations after first trimester in utero exposure to venlafaxine or duloxetine. We identified eight cohort...... studies reporting on the outcome upon in utero exposure to venlafaxine or duloxetine during the first trimester. The cumulated data for venlafaxine were 3186 exposed infants and 107 major malformations, resulting in a relative risk estimate and 95% confidence interval of 1.12 (0.......92-1.35). The corresponding data for duloxetine were 668 infants and 16 major malformations, resulting in a relative risk estimate and 95% confidence interval of 0.80 (0.46-1.29). First-trimester in utero exposure to venlafaxine is not associated with an increased risk of major congenital malformations. The amount of data...

  10. Major lipids, apolipoproteins, and risk of vascular disease

    DEFF Research Database (Denmark)

    Collaboration, Emerging Risk Factors; Di Angelantonio, Emanuele; Sarwar, Nadeem

    2009-01-01

    CONTEXT: Associations of major lipids and apolipoproteins with the risk of vascular disease have not been reliably quantified. OBJECTIVE: To assess major lipids and apolipoproteins in vascular risk. DESIGN, SETTING, AND PARTICIPANTS: Individual records were supplied on 302,430 people without...

  11. A benefit-risk review of systemic haemostatic agents - Part 1 : In major surgery

    NARCIS (Netherlands)

    Fraser, Ian S.; Porte, Robert J.; Kouides, Peter A.; Lukes, Andrea S.

    2008-01-01

    Systemic haemostatic agents play an important role in the management of blood loss during major surgery where significant blood loss is likely and their use has increased in recent times as a consequence of demand for blood products outstripping supply and the risks associated with transfusions.

  12. Residential Proximity to Major Roadways and Risk of Type 2 Diabetes Mellitus: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Zhiqing Zhao

    2016-12-01

    Full Text Available Research indicates that higher levels of traffic-related pollution exposure increase the risk of diabetes, but the association between road proximity and diabetes risk remains unclear. To assess and quantify the association between residential proximity to major roadways and type 2 diabetes, a systematic review and meta-analysis was performed. Embase, Medline, and Web of Science were searched for eligible studies. Using a random-effects meta-analysis, the summary relative risks (RRs were calculated. Bayesian meta-analysis was also performed. Eight studies (6 cohort and 2 cross-sectional with 158,576 participants were finally included. The summary unadjusted RR for type 2 diabetes associated with residential proximity to major roadways was 1.24 (95% confidence interval [CI]: 1.07–1.44, p = 0.001, I2 = 48.1%. The summary adjusted RR of type 2 diabetes associated with residential proximity to major roadways was 1.12 (95% CI: 1.03–1.22, p = 0.01, I2 = 17.9%. After excluding two cross-sectional studies, the summary results suggested that residential proximity to major roadways could increase type 2 diabetes risk (Adjusted RR = 1.13; 95% CI: 1.02–1.27, p = 0.025, I2 = 36.6%. Bayesian meta-analysis showed that the unadjusted RR and adjusted RR of type 2 diabetes associated with residential proximity to major roadways were 1.22 (95% credibility interval: 1.06–1.55 and 1.13 (95% credibility interval: 1.01–1.31, respectively. The meta-analysis suggested that residential proximity to major roadways could significantly increase risk of type 2 diabetes, and it is an independent risk factor of type 2 diabetes. More well-designed studies are needed to further strengthen the evidence.

  13. Role of Lysyl oxidase-like 1 gene polymorphisms in Pakistani patients with pseudoexfoliative glaucoma

    NARCIS (Netherlands)

    Micheal, S.; Khan, M.I.; Akhtar, F.; Ali, M.; Ahmed, A.; Hollander, A.I. den; Qamar, R.

    2012-01-01

    PURPOSE: Single nucleotide polymorphisms (SNPs) rs1048661 (p.R141L) and rs3825942 (p.G153D) in the lysyl oxidase-like 1 (LOXL1) gene have been previously reported to be associated with pseudoexfoliation glaucoma (PEXG) in various Asian and European populations, but these SNPs have not yet been

  14. LMO1 Synergizes with MYCN to Promote Neuroblastoma Initiation and Metastasis.

    Science.gov (United States)

    Zhu, Shizhen; Zhang, Xiaoling; Weichert-Leahey, Nina; Dong, Zhiwei; Zhang, Cheng; Lopez, Gonzalo; Tao, Ting; He, Shuning; Wood, Andrew C; Oldridge, Derek; Ung, Choong Yong; van Ree, Janine H; Khan, Amish; Salazar, Brittany M; Lummertz da Rocha, Edroaldo; Zimmerman, Mark W; Guo, Feng; Cao, Hong; Hou, Xiaonan; Weroha, S John; Perez-Atayde, Antonio R; Neuberg, Donna S; Meves, Alexander; McNiven, Mark A; van Deursen, Jan M; Li, Hu; Maris, John M; Look, A Thomas

    2017-09-11

    A genome-wide association study identified LMO1, which encodes an LIM-domain-only transcriptional cofactor, as a neuroblastoma susceptibility gene that functions as an oncogene in high-risk neuroblastoma. Here we show that dβh promoter-mediated expression of LMO1 in zebrafish synergizes with MYCN to increase the proliferation of hyperplastic sympathoadrenal precursor cells, leading to a reduced latency and increased penetrance of neuroblastomagenesis. The transgenic expression of LMO1 also promoted hematogenous dissemination and distant metastasis, which was linked to neuroblastoma cell invasion and migration, and elevated expression levels of genes affecting tumor cell-extracellular matrix interaction, including loxl3, itga2b, itga3, and itga5. Our results provide in vivo validation of LMO1 as an important oncogene that promotes neuroblastoma initiation, progression, and widespread metastatic dissemination. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. DISC1 pathway in brain development: exploring therapeutic targets for major psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Atsushi eKamiya

    2012-03-01

    Full Text Available Genetic risk factors for major psychiatric disorders play key roles in neurodevelopment. Thus, exploring the molecular pathways of risk genes is important not only for understanding the molecular mechanisms underlying brain development, but also to decipher how genetic disturbances affect brain maturation and functioning relevant to major mental illnesses. During the last decade, there has been significant progress in determining the mechanisms whereby risk genes impact brain development. Nonetheless, given that the majority of psychiatric disorders have etiological complexities encompassing multiple risk genes and environmental factors, the biological mechanisms of these diseases remain poorly understood. How can we move forward in our research for discovery of the biological markers and novel therapeutic targets for major mental disorders? Here we review recent progress in the neurobiology of Disrupted in schizophrenia 1 (DISC1, a major risk gene for major mental disorders, with a particular focus on its roles in cerebral cortex development. Convergent findings implicate DISC1 as part of a large, multi-step pathway implicated in various cellular processes and signal transduction. We discuss links between the DISC1 pathway and environmental factors, such as immune/inflammatory responses, which may suggest novel therapeutic targets. Existing treatments for major mental disorders are hampered by a limited number of pharmacological targets. Consequently, elucidation of the DISC1 pathway, and its association with neuropsychiatric disorders, may offer hope for novel treatment interventions.

  16. First Trimester Influenza Vaccination and Risks for Major Structural Birth Defects in Offspring.

    Science.gov (United States)

    Kharbanda, Elyse Olshen; Vazquez-Benitez, Gabriela; Romitti, Paul A; Naleway, Allison L; Cheetham, T Craig; Lipkind, Heather S; Klein, Nicola P; Lee, Grace; Jackson, Michael L; Hambidge, Simon J; McCarthy, Natalie; DeStefano, Frank; Nordin, James D

    2017-08-01

    To examine risks for major structural birth defects in infants after first trimester inactivated influenza vaccine (IIV) exposures. In this observational study, we used electronic health data from 7 Vaccine Safety Datalink sites to examine risks for selected major structural defects in infants after maternal IIV exposure. Vaccine exposures for women with continuous insurance enrollment through pregnancy who delivered singleton live births between 2004 and 2013 were identified from standardized files. Infants with continuous insurance enrollment were followed to 1 year of age. We excluded mother-infant pairs with other exposures that potentially increased their background risk for birth defects. Selected cardiac, orofacial or respiratory, neurologic, ophthalmologic or otologic, gastrointestinal, genitourinary and muscular or limb defects were identified from diagnostic codes in infant medical records using validated algorithms. Propensity score adjusted generalized estimating equations were used to estimate prevalence ratios (PRs). We identified 52 856 infants with maternal first trimester IIV exposure and 373 088 infants whose mothers were unexposed to IIV during first trimester. Prevalence (per 100 live births) for selected major structural birth defects was 1.6 among first trimester IIV exposed versus 1.5 among unexposed mothers. The adjusted PR was 1.02 (95% CI 0.94-1.10). Organ system-specific PRs were similar to the overall PR. First trimester maternal IIV exposure was not associated with an increased risk for selected major structural birth defects in this large cohort of singleton live births. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Global prevalence and major risk factors of diabetic retinopathy

    DEFF Research Database (Denmark)

    Yau, Joanne W Y; Rogers, Sophie L; Kawasaki, Ryo

    2012-01-01

    To examine the global prevalence and major risk factors for diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) among people with diabetes.......To examine the global prevalence and major risk factors for diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) among people with diabetes....

  18. Aesthetic Breast Surgery and Concomitant Procedures: Incidence and Risk Factors for Major Complications in 73,608 Cases.

    Science.gov (United States)

    Gupta, Varun; Yeslev, Max; Winocour, Julian; Bamba, Ravinder; Rodriguez-Feo, Charles; Grotting, James C; Higdon, K Kye

    2017-05-01

    Major complications following aesthetic breast surgery are uncommon and thus assessment of risk factors is challenging. To determine the incidence and risk factors of major complications following aesthetic breast surgery and concomitant procedures. A prospective cohort of patients who enrolled into the CosmetAssure (Birmingham, AL) insurance program and underwent aesthetic breast surgery between 2008 and 2013 was identified. Major complications (requiring reoperation, readmission, or emergency room visit) within 30 days of surgery were recorded. Risk factors including age, smoking, body mass index (BMI), diabetes, type of surgical facility, and combined procedures were evaluated. Among women, augmentation was the most common breast procedure (n = 41,651, 58.6%) followed by augmentation-mastopexy, mastopexy, and reduction. Overall, major complications occurred in 1.46% with hematoma (0.99%) and infection (0.25%) being most common. Augmentation-mastopexy had a higher risk of complications, particularly infection (relative risk [RR] 1.74, P procedures. Age was the only significant predictor for hematomas (RR 1.01, P procedures or abdominoplasty performed alone. Among men, correction of gynecomastia was the most common breast procedure (n = 1613, 64.6%) with a complication rate of 1.80% and smoking as a risk factor (RR 2.73, P = 0.03). Incidence of major complications after breast cosmetic surgical procedures is low. Risk factors for major complications include increasing age and BMI. Combining abdominoplasty with any breast procedure increases the risk of major complications. 2. © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

  19. Comparison of RISK-PCI, GRACE, TIMI risk scores for prediction of major adverse cardiac events in patients with acute coronary syndrome.

    Science.gov (United States)

    Jakimov, Tamara; Mrdović, Igor; Filipović, Branka; Zdravković, Marija; Djoković, Aleksandra; Hinić, Saša; Milić, Nataša; Filipović, Branislav

    2017-12-31

    To compare the prognostic performance of three major risk scoring systems including global registry for acute coronary events (GRACE), thrombolysis in myocardial infarction (TIMI), and prediction of 30-day major adverse cardiovascular events after primary percutaneous coronary intervention (RISK-PCI). This single-center retrospective study involved 200 patients with acute coronary syndrome (ACS) who underwent invasive diagnostic approach, ie, coronary angiography and myocardial revascularization if appropriate, in the period from January 2014 to July 2014. The GRACE, TIMI, and RISK-PCI risk scores were compared for their predictive ability. The primary endpoint was a composite 30-day major adverse cardiovascular event (MACE), which included death, urgent target-vessel revascularization (TVR), stroke, and non-fatal recurrent myocardial infarction (REMI). The c-statistics of the tested scores for 30-day MACE or area under the receiver operating characteristic curve (AUC) with confidence intervals (CI) were as follows: RISK-PCI (AUC=0.94; 95% CI 1.790-4.353), the GRACE score on admission (AUC=0.73; 95% CI 1.013-1.045), the GRACE score on discharge (AUC=0.65; 95% CI 0.999-1.033). The RISK-PCI score was the only score that could predict TVR (AUC=0.91; 95% CI 1.392-2.882). The RISK-PCI scoring system showed an excellent discriminative potential for 30-day death (AUC=0.96; 95% CI 1.339-3.548) in comparison with the GRACE scores on admission (AUC=0.88; 95% CI 1.018-1.072) and on discharge (AUC=0.78; 95% CI 1.000-1.058). In comparison with the GRACE and TIMI scores, RISK-PCI score showed a non-inferior ability to predict 30-day MACE and death in ACS patients. Moreover, RISK-PCI was the only scoring system that could predict recurrent ischemia requiring TVR.

  20. Aesthetic Surgical Procedures in Men: Major Complications and Associated Risk Factors.

    Science.gov (United States)

    Kaoutzanis, Christodoulos; Winocour, Julian; Yeslev, Max; Gupta, Varun; Asokan, Ishan; Roostaeian, Jason; Grotting, James C; Higdon, K Kye

    2018-03-14

    The number of men undergoing cosmetic surgery is increasing in North America. To determine the incidence and risk factors of major complications in males undergoing cosmetic surgery, compare the complication profiles between men and women, and identify specific procedures that are associated with higher risk of complications in males. A prospective cohort of patients undergoing cosmetic surgery between 2008 and 2013 was identified from the CosmetAssure database. Gender specific procedures were excluded. Primary outcome was occurrence of a major complication in males requiring emergency room visit, hospital admission, or reoperation within 30 days of the index operation. Univariate and multivariate analysis evaluated potential risk factors for major complications including age, body mass index (BMI), smoking, diabetes, type of surgical facility, type of procedure, and combined procedures. Of the 129,007 patients, 54,927 underwent gender nonspecific procedures, of which 5801 (10.6%) were males. Women showed a higher mean age (46.4 ± 14.1 vs 45.2 ± 16.7 years, P procedures (RR 3.47), and combined procedures (RR 2.56). Aesthetic surgery in men is safe with low major complication rates. Modifiable predictors of complications included BMI and combined procedures.

  1. Population information on major technological risks and specially on nuclear risk

    International Nuclear Information System (INIS)

    De Choudens, H.

    1992-01-01

    Following Chernobyl accident which has revealed in France a strong need for information on technological risks among population and a lack in its organization, the Mayor of Grenoble City who was also at this time, Environment Minister in French Government had initiated in lsere Region an important operation of consideration of action, which has to been undertaken to correct theses lacks. Among ten actions retained one of them was the creation of an Association for Information of the public for Prevention of major risks. This Association has first initiated a consultation on the perception by the population of the different major risks (Industrial and Naturals) in view of the results of this consultation, Medical Professions were the first concerned and a publication 'Medicine and Nuclear risk' has been elaborated and distributed to all doctors of the Region. A Memento on Nuclear risk as then been written and largely distributed in the region, especially in the medias. A booklet on nuclear risk and behavior in case of nuclear accident has then been realized and distributed to all people around Electronuclear Reactors of the Region and to children in the schools. In complement, public meetings have been organized in these sectors to inform, and discuss with the population. (author)

  2. Risk prediction of major complications in individuals with diabetes: the Atherosclerosis Risk in Communities Study.

    Science.gov (United States)

    Parrinello, C M; Matsushita, K; Woodward, M; Wagenknecht, L E; Coresh, J; Selvin, E

    2016-09-01

    To develop a prediction equation for 10-year risk of a combined endpoint (incident coronary heart disease, stroke, heart failure, chronic kidney disease, lower extremity hospitalizations) in people with diabetes, using demographic and clinical information, and a panel of traditional and non-traditional biomarkers. We included in the study 654 participants in the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study, with diagnosed diabetes (visit 2; 1990-1992). Models included self-reported variables (Model 1), clinical measurements (Model 2), and glycated haemoglobin (Model 3). Model 4 tested the addition of 12 blood-based biomarkers. We compared models using prediction and discrimination statistics. Successive stages of model development improved risk prediction. The C-statistics (95% confidence intervals) of models 1, 2, and 3 were 0.667 (0.64, 0.70), 0.683 (0.65, 0.71), and 0.694 (0.66, 0.72), respectively (p < 0.05 for differences). The addition of three traditional and non-traditional biomarkers [β-2 microglobulin, creatinine-based estimated glomerular filtration rate (eGFR), and cystatin C-based eGFR] to Model 3 significantly improved discrimination (C-statistic = 0.716; p = 0.003) and accuracy of 10-year risk prediction for major complications in people with diabetes (midpoint percentiles of lowest and highest deciles of predicted risk changed from 18-68% to 12-87%). These biomarkers, particularly those of kidney filtration, may help distinguish between people at low versus high risk of long-term major complications. © 2016 John Wiley & Sons Ltd.

  3. Lysyl oxidase‑like 2 is expressed in kidney tissue and is associated with the progression of tubulointerstitial fibrosis.

    Science.gov (United States)

    Choi, Sung-Eun; Jeon, Nara; Choi, Hoon Young; Shin, Jae Il; Jeong, Hyeon Joo; Lim, Beom Jin

    2017-09-01

    Tubulointerstitial fibrosis is a common end point of chronic kidney diseases, and preventing its progression is key to avoiding renal failure. Transforming growth factor‑β (TGF‑β) and associated molecules promote tubulointerstitial fibrosis; however, effective therapies targeting these molecules have yet to be developed. Lysyl oxidase‑like 2 (LOXL2), which is involved in invasive growth and metastasis of malignant neoplasms, has recently been reported to serve a key role in hepatic and pulmonary fibrosis. However, little is currently known regarding LOXL2 expression in the kidney and its involvement in tubulointerstitial fibrosis. The present study evaluated LOXL2 expression in human and mouse kidney tissues, as well as in cultured renal cells. LOXL2 protein expression was detected in glomerular capillary loops and tubular epithelial cells in human and mouse kidneys. Glomerular LOXL2 was localized to the cytoplasm of podocytes, as determined by double immunofluorescence microscopy using a podocyte marker (synaptopodin). This result was supported by western blot analysis, which demonstrated that LOXL2 protein expression is present in cultured human podocytes and HK‑2 human proximal tubular cells. In addition, the mRNA and protein expression levels of LOXL2 were higher in a mouse model of tubulointerstitial fibrosis compared with in control mice. In addition, immunohistochemistry results demonstrated that LOXL2 is present in the fibrous interstitium and infiltrating mononuclear cells in a mouse model of tubulointerstitial fibrosis. The present study demonstrated that LOXL2 is expressed in compartments of renal tissue, where it appears to contribute to the progression of tubulointerstitial fibrosis.

  4. The association between suicide risk and self-esteem in Japanese university students with major depressive episodes of major depressive disorder

    Directory of Open Access Journals (Sweden)

    Mitsui N

    2014-05-01

    Full Text Available Nobuyuki Mitsui,1 Satoshi Asakura,1,2 Yusuke Shimizu,1 Yutaka Fujii,1 Atsuhito Toyomaki,1 Yuki Kako,1 Teruaki Tanaka,1 Nobuki Kitagawa,3 Takeshi Inoue,1 Ichiro Kusumi1 1Department of Psychiatry, Hokkaido University Graduate School of Medicine, 2Health care center of Hokkaido University, Kita-ku, Sapporo, 3Department of Clinical Social Work, Health Sciences University of Hokkaido School of Nursing and Social Services, Tobetsu, Ishikari, Japan Background: The suicide risk among young adults is related to multiple factors; therefore, it is difficult to predict and prevent suicidal behavior. Aim: We conducted the present study to reveal the most important factors relating to suicidal ideation in Japanese university students with major depressive episodes (MDEs of major depressive disorder (MDD. Methods: The subjects were 30 Japanese university students who had MDEs of MDD, and were aged between 18 and 26 years old. They were divided into two groups – without suicide risk group (n=15, and with suicide risk group (n=15 – based on the results of the Mini-International Neuropsychiatric Interview. Additionally, healthy controls were recruited from the same population (n=15. All subjects completed the self-assessment scales including the Beck Depression Inventory 2nd edition (BDI-II, the Beck Hopelessness Scale (BHS, Rosenberg's Self-Esteem Scale (RSES, and SF-36v2TM (The Medical Outcomes Study 36-item short-form health survey version 2, and they were all administered a battery of neuropsychological tests. Results: The RSES score of the suicide risk group was significantly lower than the RSES score of the without suicide risk group, whereas the BDI-II score and the BHS score were not significantly different between the two groups. The mean social functioning score on the SF-36v2 of the with suicide risk group was significantly lower than that of the without suicide risk group. Conclusion: The individual's self-esteem and social functioning may play an

  5. Vigorous-intensity leisure-time physical activity and risk of major chronic disease in men.

    Science.gov (United States)

    Chomistek, Andrea K; Cook, Nancy R; Flint, Alan J; Rimm, Eric B

    2012-10-01

    Although studies have shown health benefits for moderate-intensity physical activity, there is limited evidence to support beneficial effects for high amounts of vigorous activity among middle-age and older men. The objective of this study was to examine the relationship between vigorous-intensity physical activity, compared with moderate-intensity activity, and risk of major chronic disease in men. We prospectively examined the associations between vigorous- and moderate-intensity physical activity and risk of major chronic disease among 44,551 men age 40-75 yr in 1986. Leisure-time physical activity was assessed biennially by questionnaire. During 22 yr of follow-up, we documented 14,162 incident cases of major chronic disease, including 4769 cardiovascular events, 6449 cancer events, and 2944 deaths from other causes. The HR of major chronic disease comparing ≥ 21 to 0 MET.h.wk(-1) of exercise was 0.86 (95% confidence interval (CI), 0.81-0.91) for vigorous-intensity activity and 0.85 (95% CI, 0.80-0.90) for moderate activity. For cardiovascular disease (CVD), the corresponding HRs were 0.78 (95% CI, 0.70-0.86) and 0.80 (95% CI, 0.72-0.88), respectively. When examined separately, running, tennis, and brisk walking were inversely associated with CVD risk. Furthermore, more vigorous activity was associated with lower disease risk; the HR comparing >70 to 0 MET.h.wk(-1) of vigorous-intensity exercise was 0.79 (95% CI, 0.68-0.92; P < 0.0001 for trend) for major chronic disease and 0.73 (95% CI, 0.56-0.96; P < 0.0001 for trend) for CVD. Vigorous- and moderate-intensity physical activities were associated with lower risk of major chronic disease and CVD. Increasing amounts of vigorous activity remained inversely associated with disease risk, even among men in the highest categories of exercise.

  6. A population-based longitudinal study of risk factors for suicide attempts in major depressive disorder.

    Science.gov (United States)

    Bolton, James M; Pagura, Jina; Enns, Murray W; Grant, Bridget; Sareen, Jitender

    2010-10-01

    No longitudinal study has examined risk factors for future suicide attempts in major depressive disorder in a nationally representative sample. The objective of this study was to investigate baseline sociodemographic characteristics, comorbid mental disorders, specific depressive symptoms, and previous suicidal behavior as potential risk factors for suicide attempts at 3 years follow-up. Data came from the national epidemiologic survey on alcohol and related conditions (NESARC), a large nationally representative longitudinal survey of mental illness in adults [Wave 1 (2001-2002); Wave 2 (2004-2005) n=34,653]. Logistic regression examined associations between risk factors present at Wave 1 and suicide attempts at Wave 2 (n=169) among individuals with major depressive disorder at baseline assessment (n=6004). Risk factors for incident suicide attempts at Wave 2 (n=63) were identified among those with major depressive disorder at Wave 1 and no lifetime history of suicide attempts (n=5170). Results revealed specific comorbid anxiety, personality, and substance use disorders to be associated with incident suicide attempts at Wave 2. Comorbid borderline personality disorder was strongly associated with suicide attempts in all models. Several comorbid disorders were strongly associated with suicide attempts at Wave 2 even after adjusting for previous suicidal behavior, notably posttraumatic stress disorder (adjusted odds ratio (AOR)=2.20; 95% confidence interval (95% CI) 1.27-3.83) and dependent personality disorder (AOR=4.43; 95% CI 1.93-10.18). These findings suggest that mental illness comorbidity confers an increased risk of future suicide attempts in major depressive disorder that is not solely accounted for by past suicidal behavior.

  7. Major Management Challenges and Program Risks: Small Business Administration

    Science.gov (United States)

    2001-01-01

    2001 Major Management Challenges and Program Risks Small Business AdministrationGAO-01-260 Form SF298 Citation Data Report Date ("DD MON YYYY...34) 00JAN2001 Report Type N/A Dates Covered (from... to) ("DD MON YYYY") Title and Subtitle Major Management Challenges and Program Risks Small Business ...Administration (SBA) as it seeks to aid, counsel, assist, and protect the interests of the nations small businesses and help businesses and families

  8. Risk factors for major antenatal depression among low-income African American women.

    Science.gov (United States)

    Luke, Sabrina; Salihu, Hamisu M; Alio, Amina P; Mbah, Alfred K; Jeffers, Dee; Berry, Estrellita Lo; Mishkit, Vanessa R

    2009-11-01

    Data on risk factors for major antenatal depression among African American women are scant. In this study, we seek to determine the prevalence and risk factors for major antenatal depression among low-income African American women receiving prenatal services through the Central Hillsborough Healthy Start (CHHS). Women were screened using the Edinburgh Postnatal Depression Scale (EPDS) with a cutoff of > or =13 as positive for risk of major antenatal depression. In total, 546 African American women were included in the analysis. We used logistic regression to identify risk factors for major antenatal depression. The prevalence of depressive symptomatology consistent with major antenatal depression was 25%. Maternal age was identified as the main risk factor for major antenatal depression. The association between maternal age and risk for major antenatal depression was biphasic, with a linear trend component lasting until age 30, at which point the slope changed markedly tracing a more pronounced likelihood for major depression with advancing age. Women aged > or =30 were about 5 times as likely to suffer from symptoms of major antenatal depression as teen mothers (OR = 4.62, 95% CI 2.23-9.95). The risk for major antenatal depression increases about 5-fold among low-income African American women from age 30 as compared to teen mothers. The results are consistent with the weathering effect resulting from years of cumulative stress burden due to socioeconomic marginalization and discrimination. Older African American mothers may benefit from routine antenatal depression screening for early diagnosis and intervention.

  9. Placenta previa and risk of major congenital malformations among singleton births in Finland.

    Science.gov (United States)

    Kancherla, Vijaya; Räisänen, Sari; Gissler, Mika; Kramer, Michael R; Heinonen, Seppo

    2015-06-01

    Placenta previa has been associated with adverse birth outcomes, but its association with congenital malformations is inconclusive. We examined the association between placenta previa and major congenital malformations among singleton births in Finland. We performed a retrospective population register-based study on all singletons born at or after 22+0 weeks of gestation in Finland during 2000 to 2010. We linked three national health registers: the Finnish Medical Birth Register, the Hospital Discharge Register, and the Register of Congenital Malformations, and examined several demographic and clinical characteristics among women with and without placenta previa, in association with major congenital malformations. We estimated adjusted odds ratios and 95% confidence intervals using multivariable logistic regression models. The prevalence of placenta previa was estimated as 2.65 per 1000 singleton births in Finland (95% confidence interval, 2.53-2.79). Overall, 6.2% of women with placenta previa delivered a singleton infant with a major congenital malformation, compared with 3.8% of unaffected women (p ≤ 0.001). Placenta previa was positively associated with almost 1.6-fold increased risk of major congenital malformations in the offspring, after controlling for maternal age, parity, fetal sex, smoking, socio-economic status, chorionic villus biopsy, In vitro fertilization, pre-existing diabetes, depression, preeclampsia, and prior caesarean section (adjusted odds ratio = 1.55; 95% confidence interval, 1.27-1.90). Using a large population-based study, we found that placenta previa was weakly, but significantly associated with an increased risk of major congenital malformations in singleton births. Future studies should examine the association between placenta previa and individual types of congenital malformations, specifically in high-risk pregnancies. © 2015 Wiley Periodicals, Inc.

  10. Assessment of major nuclear technologies with decision and risk analysis

    International Nuclear Information System (INIS)

    Winterfeldt, D. von

    1995-01-01

    Selecting technologies for major nuclear programs involves several complexities, including multiple stakeholders, multiple conflicting objectives, uncertainties, and risk. In addition, the programmatic risks related to the schedule, cost, and performance of these technologies often become major issues in the selection process. This paper describes a decision analysis approach for addressing these complexities in a logical manner

  11. Societal risk and major disasters

    International Nuclear Information System (INIS)

    Clement, C.F.

    1989-01-01

    A disaster can be defined as an event, or a series of events, in which a large number of people is adversely affected by a single cause. This definition includes man-made accidents, like that at Chernobyl, as well as the natural disasters that insurance companies are sometimes pleased to describe as Acts of God. In 1986 alone, 12,000 people died and 2.2 million were made homeless by 215 major accidents or disasters. The nature of risk is examined in this paper. (author)

  12. Risk of subsequent dementia among patients with bipolar disorder or major depression: a nationwide longitudinal study in Taiwan.

    Science.gov (United States)

    Chen, Mu-Hong; Li, Cheng-Ta; Tsai, Chia-Fen; Lin, Wei-Chen; Chang, Wen-Han; Chen, Tzeng-Ji; Pan, Tai-Long; Su, Tung-Ping; Bai, Ya-Mei

    2015-06-01

    Both major depression and bipolar disorder are associated with an increased risk of developing dementia. However, the differential risk of dementia between major depression and bipolar disorder is rarely investigated. Using the Taiwan National Health Insurance Research Database, a total of 2291 patients aged ≥ 55 years (major depression: 1946 and bipolar disorder: 345) and 2291 age-and sex-matched controls were enrolled between 1998 and 2008, and followed to the end of 2011. Participants who developed dementia during the follow-up were identified. Both patients with bipolar disorder [hazard ratio (HR) 5.58, 95% confidence interval (CI) 4.26-7.32] and those with major depression (HR 3.02, 95% CI 2.46-3.70) had an increased risk of developing dementia in later life, after adjusting for demographic data and medical comorbidities. The sensitivity tests after excluding the 1-year (bipolar disorder: HR 4.73, 95% CI 3.50-6.35; major depression: HR 2.62, 95% CI 2.11-3.25) and 3-year (HR 3.92, 95% CI 2.78-5.54; HR 2.21, 95% CI 1.73-2.83, respectively) follow-up duration also revealed consistent findings. Furthermore, patients with bipolar disorder were associated with an 87% increased risk (HR 1.87, 95% CI 1.48-2.37) of subsequent dementia compared with patients with major depression. Midlife individuals with bipolar disorder or major depression were associated with an elevated risk of developing dementia in later life. Further studies may be required to clarify the underlying mechanisms among major depression, bipolar disorder, and dementia, and to investigate whether prompt intervention may decrease this risk. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  13. Incidence and Risk Factors for Major Hematomas in Aesthetic Surgery: Analysis of 129,007 Patients.

    Science.gov (United States)

    Kaoutzanis, Christodoulos; Winocour, Julian; Gupta, Varun; Ganesh Kumar, Nishant; Sarosiek, Konrad; Wormer, Blair; Tokin, Christopher; Grotting, James C; Higdon, K Kye

    2017-10-16

    Postoperative hematomas are one of the most frequent complications following aesthetic surgery. Identifying risk factors for hematoma has been limited by underpowered studies from single institution experiences. To examine the incidence and identify independent risk factors for postoperative hematomas following cosmetic surgery utilizing a prospective, multicenter database. A prospectively enrolled cohort of patients who underwent aesthetic surgery between 2008 and 2013 was identified from the CosmetAssure database. Primary outcome was occurrence of major hematomas requiring emergency room visit, hospital admission, or reoperation within 30 days of the index operation. Univariate and multivariate analysis was used to identify potential risk factors for hematomas including age, gender, body mass index (BMI), smoking, diabetes, type of surgical facility, procedure by body region, and combined procedures. Of 129,007 patients, 1180 (0.91%) had a major hematoma. Mean age (42.0 ± 13.0 years vs 40.9 ± 13.9 years, P hematomas. Males suffered more hematomas than females (1.4% vs 0.9%, P Hematoma rates were higher in patients undergoing combined procedures compared to single procedures (1.1% vs 0.8%, P hematoma included age (Relative Risk [RR] 1.01), male gender (RR 1.98), the procedure being performed in a hospital setting rather than an office-based setting (RR 1.68), combined procedures (RR 1.35), and breast procedures rather than the body/extremity and face procedures (RR 1.81). Major hematoma is the most common complication following aesthetic surgery. Male patients and those undergoing breast or combined procedures have a significantly higher risk of developing hematomas. 2. © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

  14. Worldwide incidence of hepatocellular carcinoma cases attributable to major risk factors.

    Science.gov (United States)

    Baecker, Aileen; Liu, Xing; La Vecchia, Carlo; Zhang, Zuo-Feng

    2018-05-01

    To facilitate regionally specific liver cancer prevention and control, this study estimates the fraction of hepatocellular carcinoma (HCC) cases attributable to five major liver cancer risk factors by geographic region. Prevalence estimates of major HCC risk factors, including chronic infection with hepatitis B and hepatitis C, alcohol drinking, tobacco smoking, obesity, and diabetes, were extracted for each country from the literature, along with recent incidence and risk estimate data, to calculate regionally specific population attributable fractions. Overall, 44% of HCC cases worldwide were attributable to chronic hepatitis B infection, with the majority of cases occurring in Asia. Hepatitis C was responsible for 21% of cases. Lifestyle risk factors such as alcohol drinking and obesity were responsible for a larger percentage of cases in North America and Western, Central, and Eastern Europe. In addition, strong sex disparities were observed when looking at lifestyle risk factors, particularly tobacco smoking, in Asia and Africa. Prominent risk factors for HCC vary depending on the region. Our findings provide useful data for developing regionally specific guidelines for liver cancer prevention and control worldwide.

  15. Risk assessment of major hazards and its application in urban planning: a case study.

    Science.gov (United States)

    Zhou, Yafei; Liu, Mao

    2012-03-01

    With the rapid development of industry in China, the number of establishments that are proposed or under construction is increasing year by year, and many are industries that handle flammable, explosive, toxic, harmful, and dangerous substances. Accidents such as fire, explosion, and toxic diffusion inevitably happen. Accidents resulting from these major hazards in cities cause a large number of casualties and property losses. It is increasingly important to analyze the risk of major hazards in cities realistically and to suitably plan and utilize the surrounding land based on the risk analysis results, thereby reducing the hazards. A theoretical system for risk assessment of major hazards in cities is proposed in this article, and the major hazard risk for the entire city is analyzed quantitatively. Risks of various major accidents are considered together, superposition effect is analyzed, individual risk contours of the entire city are drawn out, and the level of risk in the city is assessed using "as low as reasonably practicable" guidelines. After the entire city's individual risk distribution is obtained, risk zones are divided according to corresponding individual risk value of HSE, and land-use planning suggestions are proposed. Finally, a city in China is used as an example to illustrate the risk assessment process of the city's major hazard and its application in urban land-use planning. The proposed method has a certain theoretical and practical significance in establishing and improving risk analysis of major hazard and urban land-use planning. On the one hand, major urban public risk is avoided; further, the land is utilized in the best possible way in order to obtain the maximum benefit from its use. © 2011 Society for Risk Analysis.

  16. Risk factors for and perinatal outcomes of major depression during pregnancy

    DEFF Research Database (Denmark)

    Räisänen, Sari; Lehto, Soili M; Nielsen, Henriette Svarre

    2014-01-01

    was substantial to modest for small-for-gestational age newborn (care associated with major depression, whereas SES made only a minor contribution. CONCLUSIONS: Physician-diagnosed major depression......OBJECTIVES: To identify risk factors for and the consequences (several adverse perinatal outcomes) of physician-diagnosed major depression during pregnancy treated in specialised healthcare. DESIGN: A population-based cross-sectional study. SETTING: Data were gathered from Finnish health registers...... for 1996-2010. PARTICIPANTS: All singleton births (n=511,938) for 2002-2010 in Finland. PRIMARY OUTCOME MEASURES: Prevalence, risk factors and consequences of major depression during pregnancy. RESULTS: Among 511,938 women, 0.8% experienced major depression during pregnancy, of which 46.9% had a history...

  17. Suicide Risk, Aggression and Violence in Major Psychiatric Disorders

    Directory of Open Access Journals (Sweden)

    G Mousavi

    2004-02-01

    Full Text Available Background: Aggression, violence and Suicide are important problems of mental health in our society. They almost always cause disability, death, or other social problems. Appropriate measures can be taken if the distribution of behaviors and suicide risk are well studied in various psychiatric disorders. Methods: This was a cross-sectional study. We studied 801 psychiatric patients who were admitted in a psychiatric emergency unit in Isfahan, Iran, for aggression, violence and risk of suicide. Information was obtained from a 30-item questionnaire, filled by the same physician. Results: About one-third of patients had aggression and/or violence on admission or during hours before it. It was most prevalent in men of 12-26 years old and in bipolar mood disorder patients. "High suicide risk" was markedly found in patients with major depressive disorder. Differences of these phenomena were statistically Conclusion: Our findings show a higher rate of aggression and violence in emergency psychiatric patients than in studies done in other countries. It may be due to higher prevalence of bipolar patients in the study field. The finding of "High suicidal risk" in major depression patients warrent systematic preventive programs. Keywords: Suicide risk, Aggression, Violence

  18. Major air pollutants and risk of COPD exacerbations: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Li JH

    2016-12-01

    Full Text Available Jinhui Li,1,2 Shengzhi Sun,1,2 Robert Tang,1,2 Hong Qiu,2 Qingyuan Huang,3 Tonya G Mason,2 Linwei Tian1,2 1Shenzhen Institute of Research and Innovation, Nanshan, The University of Hong Kong, Shenzhen, People’s Republic of China; 2School of Public Health, The University of Hong Kong, Pok Fu Lam, Hong Kong Special Administrative Region; 3Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Minhang, Shanghai, People’s Republic of China Background: Short-term exposure to major air pollutants (O3, CO, NO2, SO2, PM10, and PM2.5 has been associated with respiratory risk. However, evidence on the risk of chronic obstructive pulmonary disease (COPD exacerbations is still limited. The present study aimed at evaluating the associations between short-term exposure to major air pollutants and the risk of COPD exacerbations.Methods: After a systematic search up until March 30, 2016, in both English and Chinese electronic databases such as PubMed, EMBASE, and CNKI, the pooled relative risks and 95% confidence intervals were estimated by using the random-effects model. In addition, the population-attributable fractions (PAFs were also calculated, and a subgroup analysis was conducted. Heterogeneity was assessed by I2.Results: In total, 59 studies were included. In the single-pollutant model, the risks of COPD were calculated by each 10 µg/m3 increase in pollutant concentrations, with the exception of CO (100 µg/m3. There was a significant association between short-term exposure and COPD exacerbation risk for all the gaseous and particulate pollutants. The associations were strongest at lag0 and lag3 for gaseous and particulate air pollutants, respectively. The subgroup analysis not only further confirmed the overall adverse effects but also reduced the heterogeneities obviously. When 100% exposure was assumed, PAFs ranged from 0.60% to 4.31%, depending on the pollutants. The adverse health effects of SO2 and NO2

  19. Managing major chemical accidents in China: Towards effective risk information

    International Nuclear Information System (INIS)

    He Guizhen; Zhang Lei; Lu Yonglong; Mol, Arthur P.J.

    2011-01-01

    Chemical industries, from their very inception, have been controversial due to the high risks they impose on safety of human beings and the environment. Recent decades have witnessed increasing impacts of the accelerating expansion of chemical industries and chemical accidents have become a major contributor to environmental and health risks in China. This calls for the establishment of an effective chemical risk management system, which requires reliable, accurate and comprehensive data in the first place. However, the current chemical accident-related data system is highly fragmented and incomplete, as different responsible authorities adopt different data collection standards and procedures for different purposes. In building a more comprehensive, integrated and effective information system, this article: (i) reviews and assesses the existing data sources and data management, (ii) analyzes data on 976 recorded major hazardous chemical accidents in China over the last 40 years, and (iii) identifies the improvements required for developing integrated risk management in China.

  20. The risk of major nuclear accident: calculation and perception of probabilities

    International Nuclear Information System (INIS)

    Leveque, Francois

    2013-01-01

    Whereas before the Fukushima accident, already eight major accidents occurred in nuclear power plants, a number which is higher than that expected by experts and rather close to that corresponding of people perception of risk, the author discusses how to understand these differences and reconcile observations, objective probability of accidents and subjective assessment of risks, why experts have been over-optimistic, whether public opinion is irrational regarding nuclear risk, and how to measure risk and its perception. Thus, he addresses and discusses the following issues: risk calculation (cost, calculated frequency of major accident, bias between the number of observed accidents and model predictions), perceived probabilities and aversion for disasters (perception biases of probability, perception biases unfavourable to nuclear), the Bayes contribution and its application (Bayes-Laplace law, statistics, choice of an a priori probability, prediction of the next event, probability of a core fusion tomorrow)

  1. Is hypertension a major independent risk factor for retinopathy in type 1 diabetes?

    DEFF Research Database (Denmark)

    Nørgaard, K; Feldt-Rasmussen, B; Deckert, T

    1991-01-01

    Hypertension is an established risk factor for retinopathy. Whether it is an independent risk factor or acts only by association with nephropathy is not known. Therefore, we studied 273 Type 1 diabetic patients. They were divided into four groups. Group 1 (n = 55) were normotensive...... and normoalbuminuric, group 2 (n = 51) had hypertension but were normoalbuminuric, group 3 (n = 33) had nephropathy but were normotensive, and group 4 (n = 134) had nephropathy and hypertension. Hypertensive patients with normoalbuminuria (blood pressure 146 +/- 19 (+/-SD)/87 +/- 12 mmHg) had the same prevalence...... of retinopathy as normoalbuminuric normotensive patients (123 +/- 12/75 +/- 5 mmHg). Hypertensive nephropathic patients (blood pressure 147 +/- 18/87 +/- 8 mmHg) had more retinopathy than hypertensive normoalbuminuric patients despite similar blood pressure (normal retina/advanced retinopathy: 3%/73% vs 46...

  2. Risk of developing major depression and bipolar disorder among adolescents with atopic diseases: A nationwide longitudinal study in Taiwan.

    Science.gov (United States)

    Wei, Han-Ting; Lan, Wen-Hsuan; Hsu, Ju-Wei; Huang, Kai-Lin; Su, Tung-Ping; Li, Cheng-Ta; Lin, Wei-Chen; Chen, Tzeng-Ji; Bai, Ya-Mei; Chen, Mu-Hong

    2016-10-01

    Previous studies have found an increased prevalence of atopic diseases among patients with major depression and bipolar disorder. But the temporal association between atopic diseases in adolescence and the subsequent risk of developing mood disorders has been rarely investigated. Using the Taiwan National Health Insurance Research Databases, 5075 adolescents with atopic diseases (atopic cohort) and 44,729 without (non-atopic cohort) aged between 10 and 17 in 2000 were enrolled into our study and followed to the end of 2010. Subjects who developed major depression or bipolar disorder during the follow-up were identified. The atopic cohort had an increased risk of developing major depression (HR: 2.45, 95% CI: 1.93~3.11) and bipolar disorder (HR: 2.51, 95% CI: 1.71~3.67) compared to the non-atopic cohort, with a dose-dependent relationship between having a greater number of atopic comorbidities and a greater likelihood of major depression (1 atopic disease: HR: 1.80, 95% CI: 1.29~2.50; 2 atopic comorbidities: HR: 2.42, 95% CI: 1.93~3.04;≥3 atopic comorbidities: HR: 3.79, 95% CI: 3.05~4.72) and bipolar disorder (HR: 1.40, 95% CI: 0.57~3.44; HR: 2.81, 95% CI: 1.68~4.68; HR: 3.02, 95% CI: 1.69~5.38). Having atopic diseases in adolescence increased the risk of developing major depression and bipolar disorder in later life. Further studies may be required to clarify the underlying mechanism between atopy and mood disorders, and to investigate whether prompt intervention may decrease the risk of subsequent mood disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Tea consumption and the risk of five major cancers: a dose–response meta-analysis of prospective studies

    Science.gov (United States)

    2014-01-01

    Background We conducted a dose–response meta-analysis of prospective studies to summarize evidence of the association between tea consumption and the risk of breast, colorectal, liver, prostate, and stomach cancer. Methods We searched PubMed and two other databases. Prospective studies that reported risk ratios (RRs) with 95% confidence intervals (CIs) of cancer risk for ≥3 categories of tea consumption were included. We estimated an overall RR with 95% CI for an increase of three cups/day of tea consumption, and, usingrestricted cubic splines, we examined a nonlinear association between tea consumption and cancer risk. Results Forty-one prospective studies, with a total of 3,027,702 participants and 49,103 cancer cases, were included. From the pooled overall RRs, no inverse association between tea consumption and risk of five major cancers was observed. However, subgroup analysis showed that increase in consumption of three cups of black tea per day was a significant risk factor for breast cancer (RR, 1.18; 95% CI, 1.05-1.32). Conclusion Ourresults did not show a protective role of tea in five major cancers. Additional large prospective cohort studies are needed to make a convincing case for associations. PMID:24636229

  4. Anorexia nervosa and major depression: shared genetic and environmental risk factors.

    Science.gov (United States)

    Wade, T D; Bulik, C M; Neale, M; Kendler, K S

    2000-03-01

    The authors sought to derive heritability estimates for anorexia nervosa and to explore the etiology of the comorbid relationship between anorexia nervosa and major depression. They applied bivariate structural equation modeling to a broad definition of anorexia nervosa and lifetime major depression as assessed in a population-based sample of 2,163 female twins. Anorexia nervosa was estimated to have a heritability of 58% (95% confidence interval=33%-84%). The authors were unable to completely rule out a contribution of shared environment. The comorbidity between anorexia nervosa and major depression is likely due to genetic factors that influence the risk for both disorders. Although the study was limited by the small number of affected twins, the results suggest that genetic factors significantly influence the risk for anorexia nervosa and substantially contribute to the observed comorbidity between anorexia nervosa and major depression.

  5. Prospective study of major dietary patterns and colorectal cancer risk in women.

    Science.gov (United States)

    Terry, P; Hu, F B; Hansen, H; Wolk, A

    2001-12-15

    A number of prospective cohort studies have examined the relations of individual dietary variables to risk of colorectal cancer. Few studies have addressed the broader eating patterns that reflect many dietary exposures working together. Using data from a prospective study of 61,463 women, with an average follow-up period of 9.6 years (between 1987 and 1998) and 460 incident cases of colorectal cancer, the authors conducted a factor analysis to identify and examine major dietary patterns in relation to colorectal cancer risk. Using proportional hazards regression to estimate relative risks, the authors found no clear association between a "Western," "healthy," or "drinker" dietary pattern and colorectal cancer risk. However, the data suggested that consuming low amounts of foods that constitute a "healthy" dietary pattern may be associated with increased risks of colon and rectal cancers. An inverse association with the "healthy" dietary pattern was found among women under age 50 years, although the number of cancers in this age group was limited and interpretation of this finding should be cautious. In this age group, relative risks for women in increasing quintiles of the "healthy" dietary pattern, compared with the lowest quintile, were 0.74 (95% confidence interval (CI): 0.41, 1.31), 0.69 (95% CI: 0.39, 1.24), 0.59 (95% CI: 0.32, 1.07), and 0.45 (95% CI: 0.23, 0.88) (p for trend = 0.03). The role of overall eating patterns in predicting colorectal cancer risk requires further investigation.

  6. Proteolytic processing of lysyl oxidase-like-2 in the extracellular matrix is required for crosslinking of basement membrane collagen IV.

    Science.gov (United States)

    López-Jiménez, Alberto J; Basak, Trayambak; Vanacore, Roberto M

    2017-10-13

    Lysyl oxidase-like-2 (LOXL2) is an enzyme secreted into the extracellular matrix that crosslinks collagens by mediating oxidative deamination of lysine residues. Our previous work demonstrated that this enzyme crosslinks the 7S domain, a structural domain that stabilizes collagen IV scaffolds in the basement membrane. Despite its relevant role in extracellular matrix biosynthesis, little is known about the structural requirements of LOXL2 that enable collagen IV crosslinking. In this study, we demonstrate that LOXL2 is processed extracellularly by serine proteases, generating a 65-kDa form lacking the first two scavenger receptor cysteine-rich domains. Site-specific mutagenesis to prevent proteolytic processing generated a full-length enzyme that is active in vitro toward a soluble substrate, but fails to crosslink insoluble collagen IV within the extracellular matrix. In contrast, the processed form of LOXL2 binds to collagen IV and crosslinks the 7S domain. Together, our data demonstrate that proteolytic processing is an important event that allows LOXL2-mediated crosslinking of basement membrane collagen IV. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Can subsyndromal manifestations of major depression be identified in children at risk?

    Science.gov (United States)

    Uchida, M; Fitzgerald, M; Lin, K; Carrellas, N; Woodworth, H; Biederman, J

    2017-02-01

    Children of parents with major depression are at significantly increased risk for developing major depression themselves; however, not all children at genetic risk will develop major depressive disorder (MDD). We investigated the utility of subsyndromal scores on the Child Behavior Checklist (CBCL) Anxiety/Depression scale in identifying children at the highest risk for pediatric MDD from among the pool of children of parents with MDD or bipolar disorder. The sample was derived from two previously conducted longitudinal case-control family studies of psychiatrically and pediatrically referred youth and their families. For this study, probands were stratified based on the presence or absence of a parental mood disorder. Subsyndromal scores on the CBCL Anxiety/Depression scale significantly separated the children at high risk for pediatric MDD from those at low risk in a variety of functional areas, including social and academic functioning. Additionally, children at genetic risk without elevated CBCL Anxiety/Depression scale scores were largely indistinguishable from controls. These results suggest that the CBCL Anxiety/Depression scale can help identify children at highest risk for pediatric MDD. If implemented clinically, this scale would cost-effectively screen children and identify those most in need of early intervention resources to impede the progression of depression. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Global prevalence and major risk factors of diabetic retinopathy

    NARCIS (Netherlands)

    J.W.Y. Yau (Joanne W.); S.L. Rogers (Sophie); Y. Kawasaki; E.L. Lamoureux (Ecosse); J.W. Kowalski (Jonathan); T. Bek (Toke); S.-J. Chen (Shih-Jen); J.M. Dekker (Jacqueline); A.E. Fletcher (Astrid E.); J. Grauslund (Jakob); R.C.G. Haffner; U. Hamman (Ute); M.K. Ikram (Kamran); T. Kayama (Takamasa); B.E.K. Klein (Barbara); B.E.K. Klein (Barbara); S. Krishnaiah (Sannapaneni); K. Mayurasakorn (Korapat); J.P. O'Hare (Joseph); T. Orchard; M. Porta; M. Rema (Mohan); M.S. Roy (Monique); T. Sharma (Tarun); S-M. Saw (Seang-Mei); H. Taylor (Hugh); J.M. Tielsch (James); D. Varma (Dhiraj); J.J. Wang (Jie Jin); N. Wang (Ningli); S. West (Sheila); L. Zu (Liang); M. Yasuda (Maya); X. Zhang (Xinzhi); P. Mitchell (Paul); T.Y. Wong (Tien Yin)

    2012-01-01

    textabstractOBJECTIVE - To examine the global prevalence and major risk factors for diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) among people with diabetes. RESEARCH DESIGN AND METHODS - A pooled analysis using individual participant data from population-based studies

  9. Value-at-Risk and Expected Shortfall for the major digital currencies

    OpenAIRE

    Stavroyiannis, Stavros

    2017-01-01

    Digital currencies and cryptocurrencies have hesitantly started to penetrate the investors, and the next step will be the regulatory risk management framework. We examine the Value-at-Risk and Expected Shortfall properties for the major digital currencies, Bitcoin, Ethereum, Litecoin, and Ripple. The methodology used is GARCH modelling followed by Filtered Historical Simulation. We find that digital currencies are subject to a higher risk, therefore, to higher sufficient buffer and risk capit...

  10. Age as Risk Factor for Death from Pandemic (H1N1) 2009, Chile

    Science.gov (United States)

    Dabanch, Jeannette; Nájera, Manuel; González, Claudia; Guerrero, Andrea; Olea, Andrea; Fasce, Rodrigo; Morales, Cecilia; Vega, Jeanette

    2011-01-01

    Pandemic (H1N1) 2009 affected Chile during the winter of 2009. The hospitalization rate was 0.56% overall and 3.47% for persons >60 years of age at risk for severe disease and death independent of concurrent conditions. Age >60 years was the major risk factor for death from pandemic (H1N1) 2009. PMID:21762580

  11. An intron capture strategy used to identify and map a lysyl oxidase-like gene on chromosome 9 in the mouse

    Energy Technology Data Exchange (ETDEWEB)

    Wydner, K.S.; Passmore, H.C. [Rutgers Univ., Piscataway, NJ (United States); Kim, Houngho; Csiszar, K.; Boyd, C.D. [UMDNJ, New Brunswick, NJ (United States)

    1997-03-01

    An intron capture strategy involving use of polymerase chain reaction was used to identify and map the mouse homologue of a human lysyl oxidase-like gene (LOXL). Oligonucleotides complementary to conserved domains within exons 4 and 5 of the human lysyl oxidase-like gene were used to amplify the corresponding segment from mouse genomic DNA. Sequencing of the resulting mouse DNA fragment of approximately 1 kb revealed that the exon sequences at the ends of the amplified fragment are highly homologous (90% nucleotide identity) to exons 4 and 5 of the human lysyl oxidase-like gene. An AluI restriction site polymorphism within intron 4 was used to map the mouse lysyl oxidase-like gene (Loxl) to mouse Chromosome 9 in a region that shares linkage conservation with human chromosome 15q24, to which the LOXL was recently mapped. 22 refs., 3 figs.

  12. Major bleeding risks of different low-molecular-weight heparin agents: a cohort study in 12 934 patients treated for acute venous thrombosis.

    Science.gov (United States)

    van Rein, N; Biedermann, J S; van der Meer, F J M; Cannegieter, S C; Wiersma, N; Vermaas, H W; Reitsma, P H; Kruip, M J H A; Lijfering, W M

    2017-07-01

    Essentials Low-molecular-weight-heparins (LMWH) kinetics differ which may result in different bleeding risks. A cohort of 12 934 venous thrombosis patients on LMWH was followed until major bleeding. The absolute major bleeding risk was low among patients registered at the anticoagulation clinic. Once-daily dosing was associated with a lower bleeding risk as compared with twice-daily. Background Low-molecular-weight heparins (LMWHs) are considered members of a class of drugs with similar anticoagulant properties. However, pharmacodynamics and pharmacokinetics between LMWHs differ, which may result in different bleeding risks. As these agents are used by many patients, small differences may lead to a large effect on numbers of major bleeding events. Objectives To determine major bleeding risks for different LMWH agents and dosing schedules. Methods A cohort of acute venous thrombosis patients from four anticoagulation clinics who used an LMWH and a vitamin K antagonist were followed until they ceased LMWH treatment or until major bleeding. Exposures were classified according to different types of LMWHs and for b.i.d. and o.d. use. Cumulative incidences for major bleeding per 1000 patients and risk ratios were calculated and adjusted for study center. Results The study comprised 12 934 patients with a mean age of 59 years; 6218 (48%) were men. The cumulative incidence of major bleeding was 2.5 per 1000 patients (95% confidence interval [CI], 1.7-3.5). Enoxaparin b.i.d. or o.d. was associated with a relative bleeding risk of 1.7 (95% CI, 0.2-17.5) compared with nadroparin o.d. In addition, a nadroparin b.i.d. dosing schedule was associated with a 2.0-fold increased major bleeding risk (95% CI, 0.8-5.1) as compared with a nadroparin o.d. dosing schedule. Conclusions Absolute major bleeding rates were low for all LMWH agents and dosing schedules in a large unselected cohort. Nevertheless, twice-daily dosing with nadroparin appeared to be associated with an increased

  13. Functional and structural brain correlates of risk for major depression in children with familial depression

    Directory of Open Access Journals (Sweden)

    Xiaoqian J. Chai

    2015-01-01

    Full Text Available Despite growing evidence for atypical amygdala function and structure in major depression, it remains uncertain as to whether these brain differences reflect the clinical state of depression or neurobiological traits that predispose individuals to major depression. We examined function and structure of the amygdala and associated areas in a group of unaffected children of depressed parents (at-risk group and a group of children of parents without a history of major depression (control group. Compared to the control group, the at-risk group showed increased activation to fearful relative to neutral facial expressions in the amygdala and multiple cortical regions, and decreased activation to happy relative to neutral facial expressions in the anterior cingulate cortex and supramarginal gyrus. At-risk children also exhibited reduced amygdala volume. The extensive hyperactivation to negative facial expressions and hypoactivation to positive facial expressions in at-risk children are consistent with behavioral evidence that risk for major depression involves a bias to attend to negative information. These functional and structural brain differences between at-risk children and controls suggest that there are trait neurobiological underpinnings of risk for major depression.

  14. Distribution of major health risks: findings from the Global Burden of Disease study.

    Directory of Open Access Journals (Sweden)

    Anthony Rodgers

    2004-10-01

    Full Text Available Most analyses of risks to health focus on the total burden of their aggregate effects. The distribution of risk-factor-attributable disease burden, for example by age or exposure level, can inform the selection and targeting of specific interventions and programs, and increase cost-effectiveness.For 26 selected risk factors, expert working groups conducted comprehensive reviews of data on risk-factor exposure and hazard for 14 epidemiological subregions of the world, by age and sex. Age-sex-subregion-population attributable fractions were estimated and applied to the mortality and burden of disease estimates from the World Health Organization Global Burden of Disease database. Where possible, exposure levels were assessed as continuous measures, or as multiple categories. The proportion of risk-factor-attributable burden in different population subgroups, defined by age, sex, and exposure level, was estimated. For major cardiovascular risk factors (blood pressure, cholesterol, tobacco use, fruit and vegetable intake, body mass index, and physical inactivity 43%-61% of attributable disease burden occurred between the ages of 15 and 59 y, and 87% of alcohol-attributable burden occurred in this age group. Most of the disease burden for continuous risks occurred in those with only moderately raised levels, not among those with levels above commonly used cut-points, such as those with hypertension or obesity. Of all disease burden attributable to being underweight during childhood, 55% occurred among children 1-3 standard deviations below the reference population median, and the remainder occurred among severely malnourished children, who were three or more standard deviations below median.Many major global risks are widely spread in a population, rather than restricted to a minority. Population-based strategies that seek to shift the whole distribution of risk factors often have the potential to produce substantial reductions in disease burden.

  15. Risk of major depression in patients with chronic renal failure on different treatment modalities: A matched-cohort and population-based study in Taiwan.

    Science.gov (United States)

    Chen, Shih-Feng; Wang, I-Jen; Lang, Hui-Chu

    2016-01-01

    The influence of different treatment modalities on the risk of developing major depression in patients with chronic renal failure (CRF) is not well understood. We aimed to explore the incidence of major depression among patients with CRF who were on different dialysis modalities, who had received renal transplantation (RT), and those who had not yet received any of the aforementioned renal replacement therapies. We conducted a population-based retrospective cohort study using a national health insurance research database. This study investigated 89,336 study controls, 17,889 patients with chronic kidney disease on conservative treatment, 3823 patients on hemodialysis (HD), 351 patients on peritoneal dialysis (PD), and 322 patients who had RT. We followed all individuals until the occurrence of major depression or the date of loss to follow-up. The PD group had the highest risk (hazard ratio [HR] 2.43; 95% confidence interval [CI] 1.26-4.69), whereas the RT group had the lowest risk (HR 0.18; 95% CI 0.03-1.29) of developing major depression compared with the control group. Patients initiated on PD had a higher risk of developing major depression than patients initiated on HD (pairwise comparison: HR 2.20; 95% CI 1.09-4.46). Different treatment modalities are associated with different risks of developing major depression in patients with CRF. Among renal replacement therapies, patients who have had RT have the lowest risk of developing major depression. Patients who initiate renal therapy on PD may have a higher risk of major depression compared with patients who initiate renal therapy on HD. © 2015 International Society for Hemodialysis.

  16. Suicide risk in placebo-controlled studies of major depression

    NARCIS (Netherlands)

    Storosum, J. G.; van Zwieten, B. J.; van den Brink, W.; Gersons, B. P.; Broekmans, A. W.

    2001-01-01

    The purpose of this study was to determine if fear of an increased risk of attempted suicide in placebo groups participating in placebo-controlled studies is an argument against the performance of placebo-controlled trials in studies of major depression. All short-term and long-term,

  17. Female Gender and Acne Disease Are Jointly and Independently Associated with the Risk of Major Depression and Suicide: A National Population-Based Study

    Directory of Open Access Journals (Sweden)

    Yi-Chien Yang

    2014-01-01

    Full Text Available Acne is a common disease in adolescence with female preponderance. It could cause poor self-esteem and social phobia. Previous studies based on questionnaires from several thousands of adolescents showed that acne is associated with major depression and suicide. However, the gender- and age-specific risk of depression and suicide in patients with acne remain largely unknown. Using a database from the National Health Insurance, which included 98% of the population of Taiwan in 2006, we identified patients of acne, major depression, and suicide based on ICD-9-CM codes. Totally 47111 patients with acne were identified (16568 males and 30543 females from 1 million subjects. The youths of 7–12 years had the highest prevalence of acne (14.39%. Major depression was more common in those with acne (0.77% than controls (0.56% , P < 0.0001 regardless of gender. Multiple logistic regression showed an increased risk of major depression in women without acne (OR = 1.85, 95% CI 1.75–1.96. The risk is additive in women with acne (OR = 2.78, 95% CI 2.43–3.17. Similar additive risk of suicide was noticed in women with acne. In conclusion, acne and gender, independently and jointly, are associated with major depression and suicide. Special medical support should be warranted in females with acne for the risk of major depression and suicide.

  18. The risk of a major nuclear accident: calculation and perception of probabilities

    International Nuclear Information System (INIS)

    Leveque, Francois

    2013-07-01

    The accident at Fukushima Daiichi, Japan, occurred on 11 March 2011. This nuclear disaster, the third on such a scale, left a lasting mark in the minds of hundreds of millions of people. Much as Three Mile Island or Chernobyl, yet another place will be permanently associated with a nuclear power plant which went out of control. Fukushima Daiichi revived the issue of the hazards of civil nuclear power, stirring up all the associated passion and emotion. The whole of this paper is devoted to the risk of a major nuclear accident. By this we mean a failure initiating core meltdown, a situation in which the fuel rods melt and mix with the metal in their cladding. Such accidents are classified as at least level 5 on the International Nuclear Event Scale. The Three Mile Island accident, which occurred in 1979 in the United States, reached this level of severity. The explosion of reactor 4 at the Chernobyl plant in Ukraine in 1986 and the recent accident in Japan were classified as class 7, the highest grade on this logarithmic scale. The main difference between the top two levels and level 5 relates to a significant or major release of radioactive material to the environment. In the event of a level-5 accident, damage is restricted to the inside of the plant, whereas, in the case of level-7 accidents, huge areas of land, above or below the surface, and/or sea may be contaminated. Before the meltdown of reactors 1, 2 and 3 at Fukushima Daiichi, eight major accidents affecting nuclear power plants had occurred worldwide. This is a high figure compared with the one calculated by the experts. Observations in the field do not appear to fit the results of the probabilistic models of nuclear accidents produced since the 1970's. Oddly enough the number of major accidents is closer to the risk as perceived by the general public. In general we tend to overestimate any risk relating to rare, fearsome accidents. What are we to make of this divergence? How are we to reconcile

  19. Obesity genes and risk of major depressive disorder in a multiethnic population: a cross-sectional study.

    Science.gov (United States)

    Samaan, Zainab; Lee, Yvonne K; Gerstein, Hertzel C; Engert, James C; Bosch, Jackie; Mohan, Viswanathan; Diaz, Rafael; Yusuf, Salim; Anand, Sonia S; Meyre, David

    2015-12-01

    Observational studies have shown a positive association between obesity (body mass index [BMI] ≥ 30 kg/m2) and depression. Around 120 obesity-associated loci have been identified, but genetic variants associated with depression remain elusive. Recently, our team reported that the fat mass and obesity-associated (FTO) gene rs9939609 obesity-risk variant is paradoxically inversely associated with the risk of depression. This finding raises the question as to whether other obesity-associated genetic variants are also associated with depression. Twenty-one obesity gene variants other than FTO were selected from a custom ∼50,000 single-nucleotide polymorphisms (SNPs) genotyping array (ITMAT-Broad-CARe array). Associations of these 21 SNPs and an unweighted genotype score with BMI and major depressive disorder (determined using the DSM-IV diagnostic criteria) were tested in 3,209 cases and 14,195 noncases, using baseline data collected from July 2001 to August 2003 from the multiethnic EpiDREAM study. Body mass index was positively associated with depression status (odds ratio [OR] = 1.02; 95% CI, 1.02-1.03 per BMI unit; P = 2.9 × 10(-12), adjusted for age, sex, and ethnicity). Six of 21 genetic variants (rs1514176 [TNN13K], rs2206734 [CDKAL1], rs11671664 [GIPR], rs2984618 [TAL1], rs3824755 [NT5C2], and rs7903146 [TCF7L2]) and the genotype score were significantly associated with BMI (1.47 × 10(-14) ≤ P ≤ .04). Of the 21 SNPs, TAL1 rs2984618 obesity-risk allele was associated with a higher risk of major depressive disorder (P = 1.79 × 10(-4), adjusted for age, sex, BMI, and ethnicity), and BDNF rs1401635 demonstrated significant ethnic-dependent association with major depressive disorder (OR = 0.88; 95% CI, 0.80-0.97; P = .01 in non-Europeans and OR = 1.11; 95% CI, 1.02-1.20; P = .02 in Europeans; Pinteraction = 2.73 × 10(-4)). The genotype score, calculated with or without FTO rs9939609, and adjusted for the same covariates, was not associated with

  20. Genetic association between NRG1 and schizophrenia, major depressive disorder, bipolar disorder in Han Chinese population.

    Science.gov (United States)

    Wen, Zujia; Chen, Jianhua; Khan, Raja Amjad Waheed; Song, Zhijian; Wang, Meng; Li, Zhiqiang; Shen, Jiawei; Li, Wenjin; Shi, Yongyong

    2016-04-01

    Schizophrenia, major depressive disorder, and bipolar disorder are three major psychiatric disorders affecting around 0.66%, 3.3%, and 1.5% of the Han Chinese population respectively. Several genetic linkage analyses and genome wide association studies identified NRG1 as a susceptibility gene of schizophrenia, which was validated by its role in neurodevelopment, glutamate, and other neurotransmitter receptor expression regulation. To further investigate whether NRG1 is a shared risk gene for major depressive disorder, bipolar disorder as well as schizophrenia, we performed an association study among 1,248 schizophrenia cases, 1,056 major depression cases, 1,344 bipolar disorder cases, and 1,248 controls. Totally 15 tag SNPs were genotyped and analyzed, and no population stratification was found in our sample set. Among the sites, rs4236710 (corrected Pgenotye  = 0.015) and rs4512342 (Pallele  = 0.03, Pgenotye  = 0.045 after correction) were associated with schizophrenia, and rs2919375 (corrected Pgenotye  = 0.004) was associated with major depressive disorder. The haplotype rs4512342-rs6982890 showed association with schizophrenia (P = 0.03 for haplotype "TC" after correction), and haplotype rs4531002-rs11989919 proved to be a shared risk factor for both major depressive disorder ("CC": corrected P = 0.009) and bipolar disorder ("CT": corrected P = 0.003). Our results confirmed that NRG1 was a shared common susceptibility gene for major mental disorders in Han Chinese population. © 2016 Wiley Periodicals, Inc.

  1. Putting risk analysis into perspective: a comparative review of major societal risk studies of nuclear power

    International Nuclear Information System (INIS)

    Dooley, J.E.; Hansson, B.; Kaspersson, R.; ORiordan, T.; Paschen, H.

    1983-04-01

    The emphasis in this final report of the project Evaluation of major Swedish energy risk assessments in an international perspective is shifted towards the comparative aspect. The comprehensive nuclear risk study has been used as an instrument to satisfy many needs simultaneously. The research consisted of an examination of existing risk studies of five nations, namely West Germany, UK, US, Canada and Sweden. The effect of nuclear risk studies on society at large and on public attitude towards nuclear power in particular is discussed. Finally, the effect on the nuclear establishment is analysed. (G.B.)

  2. Birth order and risk taking in athletics: a meta-analysis and study of major league baseball.

    Science.gov (United States)

    Sulloway, Frank J; Zweigenhaft, Richard L

    2010-11-01

    According to expectations derived from evolutionary theory, younger siblings are more likely than older siblings to participate in high-risk activities. The authors test this hypothesis by conducting a meta-analysis of 24 previous studies involving birth order and participation in dangerous sports. The odds of laterborns engaging in such activities were 1.48 times greater than for firstborns (N = 8,340). The authors also analyze performance data on 700 brothers who played major league baseball. Consistent with their greater expected propensity for risk taking, younger brothers were 10.6 times more likely to attempt the high-risk activity of base stealing and 3.2 times more likely to steal bases successfully (odds ratios). In addition, younger brothers were significantly superior to older brothers in overall batting success, including two measures associated with risk taking. As expected, significant heterogeneity among various performance measures for major league baseball players indicated that older and younger brothers excelled in different aspects of the game.

  3. Eating disorder risk, exercise dependence, and body weight dissatisfaction among female nutrition and exercise science university majors.

    Science.gov (United States)

    Harris, Natalie; Gee, David; d'Acquisto, Debra; Ogan, Dana; Pritchett, Kelly

    2015-09-01

    Past research has examined eating disorder risk among college students majoring in Nutrition and has suggested an increased risk, while other studies contradict these results. Exercise Science majors, however, have yet to be fully examined regarding their risk for eating disorders and exercise dependence. Based on pressures to fit the image associated with careers related to these two disciplines, research is warranted to examine the potential risk for both eating disorder and exercise dependence. The purpose of this study is to compare eating disorder risk, exercise dependence, and body weight dissatisfaction (BWD) between Nutrition and Exercise Science majors, compared to students outside of these career pathways. Participants (n = 89) were divided into three groups based on major; Nutrition majors (NUTR; n = 31), Exercise Science majors (EXSC; n = 30), and other majors (CON; n = 28). Participants were given the EAT-26 questionnaire and the Exercise Dependence Scale. BWD was calculated as the discrepancy between actual BMI and ideal BMI. The majority of participants expressed a desire to weigh less (83%) and EXSC had significantly (p = .03) greater BWD than NUTR. However, there were no significant differences in eating disorder risk or exercise dependence among majors. This study suggested there was no significant difference in eating disorder risk or exercise dependence between the three groups (NUTR, EXSC, and CON).

  4. The GSK3B gene confers risk for both major depressive disorder and schizophrenia in the Han Chinese population.

    Science.gov (United States)

    Chen, Jianhua; Wang, Meng; Waheed Khan, Raja Amjad; He, Kuanjun; Wang, Qingzhong; Li, Zhiqiang; Shen, Jiawei; Song, Zhijian; Li, Wenjin; Wen, Zujia; Jiang, Yiwen; Xu, Yifeng; Shi, Yongyong; Ji, Weidong

    2015-10-01

    Glycogen synthease kinase-3B is a key gene encoding a protein kinase which is abundant in brain, and is involved in signal transduction cascades of neuronal cell development and energy metabolism. Previous researches proposed GSK3B as a potential region for schizophrenia. To validate the susceptibility of GSK3B to major depressive disorder, and to investigate the overlapping risk conferred by GSK3B for mental disorders, we performed a large-scale case-control study, analyzed 6 tag single nucleotide polymorphisms using TaqMan® technology in 1,045 major depressive disorder patients, 1,235 schizophrenia patients and 1,235 normal controls of Han Chinese origin. We found rs334535 (Pallele=2.79E-03, Pgenotype=5.00E-03, OR=1.429) and rs2199503 (Pallele=0.020, Pgenotype= 0.040, OR=1.157) showed association with major depressive disorder before Bonferroni correction. rs6771023 (adjusted Pallele=1.64E-03, adjusted Pgenotype=6.00E-03, OR=0.701) and rs2199503 (adjusted Pallele=0.001, adjusted Pgenotype=0.002, OR=1.251) showed significant association with schizophrenia after Bonferroni correction. rs2199503 (adjusted Pallele=1.70E-03, adjusted Pgenotype=0.006, OR=1.208) remained to be significant in the combined cases of major depressive disorder and schizophrenia after Bonferroni correction. Further validations of our findings in samples with larger scale are suggested, and functional genomic study is needed to elucidate the role of GSK3B in signal pathway and psychiatric disorders. Our results provide evidence that the GSK3B gene could be a promising region which contains genetic risk for both major depressive disorder and schizophrenia in the Han Chinese population. The study on variants conferring overlapping risk for multiple psychiatric disorders could be tangible pathogenesis support and clinical or diagnostic references. Copyright © 2015. Published by Elsevier B.V.

  5. Major risks and financial guarantees provided by the State in France

    International Nuclear Information System (INIS)

    Brassard, Guy

    2012-01-01

    France's system for indemnifying damage from natural catastrophe is exemplary, whether for floods, storms, or subsidence. However, France is not equipped with the financial capacity to deal with the damage resulting from an exceptional disaster, such as an earthquake on the Mediterranean coast, or a nuclear meltdown. Major catastrophes could be a significant risk to the financial stability of the State today, because the State is in fact the ultimate insurer of its citizens and its institutions. It would be wise to built up reserves in order to enhance the financial resources of the State and to provide a uniform guarantee covering major risks, whatever the cause of the damage may be. (author)

  6. The excess risk of major osteoporotic fractures in hypothyroidism is driven by cumulative hyperthyroid as opposed to hypothyroid time

    DEFF Research Database (Denmark)

    Abrahamsen, Bo; Jørgensen, Henrik L; Laulund, Anne Sofie

    2015-01-01

    was not associated with an increased risk of hip fracture (HR 0.90; 95% CI, 0.80 to 1.02) or major osteoporotic fractures (HR 0.97; 95% CI, 0.90 to 1.05), nor was subsequent thyroxine prescription predictive of increased risk of fractures. The number of subsequent 6-month periods with low TSH-suggesting excessive...

  7. The NVL gene confers risk for both major depressive disorder and schizophrenia in the Han Chinese population.

    Science.gov (United States)

    Wang, Meng; Chen, Jianhua; He, Kuanjun; Wang, Qingzhong; Li, Zhiqiang; Shen, Jiawei; Wen, Zujia; Song, Zhijian; Xu, Yifeng; Shi, Yongyong

    2015-10-01

    NVL (nuclear VCP (valosin containing protein)/p97-Like), a member of the AAA-ATPase (ATPases associated with various cellular activities) family, encodes a novel hTERT (human telomerase reverse transcriptase)-interacting protein NVL2 which is a telomerase component essential for holoenzyme assembly. Previous researches have reported the impacts of telomerase activity on mental illness and the potential association between NVL and major depressive disorder. To validate the susceptibility of NVL to major depressive disorder, and to investigate the overlapping risk conferred by NVL for both major depressive disorder and schizophrenia, we analyzed 9 tag single nucleotide polymorphisms (tag SNPs) using TaqMan® technology, in 1045 major depressive disorder patients, 1235 schizophrenia patients and 1235 normal controls of Han Chinese origin. We found that rs10916583 (P(allele) = 0.020, P(genotype) = 0.028, OR = 1.156) and rs16846649 (adjusted P(allele) = 0.014, P(genotype) = 0.007, OR = 0.718) were associated with major depressive disorder, while rs10916583 (adjusted P(allele) = 1.08E-02, OR = 1.213), rs16846649 (adjusted P(allele) = 7.40E-06, adjusted P(genotype) = 8.07E-05, OR = 0.598) and rs10799541 (adjusted P(allele) = 8.10E-03, adjusted P(genotype) = 0.049, OR= 0.826) showed statistically significant association with schizophrenia after Bonferroni correction. Furthermore, rs10916583 (adjusted P(allele) = 9.00E-03, adjusted P(genotype) = 3.15E-02, OR = 1.187) and rs16846649 (adjusted P(allele) = 8.92E-06, adjusted P(genotype) = 8.84E-05, OR = 0.653) remained strongly associated with the analysis of combined cases of major depressive disorder and schizophrenia after Bonferroni correction. Our results indicated that the NVL gene may contain overlapping common genetic risk factors for major depressive disorder and schizophrenia in the Han Chinese population. The roles of NVL in telomerase biogenesis were also highlighted in psychiatric pathogenesis. The study on

  8. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression.

    Science.gov (United States)

    Wray, Naomi R; Ripke, Stephan; Mattheisen, Manuel; Trzaskowski, Maciej; Byrne, Enda M; Abdellaoui, Abdel; Adams, Mark J; Agerbo, Esben; Air, Tracy M; Andlauer, Till M F; Bacanu, Silviu-Alin; Bækvad-Hansen, Marie; Beekman, Aartjan F T; Bigdeli, Tim B; Binder, Elisabeth B; Blackwood, Douglas R H; Bryois, Julien; Buttenschøn, Henriette N; Bybjerg-Grauholm, Jonas; Cai, Na; Castelao, Enrique; Christensen, Jane Hvarregaard; Clarke, Toni-Kim; Coleman, Jonathan I R; Colodro-Conde, Lucía; Couvy-Duchesne, Baptiste; Craddock, Nick; Crawford, Gregory E; Crowley, Cheynna A; Dashti, Hassan S; Davies, Gail; Deary, Ian J; Degenhardt, Franziska; Derks, Eske M; Direk, Nese; Dolan, Conor V; Dunn, Erin C; Eley, Thalia C; Eriksson, Nicholas; Escott-Price, Valentina; Kiadeh, Farnush Hassan Farhadi; Finucane, Hilary K; Forstner, Andreas J; Frank, Josef; Gaspar, Héléna A; Gill, Michael; Giusti-Rodríguez, Paola; Goes, Fernando S; Gordon, Scott D; Grove, Jakob; Hall, Lynsey S; Hannon, Eilis; Hansen, Christine Søholm; Hansen, Thomas F; Herms, Stefan; Hickie, Ian B; Hoffmann, Per; Homuth, Georg; Horn, Carsten; Hottenga, Jouke-Jan; Hougaard, David M; Hu, Ming; Hyde, Craig L; Ising, Marcus; Jansen, Rick; Jin, Fulai; Jorgenson, Eric; Knowles, James A; Kohane, Isaac S; Kraft, Julia; Kretzschmar, Warren W; Krogh, Jesper; Kutalik, Zoltán; Lane, Jacqueline M; Li, Yihan; Li, Yun; Lind, Penelope A; Liu, Xiaoxiao; Lu, Leina; MacIntyre, Donald J; MacKinnon, Dean F; Maier, Robert M; Maier, Wolfgang; Marchini, Jonathan; Mbarek, Hamdi; McGrath, Patrick; McGuffin, Peter; Medland, Sarah E; Mehta, Divya; Middeldorp, Christel M; Mihailov, Evelin; Milaneschi, Yuri; Milani, Lili; Mill, Jonathan; Mondimore, Francis M; Montgomery, Grant W; Mostafavi, Sara; Mullins, Niamh; Nauck, Matthias; Ng, Bernard; Nivard, Michel G; Nyholt, Dale R; O'Reilly, Paul F; Oskarsson, Hogni; Owen, Michael J; Painter, Jodie N; Pedersen, Carsten Bøcker; Pedersen, Marianne Giørtz; Peterson, Roseann E; Pettersson, Erik; Peyrot, Wouter J; Pistis, Giorgio; Posthuma, Danielle; Purcell, Shaun M; Quiroz, Jorge A; Qvist, Per; Rice, John P; Riley, Brien P; Rivera, Margarita; Saeed Mirza, Saira; Saxena, Richa; Schoevers, Robert; Schulte, Eva C; Shen, Ling; Shi, Jianxin; Shyn, Stanley I; Sigurdsson, Engilbert; Sinnamon, Grant B C; Smit, Johannes H; Smith, Daniel J; Stefansson, Hreinn; Steinberg, Stacy; Stockmeier, Craig A; Streit, Fabian; Strohmaier, Jana; Tansey, Katherine E; Teismann, Henning; Teumer, Alexander; Thompson, Wesley; Thomson, Pippa A; Thorgeirsson, Thorgeir E; Tian, Chao; Traylor, Matthew; Treutlein, Jens; Trubetskoy, Vassily; Uitterlinden, André G; Umbricht, Daniel; Van der Auwera, Sandra; van Hemert, Albert M; Viktorin, Alexander; Visscher, Peter M; Wang, Yunpeng; Webb, Bradley T; Weinsheimer, Shantel Marie; Wellmann, Jürgen; Willemsen, Gonneke; Witt, Stephanie H; Wu, Yang; Xi, Hualin S; Yang, Jian; Zhang, Futao; Arolt, Volker; Baune, Bernhard T; Berger, Klaus; Boomsma, Dorret I; Cichon, Sven; Dannlowski, Udo; de Geus, E C J; DePaulo, J Raymond; Domenici, Enrico; Domschke, Katharina; Esko, Tõnu; Grabe, Hans J; Hamilton, Steven P; Hayward, Caroline; Heath, Andrew C; Hinds, David A; Kendler, Kenneth S; Kloiber, Stefan; Lewis, Glyn; Li, Qingqin S; Lucae, Susanne; Madden, Pamela F A; Magnusson, Patrik K; Martin, Nicholas G; McIntosh, Andrew M; Metspalu, Andres; Mors, Ole; Mortensen, Preben Bo; Müller-Myhsok, Bertram; Nordentoft, Merete; Nöthen, Markus M; O'Donovan, Michael C; Paciga, Sara A; Pedersen, Nancy L; Penninx, Brenda W J H; Perlis, Roy H; Porteous, David J; Potash, James B; Preisig, Martin; Rietschel, Marcella; Schaefer, Catherine; Schulze, Thomas G; Smoller, Jordan W; Stefansson, Kari; Tiemeier, Henning; Uher, Rudolf; Völzke, Henry; Weissman, Myrna M; Werge, Thomas; Winslow, Ashley R; Lewis, Cathryn M; Levinson, Douglas F; Breen, Gerome; Børglum, Anders D; Sullivan, Patrick F

    2018-05-01

    Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.

  9. Managing major chemical accidents in China: Towards effective risk information

    NARCIS (Netherlands)

    He, G.; Zhang, L.; Lu, Y.; Mol, A.P.J.

    2011-01-01

    Chemical industries, from their very inception, have been controversial due to the high risks they impose on safety of human beings and the environment. Recent decades have witnessed increasing impacts of the accelerating expansion of chemical industries and chemical accidents have become a major

  10. Major bleeding and intracranial hemorrhage risk prediction in patients with atrial fibrillation: Attention to modifiable bleeding risk factors or use of a bleeding risk stratification score? A nationwide cohort study.

    Science.gov (United States)

    Chao, Tze-Fan; Lip, Gregory Y H; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Liao, Jo-Nan; Chung, Fa-Po; Chen, Tzeng-Ji; Chen, Shih-Ann

    2018-03-01

    While modifiable bleeding risks should be addressed in all patients with atrial fibrillation (AF), use of a bleeding risk score enables clinicians to 'flag up' those at risk of bleeding for more regular patient contact reviews. We compared a risk assessment strategy for major bleeding and intracranial hemorrhage (ICH) based on modifiable bleeding risk factors (referred to as a 'MBR factors' score) against established bleeding risk stratification scores (HEMORR 2 HAGES, HAS-BLED, ATRIA, ORBIT). A nationwide cohort study of 40,450 AF patients who received warfarin for stroke prevention was performed. The clinical endpoints included ICH and major bleeding. Bleeding scores were compared using receiver operating characteristic (ROC) curves (areas under the ROC curves [AUCs], or c-index) and the net reclassification index (NRI). During a follow up of 4.60±3.62years, 1581 (3.91%) patients sustained ICH and 6889 (17.03%) patients sustained major bleeding events. All tested bleeding risk scores at baseline were higher in those sustaining major bleeds. When compared to no ICH, patients sustaining ICH had higher baseline HEMORR 2 HAGES (p=0.003), HAS-BLED (pbleeding scores, c-indexes were significantly higher compared to MBR factors (pbleeding. C-indexes for the MBR factors score was significantly lower compared to all other scores (De long test, all pbleeding risk scores for major bleeding (all pbleeding risk scores had modest predictive value for predicting major bleeding but the best predictive value and NRI was found for the HAS-BLED score. Simply depending on modifiable bleeding risk factors had suboptimal predictive value for the prediction of major bleeding in AF patients, when compared to the HAS-BLED score. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  11. The association between suicide risk and self-esteem in Japanese university students with major depressive episodes of major depressive disorder.

    Science.gov (United States)

    Mitsui, Nobuyuki; Asakura, Satoshi; Shimizu, Yusuke; Fujii, Yutaka; Toyomaki, Atsuhito; Kako, Yuki; Tanaka, Teruaki; Kitagawa, Nobuki; Inoue, Takeshi; Kusumi, Ichiro

    2014-01-01

    The suicide risk among young adults is related to multiple factors; therefore, it is difficult to predict and prevent suicidal behavior. We conducted the present study to reveal the most important factors relating to suicidal ideation in Japanese university students with major depressive episodes (MDEs) of major depressive disorder (MDD). The subjects were 30 Japanese university students who had MDEs of MDD, and were aged between 18 and 26 years old. They were divided into two groups - without suicide risk group (n=15), and with suicide risk group (n=15) - based on the results of the Mini-International Neuropsychiatric Interview. Additionally, healthy controls were recruited from the same population (n=15). All subjects completed the self-assessment scales including the Beck Depression Inventory 2nd edition (BDI-II), the Beck Hopelessness Scale (BHS), Rosenberg's Self-Esteem Scale (RSES), and SF-36v2™ (The Medical Outcomes Study 36-item short-form health survey version 2), and they were all administered a battery of neuropsychological tests. The RSES score of the suicide risk group was significantly lower than the RSES score of the without suicide risk group, whereas the BDI-II score and the BHS score were not significantly different between the two groups. The mean social functioning score on the SF-36v2 of the with suicide risk group was significantly lower than that of the without suicide risk group. The individual's self-esteem and social functioning may play an important role in suicide risk among young adults with MDEs of MDD.

  12. Cognitive complexity of the medical record is a risk factor for major adverse events.

    Science.gov (United States)

    Roberson, David; Connell, Michael; Dillis, Shay; Gauvreau, Kimberlee; Gore, Rebecca; Heagerty, Elaina; Jenkins, Kathy; Ma, Lin; Maurer, Amy; Stephenson, Jessica; Schwartz, Margot

    2014-01-01

    Patients in tertiary care hospitals are more complex than in the past, but the implications of this are poorly understood as "patient complexity" has been difficult to quantify. We developed a tool, the Complexity Ruler, to quantify the amount of data (as bits) in the patient’s medical record. We designated the amount of data in the medical record as the cognitive complexity of the medical record (CCMR). We hypothesized that CCMR is a useful surrogate for true patient complexity and that higher CCMR correlates with risk of major adverse events. The Complexity Ruler was validated by comparing the measured CCMR with physician rankings of patient complexity on specific inpatient services. It was tested in a case-control model of all patients with major adverse events at a tertiary care pediatric hospital from 2005 to 2006. The main outcome measure was an externally reported major adverse event. We measured CCMR for 24 hours before the event, and we estimated lifetime CCMR. Above empirically derived cutoffs, 24-hour and lifetime CCMR were risk factors for major adverse events (odds ratios, 5.3 and 6.5, respectively). In a multivariate analysis, CCMR alone was essentially as predictive of risk as a model that started with 30-plus clinical factors. CCMR correlates with physician assessment of complexity and risk of adverse events. We hypothesize that increased CCMR increases the risk of physician cognitive overload. An automated version of the Complexity Ruler could allow identification of at-risk patients in real time.

  13. The risk of major and any (non-hip) fragility fracture after hip fracture in the United Kingdom : 2000-2010

    NARCIS (Netherlands)

    Gibson-Smith, D; Klop, C; Elders, P J M; Welsing, P M J; van Schoor, N; Leufkens, H G M; Harvey, N C; van Staa, T P; de Vries, F

    2014-01-01

    UNLABELLED: The risk of a subsequent major or any fracture after a hip fracture and secular trends herein were examined. Within 1 year, 2.7 and 8.4% of patients sustained a major or any (non-hip) fracture, which increased to 14.7 and 32.5% after 5 years. Subsequent fracture rates increased during

  14. South Asian Ethnicity as a Risk Factor for Major Adverse Cardiovascular Events after Renal Transplantation

    Science.gov (United States)

    Vangala, Sai K.; Silver, Samuel A.; Wong, Steven C.W.; Huang, Michael; Rapi, Lindita; Nash, Michelle M.; Zaltzman, Jeffrey S.

    2011-01-01

    Summary Background and objectives South Asians (SAs) comprise 25% of all Canadian visible minorities. SAs constitute a group at high risk for cardiovascular disease in the general population, but the risk in SA kidney transplant recipients has never been studied. Design, setting, participants, & measurements In a cohort study of 864 kidney recipients transplanted from 1998 to 2007 and followed to June 2009, we identified risk factors including ethnicity associated with major cardiac events (MACEs, a composite of nonfatal myocardial infarction, coronary intervention, and cardiac death) within and beyond 3 months after transplant. Kaplan-Meier methodology and multivariate Cox regression analysis were used to determine risk factors for MACEs. Results There was no difference among SAs (n = 139), whites (n = 550), blacks (n = 65), or East Asians (n = 110) in baseline risk, including pre-existing cardiac disease. Post-transplant MACE rate in SAs was 4.4/100 patient-years compared with 1.31, 1.16, and 1.61/100 patient-years in whites, blacks, and East Asians, respectively (P diabetes, systolic BP, and prior cardiac disease. SAs also experienced more MACEs within 3 months after transplant compared with whites (P < 0.0001), blacks (P = 0.04), and East Asians (P = 0.006). However, graft and patient survival was similar to other groups. Conclusions SA ethnicity is an independent risk factor for post-transplant cardiac events. Further study of this high-risk group is warranted. PMID:20884776

  15. Higher 5-HT1A autoreceptor binding as an endophenotype for major depressive disorder identified in high risk offspring - A pilot study.

    Science.gov (United States)

    Milak, Matthew S; Pantazatos, Spiro; Rashid, Rain; Zanderigo, Francesca; DeLorenzo, Christine; Hesselgrave, Natalie; Ogden, R Todd; Oquendo, Maria A; Mulhern, Stephanie T; Miller, Jeffrey M; Burke, Ainsley K; Parsey, Ramin V; Mann, J John

    2018-04-13

    Higher serotonin-1A (5-HT 1A ) receptor binding potential (BP F ) has been found in major depressive disorder (MDD) during and between major depressive episodes. We investigated whether higher 5-HT 1A binding is a biologic trait transmitted to healthy high risk (HR) offspring of MDD probands. Data were collected contemporaneously from: nine HR, 30 depressed not-recently medicated (NRM) MDD, 18 remitted NRM MDD, 51 healthy volunteer (HV) subjects. Subjects underwent positron emission tomography (PET) using [ 11 C]WAY100635 to quantify 5-HT 1A BP F , estimated using metabolite, free fraction-corrected arterial input function and cerebellar white matter as reference region. Multivoxel pattern analyses (MVPA) of PET data evaluated group status classification of individuals. When tested across 13 regions of interest, an effect of diagnosis is found on BP F which remains significant after correction for sex, age, injected mass and dose: HR have higher BP F than HV (84.3% higher in midbrain raphe, 40.8% higher in hippocampus, mean BP F across all 13 brain regions is 49.9% ± 11.8% higher). Voxel-level BP F maps distinguish HR vs. HV. Elevated 5-HT 1A BP F appears to be a familially transmitted trait abnormality. Future studies are needed to replicate this finding in a larger cohort and demonstrate the link to the familial transmission of mood disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Cost control and risk mitigation of major projects

    International Nuclear Information System (INIS)

    Caddy, D.G.

    1993-01-01

    In this paper and presentation, the four major types of estimates will be discussed, i.e., capacity factored, equipment factored, semi-detailed and detailed. Key relationships between particular portions of estimates will be discussed such as the relationship between direct field labor and indirect field costs. Having set the basis for developing a project's cost through estimating, the paper will then list and discuss the fifteen key steps which must be followed to control the costs of a project. Next, the subject of allowances and contingency will be discussed and defined and the differences between the two will be highlighted. Having established exactly what contingency is, the subject of risk analysis through RANGE estimating will be discussed. The methods used to establish a precise contingency and probability of an over/under run will be discussed. Finally, the paper will discuss the methods by which a project manager, owner or contractor can mitigate risks; that is to eliminate, transfer or minimize their effect

  17. Urban-hazard risk analysis: mapping of heat-related risks in the elderly in major Italian cities.

    Science.gov (United States)

    Morabito, Marco; Crisci, Alfonso; Gioli, Beniamino; Gualtieri, Giovanni; Toscano, Piero; Di Stefano, Valentina; Orlandini, Simone; Gensini, Gian Franco

    2015-01-01

    Short-term impacts of high temperatures on the elderly are well known. Even though Italy has the highest proportion of elderly citizens in Europe, there is a lack of information on spatial heat-related elderly risks. Development of high-resolution, heat-related urban risk maps regarding the elderly population (≥ 65). A long time-series (2001-2013) of remote sensing MODIS data, averaged over the summer period for eleven major Italian cities, were downscaled to obtain high spatial resolution (100 m) daytime and night-time land surface temperatures (LST). LST was estimated pixel-wise by applying two statistical model approaches: 1) the Linear Regression Model (LRM); 2) the Generalized Additive Model (GAM). Total and elderly population density data were extracted from the Joint Research Centre population grid (100 m) from the 2001 census (Eurostat source), and processed together using "Crichton's Risk Triangle" hazard-risk methodology for obtaining a Heat-related Elderly Risk Index (HERI). The GAM procedure allowed for improved daytime and night-time LST estimations compared to the LRM approach. High-resolution maps of daytime and night-time HERI levels were developed for inland and coastal cities. Urban areas with the hazardous HERI level (very high risk) were not necessarily characterized by the highest temperatures. The hazardous HERI level was generally localized to encompass the city-centre in inland cities and the inner area in coastal cities. The two most dangerous HERI levels were greater in the coastal rather than inland cities. This study shows the great potential of combining geospatial technologies and spatial demographic characteristics within a simple and flexible framework in order to provide high-resolution urban mapping of daytime and night-time HERI. In this way, potential areas for intervention are immediately identified with up-to-street level details. This information could support public health operators and facilitate coordination for heat

  18. Urban-hazard risk analysis: mapping of heat-related risks in the elderly in major Italian cities.

    Directory of Open Access Journals (Sweden)

    Marco Morabito

    Full Text Available Short-term impacts of high temperatures on the elderly are well known. Even though Italy has the highest proportion of elderly citizens in Europe, there is a lack of information on spatial heat-related elderly risks.Development of high-resolution, heat-related urban risk maps regarding the elderly population (≥ 65.A long time-series (2001-2013 of remote sensing MODIS data, averaged over the summer period for eleven major Italian cities, were downscaled to obtain high spatial resolution (100 m daytime and night-time land surface temperatures (LST. LST was estimated pixel-wise by applying two statistical model approaches: 1 the Linear Regression Model (LRM; 2 the Generalized Additive Model (GAM. Total and elderly population density data were extracted from the Joint Research Centre population grid (100 m from the 2001 census (Eurostat source, and processed together using "Crichton's Risk Triangle" hazard-risk methodology for obtaining a Heat-related Elderly Risk Index (HERI.The GAM procedure allowed for improved daytime and night-time LST estimations compared to the LRM approach. High-resolution maps of daytime and night-time HERI levels were developed for inland and coastal cities. Urban areas with the hazardous HERI level (very high risk were not necessarily characterized by the highest temperatures. The hazardous HERI level was generally localized to encompass the city-centre in inland cities and the inner area in coastal cities. The two most dangerous HERI levels were greater in the coastal rather than inland cities.This study shows the great potential of combining geospatial technologies and spatial demographic characteristics within a simple and flexible framework in order to provide high-resolution urban mapping of daytime and night-time HERI. In this way, potential areas for intervention are immediately identified with up-to-street level details. This information could support public health operators and facilitate coordination for heat

  19. Association of major dietary patterns with obesity risk among Mongolian men and women.

    Science.gov (United States)

    Dugee, Otgontuya; Khor, Geok Lin; Lye, Munn-Sann; Luvsannyam, Lhagva; Janchiv, Oyunbileg; Jamyan, Batjargal; Esa, Norhaizan

    2009-01-01

    Mongolia is experiencing changes in its unique nomadic lifestyle and dietary habits in the last two decades with accompanying increase in obesity rate. The dietary pattern approach, which investigates the overall diet in relation to obesity risks, has become appealing in nutrition epidemiology. The aim of this study was to identify major dietary patterns of the Mongolian adults in relation to the risk of having obesity. Dietary intake of a total 418 adults aged ? 25 years was assessed by using a food frequency questionnaire with 68 items. An exploratory factor analysis resulted in three dietary patterns: transitional high in processed meat and potato, traditional rich in whole milk, fats and oils and healthy with greater intake of whole grains, mixed vegetables and fruits. Individuals in the upper quintile of the transitional pattern had significantly greater risk of obesity (BMI > or =25 kg/m2: OR=2.47; 95% CI=1.04-5.86) while subjects in the highest quintile of the healthy dietary pattern were found to have significantly decreased risk of obesity (OR: 0.49; 95% CI=0.25-0.95). Men in the highest quintile of the transitional pattern had greater risk of abdominal obesity WC > or =90 cm: OR= 4.08; 95% CI=1.11-14.97) than those in the lowest quintile. Women in the top quintile of the traditional pattern had a greater odds of having abdominal obesity (WC > or =80 cm: OR=4.59; 95% CI=1.58-13.30) than those in the lowest quintile. The study suggests that public health efforts be targeted at adults in Mongolia to address the undesirable aspects of the transitional and the traditional dietary patterns.

  20. Caesarean Section at Full Dilatation and Risk of Major Obstetric Haemorrhage

    LENUS (Irish Health Repository)

    O’Dwyer, V

    2018-03-01

    The purpose of the study was to examine the risk factors for caesarean section (CS) at full dilatation and to assess the risk and management of haemorrhage. The study took place in a tertiary referral maternity hospital. Women who had a CS at full dilatation were included. Clinical and demographic details were recorded. There were 199 cases. The average age was 30.3 years and average BMI was 25.8kg\\/m2. There were 79.9 % (159) primigravidas and 20.1% (40) multigravidas. The average gestation at delivery was 39.4 weeks. Labour was induced in 46.9 % (92) and spontaneous in 53.8% (107). Oxytocin was used in 67.8 % (135). An instrumental delivery was attempted in 46.7 % (93). The rate of malposition was 46.5 % (92). The average birthweight was 3,629g and 9 babies weighed ≥4.5kg. The average estimated blood loss (EBL) was 665mls and 34 had EBL>1L. Most had an oxytocin infusion (141). Other uterotonic agents were used in 70 women. Seven women had blood transfusions. The highest rate of CS at full dilatation was in primigravidas due to malposition. There was a low rate of major obstetric haemorrhage.

  1. Bacterial genus is a risk factor for major amputation in patients with diabetic foot.

    Science.gov (United States)

    Cardoso, Natália Anício; Cisneiros, Lígia DE Loiola; Machado, Carla Jorge; Cenedezi, Juliana Merlin; Procópio, Ricardo Jayme; Navarro, Túlio Pinho

    2017-01-01

    to evaluate whether bacterial genus is a risk factor for major amputation in patients with diabetic foot and infected ulcer. we conducted a case-control, observational study of 189 patients with infected ulcers in diabetic feet admitted to the Vascular Surgery Service of the Risoleta Tolentino Neves Hospital, from January 2007 to December 2012. The bacteriological evaluation was performed in deep tissue cultures from the lesions and amputation was considered major when performed above the foot'smiddle tarsus. the patients'mean age was 61.9±12.7 years; 122 (64.6%) were men. The cultures were positive in 86.8%, being monomicrobial in 72% of the cases. In patients with major amputation, Acinetobacter spp. (24.4%), Morganella spp. (24.4%), Proteus spp. (23.1%) and Enterococcus spp. (19.2%) were the most frequent types of bacteria. The most commonly isolated species were Acinetobacter baumannii, Morganella morganii, Pseudomonas aeruginosa and Proteus mirabilis. As predictors of major amputation, we identified the isolation of the generaAcinetobacter spp. and Klebsiella spp., serum creatinine ≥1.3mg/dl and hemoglobin creatinina ≥1,3mg/dl e de hemoglobina <11g/dl. os gêneros bacterianos Acinetobacter spp. e Klebsiella spp. identificados nas úlceras infectadas dos pacientes com pé diabético associaram-se a maior incidência de amputação maior.

  2. High risk for major nonlimb anomalies associated with lower-limb deficiency: a population-based study.

    Science.gov (United States)

    Syvänen, Johanna; Nietosvaara, Yrjänä; Ritvanen, Annukka; Koskimies, Eeva; Kauko, Tommi; Helenius, Ilkka

    2014-11-19

    The aims of this study were to determine the prevalence of congenital lower-limb reduction defects and associated mortality, to evaluate lower-limb deficiencies by type of reduction, and to identify patterns of associated anomalies. We conducted a population-based study with use of data from the Finnish Register of Congenital Malformations and Care Register for Health Care. All cases of lower-limb deficiency among live births, stillbirths, spontaneous abortions, and terminations of pregnancy due to fetal anomalies from 1993 to 2008 were included. We analyzed medical records and classified lower-limb reduction defects. Associated major anomalies were recorded, and perinatal mortality and infant mortality were calculated. Two hundred and sixty-six cases with lower-limb deficiency were identified, with a total prevalence of 2.8 per 10,000 births, a birth prevalence of 2.2 per 10,000 births, and a live-birth prevalence of 2.1 per 10,000 live births. Terminal transverse limb reductions accounted for 44.7% of the cases; longitudinal reductions, 22.9%; intercalary reductions, 7.9%; multiple reductions, 8.3%; and split-foot malformations, 4.5%. In addition to lower-limb deficiency, 47.7% of the cases had other major anomalies; anomalies of internal organs were noted in 26.3% of the cases, anomalies of the axial skeleton in 13.5% of cases, and central nervous system anomalies in 12.8%. Upper-limb reductions were observed in 32.0% of the cases. The relative risk (RR) for associated major anomalies was 12.54 (95% confidence interval [CI], 11.06 to 14.23) compared with the general figures for major congenital anomalies in Finland. The RR for associated anomalies was higher (1.75; 95% CI, 1.20 to 2.53) for longitudinal preaxial lower-limb deficiencies than for the other types of lower-limb reductions. Perinatal mortality was seventy-eight per 1000 births. All infant deaths were associated with chromosomal abnormalities, other known syndromes, or additional congenital

  3. The incidence and risk factors of meningitis after major craniotomy in China: a retrospective cohort study.

    Science.gov (United States)

    Chen, Chen; Zhang, Bingyan; Yu, Shenglei; Sun, Feng; Ruan, Qiaoling; Zhang, Wenhong; Shao, Lingyun; Chen, Shu

    2014-01-01

    Meningitis after neurosurgery can result in severe morbidity and high mortality. Incidence varies among regions and limited data are focused on meningitis after major craniotomy. This retrospective cohort study aimed to determine the incidence, risk factors and microbiological spectrum of postcraniotomy meningitis in a large clinical center of Neurosurgery in China. Patients who underwent neurosurgeries at the Department of Neurosurgery in Huashan Hospital, the largest neurosurgery center in Asia and the Pacific, between 1st January and 31st December, 2008 were selected. Individuals with only shunts, burr holes, stereotactic surgery, transsphenoidal or spinal surgery were excluded. The complete medical records of each case were reviewed, and data on risk factors were extracted and evaluated for meningitis. A total of 65 meningitides were identified among 755 cases in the study, with an incidence of 8.60%. The risk of meningitis was increased by the presence of diabetes mellitus (odds ratio [OR], 6.27; P = 0.009), the use of external ventricular drainage (OR, 4.30; P = 0.003) and the use of lumbar drainage (OR, 17.23; PMeningitis remains an important source of morbidity and mortality after major craniotomy. Diabetic patients or those with cerebral spinal fluid shunts carry significant high risk of infection. Thus, identification of the risk factors as soon as possible will help physicians to improve patient care.

  4. Robust symptom networks in recurrent major depression across different levels of genetic and environmental risk

    NARCIS (Netherlands)

    van Loo, H.M.; Van Borkulo, C.D.; Peterson, R.E.; Fried, E.I.; Aggen, S.H.; Borsboom, D.; Kendler, K.S.

    BACKGROUND: Genetic risk and environmental adversity-both important risk factors for major depression (MD)-are thought to differentially impact on depressive symptom types and associations. Does heterogeneity in these risk factors result in different depressive symptom networks in patients with MD?

  5. Risk Factors as Major Determinants of Resilience: A Replication Study.

    Science.gov (United States)

    Eshel, Yohanan; Kimhi, Shaul; Lahad, Mooli; Leykin, Dmitry; Goroshit, Marina

    2018-03-16

    The present study was conducted in the context of current concerns about replication in psychological research. It claims that risk factors should be regarded as an integral part of the definition of individual resilience, which should be defined in terms of the balance between individual strength or protective factors, and individual vulnerability or risk factors (IND-SVR). Five independent samples, including 3457 Israeli participants, were employed to determine the effects of resilience promoting and resilience suppressing variables on the IND-SVR index of resilience, and on its two components: recovery from adversity, and distress symptoms. Five path analyses were employed for determining the role of distress symptoms as a measure of psychological resilience, as compared to other indices of this resilience. Results indicated the major role of risk factors (distress symptoms) as an integral component of resilience. This role was generally replicated in the five investigated samples. Risk factors are legitimate, valid, and useful parts of the definition of psychological resilience. Resilience research has shifted away from studying individual risk factors to investigating the process through which individuals overcome the hardships they experience. The present data seem to suggest that this shift should be reexamined.

  6. The Burden of Cardiovascular Disease Attributable to Major Modifiable Risk Factors in Indonesia

    Directory of Open Access Journals (Sweden)

    Mohammad Akhtar Hussain

    2016-10-01

    Full Text Available Background: In Indonesia, coronary heart disease (CHD and stroke are estimated to cause more than 470 000 deaths annually. In order to inform primary prevention policies, we estimated the sex- and age-specific burden of CHD and stroke attributable to five major and modifiable vascular risk factors: cigarette smoking, hypertension, diabetes, elevated total cholesterol, and excess body weight. Methods: Population attributable risks for CHD and stroke attributable to these risk factors individually were calculated using summary statistics obtained for prevalence of each risk factor specific to sex and to two age categories (<55 and ≥55 years from a national survey in Indonesia. Age- and sex-specific relative risks for CHD and stroke associated with each of the five risk factors were derived from prospective data from the Asia-Pacific region. Results: Hypertension was the leading vascular risk factor, explaining 20%–25% of all CHD and 36%–42% of all strokes in both sexes and approximately one-third of all CHD and half of all strokes across younger and older age groups alike. Smoking in men explained a substantial proportion of vascular events (25% of CHD and 17% of strokes. However, given that these risk factors are likely to be strongly correlated, these population attributable risk proportions are likely to be overestimates and require verification from future studies that are able to take into account correlation between risk factors. Conclusions: Implementation of effective population-based prevention strategies aimed at reducing levels of major cardiovascular risk factors, especially blood pressure, total cholesterol, and smoking prevalence among men, could reduce the growing burden of CVD in the Indonesian population.

  7. Incorporation of Indigenous Forces in Major Theater War: Advantages, Risks and Considerations

    Science.gov (United States)

    2004-05-03

    training exercises and programs like the International Military Education and Training (IMET) program, to name a few, the United States has a far better...USAWC STRATEGY RESEARCH PROJECT INCORPORATION OF INDIGENOUS FORCES IN MAJOR THEATER WAR: ADVANTAGES , RISKS AND CONSIDERATIONS by Ms. Priscilla... Advantages , Risks and Considerations 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Priscilla Sellers 5d. PROJECT NUMBER

  8. Major stressful life events in adulthood and risk of multiple sclerosis

    DEFF Research Database (Denmark)

    Nielsen, Nete Munk; Bager, Peter; Simonsen, Jacob

    2014-01-01

    It is unclear whether psychological stress is associated with increased risk of multiple sclerosis (MS). We studied the association between major stressful life events and MS in a nationwide cohort study using death of a child or a spouse or marital dissolution as indicators of severe stress....

  9. Relative Hazard and Risk Measure Calculation Methodology Rev 1

    International Nuclear Information System (INIS)

    Stenner, Robert D.; White, Michael K.; Strenge, Dennis L.; Aaberg, Rosanne L.; Andrews, William B.

    2000-01-01

    Documentation of the methodology used to calculate relative hazard and risk measure results for the DOE complex wide risk profiles. This methodology is used on major site risk profiles. In February 1997, the Center for Risk Excellence (CRE) was created and charged as a technical, field-based partner to the Office of Science and Risk Policy (EM-52). One of the initial charges to the CRE is to assist the sites in the development of ''site risk profiles.'' These profiles are to be relatively short summaries (periodically updated) that present a broad perspective on the major risk related challenges that face the respective site. The risk profiles are intended to serve as a high-level communication tool for interested internal and external parties to enhance the understanding of these risk-related challenges. The risk profiles for each site have been designed to qualitatively present the following information: (1) a brief overview of the site, (2) a brief discussion on the historical mission of the site, (3) a quote from the site manager indicating the site's commitment to risk management, (4) a listing of the site's top risk-related challenges, (5) a brief discussion and detailed table presenting the site's current risk picture, (6) a brief discussion and detailed table presenting the site's future risk reduction picture, and (7) graphic illustrations of the projected management of the relative hazards at the site. The graphic illustrations were included to provide the reader of the risk profiles with a high-level mental picture to associate with all the qualitative information presented in the risk profile. Inclusion of these graphic illustrations presented the CRE with the challenge of how to fold this high-level qualitative risk information into a system to produce a numeric result that would depict the relative change in hazard, associated with each major risk management action, so it could be presented graphically. This report presents the methodology developed

  10. Neuroticism Predicts Subsequent Risk of Major Depression for Whites but Not Blacks

    Directory of Open Access Journals (Sweden)

    Shervin Assari

    2017-09-01

    Full Text Available Cultural and ethnic differences in psychosocial and medical correlates of negative affect are well documented. This study aimed to compare blacks and whites for the predictive role of baseline neuroticism (N on subsequent risk of major depressive episodes (MDD 25 years later. Data came from the Americans’ Changing Lives (ACL Study, 1986–2011. We used data on 1219 individuals (847 whites and 372 blacks who had data on baseline N in 1986 and future MDD in 2011. The main predictor of interest was baseline N, measured using three items in 1986. The main outcome was 12 months MDD measured using the Composite International Diagnostic Interview (CIDI at 2011. Covariates included baseline demographics (age and gender, socioeconomics (education and income, depressive symptoms [Center for Epidemiologic Studies Depression Scale (CES-D], stress, health behaviors (smoking and driking, and physical health [chronic medical conditions, obesity, and self-rated health (SRH] measured in 1986. Logistic regressions were used to test the predictive role of baseline N on subsequent risk of MDD 25 years later, net of covariates. The models were estimated in the pooled sample, as well as blacks and whites. In the pooled sample, baseline N predicted subsequent risk of MDD 25 years later (OR = 2.23, 95%CI = 1.14–4.34, net of covariates. We also found a marginally significant interaction between race and baseline N on subsequent risk of MDD (OR = 0.37, 95% CI = 0.12–1.12, suggesting a stronger effect for whites compared to blacks. In race-specific models, among whites (OR = 2.55; 95% CI = 1.22–5.32 but not blacks (OR = 0.90; 95% CI = 0.24–3.39, baseline N predicted subsequent risk of MDD. Black-white differences in socioeconomics and physical health could not explain the racial differences in the link between N and MDD. Blacks and whites differ in the salience of baseline N as a psychological determinant of MDD risk over a long period of time. This finding

  11. An Impermeant Ganetespib Analog Inhibits Extracellular Hsp90-Mediated Cancer Cell Migration that Involves Lysyl Oxidase 2-like Protein

    Energy Technology Data Exchange (ETDEWEB)

    McCready, Jessica [Department of Natural Sciences, Assumption College, Worcester, MA 01609 (United States); Wong, Daniel S. [Department of Developmental Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111 (United States); Cell and Molecular Physiology Program, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111 (United States); Burlison, Joseph A.; Ying, Weiwen [Synta Pharmaceuticals, Lexington, MA 02421 (United States); Jay, Daniel G., E-mail: daniel.jay@tufts.edu [Department of Developmental Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111 (United States); Cell and Molecular Physiology Program, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111 (United States)

    2014-04-30

    Extracellular Hsp90 (eHsp90) activates a number of client proteins outside of cancer cells required for migration and invasion. Therefore, eHsp90 may serve as a novel target for anti-metastatic drugs as its inhibition using impermeant Hsp90 inhibitors would not affect the numerous vital intracellular Hsp90 functions in normal cells. While some eHsp90 clients are known, it is important to establish other proteins that act outside the cell to validate eHsp90 as a drug target to limit cancer spread. Using mass spectrometry we identified two precursor proteins Galectin 3 binding protein (G3BP) and Lysyl oxidase 2-like protein (LOXL2) that associate with eHsp90 in MDA-MB231 breast cancer cell conditioned media and confirmed that LOXL2 binds to eHsp90 in immunoprecipitates. We introduce a novel impermeant Hsp90 inhibitor STA-12-7191 derived from ganetespib and show that it is markedly less toxic to cells and can inhibit cancer cell migration in a dose dependent manner. We used STA-12-7191 to test if LOXL2 and G3BP are potential eHsp90 clients. We showed that while LOXL2 can increase wound healing and compensate for STA-12-7191-mediated inhibition of wound closure, addition of G3BP had no affect on this assay. These findings support of role for LOXL2 in eHsp90 stimulated cancer cell migration and provide preliminary evidence for the use of STA-12-7191 to inhibit eHsp90 to limit cancer invasion.

  12. An Impermeant Ganetespib Analog Inhibits Extracellular Hsp90-Mediated Cancer Cell Migration that Involves Lysyl Oxidase 2-like Protein

    International Nuclear Information System (INIS)

    McCready, Jessica; Wong, Daniel S.; Burlison, Joseph A.; Ying, Weiwen; Jay, Daniel G.

    2014-01-01

    Extracellular Hsp90 (eHsp90) activates a number of client proteins outside of cancer cells required for migration and invasion. Therefore, eHsp90 may serve as a novel target for anti-metastatic drugs as its inhibition using impermeant Hsp90 inhibitors would not affect the numerous vital intracellular Hsp90 functions in normal cells. While some eHsp90 clients are known, it is important to establish other proteins that act outside the cell to validate eHsp90 as a drug target to limit cancer spread. Using mass spectrometry we identified two precursor proteins Galectin 3 binding protein (G3BP) and Lysyl oxidase 2-like protein (LOXL2) that associate with eHsp90 in MDA-MB231 breast cancer cell conditioned media and confirmed that LOXL2 binds to eHsp90 in immunoprecipitates. We introduce a novel impermeant Hsp90 inhibitor STA-12-7191 derived from ganetespib and show that it is markedly less toxic to cells and can inhibit cancer cell migration in a dose dependent manner. We used STA-12-7191 to test if LOXL2 and G3BP are potential eHsp90 clients. We showed that while LOXL2 can increase wound healing and compensate for STA-12-7191-mediated inhibition of wound closure, addition of G3BP had no affect on this assay. These findings support of role for LOXL2 in eHsp90 stimulated cancer cell migration and provide preliminary evidence for the use of STA-12-7191 to inhibit eHsp90 to limit cancer invasion

  13. Serum LAG-3 and DKK-1 levels in patients with gastric cancer and their correlation with clinical pathological characteristics

    Directory of Open Access Journals (Sweden)

    Yu-Fang Liu

    2017-04-01

    Full Text Available Objective: To study the correlation of serum LAG-3 and DKK-1 levels with cancer cell proliferation, invasion, angiogenesis and other clinical pathological characteristics in patients with gastric cancer. Methods: 48 patients who were diagnosed with early gastric cancer in our hospital between June 2014 and October 2016 were selected as the gastric cancer group of the research, 50 healthy volunteers who received physical examination in our hospital during the same period were selected as the control group of the research, serum was collected to determine the levels of lymphocyte activation gene-3 (LAG-3, Dickkopf-1 (DKK-1 and angiogenesis molecules, and the gastric cancer tissue and the tissue adjacent to carcinoma were collected to determine the expression of proliferation and invasion-related molecules. Results: Serum LAG-1, DKK-1, angiogenin-1 (Ang-1, Ang-2, vascular endothelial growth factor (VEGF and basic fibroblast growth factor (bFGF levels of gastric cancer group were significantly higher than those of control group (P<0.05, and EPHA2, LOXL2, PCNA, Akt, CyclinD1, MYH-9, CXCR7, KDM1A and CatB mRNA expression in gastric cancer tissue were significantly higher than those in the tissue adjacent to carcinoma (P<0.05; serum Ang-1, Ang-2, VEGF and bFGF levels as well as EPHA2, LOXL2, PCNA, Akt, CyclinD1, MYH-9, CXCR7, KDM1A and CatB mRNA expression in gastric cancer tissue of patients with gastric cancer were positively correlated with serum LAG-3 and DKK-1 levels. Conclusion: Serum LAG-3 and DKK-1 levels are valuable to diagnose early gastric cancer and can assess the cancer cell proliferation, invasion, angiogenesis and other clinical pathological characteristics in gastric cancer tissue.

  14. Paracetamol, Ibuprofen, and Recurrent Major Cardiovascular and Major Bleeding Events in 19 120 Patients With Recent Ischemic Stroke.

    Science.gov (United States)

    Gonzalez-Valcarcel, Jaime; Sissani, Leila; Labreuche, Julien; Bousser, Marie-Germaine; Chamorro, Angel; Fisher, Marc; Ford, Ian; Fox, Kim M; Hennerici, Michael G; Mattle, Heinrich P; Rothwell, Peter M; Steg, Philippe Gabriel; Vicaut, Eric; Amarenco, Pierre

    2016-04-01

    The presumed safety of paracetamol in high-cardiovascular risk patients has been questioned. We determined whether paracetamol or ibuprofen use is associated with major cardiovascular events (MACE) or major bleeding in 19 120 patients with recent ischemic stroke or transient ischemic attack of mainly atherothrombotic origin included in the Prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) trial. We performed 2 nested case-control analysis (2153 cases with MACE during trial follow-up and 4306 controls matched on Essen stroke risk score; 809 cases with major bleeding matched with 1616 controls) and a separate time-varying analysis. 12.3% were prescribed paracetamol and 2.5% ibuprofen. Median duration of treatment was 14 (interquartile range 5-145) days for paracetamol and 9 (5-30) days for ibuprofen. Paracetamol, but not ibuprofen, was associated with increased risk of MACE (odds ratio 1.21, 95% confidence interval [CI] 1.04-1.42) or a major bleeding (odds ratio 1.60, 95% CI 1.26-2.03), with no impact of daily dose and duration of paracetamol treatment. Time-varying analysis found an increased risk of MACE with both paracetamol (hazard ratio 1.22, 95% CI 1.05-1.43) and ibuprofen (hazard ratio 1.47, 95% CI 1.06-2.03) and of major bleeding with paracetamol (hazard ratio 1.95, 95% CI 1.45-2.62). There was a weak and inconsistent signal for association between paracetamol or ibuprofen and MACE or major bleeding, which may be related to either a genuine but modest effect of these drugs or to residual confounding. http://www.isrctn.com. Unique identifier: ISRCTN66157730. © 2016 American Heart Association, Inc.

  15. SORL1 rare variants: a major risk factor for familial early-onset Alzheimer's disease.

    Science.gov (United States)

    Nicolas, G; Charbonnier, C; Wallon, D; Quenez, O; Bellenguez, C; Grenier-Boley, B; Rousseau, S; Richard, A-C; Rovelet-Lecrux, A; Le Guennec, K; Bacq, D; Garnier, J-G; Olaso, R; Boland, A; Meyer, V; Deleuze, J-F; Amouyel, P; Munter, H M; Bourque, G; Lathrop, M; Frebourg, T; Redon, R; Letenneur, L; Dartigues, J-F; Génin, E; Lambert, J-C; Hannequin, D; Campion, D

    2016-06-01

    The SORL1 protein plays a protective role against the secretion of the amyloid β peptide, a key event in the pathogeny of Alzheimer's disease. We assessed the impact of SORL1 rare variants in early-onset Alzheimer's disease (EOAD) in a case-control setting. We conducted a whole exome analysis among 484 French EOAD patients and 498 ethnically matched controls. After collapsing rare variants (minor allele frequency ≤1%), we detected an enrichment of disruptive and predicted damaging missense SORL1 variants in cases (odds radio (OR)=5.03, 95% confidence interval (CI)=(2.02-14.99), P=7.49.10(-5)). This enrichment was even stronger when restricting the analysis to the 205 cases with a positive family history (OR=8.86, 95% CI=(3.35-27.31), P=3.82.10(-7)). We conclude that predicted damaging rare SORL1 variants are a strong risk factor for EOAD and that the association signal is mainly driven by cases with positive family history.

  16. Higher risk of developing major depression and bipolar disorder in later life among adolescents with asthma: a nationwide prospective study.

    Science.gov (United States)

    Chen, Mu-Hong; Su, Tung-Ping; Chen, Ying-Sheue; Hsu, Ju-Wei; Huang, Kai-Lin; Chang, Wen-Han; Chen, Tzeng-Ji; Bai, Ya-Mei

    2014-02-01

    Previous studies have suggested an immunological dysfunction in mood disorders, but rarely have investigated the temporal association between allergic diseases and mood disorders. Using the Taiwan National Health Insurance Research Database, we attempted to investigate the association between asthma in early adolescence and the risk of unipolar depression and bipolar disorder in later life. In all, 1453 adolescents with asthma aged between 10 and 15 years and 5812 age-/gender-matched controls were selected in 1998-2000. Subjects with unipolar depression and bipolar disorder that occurred up to the end of follow-up (December 31 2010) were identified. Adolescents with asthma had a higher incidence of major depression (2.8% vs. 1.1%, p bipolar disorder (1.0% vs. 0.3%, p adolescence was associated with an increased risk of developing major depression (hazard ratio [HR]: 1.81, 95% confidence interval [CI]: 1.14-2.89), any depressive disorder (HR: 1.74, 95% CI: 1.27-2.37), and bipolar disorder (HR: 2.27, 95% CI: 1.01-5.07), after adjusting for demographic data and comorbid allergic diseases. Adolescents with asthma had an elevated risk of developing mood disorders in later life. Further studies would be required to investigate the underlying mechanisms for this comorbid association and elucidate whether prompt intervention for asthma would decrease the risk of developing mood disorders. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. The YWHAE gene confers risk to major depressive disorder in the male group of Chinese Han population.

    Science.gov (United States)

    Liu, Jie; Zhang, Hong-Xin; Li, Zhi-Qiang; Li, Tao; Li, Jun-Yan; Wang, Ti; Li, You; Feng, Guo-Yin; Shi, Yong-Yong; He, Lin

    2017-07-03

    Schizophrenia and major depressive disorder are two major psychiatric illnesses that may share specific genetic risk factors to a certain extent. Increasing evidence suggests that the two disorders might be more closely related than previously considered. To investigate whether YWHAE gene plays a significant role in major depressive disorder in Han Chinese population, we recruited 1135 unrelated major depressive disorder patients (485 males, 650 females) and 989 unrelated controls (296 males, 693 females) of Chinese Han origin. Eleven common SNPs were genotyped using TaqMan® technology. In male-group, the allele and genotype frequencies of rs34041110 differed significantly between patients and control (P allele =0.036486, OR[95%CI]: 1.249442(1.013988-1.539571); P genotype =0.045301). Also in this group, allele and genotype frequencies of rs1532976 differed significantly (P allele =0.013242, OR[95%CI]: 1.302007(1.056501-1.604563); genotype: P=0.039152). Haplotype-analyses showed that, in male-group, positive association with major depressive disorder was found for the A-A-C-G haplotype of rs3752826-rs2131431-rs1873827-rs12452627 (χ 2 =20.397, P=6.38E-06, OR[95%CI]: 7.442 [2.691-20.583]), its C-A-C-G haplotype (χ 2 =19.122, P=1.24E-05, OR and 95%CI: 0.402 [0.264-0.612]), its C-C-T-G haplotype (χ 2 =9.766, P=0.001785, OR[95%CI]: 5.654 [1.664-19.211]). In female-group, positive association was found for the A-A-C-G haplotype of rs3752826-rs2131431-rs1873827-rs12452627 (χ 2 =78.628, P=7.94E-19, OR[95%CI]: 50.043 [11.087-225.876]), its A-C-T-G haplotype (χ 2 =38.806, P=4.83E-10, OR[95%CI]: 0.053 [0.015-0.192]), the C-A-C-G haplotype (χ 2 =18.930, P=1.37E-05, OR[95%CI]: 0.526 [0.392-0.705]), and the C-C-T-G haplotype (χ 2 =38.668, P=5.18E-10, OR[95%CI]: 6.130 [3.207-11.716]). Our findings support YWHAE being a risk gene for Major Depressive Disorder in the Han Chinese population. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Chinese Registry of rheumatoid arthritis (CREDIT): II. prevalence and risk factors of major comorbidities in Chinese patients with rheumatoid arthritis.

    Science.gov (United States)

    Jin, Shangyi; Li, Mengtao; Fang, Yongfei; Li, Qin; Liu, Ju; Duan, Xinwang; Liu, Yi; Wu, Rui; Shi, Xiaofei; Wang, Yongfu; Jiang, Zhenyu; Wang, Yanhong; Yu, Chen; Wang, Qian; Tian, Xinping; Zhao, Yan; Zeng, Xiaofeng

    2017-11-15

    Rheumatoid arthritis patients are at higher risk of developing comorbidities. The main objective of this study was to evaluate the prevalence of major comorbidities in Chinese rheumatoid arthritis patients. We also aimed to identify factors associated with these comorbidities. Baseline demographic, clinical characteristics and comorbidity data from RA patients enrolled in the Chinese Registry of rhEumatoiD arthrITis (CREDIT) from Nov 2016 to August 2017 were presented and compared with those from five other registries across the world. Possible factors related to three major comorbidities (cardiovascular disease, fragility fracture and malignancy) were identified using multivariate logistic regression analyses. A total of 13,210 RA patients were included (80.6% female, mean age 52.9 years and median RA duration 4.0 years). Baseline prevalence rates of major comorbidities were calculated: CVD, 2.2% (95% CI 2.0-2.5%); fragility fracture, 1.7% (95% CI 1.5-1.9%); malignancy, 0.6% (95% CI 0.5-0.7%); overall major comorbidities, 4.2% (95% CI 3.9-4.6%). Advanced age was associated with all comorbidities. Male gender and disease duration were positively related to CVD. Female sex and longer disease duration were potential risk factors for fragility fractures. Ever use of methotrexate (MTX) was negatively related to baseline comorbidities. Patients with rheumatoid arthritis in China have similar prevalence of comorbidities with other Asian countries. Advanced age and long disease duration are possible risk factors for comorbidities. On the contrary, MTX may protect RA patients from several major comorbidities, supporting its central role in the management of rheumatoid arthritis.

  19. The incidence and risk factors of meningitis after major craniotomy in China: a retrospective cohort study.

    Directory of Open Access Journals (Sweden)

    Chen Chen

    Full Text Available BACKGROUND: Meningitis after neurosurgery can result in severe morbidity and high mortality. Incidence varies among regions and limited data are focused on meningitis after major craniotomy. AIM: This retrospective cohort study aimed to determine the incidence, risk factors and microbiological spectrum of postcraniotomy meningitis in a large clinical center of Neurosurgery in China. METHODS: Patients who underwent neurosurgeries at the Department of Neurosurgery in Huashan Hospital, the largest neurosurgery center in Asia and the Pacific, between 1st January and 31st December, 2008 were selected. Individuals with only shunts, burr holes, stereotactic surgery, transsphenoidal or spinal surgery were excluded. The complete medical records of each case were reviewed, and data on risk factors were extracted and evaluated for meningitis. RESULTS: A total of 65 meningitides were identified among 755 cases in the study, with an incidence of 8.60%. The risk of meningitis was increased by the presence of diabetes mellitus (odds ratio [OR], 6.27; P = 0.009, the use of external ventricular drainage (OR, 4.30; P = 0.003 and the use of lumbar drainage (OR, 17.23; P<0.001. The isolated microorganisms included Acinetobacter baumannii, Enterococcus sp, Streptococcus intermedius and Klebsiella pneumonia. CONCLUSIONS: Meningitis remains an important source of morbidity and mortality after major craniotomy. Diabetic patients or those with cerebral spinal fluid shunts carry significant high risk of infection. Thus, identification of the risk factors as soon as possible will help physicians to improve patient care.

  20. Urban-Hazard Risk Analysis: Mapping of Heat-Related Risks in the Elderly in Major Italian Cities

    Science.gov (United States)

    Morabito, Marco; Crisci, Alfonso; Gioli, Beniamino; Gualtieri, Giovanni; Toscano, Piero; Di Stefano, Valentina; Orlandini, Simone; Gensini, Gian Franco

    2015-01-01

    Background Short-term impacts of high temperatures on the elderly are well known. Even though Italy has the highest proportion of elderly citizens in Europe, there is a lack of information on spatial heat-related elderly risks. Objectives Development of high-resolution, heat-related urban risk maps regarding the elderly population (≥65). Methods A long time-series (2001–2013) of remote sensing MODIS data, averaged over the summer period for eleven major Italian cities, were downscaled to obtain high spatial resolution (100 m) daytime and night-time land surface temperatures (LST). LST was estimated pixel-wise by applying two statistical model approaches: 1) the Linear Regression Model (LRM); 2) the Generalized Additive Model (GAM). Total and elderly population density data were extracted from the Joint Research Centre population grid (100 m) from the 2001 census (Eurostat source), and processed together using “Crichton’s Risk Triangle” hazard-risk methodology for obtaining a Heat-related Elderly Risk Index (HERI). Results The GAM procedure allowed for improved daytime and night-time LST estimations compared to the LRM approach. High-resolution maps of daytime and night-time HERI levels were developed for inland and coastal cities. Urban areas with the hazardous HERI level (very high risk) were not necessarily characterized by the highest temperatures. The hazardous HERI level was generally localized to encompass the city-centre in inland cities and the inner area in coastal cities. The two most dangerous HERI levels were greater in the coastal rather than inland cities. Conclusions This study shows the great potential of combining geospatial technologies and spatial demographic characteristics within a simple and flexible framework in order to provide high-resolution urban mapping of daytime and night-time HERI. In this way, potential areas for intervention are immediately identified with up-to-street level details. This information could support public

  1. Light water reactor accidents - is there really a major public risk

    Energy Technology Data Exchange (ETDEWEB)

    Levenson, M [Bechtel Power Corp., San Francisco, CA (USA)

    1983-04-01

    During the past decade, a major mismatch has developed between the actual public risk from nuclear power and the public perception of that risk. Extensive analyses have been performed on the probability of accidents at nuclear power plants, but such analyses have used assumed consequences rather than those that have been scientifically derived. The assumed consequences have been overstated and needlessly scare the public or lead to unwarranted evacuations. The 40 years of experience in research, development and testing, and the history of actual accidents, provide a sound basis for assessment-a basis that has not been utilized.

  2. Melancholic features and hostility are associated with suicidality risk in Asian patients with major depressive disorder.

    Science.gov (United States)

    Jeon, Hong Jin; Peng, Daihui; Chua, Hong Choon; Srisurapanont, Manit; Fava, Maurizio; Bae, Jae-Nam; Man Chang, Sung; Hong, Jin Pyo

    2013-06-01

    Suicide rates are higher in East-Asians than other populations, and especially high in Koreans. However, little is known about suicidality risk and melancholic features in Asian patients with major depressive disorder (MDD). Drug-free MDD outpatients were included from 13 centers across five ethnicities consisting of Chinese (n=290), Korean (n=101), Thai (n=102), Indian (n=27), and Malay (n=27). All were interviewed using the Mini-International Neuropsychiatric Interview (M.I.N.I.), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Symptoms Checklist 90-Revised (SCL-90-R). Of 547 subjects, 177 MDD patients showed melancholic features (32.4%). These melancholic MDD patients revealed significantly higher suicidality risk (pdepression (pdifference in higher hostility. Adjusted odds ratios of melancholic features and hostility for moderate to high suicidality risk were 1.79 (95% CI=1.15-2.79) and 2.45 (95% CI=1.37-4.38), after adjusting for age, sex, education years, and depression severity. Post-hoc analyses showed that suicidality risk was higher in Korean and Chinese than that of Thai, Indian and Malay in MDD subjects with melancholic features, although depression severity showed no significant differences among the ethnicities. Suicidality risk is associated with both melancholic features and hostility and it shows cross-ethnic differences in Asian MDD patients, independent of depression severity. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. The Regulation of Major Risks in Relation to Large Nuclear Installations in France

    International Nuclear Information System (INIS)

    Phan Van, L.

    1991-01-01

    Recently, major risk prevention has generated legislative and regulatory texts in French law, particularly regarding nuclear installations. This article reviews the context and analyses the scope of the new regulations. They require the nuclear operator to take preventive measures, namely more stringent obligations from the safety viewpoint to inform the public. These include risk assessments and preparing emergency plans in case if accidents. (NEA)

  4. Insight into mental illness and child maltreatment risk among mothers with major psychiatric disorders.

    Science.gov (United States)

    Mullick, M; Miller, L J; Jacobsen, T

    2001-04-01

    This study examined the relationship between insight into mental illness and current child maltreatment risk among mothers who had a major psychiatric disorder and who had lost custody of a child because of abuse, neglect, or having placed the child at risk of harm. Specifically, a measure of insight was examined in relation to systematically observed parenting behaviors known to be correlated with past child maltreatment and in relation to a comprehensive clinical determination of risk. Forty-four mothers who had a major psychiatric disorder were independently rated for their insight into their illness, the quality of mother-child interaction, and the overall clinical risk of maltreatment. Better insight into mental illness was associated with more sensitive mothering behavior and with lower assessed clinical risk of maltreatment. The association remained when mothers with current psychotic symptoms were excluded from the analyses. Better insight did not appear to be associated with past psychotic symptoms, maternal psychiatric diagnosis, or the mother's level of education. Insight into mental illness may function as a protective factor that influences the risk of child maltreatment in mothers with mental illness. Measures of insight could be usefully incorporated into comprehensive parenting assessments for mothers with psychiatric disorders.

  5. Association of ABO blood groups and major ischaemic heart disease risk factors

    International Nuclear Information System (INIS)

    Lutf-Ullah, L.; Akhtar, B.; Noor-Us-Saba; Hanif, A.; Khan, B.Z.; Bukhshi, I.M.

    2010-01-01

    To study the association of ABO blood groups with major ischaemic heart disease risk factors. Setting: Department of Cardiology, Mayo hospital, Lahore over a period of two years from January 2008 to December 2009. Study Design: Analytic comparative study. Subjects and Methods: The study group included 907 patients of ischaemic heart disease (IHD). The distribution of ABO blood groups in IHD patients was compared for presence or absence of major IHD risk factors. Data was analyzed using SPSS 16. ANOVA and Chi-square tests for significance were used. P-value less than 0.05 was taken as significant. Results: In this study, the following pattern of ABO blood groups was observed in IHD patients : blood group A 251 (27.67%); blood group B 329 (36.27%); blood group O 235 (25.91%); blood group AB 92 (10.14%). We found no relation-ship of ABO blood groups with age (p-value = 0.234), gender (p-value = 0.093), hypertension (p-value = 0.230), diabetes mellitus (p-value = 0.801), family history of IHD (p-value = 0.277), transverse ear lobe crease (p-value = 0.231), total cholesterol (p-value = 0.797), triglycerides (p-value = 0.351), low density lipoprotein (p-value = 0.078), high density lipoprotein (p-value = 0.114). Similarly no relationship was found of smoking, weight, height and body mass index with ABO blood groups, p-values 0.428, 0.528, 0.908 and 0.455 respectively. Conclusion: There is no association of ABO blood groups and major ischaemic heart disease risk factors. (author)

  6. Atomic force microscopy-based antibody recognition imaging of proteins in the pathological deposits in Pseudoexfoliation Syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Creasey, Rhiannon [School of Chemical and Physical Sciences, Flinders University of SA, GPO Box 2100, Adelaide, SA 5001 (Australia); Sharma, Shiwani [School of Medicine, Ophthalmology, Flinders University of SA, GPO Box 2100, Adelaide, SA 5001 (Australia); Gibson, Christopher T. [School of Chemical and Physical Sciences, Flinders University of SA, GPO Box 2100, Adelaide, SA 5001 (Australia); Craig, Jamie E. [School of Medicine, Ophthalmology, Flinders University of SA, GPO Box 2100, Adelaide, SA 5001 (Australia); Ebner, Andreas [Institute for Biophysics, Johannes Kepler Universitaet Linz, Altenbergerstr. 69, A-4040 Linz (Austria); Becker, Thomas [Nanochemistry Research Institute, Curtin University, GPO Box U1987, Perth, 6845 WA (Australia); Hinterdorfer, Peter [Institute for Biophysics, Johannes Kepler Universitaet Linz, Altenbergerstr. 69, A-4040 Linz (Austria); Voelcker, Nicolas H., E-mail: nico.voelcker@flinders.edu.au [School of Chemical and Physical Sciences, Flinders University of SA, GPO Box 2100, Adelaide, SA 5001 (Australia)

    2011-07-15

    The phenomenon of protein aggregation is of considerable interest to various disciplines, including the field of medicine. A range of disease pathologies are associated with this phenomenon. One of the ocular diseases hallmarked by protein aggregation is the Pseudoexfoliation (PEX) Syndrome. This condition is characterized by the deposition of insoluble proteinaceous material on the anterior human lens capsule. Genomic and proteomic analyses have revealed an association of specific genetic markers and various proteins, respectively, with PEX syndrome. However, the ultrastructure of the protein aggregates is poorly characterized. This study seeks to build capacity to determine the molecular nature of PEX aggregates on human lens capsules in their native state by AFM-based antibody recognition imaging. Lysyl oxidase-Like 1 (LOXL1), a protein identified as a component of PEX aggregates, is detected by an antibody-modified AFM probe. Topographical AFM images and antibody recognition images are obtained using three AFM-based techniques: TREC, phase and force-volume imaging. LOXL1 is found to be present on the lens capsule surface, and is localized around fibrous protein aggregates. Our evaluation shows that TREC imaging is best suited for human tissue imaging and holds significant potential for imaging of human disease tissues in their native state. -- Highlights: {yields} Atomic force microscopy techniques were applied to diseased human tissues. {yields} LOXL1 protein was detected on the small fibers of Pseudoexfoliation deposits. {yields} PicoTREC was the optimum technique for investigating protein aggregates.

  7. Longitudinal social-interpersonal functioning among higher-risk responders to acute-phase cognitive therapy for recurrent major depressive disorder.

    Science.gov (United States)

    Vittengl, Jeffrey R; Clark, Lee Anna; Thase, Michael E; Jarrett, Robin B

    2016-07-15

    Social-interpersonal dysfunction increases disability in major depressive disorder (MDD). Here we clarified the durability of improvements in social-interpersonal functioning made during acute-phase cognitive therapy (CT), whether continuation CT (C-CT) or fluoxetine (FLX) further improved functioning, and relations of functioning with depressive symptoms and relapse/recurrence. Adult outpatients (N=241) with recurrent MDD who responded to acute-phase CT with higher risk of relapse (due to unstable or partial remission) were randomized to 8 months of C-CT, FLX, or pill placebo plus clinical management (PBO) and followed 24 additional months. We analyzed repeated measures of patients' social adjustment, interpersonal problems, dyadic adjustment, depressive symptoms, and major depressive relapse/recurrence. Large improvements in social-interpersonal functioning occurring during acute-phase CT (median d=1.4) were maintained, with many patients (median=66%) scoring in normal ranges for 32 months. Social-interpersonal functioning did not differ significantly among C-CT, FLX, and PBO arms. Beyond concurrently measured residual symptoms, deterioration in social-interpersonal functioning preceded and predicted upticks in depressive symptoms and major depressive relapse/recurrence. Results may not generalize to other patient populations, treatment protocols, or measures of social-interpersonal functioning. Mechanisms of risk connecting poorer social-interpersonal functioning with depression were not studied. Average improvements in social-interpersonal functioning among higher-risk responders to acute phase CT are durable for 32 months. After acute-phase CT, C-CT or FLX may not further improve social-interpersonal functioning. Among acute-phase CT responders, deteriorating social-interpersonal functioning provides a clear, measurable signal of risk for impending major depressive relapse/recurrence and opportunity for preemptive intervention. Copyright © 2016 Elsevier B

  8. Carotid Stenting in Patients With High Risk Versus Standard Risk for Open Carotid Endarterectomy (REAL-1 Trial).

    Science.gov (United States)

    De Haro, Joaquin; Michel, Ignacio; Bleda, Silvia; Cañibano, Cristina; Acin, Francisco

    2017-07-15

    Carotid stenting (CAS) has been mainly offered to those patients considered at "high risk" for open carotid endarterectomy based on available data from large randomized clinical trials. However, several recent studies have called medical "high risk" into question for CAS indication. The REAL-1 trial evaluated the safety and perioperative and long-term effectiveness in patients with significant carotid artery stenosis with "high-risk" criteria treated with CAS and proximal protection device (MOMA) compared with those with standard surgical-risk features. This nonrandomized double-arm registry included 125 patients (40% symptomatic), 71 (56%) with "standard-risk" and 54 (44%) with "high-risk" criteria. The primary end point was the cumulative incidence of any major adverse event, a composite of stroke, myocardial infarction, and death within 30 days after the intervention or ipsilateral stroke after 30 days and up to 4 years. There was no significant difference in primary end point rate at 30 days between patients at "standard risk" and those with "high risk" (1.4% vs 1.9% respectively; hazard ratio for "standard risk" 1.1; 95% CI 0.8 to 1.2, p = 0.77) nor estimated 4-year rate of ipsilateral stroke (1.3% vs 1.8%; hazard ratio for "standard risk" 1.05, 95% CI 0.86 to 1.14, p = 0.9). In conclusion, 4-year postprocedure results demonstrated that CAS with proximal device (MOMA) is safe and effective for patients with and without "high-risk" for carotid endarterectomy. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. No Major Host Genetic Risk Factor Contributed to A(H1N1)2009 Influenza Severity.

    Science.gov (United States)

    Garcia-Etxebarria, Koldo; Bracho, María Alma; Galán, Juan Carlos; Pumarola, Tomàs; Castilla, Jesús; Ortiz de Lejarazu, Raúl; Rodríguez-Dominguez, Mario; Quintela, Inés; Bonet, Núria; Garcia-Garcerà, Marc; Domínguez, Angela; González-Candelas, Fernando; Calafell, Francesc

    2015-01-01

    While most patients affected by the influenza A(H1N1) pandemic experienced mild symptoms, a small fraction required hospitalization, often without concomitant factors that could explain such a severe course. We hypothesize that host genetic factors could contribute to aggravate the disease. To test this hypothesis, we compared the allele frequencies of 547,296 genome-wide single nucleotide polymorphisms (SNPs) between 49 severe and 107 mild confirmed influenza A cases, as well as against a general population sample of 549 individuals. When comparing severe vs. mild influenza A cases, only one SNP was close to the conventional p = 5×10-8. This SNP, rs28454025, sits in an intron of the GSK233 gene, which is involved in a neural development, but seems not to have any connections with immunological or inflammatory functions. Indirectly, a previous association reported with CD55 was replicated. Although sample sizes are low, we show that the statistical power in our design was sufficient to detect highly-penetrant, quasi-Mendelian genetic factors. Hence, and assuming that rs28454025 is likely to be a false positive, no major genetic factor was detected that could explain poor influenza A course.

  10. "Nudges" to Prevent Behavioral Risk Factors Associated With Major Depressive Disorder.

    Science.gov (United States)

    Woodend, Ashleigh; Schölmerich, Vera; Denktaş, Semiha

    2015-11-01

    Major depressive disorder-colloquially called "depression"-is a primary global cause of disability. Current preventive interventions, such as problem-solving therapy, are effective but also expensive. "Nudges" are easy and cheap interventions for altering behavior. We have explored how nudging can reduce three behavioral risk factors of depression: low levels of physical activity, inappropriate coping mechanisms, and inadequate maintenance of social ties. These nudges use cognitive biases associated with these behavioral risks, such as valuing the present more than the future, following the herd or the norm, making different choices in light of equivalent conditions, and deciding on the basis of salience or attachment to status quo.

  11. Association between influenza vaccination and reduced risks of major adverse cardiovascular events in elderly patients.

    Science.gov (United States)

    Chiang, Ming-Hsien; Wu, Hau-Hsin; Shih, Chia-Jen; Chen, Yung-Tai; Kuo, Shu-Chen; Chen, Te-Li

    2017-11-01

    This study was conducted to determine the protective effect of influenza vaccine against primary major adverse cardiovascular events (MACEs) in elderly patients, especially those with influenza-like illness (ILI). This retrospective, population-based case-control study of an elderly population (age≥65 years) was conducted using Taiwan's National Health Insurance Research Database (2000-2013). One control was selected for each MACE case (n=80,363 each), matched according to age, year of study entry, and predisposing factors for MACEs. ILI and MACEs (myocardial infarction [MI] and ischemic stroke) were defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification. Odds ratios (ORs) were calculated for the association between MACEs and vaccination. Influenza vaccination received in the previous year was associated with reduced risks of primary MACEs overall (adjusted OR [aOR] 0.80, 95% CI 0.78-0.82, Prisks of MACEs (aOR 1.24, 95% CI 1.18-1.29, PVaccination attenuated the heightened risks associated with ILI (MACEs: aOR 0.99, 95% CI 0.92-1.07, P=.834; MI: aOR 1.05, 95% CI 0.92-1.21, P=.440; ischemic stroke: aOR 0.96, 95% CI 0.89-1.05, P=.398). Results of this study suggest that influenza vaccination is associated with reduced primary MACE risks in the elderly population, including those with ILI. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Major depression as a risk factor for high blood pressure: epidemiologic evidence from a national longitudinal study.

    Science.gov (United States)

    Patten, Scott B; Williams, Jeanne V A; Lavorato, Dina H; Campbell, Norman R C; Eliasziw, Michael; Campbell, Tavis S

    2009-04-01

    To determine whether major depression (MD) leads to an increased risk of new-onset high blood pressure diagnoses. The data source was the Canadian National Population Health Survey (NPHS). The NPHS included a short-form version of the Composite International Diagnostic Interview (CIDI-SF) to assess MD and collected self-report data about professionally diagnosed high blood pressure and the use of antihypertensive medications. The analysis included 12,270 respondents who did not report high blood pressure or the use of antihypertensive medications at a baseline interview conducted in 1994. Proportional hazards models were used to compare the incidence of high blood pressure in respondents with and without MD during 10 years of subsequent follow-up. After adjustment for age, the risk of developing high blood pressure was elevated in those with MD. The hazard ratio was 1.6 (95% Confidence Interval = 1.2-2.1), p = .001, indicating a 60% increase in risk. Adjustment for additional covariates did not alter the association. MD may be a risk factor for new-onset high blood pressure. Epidemiologic data cannot definitely confirm a causal role, and the association may be due to shared etiologic factors. However, the increased risk may warrant closer monitoring of blood pressure in people with depressive disorders.

  13. Are passive smoking, air pollution and obesity a greater mortality risk than major radiation incidents?

    Directory of Open Access Journals (Sweden)

    Smith Jim T

    2007-04-01

    Full Text Available Abstract Background Following a nuclear incident, the communication and perception of radiation risk becomes a (perhaps the major public health issue. In response to such incidents it is therefore crucial to communicate radiation health risks in the context of other more common environmental and lifestyle risk factors. This study compares the risk of mortality from past radiation exposures (to people who survived the Hiroshima and Nagasaki atomic bombs and those exposed after the Chernobyl accident with risks arising from air pollution, obesity and passive and active smoking. Methods A comparative assessment of mortality risks from ionising radiation was carried out by estimating radiation risks for realistic exposure scenarios and assessing those risks in comparison with risks from air pollution, obesity and passive and active smoking. Results The mortality risk to populations exposed to radiation from the Chernobyl accident may be no higher than that for other more common risk factors such as air pollution or passive smoking. Radiation exposures experienced by the most exposed group of survivors of Hiroshima and Nagasaki led to an average loss of life expectancy significantly lower than that caused by severe obesity or active smoking. Conclusion Population-averaged risks from exposures following major radiation incidents are clearly significant, but may be no greater than those from other much more common environmental and lifestyle factors. This comparative analysis, whilst highlighting inevitable uncertainties in risk quantification and comparison, helps place the potential consequences of radiation exposures in the context of other public health risks.

  14. Using MFM methodology to generate and define major accident scenarios for quantitative risk assessment studies

    DEFF Research Database (Denmark)

    Hua, Xinsheng; Wu, Zongzhi; Lind, Morten

    2017-01-01

    to calculate likelihood of each MAS. Combining the likelihood of each scenario with a qualitative risk matrix, each major accident scenario is thereby ranked for consideration for detailed consequence analysis. The methodology is successfully highlighted using part of BMA-process for production of hydrogen......Generating and defining Major Accident Scenarios (MAS) are commonly agreed as the key step for quantitative risk assessment (QRA). The aim of the study is to explore the feasibility of using Multilevel Flow Modeling (MFM) methodology to formulating MAS. Traditionally this is usually done based...

  15. Changes in geriatric nutritional risk index and risk of major adverse cardiac and cerebrovascular events in incident peritoneal dialysis patients

    Directory of Open Access Journals (Sweden)

    Mi Jung Lee

    2017-12-01

    Full Text Available Background: Geriatric nutritional risk index (GNRI is a validated nutritional assessment method, and lower GNRI values are closely associated with adverse clinical outcomes in dialysis patients. This study investigated the impact of changes in GNRI during the first year of dialysis on cardiovascular outcomes in incident peritoneal dialysis (PD patients. Methods: We reviewed medical records in 133 incident PD patients to determine GNRI at the start of PD and after 12 months. Patients were categorized into improved (delta GNRI > 0 and worsening/stationary (delta GNRI ≤ 0 groups. The primary outcome was major adverse cardiac and cerebrovascular events (MACCEs. Results: During a mean follow-up of 51.1 months, the primary outcome was observed in 42 patients (31.6%. The baseline GNRI at PD initiation was not significantly associated with MACCEs (log-rank test, P = 0.40. However, the cumulative event-free rate was significantly lower in the worsening or stationary GNRI group than in the improved group (log-rank test, P = 0.004. Multivariate Cox analysis revealed that a worsening or stationary GNRI was independently associated with higher risk for MACCEs (hazard ratio, 2.47; 95% confidence interval, 1.15–5.29; P = 0.02. In subgroup analysis, patients with worsening or stationary GNRI were at significantly greater risk for MACCEs in both the lower (P = 0.04 and higher (P = 0.01 baseline GNRI groups. Conclusion: Baseline GNRI was not associated with MACCEs, but patients with deteriorating or stationary nutritional status were at significantly greater risk for MACCEs, suggesting that serial monitoring of nutritional status is important to stratify cardiovascular risk in incident PD patients.

  16. Antidepressant use during pregnancy and the risk of major congenital malformations in a cohort of depressed pregnant women: an updated analysis of the Quebec Pregnancy Cohort.

    Science.gov (United States)

    Bérard, Anick; Zhao, Jin-Ping; Sheehy, Odile

    2017-01-12

    Antidepressant use during gestation has been associated with risk of major congenital malformations but estimates can lack statistical power or be confounded by maternal depression. We aimed to determine the association between first-trimester exposure to antidepressants and the risk of major congenital malformations in a cohort of depressed/anxious women. Data were obtained from the Quebec Pregnancy Cohort (QPC). All pregnancies with a diagnosis of depression or anxiety, or exposed to antidepressants in the 12 months before pregnancy, and ending with a live-born singleton were included. Antidepressant classes (selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants (TCA) and other antidepressants) and types were individually compared with non-exposure during the first trimester (depressed untreated). Major congenital malformations overall and organ-specific malformations in the first year of life were identified. 18 487 pregnant women were included. When looking at the specific types of antidepressant used during the first trimester, only citalopram was increasing the risk of major congenital malformations (adjusted OR, (aOR) 1.36, 95% CI 1.08 to 1.73; 88 exposed cases), although there was a trend towards increased risk for the most frequently used antidepressants. Antidepressants with serotonin reuptake inhibition effect (SSRI, SNRI, amitriptyline (the most used TCA)) increased the risk of certain organ-specific defects: paroxetine increased the risk of cardiac defects (aOR 1.45, 95% CI 1.12 to 1.88), and ventricular/atrial septal defects (aOR 1.39, 95% CI 1.00 to 1.93); citalopram increased the risk of musculoskeletal defects (aOR 1.92, 95% CI 1.40 to 2.62), and craniosynostosis (aOR 3.95, 95% CI 2.08 to 7.52); TCA was associated with eye, ear, face and neck defects (aOR 2.45, 95% CI 1.05 to 5.72), and digestive defects (aOR 2.55, 95% CI 1.40 to 4.66); and venlafaxine was associated with

  17. Risk factors for suicide completion in major depression: a case-control study of impulsive and aggressive behaviors in men.

    Science.gov (United States)

    Dumais, A; Lesage, A D; Alda, M; Rouleau, G; Dumont, M; Chawky, N; Roy, M; Mann, J J; Benkelfat, C; Turecki, Gustavo

    2005-11-01

    Major depression is a major risk factor for suicide. However, not all individuals with major depression commit suicide. Impulsive and aggressive behaviors have been proposed as risk factors for suicide, but it remains unclear whether their effect on the risk of suicide is at least partly explained by axis I disorders commonly associated with suicide, such as major depression. With a case-control design, a comparison of the level of impulsive and aggressive behaviors and the prevalence of associated psychopathology was carried out with control for the presence of primary psychopathology. One hundred and four male suicide completers who died during an episode of major depression and 74 living depressed male comparison subjects were investigated with proxy-based interviews by using structured diagnostic instruments and personality trait assessments. The authors found that current (6-month prevalence) alcohol abuse/dependence, current drug abuse/dependence, and cluster B personality disorders increased the risk of suicide in individuals with major depression. Also, higher levels of impulsivity and aggression were associated with suicide. An analysis by age showed that these risk factors were more specific to younger suicide victims (ages 18-40). A multivariate analysis indicated that current alcohol abuse/dependence and cluster B personality disorder were two independent predictors of suicide. Impulsive-aggressive personality disorders and alcohol abuse/dependence were two independent predictors of suicide in major depression, and impulsive and aggressive behaviors seem to underlie these risk factors. A developmental hypothesis of suicidal behavior, with impulsive and aggressive behaviors as the starting point, is discussed.

  18. BRIP1 (BACH1 variants and familial breast cancer risk: a case-control study

    Directory of Open Access Journals (Sweden)

    Bugert Peter

    2007-05-01

    Full Text Available Abstract Background Inactivating and truncating mutations of the nuclear BRCA1-interacting protein 1 (BRIP1 have been shown to be the major cause of Fanconi anaemia and, due to subsequent alterations of BRCA1 function, predispose to breast cancer (BC. Methods We investigated the effect of BRIP1 -64G>A and Pro919Ser on familial BC risk by means of TaqMan allelic discrimination, analysing BRCA1/BRCA2 mutation-negative index patients of 571 German BC families and 712 control individuals. Results No significant differences in genotype frequencies between BC cases and controls for BRIP1 -64G>A and Pro919Ser were observed. Conclusion We found no effect of the putatively functional BRIP1 variants -64G>A and Pro919Ser on the risk of familial BC.

  19. Do women in major cities experience better health? A comparison of chronic conditions and their risk factors between women living in major cities and other cities in Indonesia.

    Science.gov (United States)

    Christiani, Yodi; Byles, Julie E; Tavener, Meredith; Dugdale, Paul

    2015-01-01

    Inhabitants of rural areas can be tempted to migrate to urban areas for the type and range of facilities available. Although urban inhabitants may benefit from greater access to human and social services, living in a big city can also bring disadvantages to some residents due to changes in social and physical environments. We analysed data from 4,208 women aged >15 years old participating in the fourth wave of the Indonesia Family Life Survey. Chronic condition risk factors - systolic and diastolic blood pressure (SBP and DBP), body mass index (BMI), and tobacco use - among women in four major cities in Indonesia (Jakarta, Surabaya, Medan, and Bandung) were compared against other cities. Fractional polynomial regression models were applied to examine the association between living in the major cities and SBP, DBP, BMI, and tobacco use. The models were also adjusted for age, education, employment status, migration status, ethnic groups, and religion. The patterns of SBP, DBP, and BMI were plotted and contrasted between groups of cities. Chronic condition prevalence was higher for women in major cities than in contrasting cities (p<0.005). Living in major cities increased the risk of having higher SBP, DBP, BMI and being a current smoker. Chronic disease risk factors in major cities were evident from younger ages. Women residing in Indonesia's major cities have a higher risk of developing chronic conditions, starting at younger ages. The findings highlight the challenges inherent in providing long-term healthcare with its associated cost within major Indonesian cities and the importance of chronic disease prevention programmes targeting women at an early age.

  20. Do women in major cities experience better health? A comparison of chronic conditions and their risk factors between women living in major cities and other cities in Indonesia

    Directory of Open Access Journals (Sweden)

    Yodi Christiani

    2015-12-01

    Full Text Available Background: Inhabitants of rural areas can be tempted to migrate to urban areas for the type and range of facilities available. Although urban inhabitants may benefit from greater access to human and social services, living in a big city can also bring disadvantages to some residents due to changes in social and physical environments. Design: We analysed data from 4,208 women aged >15 years old participating in the fourth wave of the Indonesia Family Life Survey. Chronic condition risk factors – systolic and diastolic blood pressure (SBP and DBP, body mass index (BMI, and tobacco use – among women in four major cities in Indonesia (Jakarta, Surabaya, Medan, and Bandung were compared against other cities. Fractional polynomial regression models were applied to examine the association between living in the major cities and SBP, DBP, BMI, and tobacco use. The models were also adjusted for age, education, employment status, migration status, ethnic groups, and religion. The patterns of SBP, DBP, and BMI were plotted and contrasted between groups of cities. Results: Chronic condition prevalence was higher for women in major cities than in contrasting cities (p<0.005. Living in major cities increased the risk of having higher SBP, DBP, BMI and being a current smoker. Chronic disease risk factors in major cities were evident from younger ages. Conclusions: Women residing in Indonesia's major cities have a higher risk of developing chronic conditions, starting at younger ages. The findings highlight the challenges inherent in providing long-term healthcare with its associated cost within major Indonesian cities and the importance of chronic disease prevention programmes targeting women at an early age.

  1. Report by the Delegate for major risks for 2010

    International Nuclear Information System (INIS)

    Michel, Laurent

    2011-01-01

    The first part of this report comments the major natural and industrial disasters which occurred in 2010 in France (Xynthia tempest, flooding, and forest fires) and in other countries. It also proposes some lessons from these disasters. The second part discusses the evolution towards a resilient society by a combined approach of sustainable development, of cultural good safeguarding, and person protection. It also discusses a prospective approach regarding natural hazards and technological accidents, adapted procedures, governance and land planning, the evolution of information and alarm systems, and emerging risks. The third part addresses the adaptation to natural hazards: frameworks and strategies, actions (regulatory prevention, flooding management, safety of hydraulic works, seismic plan). It assesses the financial and budgetary means brought by the State and its partners, and discusses some perspectives. It addresses the technological risks: legal and regulatory evolutions, safety of hazardous industrial installations, consequences of technological accidents. The next part deals with the control of civilian nuclear installations by the ASN. The last part presents the different involved structures and authorities

  2. SU-F-T-243: Major Risks in Radiotherapy. A Review Based On Risk Analysis Literature

    Energy Technology Data Exchange (ETDEWEB)

    López-Tarjuelo, J; Guasp-Tortajada, M; Iglesias-Montenegro, N; Monasor-Denia, P [Servicio de Radiofísica y Protección Radiológica, Consorcio Hospitalario Provincial de Castellón, Castellón de la Plana, España/Spain (Spain); Bouché-Babiloni, A; Morillo-Macías, V; Ferrer-Albiach, C [Servicio de Oncología Radioterápica, Consorcio Hospitalario Provincial de Castellón, Castellón de la Plana, España/Spain (Spain)

    2016-06-15

    Purpose: We present a literature review of risk analyses in radiotherapy to highlight the most reported risks and facilitate the spread of this valuable information so that professionals can be aware of these major threats before performing their own studies. Methods: We considered studies with at least an estimation of the probability of occurrence of an adverse event (O) and its associated severity (S). They cover external beam radiotherapy, brachytherapy, intraoperative radiotherapy, and stereotactic techniques. We selected only the works containing a detailed ranked series of elements or failure modes and focused on the first fully reported quartile as much. Afterward, we sorted the risk elements according to a regular radiotherapy procedure so that the resulting groups were cited in several works and be ranked in this way. Results: 29 references published between 2007 and February 2016 were studied. Publication trend has been generally rising. The most employed analysis has been the Failure mode and effect analysis (FMEA). Among references, we selected 20 works listing 258 ranked risk elements. They were sorted into 31 groups appearing at least in two different works. 11 groups appeared in at least 5 references and 5 groups did it in 7 or more papers. These last sets of risks where choosing another set of images or plan for planning or treating, errors related with contours, errors in patient positioning for treatment, human mistakes when programming treatments, and planning errors. Conclusion: There is a sufficient amount and variety of references for identifying which failure modes or elements should be addressed in a radiotherapy department before attempting a specific analysis. FMEA prevailed, but other studies such as “risk matrix” or “occurrence × severity” analyses can also lead professionals’ efforts. Risk associated with human actions ranks very high; therefore, they should be automated or at least peer-reviewed.

  3. SU-F-T-243: Major Risks in Radiotherapy. A Review Based On Risk Analysis Literature

    International Nuclear Information System (INIS)

    López-Tarjuelo, J; Guasp-Tortajada, M; Iglesias-Montenegro, N; Monasor-Denia, P; Bouché-Babiloni, A; Morillo-Macías, V; Ferrer-Albiach, C

    2016-01-01

    Purpose: We present a literature review of risk analyses in radiotherapy to highlight the most reported risks and facilitate the spread of this valuable information so that professionals can be aware of these major threats before performing their own studies. Methods: We considered studies with at least an estimation of the probability of occurrence of an adverse event (O) and its associated severity (S). They cover external beam radiotherapy, brachytherapy, intraoperative radiotherapy, and stereotactic techniques. We selected only the works containing a detailed ranked series of elements or failure modes and focused on the first fully reported quartile as much. Afterward, we sorted the risk elements according to a regular radiotherapy procedure so that the resulting groups were cited in several works and be ranked in this way. Results: 29 references published between 2007 and February 2016 were studied. Publication trend has been generally rising. The most employed analysis has been the Failure mode and effect analysis (FMEA). Among references, we selected 20 works listing 258 ranked risk elements. They were sorted into 31 groups appearing at least in two different works. 11 groups appeared in at least 5 references and 5 groups did it in 7 or more papers. These last sets of risks where choosing another set of images or plan for planning or treating, errors related with contours, errors in patient positioning for treatment, human mistakes when programming treatments, and planning errors. Conclusion: There is a sufficient amount and variety of references for identifying which failure modes or elements should be addressed in a radiotherapy department before attempting a specific analysis. FMEA prevailed, but other studies such as “risk matrix” or “occurrence × severity” analyses can also lead professionals’ efforts. Risk associated with human actions ranks very high; therefore, they should be automated or at least peer-reviewed.

  4. Risk of stroke/systemic embolism, major bleeding and associated costs in non-valvular atrial fibrillation patients who initiated apixaban, dabigatran or rivaroxaban compared with warfarin in the United States Medicare population.

    Science.gov (United States)

    Amin, Alpesh; Keshishian, Allison; Trocio, Jeffrey; Dina, Oluwaseyi; Le, Hannah; Rosenblatt, Lisa; Liu, Xianchen; Mardekian, Jack; Zhang, Qisu; Baser, Onur; Vo, Lien

    2017-09-01

    To compare the risk and cost of stroke/systemic embolism (SE) and major bleeding between each direct oral anticoagulant (DOAC) and warfarin among non-valvular atrial fibrillation (NVAF) patients. Patients (≥65 years) initiating warfarin or DOACs (apixaban, rivaroxaban, and dabigatran) were selected from the Medicare database from 1 January 2013 to 31 December 2014. Patients initiating each DOAC were matched 1:1 to warfarin patients using propensity score matching to balance demographics and clinical characteristics. Cox proportional hazards models were used to estimate the risks of stroke/SE and major bleeding of each DOAC vs. warfarin. Two-part models were used to compare the stroke/SE- and major-bleeding-related medical costs between matched cohorts. Of the 186,132 eligible patients, 20,803 apixaban-warfarin pairs, 52,476 rivaroxaban-warfarin pairs, and 16,731 dabigatran-warfarin pairs were matched. Apixaban (hazard ratio [HR] = 0.40; 95% confidence interval [CI] 0.31, 0.53) and rivaroxaban (HR = 0.72; 95% CI 0.63, 0.83) were significantly associated with lower risk of stroke/SE compared to warfarin. Apixaban (HR = 0.51; 95% CI 0.44, 0.58) and dabigatran (HR = 0.79; 95% CI 0.69, 0.91) were significantly associated with lower risk of major bleeding; rivaroxaban (HR = 1.17; 95% CI 1.10, 1.26) was significantly associated with higher risk of major bleeding compared to warfarin. Compared to warfarin, apixaban ($63 vs. $131) and rivaroxaban ($93 vs. $139) had significantly lower stroke/SE-related medical costs; apixaban ($292 vs. $529) and dabigatran ($369 vs. $450) had significantly lower major bleeding-related medical costs. Among the DOACs in the study, only apixaban is associated with a significantly lower risk of stroke/SE and major bleeding and lower related medical costs compared to warfarin.

  5. Suicidal risk factors of recurrent major depression in Han Chinese women.

    Directory of Open Access Journals (Sweden)

    Yuzhang Zhu

    Full Text Available The relationship between suicidality and major depression is complex. Socio- demography, clinical features, comorbidity, clinical symptoms, and stressful life events are important factors influencing suicide in major depression, but these are not well defined. Thus, the aim of the present study was to assess the associations between the above-mentioned factors and suicide ideation, suicide plan, and suicide attempt in 6008 Han Chinese women with recurrent major depression (MD. Patients with any suicidality had significantly more MD symptoms, a significantly greater number of stressful life events, a positive family history of MD, a greater number of episodes, a significant experience of melancholia, and earlier age of onset. Comorbidity with dysthymia, generalized anxiety disorder (GAD, social phobia, and animal phobia was seen in suicidal patients. The present findings indicate that specific factors act to increase the likelihood of suicide in MD. Our results may help improve the clinical assessment of suicide risk in depressed patients, especially for women.

  6. SEEDi1.0-3.0 strategies for major noncommunicable diseases in China.

    Science.gov (United States)

    Hu, Chun-Song; Tkebuchava, Tengiz

    2017-07-01

    The purpose of this article is to briefly introduce the status and challenges of major noncommunicable diseases (mNCDs), which include cardiovascular disease, diabetes and cancer, as well as related risk factors, such as environmental pollution, smoking, obesity and sleep disorders. "S-E-E-D" rules or the strategies of "S-E-E-D" intervention (SEEDi) consist of four core healthy elements: sleep, emotion, exercise and diet. The history of SEEDi 1.0-3.0 is also introduced, which includes versions 1.0, 1.5, 2.0 and 3.0 of the program. These guidelines are suitable for prevention and control of mNCDs. Not only the "Healthy China" initiated in China's "13th Five-year Plan," but also the "Healthy World" philosophy needs SEEDi 1.0-3.0 strategies for control of mNCDs.

  7. Cardiovascular risk factors are major determinants of thrombotic risk in patients with the lupus anticoagulant.

    Science.gov (United States)

    Posch, Florian; Gebhart, Johanna; Rand, Jacob H; Koder, Silvia; Quehenberger, Peter; Pengo, Vittorio; Ay, Cihan; Pabinger, Ingrid

    2017-03-10

    Patients with the lupus anticoagulant (LA) are at an increased risk of thrombotic events, which in turn increase the risk of death. Understanding the determinants of thrombotic risk in patients with LA may pave the way towards targeted thromboprophylaxis. In the Vienna Lupus Anticoagulant and Thrombosis Study (LATS), we systematically evaluate risk factors for thrombotic events in patients with LA. We followed 150 patients (mean age: 41.3 years, female gender: n = 122 (81.3%), history of thrombosis or pregnancy complications: n = 111 (74.0%)), who tested repeatedly positive for LA until development of thrombosis, death, or censoring. The primary endpoint was a composite of arterial or venous thrombotic events (TEs). During a median follow-up of 9.5 years (range: 12 days-13.6 years) and 1076 person-years, 32 TEs occurred (arterial: n = 16, venous: n = 16; cumulative 10-year TE incidence: 24.3%). A prolonged lupus-sensitive activated partial thromboplastin time (aPTT-LA) (adjusted subdistribution hazard ratio (SHR) = 2.31, 95% CI: 1.07--5.02), diabetes (adjusted SHR = 4.39, 95% CI: 1.42-13.57), and active smoking (adjusted SHR = 2.31, 95% CI: 1.14-5.02) emerged as independent risk factors of both arterial and venous thrombotic risk. A risk model that includes a prolonged lupus-sensitive aPTT, smoking, and diabetes enabled stratification of LA patients into subgroups with a low, intermediate, and high risk of thrombosis (5-year TE risk of 9.7% (n = 77), 30.9% (n = 51), and 56.8% (n = 22). Long-term thrombotic risk in patients with LA is clustered within subjects harboring typical cardiovascular risk factors in addition to a prolonged lupus-sensitive aPTT, whereas patients with none of these risk factors represent a large subgroup with a low risk of thrombosis.

  8. Excess risk of major vascular diseases associated with airflow obstruction: a 9-year prospective study of 0.5 million Chinese adults

    Directory of Open Access Journals (Sweden)

    Kurmi OP

    2018-03-01

    Full Text Available Om P Kurmi,1 Liming Li,2 Kourtney J Davis,3 Jenny Wang,1 Derrick A Bennett,1 Ka Hung Chan,1 Ling Yang,1 Yiping Chen,1 Yu Guo,4 Zheng Bian,4 Junshi Chen,5 Liuping Wei,6 Donghui Jin,7 Rory Collins,1 Richard Peto,1 Zhengming Chen1 On behalf of the China Kadoorie Biobank collaborative group 1Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK; 2Department of Epidemiology, School of Public Health, Peking University Health Science Center, Beijing, China; 3Real World Evidence and Epidemiology, GlaxoSmithKline, Collegeville, PA, USA; 4Chinese Academy of Medical Sciences, Beijing China; 5China National Center for Food Safety Risk Assessment, Beijing, China; 6NCDs Prevention and Control Department, Liuzhou CDC, Liuzhou, China; 7NCDs Prevention and Control Department, Hunan CDC, Changsha, China Background: China has high COPD rates, even among never-regular smokers. Little is known about nonrespiratory disease risks, especially vascular morbidity and mortality after developing airflow obstruction (AFO in Chinese adults. Objective: We aimed to investigate the prospective association of prevalent AFO with major vascular morbidity and mortality. Materials and methods: In 2004–2008, a nationwide prospective cohort study recruited 512,891 men and women aged 30–79 years from 10 diverse localities across China, tracking cause-specific mortality and coded episodes of hospitalization for 9 years. Cox regression yielded adjusted HRs for vascular diseases comparing individuals with spirometry-defined prevalent AFO at baseline to those without. Results: Of 489,382 participants with no vascular disease at baseline, 6.8% had AFO, with prevalence rising steeply with age. Individuals with prevalent AFO had significantly increased vascular mortality (n=1,429, adjusted HR 1.29, 95% CI 1.21–1.36. There were also increased risks of hemorrhagic stroke (n=823, HR 1.18, 95% CI 1.09–1

  9. Identification of Major Risk Sources for Surface Water Pollution by Risk Indexes (RI) in the Multi-Provincial Boundary Region of the Taihu Basin, China.

    Science.gov (United States)

    Yao, Hong; Li, Weixin; Qian, Xin

    2015-08-21

    Environmental safety in multi-district boundary regions has been one of the focuses in China and is mentioned many times in the Environmental Protection Act of 2014. Five types were categorized concerning the risk sources for surface water pollution in the multi-provincial boundary region of the Taihu basin: production enterprises, waste disposal sites, chemical storage sites, agricultural non-point sources and waterway transportations. Considering the hazard of risk sources, the purification property of environmental medium and the vulnerability of risk receptors, 52 specific attributes on the risk levels of each type of risk source were screened out. Continuous piecewise linear function model, expert consultation method and fuzzy integral model were used to calculate the integrated risk indexes (RI) to characterize the risk levels of pollution sources. In the studied area, 2716 pollution sources were characterized by RI values. There were 56 high-risk sources screened out as major risk sources, accounting for about 2% of the total. The numbers of sources with high-moderate, moderate, moderate-low and low pollution risk were 376, 1059, 101 and 1124, respectively, accounting for 14%, 38%, 5% and 41% of the total. The procedure proposed could be included in the integrated risk management systems of the multi-district boundary region of the Taihu basin. It could help decision makers to identify major risk sources in the risk prevention and reduction of surface water pollution.

  10. Perioperative risk factors for postoperative pneumonia after major oral cancer surgery: A retrospective analysis of 331 cases.

    Science.gov (United States)

    Xu, Jieyun; Hu, Jing; Yu, Pei; Wang, Weiwang; Hu, Xingxue; Hou, Jinsong; Fang, Silian; Liu, Xiqiang

    2017-01-01

    Postoperative pneumonia (POP) is common and results in prolonged hospital stays, higher costs, increased morbidity and mortality. However, data on the incidence and risk factors of POP after oral and maxillofacial surgery are rare. This study aims to identify perioperative risk factors for POP after major oral cancer (OC) surgery. Perioperative data and patient records of 331 consecutive subjects were analyzed in the period of April 2014 to March 2016. We individually traced each OC patient for a period to discharge from the hospital or 45 days after surgery, whichever occur later. The incidence of POP after major OC surgery with free flap construction or major OC surgery was 11.6% or 4.5%, respectively. Patient-related risk factors for POP were male sex, T stage, N stage, clinical stage and preoperative serum albumin level. Among the investigated procedure-related variables, incision grade, mandibulectomy, free flap reconstruction, tracheotomy, intraoperative blood loss, and the length of the operation were shown to be associated with the development of POP. Postoperative hospital stay was also significantly related to increased incidence of POP. Using a multivariable logistic regression model, we identified male sex, preoperative serum albumin level, operation time and postoperative hospital stay as independent risk factors for POP. Several perioperative risk factors can be identified that are associated with POP. At-risk oral cancer patients should be subjected to intensified postoperative pulmonary care.

  11. Financial risks in major investment projects

    International Nuclear Information System (INIS)

    Segelod, Esbjoern

    2006-01-01

    We have probably all read about large projects which proved far more expensive than anticipated, projects such as the Channel tunnel which cost 80% more than planned, and the oil pipeline between the oil field in Prudhoe Bay in Northern Alaska and the oil terminal in Vadez in the south which overran its budget by 1,000%. The purpose of this paper is to summarise our knowledge of the risk of cost escalation. Which projects are more likely than others to be hit by cost escalation, and why

  12. Major stressful life events and other risk factors for first admission with mania

    DEFF Research Database (Denmark)

    Kessing, L.V.; Agerbo, E.; Mortensen, P.B.

    2004-01-01

    OBJECTIVES: To investigate whether first admission with mania is associated with the occurrence of death in the family or with major stressful life events and to explore whether the associations change with age. METHODS: Case register study with linkage of the Danish Psychiatric Central Research...... was found on the association between life events and the first admission with mania, totally, or for men or women, separately regarding ageing. CONCLUSIONS: The occurrence of death in the family and the experience of major life events are associated with increased risk of first admission with bipolar...

  13. Sex similarities and differences in risk factors for recurrence of major depression.

    Science.gov (United States)

    van Loo, Hanna M; Aggen, Steven H; Gardner, Charles O; Kendler, Kenneth S

    2017-11-27

    Major depression (MD) occurs about twice as often in women as in men, but it is unclear whether sex differences subsist after disease onset. This study aims to elucidate potential sex differences in rates and risk factors for MD recurrence, in order to improve prediction of course of illness and understanding of its underlying mechanisms. We used prospective data from a general population sample (n = 653) that experienced a recent episode of MD. A diverse set of potential risk factors for recurrence of MD was analyzed using Cox models subject to elastic net regularization for males and females separately. Accuracy of the prediction models was tested in same-sex and opposite-sex test data. Additionally, interactions between sex and each of the risk factors were investigated to identify potential sex differences. Recurrence rates and the impact of most risk factors were similar for men and women. For both sexes, prediction models were highly multifactorial including risk factors such as comorbid anxiety, early traumas, and family history. Some subtle sex differences were detected: for men, prediction models included more risk factors concerning characteristics of the depressive episode and family history of MD and generalized anxiety, whereas for women, models included more risk factors concerning early and recent adverse life events and socioeconomic problems. No prominent sex differences in risk factors for recurrence of MD were found, potentially indicating similar disease maintaining mechanisms for both sexes. Course of MD is a multifactorial phenomenon for both males and females.

  14. Do major depressive disorder and dysthymic disorder confer differential risk for suicide?

    Science.gov (United States)

    Witte, Tracy K; Timmons, Katherine A; Fink, Erin; Smith, April R; Joiner, Thomas E

    2009-05-01

    Although there has been a tremendous amount of research examining the risk conferred for suicide by depression in general, relatively little research examines the risk conferred by specific forms of depressive illness (e.g., dysthymic disorder, single episode versus recurrent major depressive disorder [MDD]). The purpose of the current study was to examine differences in suicidal ideation, clinician-rated suicide risk, suicide attempts, and family history of suicide in a sample of outpatients diagnosed with various forms of depressive illness. To accomplish this aim, we conducted a cluster analysis using the aforementioned suicide-related variables in a sample of 494 outpatients seen between January 2001 and July 2007 at the Florida State University Psychology Clinic. Patients were diagnosed using DSM-IV criteria. Two distinct clusters emerged that were indicative of lower and higher risk for suicide. After controlling for the number of comorbid Axis I and Axis II diagnoses, the only depressive illness that significantly predicted cluster membership was recurrent MDD, which tripled an individual's likelihood of being assigned to the higher risk cluster. The use of a cross-sectional design; the relatively low suicide risk in our sample; the relatively small number of individuals with double depression. Our results demonstrate the importance of both chronicity and severity of depression in terms of predicting increased suicide risk. Among the various forms of depressive illness examined, only recurrent MDD appeared to confer greater risk for suicide.

  15. Identification of Major Risk Sources for Surface Water Pollution by Risk Indexes (RI in the Multi-Provincial Boundary Region of the Taihu Basin, China

    Directory of Open Access Journals (Sweden)

    Hong Yao

    2015-08-01

    Full Text Available Environmental safety in multi-district boundary regions has been one of the focuses in China and is mentioned many times in the Environmental Protection Act of 2014. Five types were categorized concerning the risk sources for surface water pollution in the multi-provincial boundary region of the Taihu basin: production enterprises, waste disposal sites, chemical storage sites, agricultural non-point sources and waterway transportations. Considering the hazard of risk sources, the purification property of environmental medium and the vulnerability of risk receptors, 52 specific attributes on the risk levels of each type of risk source were screened out. Continuous piecewise linear function model, expert consultation method and fuzzy integral model were used to calculate the integrated risk indexes (RI to characterize the risk levels of pollution sources. In the studied area, 2716 pollution sources were characterized by RI values. There were 56 high-risk sources screened out as major risk sources, accounting for about 2% of the total. The numbers of sources with high-moderate, moderate, moderate-low and low pollution risk were 376, 1059, 101 and 1124, respectively, accounting for 14%, 38%, 5% and 41% of the total. The procedure proposed could be included in the integrated risk management systems of the multi-district boundary region of the Taihu basin. It could help decision makers to identify major risk sources in the risk prevention and reduction of surface water pollution.

  16. Identification of Major Risk Sources for Surface Water Pollution by Risk Indexes (RI) in the Multi-Provincial Boundary Region of the Taihu Basin, China

    Science.gov (United States)

    Yao, Hong; Li, Weixin; Qian, Xin

    2015-01-01

    Environmental safety in multi-district boundary regions has been one of the focuses in China and is mentioned many times in the Environmental Protection Act of 2014. Five types were categorized concerning the risk sources for surface water pollution in the multi-provincial boundary region of the Taihu basin: production enterprises, waste disposal sites, chemical storage sites, agricultural non-point sources and waterway transportations. Considering the hazard of risk sources, the purification property of environmental medium and the vulnerability of risk receptors, 52 specific attributes on the risk levels of each type of risk source were screened out. Continuous piecewise linear function model, expert consultation method and fuzzy integral model were used to calculate the integrated risk indexes (RI) to characterize the risk levels of pollution sources. In the studied area, 2716 pollution sources were characterized by RI values. There were 56 high-risk sources screened out as major risk sources, accounting for about 2% of the total. The numbers of sources with high-moderate, moderate, moderate-low and low pollution risk were 376, 1059, 101 and 1124, respectively, accounting for 14%, 38%, 5% and 41% of the total. The procedure proposed could be included in the integrated risk management systems of the multi-district boundary region of the Taihu basin. It could help decision makers to identify major risk sources in the risk prevention and reduction of surface water pollution. PMID:26308032

  17. Perceived parenting and risk for major depression in Chinese women.

    Science.gov (United States)

    Gao, J; Li, Y; Cai, Y; Chen, J; Shen, Y; Ni, S; Wei, Y; Qiu, Y; Zhu, X; Liu, Y; Lu, C; Chen, C; Niu, Q; Tang, C; Yang, Y; Wang, Q; Cui, W; Xia, J; Liu, T; Zhang, J; Zhao, B; Guo, Z; Pan, J; Chen, H; Luo, Y; Sun, L; Xiao, X; Chen, Q; Zhao, X; He, F; Lv, L; Guo, L; Liu, L; Li, H; Shi, S; Flint, J; Kendler, K S; Tao, M

    2012-05-01

    In Western countries, a history of major depression (MD) is associated with reports of received parenting that is low in warmth and caring and high in control and authoritarianism. Does a similar pattern exist in women in China? Received parenting was assessed by a shortened version of the Parental Bonding Instrument (PBI) in two groups of Han Chinese women: 1970 clinically ascertained cases with recurrent MD and 2597 matched controls. MD was assessed at personal interview. Factor analysis of the PBI revealed three factors for both mothers and fathers: warmth, protectiveness, and authoritarianism. Lower warmth and protectiveness and higher authoritarianism from both mother and father were significantly associated with risk for recurrent MD. Parental warmth was positively correlated with parental protectiveness and negatively correlated with parental authoritarianism. When examined together, paternal warmth was more strongly associated with lowered risk for MD than maternal warmth. Furthermore, paternal protectiveness was negatively and maternal protectiveness positively associated with risk for MD. Although the structure of received parenting is very similar in China and Western countries, the association with MD is not. High parental protectiveness is generally pathogenic in Western countries but protective in China, especially when received from the father. Our results suggest that cultural factors impact on patterns of parenting and their association with MD.

  18. Lysyl oxidases regulate fibrillar collagen remodelling in idiopathic pulmonary fibrosis

    NARCIS (Netherlands)

    Tjin, Gavin; White, Eric S; Faiz, Alen; Sicard, Delphine; Tschumperlin, Daniel J; Mahar, Annabelle; Kable, Eleanor P W; Burgess, Janette K

    2017-01-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease of the lung with feweffective therapeutic options. Structural remodelling of the extracellular matrix [i.e. collagen cross-linkingmediated by the lysyl oxidase (LO) family of enzymes (LOX, LOXL1-4)] might contribute to disease

  19. The galaxy major merger fraction to {z} 1

    Science.gov (United States)

    López-Sanjuan, C.; Balcells, M.; Pérez-González, P. G.; Barro, G.; García-Dabó, C. E.; Gallego, J.; Zamorano, J.

    2009-07-01

    Aims: The importance of disc-disc major mergers in galaxy evolution remains uncertain. We study the major merger fraction in a SPITZER/IRAC-selected catalogue in the GOODS-S field up to z 1 for luminosity- and mass-limited samples. Methods: We select disc-disc merger remnants on the basis of morphological asymmetries/distortions, and address three main sources of systematic errors: (i) we explicitly apply morphological K-corrections; (ii) we measure asymmetries in galaxies artificially redshifted to zd = 1.0 to deal with loss of morphological information with redshift; and (iii) we take into account the observational errors in z and A, which tend to overestimate the merger fraction, though use of maximum likelihood techniques. Results: We obtain morphological merger fractions (f_m^mph) below 0.06 up to z 1. Parameterizing the merger fraction evolution with redshift as f_m^mph(z) = f_m^mph(0) (1+z)^m, we find that m = 1.8 ± 0.5 for MB ≤ -20 galaxies, while m = 5.4 ± 0.4 for Mstar ≥ 1010 M⊙ galaxies. When we translate our merger fractions to merger rates (Re_m^mph), their evolution, parameterized as Re_m^mph(z) = Re_m^mph(0) (1+z)^n, is quite similar in both cases: n = 3.3 ± 0.8 for MB ≤ -20 galaxies, and n = 3.5 ± 0.4 for Mstar ≥ 1010 M⊙ galaxies. Conclusions: Our results imply that only 8% of today's Mstar ≥ 1010 M⊙ galaxies have undergone a disc-disc major merger since z 1. In addition, 21% of Mstar ≥ 1010 M⊙ galaxies at z 1 have undergone one of these mergers since z 1.5. This suggests that disc-disc major mergers are not the dominant process in the evolution of Mstar ≥ 1010 M⊙ galaxies since z 1, with only 0.2 disc-disc major mergers per galaxy, but may be an important process at z > 1, with ˜1 merger per galaxy at 1 < z < 3.

  20. Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence.

    Science.gov (United States)

    Andersen, Allan M; Pietrzak, Robert H; Kranzler, Henry R; Ma, Li; Zhou, Hang; Liu, Xiaoming; Kramer, John; Kuperman, Samuel; Edenberg, Howard J; Nurnberger, John I; Rice, John P; Tischfield, Jay A; Goate, Alison; Foroud, Tatiana M; Meyers, Jacquelyn L; Porjesz, Bernice; Dick, Danielle M; Hesselbrock, Victor; Boerwinkle, Eric; Southwick, Steven M; Krystal, John H; Weissman, Myrna M; Levinson, Douglas F; Potash, James B; Gelernter, Joel; Han, Shizhong

    2017-11-01

    Major depressive disorder (MDD) and alcohol dependence (AD) are heritable disorders with significant public health burdens, and they are frequently comorbid. Common genetic factors that influence the co-occurrence of MDD and AD have been sought in family, twin, and adoption studies, and results to date have been promising but inconclusive. To examine whether AD and MDD overlap genetically, using a polygenic score approach. Association analyses were conducted between MDD polygenic risk score (PRS) and AD case-control status in European ancestry samples from 4 independent genome-wide association study (GWAS) data sets: the Collaborative Study on the Genetics of Alcoholism (COGA); the Study of Addiction, Genetics, and Environment (SAGE); the Yale-Penn genetic study of substance dependence; and the National Health and Resilience in Veterans Study (NHRVS). Results from a meta-analysis of MDD (9240 patients with MDD and 9519 controls) from the Psychiatric Genomics Consortium were applied to calculate PRS at thresholds from P men; mean [SD] age, 38.2 [10.8] years) and 522 controls (151 [28.9.%] men; age [SD], 43.9 [11.6] years) from COGA; 631 cases (333 [52.8%] men; age [SD], 35.0 [7.7] years) and 756 controls (260 [34.4%] male; age [SD] 36.1 [7.7] years) from SAGE; 2135 cases (1375 [64.4%] men; age [SD], 39.4 [11.5] years) and 350 controls (126 [36.0%] men; age [SD], 43.5 [13.9] years) from Yale-Penn; and 317 cases (295 [93.1%] men; age [SD], 59.1 [13.1] years) and 1719 controls (1545 [89.9%] men; age [SD], 64.5 [13.3] years) from NHRVS. Higher MDD PRS was associated with a significantly increased risk of AD in all samples (COGA: best P = 1.7 × 10-6, R2 = 0.026; SAGE: best P = .001, R2 = 0.01; Yale-Penn: best P = .035, R2 = 0.0018; and NHRVS: best P = .004, R2 = 0.0074), with stronger evidence for association after meta-analysis of the 4 samples (best P = 3.3 × 10-9). In analyses adjusted for MDD status in 3 AD GWAS data

  1. “Nudges” to Prevent Behavioral Risk Factors Associated With Major Depressive Disorder

    Science.gov (United States)

    Schölmerich, Vera; Denktaş, Semiha

    2015-01-01

    Major depressive disorder—colloquially called “depression”—is a primary global cause of disability. Current preventive interventions, such as problem-solving therapy, are effective but also expensive. “Nudges” are easy and cheap interventions for altering behavior. We have explored how nudging can reduce three behavioral risk factors of depression: low levels of physical activity, inappropriate coping mechanisms, and inadequate maintenance of social ties. These nudges use cognitive biases associated with these behavioral risks, such as valuing the present more than the future, following the herd or the norm, making different choices in light of equivalent conditions, and deciding on the basis of salience or attachment to status quo. PMID:26378823

  2. Perioperative risk factors for postoperative pneumonia after major oral cancer surgery: A retrospective analysis of 331 cases.

    Directory of Open Access Journals (Sweden)

    Jieyun Xu

    Full Text Available Postoperative pneumonia (POP is common and results in prolonged hospital stays, higher costs, increased morbidity and mortality. However, data on the incidence and risk factors of POP after oral and maxillofacial surgery are rare. This study aims to identify perioperative risk factors for POP after major oral cancer (OC surgery.Perioperative data and patient records of 331 consecutive subjects were analyzed in the period of April 2014 to March 2016. We individually traced each OC patient for a period to discharge from the hospital or 45 days after surgery, whichever occur later.The incidence of POP after major OC surgery with free flap construction or major OC surgery was 11.6% or 4.5%, respectively. Patient-related risk factors for POP were male sex, T stage, N stage, clinical stage and preoperative serum albumin level. Among the investigated procedure-related variables, incision grade, mandibulectomy, free flap reconstruction, tracheotomy, intraoperative blood loss, and the length of the operation were shown to be associated with the development of POP. Postoperative hospital stay was also significantly related to increased incidence of POP. Using a multivariable logistic regression model, we identified male sex, preoperative serum albumin level, operation time and postoperative hospital stay as independent risk factors for POP.Several perioperative risk factors can be identified that are associated with POP. At-risk oral cancer patients should be subjected to intensified postoperative pulmonary care.

  3. 76 FR 71465 - Defense Federal Acquisition Regulation Supplement: Management of Manufacturing Risk in Major...

    Science.gov (United States)

    2011-11-18

    ... Government procurement. Mary Overstreet, Editor, Defense Acquisition Regulations System. Interim Rule Adopted... Federal Acquisition Regulation Supplement: Management of Manufacturing Risk in Major Defense Acquisition...). ACTION: Final rule. SUMMARY: DoD is adopting as final, without change, an interim rule amending the...

  4. Risk analysis and evaluation of agricultural drought disaster in the major grain-producing areas, China

    Directory of Open Access Journals (Sweden)

    Zongtang Xie

    2016-09-01

    Full Text Available The analysis and evaluation of agricultural drought risk can assist in reducing regional disasters and agricultural drought losses. Because of the uncertainties and incomplete agricultural drought information, this paper employed an information diffusion technology and information matrix to identify a drought disaster risk distribution and to quantify the relationship between the annual drought-affected rate and the grain production losses in China's major grain-producing areas. From the assessment results, provincial drought disaster risk spatial distribution maps for each major grain-producing area in China were obtained. These risk patterns showed that the probability of drought fell when the annual drought-covered rate and the annual drought-affected rate increased, and that the high risk areas were located primarily in China's northern and central provinces. These results can provide the basis for the development of effective drought mitigation strategies which would be able to inform possible drought situations and allow for easier decision-making on drought resistance strategies. The fuzzy relationship between the annual drought-affected rate and the drought-caused grain production losses provides vital information for the development of disaster compensation plans. Furthermore, the results of this study indicated that the proposed methods had superior detection stability and higher precision. We hope that by conducting such agricultural drought risk analysis, the results are able to provide the basis for the development of drought mitigation strategies to reduce future losses.

  5. Modifiable risk factors predicting major depressive disorder at four year follow-up: a decision tree approach.

    Science.gov (United States)

    Batterham, Philip J; Christensen, Helen; Mackinnon, Andrew J

    2009-11-22

    Relative to physical health conditions such as cardiovascular disease, little is known about risk factors that predict the prevalence of depression. The present study investigates the expected effects of a reduction of these risks over time, using the decision tree method favoured in assessing cardiovascular disease risk. The PATH through Life cohort was used for the study, comprising 2,105 20-24 year olds, 2,323 40-44 year olds and 2,177 60-64 year olds sampled from the community in the Canberra region, Australia. A decision tree methodology was used to predict the presence of major depressive disorder after four years of follow-up. The decision tree was compared with a logistic regression analysis using ROC curves. The decision tree was found to distinguish and delineate a wide range of risk profiles. Previous depressive symptoms were most highly predictive of depression after four years, however, modifiable risk factors such as substance use and employment status played significant roles in assessing the risk of depression. The decision tree was found to have better sensitivity and specificity than a logistic regression using identical predictors. The decision tree method was useful in assessing the risk of major depressive disorder over four years. Application of the model to the development of a predictive tool for tailored interventions is discussed.

  6. Modifiable risk factors predicting major depressive disorder at four year follow-up: a decision tree approach

    Directory of Open Access Journals (Sweden)

    Christensen Helen

    2009-11-01

    Full Text Available Abstract Background Relative to physical health conditions such as cardiovascular disease, little is known about risk factors that predict the prevalence of depression. The present study investigates the expected effects of a reduction of these risks over time, using the decision tree method favoured in assessing cardiovascular disease risk. Methods The PATH through Life cohort was used for the study, comprising 2,105 20-24 year olds, 2,323 40-44 year olds and 2,177 60-64 year olds sampled from the community in the Canberra region, Australia. A decision tree methodology was used to predict the presence of major depressive disorder after four years of follow-up. The decision tree was compared with a logistic regression analysis using ROC curves. Results The decision tree was found to distinguish and delineate a wide range of risk profiles. Previous depressive symptoms were most highly predictive of depression after four years, however, modifiable risk factors such as substance use and employment status played significant roles in assessing the risk of depression. The decision tree was found to have better sensitivity and specificity than a logistic regression using identical predictors. Conclusion The decision tree method was useful in assessing the risk of major depressive disorder over four years. Application of the model to the development of a predictive tool for tailored interventions is discussed.

  7. Accumulation of Major Life Events in Childhood and Adult Life and Risk of Type 2 Diabetes Mellitus.

    Directory of Open Access Journals (Sweden)

    Jolene Masters Pedersen

    Full Text Available The aim of the study was to estimate the effect of the accumulation of major life events (MLE in childhood and adulthood, in both the private and working domains, on risk of type 2 diabetes mellitus (T2DM. Furthermore, we aimed to test the possible interaction between childhood and adult MLE and to investigate modification of these associations by educational attainment.The study was based on 4,761 participants from the Copenhagen City Heart Study free of diabetes at baseline and followed for 10 years. MLE were categorized as 0, 1, 2, 3 or more events. Multivariate logistic regression models adjusted for age, sex, education and family history of diabetes were used to estimate the association between MLE and T2DM.In childhood, experiencing 3 or more MLE was associated with a 69% higher risk of developing T2DM (Odds Ratio (OR 1.69; 95% Confidence Interval (CI 1.60, 3.27. The accumulation of MLE in adult private (p-trend = 0.016 and work life (p-trend = 0.049 was associated with risk of T2DM in a dose response manner. There was no evidence that experiencing MLE in both childhood and adult life was more strongly associated with T2DM than experiencing events at only one time point. There was some evidence that being simultaneously exposed to childhood MLE and short education (OR 2.28; 95% C.I. 1.45, 3.59 and work MLE and short education (OR 2.86; 95% C.I. 1.62, 5.03 was associated with higher risk of T2DM, as the joint effects were greater than the sum of their individual effects.Findings from this study suggest that the accumulation of MLE in childhood, private adult life and work life, respectively, are risk factors for developing T2DM.

  8. Perceived parenting and risk for major depression in Chinese women

    Science.gov (United States)

    Gao, J.; Li, Y.; Cai, Y.; Chen, J.; Shen, Y.; Ni, S.; Wei, Y.; Qiu, Y.; Zhu, X.; Liu, Y.; Lu, C.; Chen, C.; Niu, Q.; Tang, C.; Yang, Y.; Wang, Q.; Cui, W.; Xia, J.; Liu, T.; Zhang, J.; Zhao, B.; Guo, Z.; Pan, J.; Chen, H.; Luo, Y.; Sun, L.; Xiao, X.; Chen, Q.; Zhao, X.; He, F.; Lv, L.; Guo, L.; Liu, L.; Li, H.; Shi, S.; Flint, J.; Kendler, K. S.; Tao, M.

    2012-01-01

    Background In Western countries, a history of major depression (MD) is associated with reports of received parenting that is low in warmth and caring and high in control and authoritarianism. Does a similar pattern exist in women in China? Method Received parenting was assessed by a shortened version of the Parental Bonding Instrument (PBI) in two groups of Han Chinese women: 1970 clinically ascertained cases with recurrent MD and 2597 matched controls. MD was assessed at personal interview. Results Factor analysis of the PBI revealed three factors for both mothers and fathers: warmth, protectiveness, and authoritarianism. Lower warmth and protectiveness and higher authoritarianism from both mother and father were significantly associated with risk for recurrent MD. Parental warmth was positively correlated with parental protectiveness and negatively correlated with parental authoritarianism. When examined together, paternal warmth was more strongly associated with lowered risk for MD than maternal warmth. Furthermore, paternal protectiveness was negatively and maternal protectiveness positively associated with risk for MD. Conclusions Although the structure of received parenting is very similar in China and Western countries, the association with MD is not. High parental protectiveness is generally pathogenic in Western countries but protective in China, especially when received from the father. Our results suggest that cultural factors impact on patterns of parenting and their association with MD. PMID:21943491

  9. Low prevalence of human immunodeficiency virus type-1 (HIV-1) infection in population attending a major hospital in New Delhi, India.

    Science.gov (United States)

    Aggarwal, R K; Chattopadhya, D; Kumari, S

    1996-03-01

    During 4 year period between April 1990 and March 1994, 4120 specimens from the patients attending out patient departments of Medical, Surgical and Antenatal units of a major city hospital were tested for HIV infection as a part of an on-going sentinel surveillance programme. In addition, 1440 specimens from the patients attending STD clinic of the same hospital and 862 females seeking termination of pregnancy from a near by hospital were included for comparison. It was found that only 3 individuals with high risk behaviours out of 2002 females attending antenatal clinic showed evidence of HIV infection (rate 1.49 per 1000). The corresponding rate for the group of patients attending STD clinic and seeking termination of pregnancy were 3 out of 1440 (rate 2.15 per 1000) and 1 out of 862 (rate 1.16 per 1000) respectively. It was noted that prevalence of HIV infection in the hospital attending population with unspecified risk factor (medical, surgical and antenatal clinics) was not a matter of serious concern. The importance of finding out risk factors in females attending antenatal clinic is evident from the study.

  10. Risk analysis and evaluation of agricultural drought disaster in the major grain-producing areas, China

    OpenAIRE

    Zongtang Xie; Jiuping Xu; Yanfei Deng

    2016-01-01

    The analysis and evaluation of agricultural drought risk can assist in reducing regional disasters and agricultural drought losses. Because of the uncertainties and incomplete agricultural drought information, this paper employed an information diffusion technology and information matrix to identify a drought disaster risk distribution and to quantify the relationship between the annual drought-affected rate and the grain production losses in China's major grain-producing areas. From the asse...

  11. Female gender and acne disease are jointly and independently associated with the risk of major depression and suicide: a national population-based study.

    Science.gov (United States)

    Yang, Yi-Chien; Tu, Hung-Pin; Hong, Chien-Hui; Chang, Wei-Chao; Fu, Hung-Chun; Ho, Ji-Chen; Chang, Wei-Pin; Chuang, Hung-Yi; Lee, Chih-Hung

    2014-01-01

    Acne is a common disease in adolescence with female preponderance. It could cause poor self-esteem and social phobia. Previous studies based on questionnaires from several thousands of adolescents showed that acne is associated with major depression and suicide. However, the gender- and age-specific risk of depression and suicide in patients with acne remain largely unknown. Using a database from the National Health Insurance, which included 98% of the population of Taiwan in 2006, we identified patients of acne, major depression, and suicide based on ICD-9-CM codes. Totally 47111 patients with acne were identified (16568 males and 30543 females) from 1 million subjects. The youths of 7-12 years had the highest prevalence of acne (14.39%). Major depression was more common in those with acne (0.77%) than controls (0.56% , P suicide was noticed in women with acne. In conclusion, acne and gender, independently and jointly, are associated with major depression and suicide. Special medical support should be warranted in females with acne for the risk of major depression and suicide.

  12. Risk of developing major depressive disorder and anxiety disorders among adolescents and adults with atopic dermatitis: a nationwide longitudinal study.

    Science.gov (United States)

    Cheng, Chih-Ming; Hsu, Ju-Wei; Huang, Kai-Lin; Bai, Ya-Mei; Su, Tung-Ping; Li, Cheng-Ta; Yang, Albert C; Chang, Wen-Han; Chen, Tzeng-Ji; Tsai, Shih-Jen; Chen, Mu-Hong

    2015-06-01

    Previous cross-sectional studies have suggested a comorbid association between atopic dermatitis (AD) and depressive disorder as well as anxiety disorders, but the temporal relationship was not determined. Using the Taiwan National Health Insurance Research Database, 8208 AD patients aged 12 and older without psychiatric history and age-/sex-matched (1:1) controls between 1998 and 2008 were enrolled in our study and followed to the end of 2011. Subjects who developed major depression, any depressive disorder, and anxiety disorders during the follow-up were identified. The Cox regression analysis after adjusting for demographic data and atopic comorbidities demonstrated that patients with AD had an elevated risk of developing major depression (hazard ratio [HR]: 6.56, 95% confidence interval [CI]: 3.64-11.84), any depressive disorder (HR: 5.44, 95% CI: 3.99-7.44), and anxiety disorders (HR: 3.57, 95% CI: 2.55-4.98). Stratified by age group, both adolescents and adults with AD were prone to developing major depression (HR: 4.26, 95% CI: 1.39-13.13; HR: 7.56, 95% CI: 3.75-15.23), any depressive disorder (HR: 4.38, 95% CI: 2.09-9.18; HR: 5.66, 95% CI: 4.01-7.99), and anxiety disorders (HR: 5.40, 95% CI: 2.02-14.39; HR: 3.36, 95% CI: 2.38-4.80). AD in both adolescence and adulthood increased the risk of developing major depression, any depressive disorder, and anxiety disorders in later life. Further studies would be required to clarify the possible underlying mechanism between AD and depression as well as anxiety disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Major dietary patterns and cardiovascular risk factors from childhood to adulthood. The Cardiovascular Risk in Young Finns Study.

    Science.gov (United States)

    Mikkilä, Vera; Räsänen, Leena; Raitakari, Olli T; Marniemi, Jukka; Pietinen, Pirjo; Rönnemaa, Tapani; Viikari, Jorma

    2007-07-01

    Studies on the impact of single nutrients on the risk of CVD have often given inconclusive results. Recent research on dietary patterns has offered promising information on the effects of diet as a whole on the risk of CVD. The Cardiovascular Risk in Young Finns Study is an ongoing, prospective cohort study with a 21-year follow-up to date. The subjects were children and adolescents at baseline (3-18 years, n 1768) and adults at the latest follow-up study (24-39 years, n 1037). We investigated the associations between two major dietary patterns and several risk factors for CVD. In longitudinal analyses with repeated measurements, using multivariate mixed linear regression models, the traditional dietary pattern (characterised by high consumption of rye, potatoes, butter, sausages, milk and coffee) was independently associated with total and LDL cholesterol concentrations, apolipoprotein B and C-reactive protein concentrations among both genders, and also with systolic blood pressure and insulin levels among women and concentrations of homocysteine among men (P health-conscious food choices (such as high consumption of vegetables, legumes and nuts, tea, rye, cheese and other dairy products, and alcoholic beverages) was inversely, but less strongly associated with cardiovascular risk factors. Our results support earlier findings that dietary patterns have a role in the development of CVD.

  14. Suicide risk and prevalence of major depressive disorder (MDD) among individuals infected with HIV-1 subtype C versus B in Southern Brazil.

    Science.gov (United States)

    de Almeida, Sergio Monteiro; Barbosa, Francisco Jaime; Kamat, Rujvi; de Pereira, Ana Paula; Raboni, Sonia Mara; Rotta, Indianara; Ribeiro, Clea Elisa; Cherner, Mariana; Ellis, Ronald J; Atkinson, Joseph Hampton

    2016-12-01

    Major depressive disorder (MDD) is among the most prevalent neuropsychiatric disorders associated with HIV infection; however, its risks and neurobiologic correlates in diverse cultures are poorly understood. This study aimed to examine the frequency of MDD among HIV+ participants in southern Brazil. We hypothesized that the frequency and severity of MDD would be higher among individuals with HIV+ compared with HIV- and higher in HIV subtype B compared with C. Individuals with HIV (n = 39) as well as seronegative controls (n = 22) were enrolled in a cross-sectional, prospective, observational study. Current and lifetime history of MDD was diagnosed by MINI-Plus; symptom severity was assessed by Beck Depression Inventory-II (BDI-II). Current and past episodes of MDD were significantly more frequent in the HIV+ versus HIV- group: current MDD, 15 (38.5 %) vs. 0 (0 %), p = 0.0004; past MDD, 24 (61.5 %) vs. 3 (13.6 %), p = 0.0004. The median BDI-II score in the HIV+ group was significantly higher than that in the HIV- (13 (8-27.5) vs. 2.5 (1-5.5); p suicide risk, defined as during the last month, was found in 18 % of participants in the HIV-positive and none in the HIV-negative group. Neither current MDD frequency (8 (57.1 %) vs. 6 (40 %), p = 0.47) nor BDI-II score differed across subtypes B and C. HIV+ group may be more likely to experience current MDD than HIV-. This was the first study to compare the frequency and severity of MDD in HIV subtypes B and C; we found no difference between HIV subtypes B and C.

  15. Expression and subcellular localization of ORC1 in Leishmania major

    International Nuclear Information System (INIS)

    Kumar, Diwakar; Mukherji, Agnideep; Saha, Swati

    2008-01-01

    The mechanism of DNA replication is highly conserved in eukaryotes, with the process being preceded by the ordered assembly of pre-replication complexes (pre-RCs). Pre-RC formation is triggered by the association of the origin replication complex (ORC) with chromatin. Leishmania major appears to have only one ORC ortholog, ORC1. ORC1 in other eukaryotes is the largest of the ORC subunits and is believed to play a significant role in modulating replication initiation. Here we report for the first time, the cloning of ORC1 from L. major, and the analysis of its expression in L. major promastigotes. In human cells ORC1 levels have been found to be upregulated in G1 and subsequently degraded, thus playing a role in controlling replication initiation. We examine the subcellular localization of L. major ORC1 in relation to the different stages of the cell cycle. Our results show that, unlike what is widely believed to be the case with ORC1 in human cells, ORC1 in L. major is nuclear at all stages of the cell cycle

  16. Major depressive disorder and suicidality in early HIV infection and its association with risk factors and negative outcomes as seen in semi-urban and rural Uganda.

    Science.gov (United States)

    Kinyanda, Eugene; Nakasujja, Noeline; Levin, Jonathan; Birabwa, Harriet; Mpango, Richard; Grosskurth, Heiner; Seedat, Soraya; Patel, Vikram

    2017-04-01

    There is a paucity of research into the psychiatric problems associated with early stage HIV clinical disease in sub-Saharan Africa. A cross sectional study was undertaken among 899 adult ART naïve persons in early stage HIV clinical disease (participants with CD4≥250 and who were at WHO clinical Stage I or II) attending a semi-urban and a rural clinic in Uganda. The prevalence of major depressive disorder in this study was 14.0% [95% CI 11.7-6.3%] while that of 'moderate to high risk for suicidality' was 2.8% [95% CI 1.7%; 3.9%]. Multivariable analyses found that factors in the socio-demographic, vulnerability/protective and stress (only for major depressive disorder) domains were significantly associated with both major depressive disorder and 'moderate to high risk for suicidality'. Major depressive disorder but not 'moderate to high risk for suicidality' was significantly associated with impaired psychosocial functioning, greater utilisation of health services and non-adherence to septrin/dasone. Neither major depressive disorder nor 'moderate to high risk for suicidality' was associated with CD4 counts, risky sexual behaviour nor with non-utilisation of condoms. The bidirectional nature of some of the relationships between the investigated psychiatric problems, risk factors and outcomes in this cross sectional study makes it difficult to elucidate the actual direction of causality. Early stage HIV clinical disease is associated with considerable major depressive disorder and 'moderate to high risk for suicidality'. Therefore there is a need to integrate mental health into HIV interventions that target early stage HIV disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. A clinical risk stratification tool for predicting treatment resistance in major depressive disorder.

    Science.gov (United States)

    Perlis, Roy H

    2013-07-01

    Early identification of depressed individuals at high risk for treatment resistance could be helpful in selecting optimal setting and intensity of care. At present, validated tools to facilitate this risk stratification are rarely used in psychiatric practice. Data were drawn from the first two treatment levels of a multicenter antidepressant effectiveness study in major depressive disorder, the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) cohort. This cohort was divided into training, testing, and validation subsets. Only clinical or sociodemographic variables available by or readily amenable to self-report were considered. Multivariate models were developed to discriminate individuals reaching remission with a first or second pharmacological treatment trial from those not reaching remission despite two trials. A logistic regression model achieved an area under the receiver operating characteristic curve exceeding .71 in training, testing, and validation cohorts and maintained good calibration across cohorts. Performance of three alternative models with machine learning approaches--a naïve Bayes classifier and a support vector machine, and a random forest model--was less consistent. Similar performance was observed between more and less severe depression, men and women, and primary versus specialty care sites. A web-based calculator was developed that implements this tool and provides graphical estimates of risk. Risk for treatment resistance among outpatients with major depressive disorder can be estimated with a simple model incorporating baseline sociodemographic and clinical features. Future studies should examine the performance of this model in other clinical populations and its utility in treatment selection or clinical trial design. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  18. [Analysis of risk factors of fatal outcome in pregnant and puerperant patients with severe H1N1 influenza].

    Science.gov (United States)

    Zabolotskikh, I B; Penzhoian, G A; Musaeva, T S; Goncharenko, S I

    2010-01-01

    As well as previous epidemics and pandemias of influenza, the 2009 H1N1 influenza pandemia increases the risk of severe illness in pregnant. Data were reported for 28 pregnant and 2 postpartum women who have been hospitalized in ICUs of Krasnodar Region with H1N1 influenza diagnosis. The laboratory tests for H1N1 were negative in 53.3% of suspected cases of H1N1 influenza (16 of 30). The major lethal risk factor in pregnant with H1N1 influenza is a development of septic shock with low PaO2\\FiO2 ratio (less than 140) and high Murray's Acute Lung Injury Score (higher than 2.5). High Apache II, Apache III, SAPS 2, SAPS 3 and SOFA scores are the additional lethal risk factors. Lethal outcomes were more frequent in the end of the second trimester of pregnancy.

  19. Major adverse cardiovascular event reduction with GLP-1 and SGLT2 agents: evidence and clinical potential

    Science.gov (United States)

    Røder, Michael E.

    2017-01-01

    Treatment of patients with type 2 diabetes is directed against treating symptoms of hyperglycemia, minimizing the risk of hypoglycemia, and the risk of microvascular and macrovascular complications. The majority of patients with type 2 diabetes die from cardiovascular or cerebrovascular disease. Future therapies should therefore focus on reducing cardiovascular morbidity in this high-risk population. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are two drug classes with proven antihyperglycemic effect in type 2 diabetes. However, these drugs seem to have other effects such as weight reduction, low risk of hypoglycemia, and blood pressure reduction. Emerging evidence suggests pleiotropic effects, which potentially could be important in reducing cardiovascular risk. Prompted by regulatory authorities demanding cardiovascular outcome trials (CVOTs) assessing the cardiovascular safety of new antihyperglycemic drug candidates, many CVOTs are ongoing and a few of these are finalized. Somewhat surprising recent CVOTs in both drug classes have shown promising data on cardiovascular morbidity and mortality in patients with a very high risk of cardiovascular events. It is uncertain whether this is a class effect of the two drug classes, and it is yet unproven whether long-term cardiovascular benefits of these drugs can be extrapolated to populations at lower risk of cardiovascular disease. The aim of the present review is to give an overview of our current knowledge of the GLP-1RA and SGLT2-i classes, with specific focus on mechanisms of action, effects on cardiovascular risk factors and cardiovascular morbidity and mortality from the CVOTs presently available. The clinical potential of these data is discussed. PMID:29344329

  20. Distortion product otoacoustic emissions in college music majors and nonmusic majors

    Directory of Open Access Journals (Sweden)

    Rebecca L. Warner Henning

    2016-01-01

    Full Text Available The presence and absence of distortion product otoacoustic emissions (DPOAEs as well as DPOAE amplitudes were compared between college music majors and a control group of nonmusic majors. Participants included 28 music majors and 35 nonmusic majors enrolled at a university with ages ranging from 18-25 years. DPOAEs and hearing thresholds were measured bilaterally on all the participants. DPOAE amplitudes were analyzed at the following f2 frequencies: 1,187 Hz, 1,500 Hz, 1,906 Hz, 2,531 Hz, 3,031 Hz, 3812 Hz, 4,812 Hz, and 6,031 Hz. Significantly more music majors (7/28 than nonmusic majors (0/35 exhibited absent DPOAEs for at least one frequency in at least one ear. Both groups of students reported similar histories of recreational and occupational noise exposures that were unrelated to studying music, and none of the students reported high levels of noise exposure within the previous 48 h. There were no differences in audiometric thresholds between the groups at any frequency. At DPOAE f2 frequencies from 3,031 Hz to 6,031 Hz, nonsignificantly lower amplitudes of 2-4 dB were seen in the right ears of music majors versus nonmajors, and in the right ears of music majors playing brass instruments compared to music majors playing nonbrass instruments. Given the greater prevalence of absent DPOAEs in university music majors compared to nonmusic majors, it appears that early stages of cochlear damage may be occurring in this population. Additional research, preferably longitudinal and across multiple colleges/universities, would be beneficial to more definitively determine when the music students begin to show signs of cochlear damage, and to identify whether any particular subgroups of music majors are at a greater risk of cochlear damage.

  1. Objectives and Design of BLEEDS: A Cohort Study to Identify New Risk Factors and Predictors for Major Bleeding during Treatment with Vitamin K Antagonists.

    Science.gov (United States)

    van Rein, Nienke; Lijfering, Willem M; Bos, Mettine H A; Herruer, Martien H; Vermaas, Helga W; van der Meer, Felix J M; Reitsma, Pieter H

    2016-01-01

    Risk scores for patients who are at high risk for major bleeding complications during treatment with vitamin K antagonists (VKAs) do not perform that well. BLEEDS was initiated to search for new biomarkers that predict bleeding in these patients. To describe the outline and objectives of BLEEDS and to examine whether the study population is generalizable to other VKA treated populations. A cohort was created consisting of all patients starting VKA treatment at three Dutch anticoagulation clinics between January-2012 and July-2014. We stored leftover plasma and DNA following analysis of the INR. Of 16,706 eligible patients, 16,570 (99%) were included in BLEEDS and plasma was stored from 13,779 patients (83%). Patients had a mean age of 70 years (SD 14), 8713 were male (53%). The most common VKA indications were atrial fibrillation (10,876 patients, 66%) and venous thrombosis (3920 patients, 24%). 326 Major bleeds occurred during 17,613 years of follow-up (incidence rate 1.85/100 person years, 95%CI 1.66-2.06). The risk for major bleeding was highest in the initial three months of VKA treatment and increased when the international normalized ratio increased. These results and characteristics are in concordance with results from other VKA treated populations. BLEEDS is generalizable to other VKA treated populations and will permit innovative and unbiased research of biomarkers that may predict major bleeding during VKA treatment.

  2. Adverse Childhood Experiences and Risk for First-Episode Major Depression During the Menopause Transition.

    Science.gov (United States)

    Epperson, C Neill; Sammel, Mary D; Bale, Tracy L; Kim, Deborah R; Conlin, Sarah; Scalice, Stephanie; Freeman, Katharine; Freeman, Ellen W

    2017-03-01

    Stress exposures may have a differential impact on risk and resilience for depression depending on their timing across development. We sought to determine whether adverse childhood experiences (ACEs) and their onset with respect to puberty contribute to the increased risk observed in first-episode major depressive disorder (MDD) during the menopause transition. Participants were from the Penn Ovarian Aging Study cohort, which is composed of women from Philadelphia County, Pennsylvania, who underwent behavioral, cognitive, and endocrine evaluations approximately yearly from 1996 to 2012 and completed the Adverse Childhood Experiences Questionnaire at study end point (n = 243). ACEs that first occurred 2 or more years before menarche were considered prepubertal. Incident menopause MDD was defined as first observed onset of the disorder in the perimenopause to postmenopause transition using the Structured Clinical Interview for DSM-III-R and the Primary Care Evaluation of Mental Disorders. Incident menopause MDD occurred in 48% of the 100 women who reported lifetime MDD. Women reporting ≥ 2 total ACEs were at significantly greater risk for lifetime MDD (adjusted odds ratio [aOR] = 2.05, P = .034) and incident menopause MDD (aOR = 2.58, P = .03) compared to those reporting 0 ACEs; women with ≥ 2 postpubertal ACEs were 2.3 times more likely to experience incidence menopause MDD (P = .024) after controlling for race, smoking, body mass index, and employment. Experiencing only 1 ACE in the prepubertal window, regardless of additional ACEs in postpuberty, was associated with reduced risk for lifetime and incident menopause MDD. Timing and number of adverse experiences with respect to puberty differentially impacted risk and resilience for MDD across the female life span and during the menopause transition in this community cohort. © Copyright 2017 Physicians Postgraduate Press, Inc.

  3. The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

    Science.gov (United States)

    Pereyra, Florencia; Jia, Xiaoming; McLaren, Paul J; Telenti, Amalio; de Bakker, Paul I W; Walker, Bruce D; Ripke, Stephan; Brumme, Chanson J; Pulit, Sara L; Carrington, Mary; Kadie, Carl M; Carlson, Jonathan M; Heckerman, David; Graham, Robert R; Plenge, Robert M; Deeks, Steven G; Gianniny, Lauren; Crawford, Gabriel; Sullivan, Jordan; Gonzalez, Elena; Davies, Leela; Camargo, Amy; Moore, Jamie M; Beattie, Nicole; Gupta, Supriya; Crenshaw, Andrew; Burtt, Noël P; Guiducci, Candace; Gupta, Namrata; Gao, Xiaojiang; Qi, Ying; Yuki, Yuko; Piechocka-Trocha, Alicja; Cutrell, Emily; Rosenberg, Rachel; Moss, Kristin L; Lemay, Paul; O'Leary, Jessica; Schaefer, Todd; Verma, Pranshu; Toth, Ildiko; Block, Brian; Baker, Brett; Rothchild, Alissa; Lian, Jeffrey; Proudfoot, Jacqueline; Alvino, Donna Marie L; Vine, Seanna; Addo, Marylyn M; Allen, Todd M; Altfeld, Marcus; Henn, Matthew R; Le Gall, Sylvie; Streeck, Hendrik; Haas, David W; Kuritzkes, Daniel R; Robbins, Gregory K; Shafer, Robert W; Gulick, Roy M; Shikuma, Cecilia M; Haubrich, Richard; Riddler, Sharon; Sax, Paul E; Daar, Eric S; Ribaudo, Heather J; Agan, Brian; Agarwal, Shanu; Ahern, Richard L; Allen, Brady L; Altidor, Sherly; Altschuler, Eric L; Ambardar, Sujata; Anastos, Kathryn; Anderson, Ben; Anderson, Val; Andrady, Ushan; Antoniskis, Diana; Bangsberg, David; Barbaro, Daniel; Barrie, William; Bartczak, J; Barton, Simon; Basden, Patricia; Basgoz, Nesli; Bazner, Suzane; Bellos, Nicholaos C; Benson, Anne M; Berger, Judith; Bernard, Nicole F; Bernard, Annette M; Birch, Christopher; Bodner, Stanley J; Bolan, Robert K; Boudreaux, Emilie T; Bradley, Meg; Braun, James F; Brndjar, Jon E; Brown, Stephen J; Brown, Katherine; Brown, Sheldon T; Burack, Jedidiah; Bush, Larry M; Cafaro, Virginia; Campbell, Omobolaji; Campbell, John; Carlson, Robert H; Carmichael, J Kevin; Casey, Kathleen K; Cavacuiti, Chris; Celestin, Gregory; Chambers, Steven T; Chez, Nancy; Chirch, Lisa M; Cimoch, Paul J; Cohen, Daniel; Cohn, Lillian E; Conway, Brian; Cooper, David A; Cornelson, Brian; Cox, David T; Cristofano, Michael V; Cuchural, George; Czartoski, Julie L; Dahman, Joseph M; Daly, Jennifer S; Davis, Benjamin T; Davis, Kristine; Davod, Sheila M; DeJesus, Edwin; Dietz, Craig A; Dunham, Eleanor; Dunn, Michael E; Ellerin, Todd B; Eron, Joseph J; Fangman, John J W; Farel, Claire E; Ferlazzo, Helen; Fidler, Sarah; Fleenor-Ford, Anita; Frankel, Renee; Freedberg, Kenneth A; French, Neel K; Fuchs, Jonathan D; Fuller, Jon D; Gaberman, Jonna; Gallant, Joel E; Gandhi, Rajesh T; Garcia, Efrain; Garmon, Donald; Gathe, Joseph C; Gaultier, Cyril R; Gebre, Wondwoosen; Gilman, Frank D; Gilson, Ian; Goepfert, Paul A; Gottlieb, Michael S; Goulston, Claudia; Groger, Richard K; Gurley, T Douglas; Haber, Stuart; Hardwicke, Robin; Hardy, W David; Harrigan, P Richard; Hawkins, Trevor N; Heath, Sonya; Hecht, Frederick M; Henry, W Keith; Hladek, Melissa; Hoffman, Robert P; Horton, James M; Hsu, Ricky K; Huhn, Gregory D; Hunt, Peter; Hupert, Mark J; Illeman, Mark L; Jaeger, Hans; Jellinger, Robert M; John, Mina; Johnson, Jennifer A; Johnson, Kristin L; Johnson, Heather; Johnson, Kay; Joly, Jennifer; Jordan, Wilbert C; Kauffman, Carol A; Khanlou, Homayoon; Killian, Robert K; Kim, Arthur Y; Kim, David D; Kinder, Clifford A; Kirchner, Jeffrey T; Kogelman, Laura; Kojic, Erna Milunka; Korthuis, P Todd; Kurisu, Wayne; Kwon, Douglas S; LaMar, Melissa; Lampiris, Harry; Lanzafame, Massimiliano; Lederman, Michael M; Lee, David M; Lee, Jean M L; Lee, Marah J; Lee, Edward T Y; Lemoine, Janice; Levy, Jay A; Llibre, Josep M; Liguori, Michael A; Little, Susan J; Liu, Anne Y; Lopez, Alvaro J; Loutfy, Mono R; Loy, Dawn; Mohammed, Debbie Y; Man, Alan; Mansour, Michael K; Marconi, Vincent C; Markowitz, Martin; Marques, Rui; Martin, Jeffrey N; Martin, Harold L; Mayer, Kenneth Hugh; McElrath, M Juliana; McGhee, Theresa A; McGovern, Barbara H; McGowan, Katherine; McIntyre, Dawn; Mcleod, Gavin X; Menezes, Prema; Mesa, Greg; Metroka, Craig E; Meyer-Olson, Dirk; Miller, Andy O; Montgomery, Kate; Mounzer, Karam C; Nagami, Ellen H; Nagin, Iris; Nahass, Ronald G; Nelson, Margret O; Nielsen, Craig; Norene, David L; O'Connor, David H; Ojikutu, Bisola O; Okulicz, Jason; Oladehin, Olakunle O; Oldfield, Edward C; Olender, Susan A; Ostrowski, Mario; Owen, William F; Pae, Eunice; Parsonnet, Jeffrey; Pavlatos, Andrew M; Perlmutter, Aaron M; Pierce, Michael N; Pincus, Jonathan M; Pisani, Leandro; Price, Lawrence Jay; Proia, Laurie; Prokesch, Richard C; Pujet, Heather Calderon; Ramgopal, Moti; Rathod, Almas; Rausch, Michael; Ravishankar, J; Rhame, Frank S; Richards, Constance Shamuyarira; Richman, Douglas D; Rodes, Berta; Rodriguez, Milagros; Rose, Richard C; Rosenberg, Eric S; Rosenthal, Daniel; Ross, Polly E; Rubin, David S; Rumbaugh, Elease; Saenz, Luis; Salvaggio, Michelle R; Sanchez, William C; Sanjana, Veeraf M; Santiago, Steven; Schmidt, Wolfgang; Schuitemaker, Hanneke; Sestak, Philip M; Shalit, Peter; Shay, William; Shirvani, Vivian N; Silebi, Vanessa I; Sizemore, James M; Skolnik, Paul R; Sokol-Anderson, Marcia; Sosman, James M; Stabile, Paul; Stapleton, Jack T; Starrett, Sheree; Stein, Francine; Stellbrink, Hans-Jurgen; Sterman, F Lisa; Stone, Valerie E; Stone, David R; Tambussi, Giuseppe; Taplitz, Randy A; Tedaldi, Ellen M; Telenti, Amalio; Theisen, William; Torres, Richard; Tosiello, Lorraine; Tremblay, Cecile; Tribble, Marc A; Trinh, Phuong D; Tsao, Alice; Ueda, Peggy; Vaccaro, Anthony; Valadas, Emilia; Vanig, Thanes J; Vecino, Isabel; Vega, Vilma M; Veikley, Wenoah; Wade, Barbara H; Walworth, Charles; Wanidworanun, Chingchai; Ward, Douglas J; Warner, Daniel A; Weber, Robert D; Webster, Duncan; Weis, Steve; Wheeler, David A; White, David J; Wilkins, Ed; Winston, Alan; Wlodaver, Clifford G; van't Wout, Angelique; Wright, David P; Yang, Otto O; Yurdin, David L; Zabukovic, Brandon W; Zachary, Kimon C; Zeeman, Beth; Zhao, Meng

    2010-12-10

    Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.

  4. The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation

    Science.gov (United States)

    Pereyra, Florencia; Jia, Xiaoming; McLaren, Paul J.; Telenti, Amalio; de Bakker, Paul I.W.; Walker, Bruce D.; Jia, Xiaoming; McLaren, Paul J.; Ripke, Stephan; Brumme, Chanson J.; Pulit, Sara L.; Telenti, Amalio; Carrington, Mary; Kadie, Carl M.; Carlson, Jonathan M.; Heckerman, David; de Bakker, Paul I.W.; Pereyra, Florencia; de Bakker, Paul I.W.; Graham, Robert R.; Plenge, Robert M.; Deeks, Steven G.; Walker, Bruce D.; Gianniny, Lauren; Crawford, Gabriel; Sullivan, Jordan; Gonzalez, Elena; Davies, Leela; Camargo, Amy; Moore, Jamie M.; Beattie, Nicole; Gupta, Supriya; Crenshaw, Andrew; Burtt, Noël P.; Guiducci, Candace; Gupta, Namrata; Carrington, Mary; Gao, Xiaojiang; Qi, Ying; Yuki, Yuko; Pereyra, Florencia; Piechocka-Trocha, Alicja; Cutrell, Emily; Rosenberg, Rachel; Moss, Kristin L.; Lemay, Paul; O’Leary, Jessica; Schaefer, Todd; Verma, Pranshu; Toth, Ildiko; Block, Brian; Baker, Brett; Rothchild, Alissa; Lian, Jeffrey; Proudfoot, Jacqueline; Alvino, Donna Marie L.; Vine, Seanna; Addo, Marylyn M.; Allen, Todd M.; Altfeld, Marcus; Henn, Matthew R.; Le Gall, Sylvie; Streeck, Hendrik; Walker, Bruce D.; Haas, David W.; Kuritzkes, Daniel R.; Robbins, Gregory K.; Shafer, Robert W.; Gulick, Roy M.; Shikuma, Cecilia M.; Haubrich, Richard; Riddler, Sharon; Sax, Paul E.; Daar, Eric S.; Ribaudo, Heather J.; Agan, Brian; Agarwal, Shanu; Ahern, Richard L.; Allen, Brady L.; Altidor, Sherly; Altschuler, Eric L.; Ambardar, Sujata; Anastos, Kathryn; Anderson, Ben; Anderson, Val; Andrady, Ushan; Antoniskis, Diana; Bangsberg, David; Barbaro, Daniel; Barrie, William; Bartczak, J.; Barton, Simon; Basden, Patricia; Basgoz, Nesli; Bazner, Suzane; Bellos, Nicholaos C.; Benson, Anne M.; Berger, Judith; Bernard, Nicole F.; Bernard, Annette M.; Birch, Christopher; Bodner, Stanley J.; Bolan, Robert K.; Boudreaux, Emilie T.; Bradley, Meg; Braun, James F.; Brndjar, Jon E.; Brown, Stephen J.; Brown, Katherine; Brown, Sheldon T.; Burack, Jedidiah; Bush, Larry M.; Cafaro, Virginia; Campbell, Omobolaji; Campbell, John; Carlson, Robert H.; Carmichael, J. Kevin; Casey, Kathleen K.; Cavacuiti, Chris; Celestin, Gregory; Chambers, Steven T.; Chez, Nancy; Chirch, Lisa M.; Cimoch, Paul J.; Cohen, Daniel; Cohn, Lillian E.; Conway, Brian; Cooper, David A.; Cornelson, Brian; Cox, David T.; Cristofano, Michael V.; Cuchural, George; Czartoski, Julie L.; Dahman, Joseph M.; Daly, Jennifer S.; Davis, Benjamin T.; Davis, Kristine; Davod, Sheila M.; Deeks, Steven G.; DeJesus, Edwin; Dietz, Craig A.; Dunham, Eleanor; Dunn, Michael E.; Ellerin, Todd B.; Eron, Joseph J.; Fangman, John J.W.; Farel, Claire E.; Ferlazzo, Helen; Fidler, Sarah; Fleenor-Ford, Anita; Frankel, Renee; Freedberg, Kenneth A.; French, Neel K.; Fuchs, Jonathan D.; Fuller, Jon D.; Gaberman, Jonna; Gallant, Joel E.; Gandhi, Rajesh T.; Garcia, Efrain; Garmon, Donald; Gathe, Joseph C.; Gaultier, Cyril R.; Gebre, Wondwoosen; Gilman, Frank D.; Gilson, Ian; Goepfert, Paul A.; Gottlieb, Michael S.; Goulston, Claudia; Groger, Richard K.; Gurley, T. Douglas; Haber, Stuart; Hardwicke, Robin; Hardy, W. David; Harrigan, P. Richard; Hawkins, Trevor N.; Heath, Sonya; Hecht, Frederick M.; Henry, W. Keith; Hladek, Melissa; Hoffman, Robert P.; Horton, James M.; Hsu, Ricky K.; Huhn, Gregory D.; Hunt, Peter; Hupert, Mark J.; Illeman, Mark L.; Jaeger, Hans; Jellinger, Robert M.; John, Mina; Johnson, Jennifer A.; Johnson, Kristin L.; Johnson, Heather; Johnson, Kay; Joly, Jennifer; Jordan, Wilbert C.; Kauffman, Carol A.; Khanlou, Homayoon; Killian, Robert K.; Kim, Arthur Y.; Kim, David D.; Kinder, Clifford A.; Kirchner, Jeffrey T.; Kogelman, Laura; Kojic, Erna Milunka; Korthuis, P. Todd; Kurisu, Wayne; Kwon, Douglas S.; LaMar, Melissa; Lampiris, Harry; Lanzafame, Massimiliano; Lederman, Michael M.; Lee, David M.; Lee, Jean M.L.; Lee, Marah J.; Lee, Edward T.Y.; Lemoine, Janice; Levy, Jay A.; Llibre, Josep M.; Liguori, Michael A.; Little, Susan J.; Liu, Anne Y.; Lopez, Alvaro J.; Loutfy, Mono R.; Loy, Dawn; Mohammed, Debbie Y.; Man, Alan; Mansour, Michael K.; Marconi, Vincent C.; Markowitz, Martin; Marques, Rui; Martin, Jeffrey N.; Martin, Harold L.; Mayer, Kenneth Hugh; McElrath, M. Juliana; McGhee, Theresa A.; McGovern, Barbara H.; McGowan, Katherine; McIntyre, Dawn; Mcleod, Gavin X.; Menezes, Prema; Mesa, Greg; Metroka, Craig E.; Meyer-Olson, Dirk; Miller, Andy O.; Montgomery, Kate; Mounzer, Karam C.; Nagami, Ellen H.; Nagin, Iris; Nahass, Ronald G.; Nelson, Margret O.; Nielsen, Craig; Norene, David L.; O’Connor, David H.; Ojikutu, Bisola O.; Okulicz, Jason; Oladehin, Olakunle O.; Oldfield, Edward C.; Olender, Susan A.; Ostrowski, Mario; Owen, William F.; Pae, Eunice; Parsonnet, Jeffrey; Pavlatos, Andrew M.; Perlmutter, Aaron M.; Pierce, Michael N.; Pincus, Jonathan M.; Pisani, Leandro; Price, Lawrence Jay; Proia, Laurie; Prokesch, Richard C.; Pujet, Heather Calderon; Ramgopal, Moti; Rathod, Almas; Rausch, Michael; Ravishankar, J.; Rhame, Frank S.; Richards, Constance Shamuyarira; Richman, Douglas D.; Robbins, Gregory K.; Rodes, Berta; Rodriguez, Milagros; Rose, Richard C.; Rosenberg, Eric S.; Rosenthal, Daniel; Ross, Polly E.; Rubin, David S.; Rumbaugh, Elease; Saenz, Luis; Salvaggio, Michelle R.; Sanchez, William C.; Sanjana, Veeraf M.; Santiago, Steven; Schmidt, Wolfgang; Schuitemaker, Hanneke; Sestak, Philip M.; Shalit, Peter; Shay, William; Shirvani, Vivian N.; Silebi, Vanessa I.; Sizemore, James M.; Skolnik, Paul R.; Sokol-Anderson, Marcia; Sosman, James M.; Stabile, Paul; Stapleton, Jack T.; Starrett, Sheree; Stein, Francine; Stellbrink, Hans-Jurgen; Sterman, F. Lisa; Stone, Valerie E.; Stone, David R.; Tambussi, Giuseppe; Taplitz, Randy A.; Tedaldi, Ellen M.; Telenti, Amalio; Theisen, William; Torres, Richard; Tosiello, Lorraine; Tremblay, Cecile; Tribble, Marc A.; Trinh, Phuong D.; Tsao, Alice; Ueda, Peggy; Vaccaro, Anthony; Valadas, Emilia; Vanig, Thanes J.; Vecino, Isabel; Vega, Vilma M.; Veikley, Wenoah; Wade, Barbara H.; Walworth, Charles; Wanidworanun, Chingchai; Ward, Douglas J.; Warner, Daniel A.; Weber, Robert D.; Webster, Duncan; Weis, Steve; Wheeler, David A.; White, David J.; Wilkins, Ed; Winston, Alan; Wlodaver, Clifford G.; Wout, Angelique van’t; Wright, David P.; Yang, Otto O.; Yurdin, David L.; Zabukovic, Brandon W.; Zachary, Kimon C.; Zeeman, Beth; Zhao, Meng

    2011-01-01

    Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA–viral peptide interaction as the major factor modulating durable control of HIV infection. PMID:21051598

  5. The effects of diabetes on the risks of major cardiovascular diseases and death in the Asia-Pacific region.

    Science.gov (United States)

    Woodward, M; Zhang, X; Barzi, F; Pan, W; Ueshima, H; Rodgers, A; MacMahon, S

    2003-02-01

    To provide reliable age- and region-specific estimates of the associations between diabetes and major cardiovascular diseases and death in populations from the Asia-Pacific region. Twenty-four cohort studies from Asia, Australia, and New Zealand (median follow-up, 5.4 years) provided individual participant data from 161,214 people (58% from Asia) of whom 4,873 had a history of diabetes at baseline. The associations of diabetes with the risks of coronary heart disease, stroke, and cause-specific mortality during follow-up were estimated using time-dependent Cox models, stratified by study cohort and sex and adjusted for age at risk. In all, 9,277 deaths occurred (3,635 from cardiovascular disease). The hazard ratio (95% CI) associated with diabetes was 1.97 (1.72-2.25) for fatal cardiovascular disease; there were similar hazard ratios for fatal coronary heart disease, fatal stroke, and composites of fatal and nonfatal outcomes. For all cardiovascular outcomes, hazard ratios were similar in Asian and non-Asian populations and in men and women, but were greater in younger than older individuals. For noncardiovascular death, the hazard ratio was 1.56 (1.38-1.77), with separately significant increases in the risks of death from renal disease, cancer, respiratory infections, and other infective causes. The hazard ratio for all-causes mortality was 1.68 (1.55-1.84), with similar ratios in Asian and non-Asian populations, but with significantly higher ratios in younger than older individuals. The relative effect of diabetes on the risks of cardiovascular disease and death in Asian populations is much the same as that in the largely Caucasian populations of Australia and New Zealand. Hazard ratios were severalfold greater in younger people than older people. The rapidly growing prevalence of diabetes in Asia heralds a large increase in the incidence of diabetes-related death in the coming decades.

  6. Major malformation risk, pregnancy outcomes, and neurodevelopmental outcomes associated with metformin use during pregnancy.

    Science.gov (United States)

    Andrade, Chittaranjan

    2016-04-01

    There are several reasons why metformin treatment may be considered for women in neuropsychiatric practice. These include prevention or attenuation of antipsychotic-associated weight gain, prevention or treatment of gestational diabetes mellitus (GDM), treatment of type 2 diabetes mellitus, and improvement of conception chances and pregnancy outcomes in the presence of polycystic ovarian disease (PCOD). This article examines the benefits and risks associated with metformin use during pregnancy. The available data suggest that metformin exposure during the first trimester is not associated with major congenital malformations; that metformin reduces the risk of early pregnancy loss, preeclampsia, preterm delivery, and GDM in women with PCOD; that metformin is associated with at least comparable benefits relative to insulin treatment in women with mild GDM; and that neurodevelopmental outcomes at age 1.5-2.5 years are comparable after gestational exposure to metformin and insulin. Whereas study designs were not always ideal and sample sizes were mostly small to modest, the study findings are more encouraging than discouraging and can guide shared decision-making in women who are receiving or may need metformin during pregnancy. © Copyright 2016 Physicians Postgraduate Press, Inc.

  7. Risk factors of major noncommunicable diseases in Bahrain. The need for a surveillance system.

    Science.gov (United States)

    Hamadeh, Randah R

    2004-09-01

    Noncommunicable diseases NCDs are the major cause of morbidity and mortality in Bahrain. The review examines the prevalence of risk factors of major NCDs from the available literature and determines the impact of the rapid socio economic changes on their burden. It further recommends ways of improving their reporting and monitoring. Smoking, obesity, diabetes, hypertension, hyperlipidemia, physical activity and nutrition are considered. The review points out that data on some of the factors is available but deficient for others. The call for the establishment of an integrated surveillance system using the World Health Organization STEPwise approach is stressed.

  8. Clinical features of and risk factors for major depression with history of postpartum episodes in Han Chinese women: A retrospective study.

    Science.gov (United States)

    Yang, Fuzhong; Gardner, Charles O; Bigdeli, Tim; Gao, Jingfang; Zhang, Zhen; Tao, Ming; Liu, Ying; Li, Youhui; Wang, Gang; Shi, Jianguo; Gao, Chengge; Zhang, Kerang; Li, Kan; Wang, Xumei; Liu, Lanfen; Sun, Jing; Du, Bo; Shi, Shenxun; Zhang, Jingbei; Wu, Wenyuan; Wang, Xueyi; Shen, Jianhua; Liu, Tiebang; Gu, Danhua; Liang, Wei; Deng, Hong; Pan, Jiyang; Yang, Lijun; Jian, Hu; Jiang, Guoqin; Meng, Huaqing; Miao, Guodong; Li, Yi; Hu, Chunmei; Huang, Guoping; Zhang, Yutang; Chen, Yunchun; Ha, Baowei; Gao, Shu; Fang, Xiang; Mei, Qiyi; Hong, Xiaohong; Yang, Donglin; Liu, Tieqiao; Fengyu, Yu; Zhong, Hui; Sang, Hong; Chen, Guibing; Cai, Min; Song, Yan; Dong, Jicheng; Shen, Zhenmin; Zhang, Wei; Wang, Xiaoping; Pan, Runde; Liu, Xiaojuan; Li, Yi; Liu, Zhengrong; Zhang, Qiwen; Li, Gongying; Flint, Jonathan; Kendler, Kenneth S

    2015-09-01

    We sought to investigate the clinical features of and risk factors for recurrent major depression (MD) with history of postpartum episodes (PPD) in Han Chinese women and the differences between first-onset postpartum MD (MD that has its first lifetime depressive episode in the postpartum period) and first-onset non-postpartum MD (MD with history of PPD and has its first lifetime depressive episode in a period other than postpartum). Data were derived from the China, Oxford and Virginia Commonwealth University Experimental Research on Genetic Epidemiology (CONVERGE) study (N=6017 cases) and analyzed in two steps. We first examined the clinical features of and risk factors for MD patients with (N=981) or without (N=4410) a history of PPD. We then compared the differences between first-onset postpartum MD (N=583) and first-onset non-postpartum MD (N=398) in those with a history of PPD. Linear, logistic and multinomial logistic models were employed to measure the associations. A history of PPD was associated with more guilt feelings, greater psychiatric comorbidity, higher neuroticism, earlier onset and more chronicity (OR 0.2-2.8). Severe premenstrual symptoms (PMS) and more childbirths increased the risk of PPD, as did a family history of MD, childhood sexual abuse, stressful life events and lack of social support (OR 1.1-1.3). In the MD with history of PPD subsample, first-onset postpartum MD was associated with fewer recurrent major depressive episodes, less psychiatric comorbidity, lower neuroticism, less severe PMS and fewer disagreements with their husbands (OR 0.5-0.8), but more childbirths (OR 1.2). Data were obtained retrospectively through interview and recall bias may have affected the results. MD with history of PPD in Han Chinese women is typically chronic and severe, with particular risk factors including severe PMS and more childbirths. First-onset postpartum MD and first-onset non-postpartum MD can be partly differentiated by their clinical features

  9. The longitudinal joint effect of obesity and major depression on work performance impairment.

    Science.gov (United States)

    Nigatu, Yeshambel T; Reijneveld, Sijmen A; Penninx, Brenda W J H; Schoevers, Robert A; Bültmann, Ute

    2015-05-01

    We examined the longitudinal effect of obesity, major depression, and their combination on work performance impairment (WPI). We collected longitudinal data (2004-2013) on 1726 paid employees from the Netherlands Study of Depression and Anxiety at baseline and 2-, 4-, and 6-year follow-up. We defined obesity with body mass index and waist circumference. We diagnosed major depression with the Composite International Diagnostic Interview 2.1. We assessed work performance impairment with a questionnaire for illness-associated costs. We used generalized estimating equations for modeling, and estimated interaction on the additive scale. Obesity, abdominal obesity, and major depression were longitudinally associated with increased risk of high WPI. The combinations of obesity and major depression, and of abdominal obesity and major depression were associated with increased risk of high WPI (odds ratios of 2.36 [95% confidence interval = 1.61, 3.44] and 1.88 [95% confidence interval = 1.40, 2.53], respectively), but the relative excess risks attributable to interaction were nonsignificant. The longitudinal joint effect of obesity and major depression on high WPI implies that obesity intervention may be more beneficial for individuals with major depression than those without regarding risk of high WPI, if confirmed in a large, representative sample.

  10. Risk - hazardous incident - communication 1

    International Nuclear Information System (INIS)

    Gerling, R.; Obermeier, O.P.

    1994-01-01

    Terms such as 'risk', 'hazardous incident', and 'communication' have become major catchwords in discussions about present-day problems, and may be reduced to a common denominator: disaster. Such an association, however, is inappropriate, as the concept indicated by the term 'risk' for instance covers a wide scale of possible danger. Even the term 'hazardous incident' describes events or conditions that are very different in terms of possible danger, let alone disastrous effects. The discrepancy to be observed between the facts and the public perception usually is due to the fact that people have little insight into the complex of problems involved, and to insufficient communication between the world of experts and the general public. The contributions to this publication present information and discuss a variety of solution sets to improve the communication problems in the context of the problem area of 'risk - hazardous incident - communication'. (orig./CB) [de

  11. Gene Cloning of Iranian Leishmania major Mannose-1-Phosphate Guanyltransferase

    Directory of Open Access Journals (Sweden)

    R Salehi

    2009-07-01

    Full Text Available "nBackground: Leishmania is an obligatory intracellular protozoan parasite, which infects human be­ings when infected sand fly vector takes a blood meal.  Most efforts are towards designing an effective vaccine to prevent leishmaniasis. In this way, development of candidate antigen for vaccine has spe­cial im­portant. In this study, we cloned mannose-1-phosphate guanyltransferase gene of Iranian L .major in pET32a expression vector. "nMethods: Primers based on L. major mannose-1-phosphate guanyltransferase sequence gene was de­signed and synthesized. DNA of Leishmania promastigotes was extracted and PCR reaction was done. PCR product was cloned into pTZ57R and sub cloned into pET32a expression vector. "nResults: Recombinant plasmid containing 1140 bp as L. major mannose-1-phosphate guanyltrans­ferase gene was extracted and confirmed by restriction analysis. PCR product was sequenced and de­posited to GenBank. There were some differences in amino acid sequences between Iranian L. major mannose-1-phosphate guanyltransferase and others previously accepted in GenBank "nConclusion: We amplified and cloned Iranian L. major mannose-1-phosphate guanyltransferase successfully.

  12. Posttraumatic stress disorder increases risk for suicide attempt in adults with recurrent major depression.

    Science.gov (United States)

    Stevens, Daniel; Wilcox, Holly C; MacKinnon, Dean F; Mondimore, Francis M; Schweizer, Barbara; Jancic, Dunya; Coryell, William H; Weissman, Myrna M; Levinson, Douglas F; Potash, James B

    2013-10-01

    Genetics of Recurrent Early-Onset Depression study (GenRED II) data were used to examine the relationship between posttraumatic stress disorder (PTSD) and attempted suicide in a population of 1,433 individuals with recurrent early-onset major depressive disorder (MDD). We tested the hypothesis that PTSD resulting from assaultive trauma increases risk for attempted suicide among individuals with recurrent MDD. Data on lifetime trauma exposures and clinical symptoms were collected using the Diagnostic Interview for Genetic Studies version 3.0 and best estimate diagnoses of MDD, PTSD, and other DSM-IV Axis I disorders were reported with best estimated age of onset. The lifetime prevalence of suicide attempt in this sample was 28%. Lifetime PTSD was diagnosed in 205 (14.3%) participants. We used discrete time-survival analyses to take into account timing in the PTSD-suicide attempt relationship while adjusting for demographic variables (gender, race, age, and education level) and comorbid diagnoses prior to trauma exposure. PTSD was an independent predictor of subsequent suicide attempt (HR = 2.5, 95% CI: 1.6, 3.8; P < .0001). Neither assaultive nor nonassaultive trauma without PTSD significantly predicted subsequent suicide attempt after Bonferroni correction. The association between PTSD and subsequent suicide attempt was driven by traumatic events involving assaultive violence (HR = 1.7, 95% CI: 1.3, 2.2; P< .0001). Among those with recurrent MDD, PTSD appears to be a vulnerability marker of maladaptive responses to traumatic events and an independent risk factor for attempted suicide. Additional studies examining differences between those with and without PTSD on biological measures might shed light on this potential vulnerability. © 2013 Wiley Periodicals, Inc.

  13. Spine-hip T-score difference predicts major osteoporotic fracture risk independent of FRAX(®): a population-based report from CAMOS.

    Science.gov (United States)

    Leslie, William D; Kovacs, Christopher S; Olszynski, Wojciech P; Towheed, Tanveer; Kaiser, Stephanie M; Prior, Jerilynn C; Josse, Robert G; Jamal, Sophie A; Kreiger, Nancy; Goltzman, David

    2011-01-01

    The WHO fracture risk assessment tool (FRAX(®)) estimates an individual's 10-yr major osteoporotic and hip fracture probabilities. When bone mineral density (BMD) is included in the FRAX calculation, only the femoral neck measurement can be used. Recently, a procedure was reported for adjusting major osteoporotic fracture probability from FRAX with femoral neck BMD based on the difference (offset) between the lumbar spine and the femoral neck T-score values. The objective of the current analysis was to independently evaluate this algorithm in a population-based cohort of 4575 women and 1813 men aged 50 yr and older from the Canadian Multicentre Osteoporosis Study. For women and men combined, there was a 15% (95% confidence interval 7-24%) increase in major osteoporotic fracture risk for each offset T-score after adjusting for FRAX probability calculated with femoral neck BMD. The effect was stronger in women than men, but a significant sex interaction was not detected. Among the full cohort, 5.5% had their risk category reclassified after using the offset adjustment. Sex- and age-dependent offsets (equivalent to an offset based on Z-scores) showed improved risk classification among individuals designated to be at moderate risk with the conventional FRAX probability measurement. In summary, the T-score difference between the lumbar spine and femoral neck is an independent risk factor for major osteoporotic fractures that is independent of the FRAX probability calculated with femoral neck BMD. Copyright © 2011 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

  14. No Major Host Genetic Risk Factor Contributed to A(H1N12009 Influenza Severity.

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    Koldo Garcia-Etxebarria

    Full Text Available While most patients affected by the influenza A(H1N1 pandemic experienced mild symptoms, a small fraction required hospitalization, often without concomitant factors that could explain such a severe course. We hypothesize that host genetic factors could contribute to aggravate the disease. To test this hypothesis, we compared the allele frequencies of 547,296 genome-wide single nucleotide polymorphisms (SNPs between 49 severe and 107 mild confirmed influenza A cases, as well as against a general population sample of 549 individuals. When comparing severe vs. mild influenza A cases, only one SNP was close to the conventional p = 5×10-8. This SNP, rs28454025, sits in an intron of the GSK233 gene, which is involved in a neural development, but seems not to have any connections with immunological or inflammatory functions. Indirectly, a previous association reported with CD55 was replicated. Although sample sizes are low, we show that the statistical power in our design was sufficient to detect highly-penetrant, quasi-Mendelian genetic factors. Hence, and assuming that rs28454025 is likely to be a false positive, no major genetic factor was detected that could explain poor influenza A course.

  15. Betel nut usage is a major risk factor for coronary artery disease.

    Science.gov (United States)

    Khan, Muhammad Shahzeb; Bawany, Faizan Imran; Ahmed, Muhammad Umer; Hussain, Mehwish; Khan, Asadullah; Lashari, Muhammad Nawaz

    2013-12-27

    The objective of our study was to assess betel nut usage as one of the major risk factors associated with coronary artery disease. This case control study consisted of 300 controls and 300 cases. A structured questionnaire was administered to the participants to assess consumption of betel nut and confounding variables. A respondent was considered a regular consumer of betel nut if he/she consumed one or more pieces of betel nut every day for a period of greater than 6 months. About 8 in 10 betel nut chewers developed coronary artery disease. After adjusting for diabetes and hypertension, the odds ratio analysis depicted 7.72 times greater likelihood for coronary artery disease in patients who chewed betel nut for more than 10 years. Our study concludes that betel nut chewing is a significant risk factor leading to the development of coronary artery disease.

  16. Analysis of major risk factors affecting those working in the agrarian sector (based on a sociological survey).

    Science.gov (United States)

    Krekoten, Olena M; Dereziuk, Anatolii V; Ihnaschuk, Olena V; Holovchanska, Svitlana E

    Issues related to labour potential, its state and problems have consistently been a focus of attention for the International Labour Organisation (ILO). Its respective analysis shows that labour potential problems remain unresolved in many countries of the world. According to the World Health Organisation (WHO), adverse working conditions are among major factors of occupational disease development in Europe and the reason for disabilities of economically active population during 2.5% of their lifetime. The aim of the present study is to identify and analyse major risk factors, which have a bearing on people working in agriculture in the course of exercising their occupation, with account of forms of ownership of agricultural enterprises. Carried out was a cross-sectional study involving a sociological survey of 412 respondents - those working in agriculture - who made up the primary group and the control group. The study revealed 21 risk factors, 9 of which were work-related. A modified elementary cybernetic model of studying impact efficiency was developed with the view of carrying out a structural analysis of the sample group and choosing relevant methodological approaches. It has been established that harmful factors related to working environment and one's lifestyle are decisive in the agrarian sector, particularly for workers of privately owned businesses. For one out of three respondents harmful working conditions manifested themselves as industrial noise (31.7±3.4), vibration (29.0±2.1) trunk bending and constrained working posture (36.6±3.4). The vast majority of agricultural workers (91.6±2.5) admitted they could not afford proper rest during their annual leave; male respondents abused alcohol (70.6±3.0) and smoking (41.4±2.0 per 100 workers). The research established the structure of risk factors, which is sequentially represented by the following groups: behavioral (smoking, drinking of alcohol, rest during annual leave, physical culture), working

  17. Obesity as a Major Risk Factor for Cancer

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    Giovanni De Pergola

    2013-01-01

    Full Text Available The number of cancer cases caused by being obese is estimated to be 20% with the increased risk of malignancies being influenced by diet, weight change, and body fat distribution together with physical activity. Reports from the International Agency for Research into Cancer and the World Cancer Research Fund (WCRF have shown that the strongest evidence exists for an association of obesity with the following cancer types: endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal, whereas the less common malignancies are leukemia, non-Hodgkin’s lymphoma, multiple myeloma, malignant melanoma, and thyroid tumours. To be able to develop novel methods in prevention and treatment, we first must understand the underlying processes which link cancer to obesity. Four main systems have been identified as potential producers of cancer in obesity: insulin, insulin-like growth factor-I, sex steroids, and adipokines. Various novel candidate mechanisms have been proposed: chronic inflammation, oxidative stress, crosstalk between tumour cells and surrounding adipocytes, migrating adipose stromal cells, obesity-induced hypoxia, shared genetic susceptibility, and the functional defeat of immune function. Herein, we review the major pathogenic links between obesity and susceptibility to cancer.

  18. The presence of both serotonin 1A receptor (HTR1A and dopamine transporter (DAT1 gene variants increase the risk of borderline personality disorder

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    Peter R Joyce

    2014-01-01

    Full Text Available Dysfunction in the dopaminergic and serotonergic neurotransmitter systems has been demonstrated to be important in the aetiology of Borderline personality disorder (BPD. We investigated the relationship of two BPD risk factors, the HTR1A promoter polymorphism -1019C>G (rs6295 and the DAT1 repeat allele, with BPD in a major depressive disorder cohort of 367 patients. Out-patients with major depressive disorder were recruited for two treatment trials and assessed for personality disorders, including BPD. DNA samples were collected and the rs6295 polymorphism was detected with a TaqMan® assay. The DAT1 repeat allele was genotyped using a modified PCR method. The impact of polymorphisms on BPD was statistically analysed using uncontrolled logistic and multiple logistic regression models. BPD patients had higher frequencies of the DAT1 9,9 (OR=2.67 and 9,10 (OR=3.67 genotypes and also those homozygous HTR1A G allele (OR=2.03. No significant interactions between HTR1A and DAT1 genotypes, were observed; however, an increased risk of BPD was observed for those patients who were either 9,10; G,G (OR=6.64 and 9,9; C,G (OR=5.42. Furthermore, the odds of BPD in patients exhibiting high-risk variants of these two genes differed from those of patients in low-risk groups by up to a factor of 9. Our study provides evidence implicating the importance of the serotonergic and dopaminergic systems in BPD and that the interaction between genes from different neurotransmitters may play a role in the susceptibility to BPD.

  19. Left atrial enlargement increases the risk of major adverse cardiac events independent of coronary vasodilator capacity

    Energy Technology Data Exchange (ETDEWEB)

    Koh, Angela S. [Brigham and Women' s Hospital, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Boston, MA (United States); National Heart Centre Singapore, Singapore (Singapore); Murthy, Venkatesh L.; Sitek, Arkadiusz; Gayed, Peter; Bruyere, John; Di Carli, Marcelo F. [Brigham and Women' s Hospital, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Boston, MA (United States); Wu, Justina [Brigham and Women' s Hospital, Division of Cardiology, Department of Medicine, and the Noninvasive Cardiovascular Imaging Program, Departments of Medicine (Cardiology) and Radiology, Boston, MA (United States); Dorbala, Sharmila [Brigham and Women' s Hospital, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Boston, MA (United States); Brigham and Women' s Hospital, Department of Radiology and the Division of Cardiology, Noninvasive Cardiovascular Imaging Section, Boston, MA (United States)

    2015-09-15

    Longstanding uncontrolled atherogenic risk factors may contribute to left atrial (LA) hypertension, LA enlargement (LAE) and coronary vascular dysfunction. Together they may better identify risk of major adverse cardiac events (MACE). The aim of this study was to test the hypothesis that chronic LA hypertension as assessed by LAE modifies the relationship between coronary vascular function and MACE. In 508 unselected subjects with a normal clinical {sup 82}Rb PET/CT, ejection fraction ≥40 %, no prior coronary artery disease, valve disease or atrial fibrillation, LAE was determined based on LA volumes estimated from the hybrid perfusion and CT transmission scan images and indexed to body surface area. Absolute myocardial blood flow and global coronary flow reserve (CFR) were calculated. Subjects were systematically followed-up for the primary end-point - MACE - a composite of all-cause death, myocardial infarction, hospitalization for heart failure, stroke, coronary artery disease progression or revascularization. During a median follow-up of 862 days, 65 of the subjects experienced a composite event. Compared with subjects with normal LA size, subjects with LAE showed significantly lower CFR (2.25 ± 0.83 vs. 1.95 ± 0.80, p = 0.01). LAE independently and incrementally predicted MACE even after accounting for clinical risk factors, medication use, stress left ventricular ejection fraction, stress left ventricular end-diastolic volume index and CFR (chi-squared statistic increased from 30.9 to 48.3; p = 0.001). Among subjects with normal CFR, those with LAE had significantly worse event-free survival (risk adjusted HR 5.4, 95 % CI 2.3 - 12.8, p < 0.0001). LAE and reduced CFR are related but distinct cardiovascular adaptations to atherogenic risk factors. LAE is a risk marker for MACE independent of clinical factors and left ventricular volumes; individuals with LAE may be at risk of MACE despite normal coronary vascular function. (orig.)

  20. [Major nutrition-related risk factors of ischemic heart disease: dyslipoproteinemia, obesity, hypertension, glucose intolerance].

    Science.gov (United States)

    Pados, G

    1999-07-11

    Of the major risk factors of coronary heart disease dyslipoproteinemia, obesity, hypertension, and diabetes are nutrition related and can be considered of metabolic origin. Dyslipoproteinemia affects 2/3 of the adult population. The risk of coronary heart disease can be decreased 2-5 fold by lowering hypercholesterinemia; atherosclerosis in the coronaries may regress and total mortality may decrease. Atherogenic dyslipidemia (i.e. hypertriglyceridaemia, low HDL cholesterol levels, elevated concentrations of small dense LDL) increases the risk as part of the metabolic syndrome. Obesity is already highly prevalent, and it is affecting ever growing proportions of the adult population. Abdominal obesity furthermore predisposes patients to complications. No effective therapy is available for obesity. 3/4 of hypertensive patients are obese and more than half of them have insulin resistance. By decreasing blood pressure, the risk of stroke decreases by about 40%, that of coronary heart disease by 14-30%. Slimming cures are the most important non-pharmacological way of treating hypertension. 5% of the population has diabetes mellitus, and a further 5% has impaired glucose tolerance. Type 2 diabetes predisposes patients to macrovascular complications. The risk of coronary heart disease can be decreased by controlling diabetes by e.g. metformin.

  1. Genetic risk variants in the CDKN2A/B, RTEL1 and EGFR genes are associated with somatic biomarkers in glioma.

    Science.gov (United States)

    Ghasimi, Soma; Wibom, Carl; Dahlin, Anna M; Brännström, Thomas; Golovleva, Irina; Andersson, Ulrika; Melin, Beatrice

    2016-05-01

    During the last years, genome wide association studies have discovered common germline genetic variants associated with specific glioma subtypes. We aimed to study the association between these germline risk variants and tumor phenotypes, including copy number aberrations and protein expression. A total of 91 glioma patients were included. Thirteen well known genetic risk variants in TERT, EGFR, CCDC26, CDKN2A, CDKN2B, PHLDB1, TP53, and RTEL1 were selected for investigation of possible correlations with the glioma somatic markers: EGFR amplification, 1p/19q codeletion and protein expression of p53, Ki-67, and mutated IDH1. The CDKN2A/B risk variant, rs4977756, and the CDKN2B risk variant, rs1412829 were inversely associated (p = 0.049 and p = 0.002, respectively) with absence of a mutated IDH1, i.e., the majority of patients homozygous for the risk allele showed no or low expression of mutated IDH1. The RTEL1 risk variant, rs6010620 was associated (p = 0.013) with not having 1p/19q codeletion, i.e., the majority of patients homozygous for the risk allele did not show 1p/19q codeletion. In addition, the EGFR risk variant rs17172430 and the CDKN2B risk variant rs1412829, both showed a trend for association (p = 0.055 and p = 0.051, respectively) with increased EGFR copy number, i.e., the majority of patients homozygote for the risk alleles showed chromosomal gain or amplification of EGFR. Our findings indicate that CDKN2A/B risk genotypes are associated with primary glioblastoma without IDH mutation, and that there is an inverse association between RTEL1 risk genotypes and 1p/19q codeletion, suggesting that these genetic variants have a molecular impact on the genesis of high graded brain tumors. Further experimental studies are needed to delineate the functional mechanism of the association between genotype and somatic genetic aberrations.

  2. [Prediction value of deceleration capacity of rate and GRACE risk score on major adverse cardiac events in patients with acute myocardial infarction].

    Science.gov (United States)

    Gao, L; Chen, Y D; Shi, Y J; Xue, H; Wang, J L

    2016-07-24

    To investigate the prediction value of deceleration capacity of rate (DC) and GRACE risk score for cardiovascular events in AMI patients. Consecutive AMI patients with sinus rhythm hospitalized in our department during August 2012 to August 2013 were included in this prospective study. 24-hour ECG Holter monitoring was performed within 1 week, and the DC value was analyzed, GRACE risk score was acquired with the application of GRACE risk score calculator. Patients were followed up for more than 1 year and major adverse cardiac events (MACE) were obtained. Analysised the Kaplan Meier survival according to DC and GRACE score risk stratification respectively. A total of 157 patients were enrolled in the study (average age: (58.9±12.7)years old). The average follow-up was (20.54±2.85) months. Mortality during follow-up was significantly higher in patients with DC>2.5 compared to patients with DC≤2.5 (Prisk stratification was 0.898 (95%CI 0.840-0.940, Prisk stratification was 0.786 (95%CI 0.714-0.847, Prisk stratification was 0.708 (95%CI 0.652-0.769, Prisk patients than those with intermediate and low risk patients according to DC risk stratification in intermediate and low risk patients by GRACE risk stratification (Prisk stratification is superior to GRACE risk score on outcome assessment in this AMI patient cohort.

  3. Meat consumption is a major risk factor for hepatitis E virus infection.

    Directory of Open Access Journals (Sweden)

    Ed Slot

    Full Text Available The incidence of autochthonous hepatitis E virus genotype 3 (HEV gt3 infections in Western Europe is high. Although pigs are a major reservoir of the virus, the exact sources and transmission route(s of HEV gt3 to humans remain unclear.To determine the role of meat consumption at a population level, the seroprevalence of anti-HEV IgG antibodies was compared between Dutch blood donors with a vegetarian lifestyle and donors who consume meat on a daily basis.The age-weighted anti-HEV IgG seroprevalence among donors not eating meat was significantly lower than among meat-eating donors (12.4% vs 20.5%, p = 0.002. For both groups the prevalence strongly increased with age and the difference in prevalence was apparent for all age groups.Compared with meat-eating donors, the incidence of HEV infection is significantly lower among donors not eating meat, indicating that meat consumption is a major risk factor for HEV infection.

  4. Increasing the Risk of Spontaneous Abortion and Major Malformations in Newborns Following Use of Serotonin Reuptake Inhibitors during Pregnancy: a Systematic Review and Updated Meta-Analysis

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    Mohammad Abdollahi

    2012-11-01

    Full Text Available Selective serotonin reuptake inhibitors (SSRIs are the most frequently used antidepressants during pregnancy. There are conflicting results about their influence on pregnancy outcomes.The goal of this study was to update our previous meta-analysis about pregnancy outcomes following exposure to SSRIs. For this purpose, all relevant databases were searched from 1990 to March 2012 for studies investigating the pregnancy outcomes following exposure to any therapeutic dosage of any SSRI (fluoxetine, paroxetine, citalopram, escitalopram, sertraline, fluvoxamine during pregnancy. Types of outcome investigated were spontaneousabortion, major malformations, cardiovascular malformations, and minor malformations. A total of 25 studies met our criteria and were included in the meta-analysis. The odds ratio (OD values are 1.87 (95% CI: 1.5 to 2.33, P< 0.0001 for spontaneous abortion, 1.272 (95%CI: 1.098 to 1.474, P = 0.0014 for major malformations, 1.192 (95% CI: 0.39 to 3.644, P=0.7578 for cardiovascular malformations, and 1.36 (95% CI: 0.61 to 3.04, P= 0.4498 for minor malformations. The results demonstrated that SSRIs increase the risk of spontaneousabortion and major malformations during pregnancy while they don’t increase the risk of cardiovascular malformations and minor malformations. Our previous meta-analysis only showed an increase in the risk of spontaneous abortion following the use of SSRIs duringpregnancy. This might be due to increase in the number of studies included or addition of two new SSRIs (citalopram and escitalopram. The message to researchers is to try considering SSRIs individually during pregnancy to reduce heterogeneity, although all are aware ofinevitable limitations to study on pregnant mothers.

  5. Built Environment, Selected Risk Factors and Major Cardiovascular Disease Outcomes: A Systematic Review.

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    Pasmore Malambo

    Full Text Available Built environment attributes have been linked to cardiovascular disease (CVD risk. Therefore, identifying built environment attributes that are associated with CVD risk is relevant for facilitating effective public health interventions.To conduct a systematic review of literature to examine the influence of built environmental attributes on CVD risks.Multiple database searches including Science direct, CINAHL, Masterfile Premier, EBSCO and manual scan of reference lists were conducted.Studies published in English between 2005 and April 2015 were included if they assessed one or more of the neighborhood environmental attributes in relation with any major CVD outcomes and selected risk factors among adults.Author(s, country/city, sex, age, sample size, study design, tool used to measure neighborhood environment, exposure and outcome assessments and associations were extracted from eligible studies.Eighteen studies met the inclusion criteria. Most studies used both cross-sectional design and Geographic Information System (GIS to assess the neighborhood environmental attributes. Neighborhood environmental attributes were significantly associated with CVD risk and CVD outcomes in the expected direction. Residential density, safety from traffic, recreation facilities, street connectivity and high walkable environment were associated with physical activity. High walkable environment, fast food restaurants, supermarket/grocery stores were associated with blood pressure, body mass index, diabetes mellitus and metabolic syndrome. High density traffic, road proximity and fast food restaurants were associated with CVDs outcomes.This study confirms the relationship between neighborhood environment attributes and CVDs and risk factors. Prevention programs should account for neighborhood environmental attributes in the communities where people live.

  6. Genes responsible for vaginal extracellular matrix metabolism are modulated by women's reproductive cycle and menopause

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    Oksana Shynlova

    2013-04-01

    Full Text Available Objectives To analyze the expression of genes involved in extracellular matrix (ECM biogenesis and remodeling in vaginal tissue of women with clinically normal pelvic floor support (defined as controls according to the phase of menstrual cycle and postmenopausal women with and without pelvic organ prolapse (POP. Materials and Methods This study examined the expression of matrix metalloproteinases (MMPs, their tissue inhibitors (TIMPs, and the Lysyl oxidase (LOX family genes in the anterior vaginal wall of Caucasian women by real-time RT-PCR. Initially, mRNA expression was assessed in premenopausal controls in the secretory (group 1, n = 10 vs. proliferative (group 2, n = 8 phase of menstrual cycle. In addition, we compared premenopausal controls in the proliferative phase (group 2 vs. postmenopausal controls (group 3, n = 5. Finally, we analyzed postmenopausal controls (group 3 vs. postmenopausal women with advanced POP (group 4, n = 13. Results According to the phase of menstrual cycle, MMP1 was significantly reduced (p = 0.003, whereas the expression of TIMP1 and LOXL4 was significantly up-regulated during proliferative phase (both p < 0.01 when compared to the secretory phase in premenopausal control women. Regarding menopausal status/ageing, all MMPs were down-regulated, while TIMP3, TIMP4 and LOXL2 were significantly up-regulated in postmenopausal control women when compared to premenopausal controls (p = 0.005, p = 0.01 and p < 0.001, correspondingly. TIMP4 and LOXL2 mRNA levels were significantly decreased in postmenopausal POP patients compared to asymptomatic postmenopausal controls (p < 0.01 for both. Conclusions Our results indicate that ovarian cycle and age-related changes influence the expression of genes encoding proteins responsible for ECM metabolism in human vagina. Moreover, POP is associated with alteration in vaginal ECM components after menopause.

  7. Alcohol screening and risk of postoperative complications in male VA patients undergoing major non-cardiac surgery.

    Science.gov (United States)

    Bradley, Katharine A; Rubinsky, Anna D; Sun, Haili; Bryson, Chris L; Bishop, Michael J; Blough, David K; Henderson, William G; Maynard, Charles; Hawn, Mary T; Tønnesen, Hanne; Hughes, Grant; Beste, Lauren A; Harris, Alex H S; Hawkins, Eric J; Houston, Thomas K; Kivlahan, Daniel R

    2011-02-01

    Patients who misuse alcohol are at increased risk for surgical complications. Four weeks of preoperative abstinence decreases the risk of complications, but practical approaches for early preoperative identification of alcohol misuse are needed. To evaluate whether results of alcohol screening with the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C) questionnaire-up to a year before surgery-were associated with the risk of postoperative complications. This is a cohort study. Male Veterans Affairs (VA) patients were eligible if they had major noncardiac surgery assessed by the VA's Surgical Quality Improvement Program (VASQIP) in fiscal years 2004-2006, and completed the AUDIT-C alcohol screening questionnaire (0-12 points) on a mailed survey within 1 year before surgery. One or more postoperative complication(s) within 30 days of surgery based on VASQIP nurse medical record reviews. Among 9,176 eligible men, 16.3% screened positive for alcohol misuse with AUDIT-C scores ≥ 5, and 7.8% had postoperative complications. Patients with AUDIT-C scores ≥ 5 were at significantly increased risk for postoperative complications, compared to patients who drank less. In analyses adjusted for age, smoking, and days from screening to surgery, the estimated prevalence of postoperative complications increased from 5.6% (95% CI 4.8-6.6%) in patients with AUDIT-C scores 1-4, to 7.9% (6.3-9.7%) in patients with AUDIT-Cs 5-8, 9.7% (6.6-14.1%) in patients with AUDIT-Cs 9-10 and 14.0% (8.9-21.3%) in patients with AUDIT-Cs 11-12. In fully-adjusted analyses that included preoperative covariates potentially in the causal pathway between alcohol misuse and complications, the estimated prevalence of postoperative complications increased significantly from 4.8% (4.1-5.7%) in patients with AUDIT-C scores 1-4, to 6.9% (5.5-8.7%) in patients with AUDIT-Cs 5-8 and 7.5% (5.0-11.3%) among those with AUDIT-Cs 9-10. AUDIT-C scores of 5 or more up to a year before surgery were

  8. A Multi-Breed Genome-Wide Association Analysis for Canine Hypothyroidism Identifies a Shared Major Risk Locus on CFA12.

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    Matteo Bianchi

    Full Text Available Hypothyroidism is a complex clinical condition found in both humans and dogs, thought to be caused by a combination of genetic and environmental factors. In this study we present a multi-breed analysis of predisposing genetic risk factors for hypothyroidism in dogs using three high-risk breeds--the Gordon Setter, Hovawart and the Rhodesian Ridgeback. Using a genome-wide association approach and meta-analysis, we identified a major hypothyroidism risk locus shared by these breeds on chromosome 12 (p = 2.1x10(-11. Further characterisation of the candidate region revealed a shared ~167 kb risk haplotype (4,915,018-5,081,823 bp, tagged by two SNPs in almost complete linkage disequilibrium. This breed-shared risk haplotype includes three genes (LHFPL5, SRPK1 and SLC26A8 and does not extend to the dog leukocyte antigen (DLA class II gene cluster located in the vicinity. These three genes have not been identified as candidate genes for hypothyroid disease previously, but have functions that could potentially contribute to the development of the disease. Our results implicate the potential involvement of novel genes and pathways for the development of canine hypothyroidism, raising new possibilities for screening, breeding programmes and treatments in dogs. This study may also contribute to our understanding of the genetic etiology of human hypothyroid disease, which is one of the most common endocrine disorders in humans.

  9. Major hazard risk indicators for monitoring of trends in the Norwegian offshore petroleum sector

    International Nuclear Information System (INIS)

    Vinnem, Jan Erik; Aven, Terje; Husebo, Torleif; Seljelid, Jorunn; Tveit, Odd J.

    2006-01-01

    The Petroleum Safety Authority Norway (PSA, formerly Norwegian Petroleum Directorate) took in 1999 the initiative to develop a method in order to assess trends and status for the risk levels in the Norwegian offshore petroleum industry. A method was developed, and a pilot study report was issued in April 2001, covering the period 1996-2000. Annual updates have been performed since then, and the latest report covers the period 1996-2004. The statistical approach is based on recording occurrence of near misses and relevant incidents, performance of barriers and results from risk assessments. Of similar importance is an evaluation of safety culture, motivation, communication and perceived risk. This is covered through the use of social science methods, such as questionnaire surveys and a number of interviews, audit and inspection reports as well as accident and incident investigations. There are also indicators for occupational accidents and occupational illness/-physical working environment factors. The focus is on the major hazard risk components for personnel staying on the offshore installations. An overview of the indicators used to illustrate these risk aspects is presented, followed by a discussion of the analytical approach used for these indicators. Results from the risk assessment for the Norwegian Continental Shelf in the period 1996-2004 are used throughout for illustration, and discussion of challenges

  10. A pragmatic multi-centre randomised controlled trial of fluid loading in high-risk surgical patients undergoing major elective surgery--the FOCCUS study.

    Science.gov (United States)

    Cuthbertson, Brian H; Campbell, Marion K; Stott, Stephen A; Elders, Andrew; Hernández, Rodolfo; Boyers, Dwayne; Norrie, John; Kinsella, John; Brittenden, Julie; Cook, Jonathan; Rae, Daniela; Cotton, Seonaidh C; Alcorn, David; Addison, Jennifer; Grant, Adrian

    2011-01-01

    Fluid strategies may impact on patient outcomes in major elective surgery. We aimed to study the effectiveness and cost-effectiveness of pre-operative fluid loading in high-risk surgical patients undergoing major elective surgery. This was a pragmatic, non-blinded, multi-centre, randomised, controlled trial. We sought to recruit 128 consecutive high-risk surgical patients undergoing major abdominal surgery. The patients underwent pre-operative fluid loading with 25 ml/kg of Ringer's solution in the six hours before surgery. The control group had no pre-operative fluid loading. The primary outcome was the number of hospital days after surgery with cost-effectiveness as a secondary outcome. A total of 111 patients were recruited within the study time frame in agreement with the funder. The median pre-operative fluid loading volume was 1,875 ml (IQR 1,375 to 2,025) in the fluid group compared to 0 (IQR 0 to 0) in controls with days in hospital after surgery 12.2 (SD 11.5) days compared to 17.4 (SD 20.0) and an adjusted mean difference of 5.5 days (median 2.2 days; 95% CI -0.44 to 11.44; P = 0.07). There was a reduction in adverse events in the fluid intervention group (P = 0.048) and no increase in fluid based complications. The intervention was less costly and more effective (adjusted average cost saving: £2,047; adjusted average gain in benefit: 0.0431 quality adjusted life year (QALY)) and has a high probability of being cost-effective. Pre-operative intravenous fluid loading leads to a non-significant reduction in hospital length of stay after high-risk major surgery and is likely to be cost-effective. Confirmatory work is required to determine whether these effects are reproducible, and to confirm whether this simple intervention could allow more cost-effective delivery of care. Prospective Clinical Trials, ISRCTN32188676.

  11. On improvement in ejection fraction with iron chelation in thalassemia major and the risk of future heart failure

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    Carpenter JP

    2011-09-01

    Full Text Available Abstract Background Trials of iron chelator regimens have increased the treatment options for cardiac siderosis in beta-thalassemia major (TM patients. Treatment effects with improved left ventricular (LV ejection fraction (EF have been observed in patients without overt heart failure, but it is unclear whether these changes are clinically meaningful. Methods This retrospective study of a UK database of TM patients modelled the change in EF between serial scans measured by cardiovascular magnetic resonance (CMR to the relative risk (RR of future development of heart failure over 1 year. Patients were divided into 2 strata by baseline LVEF of 56-62% (below normal for TM and 63-70% (lower half of the normal range for TM. Results A total of 315 patients with 754 CMR scans were analyzed. A 1% absolute increase in EF from baseline was associated with a statistically significant reduction in the risk of future development of heart failure for both the lower EF stratum (EF 56-62%, RR 0.818, p Conclusion These data show that during treatment with iron chelators for cardiac siderosis, small increases in LVEF in TM patients are associated with a significantly reduced risk of the development of heart failure. Thus the iron chelator induced improvements in LVEF of 2.6% to 3.1% that have been observed in randomized controlled trials, are associated with risk reductions of 25.5% to 46.4% for the development of heart failure over 12 months, which is clinically meaningful. In cardiac iron overload, heart mitochondrial dysfunction and its relief by iron chelation may underlie the changes in LV function.

  12. Residential proximity to major roads and obstetrical complications.

    Science.gov (United States)

    Yorifuji, Takashi; Naruse, Hiroo; Kashima, Saori; Murakoshi, Takeshi; Doi, Hiroyuki

    2015-03-01

    Exposure to air pollution is linked with an increased risk of preterm births. To provide further evidence on this relationship, we evaluated the association between proximity to major roads--as an index for air pollution exposure--and various obstetrical complications. Data were extracted from a database maintained by the perinatal hospital in Shizuoka, Japan. We restricted the analysis to mothers with singleton pregnancies of more than 22 weeks of gestation from 1997 to 2012 (n=19,077). Using the geocoded residential information, each mother was assigned proximity to major roads. We then estimated multivariate adjusted odds ratios and their 95% confidence intervals (CIs) for the effects of proximity to major roads on various obstetrical complications (preeclampsia, gestational diabetes mellitus, placenta abruption, placenta previa, preterm premature rupture of membrane (pPROM), preterm labor, and preterm births). We found positive associations of proximity to major roads with preeclampsia and pPROM. Living within 200 m increased the odds of preeclampsia by 1.3 times (95% CI, 1.0-1.8) and pPROM by 1.6 times (95% CI, 1.1-2.2). Furthermore, living within 200 m increased the odds of preterm births by 1.4 fold (95% CI, 1.2-1.7). Exposure to traffic-related air pollution increased the risk of preeclampsia and pPROM in this study. We propose a mechanism responsible for the association between air pollution and preterm births. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer

    Science.gov (United States)

    Win, Aung Ko; Jenkins, Mark A.; Dowty, James G.; Antoniou, Antonis C.; Lee, Andrew; Giles, Graham G.; Buchanan, Daniel D.; Clendenning, Mark; Rosty, Christophe; Ahnen, Dennis J.; Thibodeau, Stephen N.; Casey, Graham; Gallinger, Steven; Le Marchand, Loïc; Haile, Robert W.; Potter, John D.; Zheng, Yingye; Lindor, Noralane M.; Newcomb, Polly A.; Hopper, John L.; MacInnis, Robert J.

    2016-01-01

    Background While high-risk mutations in identified major susceptibility genes (DNA mismatch repair genes and MUTYH) account for some familial aggregation of colorectal cancer, their population prevalence and the causes of the remaining familial aggregation are not known. Methods We studied the families of 5,744 colorectal cancer cases (probands) recruited from population cancer registries in the USA, Canada and Australia and screened probands for mutations in mismatch repair genes and MUTYH. We conducted modified segregation analyses using the cancer history of first-degree relatives, conditional on the proband’s age at diagnosis. We estimated the prevalence of mutations in the identified genes, the prevalence of and hazard ratio for unidentified major gene mutations, and the variance of the residual polygenic component. Results We estimated that 1 in 279 of the population carry mutations in mismatch repair genes (MLH1= 1 in 1946, MSH2= 1 in 2841, MSH6= 1 in 758, PMS2= 1 in 714), 1 in 45 carry mutations in MUTYH, and 1 in 504 carry mutations associated with an average 31-fold increased risk of colorectal cancer in unidentified major genes. The estimated polygenic variance was reduced by 30–50% after allowing for unidentified major genes and decreased from 3.3 for age colorectal cancer. Impact Our findings could aid gene discovery and development of better colorectal cancer risk prediction models. PMID:27799157

  14. Knowledge, attitudes, and practices toward malaria risk and prevention among frequent business travelers of a major oil and gas company.

    Science.gov (United States)

    Berg, Johannes; Breederveld, Daan; Roukens, Anna H; Hennink, Yvonne; Schouten, Marjolijn; Wendt, Judy K; Visser, Leo G

    2011-01-01

    Despite significant morbidity and mortality among business travelers due to malaria, very little has been published on knowledge, attitudes, and practices (KAP) toward malaria risk. The aim of this study was to assess KAP among frequent international business travelers (FBT) and to identify recommendations for improving malaria prevention that could be applied to the wider FBT community in occupational health. A retrospective web-based survey was conducted in 2005 among self-registered FBT of an oil and gas company based in the Netherlands. The survey was completed by 328 of the 608 self-registered FBT (54%). Fifty-four percent of respondents had visited a high-risk area for malaria. Most respondents (96%) were experienced travelers; the majority (71%) sought health advice before their trip and made use of a company health resource. Fever was recognized as a malaria symptom by all FBT; travel to high-risk malaria areas was correctly identified by 96%, and 99% of these travelers adhered to use of adequate personal protective measures. The proportion of travelers carrying appropriate anti-malaria drug regimen was positively associated with receiving company advice among FBT traveling to high-risk destinations (RR = 2.10, 95% CI: 1.21-3.67), but not for those traveling to low- or no-risk destinations. Only 8% (14) of those going to a high-risk area were not carrying malaria prophylaxis. One in five of FBT traveling to no-risk areas were unnecessarily carrying malaria prophylaxis. The majority of KAP results were excellent. We postulate that a company culture with a strong focus on health, safety, security, and environment can positively contribute to high KAP scores. Notwithstanding the excellent findings, this study also provides a cautionary tale for company health functions against overprescribing of malaria prophylaxis. It demonstrates the need for constant review and audit of adherence to quality criteria. © 2011 International Society of Travel Medicine.

  15. NASA Risk Management Handbook. Version 1.0

    Science.gov (United States)

    Dezfuli, Homayoon; Benjamin, Allan; Everett, Christopher; Maggio, Gaspare; Stamatelatos, Michael; Youngblood, Robert; Guarro, Sergio; Rutledge, Peter; Sherrard, James; Smith, Curtis; hide

    2011-01-01

    The purpose of this handbook is to provide guidance for implementing the Risk Management (RM) requirements of NASA Procedural Requirements (NPR) document NPR 8000.4A, Agency Risk Management Procedural Requirements [1], with a specific focus on programs and projects, and applying to each level of the NASA organizational hierarchy as requirements flow down. This handbook supports RM application within the NASA systems engineering process, and is a complement to the guidance contained in NASA/SP-2007-6105, NASA Systems Engineering Handbook [2]. Specifically, this handbook provides guidance that is applicable to the common technical processes of Technical Risk Management and Decision Analysis established by NPR 7123.1A, NASA Systems Engineering Process and Requirements [3]. These processes are part of the \\Systems Engineering Engine. (Figure 1) that is used to drive the development of the system and associated work products to satisfy stakeholder expectations in all mission execution domains, including safety, technical, cost, and schedule. Like NPR 7123.1A, NPR 8000.4A is a discipline-oriented NPR that intersects with product-oriented NPRs such as NPR 7120.5D, NASA Space Flight Program and Project Management Requirements [4]; NPR 7120.7, NASA Information Technology and Institutional Infrastructure Program and Project Management Requirements [5]; and NPR 7120.8, NASA Research and Technology Program and Project Management Requirements [6]. In much the same way that the NASA Systems Engineering Handbook is intended to provide guidance on the implementation of NPR 7123.1A, this handbook is intended to provide guidance on the implementation of NPR 8000.4A. 1.2 Scope and Depth This handbook provides guidance for conducting RM in the context of NASA program and project life cycles, which produce derived requirements in accordance with existing systems engineering practices that flow down through the NASA organizational hierarchy. The guidance in this handbook is not meant

  16. Identification of a DMBT1 polymorphism associated with increased breast cancer risk and decreased promoter activity

    DEFF Research Database (Denmark)

    Tchatchou, Sandrine; Riedel, Angela; Lyer, Stefan

    2010-01-01

    ,466 unrelated German controls. Promoter studies in breast cancer cells demonstrate that the risk-increasing DMBT1 -93T allele displays significantly decreased promoter activity compared to the DMBT1 -93C allele, resulting in a loss of promoter activity. The data suggest that DMBT1 polymorphisms in the 5'-region......According to present estimations, the unfavorable combination of alleles with low penetrance but high prevalence in the population might account for the major part of hereditary breast cancer risk. Deleted in Malignant Brain Tumors 1 (DMBT1) has been proposed as a tumor suppressor for breast cancer...... and other cancer types. Genomewide mapping in mice further identified Dmbt1 as a potential modulator of breast cancer risk. Here, we report the association of two frequent and linked single-nucleotide polymorphisms (SNPs) with increased breast cancer risk in women above the age of 60 years: DMBT1 c.-93C...

  17. Populations at risk for severe or complicated Avian Influenza H5N1: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Dominik Mertz

    Full Text Available BACKGROUND: Little is known about risk factors for severe outcomes in patients infected with H5N1 and no systematic review has been conducted. Understanding risk factors is an important step for prioritizing prophylaxis or treatment in the event of a pandemic. OBJECTIVES: To systematically evaluate risk factors for severe outcomes in patients with avian influenza H5N1 infection. DATA SOURCES: MEDLINE, EMBASE, CINAHL, GlobalHealth, and CENTRAL through March 2011. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Observational studies of any design published in English, French, Spanish, German or Korean that reported on risk factor-outcome combinations of interest in participants with confirmed H5N1 infections. Outcomes considered included death, ventilator support, hospital and ICU admission, pneumonia, and composite outcomes. STUDY APPRAISAL: Risk of bias was assessed using the Newcastle-Ottawa scale (NOS. RESULTS: We identified 20 studies reporting on 999 patients infected with H5N1. The majority of studies (n = 14, 70% were at intermediate risk of bias, i.e. 4-6 points on the NOS. Females were at increased risk of death (OR 1.75, 95% CI 1.27-2.44, while young age, in particular <5 years of age (OR 0.44, 95% CI 0.25-0.79 for death, was protective. Data on traditional risk factors was scarce and requires further studies. Another major limitation in the published literature was lack of adjustment for confounders. INTERPRETATION: Females were at increased risk for complications following H5N1 infection while young age protected against severe outcomes. Research on traditional risk factors was limited and is required.

  18. 12 CFR 932.1 - Risk management.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Risk management. 932.1 Section 932.1 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOME LOAN BANK RISK MANAGEMENT AND CAPITAL STANDARDS FEDERAL HOME LOAN BANK CAPITAL REQUIREMENTS § 932.1 Risk management. Before its new capital plan may take...

  19. 26 CFR 1.953-3 - Risks deemed to be United States risks.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 10 2010-04-01 2010-04-01 false Risks deemed to be United States risks. 1.953-3... TAX (CONTINUED) INCOME TAXES Controlled Foreign Corporations § 1.953-3 Risks deemed to be United States risks. (a) Artificial arrangements. For purposes of paragraph (a) of § 1.953-1, the term “United...

  20. Left atrial enlargement increases the risk of major adverse cardiac events independent of coronary vasodilator capacity.

    Science.gov (United States)

    Koh, Angela S; Murthy, Venkatesh L; Sitek, Arkadiusz; Gayed, Peter; Bruyere, John; Wu, Justina; Di Carli, Marcelo F; Dorbala, Sharmila

    2015-09-01

    Longstanding uncontrolled atherogenic risk factors may contribute to left atrial (LA) hypertension, LA enlargement (LAE) and coronary vascular dysfunction. Together they may better identify risk of major adverse cardiac events (MACE). The aim of this study was to test the hypothesis that chronic LA hypertension as assessed by LAE modifies the relationship between coronary vascular function and MACE. In 508 unselected subjects with a normal clinical (82)Rb PET/CT, ejection fraction ≥40 %, no prior coronary artery disease, valve disease or atrial fibrillation, LAE was determined based on LA volumes estimated from the hybrid perfusion and CT transmission scan images and indexed to body surface area. Absolute myocardial blood flow and global coronary flow reserve (CFR) were calculated. Subjects were systematically followed-up for the primary end-point - MACE - a composite of all-cause death, myocardial infarction, hospitalization for heart failure, stroke, coronary artery disease progression or revascularization. During a median follow-up of 862 days, 65 of the subjects experienced a composite event. Compared with subjects with normal LA size, subjects with LAE showed significantly lower CFR (2.25 ± 0.83 vs. 1.95 ± 0.80, p = 0.01). LAE independently and incrementally predicted MACE even after accounting for clinical risk factors, medication use, stress left ventricular ejection fraction, stress left ventricular end-diastolic volume index and CFR (chi-squared statistic increased from 30.9 to 48.3; p = 0.001). Among subjects with normal CFR, those with LAE had significantly worse event-free survival (risk adjusted HR 5.4, 95 % CI 2.3 - 12.8, p < 0.0001). LAE and reduced CFR are related but distinct cardiovascular adaptations to atherogenic risk factors. LAE is a risk marker for MACE independent of clinical factors and left ventricular volumes; individuals with LAE may be at risk of MACE despite normal coronary vascular function.

  1. 7 CFR 3052.520 - Major program determination.

    Science.gov (United States)

    2010-01-01

    ... Auditors § 3052.520 Major program determination. (a) General. The auditor shall use a risk-based approach... section shall be followed. (b) Step 1. (1) The auditor shall identify the larger Federal programs, which... providing loans significantly affects the number or size of Type A programs, the auditor shall consider this...

  2. Technical risk audit method (tram): development and application to the auditing of major hazard sites

    International Nuclear Information System (INIS)

    Maddison, T.; Kirk, P.; Stansfield, R.

    1998-01-01

    The Technical Risk Audit Method (TRAM) has been developed by the UK Health and Safety Executive (UK HSE) as a risk-based auditing and inspection tool for application to Major Hazard process plant covered by the Seveso-I/Seveso-II directives. The objective of TRAM is to provide a framework in which plant inspection or audit can be undertaken and results collated. TRAM comprises a paper audit procedure and a software tool which is used to analyse the results. TRAM includes a semi-quantitative risk model, which may be used to rank risks both within and between similar facilities, using qualitative data collected during the inspection. The results of this qualitative analysis may be used to identify where inspector resources would be best deployed. To date, TRAM has been applied to a number of LPG storage and processing facilities in the UK, and the lessons learnt are being used to develop a robust version suitable for use by inspectors. The methodology will be made consistent with the risk model included in IEC 61508 'Functional safety of electrical/electronic/programmable electronic safety-related systems' to permit its application to a wide range of process plant and other hazardous facilities. (authors)

  3. CCL3L1-CCR5 genotype improves the assessment of AIDS Risk in HIV-1-infected individuals.

    Science.gov (United States)

    Kulkarni, Hemant; Agan, Brian K; Marconi, Vincent C; O'Connell, Robert J; Camargo, Jose F; He, Weijing; Delmar, Judith; Phelps, Kenneth R; Crawford, George; Clark, Robert A; Dolan, Matthew J; Ahuja, Sunil K

    2008-09-08

    Whether vexing clinical decision-making dilemmas can be partly addressed by recent advances in genomics is unclear. For example, when to initiate highly active antiretroviral therapy (HAART) during HIV-1 infection remains a clinical dilemma. This decision relies heavily on assessing AIDS risk based on the CD4+ T cell count and plasma viral load. However, the trajectories of these two laboratory markers are influenced, in part, by polymorphisms in CCR5, the major HIV coreceptor, and the gene copy number of CCL3L1, a potent CCR5 ligand and HIV-suppressive chemokine. Therefore, we determined whether accounting for both genetic and laboratory markers provided an improved means of assessing AIDS risk. In a prospective, single-site, ethnically-mixed cohort of 1,132 HIV-positive subjects, we determined the AIDS risk conveyed by the laboratory and genetic markers separately and in combination. Subjects were assigned to a low, moderate or high genetic risk group (GRG) based on variations in CCL3L1 and CCR5. The predictive value of the CCL3L1-CCR5 GRGs, as estimated by likelihood ratios, was equivalent to that of the laboratory markers. GRG status also predicted AIDS development when the laboratory markers conveyed a contrary risk. Additionally, in two separate and large groups of HIV+ subjects from a natural history cohort, the results from additive risk-scoring systems and classification and regression tree (CART) analysis revealed that the laboratory and CCL3L1-CCR5 genetic markers together provided more prognostic information than either marker alone. Furthermore, GRGs independently predicted the time interval from seroconversion to CD4+ cell count thresholds used to guide HAART initiation. The combination of the laboratory and genetic markers captures a broader spectrum of AIDS risk than either marker alone. By tracking a unique aspect of AIDS risk distinct from that captured by the laboratory parameters, CCL3L1-CCR5 genotypes may have utility in HIV clinical management

  4. 29 CFR 99.520 - Major program determination.

    Science.gov (United States)

    2010-07-01

    ... Auditors § 99.520 Major program determination. (a) General. The auditor shall use a risk-based approach to... followed. (b) Step 1. (1) The auditor shall identify the larger Federal programs, which shall be labeled... size of Type A programs, the auditor shall consider this Federal program as a Type A program and...

  5. B-1 cells modulate the murine macrophage response to Leishmania major infection.

    Science.gov (United States)

    Arcanjo, Angelica F; Nunes, Marise P; Silva-Junior, Elias B; Leandro, Monique; da Rocha, Juliana Dutra Barbosa; Morrot, Alexandre; Decote-Ricardo, Debora; Freire-de-Lima, Celio Geraldo

    2017-05-26

    To investigate the modulatory effect of B-1 cells on murine peritoneal macrophages infected with Leishmania major ( L. major ) in vitro . Peritoneal macrophages obtained from BALB/c and BALB/c XID mice were infected with L. major and cultured in the presence or absence of B-1 cells obtained from wild-type BALB/c mice. Intracellular amastigotes were counted, and interleukin-10 (IL-10) production was quantified in the cellular supernatants using an enzyme-linked immunosorbent assay. The levels of the lipid mediator prostaglandin E2 (PGE 2 ) were determined using a PGE 2 enzyme immunoassay kit (Cayman Chemical, Ann Arbor, MI), and the number of lipid bodies was quantified in the cytoplasm of infected macrophages in the presence and absence of B-1 cells. Culturing the cells with selective PGE 2 -neutralizing drugs inhibited PGE 2 production and confirmed the role of this lipid mediator in IL-10 production. In contrast, we demonstrated that B-1 cells derived from IL-10 KO mice did not favor the intracellular growth of L. major . We report that B-1 cells promote the growth of L. major amastigotes inside peritoneal murine macrophages. We demonstrated that the modulatory effect was independent of physical contact between the cells, suggesting that soluble factor(s) were released into the cultures. We demonstrated in our co-culture system that B-1 cells trigger IL-10 production by L. major -infected macrophages. Furthermore, the increased secretion of IL-10 was attributed to the presence of the lipid mediator PGE 2 in supernatants of L. major -infected macrophages. The presence of B-1 cells also favors the production of lipid bodies by infected macrophages. In contrast, we failed to obtain the same effect on parasite replication inside L. major -infected macrophages when the B-1 cells were isolated from IL-10 knockout mice. Our results show that elevated levels of PGE 2 and IL-10 produced by B-1 cells increase L. major growth, as indicated by the number of parasites in cell

  6. Major League Baseball pitch velocity and pitch type associated with risk of ulnar collateral ligament injury.

    Science.gov (United States)

    Keller, Robert A; Marshall, Nathan E; Guest, John-Michael; Okoroha, Kelechi R; Jung, Edward K; Moutzouros, Vasilios

    2016-04-01

    The number of Major League Baseball (MLB) pitchers requiring ulnar collateral ligament (UCL) reconstructions is increasing. Recent literature has attempted to correlate specific stresses placed on the throwing arm to risk for UCL injury, with limited results. Eighty-three MLB pitchers who underwent primary UCL reconstruction were evaluated. Pitching velocity and percent of pitch type thrown (fastball, curve ball, slider, and change-up) were evaluated 2 years before and after surgery. Data were compared with control pitchers matched for age, position, size, innings pitched, and experience. The evaluation of pitch velocity compared with matched controls found no differences in pre-UCL reconstruction pitch velocities for fastballs (91.5 vs. 91.2 miles per hour [mph], P = .69), curveballs (78.2 vs. 77.9 mph, P = .92), sliders (83.3 vs. 83.5 mph, P = .88), or change-ups (83.9 vs. 83.8 mph, P = .96). When the percentage of pitches thrown was evaluated, UCL reconstructed pitchers pitch significantly more fastballs than controls (46.7% vs. 39.4%, P = .035). This correlated to a 2% increase in risk for UCL injury for every 1% increase in fastballs thrown. Pitching more than 48% fastballs was a significant predictor of UCL injury, because pitchers over this threshold required reconstruction (P = .006). MLB pitchers requiring UCL reconstruction do not pitch at higher velocities than matched controls, and pitch velocity does not appear to be a risk factor for UCL reconstruction. However, MLB pitchers who pitch a high percentage of fastballs may be at increased risk for UCL injury because pitching a higher percent of fastballs appears to be a risk factor for UCL reconstruction. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  7. Produced water radionuclide hazard/risk assessment, Phase 1

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, L.D.; Meinhold, A.F.; Nagy, J.

    1991-06-01

    Petroleum production may be accompanied by the production of saline water, called produced water.'' Produced water discharged into freshwater streams, estuaries, coastal and outer continental shelf waters can contained enhanced levels of radium isotopes. This document reports on the first phase of a study to estimate the risk to human health and the environment from radium discharged in produced water. The study involved five major steps: (1) evaluate the usefulness of available produced water outfall data for developing estimates of radium environmental concentrations; (2) review the literature on the bioaccumulation of radium by aquatic organism; (3) review the literature on the effects of radiation on aquatic organisms; (4) review the information available concerning the human health risks associated with exposure to Ra-226 and Ra-228 and (5) perform a conservative, screening-level assessment of the health and environmental risks posed by Ra-226 and Ra-228 discharged in produced waters. A screening-level analysis was performed to determine whether radium discharged to coastal Louisiana in produced waters presents potential health or environmental risks requiring further study. This conservative assessment suggested that no detectable impact on populations of fish, molluscs or crustaceans from radium discharged in produced waters is likely. The analysis also suggested that there is a potential for risk were an individual to ingest a large amount of seafood harvested near a produced water discharge point over a lifetime. The number of excess cancers predicted per year under a conservative scenario is comparable to those expected to result from background concentrations of radium.

  8. Produced water radionuclide hazard/risk assessment, Phase 1

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, L.D.; Meinhold, A.F.; Nagy, J.

    1991-06-01

    Petroleum production may be accompanied by the production of saline water, called ``produced water.`` Produced water discharged into freshwater streams, estuaries, coastal and outer continental shelf waters can contained enhanced levels of radium isotopes. This document reports on the first phase of a study to estimate the risk to human health and the environment from radium discharged in produced water. The study involved five major steps: (1) evaluate the usefulness of available produced water outfall data for developing estimates of radium environmental concentrations; (2) review the literature on the bioaccumulation of radium by aquatic organism; (3) review the literature on the effects of radiation on aquatic organisms; (4) review the information available concerning the human health risks associated with exposure to Ra-226 and Ra-228 and (5) perform a conservative, screening-level assessment of the health and environmental risks posed by Ra-226 and Ra-228 discharged in produced waters. A screening-level analysis was performed to determine whether radium discharged to coastal Louisiana in produced waters presents potential health or environmental risks requiring further study. This conservative assessment suggested that no detectable impact on populations of fish, molluscs or crustaceans from radium discharged in produced waters is likely. The analysis also suggested that there is a potential for risk were an individual to ingest a large amount of seafood harvested near a produced water discharge point over a lifetime. The number of excess cancers predicted per year under a conservative scenario is comparable to those expected to result from background concentrations of radium.

  9. Produced water radionuclide hazard/risk assessment, Phase 1

    International Nuclear Information System (INIS)

    Hamilton, L.D.; Meinhold, A.F.; Nagy, J.

    1991-06-01

    Petroleum production may be accompanied by the production of saline water, called ''produced water.'' Produced water discharged into freshwater streams, estuaries, coastal and outer continental shelf waters can contained enhanced levels of radium isotopes. This document reports on the first phase of a study to estimate the risk to human health and the environment from radium discharged in produced water. The study involved five major steps: (1) evaluate the usefulness of available produced water outfall data for developing estimates of radium environmental concentrations; (2) review the literature on the bioaccumulation of radium by aquatic organism; (3) review the literature on the effects of radiation on aquatic organisms; (4) review the information available concerning the human health risks associated with exposure to Ra-226 and Ra-228 and (5) perform a conservative, screening-level assessment of the health and environmental risks posed by Ra-226 and Ra-228 discharged in produced waters. A screening-level analysis was performed to determine whether radium discharged to coastal Louisiana in produced waters presents potential health or environmental risks requiring further study. This conservative assessment suggested that no detectable impact on populations of fish, molluscs or crustaceans from radium discharged in produced waters is likely. The analysis also suggested that there is a potential for risk were an individual to ingest a large amount of seafood harvested near a produced water discharge point over a lifetime. The number of excess cancers predicted per year under a conservative scenario is comparable to those expected to result from background concentrations of radium

  10. Prevalence and risk factors of major depressive disorder in HIV/AIDS as seen in semi-urban Entebbe district, Uganda

    Directory of Open Access Journals (Sweden)

    Kinyanda Eugene

    2011-12-01

    Full Text Available Abstract Background Not much is known about the risk factors of major depressive disorder (MDD in HIV/AIDS in the African socio-cultural context. Therefore a study was undertaken to examine the prevalence and risk factors of MDD in HIV/AIDS in semi-urban Uganda. Methods A cross-sectional study was undertaken among 618 respondents attending two HIV clinics in Uganda. Results Prevalence of MDD was 8.1%. Factors associated with MDD at univariate analysis only were female gender, family history of mental illness, negative coping style, alcohol dependency disorder, food insecurity and stress; not associated with MDD were social support, neurocognitive impairment, CD4 counts and BMI. Factors independently associated with MDD were psychosocial impairment, adverse life events, post traumatic stress disorder, generalised anxiety disorder and life-time attempted suicide. Conclusion Psychological and social factors were the main risk factors of MDD among ambulatory HIV positive persons with no evidence for the role of the neurotoxic effects of HIV. Treatment approaches for MDD in this patient group should be modeled on those used among non-HIV groups.

  11. Major depressive disorder and suicide risk among adult outpatients at several general hospitals in a Chinese Han population.

    Science.gov (United States)

    Li, Haiyan; Luo, Xinni; Ke, Xiaoyin; Dai, Qing; Zheng, Wei; Zhang, Chanjuan; Cassidy, Ryan M; Soares, Jair C; Zhang, XiangYang; Ning, Yuping

    2017-01-01

    Somatic complaints are often the presenting symptoms of major depressive disorder (MDD) in the outpatient context, because this may go unrecognized. It is well understood that MDD carries an increased risk of suicide. This study aimed to identify the risk factors and association with both MDD and suicidality among Han Chinese outpatients. A multicenter study was carried out in 5189 outpatient adults (≥18 years old) in four general hospitals in Guangzhou, China. The 1392 patients who had the Patient Health Questionnaire-9 (PHQ-9) score ≥ 5, indicating depressive symptoms were offered an interview with a psychiatrist by the Mini International Neuropsychiatric Interview (MINI); 819 patients consented and completed the MINI interview. MINI module B was used to assess suicidality. Stepwise binary logistic models were used to estimate the relationship between a significant risk factor and suicide or MDD. According to with or without MDD, the secondary analysis was performed using the logistic regression model for the risk of suicidility. The current prevalence of MDD and the one month prevalence of suicidality were 3.7% and 2.3% respectively. The odds ratio of suicidality in women was more than twice that in men (OR = 2.62; 95% CI 1.45-4.76). Other risk factors which were significantly associated with suicidality were: living alone, higher education, self-reported depression, getting psychiatric diagnoses (MDD, anxiety disorders, and bipolar disorders). Significant risk factors for MDD were also noticed, such as comorbid anxiety disorders, self-reported anxiety, insomnia, suicidal ideation. It's a cross-sectional study in outpatient clinics using self-report questionnaires. This study provides valuable data about the risk factors and association of MDD and suicide risk in adult outpatients in Han Chinese. Those factors allow better the employment of preventative measures.

  12. Serum levels of nerve growth factor (NGF) in patients with major depression disorder and suicide risk.

    Science.gov (United States)

    Wiener, Carolina David; de Mello Ferreira, Sharon; Pedrotti Moreira, Fernanda; Bittencourt, Guilherme; de Oliveira, Jacqueline Flores; Lopez Molina, Mariane; Jansen, Karen; de Mattos Souza, Luciano Dias; Rizzato Lara, Diogo; Portela, Luiz Valmor; da Silva, Ricardo Azevedo; Oses, Jean Pierre

    2015-09-15

    Nerve growth factor (NGF) is an important member of the neurotrophins group and their involvement in the pathophysiology of major depression disorder (MDD) and suicide risk (SR) has been recently suggested. The aim of this study is to evaluate the changes in NGF serum levels in individuals with MDD and with or without risk of suicide, in subjects from a young population-based sample. This is a paired cross-sectional study nested in a population-based study. Individuals were rated for MDD and SR by a diagnostic interview--Mini International Neuropsychiatric Interview (M.I.N.I). The total population of the sample was comprised of 141 subjects distributed in three groups: 47 healthy controls, 47 subjects with current depressive episode without SR (MDD) and 47 subjects with current depressive episode and with SR (MDD + SR). NGF serum levels were significantly reduced in the MDD and MDD + SR groups when compared with controls (p ≤ 0.001). However, there were no differences in NGF levels between the MDD and MDD + SR groups (p = 1.000). These results suggest that reduced NGF serum levels can be a possible biomarker of MDD. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Peripheral Stent Thrombosis Leading to Acute Limb Ischemia and Major Amputation: Incidence and Risk Factors in the Aortoiliac and Femoropopliteal Arteries

    International Nuclear Information System (INIS)

    Katsanos, Konstantinos; Al-Lamki, Said A. M.; Parthipun, Aneeta; Spiliopoulos, Stavros; Patel, Sanjay Dhanji; Paraskevopoulos, Ioannis; Zayed, Hany; Diamantopoulos, Athanasios

    2017-01-01

    PurposeTo report the real-world incidence and risk factors of stent thrombosis in the aortoiliac and femoropopliteal arteries in case of bare nitinol stent (BNS) or covered nitinol stent (CNS) placement from a single-centre retrospective audit.Materials and MethodsMedical records of consecutive patients treated with peripheral stent placement for claudication or critical limb ischemia were audited for definite stent thrombosis defined as imaging confirmed stent thrombosis that presented as acute limb-threatening ischemia. Cases were stratified between aortoiliac and femoropopliteal anatomy. Cox regression analysis was employed to adjust for baseline clinical and procedural confounders and identify predictors of stent thrombosis and major limb loss.Results256 patients (n = 277 limbs) were analysed over a 5-year period (2009–2014) including 117 aortoiliac stents (34 CNS; 12.8 ± 5.0 cm and 83 BNS; 7.8 ± 4.0 cm) and 160 femoropopliteal ones (60 CNS; 21.1 ± 11.0 cm and 100 BNS; 17.5 ± 11.9 cm). Median follow-up was 1 year. Overall stent thrombosis rate was 6.1% (17/277) after a median of 43 days (range 2–192 days) and affected almost exclusively the femoropopliteal segment (12/60 in the CNS cohort vs. 4/100 in the BNS; p = 0.001). Annualized stent thrombosis rates (per 100 person-years) were 12.5% in case of CNS and 1.4% in case of BNS (HR 6.3, 95% CI 2.4–17.9; p = 0.0002). Corresponding major amputations rates were 8.7 and 2.5%, respectively (HR 4.5, 95% CI 2.7–27.9; p = 0.0006). On multivariable analysis, critical leg ischemia and CNS placement were the only predictors of stent thrombosis. Diabetes, critical leg ischemia, femoropopliteal anatomy, long stents and CNS were independent predictors of major amputations.ConclusionsPlacement of long femoropopliteal covered nitinol stents is associated with an increased incidence of acute stent thrombosis and ensuing major amputation. Risks are significantly lower in the aortoiliac vessels

  14. Peripheral Stent Thrombosis Leading to Acute Limb Ischemia and Major Amputation: Incidence and Risk Factors in the Aortoiliac and Femoropopliteal Arteries

    Energy Technology Data Exchange (ETDEWEB)

    Katsanos, Konstantinos, E-mail: katsanos@med.upatras.gr [King’s Health Partners, Department of Interventional Radiology, Imaging Sciences Division, Guy’s and St. Thomas’ Hospitals, NHS Foundation Trust (United Kingdom); Al-Lamki, Said A. M. [The Royal Hospital, Department of Radiology (Oman); Parthipun, Aneeta [King’s Health Partners, Department of Interventional Radiology, Imaging Sciences Division, Guy’s and St. Thomas’ Hospitals, NHS Foundation Trust (United Kingdom); Spiliopoulos, Stavros [ATTIKO Athens University Hospital, 2nd Department of Radiology, Interventional Radiology Unit (Greece); Patel, Sanjay Dhanji [King’s Health Partners, Academic Department of Surgery, Cardiovascular Division, Guy’s and St. Thomas’ Hospitals, NHS Foundation Trust (United Kingdom); Paraskevopoulos, Ioannis [King’s Health Partners, Department of Interventional Radiology, Imaging Sciences Division, Guy’s and St. Thomas’ Hospitals, NHS Foundation Trust (United Kingdom); Zayed, Hany [King’s Health Partners, Academic Department of Surgery, Cardiovascular Division, Guy’s and St. Thomas’ Hospitals, NHS Foundation Trust (United Kingdom); Diamantopoulos, Athanasios [King’s Health Partners, Department of Interventional Radiology, Imaging Sciences Division, Guy’s and St. Thomas’ Hospitals, NHS Foundation Trust (United Kingdom)

    2017-03-15

    PurposeTo report the real-world incidence and risk factors of stent thrombosis in the aortoiliac and femoropopliteal arteries in case of bare nitinol stent (BNS) or covered nitinol stent (CNS) placement from a single-centre retrospective audit.Materials and MethodsMedical records of consecutive patients treated with peripheral stent placement for claudication or critical limb ischemia were audited for definite stent thrombosis defined as imaging confirmed stent thrombosis that presented as acute limb-threatening ischemia. Cases were stratified between aortoiliac and femoropopliteal anatomy. Cox regression analysis was employed to adjust for baseline clinical and procedural confounders and identify predictors of stent thrombosis and major limb loss.Results256 patients (n = 277 limbs) were analysed over a 5-year period (2009–2014) including 117 aortoiliac stents (34 CNS; 12.8 ± 5.0 cm and 83 BNS; 7.8 ± 4.0 cm) and 160 femoropopliteal ones (60 CNS; 21.1 ± 11.0 cm and 100 BNS; 17.5 ± 11.9 cm). Median follow-up was 1 year. Overall stent thrombosis rate was 6.1% (17/277) after a median of 43 days (range 2–192 days) and affected almost exclusively the femoropopliteal segment (12/60 in the CNS cohort vs. 4/100 in the BNS; p = 0.001). Annualized stent thrombosis rates (per 100 person-years) were 12.5% in case of CNS and 1.4% in case of BNS (HR 6.3, 95% CI 2.4–17.9; p = 0.0002). Corresponding major amputations rates were 8.7 and 2.5%, respectively (HR 4.5, 95% CI 2.7–27.9; p = 0.0006). On multivariable analysis, critical leg ischemia and CNS placement were the only predictors of stent thrombosis. Diabetes, critical leg ischemia, femoropopliteal anatomy, long stents and CNS were independent predictors of major amputations.ConclusionsPlacement of long femoropopliteal covered nitinol stents is associated with an increased incidence of acute stent thrombosis and ensuing major amputation. Risks are significantly lower in the aortoiliac vessels

  15. Inhibition of Lysyl Oxidases Impairs Migration and Angiogenic Properties of Tumor-Associated Pericytes

    Directory of Open Access Journals (Sweden)

    Aline Lopes Ribeiro

    2017-01-01

    Full Text Available Pericytes are important cellular components of the tumor microenviroment with established roles in angiogenesis and metastasis. These two cancer hallmarks are modulated by enzymes of the LOX family, but thus far, information about LOX relevance in tumor-associated pericytes is lacking. Here, we performed a comparative characterization of normal and tumoral pericytes and report for the first time the modulatory effects of LOX enzymes on activated pericyte properties. Tumoral pericytes isolated from childhood ependymoma and neuroblastoma specimens displayed angiogenic properties in vitro and expressed typical markers, including CD146, NG2, and PDGFRβ. Expression of all LOX family members could be detected in both normal and tumor-associated pericytes. In most pericyte samples, LOXL3 was the family member displaying the highest transcript levels. Inhibition of LOX/LOXL activity with the inhibitor β-aminopropionitrile (βAPN significantly reduced migration of pericytes, while proliferation rates were kept unaltered. Formation of tube-like structures in vitro by pericytes was also significantly impaired upon inhibition of LOX/LOXL activity with βAPN, which induced more prominent effects in tumor-associated pericytes. These findings reveal a novel involvement of the LOX family of enzymes in migration and angiogenic properties of pericytes, with implications in tumor development and in therapeutic targeting tumor microenvironment constituents.

  16. Framing risk: communication messages in the Australian and Swedish print media surrounding the 2009 H1N1 pandemic.

    Science.gov (United States)

    Sandell, Tiffany; Sebar, Bernadette; Harris, Neil

    2013-12-01

    Australia and Sweden have similar immunisation rates. However, during the 2009 H1N1 pandemic the uptake of immunisation was 60% in Sweden and 18% in Australia. During pandemics, perceptions of risk are largely formed by media communication which may influence the public's response. The study aimed to compare the differences in how the media framed the 2009 H1N1 pandemic message and the associated public perceptions of risk as expressed through the uptake of vaccinations in Australia and Sweden. A qualitative content analysis was conducted on 81 articles from the Australian and Swedish print media: 45 and 36, respectively. The risk of H1N1 was communicated similarly in Australia and Sweden. However, major differences were found in how the Australian and Swedish media framed the pandemic in terms of responsibility, self-efficacy, and uncertainty. In Australia, responsibility was predominantly reported negatively, blaming various organisations for a lack of information, compared to Sweden where responsibility was placed on the community to help protect public health. Furthermore, there was limited self-efficacy measures reported in the Australian media compared to Sweden and Sweden's media was more transparent about the uncertainties of the pandemic. This study affirms the association between the framing of health messages in the media and the public's perception of risk and related behaviour. Governments need to actively incorporate the media into pandemic communication planning.

  17. The Risk Implications of Globalisation: An Exploratory Analysis of 105 Major Industrial Incidents (1971-2010).

    Science.gov (United States)

    Beck, Matthias

    2016-03-10

    This paper revisits work on the socio-political amplification of risk, which predicts that those living in developing countries are exposed to greater risk than residents of developed nations. This prediction contrasts with the neoliberal expectation that market driven improvements in working conditions within industrialising/developing nations will lead to global convergence of hazard exposure levels. It also contradicts the assumption of risk society theorists that there will be an ubiquitous increase in risk exposure across the globe, which will primarily affect technically more advanced countries. Reviewing qualitative evidence on the impact of structural adjustment reforms in industrialising countries, the export of waste and hazardous waste recycling to these countries and new patterns of domestic industrialisation, the paper suggests that workers in industrialising countries continue to face far greater levels of hazard exposure than those of developed countries. This view is confirmed when a data set including 105 major multi-fatality industrial disasters from 1971 to 2000 is examined. The paper concludes that there is empirical support for the predictions of socio-political amplification of risk theory, which finds clear expression in the data in a consistent pattern of significantly greater fatality rates per industrial incident in industrialising/developing countries.

  18. 26 CFR 1.679-0 - Outline of major topics.

    Science.gov (United States)

    2010-04-01

    ... transfers. (1) Principal purpose of tax avoidance. (2) Principal purpose of tax avoidance deemed to exist... Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Grantors and Others Treated As Substantial Owners § 1.679-0 Outline of major topics. This...

  19. Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder: a systematic review and meta-analysis.

    Science.gov (United States)

    Vancampfort, Davy; Stubbs, Brendon; Mitchell, Alex J; De Hert, Marc; Wampers, Martien; Ward, Philip B; Rosenbaum, Simon; Correll, Christoph U

    2015-10-01

    Metabolic syndrome (MetS) and its components are highly predictive of cardiovascular diseases. The primary aim of this systematic review and meta-analysis was to assess the prevalence of MetS and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder, comparing subjects with different disorders and taking into account demographic variables and psychotropic medication use. The secondary aim was to compare the MetS prevalence in persons with any of the selected disorders versus matched general population controls. The pooled MetS prevalence in people with severe mental illness was 32.6% (95% CI: 30.8%-34.4%; N = 198; n = 52,678). Relative risk meta-analyses established that there was no significant difference in MetS prevalence in studies directly comparing schizophrenia versus bipolar disorder, and in those directly comparing bipolar disorder versus major depressive disorder. Only two studies directly compared people with schizophrenia and major depressive disorder, precluding meta-analytic calculations. Older age and a higher body mass index were significant moderators in the final demographic regression model (z = -3.6, p = 0.0003, r(2)  = 0.19). People treated with all individual antipsychotic medications had a significantly (ppeople with severe mental illness had a significantly increased risk for MetS (RR = 1.58; 95% CI: 1.35-1.86; p<0.001) and all its components, except for hypertension (p = 0.07). These data suggest that the risk for MetS is similarly elevated in the diagnostic subgroups of severe mental illness. Routine screening and multidisciplinary management of medical and behavioral conditions is needed in these patients. Risks of individual antipsychotics should be considered when making treatment choices. © 2015 World Psychiatric Association.

  20. The ARIPAR project: analysis of the major accident risks connected with industrial and transportation activities in the Ravenna area

    International Nuclear Information System (INIS)

    Egidi, Demetrio; Foraboschi, Franco P.; Spadoni, Gigliola; Amendola, Aniello

    1995-01-01

    The paper describes the ARIPAR project aimed at the assessment of the major accident risks connected with storage, process and transportation of dangerous substances in the densely populated Ravenna area in Italy, which includes a large complex of chemical and petrochemical plants and minor industries, essentially distributed around an important commercial port. Large quantities of dangerous goods are involved in various transportation forms connected with the industrial and commercial activity of the port. The project started by making a complete inventory of fixed installations and transportation activities capable of provoking major fire, explosion and toxic release events; then relevant accident scenarios were developed for the single hazard sources; probabilities were assigned to the events and consequences were evaluated; finally iso-risk contours and F-N diagrams were evaluated both for the single sources and for the overall area. This required the development of a particular methodology for analysis of area risk and of associated software packages which allowed examination of the relative importance of the different activities and typologies of materials involved. The methodological approach and the results have proved to be very useful for the priority-ranking of risk mitigating interventions and physical planning in a complex area

  1. 50 CFR Table 1 to Part 226 - Major Stellar Sea Lion Rookery Sites

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Major Stellar Sea Lion Rookery Sites 1... Table 1 to Part 226—Major Stellar Sea Lion Rookery Sites Major Steller sea lion rookery sites are... 168 02.0W Ogchul I.1 53 00.0N 168 24.0W Sea Lion Rocks. (Amak) 1 55 28.0N 163 12.0W Ugamak I.1 54 14...

  2. Risk-adjusted econometric model to estimate postoperative costs: an additional instrument for monitoring performance after major lung resection.

    Science.gov (United States)

    Brunelli, Alessandro; Salati, Michele; Refai, Majed; Xiumé, Francesco; Rocco, Gaetano; Sabbatini, Armando

    2007-09-01

    The objectives of this study were to develop a risk-adjusted model to estimate individual postoperative costs after major lung resection and to use it for internal economic audit. Variable and fixed hospital costs were collected for 679 consecutive patients who underwent major lung resection from January 2000 through October 2006 at our unit. Several preoperative variables were used to develop a risk-adjusted econometric model from all patients operated on during the period 2000 through 2003 by a stepwise multiple regression analysis (validated by bootstrap). The model was then used to estimate the postoperative costs in the patients operated on during the 3 subsequent periods (years 2004, 2005, and 2006). Observed and predicted costs were then compared within each period by the Wilcoxon signed rank test. Multiple regression and bootstrap analysis yielded the following model predicting postoperative cost: 11,078 + 1340.3X (age > 70 years) + 1927.8X cardiac comorbidity - 95X ppoFEV1%. No differences between predicted and observed costs were noted in the first 2 periods analyzed (year 2004, $6188.40 vs $6241.40, P = .3; year 2005, $6308.60 vs $6483.60, P = .4), whereas in the most recent period (2006) observed costs were significantly lower than the predicted ones ($3457.30 vs $6162.70, P model may be used as a methodologic template for economic audit in our specialty and complement more traditional outcome measures in the assessment of performance.

  3. Microbial conversion of major ginsenoside Rb1 to minor ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-12-15

    Dec 15, 2009 ... minor ginsenoside Rd by Indian fermented food bacteria. Kalaiselvi ... South Korea. Accepted 17 April, 2009. Ginsenoside Rb1 is the predominant secondary metabolite (saponin) in Panax ginseng. Hydrolysis of the sugar .... culture and 200 µl of major ginsenoside Rb1. The reaction mixture was incubated ...

  4. Homer1a protein expression in schizophrenia, bipolar disorder, and major depression.

    Science.gov (United States)

    Leber, Stefan L; Llenos, Ida C; Miller, Christine L; Dulay, Jeannette R; Haybaeck, Johannes; Weis, Serge

    2017-10-01

    In recent years, there was growing interest in postsynaptic density proteins in the central nervous system. Of the most important candidates of this specialized region are proteins belonging to the Homer protein family. This family of scaffolding proteins is suspected to participate in the pathogenesis of a variety of diseases. The present study aims to compare Homer1a expression in the hippocampus and cingulate gyrus of patients with major psychiatric disorders including schizophrenia, bipolar disorder and major depression. Immunohistochemistry was used to analyze changes of Homer1a protein expression in the hippocampal formation and the cingulate gyrus from the respective disease groups. Glial cells of the cingulate gyrus gray matter showed decreased Homer1a levels in bipolar disorder when compared to controls. The same results were seen when comparing cingulate gyrus gray matter glial cells in bipolar disorder with major depression. Stratum oriens glial cells of the hippocampus showed decreased Homer1a levels in bipolar disorder when compared to controls and major depression. Stratum lacunosum glial cells showed decreased Homer1a levels in bipolar disorder when compared to major depression. In stratum oriens interneurons Homer1a levels were increased in all disease groups when compared to controls. Stratum lucidum axons showed decreased Homer1a levels in bipolar disorder when compared to controls. Our data demonstrate altered Homer1a levels in specific brain regions and cell types of patients suffering from schizophrenia, bipolar disorder and major depression. These findings support the role of Homer proteins as interesting candidates in neuropsychiatric pathophysiology and treatment.

  5. Intravenous glucagon-like peptide 1 normalizes blood glucose after major surgery in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Meier, Juris J; Weyhe, Dirk; Michaely, Mark

    2004-01-01

    of GLP-1 (1.2 pmol x kg x min) and placebo over 8 hrs, each administered in randomized order in the fasting state. C-reactive protein concentrations of 4.9+/-4.2 mg/dL indicated a systemic inflammation. Blood was drawn in 30-min intervals for glucose (glucose oxidase), insulin, C-peptide, glucagon...... practicability and the risk of hypoglycemia. Therefore, the glucose-lowering effect of the incretin hormone glucagon-like peptide 1 (GLP-1) was investigated in patients with type 2 diabetes after major surgery. DESIGN: Randomised clinical study. SETTING: A surgical unit of a university hospital. PATIENTS......, and GLP-1 (specific immunoassays). Statistics were done with repeated-measures analysis of variance and Duncan's post hoc tests. MAIN RESULTS: During the intravenous infusion of GLP-1, plasma glucose concentrations were significantly lowered, reaching the normoglycemic fasting glucose range within 150...

  6. The BRCA1 c. 5096G>A p.Arg1699Gln (R1699Q) intermediate risk variant

    DEFF Research Database (Denmark)

    Moghadasi, Setareh; Meeks, Huong D.; Vreeswijk, Maaike Pg

    2018-01-01

    studied families, to further define cancer risks and to propose adjusted clinical management of female BRCA1*R1699Q carriers. METHODS: Data were collected from 129 BRCA1*R1699Q families ascertained internationally by ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles......BACKGROUND: We previously showed that the BRCA1 variant c.5096G>A p.Arg1699Gln (R1699Q) was associated with an intermediate risk of breast cancer (BC) and ovarian cancer (OC). This study aimed to assess these cancer risks for R1699Q carriers in a larger cohort, including follow-up of previously......) consortium members. A modified segregation analysis was used to calculate BC and OC risks. Relative risks were calculated under both monogenic model and major gene plus polygenic model assumptions. RESULTS: In this cohort the cumulative risk of BC and OC by age 70 years was 20% and 6%, respectively...

  7. Novel variants in the PRDX6 Gene and the risk of Acute Lung Injury following major trauma

    Directory of Open Access Journals (Sweden)

    Localio A Russell

    2011-05-01

    Full Text Available Abstract Background Peroxiredoxin 6 (PRDX6 is involved in redox regulation of the cell and is thought to be protective against oxidant injury. Little is known about genetic variation within the PRDX6 gene and its association with acute lung injury (ALI. In this study we sequenced the PRDX6 gene to uncover common variants, and tested association with ALI following major trauma. Methods To examine the extent of variation in the PRDX6 gene, we performed direct sequencing of the 5' UTR, exons, introns and the 3' UTR in 25 African American cases and controls and 23 European American cases and controls (selected from a cohort study of major trauma, which uncovered 80 SNPs. In silico modeling was performed using Patrocles and Transcriptional Element Search System (TESS. Thirty seven novel and tagging SNPs were tested for association with ALI compared with ICU at-risk controls who did not develop ALI in a cohort study of 259 African American and 254 European American subjects that had been admitted to the ICU with major trauma. Results Resequencing of critically ill subjects demonstrated 43 novel SNPs not previously reported. Coding regions demonstrated no detectable variation, indicating conservation of the protein. Block haplotype analyses reveal that recombination rates within the gene seem low in both Caucasians and African Americans. Several novel SNPs appeared to have the potential for functional consequence using in silico modeling. Chi2 analysis of ALI incidence and genotype showed no significant association between the SNPs in this study and ALI. Haplotype analysis did not reveal any association beyond single SNP analyses. Conclusions This study revealed novel SNPs within the PRDX6 gene and its 5' and 3' flanking regions via direct sequencing. There was no association found between these SNPs and ALI, possibly due to a low sample size, which was limited to detection of relative risks of 1.93 and above. Future studies may focus on the role of

  8. Methylomic profiling of cortex samples from completed suicide cases implicates a role for PSORS1C3 in major depression and suicide.

    Science.gov (United States)

    Murphy, T M; Crawford, B; Dempster, E L; Hannon, E; Burrage, J; Turecki, G; Kaminsky, Z; Mill, J

    2017-01-03

    Major depressive disorder (MDD) represents a major social and economic health issue and constitutes a major risk factor for suicide. The molecular pathology of suicidal depression remains poorly understood, although it has been hypothesised that regulatory genomic processes are involved in the pathology of both MDD and suicidality. In this study, genome-wide patterns of DNA methylation were assessed in depressed suicide completers (n=20) and compared with non-psychiatric, sudden-death controls (n=20) using tissue from two cortical brain regions (Brodmann Area 11 (BA11) and Brodmann Area 25 (BA25)). Analyses focused on identifying differentially methylated regions (DMRs) associated with suicidal depression and epigenetic variation were explored in the context of polygenic risk scores for major depression and suicide. Weighted gene co-methylation network analysis was used to identify modules of co-methylated loci associated with depressed suicide completers and polygenic burden for MDD and suicide attempt. We identified a DMR upstream of the PSORS1C3 gene, subsequently validated using bisulfite pyrosequencing and replicated in a second set of suicide samples, which is characterised by significant hypomethylation in both cortical brain regions in MDD suicide cases. We also identified discrete modules of co-methylated loci associated with polygenic risk burden for suicide attempt, but not major depression. Suicide-associated co-methylation modules were enriched among gene networks implicating biological processes relevant to depression and suicidality, including nervous system development and mitochondria function. Our data suggest that there are coordinated changes in DNA methylation associated with suicide that may offer novel insights into the molecular pathology associated with depressed suicide completers.

  9. Methylomic profiling of cortex samples from completed suicide cases implicates a role for PSORS1C3 in major depression and suicide

    Science.gov (United States)

    Murphy, T M; Crawford, B; Dempster, E L; Hannon, E; Burrage, J; Turecki, G; Kaminsky, Z; Mill, J

    2017-01-01

    Major depressive disorder (MDD) represents a major social and economic health issue and constitutes a major risk factor for suicide. The molecular pathology of suicidal depression remains poorly understood, although it has been hypothesised that regulatory genomic processes are involved in the pathology of both MDD and suicidality. In this study, genome-wide patterns of DNA methylation were assessed in depressed suicide completers (n=20) and compared with non-psychiatric, sudden-death controls (n=20) using tissue from two cortical brain regions (Brodmann Area 11 (BA11) and Brodmann Area 25 (BA25)). Analyses focused on identifying differentially methylated regions (DMRs) associated with suicidal depression and epigenetic variation were explored in the context of polygenic risk scores for major depression and suicide. Weighted gene co-methylation network analysis was used to identify modules of co-methylated loci associated with depressed suicide completers and polygenic burden for MDD and suicide attempt. We identified a DMR upstream of the PSORS1C3 gene, subsequently validated using bisulfite pyrosequencing and replicated in a second set of suicide samples, which is characterised by significant hypomethylation in both cortical brain regions in MDD suicide cases. We also identified discrete modules of co-methylated loci associated with polygenic risk burden for suicide attempt, but not major depression. Suicide-associated co-methylation modules were enriched among gene networks implicating biological processes relevant to depression and suicidality, including nervous system development and mitochondria function. Our data suggest that there are coordinated changes in DNA methylation associated with suicide that may offer novel insights into the molecular pathology associated with depressed suicide completers. PMID:28045465

  10. The association between suicide risk and self-esteem in Japanese university students with major depressive episodes of major depressive disorder

    OpenAIRE

    Mitsui, Nobuyuki; Asakura,Satoshi; Shimizu,Yusuke; Fujii,Yutaka; Toyomaki,Atsuhito; Kako,Yuki; Tanaka,Teruaki; Kitagawa,Nobuki; Inoue,Takeshi; Kusumi,Ichiro

    2014-01-01

    Nobuyuki Mitsui,1 Satoshi Asakura,1,2 Yusuke Shimizu,1 Yutaka Fujii,1 Atsuhito Toyomaki,1 Yuki Kako,1 Teruaki Tanaka,1 Nobuki Kitagawa,3 Takeshi Inoue,1 Ichiro Kusumi1 1Department of Psychiatry, Hokkaido University Graduate School of Medicine, 2Health care center of Hokkaido University, Kita-ku, Sapporo, 3Department of Clinical Social Work, Health Sciences University of Hokkaido School of Nursing and Social Services, Tobetsu, Ishikari, Japan Background: The suicide risk among young adults is...

  11. Why do I need it? I am not at risk! Public perceptions towards the pandemic (H1N1 2009 vaccine

    Directory of Open Access Journals (Sweden)

    Ward Kirsten F

    2010-04-01

    Full Text Available Abstract Background On the 30th September 2009, the pandemic (H1N1 2009 influenza vaccine was made available to adults and children aged 10 years and over, in Australia. Acceptance of a novel vaccine is influenced by perceptions of risk including risk of infection, risk of death or severe illness and risk of serious vaccine side-effects. We surveyed a sample of residents from Sydney, Australia to ascertain their risk perception, attitudes towards the pandemic and willingness to accept the pandemic (H1N1 2009 influenza vaccine. Methods We sampled residents using a cross-sectional intercept design during the WHO Phase 6. Members of the public were approached in shopping and pedestrian malls to undertake the survey during September and October 2009. The survey measured perceived risk, seriousness of disease, recent behavioural changes, likely acceptance of the pandemic (H1N1 2009 vaccine and issues relating to uptake and perceived safety. Results Of the 627 respondents, the majority felt that they had a "very low to low" (332/627, 52.9% risk of acquiring H1N1. 24.5% (154/627 of respondents believed that the disease would "very seriously or extremely" affect their health. Nearly half (305/627, 48.6% reported that in response to the "swine flu" outbreak they had undertaken one or more of the investigated behavioural changes. Overall, the self-reported likelihood of accepting vaccination against novel H1N1 was 54.7% (343/627. Conclusions While, most participants did not believe they were at high risk of acquiring pandemic H1N1 2009, over half of the sample indicated that they would accept the vaccine. Participants who were vaccinated against the seasonal influenza were more likely to receive the H1N1 vaccine. Concerns about safety, the possibility of side effects and the vaccine development process need to be addressed.

  12. Effect of helicobacter pylori L-form infection on proliferation, apoptosis and invasion molecule expression in gastric cancer tissue

    Directory of Open Access Journals (Sweden)

    Hua Xin

    2017-05-01

    Full Text Available Objective: To study the effect of Helicobacter pylori L-form infection on proliferation, apoptosis and invasion molecule expression in gastric cancer tissue. Methods: The gastric cancer tissues surgically removed in our hospital between May 2013 and October 2016 were collected and divided into Hp negative, Hp-L negative and Hp-L positive according to the condition of helicobacter pylori infection. The proliferation, apoptosis and invasion gene expression were detected. Results: LOXL2, PCNA, CyclinD1, Rab1A, Bcl-2, Snail, N-cadherin, UHRF1 and AnnexinII mRNA expression in Hp-L-positive gastric cancer tissues were significantly higher than those in Hp-L-negative and Hp-negative gastric cancer tissues while ING5, PTPN13, Beclin1 and Mst1 mRNA expression were significantly lower than those in Hp-L-negative and Hp-negative gastric cancer tissues; LOXL2, PCNA, CyclinD1, Rab1A, Bcl-2, ING5, PTPN13, Beclin1, Mst1, Snail, N-cadherin, UHRF1 and AnnexinII mRNA expression in Hp-L-negative gastric cancer tissues were not different from those in Hpnegative gastric cancer tissues. Conclusion: Helicobacter pylori L-form infection can influence the proliferation, apoptosis and invasion gene expression to promote cell proliferation and invasion, and inhibit cell apoptosis.

  13. Epidemiology, major risk factors and genetic predisposition for breast cancer in the Pakistani population.

    Science.gov (United States)

    Shaukat, Uzma; Ismail, Muhammad; Mehmood, Nasir

    2013-01-01

    Occurrence of breast cancer is related to genetic as well as cultural, environmental and life-style factors. Variations in diversity of these factors among different ethnic groups and geographical areas emphasize the immense need for studies in all racial-ethnic populations. The incidence of breast cancer in Pakistan is highest in Asians after Jews in Israel and 2.5 times higher than that in neighboring countries like Iran and India, accounting for 34.6% of female cancers. The Pakistani population is deficient in information regarding breast cancer etiology and epidemiology, but efforts done so far had suggested consanguinity as a major risk factor for frequent mutations leading to breast cancer and has also shed light on genetic origins in different ethnic groups within Pakistan. World-wide research efforts on different ethnicities have enhanced our understanding of genetic predisposition to breast cancer but despite these discoveries, 75% of the familial risk of breast cancer remains unexplained, highlighting the fact that the majority of breast cancer susceptibility genes remain unidentified. For this purpose Pakistani population provides a strong genetic pool to elucidate the genetic etiology of breast cancer because of cousin marriages. In this review, we describe the known breast cancer predisposition factors found in the local Pakistani population and the epidemiological research work done to emphasize the importance of exploring factors/variants contributing to breast cance, in order to prevent, cure and decrease its incidence in our country.

  14. Comparative risk of major bleeding with new oral anticoagulants (NOACs) and phenprocoumon in patients with atrial fibrillation: a post-marketing surveillance study.

    Science.gov (United States)

    Hohnloser, Stefan H; Basic, Edin; Nabauer, Michael

    2017-08-01

    Non-vitamin K antagonist oral anticoagulants (NOACs) are at least as effective and safe as vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF). All pivotal trials have compared NOACs to warfarin. However, other VKAs are commonly used, for instance phenprocoumon. A retrospective cohort study using a German claims database assessed the comparative risks of bleeding leading to hospitalization during therapy with NOACs and phenprocoumon in AF patients. Endpoints consisted of major bleeding, gastrointestinal bleeding, and any bleeding. Data were collected from January 1, 2013 to March 31, 2015. Patients newly initiated on dabigatran, apixaban, rivaroxaban, or phenprocoumon were included. Hazard Ratios for bleeding events were derived from Cox proportional hazard models, adjusting for differences in baseline characteristics. Propensity score matching was performed as a sensitivity analysis. A total of 35,013 patients were identified, including 3138 on dabigatran, 3633 on apixaban, 12,063 on rivaroxaban, and 16,179 on phenprocoumon. Patients prescribed apixaban or phenprocoumon were older compared to those on dabigatran or rivaroxaban and had a higher CHA 2 DS 2 -VASc score. After adjusting for baseline confounders, apixaban was associated with lower risks of major bleeding (HR 0.68, 95% CI 0.51-0.90, p = 0.008), gastrointestinal bleeding (HR 0.53, 95% CI 0.39-0.72, p similar to that of phenprocoumon but bleeding risk with rivaroxaban was higher.

  15. Dithiocarbamates are teratogenic to developing zebrafish through inhibition of lysyl oxidase activity

    International Nuclear Information System (INIS)

    Boxtel, Antonius L. van; Kamstra, Jorke H.; Fluitsma, Donna M.; Legler, Juliette

    2010-01-01

    Dithiocarbamates (DTCs) are a class of compounds that are extensively used in agriculture as pesticides. As such, humans and wildlife are undoubtedly exposed to these chemicals. Although DTCs are thought to be relatively safe due to their short half lives, it is well established that they are teratogenic to vertebrates, especially to fish. In zebrafish, these teratogenic effects are characterized by distorted notochord development and shortened anterior to posterior axis. DTCs are known copper (Cu) chelators but this does not fully explain the observed teratogenic effects. We show here that DTCs cause malformations in zebrafish that highly resemble teratogenic effects observed by direct inhibition of a group of cuproenzymes termed lysyl oxidases (LOX). Additionally, we demonstrate that partial knockdown of three LOX genes, lox, loxl1 and loxl5b, sensitizes the developing embryo to DTC exposure. Finally, we show that DTCs directly inhibit zebrafish LOX activity in an ex vivo amine oxidase assay. Taken together, these results provide the first evidence that DTC induced teratogenic effects are, at least in part, caused by direct inhibition of LOX activity.

  16. The HLA-B*39 allele increases type 1 diabetes risk conferred by HLA-DRB1*04:04-DQB1*03:02 and HLA-DRB1*08-DQB1*04 class II haplotypes.

    Science.gov (United States)

    Mikk, M-L; Kiviniemi, M; Laine, A-P; Härkönen, T; Veijola, R; Simell, O; Knip, M; Ilonen, J

    2014-01-01

    To further characterise the effect of the HLA-B*39 allele on type 1 diabetes risk we assessed its role in different HLA-DR/DQ haplotypes and genotypes using 1764 nuclear families with a diabetic child collected in the framework of the Finnish Paediatric Diabetes Register. HLA assays were based on sequence specific hybridization using lanthanide labelled oligonucleotide probes. Transmissions of major HLA-DR/DQ haplotypes with and without the HLA-B*39 allele to diabetic index cases were analysed by direct haplotype and allele counting. The HLA-B*39 allele significantly increased the disease risk conferred by DRB1*04:04-DQA1*03-DQB1*03:02 and (DR8)-DQB1*04 haplotypes. The same effect was observed on genotype level as disease association for the HLA-B*39 allele was observed in multiple genotypes containing DRB1*04:04-DQA1*03-DQB1*03:02 or (DR8)-DQB1*04 haplotypes. Finally we considered the two common subtypes of the HLA-B*39 allele, B*39:01 and B*39:06 and observed their unequal distribution when stratified for specific DR-DQ haplotypes. The risk for type 1 diabetes conferred by certain DR/DQ haplotypes is modified by the presence of the HLA-B*39 and this confirms the independent disease predisposing effect of the HLA-B*39 allele. The results can be applied in enhancing the sensitivity and specificity of DR/DQ based screening programs for subjects at disease risk. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  17. Application of risk assessment techniques to 'major hazard' pipelines

    Energy Technology Data Exchange (ETDEWEB)

    Cox, R A

    1982-12-01

    A risk analysis for a hazardous-material pipeline (carrying LPG, ammonia, or high-pressure gas) is presented. The analysis gives results in a form that will assist the decisionmaker in pipeline planning and route selection. The large inventory of hazardous materials in such pipelines means that risks exist even though the accident record of pipeline transportation compares favorably with that for competing modes of transport. Risk analysis techniques - commonly used in the civil aviation, nuclear, and process industries - can be equally well applied to pipelines and can produce results that not only give a measure of the risk but also indicate the principal sources of risk and possible areas for improvement. A number of pipeline risk analyses have demonstrated the viability of the technique and its usefulness as an aid to practical engineering in design, planning, and maintenance/repair phases.

  18. A meta-analysis of PTGS1 and PTGS2 polymorphisms and NSAID intake on the risk of developing cancer.

    Directory of Open Access Journals (Sweden)

    Mai Nagao

    Full Text Available BACKGROUND: Several studies have investigated whether the polymorphisms in the prostaglandin endoperoxide synthase 1 (PTGS1 and PTGS2 genes and nonsteroidal anti-inflammatory drug (NSAID use are associated with cancer risk; however, those studies have produced mixed results. Therefore, we performed a meta-analysis to evaluate the association between the PTGS1 and PTGS2 polymorphisms and the effect of NSAID use on the risk of developing cancer. METHODS: We conducted a comprehensive search in PubMed through March 2012. The odds ratios (ORs with the corresponding 95% confidence intervals (CIs were calculated using the fixed-effect model or the random-effect model. RESULTS: The database search generated 13 studies that met the inclusion criteria. For PTGS1 rs3842787, NSAID users homozygous for the major allele (CC had a significantly decreased cancer risk compared with non-NSAID users (OR = 0.73, 95% CI = 0.59-0.89. For PTGS2 rs5275 and rs20417, there were no significant differences between the gene polymorphism and NSAID use on cancer risk among the 8 and 7 studies, respectively. However, in the stratified analysis by the type of cancer or ethnicity population, NSAID users homozygous for the major allele (TT in rs5275 demonstrated significantly decreased cancer risk compared with non-NSAID users in cancer type not involving colorectal adenoma (OR = 0.70, 95% CI = 0.59-0.83 and among the USA population (OR = 0.67, 95% CI = 0.56-0.82. NSAID users homozygous for the major allele (GG in rs20417 displayed a significantly decreased cancer risk than non-NSAID users among the US population (OR = 0.72, 95% CI = 0.58-0.88. For the PTGS2 rs689466 and rs2745557 SNPs, there were no significant differences. CONCLUSION: This meta-analysis suggests that the associations between PTGS polymorphisms and NSAID use on cancer risk may differ with regard to the type of cancer and nationality.

  19. Myocardial injury after surgery is a risk factor for weaning failure from mechanical ventilation in critical patients undergoing major abdominal surgery.

    Directory of Open Access Journals (Sweden)

    Shu Li

    Full Text Available Myocardial injury after noncardiac surgery (MINS is a newly proposed concept that is common among adults undergoing noncardiac surgery and associated with substantial mortality. We analyzed whether MINS was a risk factor for weaning failure in critical patients who underwent major abdominal surgery.This retrospective study was conducted in the Department of Critical Care Medicine of Peking University People's Hospital. The subjects were all critically ill patients who underwent major abdominal surgery between January 2011 and December 2013. Clinical and laboratory parameters during the perioperative period were investigated. Backward stepwise regression analysis was performed to evaluate MINS relative to the rate of weaning failure. Age, hypertension, chronic renal disease, left ventricular ejection fraction before surgery, Acute Physiologic and Chronic Health Evaluation II score, pleural effusion, pneumonia, acute kidney injury, duration of mechanical ventilation before weaning and the level of albumin after surgery were treated as independent variables.This study included 381 patients, of whom 274 were successfully weaned. MINS was observed in 42.0% of the patients. The MINS incidence was significantly higher in patients who failed to be weaned compared to patients who were successfully weaned (56.1% versus 36.5%; P<0.001. Independent predictive factors of weaning failure were MINS, age, lower left ventricular ejection fraction before surgery and lower serum albumin level after surgery. The MINS odds ratio was 4.098 (95% confidence interval, 1.07 to 15.6; P = 0.04. The patients who were successfully weaned had shorter hospital stay lengths and a higher survival rate than those who failed to be weaned.MINS is a risk factor for weaning failure from mechanical ventilation in critical patients who have undergone major abdominal surgery, independent of age, lower left ventricular ejection fraction before surgery and lower serum albumin levels after

  20. Symptoms of Major Depressive Disorder Subsequent to Child Maltreatment: Examining Change across Multiple Levels of Analysis to Identify Transdiagnostic Risk Pathways

    Science.gov (United States)

    Shenk, Chad E.; Griffin, Amanda M.; O’Donnell, Kieran J.

    2016-01-01

    Major depressive disorder (MDD) is a prevalent psychiatric condition in the child maltreatment population. However, not all children who have been maltreated will develop MDD or MDD symptoms, suggesting the presence of unique risk pathways that explain how certain children develop MDD symptoms when others do not. The current study tested several candidate risk pathways to MDD symptoms following child maltreatment: 1) neuroendocrine, 2) autonomic, 3) affective, and 4) emotion regulation. Female adolescents (N=110; Age range: 14–19) were recruited into a substantiated child maltreatment or comparison condition and completed a laboratory stressor, saliva samples, and measures of emotion regulation, negative affect, and MDD symptoms. MDD symptoms were reassessed eighteen months later. Mediational modeling revealed that emotion regulation was the only significant indirect effect of the relationship between child maltreatment and subsequent MDD symptoms, demonstrating that children exposed to maltreatment had greater difficulties managing affective states that in turn led to more severe MDD symptoms. These results highlight the importance of emotion dysregulation as a central risk pathway to MDD following child maltreatment. Areas of future research and implications for optimizing prevention and clinical intervention through the direct targeting of transdiagnostic risk pathways are discussed. PMID:26535940

  1. Risk of bleeding with dabigatran in atrial fibrillation.

    Science.gov (United States)

    Hernandez, Inmaculada; Baik, Seo Hyon; Piñera, Antonio; Zhang, Yuting

    2015-01-01

    It remains unclear whether dabigatran etexilate mesylate is associated with higher risk of bleeding than warfarin sodium in real-world clinical practice. To compare the risk of bleeding associated with dabigatran and warfarin using Medicare data. In this retrospective cohort study, we used pharmacy and medical claims in 2010 to 2011 from a 5% random sample of Medicare beneficiaries. We identified participants as those newly diagnosed as having atrial fibrillation from October 1, 2010, through October 31, 2011, and who initiated dabigatran or warfarin treatment within 60 days of initial diagnosis. We followed up patients until discontinued use or switch of anticoagulants, death, or December 31, 2011. Dabigatran users (n = 1302) and warfarin users (n = 8102). We identified any bleeding events and categorized them as major and minor bleeding by anatomical site. Major bleeding events included intracranial hemorrhage, hemoperitoneum, and inpatient or emergency department stays for hematuria, gastrointestinal, or other hemorrhage. We used a propensity score weighting mechanism to balance patient characteristics between 2 groups and Cox proportional hazards regression models to evaluate the risk of bleeding. We further examined the risk of bleeding for 4 subgroups of high-risk patients: those 75 years or older, African Americans, those with chronic kidney disease, and those with more than 7 concomitant comorbidities. Dabigatran was associated with a higher risk of bleeding relative to warfarin, with hazard ratios of 1.30 (95% CI, 1.20-1.41) for any bleeding event, 1.58 (95% CI, 1.36-1.83) for major bleeding, and 1.85 (95% CI, 1.64-2.07) for gastrointestinal bleeding. The risk of intracranial hemorrhage was higher among warfarin users, with a hazard ratio of 0.32 (95% CI, 0.20-0.50) for dabigatran compared with warfarin. Dabigatran was consistently associated with an increased risk of major bleeding and gastrointestinal hemorrhage for all subgroups analyzed. The risk of

  2. Expression of Leishmania major LmSTI1 in Yeast Pichia Pastoris

    Directory of Open Access Journals (Sweden)

    Mehdi Shokri

    2017-01-01

    Full Text Available Background: Leishmania major LmSTI1 is a conserved protein among different species of leishmania, and expressed in both amastigote and promastigote forms of L. major life cycle. It has previously been expressed in bacterial systems.Materials and Methods: To express LmSTI1 in the methylotrophic yeast         Pichia pastoris (P. pastoris, the shuttle vector pPICZA containing gene lmsti1 was constructed under the control of the AOX1 promoter. The recombinant vector was electro-transformed into P. pastoris, and induced by 0.5% methanol in the buffered medium. The expression of the LmSTI1 protein was visualized in the total soluble protein of P. pastoris by 12% SDS-PAGE, and further confirmed by Western blotting with L.major-infected mouse sera and HRP-conjugated goat anti-mouse IgG as the first and secondary antibodies, respectively.Results: The expression level was 0.2% of total soluble proteins.Conclusion: It might be possible to use this formulation as a whole yeast candidate vaccine against cutaneous leishmanization.

  3. Managing the risk of extreme climate events in Australian major wheat production systems

    Science.gov (United States)

    Luo, Qunying; Trethowan, Richard; Tan, Daniel K. Y.

    2018-06-01

    Extreme climate events (ECEs) such as drought, frost risk and heat stress cause significant economic losses in Australia. The risk posed by ECEs in the wheat production systems of Australia could be better managed through the identification of safe flowering (SFW) and optimal time of sowing (TOS) windows. To address this issue, three locations (Narrabri, Roseworthy and Merredin), three cultivars (Suntop and Gregory for Narrabri, Mace for both Roseworthy and Merredin) and 20 TOS at 1-week intervals between 1 April and 12 August for the period from 1957 to 2007 were evaluated using the Agricultural Production System sIMulator (APSIM)-Wheat model. Simulation results show that (1) the average frequency of frost events decreased with TOS from 8 to 0 days (d) across the four cases (the combination of locations and cultivars), (2) the average frequency of heat stress events increased with TOS across all cases from 0 to 10 d, (3) soil moisture stress (SMS) increased with earlier TOS before reaching a plateau and then slightly decreasing for Suntop and Gregory at Narrabri and Mace at Roseworthy while SMS increased with TOS for Mace at Merredin from 0.1 to 0.8, (4) Mace at Merredin had the earliest and widest SFW (216-260) while Mace at Roseworthy had latest SFW (257-280), (5) frost risk and heat stress determine SFW at wetter sites (i.e. Narrabri and Roseworthy) while frost risk and SMS determine SFW at drier site (i.e. Merredin) and (6) the optimal TOS (window) to maximise wheat yield are 6-20 May, 13-27 May and 15 April at Narrabri, Roseworthy and Merredin, respectively. These findings provide important and specific information for wheat growers about the management of ECE risk on farm. Furthermore, the coupling of the APSIM crop models with state-of-the-art seasonal and intra-seasonal climate forecast information provides an important tool for improved management of the risk of ECEs in economically important cropping industries in the foreseeable future.

  4. The Risk Implications of Globalisation: An Exploratory Analysis of 105 Major Industrial Incidents (1971–2010)

    Science.gov (United States)

    Beck, Matthias

    2016-01-01

    This paper revisits work on the socio-political amplification of risk, which predicts that those living in developing countries are exposed to greater risk than residents of developed nations. This prediction contrasts with the neoliberal expectation that market driven improvements in working conditions within industrialising/developing nations will lead to global convergence of hazard exposure levels. It also contradicts the assumption of risk society theorists that there will be an ubiquitous increase in risk exposure across the globe, which will primarily affect technically more advanced countries. Reviewing qualitative evidence on the impact of structural adjustment reforms in industrialising countries, the export of waste and hazardous waste recycling to these countries and new patterns of domestic industrialisation, the paper suggests that workers in industrialising countries continue to face far greater levels of hazard exposure than those of developed countries. This view is confirmed when a data set including 105 major multi-fatality industrial disasters from 1971 to 2000 is examined. The paper concludes that there is empirical support for the predictions of socio-political amplification of risk theory, which finds clear expression in the data in a consistent pattern of significantly greater fatality rates per industrial incident in industrialising/developing countries. PMID:26978378

  5. Assessment of risk of dengue and yellow fever virus transmission in three major Kenyan cities based on Stegomyia indices

    Science.gov (United States)

    Tchouassi, David P.; Bastos, Armanda D. S.; Sang, Rosemary

    2017-01-01

    Dengue (DEN) and yellow fever (YF) are re-emerging in East Africa, with contributing drivers to this trend being unplanned urbanization and increasingly adaptable anthropophilic Aedes (Stegomyia) vectors. Entomological risk assessment of these diseases remains scarce for much of East Africa and Kenya even in the dengue fever-prone urban coastal areas. Focusing on major cities of Kenya, we compared DEN and YF risk in Kilifi County (DEN-outbreak-prone), and Kisumu and Nairobi Counties (no documented DEN outbreaks). We surveyed water-holding containers for mosquito immature (larvae/pupae) indoors and outdoors from selected houses during the long rains, short rains and dry seasons (100 houses/season) in each County from October 2014-June 2016. House index (HI), Breteau index (BI) and Container index (CI) estimates based on Aedes (Stegomyia) immature infestations were compared by city and season. Aedes aegypti and Aedes bromeliae were the main Stegomyia species with significantly more positive houses outdoors (212) than indoors (88) (n = 900) (χ2 = 60.52, P < 0.0001). Overall, Ae. aegypti estimates of HI (17.3 vs 11.3) and BI (81.6 vs 87.7) were higher in Kilifi and Kisumu, respectively, than in Nairobi (HI, 0.3; BI,13). However, CI was highest in Kisumu (33.1), followed by Kilifi (15.1) then Nairobi (5.1). Aedes bromeliae indices were highest in Kilifi, followed by Kisumu, then Nairobi with HI (4.3, 0.3, 0); BI (21.3, 7, 0.7) and CI (3.3, 3.3, 0.3), at the respective sites. HI and BI for both species were highest in the long rains, compared to the short rains and dry seasons. We found strong positive correlations between the BI and CI, and BI and HI for Ae. aegypti, with the most productive container types being jerricans, drums, used/discarded containers and tyres. On the basis of established vector index thresholds, our findings suggest low-to-medium risk levels for urban YF and high DEN risk for Kilifi and Kisumu, whereas for Nairobi YF risk was low while DEN risk

  6. Assessment of risk of dengue and yellow fever virus transmission in three major Kenyan cities based on Stegomyia indices.

    Directory of Open Access Journals (Sweden)

    Sheila B Agha

    2017-08-01

    Full Text Available Dengue (DEN and yellow fever (YF are re-emerging in East Africa, with contributing drivers to this trend being unplanned urbanization and increasingly adaptable anthropophilic Aedes (Stegomyia vectors. Entomological risk assessment of these diseases remains scarce for much of East Africa and Kenya even in the dengue fever-prone urban coastal areas. Focusing on major cities of Kenya, we compared DEN and YF risk in Kilifi County (DEN-outbreak-prone, and Kisumu and Nairobi Counties (no documented DEN outbreaks. We surveyed water-holding containers for mosquito immature (larvae/pupae indoors and outdoors from selected houses during the long rains, short rains and dry seasons (100 houses/season in each County from October 2014-June 2016. House index (HI, Breteau index (BI and Container index (CI estimates based on Aedes (Stegomyia immature infestations were compared by city and season. Aedes aegypti and Aedes bromeliae were the main Stegomyia species with significantly more positive houses outdoors (212 than indoors (88 (n = 900 (χ2 = 60.52, P < 0.0001. Overall, Ae. aegypti estimates of HI (17.3 vs 11.3 and BI (81.6 vs 87.7 were higher in Kilifi and Kisumu, respectively, than in Nairobi (HI, 0.3; BI,13. However, CI was highest in Kisumu (33.1, followed by Kilifi (15.1 then Nairobi (5.1. Aedes bromeliae indices were highest in Kilifi, followed by Kisumu, then Nairobi with HI (4.3, 0.3, 0; BI (21.3, 7, 0.7 and CI (3.3, 3.3, 0.3, at the respective sites. HI and BI for both species were highest in the long rains, compared to the short rains and dry seasons. We found strong positive correlations between the BI and CI, and BI and HI for Ae. aegypti, with the most productive container types being jerricans, drums, used/discarded containers and tyres. On the basis of established vector index thresholds, our findings suggest low-to-medium risk levels for urban YF and high DEN risk for Kilifi and Kisumu, whereas for Nairobi YF risk was low while DEN risk

  7. IGF-1 and Insulin Resistance Are Major Determinants of Common Carotid Artery Thickness in Morbidly Obese Young Patients.

    Science.gov (United States)

    Sirbu, Anca; Nicolae, Horia; Martin, Sorina; Barbu, Carmen; Copaescu, Catalin; Florea, Suzana; Panea, Cristina; Fica, Simona

    2016-03-01

    We assessed the relationship between insulin resistance, serum insulin-like growth factor 1 (IGF-1) levels, and common carotid intima-media thickness (CC-IMT) in morbidly obese young patients. A total of 249 patients (aged 37.9 ± 9.8 years, body mass index [BMI] 45.6 ± 8.3 kg/m(2)) were evaluated (metabolic tests, serum IGF-1 measurements, homeostasis model assessment-insulin resistance [HOMA-IR], and ultrasonographically assessed CC-IMT) in a research program for bariatric surgery candidates. After adjusting for age, gender, BMI, systolic blood pressure, uric acid, antihypertensive and lipid-lowering treatment, metabolic syndrome, and metabolic class, both HOMA-IR and IGF-1 z-score were significantly associated with CC-IMT. These results were confirmed in logistic regression analysis, in which age (β = 1.11, P = .001), gender (β = 3.19, P = .001), HOMA-IR (β = 1.221, P = .005), and IGF-1 z-score (β = 1.734, P = .009) were the only independent determinants of abnormal CC-IMT, presumably modulating the effect of the other risk factors included in the regression. Area under the receiver-operating characteristic curve for the model was 0.841 (confidence interval: 0.776-0.907; P IGF-1 z-score are significantly associated with CC-IMT, independent of other major cardiovascular risk factors. © The Author(s) 2015.

  8. Performance of the Adult ADHD Self-Report Scale-v1.1 in Adults with Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Boadie W. Dunlop

    2018-03-01

    Full Text Available Attention deficit/hyperactivity disorder (ADHD is an under-recognized comorbid disorder among patients with mood disorders. ADHD is an independent risk factor for suicidal ideation and behavior and contributes to many aspects of impaired function in adults. Diagnosis of ADHD in Major Depressive Disorder (MDD patients is challenging due to the overlap in cognitive symptoms between the two disorders. The ADHD Self-Report Scale, version 1.1 (ASRS-v1.1 is a widely used screening instrument for ADHD in adults but its accuracy has not been evaluated previously in treatment-seeking MDD patients. We administered the ASRS-v1.1 to 55 healthy controls and 40 adults with a primary psychiatric diagnosis of MDD who were participating in clinical research studies. ADHD diagnosis was assessed via structured interview with the adult ADHD module of the Mini International Neuropsychiatric Interview Plus version 6.0.0 (MINI along with a psychiatrist’s assessment. Overall, full-syndrome ADHD was diagnosed in 12.5% of the MDD patients. MDD patients endorsed all 18 items of the ASRS-v1.1 more frequently than the healthy controls and the number of ASRS-v1.1 items endorsed correlated with levels of anxiety in the MDD patients. The ASRS-v1.1 demonstrated fair performance for identifying full syndrome DSM-IV ADHD diagnosis, with sensitivity 60%, specificity: 68.6%, positive predictive value 21.4%, negative predictive value 92.3% and total classification accuracy of 67.5%. Positive predictive value improved substantially when the ADHD criterion requiring symptom onset before age 7 was omitted. In adult MDD patients, a negative ASRS-v1.1 screen strongly suggests the absence of ADHD but positive screen results require careful evaluation to determine whether self-reported ADHD symptoms simply emerge from depression or whether comorbid ADHD is present.

  9. Genetic and Environmental Risk for Chronic Pain and the Contribution of Risk Variants for Major Depressive Disorder: A Family-Based Mixed-Model Analysis.

    Science.gov (United States)

    McIntosh, Andrew M; Hall, Lynsey S; Zeng, Yanni; Adams, Mark J; Gibson, Jude; Wigmore, Eleanor; Hagenaars, Saskia P; Davies, Gail; Fernandez-Pujals, Ana Maria; Campbell, Archie I; Clarke, Toni-Kim; Hayward, Caroline; Haley, Chris S; Porteous, David J; Deary, Ian J; Smith, Daniel J; Nicholl, Barbara I; Hinds, David A; Jones, Amy V; Scollen, Serena; Meng, Weihua; Smith, Blair H; Hocking, Lynne J

    2016-08-01

    Chronic pain is highly prevalent and a significant source of disability, yet its genetic and environmental risk factors are poorly understood. Its relationship with major depressive disorder (MDD) is of particular importance. We sought to test the contribution of genetic factors and shared and unique environment to risk of chronic pain and its correlation with MDD in Generation Scotland: Scottish Family Health Study (GS:SFHS). We then sought to replicate any significant findings in the United Kingdom Biobank study. Using family-based mixed-model analyses, we examined the contribution of genetics and shared family environment to chronic pain by spouse, sibling, and household relationships. These analyses were conducted in GS:SFHS (n = 23,960), a family- and population-based study of individuals recruited from the Scottish population through their general practitioners. We then examined and partitioned the correlation between chronic pain and MDD and estimated the contribution of genetic factors and shared environment in GS:SFHS. Finally, we used data from two independent genome-wide association studies to test whether chronic pain has a polygenic architecture and examine whether genomic risk of psychiatric disorder predicted chronic pain and whether genomic risk of chronic pain predicted MDD. These analyses were conducted in GS:SFHS and repeated in UK Biobank, a study of 500,000 from the UK population, of whom 112,151 had genotyping and phenotypic data. Chronic pain is a moderately heritable trait (heritability = 38.4%, 95% CI 33.6% to 43.9%) that is significantly concordant in spouses (variance explained 18.7%, 95% CI 9.5% to 25.1%). Chronic pain is positively correlated with depression (ρ = 0.13, 95% CI 0.11 to 0.15, p = 2.72x10-68) and shows a tendency to cluster within families for genetic reasons (genetic correlation = 0.51, 95%CI 0.40 to 0.62, p = 8.24x10-19). Polygenic risk profiles for pain, generated using independent GWAS data, were associated with

  10. Genetic and Environmental Risk for Chronic Pain and the Contribution of Risk Variants for Major Depressive Disorder: A Family-Based Mixed-Model Analysis.

    Directory of Open Access Journals (Sweden)

    Andrew M McIntosh

    2016-08-01

    Full Text Available Chronic pain is highly prevalent and a significant source of disability, yet its genetic and environmental risk factors are poorly understood. Its relationship with major depressive disorder (MDD is of particular importance. We sought to test the contribution of genetic factors and shared and unique environment to risk of chronic pain and its correlation with MDD in Generation Scotland: Scottish Family Health Study (GS:SFHS. We then sought to replicate any significant findings in the United Kingdom Biobank study.Using family-based mixed-model analyses, we examined the contribution of genetics and shared family environment to chronic pain by spouse, sibling, and household relationships. These analyses were conducted in GS:SFHS (n = 23,960, a family- and population-based study of individuals recruited from the Scottish population through their general practitioners. We then examined and partitioned the correlation between chronic pain and MDD and estimated the contribution of genetic factors and shared environment in GS:SFHS. Finally, we used data from two independent genome-wide association studies to test whether chronic pain has a polygenic architecture and examine whether genomic risk of psychiatric disorder predicted chronic pain and whether genomic risk of chronic pain predicted MDD. These analyses were conducted in GS:SFHS and repeated in UK Biobank, a study of 500,000 from the UK population, of whom 112,151 had genotyping and phenotypic data. Chronic pain is a moderately heritable trait (heritability = 38.4%, 95% CI 33.6% to 43.9% that is significantly concordant in spouses (variance explained 18.7%, 95% CI 9.5% to 25.1%. Chronic pain is positively correlated with depression (ρ = 0.13, 95% CI 0.11 to 0.15, p = 2.72x10-68 and shows a tendency to cluster within families for genetic reasons (genetic correlation = 0.51, 95%CI 0.40 to 0.62, p = 8.24x10-19. Polygenic risk profiles for pain, generated using independent GWAS data, were associated

  11. Exponentially increasing incidences of cutaneous malignant melanoma in Europe correlate with low personal annual UV doses and suggests 2 major risk factors.

    Science.gov (United States)

    Merrill, Stephen J; Ashrafi, Samira; Subramanian, Madhan; Godar, Dianne E

    2015-01-01

    For several decades the incidence of cutaneous malignant melanoma (CMM) steadily increased in fair-skinned, indoor-working people around the world. Scientists think poor tanning ability resulting in sunburns initiate CMM, but they do not understand why the incidence continues to increase despite the increased use of sunscreens and formulations offering more protection. This paradox, along with lower incidences of CMM in outdoor workers, although they have significantly higher annual UV doses than indoor workers have, perplexes scientists. We found a temporal exponential increase in the CMM incidence indicating second-order reaction kinetics revealing the existence of 2 major risk factors. From epidemiology studies, we know one major risk factor for getting CMM is poor tanning ability and we now propose the other major risk factor may be the Human Papilloma Virus (HPV) because clinicians find β HPVs in over half the biopsies. Moreover, we uncovered yet another paradox; the increasing CMM incidences significantly correlate with decreasing personal annual UV dose, a proxy for low vitamin D3 levels. We also discovered the incidence of CMM significantly increased with decreasing personal annual UV dose from 1960, when it was almost insignificant, to 2000. UV and other DNA-damaging agents can activate viruses, and UV-induced cytokines can hide HPV from immune surveillance, which may explain why CMM also occurs in anatomical locations where the sun does not shine. Thus, we propose the 2 major risk factors for getting CMM are intermittent UV exposures that result in low cutaneous levels of vitamin D3 and possibly viral infection.

  12. Characteristics of patients who suffer major osteoporotic fractures despite adhering to alendronate treatment

    DEFF Research Database (Denmark)

    Abrahamsen, B; Rubin, K H; Eiken, Pia Agnete

    2013-01-01

    .03-1.06, for each drug). Dementia (HR 1.81, 95 % CI 1.18-2.78), prior fracture (one: HR 1.17, 95 % CI 1.02-1.34; multiple: HR 1.34, 95 % CI 1.08-1.67), and ulcer disease (HR 1.45, 95 % CI 1.04-2.03) also increased the risk. Diabetes did not influence fracture risk, nor did rheumatic disorders. The risk was lower...... and associations may not be causal, it may be prudent to include dementia, ulcer disease, and Parkinson's disease to capture the risk of fractures on treatment. Lower risk in patients treated with glucocorticoids and in men probably reflects a lower treatment threshold related to guidelines.......Antiresorptive treatment reduces the risk of fractures, but most patients remain at elevated risk. We used health registers to identify predictors of new major osteoporotic fractures in patients adhering to alendronate. Risk factors showed a different pattern than in the general population...

  13. Surgery and Anesthesia Exposure Is Not a Risk Factor for Cognitive Impairment After Major Noncardiac Surgery and Critical Illness

    NARCIS (Netherlands)

    Hughes, Christopher G; Patel, Mayur B; Jackson, James C; Girard, Timothy D; Geevarghese, Sunil K; Norman, Brett C; Thompson, Jennifer L; Chandrasekhar, Rameela; Brummel, Nathan E; May, Addison K; Elstad, Mark R; Wasserstein, Mitzi L; Goodman, Richard B; Moons, Karel G; Dittus, Robert S; Ely, E Wesley; Pandharipande, Pratik P; MIND-ICU, BRAIN-ICU investigators

    OBJECTIVE: The aim of this study was to determine whether surgery and anesthesia exposure is an independent risk factor for cognitive impairment after major noncardiac surgery associated with critical illness. SUMMARY OF BACKGROUND DATA: Postoperative cognitive impairment is a prevalent individual

  14. Terrestrial Gamma Radiation Exposure Measurement and Risk Estimates in the Environments of Major Industries In Ota, Nigeria

    Directory of Open Access Journals (Sweden)

    Abodunrin Oluwasayo Peter

    2016-11-01

    Full Text Available When fast estimates are required, the in-situ method is more appropriate as this allows for quick results; preventing further exposure of the public and permitting quick intervention. Measurements of the terrestrial gamma radiation exposure have been carried out in the environments of major industries in Ota using a portable survey meter. The motivation for this study resulted from the uncertainty in the general public opinion on the effect of the presence, and activities of some of these industries in their environment. Measurements were taken twice daily within the vicinity of each industry to determine the dose levels. The mean values obtained range from 0.11 – 1.80 µSv/h. These values are within the results obtained from normal background areas except for site number 10. Annual effective dose values range from 0.25 – 5.21 mSv with a mean value of 1.21 mSv. Routine activities in some of these environments may have contributed significantly to the ambient natural background radiation resulting in high values as obtained in some of these locations. The total risks disparately estimated for cancer and genetic effects resulting from the results obtained range from 0.17 x 10-4 – 3.80 x 10-4 with a mean value of 0.94 x 10-4. These levels are within the range of the average annual risk for accidental death for all industries.

  15. Tailoring of EIA-649-1: Definition of Major (Class I) Engineering Change Proposal

    Science.gov (United States)

    2015-05-15

    MISSILE SYSTEMS CENTER TAILORING TAILORING OF EIA -649-1: DEFINITION OF MAJOR (CLASS I) ENGINEERING CHANGE PROPOSAL APPROVED FOR...PUBLIC RELEASE; DISTRIBUTION IS UNLIMITED 1 Tailoring of EIA -649-1: Definition of Major (Class I) ECP. 1. Intent of this Tailoring Document...This tailoring document remedies a requirements gap in the industry consensus standard, EIA -649-1: 2015. Specifically, this tailoring provides a

  16. Interaction between CRHR1 and BDNF genes increases the risk of recurrent major depressive disorder in Chinese population.

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    Zheman Xiao

    Full Text Available BACKGROUND: An important etiological hypothesis about depression is stress has neurotoxic effects that damage the hippocampal cells. Corticotropin-releasing hormone (CRH regulates brain-derived neurotrophic factor (BDNF expression through influencing cAMP and Ca2+ signaling pathways during the course. The aim of this study is to examine the single and combined effects of CRH receptor 1 (CRHR1 and BDNF genes in recurrent major depressive disorder (MDD. METHODOLOGY/PRINCIPAL FINDING: The sample consists of 181 patients with recurrent MDD and 186 healthy controls. Whether genetic variations interaction between CRHR1 and BDNF genes might be associated with increased susceptibility to recurrent MDD was studied by using a gene-based association analysis of single-nucleotide polymorphisms (SNPs. CRHR1 gene (rs1876828, rs242939 and rs242941 and BDNF gene (rs6265 were identified in the samples of patients diagnosed with recurrent MDD and matched controls. Allelic association between CRHR1 rs242939 and recurrent MDD was found in our sample (allelic: p = 0.018, genotypic: p = 0.022 with an Odds Ratio 0.454 (95% CI 0.266-0.775. A global test of these four haplotypes showed a significant difference between recurrent MDD group and control group (chi-2 = 13.117, df = 3, P = 0.016. Furthermore, BDNF and CRHR1 interactions were found in the significant 2-locus, gene-gene interaction models (p = 0.05 using a generalized multifactor dimensionality reduction (GMDR method. CONCLUSION: Our results suggest that an interaction between CRHR1 and BDNF genes constitutes susceptibility to recurrent MDD.

  17. Breast cancer risks and risk prediction models.

    Science.gov (United States)

    Engel, Christoph; Fischer, Christine

    2015-02-01

    BRCA1/2 mutation carriers have a considerably increased risk to develop breast and ovarian cancer. The personalized clinical management of carriers and other at-risk individuals depends on precise knowledge of the cancer risks. In this report, we give an overview of the present literature on empirical cancer risks, and we describe risk prediction models that are currently used for individual risk assessment in clinical practice. Cancer risks show large variability between studies. Breast cancer risks are at 40-87% for BRCA1 mutation carriers and 18-88% for BRCA2 mutation carriers. For ovarian cancer, the risk estimates are in the range of 22-65% for BRCA1 and 10-35% for BRCA2. The contralateral breast cancer risk is high (10-year risk after first cancer 27% for BRCA1 and 19% for BRCA2). Risk prediction models have been proposed to provide more individualized risk prediction, using additional knowledge on family history, mode of inheritance of major genes, and other genetic and non-genetic risk factors. User-friendly software tools have been developed that serve as basis for decision-making in family counseling units. In conclusion, further assessment of cancer risks and model validation is needed, ideally based on prospective cohort studies. To obtain such data, clinical management of carriers and other at-risk individuals should always be accompanied by standardized scientific documentation.

  18. Resting heart rate associates with one-year risk of major adverse cardiovascular events in patients with acute coronary syndrome after percutaneous coronary intervention.

    Science.gov (United States)

    Wang, Shao-Li; Wang, Cheng-Long; Wang, Pei-Li; Xu, Hao; Du, Jian-Peng; Zhang, Da-Wu; Gao, Zhu-Ye; Zhang, Lei; Fu, Chang-Geng; Chen, Ke-Ji; Shi, Da-Zhuo

    2016-03-01

    The study was to access the association between resting heart rate (RHR) and one-year risk of major adverse cardiovascular events (MACE) in acute coronary syndrome (ACS) patients after percutaneous coronary intervention (PCI). Patients with ACS after PCI (n = 808) were prospectively followed-up for MACE. RHR was obtained from electrocardiogram. MACE was defined as a composite of cardiac death, nonfatal recurrent myocardial infarction, ischemic-driven revascularization, and ischemic stroke. The association between RHR and one-year risk of MACE was assessed using Cox proportional hazards regression model. Compared with patients with RHR >76 bpm, the adjusted hazard ratio (AHR) was 0.51 (95% confidence intervals [CI]: 0.23-1.14; P = 0.100) for patients with RHR 76 bpm were at higher risk of MACE during one-year follow-up compared with patients with RHR 61-76 bpm. An elevated RHR ≥ 61 bpm was associated with increased risk of one-year MACE in ACS patients. © 2015 by the Society for Experimental Biology and Medicine.

  19. Improved predictive value of GRACE risk score combined with platelet reactivity for 1-year cardiovascular risk in patients with acute coronary syndrome who underwent coronary stent implantation.

    Science.gov (United States)

    Li, Shan; Liu, Hongbin; Liu, Jianfeng; Wang, Haijun

    2016-11-01

    Both high platelet reactivity (HPR) and Global Registry of Acute Coronary Events (GRACE) risk score have moderate predictive value for major adverse cardiovascular disease (CVD) events in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI), whereas the prognostic significance of GRACE risk score combined with platelet function testing remains unclear. A total of 596 patients with non-ST elevation ACS who underwent PCI were enrolled. The P2Y 12 reaction unit (PRU) value was measured by VerifyNow P2Y 12 assay and GRACE score was calculated by GRACE risk 2.0 calculator. Patients were stratified by a pre-specified cutoff value of PRU 230 and GRACE score 140 to assess 1-year risk of cardiovascular death, non-fatal myocardial infarction (MI), and stent thrombosis. Seventy-two (12.1%) patients developed CVD events during 1-year follow-up. Patients with CVD events had a higher PRU value (244.6 ± 50.9 vs. 203.7 ± 52.0, p risk independently. Compared to patients with normal platelet reactivity (NPR) and GRACE score risk (HR: 5.048; 95% CI: 2.268-11.237; p risk score yielded superior risk predictive capacity beyond GRACE score alone, which is shown by improved c-statistic value (0.871, p = 0.002) as well as net reclassification improvement (NRI 0.263, p risk of adverse CVD events. The combination of platelet function testing and GRACE score predicted 1-year CVD risk better.

  20. Major risk factors for aneurysmal subarachnoid hemorrhage in the young are modifiable.

    Science.gov (United States)

    Broderick, Joseph P; Viscoli, Catherine M; Brott, Thomas; Kernan, Walter N; Brass, Lawrence M; Feldmann, Edward; Morgenstern, Lewis B; Wilterdink, Janet Lee; Horwitz, Ralph I

    2003-06-01

    To identify risk factors for subarachnoid hemorrhage (SAH) and intracerebral hemorrhage, we designed a case-control study of men and women 18 to 49 years of age (the Hemorrhagic Stroke Project [HSP]). This report focuses on SAH. Patients were recruited from 44 hospitals in the United States. Cases with SAH must have had a ruptured aneurysm documented by angiography or surgery. Two controls, identified by random digit dialing and matched to each patient for age, sex, race, and telephone exchange, were sought for each case subject. Between 1994 and 1999, 425 patients with SAH were enrolled in HSP, and 312 cases met the criteria for aneurysmal SAH. The present analyses also included 618 matched controls. Of the 312 cases, 66% were current cigarette smokers compared with 30% of controls (adjusted odds ratio [OR], 3.73; 95% CI, 2.67 to 5.21). Cocaine use within the previous 3-day period was reported by 3% of cases and no controls (bivariate exact OR, 24.97; 95% exact CI, 3.95 to infinity; adjusted estimate not calculable). Other independent risk factors in the multivariable model included hypertension (adjusted OR, 2.21; 95% CI, 1.48 to 3.29), low body mass index (OR, 1.59; 95% CI, 1.08 to 2.35), primary family history of hemorrhagic stroke (OR, 3.83; 95% CI, 1.73 to 8.46), caffeine in pharmaceutical products (OR, 2.48; 95% CI, 1.19 to 5.20), lower educational achievement (OR, 2.36; 95% CI, 1.44 to 3.87), and nicotine in pharmaceutical products (adjusted estimate not calculable). Aneurysmal SAH may be largely a preventable disease among the young and middle-aged because several prevalent risk factors can be modified by medication (eg, hypertension) or behavioral change (eg, cigarette smoking, cocaine use). The association of caffeine and nicotine in pharmaceutical products and aneurysmal SAH warrants further study.

  1. Psychiatric comorbidities in patients with major depressive disorder

    Directory of Open Access Journals (Sweden)

    Thaipisuttikul P

    2014-11-01

    Full Text Available Papan Thaipisuttikul, Pichai Ittasakul, Punjaporn Waleeprakhon, Pattarabhorn Wisajun, Sudawan Jullagate Department of Psychiatry, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Background: Psychiatric comorbidities are common in major depressive disorder (MDD. They may worsen outcome and cause economic burden. The primary objective was to examine the prevalence of psychiatric comorbidities in MDD. The secondary objectives were to compare the presence of comorbidities between currently active and past MDD, and between patients with and without suicidal risk.Methods: This was a cross-sectional study. A total of 250 patients with lifetime MDD and age ≥18 years were enrolled. The Mini International Neuropsychiatric Interview (MINI, Thai version, was used to confirm MDD diagnosis and classify comorbidities. MDD diagnosis was confirmed in 190, and 60 patients were excluded due to diagnosis of bipolar disorder.Results: Of the 190 MDD patients, 25.8% had current MDD and 74.2% had past MDD. Eighty percent were women. The mean age at enrollment was 50 years, and at MDD onset was 41 years. Most patients were married (53.2%, employed (54.8%, and had ≥12 years of education (66.9%. There were 67 patients (35.3% with one or more psychiatric comorbidities. Comorbidities included dysthymia (19.5%, any anxiety disorders (21.1% (panic disorder [6.8%], agoraphobia [5.8%], social phobia [3.7%], obsessive–compulsive disorder [OCD] [4.7%], generalized anxiety disorder [5.3%], and post-traumatic stress disorder [4.2%], alcohol dependence (0.5%, psychotic disorder (1.6%, antisocial personality (1.1%, and eating disorders (0%. Compared with past MDD, the current MDD group had significantly higher OCD (P<0.001, psychotic disorder (P=0.048, past panic disorder (P=0.017, and suicidal risk (P<0.001. Suicidal risk was found in 32.1% of patients. Patients with suicidal risk had more comorbid anxiety disorder of any type (P=0.019 and

  2. HIV prevalence among the female sex workers in major cities in Myanmar and the risk behaviors associated with it

    Directory of Open Access Journals (Sweden)

    Swe LA

    2013-08-01

    Full Text Available Lin Aung Swe,1 Abdul Rashid2 1Beneficial Partner Group, Bahan Township, Myanmar; 2Department of Public Health Medicine, Penang Medical College, Georgetown, Malaysia Background: Myanmar is one of the countries hardest hit by the human immunodeficiency virus (HIV epidemic in Asia. Aim: The objective of the study was to determine HIV prevalence among the female sex workers in major cities in Myanmar and the risk behaviors associated with it. Methods: This cross-sectional study was conducted among female sex workers in major cities in Myanmar. Interviews were conducted by trained research assistants, in private, using a questionnaire. The HIV status of the respondents was asked and confirmed by the blood test reports from the laboratories of the Myanmar National AIDS Programme sexually transmitted infections (STI/acquired immunodeficiency syndrome (AIDS Teams and nongovernmental organizations (NGOs. Results: There were 200 respondents in this study. Out of the 136 participants who were tested for HIV, 25 (18.4% were HIV-positive. Respondents of other ethnic groups than Myanmars and other religions than Buddhist were about six times (odds ratio [OR] 5.9 and five times (OR 4.6, respectively, at higher odds of being HIV-positive. Those who were earning an income of less than 200,000 kyats were almost three times (OR 2.9 at higher odds of being HIV-positive. The difference in the age group was found to be statistically significant (P = 0.001. Respondents who did not have HIV counseling (OR 7.3, who did not use condoms (OR 1.3, and with regular partners who refused the use of condoms (OR 6.0 were at higher odds of being HIV-positive. Conclusion: HIV prevention services should include socioeconomic support programs, and the clients and regular partners of sex workers should also be targeted for behavior-change messages, to reduce condom resistance. Keywords: HIV prevalence, risk factors, Myanmar, sex workers, condom

  3. A population-based longitudinal study of recent stressful life events as risk factors for suicidal behavior in major depressive disorder.

    Science.gov (United States)

    Wang, Yunqiao; Sareen, Jitender; Afifi, Tracie O; Bolton, Shay-Lee; Johnson, Edward A; Bolton, James M

    2015-01-01

    The purpose of this study is to investigate whether the type and number of stressful life events (SLEs) will be associated with suicidal behavior in a 3-year follow-up period in persons with major depressive disorder (MDD). Data came from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative longitudinal survey of mental health in non-institutionalized adults in the United States. The survey consisted of two waves: Wave 1 (2001--2002) and Wave 2 (2004-2005), n = 34,653. Twelve past-year SLEs were assessed at baseline. These SLEs were categorized into the following groups based on previous research: Loss or victimization; Relationship, friendship, or interpersonal stress; Financial stress; and Legal problems. Only respondents with MDD at Wave 1 were included (n = 6,004). Several SLEs were strongly associated with suicide attempts, among which, "serious problems with neighbor, friend, or relative" (adjusted odds ratio [AOR] = 2.21; 95% confidence interval [95% CI]: 1.41, 3.45) and "major financial crisis, bankruptcy, or unable to pay bills" (AOR = 2.31; 95% CI: 1.45, 3.66) were the most robust predictors of suicide attempts even after adjusting for sociodemographic variables and any anxiety, substance use, or personality disorder. People with MDD who had been exposed to certain SLEs are at elevated risk for future suicide attempts, even after accounting for the demographic factors and psychiatric comorbidity.

  4. Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease.

    Science.gov (United States)

    Eriksson, D; Bianchi, M; Landegren, N; Nordin, J; Dalin, F; Mathioudaki, A; Eriksson, G N; Hultin-Rosenberg, L; Dahlqvist, J; Zetterqvist, H; Karlsson, Å; Hallgren, Å; Farias, F H G; Murén, E; Ahlgren, K M; Lobell, A; Andersson, G; Tandre, K; Dahlqvist, S R; Söderkvist, P; Rönnblom, L; Hulting, A-L; Wahlberg, J; Ekwall, O; Dahlqvist, P; Meadows, J R S; Bensing, S; Lindblad-Toh, K; Kämpe, O; Pielberg, G R

    2016-12-01

    Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology. To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls. We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10 -15 , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex. Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment. © 2016 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

  5. Critical analysis of major incidents risks in civil nuclear energy

    International Nuclear Information System (INIS)

    2000-09-01

    The differences existing between the PWR type reactors and the RBMK type reactors are explained as well as the risk associated to each type when it exists. The Ines scale, tool to give the level of an accident gravity comprises seven levels, the number seven is the most serious and corresponds to the Chernobyl accident; The number zero is of no consequence but must be mentioned as a matter of form. The incidents from 1 to 3 concern increasing incidents, affecting the nuclear power plant but not the external public. The accidents from 4 to 7 have a nature to affect the nuclear power plant and the environment. An efficient tool exists between nuclear operators it is made of the reports on incidents encountered by close reactors. Two others type reactors are coming, the high temperature type reactors and the fast neutrons reactors. different risks are evoked, terrorism, proliferation, transport and radioactive wastes. (N.C.)

  6. BACH1 Ser919Pro variant and breast cancer risk

    Directory of Open Access Journals (Sweden)

    Eerola Hannaleena

    2006-01-01

    Full Text Available Abstract Background BACH1 (BRCA1-associated C-terminal helicase 1; also known as BRCA1-interacting protein 1, BRIP1 is a helicase protein that interacts in vivo with BRCA1, the protein product of one of the major genes for hereditary predisposition to breast cancer. Previously, two BACH1 germ line missense mutations have been identified in early-onset breast cancer patients with and without family history of breast and ovarian cancer. In this study, we aimed to evaluate whether there are BACH1 genetic variants that contribute to breast cancer risk in Finland. Methods The BACH1 gene was screened for germ line alterations among probands from 43 Finnish BRCA1/2 negative breast cancer families. Recently, one of the observed common variants, Ser-allele of the Ser919Pro polymorphism, was suggested to associate with an increased breast cancer risk, and was here evaluated in an independent, large series of 888 unselected breast cancer patients and in 736 healthy controls. Results Six BACH1 germ line alterations were observed in the mutation analysis, but none of these were found to associate with the cancer phenotype. The Val193Ile variant that was seen in only one family was further screened in an independent series of 346 familial breast cancer cases and 183 healthy controls, but no additional carriers were observed. Individuals with the BACH1 Ser919-allele were not found to have an increased breast cancer risk when the Pro/Ser heterozygotes (OR 0.90; 95% CI 0.70–1.16; p = 0.427 or Ser/Ser homozygotes (OR 1.02; 95% CI 0.76–1.35; p = 0.91 were compared to Pro/Pro homozygotes, and there was no association of the variant with any breast tumor characteristics, age at cancer diagnosis, family history of cancer, or survival. Conclusion Our results suggest that the BACH1 Ser919 is not a breast cancer predisposition allele in the Finnish study population. Together with previous studies, our results also indicate that although some rare germ line variants

  7. BACH1 Ser919Pro variant and breast cancer risk

    International Nuclear Information System (INIS)

    Vahteristo, Pia; Yliannala, Kristiina; Tamminen, Anitta; Eerola, Hannaleena; Blomqvist, Carl; Nevanlinna, Heli

    2006-01-01

    BACH1 (BRCA1-associated C-terminal helicase 1; also known as BRCA1-interacting protein 1, BRIP1) is a helicase protein that interacts in vivo with BRCA1, the protein product of one of the major genes for hereditary predisposition to breast cancer. Previously, two BACH1 germ line missense mutations have been identified in early-onset breast cancer patients with and without family history of breast and ovarian cancer. In this study, we aimed to evaluate whether there are BACH1 genetic variants that contribute to breast cancer risk in Finland. The BACH1 gene was screened for germ line alterations among probands from 43 Finnish BRCA1/2 negative breast cancer families. Recently, one of the observed common variants, Ser-allele of the Ser919Pro polymorphism, was suggested to associate with an increased breast cancer risk, and was here evaluated in an independent, large series of 888 unselected breast cancer patients and in 736 healthy controls. Six BACH1 germ line alterations were observed in the mutation analysis, but none of these were found to associate with the cancer phenotype. The Val193Ile variant that was seen in only one family was further screened in an independent series of 346 familial breast cancer cases and 183 healthy controls, but no additional carriers were observed. Individuals with the BACH1 Ser919-allele were not found to have an increased breast cancer risk when the Pro/Ser heterozygotes (OR 0.90; 95% CI 0.70–1.16; p = 0.427) or Ser/Ser homozygotes (OR 1.02; 95% CI 0.76–1.35; p = 0.91) were compared to Pro/Pro homozygotes, and there was no association of the variant with any breast tumor characteristics, age at cancer diagnosis, family history of cancer, or survival. Our results suggest that the BACH1 Ser919 is not a breast cancer predisposition allele in the Finnish study population. Together with previous studies, our results also indicate that although some rare germ line variants in BACH1 may contribute to breast cancer development, the

  8. The joint impact of cognitive performance in adolescence and familial cognitive aptitude on risk for major psychiatric disorders: a delineation of four potential pathways to illness.

    Science.gov (United States)

    Kendler, K S; Ohlsson, H; Keefe, R S E; Sundquist, K; Sundquist, J

    2018-04-01

    How do joint measures of premorbid cognitive ability and familial cognitive aptitude (FCA) reflect risk for a diversity of psychiatric and substance use disorders? To address this question, we examined, using Cox models, the predictive effects of school achievement (SA) measured at age 16 and FCA-assessed from SA in siblings and cousins, and educational attainment in parents-on risk for 12 major psychiatric syndromes in 1 140 608 Swedes born 1972-1990. Four developmental patterns emerged. In the first, risk was predicted jointly by low levels of SA and high levels of FCA-that is a level of SA lower than would be predicted from the FCA. This pattern was strongest in autism spectrum disorders and schizophrenia, and weakest in bipolar illness. In these disorders, a pathologic process seems to have caused cognitive functioning to fall substantially short of familial potential. In the second pattern, seen in the internalizing conditions of major depression and anxiety disorders, risk was associated with low SA but was unrelated to FCA. Externalizing disorders-drug abuse and alcohol use disorders-demonstrated the third pattern, in which risk was predicted jointly by low SA and low FCA. The fourth pattern, seen in eating disorders, was directly opposite of that observed in externalizing disorders with risk associated with high SA and high FCA. When measured together, adolescent cognitive ability and FCA identified four developmental patterns leading to diverse psychiatric disorders. The value of cognitive assessments in psychiatric research can be substantially increased by also evaluating familial cognitive potential.

  9. Combined effects of NQO1 Pro187Ser or SULT1A1 Arg213His polymorphism and smoking on bladder cancer risk: Two meta-analyses.

    Science.gov (United States)

    Wang, Xiao-Chun; Wang, Jian; Tao, Hui-Hui; Zhang, Chao; Xu, Li-Fa

    2017-07-14

    Objectives: Cigarette smoking is the major risk factor of bladder cancer via exposure to chemical carcinogens. Nicotinamide adenine dinucleotide phosphate (NADP+): quinine oxidoreductase 1 (NQO1) and sulfotransferase 1A1 (SULT1A1) have been reported to involve in the metabolism of polycyclic aromatic hydrocarbons (PAHs) and aromatic amines. Therefore, the risk of bladder cancer (BC) may be influenced by polymorphisms in the genes that modulate metabolic detoxification in particular by interacting with cigarette smoking. Considering the limited power by the individual studies with a relatively small sample size, especially when analyzing the combined effect of polymorphisms in NQO1 and SULT1A1 genes and smoking, these 2 meta-analyses have aimed to clarify the combined effects of them on BC risk by integrating related studies. Two meta-analyses included 1341 cases and 1346 controls concerning NQO1 Pro187Ser and smoking, and 1921 cases and 1882 controls on SULT1A1 Arg213His and smoking were performed. Odds ratios (OR) and 95% confidence intervals (CI) were used for assessing the strength of the association. The result has demonstrated that smokers with NQO1 Pro/Ser or Ser/Ser genotypes have a prominent association with the risk of BC as compared with non-smokers with NQO1 Pro/Pro genotype, with OR equal to 3.71 (95% CI: 2.87-4.78, pheterogeneity = 0.376). Besides, smokers carrying SULT1A1 Arg/Arg genotypes were observed to confer 2.38 fold increased risk of BC (95% CI: 1.44-3.93, pheterogeneity = 0.001) when compared with non-smokers with SULT1A1 Arg/Arg or His/His genotypes. These findings have suggested that the NQO1 Pro187Ser or SULT1A1 Arg213His polymorphism combination with smoking significantly confer susceptibility to BC. Int J Occup Med Environ Health 2017;30(5):791-802. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  10. Combined effects of NQO1 Pro187Ser or SULT1A1 Arg213His polymorphism and smoking on bladder cancer risk: Two meta-analyses

    Directory of Open Access Journals (Sweden)

    Xiao-Chun Wang

    2017-10-01

    Full Text Available Objectives: Objectives: Cigarette smoking is the major risk factor of bladder cancer via exposure to chemical carcinogens. Nicotinamide adenine dinucleotide phosphate (NADP+: quinine oxidoreductase 1 (NQO1 and sulfotransferase 1A1 (SULT1A1 have been reported to involve in the metabolism of polycyclic aromatic hydrocarbons (PAHs and aromatic amines. Therefore, the risk of bladder cancer (BC may be influenced by polymorphisms in the genes that modulate metabolic detoxification in particular by interacting with cigarette smoking. Considering the limited power by the individual studies with a relatively small sample size, especially when analyzing the combined effect of polymorphisms in NQO1 and SULT1A1 genes and smoking, these 2 meta-analyses have aimed to clarify the combined effects of them on BC risk by integrating related studies. Material and Methods: Two meta-analyses included 1341 cases and 1346 controls concerning NQO1 Pro187Ser and smoking, and 1921 cases and 1882 controls on SULT1A1 Arg213His and smoking were performed. Odds ratios (OR and 95% confidence intervals (CI were used for assessing the strength of the association. Results: The result has demonstrated that smokers with NQO1 Pro/Ser or Ser/Ser genotypes have a prominent association with the risk of BC as compared with non-smokers with NQO1 Pro/Pro genotype, with OR equal to 3.71 (95% CI: 2.87–4.78, pheterogeneity = 0.376. Besides, smokers carrying SULT1A1 Arg/Arg genotypes were observed to confer 2.38 fold increased risk of BC (95% CI: 1.44–3.93, pheterogeneity = 0.001 when compared with non-smokers with SULT1A1 Arg/Arg or His/His genotypes. Conclusions: These findings have suggested that the NQO1 Pro187Ser or SULT1A1 Arg213His polymorphism combination with smoking significantly confer susceptibility to BC. Int J Occup Med Environ Health 2017;30(5:791–802

  11. Clustering of Major Cardiovascular Risk Factors and the Association with Unhealthy Lifestyles in the Chinese Adult Population.

    Directory of Open Access Journals (Sweden)

    Bixia Gao

    Full Text Available Previous studies indicated that lifestyle-related cardiovascular risk factors tend to be clustered in certain individuals. However, population-based studies, especially from developing countries with substantial economic heterogeneity, are extremely limited. Our study provides updated data on the clustering of cardiovascular risk factors, as well as the impact of lifestyle on those factors in China.A representative sample of adult population in China was obtained using a multistage, stratified sampling method. We investigated the clustering of four cardiovascular disease (CVD risk factors (defined as two or more of the following: hypertension, diabetes, dyslipidemia and overweight and their association with unhealthy lifestyles (habitual drinking, physical inactivity, chronic use of non-steroidal anti-inflammatory drugs (NSAIDs and a low modified Dietary Approaches to Stop Hypertension (DASH score.Among the 46,683 participants enrolled in this study, only 31.1% were free of any pre-defined CVD risk factor. A total of 20,292 subjects had clustering of CVD risk factors, and 83.5% of them were younger than 65 years old. The adjusted prevalence of CVD risk factor clustering was 36.2%, and the prevalence was higher among males than among females (37.9% vs. 34.5%. Habitual drinking, physical inactivity, and chronic use of NSAIDs were positively associated with the clustering of CVD risk factors, with ORs of 1.60 (95% confidence interval [CI] 1.40 to1.85, 1.20 (95%CI 1.11 to 1.30 and 2.17 (95%CI 1.84 to 2.55, respectively. The modified DASH score was inversely associated with the clustering of CVD risk factors, with an OR of 0.73 (95%CI 0.67 to 0.78 for those with modified DASH scores in the top tertile. The lifestyle risk factors were more prominent among participants with low socioeconomic status.Clustering of CVD risk factors was common in China. Lifestyle modification might be an effective strategy to control CVD risk factors.

  12. Act No. 87-565 of 22 July 1987 on the organization of public safety measures, forestry protection against fires and the prevention of major risks

    International Nuclear Information System (INIS)

    1987-01-01

    As defined by this Act, the objective of the public safety measures is to prevent all types of major risks and to protect persons, property and the environment, including forests, against accidents, disasters and catastrophes. It deals with the conditions for preparing preventive measures and for implementing necessary measures in case of major risks or accidents. The preparation and organization of assistance are determined within the framework of ORSEC (ORganisation des SECours) plans and emergency plans; the first assess the possibilities for facing up to disasters while the latter provide for measures and means to overcome a particular risk [fr

  13. Comparison between frailty index of deficit accumulation and fracture risk assessment tool (FRAX) in prediction of risk of fractures.

    Science.gov (United States)

    Li, Guowei; Thabane, Lehana; Papaioannou, Alexandra; Adachi, Jonathan D

    2015-08-01

    A frailty index (FI) of deficit accumulation could quantify and predict the risk of fractures based on the degree of frailty in the elderly. We aimed to compare the predictive powers between the FI and the fracture risk assessment tool (FRAX) in predicting risk of major osteoporotic fracture (hip, upper arm or shoulder, spine, or wrist) and hip fracture, using the data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) 3-year Hamilton cohort. There were 3985 women included in the study, with the mean age of 69.4 years (standard deviation [SD] = 8.89). During the follow-up, there were 149 (3.98%) incident major osteoporotic fractures and 18 (0.48%) hip fractures reported. The FRAX and FI were significantly related to each other. Both FRAX and FI significantly predicted risk of major osteoporotic fracture, with a hazard ratio (HR) of 1.03 (95% confidence interval [CI]: 1.02-1.05) and 1.02 (95% CI: 1.01-1.04) for per-0.01 increment for the FRAX and FI respectively. The HRs were 1.37 (95% CI: 1.19-1.58) and 1.26 (95% CI: 1.12-1.42) for an increase of per-0.10 (approximately one SD) in the FRAX and FI respectively. Similar discriminative ability of the models was found: c-index = 0.62 for the FRAX and c-index = 0.61 for the FI. When cut-points were chosen to trichotomize participants into low-risk, medium-risk and high-risk groups, a significant increase in fracture risk was found in the high-risk group (HR = 2.04, 95% CI: 1.36-3.07) but not in the medium-risk group (HR = 1.23, 95% CI: 0.82-1.84) compared with the low-risk women for the FI, while for FRAX the medium-risk (HR = 2.00, 95% CI: 1.09-3.68) and high-risk groups (HR = 2.61, 95% CI: 1.48-4.58) predicted risk of major osteoporotic fracture significantly only when survival time exceeded 18months (550 days). Similar findings were observed for hip fracture and in sensitivity analyses. In conclusion, the FI is comparable with FRAX in the prediction of risk of future fractures, indicating that

  14. A background risk analysis. Vol. 1

    International Nuclear Information System (INIS)

    Taylor, J.R.

    1979-01-01

    This 4-volumes report gives a background of ideas, principles, and examples which might be of use in developing practical methods for risk analysis. Some of the risk analysis techniques, described are somewhat experimental. The report is written in an introductory style, but where some point needs further justification or evaluation, this is given in the form of a chapter appendix. In this way, it is hoped that the report can serve two purposes, - as a basis for starting risk analysis work and as a basis for discussing effectiveness of risk analysis procedures. The report should be seen as a preliminary stage, prior to a program of industrial trials of risk analysis methods. Vol. 1 contains a short history of risk analysis, and chapters on risk, failures, errors and accidents, and general procedures for risk analysis. (BP)

  15. Maternal Residential Proximity to Major Roadways and Pediatric Embryonal Tumors in Offspring

    Directory of Open Access Journals (Sweden)

    Shwetha V. Kumar

    2018-03-01

    Full Text Available The environmental determinants of pediatric embryonal tumors remain unclear. Because of the growing concern over the impact of exposures to traffic-related air pollution on pediatric cancer, we conducted a population-based study evaluating the impact of maternal residential proximity to major roadways on the risk of pediatric embryonal tumors in offspring. We identified children diagnosed with neuroblastoma, Wilms tumor, retinoblastoma, or hepatoblastoma at <5 years of age from the Texas Cancer Registry and selected unaffected controls from birth certificates. Two residential proximity measures were used: (1 distance to the nearest major roadway, and (2 within 500 m of a major roadway. Logistic regression was used to estimate the adjusted odds ratio (aOR and 95% confidence interval (CI for each proximity measure on pediatric embryonal tumors. The odds of an embryonal tumor were increased in children born to mothers living within 500 m of a major roadway (aOR = 1.24, 95% CI: 1.00, 1.54. This was consistent for most tumor subtypes, with the strongest associations observed for unilateral retinoblastoma (aOR = 2.57, 95% CI: 1.28, 5.15, for every kilometer closer the mother lived to the nearest major roadway. These findings contribute to the growing evidence that traffic-related air pollution may increase risk for certain pediatric tumors.

  16. Major Risk Factors for Heart Disease: Overweight and Obesity

    Science.gov (United States)

    ... we spend more time in front of computers, video games, TV, and other electronic pastimes, we have fewer ... no other risk factors. Overweight and obesity also increase the risks for diabetes, high blood pressure, high ...

  17. Alzheimer's Disease Risk Polymorphisms Regulate Gene Expression in the ZCWPW1 and the CELF1 Loci.

    Directory of Open Access Journals (Sweden)

    Celeste M Karch

    Full Text Available Late onset Alzheimer's disease (LOAD is a genetically complex and clinically heterogeneous disease. Recent large-scale genome wide association studies (GWAS have identified more than twenty loci that modify risk for AD. Despite the identification of these loci, little progress has been made in identifying the functional variants that explain the association with AD risk. Thus, we sought to determine whether the novel LOAD GWAS single nucleotide polymorphisms (SNPs alter expression of LOAD GWAS genes and whether expression of these genes is altered in AD brains. The majority of LOAD GWAS SNPs occur in gene dense regions under large linkage disequilibrium (LD blocks, making it unclear which gene(s are modified by the SNP. Thus, we tested for brain expression quantitative trait loci (eQTLs between LOAD GWAS SNPs and SNPs in high LD with the LOAD GWAS SNPs in all of the genes within the GWAS loci. We found a significant eQTL between rs1476679 and PILRB and GATS, which occurs within the ZCWPW1 locus. PILRB and GATS expression levels, within the ZCWPW1 locus, were also associated with AD status. Rs7120548 was associated with MTCH2 expression, which occurs within the CELF1 locus. Additionally, expression of several genes within the CELF1 locus, including MTCH2, were highly correlated with one another and were associated with AD status. We further demonstrate that PILRB, as well as other genes within the GWAS loci, are most highly expressed in microglia. These findings together with the function of PILRB as a DAP12 receptor supports the critical role of microglia and neuroinflammation in AD risk.

  18. Incidence and predictors of suicide attempts in DSM-IV major depressive disorder: a five-year prospective study.

    Science.gov (United States)

    Holma, K Mikael; Melartin, Tarja K; Haukka, Jari; Holma, Irina A K; Sokero, T Petteri; Isometsä, Erkki T

    2010-07-01

    Prospective long-term studies of risk factors for suicide attempts among patients with major depressive disorder have not investigated the course of illness and state at the time of the act. Therefore, the importance of state factors, particularly time spent in risk states, for overall risk remains unknown. In the Vantaa Depression Study, a longitudinal 5-year evaluation of psychiatric patients with major depressive disorder, prospective information on 249 patients (92.6%) was available. Time spent in depressive states and the timing of suicide attempts were investigated with life charts. During the follow-up assessment period, there were 106 suicide attempts per 1,018 patient-years. The incidence rate per 1,000 patient-years during major depressive episodes was 21-fold (N=332 [95% confidence interval [CI]=258.6-419.2]), and it was fourfold during partial remission (N=62 [95% CI=34.6-92.4]) compared with full remission (N=16 [95% CI=11.2-40.2]). In the Cox proportional hazards model, suicide attempts were predicted by the months spent in a major depressive episode (hazard ratio=7.74 [95% CI=3.40-17.6]) or in partial remission (hazard ratio=4.20 [95% CI=1.71-10.3]), history of suicide attempts (hazard ratio=4.39 [95% CI=1.78-10.8]), age (hazard ratio=0.94 [95% CI=0.91-0.98]), lack of a partner (hazard ratio=2.33 [95% CI=0.97-5.56]), and low perceived social support (hazard ratio=3.57 [95% CI=1.09-11.1]). The adjusted population attributable fraction of the time spent depressed for suicide attempts was 78%. Among patients with major depressive disorder, incidence of suicide attempts varies markedly depending on the level of depression, being highest during major depressive episodes. Although previous attempts and poor social support also indicate risk, the time spent depressed is likely the major factor determining overall long-term risk.

  19. Association between proximity to major roads and sputum cell counts

    Science.gov (United States)

    Wallace, Julie; D’silva, Liesel; Brannan, John; Hargreave, Frederick E; Kanaroglou, Pavlos; Nair, Parameswaran

    2011-01-01

    BACKGROUND: Air pollution caused by motor vehicle emissions has been associated with exacerbations of obstructive airway diseases; however, the nature of the resulting bronchitis has not been quantified. OBJECTIVE: To examine whether proximity to major roads or highways is associated with an increase in sputum neutrophils or eosinophils, and to evaluate the effect of proximity to roads on spirometry and exacerbations in patients with asthma. METHODS: A retrospective study of 485 sputum cell counts from patients attending a tertiary chest clinic in Hamilton, Ontario, identified eosinophilic or neutrophilic bronchitis. Patients’ residences were geocoded to the street network of Hamilton using geographic information system software. Associations among bronchitis, lung function, and proximity to major roads and highways were examined using multinomial logistic and multivariate linear regression analyses adjusted for patient age, smoking status and corticosteroid medications. RESULTS: Patients living within 1000 m of highways showed an increased risk of bronchitis (OR 3.8 [95% CI 1.0 to 13.7]; Proad were at increased risk for an asthma exacerbation (OR 1.9 [95% CI 1.5 to 15.5]; Proad was associated with neutrophilic bronchitis, an increased risk of asthma diagnosis, asthma exacerbations and lower lung function. PMID:21369545

  20. Effect of Tryptophan Hydroxylase-2 rs7305115 SNP on suicide attempts risk in major depression

    Directory of Open Access Journals (Sweden)

    Zhang Yuqi

    2010-08-01

    Full Text Available Abstract Background Suicide and major depressive disorders (MDD are strongly associated, and genetic factors are responsible for at least part of the variability in suicide risk. We investigated whether variation at the tryptophan hydroxylase-2 (TPH2 gene rs7305115 SNP may predispose to suicide attempts in MDD. Methods We genotyped TPH2 gene rs7305115 SNP in 215 MDD patients with suicide and matched MDD patients without suicide. Differences in behavioral and personality traits according to genotypic variation were investigated by logistic regression analysis. Results There were no significant differences between MDD patients with suicide and controls in genotypic (AG and GG frequencies for rs7305115 SNP, but the distribution of AA genotype differed significantly (14.4% vs. 29.3%, p p p Conclusions The study suggested that hopelessness, negative life events and family history of suicide were risk factors of attempted suicide in MDD while the TPH2 rs7305115A remained a significant protective predictor of suicide attempts.

  1. Equestrian injuries: incidence, injury patterns, and risk factors for 10 years of major traumatic injuries.

    Science.gov (United States)

    Ball, Chad G; Ball, Jill E; Kirkpatrick, Andrew W; Mulloy, Robert H

    2007-05-01

    Horseback riding is more dangerous than motorcycle riding, skiing, football, and rugby. The purpose of this study was to identify the incidence and injury patterns, as well as risk factors associated with severe equestrian trauma. All patients with major equestrian injuries (injury severity score > or = 12) admitted between 1995 and 2005 were reviewed. A 46-question survey outlining potential rider, animal, and environmental risk factors was administered. Among 7941 trauma patients, 151 (2%) were injured on horseback (mean injury severity score, 20; mortality rate, 7%). Injuries included the chest (54%), head (48%), abdomen (22%), and extremities (17%). Forty-five percent required surgery. Survey results (55%) indicated that riders and horses were well trained, with a 47% recidivism rate. Only 9% of patients wore helmets, however, 64% believed the accident was preventable. Chest trauma previously has been underappreciated. This injury pattern may be a result of significant rider experience. Helmet and vest use will be targeted in future injury prevention strategies.

  2. [Incidence and risk factors of venous thromboembolism in major spinal surgery with no chemical or mechanical prophylaxis].

    Science.gov (United States)

    Rojas-Tomba, F; Gormaz-Talavera, I; Menéndez-Quintanilla, I E; Moriel-Durán, J; García de Quevedo-Puerta, D; Villanueva-Pareja, F

    2016-01-01

    To evaluate the incidence of venous thromboembolism in spine surgery with no chemical and mechanical prophylaxis, and to determine the specific risk factors for this complication. A historical cohort was analysed. All patients subjected to major spinal surgery, between January 2010 and September 2014, were included. No chemical or mechanical prophylaxis was administered in any patient. Active mobilisation of lower limbs was indicated immediately after surgery, and early ambulation started in the first 24-48 hours after surgery. Clinically symptomatic cases were confirmed by Doppler ultrasound of the lower limbs or chest CT angiography. A sample of 1092 cases was studied. Thromboembolic events were observed in 6 cases (.54%); 3 cases (.27%) with deep venous thrombosis and 3 cases (.27%) with pulmonary thromboembolism. A lethal case was identified (.09%). There were no cases of major bleeding or epidural haematoma. The following risk factors were identified: a multilevel fusion at more than 4 levels, surgeries longer than 130 minutes, patients older than 70 years of age, hypertension, and degenerative scoliosis. There is little scientific evidence on the prevention of thromboembolic events in spinal surgery. In addition to the disparity of prophylactic methods indicated by different specialists, it is important to weigh the risk-benefit of intra- and post-operative bleeding, and even the appearance of an epidural haematoma. Prophylaxis should be assessed in elderly patients over 70 years old, who are subjected to surgeries longer than 130 minutes, when 4 or more levels are involved. Copyright © 2015 SECOT. Published by Elsevier Espana. All rights reserved.

  3. Evolution of the major merger galaxy pair fraction at z < 1

    Energy Technology Data Exchange (ETDEWEB)

    Keenan, R. C.; Hsieh, B. C.; Lin, L.; Chou, R. C. Y.; Huang, S.; Lin, J. H.; Chang, K. H. [Academia Sinica Institute for Astronomy and Astrophysics, Taipei, Taiwan (China); Foucaud, S. [Shanghai Jiao Tong University, Shanghai (China); De Propris, R. [Finnish Centre for Astronomy with ESO (FINCA), University of Turku, Turku (Finland)

    2014-11-10

    We present a study of the largest available sample of near-infrared selected (i.e., stellar mass selected) dynamically close pairs of galaxies at low redshifts (z < 0.3). We combine this sample with new estimates of the major merger pair fraction for stellar mass selected galaxies at z < 0.8, from the Red Sequence Cluster Survey (RCS1). We construct our low-redshift K-band selected sample using photometry from the UKIRT Infrared Deep Sky Survey and the Two Micron All Sky Survey (2MASS) in the K band (∼2.2 μm). Combined with all available spectroscopy, our K-band selected sample contains ∼250, 000 galaxies and is >90% spectroscopically complete. The depth and large volume of this sample allow us to investigate the low-redshift pair fraction and merger rate of galaxies over a wide range in K-band luminosity. We find the major merger pair fraction to be flat at ∼2% as a function of K-band luminosity for galaxies in the range 10{sup 8}-10{sup 12} L {sub ☉}, in contrast to recent results from studies in the local group that find a substantially higher low-mass pair fraction. This low-redshift major merger pair fraction is ∼40%-50% higher than previous estimates drawn from K-band samples, which were based on 2MASS photometry alone. Combining with the RCS1 sample, we find a much flatter evolution (m = 0.7 ± 0.1) in the relation f {sub pair}∝(1 + z) {sup m} than indicated in many previous studies. These results indicate that a typical L ∼ L* galaxy has undergone ∼0.2-0.8 major mergers since z = 1 (depending on the assumptions of merger timescale and percentage of pairs that actually merge).

  4. Evolution of the major merger galaxy pair fraction at z < 1

    International Nuclear Information System (INIS)

    Keenan, R. C.; Hsieh, B. C.; Lin, L.; Chou, R. C. Y.; Huang, S.; Lin, J. H.; Chang, K. H.; Foucaud, S.; De Propris, R.

    2014-01-01

    We present a study of the largest available sample of near-infrared selected (i.e., stellar mass selected) dynamically close pairs of galaxies at low redshifts (z < 0.3). We combine this sample with new estimates of the major merger pair fraction for stellar mass selected galaxies at z < 0.8, from the Red Sequence Cluster Survey (RCS1). We construct our low-redshift K-band selected sample using photometry from the UKIRT Infrared Deep Sky Survey and the Two Micron All Sky Survey (2MASS) in the K band (∼2.2 μm). Combined with all available spectroscopy, our K-band selected sample contains ∼250, 000 galaxies and is >90% spectroscopically complete. The depth and large volume of this sample allow us to investigate the low-redshift pair fraction and merger rate of galaxies over a wide range in K-band luminosity. We find the major merger pair fraction to be flat at ∼2% as a function of K-band luminosity for galaxies in the range 10 8 -10 12 L ☉ , in contrast to recent results from studies in the local group that find a substantially higher low-mass pair fraction. This low-redshift major merger pair fraction is ∼40%-50% higher than previous estimates drawn from K-band samples, which were based on 2MASS photometry alone. Combining with the RCS1 sample, we find a much flatter evolution (m = 0.7 ± 0.1) in the relation f pair ∝(1 + z) m than indicated in many previous studies. These results indicate that a typical L ∼ L* galaxy has undergone ∼0.2-0.8 major mergers since z = 1 (depending on the assumptions of merger timescale and percentage of pairs that actually merge).

  5. CYP1A1 MspI Polymorphism and Cervical Carcinoma Risk in the Multi-Ethnic Population of Malaysia: a Case-Control Study.

    Science.gov (United States)

    Tan, Yee Hock; Sidik, Shiran Mohd; Syed Husain, Sharifah Noor Akmal; Lye, Munn Sann; Chong, Pei Pei

    2016-01-01

    Tobacco smoking is considered a risk factor for cervical cancer development due to the presence of tobacco based carcinogenic metabolites in cervical cells of female smokers. In this study, we investigated the role of the T3801C (MspI) polymorphism of CYP1A1, a gene encoding an enzyme necessary for the initiation of tobacco based carcinogen metabolism, on cervical cancer risk. The T to C substitution may alter CYP1A1 activities, potentially elevating cervical cancer risk. Since results of gene-disease association studies vary according to the study population, the multi-ethnic population of Malaysia provides an excellent representative cohort for identifying and comparing the cervical cancer risk among the 3 major ethnics in Southeast Asia in relation to CYP1A1 MspI polymorphism. A total of 195 Thin Prep Pap smear samples from HPV negative and cancer free females were randomly selected as controls while 106 formalin fixed paraffin embedded samples from females with invasive cervical cancer were randomly selected for the cases group. The polymorphisms were identified using restriction fragment length polymorphism (RFLP) PCR. We found no significant associations between CYP1A1 MspI polymorphism and cervical cancer in the general Malaysian female population. However, upon ethnic stratification, the variant C/C genotype was significantly associated with a 4.66-fold increase in cervical cancer risk in Malay females (95% CI= 1.21-17.9; p=0.03). No significant association was observed in the Chinese and Indian females. Additionally, there were no significant associations in the dominant model and allele frequency model analysis in both the general and ethnically stratified female population of Malaysia. Our findings suggest that the C/C genotype of CYP1A1 MspI polymorphism is associated with the development of cervical carcinoma in the Malay females of Malaysia.

  6. HNF1B and endometrial cancer risk: results from the PAGE study.

    Directory of Open Access Journals (Sweden)

    Veronica Wendy Setiawan

    Full Text Available We examined the association between HNF1B variants identified in a recent genome-wide association study and endometrial cancer in two large case-control studies nested in prospective cohorts: the Multiethnic Cohort Study (MEC and the Women's Health Initiative (WHI as part of the Population Architecture using Genomics and Epidemiology (PAGE study. A total of 1,357 incident cases of invasive endometrial cancer and 7,609 controls were included in the analysis (MEC: 426 cases/3,854 controls; WHI: 931 cases/3,755 controls. The majority of women in the WHI were European American, while the MEC included sizable numbers of African Americans, Japanese and Latinos. We estimated the odds ratios (ORs per allele and 95% confidence intervals (CIs of each SNP using unconditional logistic regression adjusting for age, body mass index, and four principal components of ancestry informative markers. The combined ORs were estimated using fixed effect models. Rs4430796 and rs7501939 were associated with endometrial cancer risk in MEC and WHI with no heterogeneity observed across racial/ethnic groups (P ≥ 0.21 or between studies (P ≥ 0.70. The OR(per allele was 0.82 (95% CI: 0.75, 0.89; P = 5.63 × 10(-6 for rs4430796 (G allele and 0.79 (95% CI: 0.73, 0.87; P = 3.77 × 10(-7 for rs7501939 (A allele. The associations with the risk of Type I and Type II tumors were similar (P ≥ 0.19. Adjustment for additional endometrial cancer risk factors such as parity, oral contraceptive use, menopausal hormone use, and smoking status had little effect on the results. In conclusion, HNF1B SNPs are associated with risk of endometrial cancer and that the associated relative risks are similar for Type I and Type II tumors.

  7. SNP association mapping across the extended major histocompatibility complex and risk of B-cell precursor acute lymphoblastic leukemia in children.

    Directory of Open Access Journals (Sweden)

    Kevin Y Urayama

    Full Text Available The extended major histocompatibility complex (xMHC is the most gene-dense region of the genome and harbors a disproportionately large number of genes involved in immune function. The postulated role of infection in the causation of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL suggests that the xMHC may make an important contribution to the risk of this disease. We conducted association mapping across an approximately 4 megabase region of the xMHC using a validated panel of single nucleotide polymorphisms (SNPs in childhood BCP-ALL cases (n=567 enrolled in the Northern California Childhood Leukemia Study (NCCLS compared with population controls (n=892. Logistic regression analyses of 1,145 SNPs, adjusted for age, sex, and Hispanic ethnicity indicated potential associations between several SNPs and childhood BCP-ALL. After accounting for multiple comparisons, one of these included a statistically significant increased risk associated with rs9296068 (OR=1.40, 95% CI=1.19-1.66, corrected p=0.036, located in proximity to HLA-DOA. Sliding window haplotype analysis identified an additional locus located in the extended class I region in proximity to TRIM27 tagged by a haplotype comprising rs1237485, rs3118361, and rs2032502 (corrected global p=0.046. Our findings suggest that susceptibility to childhood BCP-ALL is influenced by genetic variation within the xMHC and indicate at least two important regions for future evaluation.

  8. Investigating the Impact of a Genome-Wide Supported Bipolar Risk Variant of MAD1L1 on the Human Reward System.

    Science.gov (United States)

    Trost, Sarah; Diekhof, Esther K; Mohr, Holger; Vieker, Henning; Krämer, Bernd; Wolf, Claudia; Keil, Maria; Dechent, Peter; Binder, Elisabeth B; Gruber, Oliver

    2016-10-01

    Recent genome-wide association studies have identified MAD1L1 (mitotic arrest deficient-like 1) as a susceptibility gene for bipolar disorder and schizophrenia. The minor allele of the single-nucleotide polymorphism (SNP) rs11764590 in MAD1L1 was associated with bipolar disorder. Both diseases, bipolar disorder and schizophrenia, are linked to functional alterations in the reward system. We aimed at investigating possible effects of the MAD1L1 rs11764590 risk allele on reward systems functioning in healthy adults. A large homogenous sample of 224 young (aged 18-31 years) participants was genotyped and underwent functional magnetic resonance imaging (fMRI). All participants performed the 'Desire-Reason Dilemma' paradigm investigating the neural correlates that underlie reward processing and active reward dismissal in favor of a long-term goal. We found significant hypoactivations of the ventral tegmental area (VTA), the bilateral striatum and bilateral frontal and parietal cortices in response to conditioned reward stimuli in the risk allele carriers compared with major allele carriers. In the dilemma situation, functional connectivity between prefrontal brain regions and the ventral striatum was significantly diminished in the risk allele carriers. Healthy risk allele carriers showed a significant deficit of their bottom-up response to conditioned reward stimuli in the bilateral VTA and striatum. Furthermore, functional connectivity between the ventral striatum and prefrontal areas exerting top-down control on the mesolimbic reward system was reduced in this group. Similar alterations in reward processing and disturbances of prefrontal control mechanisms on mesolimbic brain circuits have also been reported in bipolar disorder and schizophrenia. Together, these findings suggest the existence of an intermediate phenotype associated with MAD1L1.

  9. Family history predicts major adverse cardiovascular events (MACE) in young adults with psoriasis

    DEFF Research Database (Denmark)

    Egeberg, Alexander; Bruun, Louise E; Mallbris, Lotus

    2016-01-01

    BACKGROUND: Patients with psoriasis may have increased risk of major adverse cardiovascular (CV) events (MACE), and a family history of CV disease (CVD) is an independent risk factor for MACE. OBJECTIVE: We investigated the risk of first-time MACE in patients with psoriasis with or without a fami....... The findings call for increased focus on a family history of CVD in CV risk assessment of patients with psoriasis.......BACKGROUND: Patients with psoriasis may have increased risk of major adverse cardiovascular (CV) events (MACE), and a family history of CV disease (CVD) is an independent risk factor for MACE. OBJECTIVE: We investigated the risk of first-time MACE in patients with psoriasis with or without a family...... history of CVD. METHODS: Between January 1, 1997, and December 31, 2011, we identified 2,722,375 individuals, including 25,774 and 4504 patients with mild and severe psoriasis, through administrative registers. Incidence rate ratios were estimated by Poisson regression. RESULTS: Mean baseline age was 26...

  10. Risk factors for postoperative delirium in patients undergoing major head and neck cancer surgery: a meta-analysis.

    Science.gov (United States)

    Zhu, Yun; Wang, Gangpu; Liu, Shengwen; Zhou, Shanghui; Lian, Ying; Zhang, Chenping; Yang, Wenjun

    2017-06-01

    Postoperative delirium is common after extensive surgery. This study aimed to collate and synthesize published literature on risk factors for delirium in patients with head and neck cancer surgery. Three databases were searched (MEDLINE, Embase, and Cochrane Library) between January 1987 and July 2016. The Newcastle Ottawa Scale (NOS) was adopted to evaluate the study quality. Pooled odds ratios or mean differences for individual risk factors were estimated using the Mantel-Haenszel and inverse-variance methods. They provided a total of 1940 patients (286 with delirium and 1654 without), and predominantly included patients undergoing head and neck cancer surgery. The incidence of postoperative delirium ranged from 11.50% to 36.11%. Ten statistically significant risk factors were identified in pooled analysis. Old age, age >70 years, male sex, duration of surgery, history of hypertension, blood transfusions, tracheotomy, American Society of Anesthesiologists physical status grade at least III, flap reconstruction and neck dissection were more likely to sustain delirium after head and neck cancer surgery. Delirium is common in patients undergoing major head neck cancer surgery. Several risk factors were consistently associated with postoperative delirium. These factors help to highlight patients at risk of developing delirium and are suitable for preventive action. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  11. Major life events and development of major depression in Parkinson's disease patients

    DEFF Research Database (Denmark)

    Rod, Naja Hulvej; Bordelon, Y; Thompson, A

    2012-01-01

    BACKGROUND AND PURPOSE: Non-motor symptoms including depression are important features of Parkinson's disease (PD). We aim to address the relationship between major life events and depression amongst PD patients free of depressive symptoms at baseline. METHODS: New-onset PD patients from California...... were recruited in 2001-2007 and followed up for 3-4 years. The participants (n = 221) were examined by neurologists and responded to comprehensive interviews that included major life events, social support, and coping measures from validated scales. Major depression was assessed using the Structured...... Clinical Interview for the DSM-IV depression module (SCID). RESULTS: More than half of all patients had experienced major life events since diagnosed with PD, and 22 patients developed a major depression. The number of life events was associated with risk of depression in an exposure-dependent manner...

  12. Isogenic Cellular Systems Model the Impact of Genetic Risk Variants in the Pathogenesis of Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Mark A. Wallet

    2017-10-01

    Full Text Available At least 57 independent loci within the human genome confer varying degrees of risk for the development of type 1 diabetes (T1D. The majority of these variants are thought to contribute to overall genetic risk by modulating host innate and adaptive immune responses, ultimately resulting in a loss of immunological tolerance to β cell antigens. Early efforts to link specific risk variants with functional alterations in host immune responses have employed animal models or genotype-selected individuals from clinical bioresource banks. While some notable genotype:phenotype associations have been described, there remains an urgent need to accelerate the discovery of causal variants and elucidate the molecular mechanisms by which susceptible alleles alter immune functions. One significant limitation has been the inability to study human T1D risk loci on an isogenic background. The advent of induced pluripotent stem cells (iPSCs and genome-editing technologies have made it possible to address a number of these outstanding questions. Specifically, the ability to drive multiple cell fates from iPSC under isogenic conditions now facilitates the analysis of causal variants in multiple cellular lineages. Bioinformatic analyses have revealed that T1D risk genes cluster within a limited number of immune signaling pathways, yet the relevant immune cell subsets and cellular activation states in which candidate risk genes impact cellular activities remain largely unknown. In this review, we summarize the functional impact of several candidate risk variants on host immunity in T1D and present an isogenic disease-in-a-dish model system for interrogating risk variants, with the goal of expediting precision therapeutics in T1D.

  13. Unique and cross-reactive T cell epitope peptides of the major Bahia grass pollen allergen, Pas n 1.

    Science.gov (United States)

    Etto, Tamara; de Boer, Carmela; Prickett, Sara; Gardner, Leanne M; Voskamp, Astrid; Davies, Janet M; O'Hehir, Robyn E; Rolland, Jennifer M

    2012-01-01

    Bahia grass pollen (BaGP) is a major cause of allergic rhinitis. Subcutaneous allergen-specific immunotherapy is effective for grass pollen allergy, but is unsuitable for patients with moderate to severe asthma due to the risk of anaphylaxis. T cell-reactive but IgE nonreactive peptides provide a safer treatment option. This study aimed to identify and characterize dominant CD4(+) T cell epitope peptides of the major BaGP allergen, Pas n 1. Pas n 1-specific T cell lines generated from the peripheral blood of BaGP-allergic subjects were tested for proliferative and cytokine response to overlapping 20-mer Pas n 1 peptides. Cross-reactivity to homologous peptides from Lol p 1 and Cyn d 1 of Ryegrass and Bermuda grass pollen, respectively, was assessed using Pas n 1 peptide-specific T cell clones. MHC class II restriction of Pas n 1 peptide T cell recognition was determined by HLA blocking assays and peptide IgE reactivity tested by dot blotting. Three Pas n 1 peptides showed dominant T cell reactivity; 15 of 18 (83%) patients responded to one or more of these peptides. T cell clones specific for dominant Pas n 1 peptides showed evidence of species-specific T cell reactivity as well as cross-reactivity with other group 1 grass pollen allergens. The dominant Pas n 1 T cell epitope peptides showed HLA binding diversity and were non-IgE reactive. The immunodominant T cell-reactive Pas n 1 peptides are candidates for safe immunotherapy for individuals, including those with asthma, who are allergic to Bahia and possibly other grass pollens. Copyright © 2012 S. Karger AG, Basel.

  14. [Chances and risks of prevention in elderly people for the three major cancers: breast-, prostate- and colorectal cancers].

    Science.gov (United States)

    Kolb, G F

    2006-06-01

    The big three, breast cancer (BC), prostate cancer (PC) and colorectal carcinoma are the most frequent malignancies world wide and also typical tumors of advanced age. Therefore the question to screen and how to screen for these tumors in the elderly is the main question for reduction of the total cancer burden and mortality in all western countries. BREAST CANCER (BC): The age related risk of BC increases from 1 : 2,500 at age 30+ to > 1 : 10 at age 80. Nevertheless, most of the national BC-Screening-Programs stop at age 60 or earlier. Therefore the majority of all advanced i. e. T (4) stages of BC are found in women age > 60. Frequently it is suggested that age related comorbidity should eliminate the benefit of treatment. Recently two longitudinal studies have clearly shown that correct standard treatment is as effective in elderly as in younger individuals. Mammography (MG) has been shown to reduce mortality of BC significantly with best results for specificity and sensitivity at age 70+. PROSTATE CANCER (PC): The screening situation of PC is quite different to BC, because risk profiles are poorly defined and the benefit of radical prostatectomy is not clearly demonstrated in the early non symptomatic stages of PC. At the other side watchful waiting leads to an elevated frequency of incontinence and enuresis as well. Two studies are now under progress and may possibly change the situation; but the final results are expected 2005-2008 at the earliest. Therefore an assisted individual decision making is the only recommendation at this time. COLORECTAL CANCER (CC): Risk groups are clearly defined. Risk of the elderly (> 60) is the average risk. The incidence increases from informed about complication rates of colonoscopy during the screening programs. There is a lack of data according accuracy of barium enema, virtual colonoscopy and genetic stool test in comparison to colonoscopy in combination with fecal occult blood test (FOBT). And adherence to screening is

  15. The impact of Cytochrome P450 CYP1A2, CYP2C9, CYP2C19 and CYP2D6 genes on suicide attempt and suicide risk-a European multicentre study on treatment-resistant major depressive disorder.

    Science.gov (United States)

    Höfer, Peter; Schosser, Alexandra; Calati, Raffaella; Serretti, Alessandro; Massat, Isabelle; Kocabas, Neslihan Aygun; Konstantinidis, Anastasios; Linotte, Sylvie; Mendlewicz, Julien; Souery, Daniel; Zohar, Joseph; Juven-Wetzler, Alzbeta; Montgomery, Stuart; Kasper, Siegfried

    2013-08-01

    Recently published data have reported associations between cytochrome P450 metabolizer status and suicidality. The aim of our study was to investigate the role of genetic polymorphisms of the cytochrome P450 genes on suicide risk and/or a personal history of suicide attempts. Two hundred forty-three major depressive disorder patients were collected in the context of a European multicentre resistant depression study and treated with antidepressants at adequate doses for at least 4 weeks. Suicidality was assessed using the Mini International Neuropsychiatric Interview and the Hamilton Rating Scale for Depression (HAM-D). Treatment response was defined as HAM-D ≤ 17 and remission as HAM-D ≤ 7 after 4 weeks of treatment with antidepressants at adequate dose. Genotyping was performed for all relevant variations of the CYP1A2 gene (*1A, *1F, *1C, *1 J, *1 K), the CYP2C9 gene (*2, *3), the CYP2C19 gene (*2, *17) and the CYP2D6 gene (*3, *4, *5, *6, *9, *19, *XN). No association between both suicide risk and personal history of suicide attempts, and the above mentioned metabolic profiles were found after multiple testing corrections. In conclusion, the investigated cytochrome gene polymorphisms do not seem to be associated with suicide risk and/or a personal history of suicide attempts, though methodological and sample size limitations do not allow definitive conclusions.

  16. Major League pitching workload after primary ulnar collateral ligament reconstruction and risk for revision surgery.

    Science.gov (United States)

    Keller, Robert A; Mehran, Nima; Marshall, Nathan E; Okoroha, Kelechi R; Khalil, Lafi; Tibone, James E; Moutzouros, Vasilios

    2017-02-01

    Literature has attempted to correlate pitching workload with risk of ulnar collateral ligament (UCL) injury; however, limited data are available in evaluating workload and its relationship with the need for revision reconstruction in Major League Baseball (MLB) pitchers. We identified 29 MLB pitchers who underwent primary UCL reconstruction surgery and subsequently required revision reconstruction and compared them with 121 MLB pitchers who underwent primary reconstruction but did not later require revision surgery. Games pitched, pitch counts, and innings pitched were evaluated and compared for the seasons after returning from primary reconstruction and for the last season pitched before undergoing revision surgery. The difference in workload between pitchers who did and did not require revision reconstruction was not statistically significant in games pitched, innings pitched, and MLB-only pitch counts. The one significant difference in workload was in total pitch counts (combined MLB and minor league), with the pitchers who required revision surgery pitching less than those who did not (primary: 1413.6 pitches vs. revision: 959.0 pitches, P = .04). In addition, pitchers who required revision surgery underwent primary reconstruction at an early age (22.9 years vs. 27.3 years, P risk for injury after primary UCL reconstruction. However, correlations of risk may be younger age and less MLB experience at the time of the primary reconstruction. Copyright © 2017. Published by Elsevier Inc.

  17. Breast and Ovarian Cancer Risk and Risk Reduction in Jewish BRCA1/2 Mutation Carriers

    Science.gov (United States)

    Finkelman, Brian S.; Rubinstein, Wendy S.; Friedman, Sue; Friebel, Tara M.; Dubitsky, Shera; Schonberger, Niecee Singer; Shoretz, Rochelle; Singer, Christian F.; Blum, Joanne L.; Tung, Nadine; Olopade, Olufunmilayo I.; Weitzel, Jeffrey N.; Lynch, Henry T.; Snyder, Carrie; Garber, Judy E.; Schildkraut, Joellen; Daly, Mary B.; Isaacs, Claudine; Pichert, Gabrielle; Neuhausen, Susan L.; Couch, Fergus J.; van't Veer, Laura; Eeles, Rosalind; Bancroft, Elizabeth; Evans, D. Gareth; Ganz, Patricia A.; Tomlinson, Gail E.; Narod, Steven A.; Matloff, Ellen; Domchek, Susan; Rebbeck, Timothy R.

    2012-01-01

    Purpose Mutations in BRCA1/2 dramatically increase the risk of both breast and ovarian cancers. Three mutations in these genes (185delAG, 5382insC, and 6174delT) occur at high frequency in Ashkenazi Jews. We evaluated how these common Jewish mutations (CJMs) affect cancer risks and risk reduction. Methods Our cohort comprised 4,649 women with disease-associated BRCA1/2 mutations from 22 centers in the Prevention and Observation of Surgical End Points Consortium. Of these women, 969 were self-identified Jewish women. Cox proportional hazards models were used to estimate breast and ovarian cancer risks, as well as risk reduction from risk-reducing salpingo-oophorectomy (RRSO), by CJM and self-identified Jewish status. Results Ninety-one percent of Jewish BRCA1/2-positive women carried a CJM. Jewish women were significantly more likely to undergo RRSO than non-Jewish women (54% v 41%, respectively; odds ratio, 1.87; 95% CI, 1.44 to 2.42). Relative risks of cancer varied by CJM, with the relative risk of breast cancer being significantly lower in 6174delT mutation carriers than in non-CJM BRCA2 carriers (hazard ratio, 0.35; 95% CI, 0.18 to 0.69). No significant difference was seen in cancer risk reduction after RRSO among subgroups. Conclusion Consistent with previous results, risks for breast and ovarian cancer varied by CJM in BRCA1/2 carriers. In particular, 6174delT carriers had a lower risk of breast cancer. This finding requires additional confirmation in larger prospective and population-based cohort studies before being integrated into clinical care. PMID:22430266

  18. Decree no 90-918 of 11 october 1990 on exercising rights to information on major risks, in implementation of Section 21 of act no 87-565 of 22 july 1987 on the organisation of public safety measures, forestry protection against fires and prevention of major risks

    International Nuclear Information System (INIS)

    1990-01-01

    This Decree specifies the content and type of information to which persons likely to be exposed to major risks must have access, in accordance with the 1987 Act. These provisions apply in the communes for which a special action plan has been prepared. The information includes a description of the risks and their foreseeable consequences for persons, property and the environment, and a statement on the preventive measures to limit their effects. A summary record of this information is established [fr

  19. TIMP-1 expression in human colorectal cancer is associated with TGF-B1, LOXL2, INHBA1, TNF-AIP6 and TIMP-2 transcript profiles

    DEFF Research Database (Denmark)

    Offenberg, Hanne Kjær; Brunner, Nils; Mansilla, Francisco

    2008-01-01

    colorectal cancer (CRC) and the other TIMPs 2-4, which have also been associated with the progression of colorectal cancer. Genome-wide expression profiling of 172 CRC and normal mucosa samples was used to identify transcript changes for the genes under investigation. We found that TIMP-1 was up...... with the synthesis of extracellullar matrix, genes involved in the TGF-beta signalling pathway, and genes that are likely transcribed by the tumour cells. These insights add to the complex picture emerging about the regulation of TIMPs in colorectal cancer....... that colorectal cancer patients have increased plasma levels of the tissue inhibitor of metalloproteinases-1 (TIMP-1), and that high plasma TIMP-1 levels are associated with short colorectal cancer patient survival. However, although TIMP-1 has been extensively studied in cancer, very little is known about how...

  20. A resilience engineering approach to assess major accident risks

    DEFF Research Database (Denmark)

    Hollnagel, E.

    2013-01-01

    This chapter describes how the principles of Resilience Engineering can be used to make a risk assessment of an Integrated Operations (IO) scenario. It refers to the case study provided in Chapter 12.......This chapter describes how the principles of Resilience Engineering can be used to make a risk assessment of an Integrated Operations (IO) scenario. It refers to the case study provided in Chapter 12....

  1. The Oft-Neglected Role of Parietal EEG Asymmetry and Risk for Major Depressive Disorder

    Science.gov (United States)

    Stewart, Jennifer L.; Towers, David N.; Coan, James A.; Allen, John J.B.

    2010-01-01

    Relatively less right parietal activity may reflect reduced arousal and signify risk for major depressive disorder (MDD). Inconsistent findings with parietal electroencephalographic (EEG) asymmetry, however, suggest issues such as anxiety comorbidity and sex differences have yet to be resolved. Resting parietal EEG asymmetry was assessed in 306 individuals (31% male) with (n = 143) and without (n = 163) a DSM-IV diagnosis of lifetime MDD and no comorbid anxiety disorders. Past MDD+ women displayed relatively less right parietal activity than current MDD+ and MDD- women, replicating prior work. Recent caffeine intake, an index of arousal, moderated the relationship between depression and EEG asymmetry for women and men. Findings suggest that sex differences and arousal should be examined in studies of depression and regional brain activity. PMID:20525011

  2. Operating performance and environmental and safety risks: A preliminary comparison of majors and independents

    International Nuclear Information System (INIS)

    Pulsipher, A.G.; Iledare, W.O.; Baumann, R.H.; Mesyanzhinov, D.

    1995-01-01

    The objective is to compare the safety and environmental records of oil and gas companies operating on the OCS in the Gulf of Mexico over the past decade. The reason for doing so is to help inform public sector policy-makers and private sector decision-makers about the potential safety and environmental risks associated with the expected increased presence of smaller independents in the domestic oil and gas industry in general and on the federal OCS in particular. The preliminary conclusion is that although independents have had a modestly high incidence of fires and explosions than the majors, the difference is not significant statistically and is largely attributable to a few ''bad actors'' rather than demonstrably poorer practice by the group as a whole

  3. Risk zoning around nuclear power plants in comparison to other major hazardous industrial installations

    International Nuclear Information System (INIS)

    Kirchsteiger, Christian

    2006-01-01

    The background and current status of the information basis leading to the definition of risk and emergency zones around Nuclear Power Plants (NPPs) in different countries in Europe and beyond are analysed. Although dependable plant-specific Probabilistic Safety Assessment (PSA) of Level 2 and/or Level 3 could in principle provide sufficiently detailed input to define the geographical dimension of a NPP's risk and emergency zones, the analysis of the status in some European and other countries shows that other, 'deterministic' approaches using a Reference Accident are actually used in practice. Regarding use of Level 2 PSA for emergency planning, the approach so far has been to use the Level 2 PSA information retrospectively to provide the justification for the choice of Reference Accident(s) used to define the emergency plans and Emergency Planning Zones (EPZs). There are significant differences in the EPZs that are defined in different countries, ranging from about 1 km to 30 km. Further, there is a striking contrast in the extent of using probabilistic information to define emergency zones between the nuclear and other high risk industry sectors, such as the chemical process industry, and the reasons for these differences are not entirely clear, but seem to be more related to risk perception than actual risk potential. Finally, based on consensus discussions at a recent JRC/OECD International Seminar on Risk and Emergency Zoning around NPPs, recommendations are given in the areas of more comprehensive use of available risk information for risk zoning purposes, risk communication and comparative risk assessment. (author)

  4. A Cross Sectional Study of Kretek Smoking in Indonesia as a Major Risk to Public Health.

    Science.gov (United States)

    Palipudi, Krishna; Mbulo, Lazarous; Kosen, Soewarte; Tjandra, Aditama; Kadarmanto; Qureshi, Farukh; Andes, Linda; Sinha, Dhirendra N; Asma, Samira

    2015-01-01

    Tobacco smoking is a major cause of preventable disease and death worldwide. Kreteks are clove-flavored cigarettes made from a combination of tobacco and ground-clove mixed with a sauce, smoked widely in Indonesia. Because health and social consequences of kretek smoking are potentially as great as those of traditional cigarettes, this study examines the prevalence of kretek smoking in Indonesia and associated risk factors. The study used nationally representative Indonesia Global Adult Tobacco Survey data. Multiple logistic regression analysis was employed to identify correlates of kretek smoking. One- third of Indonesian adults smoked tobacco of which about 90.0% smoked kreteks. Prevalence of kretek smoking among men (60.9%) was more than 25 times the rate among women (2.3%). Overall, the highest prevalence of kretek use was in the age group 45-54 years (36.5%), followed by 34-44 (35.1%), 25-34 (34.2 %), and 55-64 years (32.8%). By wealth index, prevalence of kreteks smoking among those in the middle index was almost 50% above the rate for the wealthiest group (36.4% vs 24.8% respectively). Logistic regression results showed that being male, being older, having less education, and being less wealthy were significant predictors of kretek smoking, while urban vs rural residence was not. Kretek smoking is common in Indonesia and is entrenched in the sociocultural fabric of the country. However, potential consequences of kretek smoking, particularly as risks for noncommunicable diseases, underscore the importance of a comprehensive approach to tobacco control as outlined in the World Health Organization's MPOWER strategies.

  5. Bipolar polygenic loading and bipolar spectrum features in major depressive disorder

    Science.gov (United States)

    Wiste, Anna; Robinson, Elise B; Milaneschi, Yuri; Meier, Sandra; Ripke, Stephan; Clements, Caitlin C; Fitzmaurice, Garrett M; Rietschel, Marcella; Penninx, Brenda W; Smoller, Jordan W; Perlis, Roy H

    2014-01-01

    Objectives Family and genetic studies indicate overlapping liability for major depressive disorder and bipolar disorder. The purpose of this study was to determine whether this shared genetic liability influences clinical presentation. Methods A polygenic risk score for bipolar disorder, derived from a large genome-wide association meta-analysis, was generated for each subject of European–American ancestry (n = 1,274) in the Sequential Treatment Alternatives to Relieve Depression study (STAR*D) outpatient major depressive disorder cohort. A hypothesis-driven approach was used to test for association between bipolar disorder risk score and features of depression associated with bipolar disorder in the literature. Follow-up analyses were performed in two additional cohorts. Results A generalized linear mixed model including seven features hypothesized to be associated with bipolar spectrum illness was significantly associated with bipolar polygenic risk score [F = 2.07, degrees of freedom (df) = 7, p = 0.04). Features included early onset, suicide attempt, recurrent depression, atypical depression, subclinical mania, subclinical psychosis, and severity. Post-hoc univariate analyses demonstrated that the major contributors to this omnibus association were onset of illness at age ≤ 18 years [odds ratio (OR) = 1.2, p = 0.003], history of suicide attempt (OR = 1.21, p = 0.03), and presence of at least one manic symptom (OR = 1.16, p = 0.02). The maximal variance in these traits explained by polygenic score ranged from 0.8–1.1%. However, analyses in two replication cohorts testing a five feature model did not support this association. Conclusions Bipolar genetic loading appeared to be associated with bipolar-like presentation in major depressive disorder in the primary analysis. However, results are at most inconclusive because of lack of replication. Replication efforts are challenged by different ascertainment and assessment strategies in the different cohorts

  6. Configuration of risk monitor system by plant defense-in-depth risk monitor and reliability monitor

    International Nuclear Information System (INIS)

    Yoshikawa, Hidekazu; Lind Morten; Yang Ming; Hashim Muhammad; Zhang Zhijian

    2012-01-01

    A new method of risk monitor system of a nuclear power plant has been proposed from the aspect by what degree of safety functions incorporated in the plant system is maintained by multiple barriers of defense-in-depth (DiD). Wherein, the central idea is plant DiD risk monitor and reliability monitor derived from the five aspects of (1) design principle of nuclear safety based on DiD concept, (2) definition of risk and risk to be monitored, (3) severe accident phenomena as major risk, (4) scheme of risk ranking, and (5) dynamic risk display. In this paper, the overall frame of the proposed risk monitor system is summarized and the detailed discussion is made on major items such as definition of risk and risk ranking, anatomy of fault occurrence, two-layer configuration of risk monitor, how to configure individual elements of plant DiD risk monitor, and lastly how to apply for a PWR safety system. (author)

  7. Assessing the contribution of borderline personality disorder and features to suicide risk in psychiatric inpatients with bipolar disorder, major depression and schizoaffective disorder.

    Science.gov (United States)

    Zeng, Ruifan; Cohen, Lisa J; Tanis, Thachell; Qizilbash, Azra; Lopatyuk, Yana; Yaseen, Zimri S; Galynker, Igor

    2015-03-30

    Suicidal behavior often accompanies both borderline personality disorder (BPD) and severe mood disorders, and comorbidity between the two appears to further increase suicide risk. The current study aims to quantify the risk of suicidality conferred by comorbid BPD diagnosis or features in three affective disorders: major depressive disorder (MDD), bipolar disorder (BP) and schizoaffective disorder. One hundred forty-nine (149) psychiatric inpatients were assessed by SCID I and II, and the Columbia Suicide Severity Rating Scale. Logistic regression analyses investigated the associations between previous suicide attempt and BPD diagnosis or features in patients with MDD, BP, and schizoaffective disorder, as well as a history of manic or major depressive episodes, and psychotic symptoms. Comorbid BPD diagnosis significantly increased suicide risk in the whole sample, and in those with MDD, BP, and history of depressive episode or psychotic symptoms. Each additional borderline feature also increased risk of past suicide attempt in these same groups (excepting BP) and in those with a previous manic episode. Of the BPD criteria, only unstable relationships and impulsivity independently predicted past suicide attempt. Overall, among patients with severe mood disorders, the presence of comorbid BPD features or disorder appears to substantially increase the risk of suicide attempts. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Use of the Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) for improving the accuracy of the risk classification of type 1 diabetes.

    Science.gov (United States)

    Sosenko, Jay M; Skyler, Jay S; Mahon, Jeffrey; Krischer, Jeffrey P; Greenbaum, Carla J; Rafkin, Lisa E; Beam, Craig A; Boulware, David C; Matheson, Della; Cuthbertson, David; Herold, Kevan C; Eisenbarth, George; Palmer, Jerry P

    2014-04-01

    OBJECTIVE We studied the utility of the Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) for improving the accuracy of type 1 diabetes (T1D) risk classification in TrialNet Natural History Study (TNNHS) participants. RESEARCH DESIGN AND METHODS The cumulative incidence of T1D was compared between normoglycemic individuals with DPTRS values >7.00 and dysglycemic individuals in the TNNHS (n = 991). It was also compared between individuals with DPTRS values 7.00 among those with dysglycemia and those with multiple autoantibodies in the TNNHS. DPTRS values >7.00 were compared with dysglycemia for characterizing risk in Diabetes Prevention Trial-Type 1 (DPT-1) (n = 670) and TNNHS participants. The reliability of DPTRS values >7.00 was compared with dysglycemia in the TNNHS. RESULTS The cumulative incidence of T1D for normoglycemic TNNHS participants with DPTRS values >7.00 was comparable to those with dysglycemia. Among those with dysglycemia, the cumulative incidence was much higher (P 7.00 than for those with values 7.00). Dysglycemic individuals in DPT-1 were at much higher risk for T1D than those with dysglycemia in the TNNHS (P 7.00. The proportion in the TNNHS reverting from dysglycemia to normoglycemia at the next visit was higher than the proportion reverting from DPTRS values >7.00 to values <7.00 (36 vs. 23%). CONCLUSIONS DPTRS thresholds can improve T1D risk classification accuracy by identifying high-risk normoglycemic and low-risk dysglycemic individuals. The 7.00 DPTRS threshold characterizes risk more consistently between populations and has greater reliability than dysglycemia.

  9. Specificity of drug transport mediated by CaMDR1: a major facilitator ...

    Indian Academy of Sciences (India)

    Unknown

    CaMDR1 encodes a major facilitator superfamily (MFS) protein in Candida albicans whose expression has been linked to .... by plaque assay and the integration of CaMDR1 at the ... with recombinant virus, vAcCaMDR1 and cells infected.

  10. Increased long-term risk of major adverse cardiovascular events in patients with carbon monoxide poisoning: A population-based study in Taiwan.

    Directory of Open Access Journals (Sweden)

    Chung-Shun Wong

    Full Text Available Carbon monoxide (CO poisoning may cause toxicity to the cardiovascular system. However, the association between CO poisoning and the risk of major adverse cardiovascular events (MACE remains unestablished. We investigated the incidence of MACE after CO poisoning in Taiwan and evaluated whether CO-poisoned individuals had a higher risk of MACE than did the general population.Using Taiwan's National Health Insurance Research Database (NHIRD during 2005-2013, a nationwide population-based cohort study was conducted among patients who experienced CO poisoning between 2005 and 2013. CO poisoning was defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes. The study cohort comprised patients with CO poisoning between 2005 and 2010 (N = 13,939. Each patient was matched according to age, sex and index date with four randomly selected controls from the comparison cohort (N = 55,756. All patients were followed from the study date until MACE development, death, or the end of 2013. The hazard ratios for MACE were compared between the two cohorts by using Cox proportional hazards regressions analyses.Incident cases of MACE were identified from the NHIRD. After adjustment for potential confounders, the study cohort was independently associated with a higher MACE risk (adjusted hazard ratio, 2.00; 95% confidence interval, 1.83-2.18.This population-based cohort study indicated that patients with CO poisoning have a higher risk of MACE than do individuals without CO poisoning.

  11. A pragmatic multi-centre randomised controlled trial of fluid loading and level of dependency in high-risk surgical patients undergoing major elective surgery: trial protocol

    Directory of Open Access Journals (Sweden)

    Norrie John

    2010-04-01

    Full Text Available Abstract Background Patients undergoing major elective or urgent surgery are at high risk of death or significant morbidity. Measures to reduce this morbidity and mortality include pre-operative optimisation and use of higher levels of dependency care after surgery. We propose a pragmatic multi-centre randomised controlled trial of level of dependency and pre-operative fluid therapy in high-risk surgical patients undergoing major elective surgery. Methods/Design A multi-centre randomised controlled trial with a 2 * 2 factorial design. The first randomisation is to pre-operative fluid therapy or standard regimen and the second randomisation is to routine intensive care versus high dependency care during the early post-operative period. We intend to recruit 204 patients undergoing major elective and urgent abdominal and thoraco-abdominal surgery who fulfil high-risk surgical criteria. The primary outcome for the comparison of level of care is cost-effectiveness at six months and for the comparison of fluid optimisation is the number of hospital days after surgery. Discussion We believe that the results of this study will be invaluable in determining the future care and clinical resource utilisation for this group of patients and thus will have a major impact on clinical practice. Trial Registration Trial registration number - ISRCTN32188676

  12. Co-aggregation of major psychiatric disorders in individuals with first-degree relatives with schizophrenia: a nationwide population-based study.

    Science.gov (United States)

    Cheng, C-M; Chang, W-H; Chen, M-H; Tsai, C-F; Su, T-P; Li, C-T; Tsai, S-J; Hsu, J-W; Huang, K-L; Lin, W-C; Chen, T-J; Bai, Y-M

    2017-11-07

    A previous genetic study has suggested that schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) share common disease-associated genes. However, whether individuals with first-degree relatives (FDRs) with schizophrenia have a higher risk of these major psychiatric disorders requires further investigation. This study used Taiwan's National Health Insurance Research Database and identified 151 650 patients with schizophrenia and 227 967 individuals with FDRs with schizophrenia. The relative risks (RRs) of schizophrenia and other major psychiatric disorders were assessed in individuals with FDRs with schizophrenia. The individuals with FDRs with schizophrenia exhibited higher RRs (95% confidence interval) of major psychiatric disorders, namely schizophrenia (4.76, 4.65-4.88), bipolar disorder (3.23, 3.12-3.35), major depressive disorder (2.05, 2.00-2.10), ASD (2.55, 2.35-2.77) and ADHD (1.31, 1.25-1.37) than were found in the total population. Several sensitivity analyses were conducted to confirm these results. A dose-dependent relationship was observed between the risks of major psychiatric disorders and the numbers of FDRs with schizophrenia. The increased risks of major psychiatric disorders were consistent in different family relationships, namely among parents, offspring, siblings and twins. Our study supports the familial dose-dependent co-aggregation of schizophrenia, bipolar disorder, major depressive disorder, ASD and ADHD, and our results may prompt governmental public health departments and psychiatrists to focus on the mental health of individuals with FDRs with schizophrenia.Molecular Psychiatry advance online publication, 7 November 2017; doi:10.1038/mp.2017.217.

  13. Prokofiev: Piano Concertos - N1 in Dflat major, Op. 10 / David J. Fanning

    Index Scriptorium Estoniae

    Fanning, David J.

    1990-01-01

    Uuest heliplaadist "Prokofiev: Piano Concertos - N1 in Dflat major, Op. 10, N4 in Bflat major, Op.53 "for the left hand", N5 in Gmajor, Op.55. Boris Berman (piano) Royal Concertgebouw Orchestra, Neeme Järvi". Chandos ABTD 1424. CHAN 8791

  14. Prediction of Early Recurrent Thromboembolic Event and Major Bleeding in Patients With Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema: The ALESSA Score Study.

    Science.gov (United States)

    Paciaroni, Maurizio; Agnelli, Giancarlo; Caso, Valeria; Tsivgoulis, Georgios; Furie, Karen L; Tadi, Prasanna; Becattini, Cecilia; Falocci, Nicola; Zedde, Marialuisa; Abdul-Rahim, Azmil H; Lees, Kennedy R; Alberti, Andrea; Venti, Michele; Acciarresi, Monica; D'Amore, Cataldo; Mosconi, Maria Giulia; Cimini, Ludovica Anna; Procopio, Antonio; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Cappellari, Manuel; Putaala, Jukka; Tomppo, Liisa; Tatlisumak, Turgut; Bandini, Fabio; Marcheselli, Simona; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Masotti, Luca; Vannucchi, Vieri; Sohn, Sung-Il; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Acampa, Maurizio; Martini, Giuseppe; Ntaios, George; Karagkiozi, Efstathia; Athanasakis, George; Makaritsis, Kostantinos; Vadikolias, Kostantinos; Liantinioti, Chrysoula; Chondrogianni, Maria; Mumoli, Nicola; Consoli, Domenico; Galati, Franco; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Corea, Francesco; Ageno, Walter; Bellesini, Marta; Colombo, Giovanna; Silvestrelli, Giorgio; Ciccone, Alfonso; Scoditti, Umberto; Denti, Licia; Mancuso, Michelangelo; Maccarrone, Miriam; Orlandi, Giovanni; Giannini, Nicola; Gialdini, Gino; Tassinari, Tiziana; De Lodovici, Maria Luisa; Bono, Giorgio; Rueckert, Christina; Baldi, Antonio; D'Anna, Sebastiano; Toni, Danilo; Letteri, Federica; Giuntini, Martina; Lotti, Enrico Maria; Flomin, Yuriy; Pieroni, Alessio; Kargiotis, Odysseas; Karapanayiotides, Theodore; Monaco, Serena; Baronello, Mario Maimone; Csiba, Laszló; Szabó, Lilla; Chiti, Alberto; Giorli, Elisa; Del Sette, Massimo; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Michel, Patrik; Vanacker, Peter; Barlinn, Kristian; Pallesen, Lars-Peder; Kepplinger, Jessica; Bodechtel, Ulf; Gerber, Johannes; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Gourbali, Vanessa; Yaghi, Shadi

    2017-03-01

    This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P =0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30-1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632-0.763; P =0.0001) for ischemic outcome events and 0.585 (0.493-0.678; P =0.10) for major bleedings. The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763; P =0.009) for ischemic outcome events and 0.407 (0.275-0.540; P =0.14) for hemorrhagic outcome events. In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings. © 2017 American Heart Association, Inc.

  15. Age, gender and hypertension as major risk factors in development of subclinical atherosclerosis

    Directory of Open Access Journals (Sweden)

    Ajla Rahimić Ćatić

    2013-04-01

    Full Text Available Introduction: Intima-media thickness (IMT measurement of the common carotid artery (CCA is considered as useful indicator of carotid atherosclerosis. Early detection of atherosclerosis and its associated risk factors is important to prevent stroke and heart diseases. The aim of the present study was to investigate which risk factors are better determinants of subclinical atherosclerosis, measured by common carotidartery intima media thickness (CCA-IMT.Methods: A total of 74 subjects were randomly selected in this cross – sectional study. Information on the patient’s medical history and laboratory fi ndings were obtained from their clinical records. Risk factors relevant to this study were age, gender, cigarette smoking status, diabetes, hypertension and dyslipidemia. Ultrasound scanning of carotid arteries was performed with a 7,5 MHz linear array transducer (GE Voluson730 pro. The highest value of six common carotid artery measurements was taken as the fi nal IMT. Increased CCA-IMT was defi ned when it was > 1 mm.Results: Our data demonstrated higher CCA-IMT values in male patients compared with female patients. Increased CCA-IMT was the most closely related to age (PConclusion: Age, gender and hypertension are the most important risk factors in development of carotid atherosclerosis. Early detection of atherosclerosis among high-risk populations is important in order to prevent stroke and heart diseases, which are leading causes of death worldwide.

  16. Interaction of cytochrome P4501A1 genotypes with other risk factors and susceptibility to lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Shah, Parag P.; Singh, Arvind P.; Singh, Madhu; Mathur, Neeraj [Developmental Toxicology Division, Industrial Toxicology Research Centre, P.O. Box 80, M.G. Marg, Lucknow 226001 (India); Pant, Mohan C. [Department of Radiotherapy, King George' s Medical University, Shahmina Road, Lucknow 226001 (India); Mishra, Bhartendu N. [Department of Biotechnology, IET, Sitapur Road, Lucknow 226021 (India); Parmar, Devendra [Developmental Toxicology Division, Industrial Toxicology Research Centre, P.O. Box 80, M.G. Marg, Lucknow 226001 (India)], E-mail: parmar_devendra@hotmail.com

    2008-03-01

    Lung cancer is the most common cause of death throughout the world with cigarette smoking being established as the major etiological factor in lung cancer. Since not much information is available regarding the polymorphism in drug metabolizing enzymes and lung cancer risk in the Indian population, the present case-control study attempted to investigate the association of polymorphisms in cytochrome P450 1A1 (CYP1A1) and glutathione-S-transferase M1 (GSTM1) with risk to squamous cell carcinoma of lung malignancy. Patients suffering from lung cancer (n = 200) and visiting OPD facility of Department of Radiotherapy, King George's Medical University, Lucknow, were included in the study. Equal number (n = 200) of age and sex matched healthy individuals were also enrolled in the study. Our data revealed that the variant genotypes of CYP1A1*2A, CYP1A1*2C and CYP1A1*4 were found to be over represented in the lung cancer patients when compared to controls. CYP1A1*2A variant genotypes (combined heterozygous and mutant genotypes) revealed significant association towards the lung cancer risk (OR: 1.93, 95%CI: 1.28-2.89, p = 0.002). Likewise, GSTM1 null genotypes were found to be over represented in patients when compared to controls. Haplotype analysis revealed that CYP1A1 haplotype, C-G-C increased the lung cancer risk (OR: 3.90, 95%CI: 1.00-15.04, p = 0.025) in the patients. The lung cancer risk was increased several two-to fourfold in the patients carrying the genotype combinations of CYP1A1*2A and GSTM1 suggesting the role of gene-gene interaction in lung cancer. Cigarette smoking or tobacco chewing or alcohol consumption was also found to interact with CYP1A1 genotypes in increasing the risk to lung cancer further demonstrating the role of gene-environment interaction in development of lung cancer.

  17. Interaction of cytochrome P4501A1 genotypes with other risk factors and susceptibility to lung cancer

    International Nuclear Information System (INIS)

    Shah, Parag P.; Singh, Arvind P.; Singh, Madhu; Mathur, Neeraj; Pant, Mohan C.; Mishra, Bhartendu N.; Parmar, Devendra

    2008-01-01

    Lung cancer is the most common cause of death throughout the world with cigarette smoking being established as the major etiological factor in lung cancer. Since not much information is available regarding the polymorphism in drug metabolizing enzymes and lung cancer risk in the Indian population, the present case-control study attempted to investigate the association of polymorphisms in cytochrome P450 1A1 (CYP1A1) and glutathione-S-transferase M1 (GSTM1) with risk to squamous cell carcinoma of lung malignancy. Patients suffering from lung cancer (n = 200) and visiting OPD facility of Department of Radiotherapy, King George's Medical University, Lucknow, were included in the study. Equal number (n = 200) of age and sex matched healthy individuals were also enrolled in the study. Our data revealed that the variant genotypes of CYP1A1*2A, CYP1A1*2C and CYP1A1*4 were found to be over represented in the lung cancer patients when compared to controls. CYP1A1*2A variant genotypes (combined heterozygous and mutant genotypes) revealed significant association towards the lung cancer risk (OR: 1.93, 95%CI: 1.28-2.89, p = 0.002). Likewise, GSTM1 null genotypes were found to be over represented in patients when compared to controls. Haplotype analysis revealed that CYP1A1 haplotype, C-G-C increased the lung cancer risk (OR: 3.90, 95%CI: 1.00-15.04, p = 0.025) in the patients. The lung cancer risk was increased several two-to fourfold in the patients carrying the genotype combinations of CYP1A1*2A and GSTM1 suggesting the role of gene-gene interaction in lung cancer. Cigarette smoking or tobacco chewing or alcohol consumption was also found to interact with CYP1A1 genotypes in increasing the risk to lung cancer further demonstrating the role of gene-environment interaction in development of lung cancer

  18. Genetic examination of SETD7 and SUV39H1/H2 methyltransferases and the risk of diabetes complications in patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Syreeni, Anna; El-Osta, Assam; Forsblom, Carol

    2011-01-01

    Hyperglycemia plays a pivotal role in the development and progression of vascular complications, which are the major sources of morbidity and mortality in diabetes. Furthermore, these vascular complications often persist and progress despite improved glucose control, possibly as a result of prior......, and SUV39H2 methyltransferases as predictors of risk for micro- and macrovascular complications in type 1 diabetes....

  19. Pleiotropic Associations of Allelic Variants in a 2q22 Region with Risks of Major Human Diseases and Mortality.

    Directory of Open Access Journals (Sweden)

    Alexander M Kulminski

    2016-11-01

    Full Text Available Gaining insights into genetic predisposition to age-related diseases and lifespan is a challenging task complicated by the elusive role of evolution in these phenotypes. To gain more insights, we combined methods of genome-wide and candidate-gene studies. Genome-wide scan in the Atherosclerosis Risk in Communities (ARIC Study (N = 9,573 was used to pre-select promising loci. Candidate-gene methods were used to comprehensively analyze associations of novel uncommon variants in Caucasians (minor allele frequency~2.5% located in band 2q22.3 with risks of coronary heart disease (CHD, heart failure (HF, stroke, diabetes, cancer, neurodegenerative diseases (ND, and mortality in the ARIC study, the Framingham Heart Study (N = 4,434, and the Health and Retirement Study (N = 9,676. We leveraged the analyses of pleiotropy, age-related heterogeneity, and causal inferences. Meta-analysis of the results from these comprehensive analyses shows that the minor allele increases risks of death by about 50% (p = 4.6×10-9, CHD by 35% (p = 8.9×10-6, HF by 55% (p = 9.7×10-5, stroke by 25% (p = 4.0×10-2, and ND by 100% (p = 1.3×10-3. This allele also significantly influences each of two diseases, diabetes and cancer, in antagonistic fashion in different populations. Combined significance of the pleiotropic effects was p = 6.6×10-21. Causal mediation analyses show that endophenotypes explained only small fractions of these effects. This locus harbors an evolutionary conserved gene-desert region with non-coding intergenic sequences likely involved in regulation of protein-coding flanking genes ZEB2 and ACVR2A. This region is intensively studied for mutations causing severe developmental/genetic disorders. Our analyses indicate a promising target region for interventions aimed to reduce risks of many major human diseases and mortality.

  20. Effect of depression on Helicobacter pylori infection in patients with gastric cancer and its correlation with oncogene expression

    Institute of Scientific and Technical Information of China (English)

    Chun-Rong Xiao

    2017-01-01

    Objective: To study the effect of depression on Helicobacter pylori (H. pylori) infection in patients with gastric cancer and its correlation with oncogene expression. Methods: A total of 82 patients who accepted radical operation for gastric cancer in Zigong Third People's Hospital between March 2015 and February 2017 were selected as the research subjects and divided into depression group and non-depression group according to the preoperative HAMD scores, and helicobacter pylori infection as well as the mRNA expression of proliferation genes and invasion genes in gastric cancer lesions was detected. Results: The positive rate of H. pylori in gastric cancer lesions of depression group was significantly higher than that of non-depression group; LOXL2, RAB1A, UHRF1, Slug and ADAM8 mRNA expression in gastric cancer lesions of depression group were significantly higher than those of non-depression group while MTS1, NOX, E-cadherin and TIMP1 mRNA expression were significantly lower than those of non-depression group; LOXL2, RAB1A, UHRF1, Slug and ADAM8 mRNA expression in H. pylori-positive gastric cancer lesions of depression group were significantly higher than those in H. pylori-negative gastric cancer lesions of depression group while MTS1, NOX, E-cadherin and TIMP1 mRNA expression were significantly lower than those in H. pylori-negative gastric cancer lesions of depression group. Conclusion: Depression can increase the H. pylori infection rate and promote the proliferation and invasion of cancer cells in gastric cancer lesions.

  1. Increased risk of developing stroke for patients with major affective disorder--a registry study

    DEFF Research Database (Denmark)

    Nilsson, Flemming M; Kessing, Lars V

    2004-01-01

    and cerebrovascular diseases in hospitalised patients. The main finding of this study was that patients with depression severe enough to be hospitalised, seem to be at an increased risk of developing cerebrovascular disease. The hazard ratio of getting a diagnosis of stroke after initially having been discharged......Only a few studies have evaluated depressive disorder as a risk factor for cerebrovascular disease. In a hospital discharge register with nation-wide coverage of all hospitals in Denmark we used linkage between the somatic and psychiatric registries to study comorbidity between affective disorders...... with a diagnosis of depression was found to be 1.22 (95% Confidence Interval: 1.06-1.41). In the group of patients with manic/bipolar disorder no association was found concerning development of stroke. In elderly with first time depression admitted to hospital, neurological disorders should be carefully evaluated...

  2. Mutation in APOA1 predicts increased risk of ischaemic heart disease and total mortality without low HDL cholesterol levels

    DEFF Research Database (Denmark)

    Haase, C L; Frikke-Schmidt, R; Nordestgaard, B G

    2011-01-01

    levels. Mutations in apolipoprotein (apo) A-I, the major protein constituent of HDL, might be associated with low HDL cholesterol and predispose to IHD and early death. DESIGN: We resequenced APOA1 in 190 individuals and examined the effect of mutations on HDL cholesterol, risk of IHD, myocardial...

  3. 38 CFR 41.520 - Major program determination.

    Science.gov (United States)

    2010-07-01

    ... major programs. This risk-based approach shall include consideration of: Current and prior audit... of prior audit findings under § 41.510(a)(7) do not preclude the Type A program from being low-risk... this section), except this paragraph (e)(2)(i)(A) does not require the auditor to audit more high-risk...

  4. 18 CFR 260.1 - FERC Form No. 2, Annual report for Major natural gas companies.

    Science.gov (United States)

    2010-04-01

    ... report for Major natural gas companies. 260.1 Section 260.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY APPROVED FORMS, NATURAL GAS ACT STATEMENTS AND REPORTS (SCHEDULES) § 260.1 FERC Form No. 2, Annual report for Major natural gas companies. (a...

  5. Adult height and the risk of cause-specific death and vascular morbidity in 1 million people: individual participant meta-analysis

    Science.gov (United States)

    Wormser, David; Angelantonio, Emanuele Di; Kaptoge, Stephen; Wood, Angela M; Gao, Pei; Sun, Qi; Walldius, Göran; Selmer, Randi; Verschuren, WM Monique; Bueno-de-Mesquita, H Bas; Engström, Gunnar; Ridker, Paul M; Njølstad, Inger; Iso, Hiroyasu; Holme, Ingar; Giampaoli, Simona; Tunstall-Pedoe, Hugh; Gaziano, J Michael; Brunner, Eric; Kee, Frank; Tosetto, Alberto; Meisinger, Christa; Brenner, Hermann; Ducimetiere, Pierre; Whincup, Peter H; Tipping, Robert W; Ford, Ian; Cremer, Peter; Hofman, Albert; Wilhelmsen, Lars; Clarke, Robert; de Boer, Ian H; Jukema, J Wouter; Ibañez, Alejandro Marín; Lawlor, Debbie A; D'Agostino, Ralph B; Rodriguez, Beatriz; Casiglia, Edoardo; Stehouwer, Coen DA; Simons, Leon A; Nietert, Paul J; Barrett-Connor, Elizabeth; Panagiotakos, Demosthenes B; Björkelund, Cecilia; Strandberg, Timo E; Wassertheil-Smoller, Sylvia; Blazer, Dan G; Meade, Tom W; Welin, Lennart; Svärdsudd, Kurt; Woodward, Mark; Nissinen, Aulikki; Kromhout, Daan; Jørgensen, Torben; Tilvis, Reijo S; Guralnik, Jack M; Rosengren, Annika; Taylor, James O; Kiechl, Stefan; Dagenais, Gilles R; Gerry, F; Fowkes, R; Wallace, Robert B; Khaw, Kay-Tee; Shaffer, Jonathan A; Visser, Marjolein; Kauhanen, Jussi; Salonen, Jukka T; Gallacher, John; Ben-Shlomo, Yoav; Kitamura, Akihiko; Sundström, Johan; Wennberg, Patrik; Kiyohara, Yutaka; Daimon, Makoto; de la Cámara, Agustin Gómez; Cooper, Jackie A; Onat, Altan; Devereux, Richard; Mukamal, Kenneth J; Dankner, Rachel; Knuiman, Matthew W; Crespo, Carlos J; Gansevoort, Ron T; Goldbourt, Uri; Nordestgaard, Børge G; Shaw, Jonathan E; Mussolino, Michael; Nakagawa, Hidaeki; Fletcher, Astrid; Kuller, Lewis H; Gillum, Richard F; Gudnason, Vilmundur; Assmann, Gerd; Wald, Nicholas; Jousilahti, Pekka R; Greenland, Philip; Trevisan, Maurizio; Ulmer, Hanno; Butterworth, Adam S; Folsom, Aaron R; Davey-Smith, George; Hu, Frank B; Danesh, John; Tipping, Robert W; Ford, Charles E; Simpson, Lara M; Walldius, Göran; Jungner, Ingmar; Folsom, Aaron R; Demerath, Ellen W; Franceschini, Nora; Lutsey, Pamela L; Panagiotakos, Demosthenes B; Pitsavos, Christos; Chrysohoou, Christina; Stefanadis, Christodoulos; Shaw, Jonathan E; Atkins, Robert; Zimmet, Paul Z; Barr, Elizabeth LM; Knuiman, Matthew W; Whincup, Peter H; Wannamethee, S Goya; Morris, Richard W; Willeit, Johann; Kiechl, Stefan; Weger, Siegfried; Oberhollenzer, Friedrich; Wald, Nicholas; Ebrahim, Shah; Lawlor, Debbie A; Gallacher, John; Ben-Shlomo, Yoav; Yarnell, John WG; Casiglia, Edoardo; Tikhonoff, Valérie; Greenland, Philip; Shay, Christina M; Garside, Daniel B; Nietert, Paul J; Sutherland, Susan E; Bachman, David L; Keil, Julian E; de Boer, Ian H; Kizer, Jorge R; Psaty, Bruce M; Mukamal, Kenneth J; Nordestgaard, Børge G; Tybjærg-Hansen, Anne; Jensen, Gorm B; Schnohr, Peter; Giampaoli, Simona; Palmieri, Luigi; Panico, Salvatore; Pilotto, Lorenza; Vanuzzo, Diego; de la Cámara, Agustin Gómez; Simons, Leon A; Simons, Judith; McCallum, John; Friedlander, Yechiel; Gerry, F; Fowkes, R; Price, Jackie F; Lee, Amanda J; Taylor, James O; Guralnik, Jack M; Phillips, Caroline L; Wallace, Robert B; Kohout, Frank J; Cornoni-Huntley, Joan C; Guralnik, Jack M; Blazer, Dan G; Guralnik, Jack M; Phillips, Caroline L; Phillips, Caroline L; Guralnik, Jack M; Khaw, Kay-Tee; Wareham, Nicholas J; Brenner, Hermann; Schöttker, Ben; Müller, Heiko; Rothenbacher, Dietrich; Wennberg, Patrik; Jansson, Jan-Håkan; Nissinen, Aulikki; Donfrancesco, Chiara; Giampaoli, Simona; Woodward, Mark; Vartiainen, Erkki; Jousilahti, Pekka R; Harald, Kennet; Salomaa, Veikko; D'Agostino, Ralph B; Vasan, Ramachandran S; Fox, Caroline S; Pencina, Michael J; Daimon, Makoto; Oizumi, Toshihide; Kayama, Takamasa; Kato, Takeo; Bladbjerg, Else-Marie; Jørgensen, Torben; Møller, Lars; Jespersen, Jørgen; Dankner, Rachel; Chetrit, Angela; Lubin, Flora; Svärdsudd, Kurt; Eriksson, Henry; Welin, Lennart; Lappas, Georgios; Rosengren, Annika; Lappas, Georgios; Welin, Lennart; Svärdsudd, Kurt; Eriksson, Henry; Lappas, Georgios; Bengtsson, Calle; Lissner, Lauren; Björkelund, Cecilia; Cremer, Peter; Nagel, Dorothea; Strandberg, Timo E; Salomaa, Veikko; Tilvis, Reijo S; Miettinen, Tatu A; Tilvis, Reijo S; Strandberg, Timo E; Kiyohara, Yutaka; Arima, Hisatomi; Doi, Yasufumi; Ninomiya, Toshiharu; Rodriguez, Beatriz; Dekker, Jacqueline M; Nijpels, Giel; Stehouwer, Coen DA; Hu, Frank B; Sun, Qi; Rimm, Eric B; Willett, Walter C; Iso, Hiroyasu; Kitamura, Akihiko; Yamagishi, Kazumasa; Noda, Hiroyuki; Goldbourt, Uri; Vartiainen, Erkki; Jousilahti, Pekka R; Harald, Kennet; Salomaa, Veikko; Kauhanen, Jussi; Salonen, Jukka T; Kurl, Sudhir; Tuomainen, Tomi-Pekka; Poppelaars, Jan L; Deeg, Dorly JH; Visser, Marjolein; Meade, Tom W; De Stavola, Bianca Lucia; Hedblad, Bo; Nilsson, Peter; Engström, Gunnar; Verschuren, WM Monique; Blokstra, Anneke; de Boer, Ian H; Shea, Steven J; Meisinger, Christa; Thorand, Barbara; Koenig, Wolfgang; Döring, Angela; Verschuren, WM Monique; Blokstra, Anneke; Bueno-de-Mesquita, H Bas; Wilhelmsen, Lars; Rosengren, Annika; Lappas, Georgios; Fletcher, Astrid; Nitsch, Dorothea; Kuller, Lewis H; Grandits, Greg; Tverdal, Aage; Selmer, Randi; Nystad, Wenche; Mussolino, Michael; Gillum, Richard F; Hu, Frank B; Sun, Qi; Manson, JoAnn E; Rimm, Eric B; Hankinson, Susan E; Meade, Tom W; De Stavola, Bianca Lucia; Cooper, Jackie A; Bauer, Kenneth A; Davidson, Karina W; Kirkland, Susan; Shaffer, Jonathan A; Shimbo, Daichi; Kitamura, Akihiko; Iso, Hiroyasu; Sato, Shinichi; Holme, Ingar; Selmer, Randi; Tverdal, Aage; Nystad, Wenche; Nakagawa, Hidaeki; Miura, Katsuyuki; Sakurai, Masaru; Ducimetiere, Pierre; Jouven, Xavier; Bakker, Stephan JL; Gansevoort, Ron T; van der Harst, Pim; Hillege, Hans L; Crespo, Carlos J; Garcia-Palmieri, Mario R; Kee, Frank; Amouyel, Philippe; Arveiler, Dominique; Ferrières, Jean; Schulte, Helmut; Assmann, Gerd; Jukema, J Wouter; de Craen, Anton JM; Sattar, Naveed; Stott, David J; Cantin, Bernard; Lamarche, Benoît; Després, Jean-Pierre; Dagenais, Gilles R; Barrett-Connor, Elizabeth; Bergstrom, Jaclyn; Bettencourt, Richele R; Buisson, Catherine; Gudnason, Vilmundur; Aspelund, Thor; Sigurdsson, Gunnar; Thorsson, Bolli; Trevisan, Maurizio; Hofman, Albert; Ikram, M Arfan; Tiemeier, Henning; Witteman, Jacqueline CM; Tunstall-Pedoe, Hugh; Tavendale, Roger; Lowe, Gordon DO; Woodward, Mark; Devereux, Richard; Yeh, Jeun-Liang; Ali, Tauqeer; Calhoun, Darren; Ben-Shlomo, Yoav; Davey-Smith, George; Onat, Altan; Can, Günay; Nakagawa, Hidaeki; Sakurai, Masaru; Nakamura, Koshi; Morikawa, Yuko; Njølstad, Inger; Mathiesen, Ellisiv B; Løchen, Maja-Lisa; Wilsgaard, Tom; Sundström, Johan; Ingelsson, Erik; Michaëlsson, Karl; Cederholm, Tommy; Gaziano, J Michael; Buring, Julie; Ridker, Paul M; Gaziano, J Michael; Ridker, Paul M; Ulmer, Hanno; Diem, Günter; Concin, Hans; Rodeghiero, Francesco; Tosetto, Alberto; Wassertheil-Smoller, Sylvia; Manson, JoAnn E; Marmot, Michael; Clarke, Robert; Fletcher, Astrid; Brunner, Eric; Shipley, Martin; Kivimaki, Mika; Ridker, Paul M; Buring, Julie; Ford, Ian; Robertson, Michele; Ibañez, Alejandro Marín; Feskens, Edith; Geleijnse, Johanna M; Kromhout, Daan; Walker, Matthew; Watson, Sarah; Alexander, Myriam; Butterworth, Adam S; Angelantonio, Emanuele Di; Franco, Oscar H; Gao, Pei; Gobin, Reeta; Haycock, Philip; Kaptoge, Stephen; Seshasai, Sreenivasa R Kondapally; Lewington, Sarah; Pennells, Lisa; Rapsomaniki, Eleni; Sarwar, Nadeem; Thompson, Alexander; Thompson, Simon G; Walker, Matthew; Watson, Sarah; White, Ian R; Wood, Angela M; Wormser, David; Zhao, Xiaohui; Danesh, John

    2012-01-01

    Background The extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain. Methods We calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual–participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies. Results For people born between 1900 and 1960, mean adult height increased 0.5–1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96–0.99) for death from any cause, 0.94 (0.93–0.96) for death from vascular causes, 1.04 (1.03–1.06) for death from cancer and 0.92 (0.90–0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12–1.42) for risk of melanoma death to 0.84 (0.80–0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators. Conclusion Adult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases. PMID:22825588

  6. Increasing risk of compound flooding from storm surge and rainfall for major US coastal cities

    Science.gov (United States)

    Wahl, Thomas; Jain, Shaleen; Bender, Jens; Meyers, Steven; Luther, Mark

    2016-04-01

    Flood risk is a well-known facet of natural hazards along the US coastline where nearly 40% of the population resides in coastal counties. Given the heavy reliance on the coastal zone for natural resources and economic activity, flood preparedness and safety is a key element of long-term resilience. A clear understanding of the various flood types and changes in the frequency of their occurrence is critical towards reliable estimates of vulnerability and potential impacts in the near-term as well as into the future. When the two main flood drivers for coastal areas storm surge and heavy precipitation occur in tandem the potential for significant flooding is much greater than from either in isolation. Exploring the probability of these 'compound events' and understanding the processes driving them is essential to mitigate the associated high impact risks. For the contiguous US the likelihood of the joint occurrence of the two phenomena is largely unknown. Here we show - using storm surge and precipitation records spanning the last century - that the risk of compound flooding is higher for the US east and Gulf coasts, relative to the west coast. We also show that the number of compound events has increased significantly over the last century along large coastline stretches including many of the major coastal cities. For New York City - as an example - this increase is attributed to a shift towards storm surge weather patterns also favouring high precipitation. Preliminary analyses reveal that these synoptic scale changes are closely linked to large scale and low frequency climate variations. Our results demonstrate the importance of assessing the risk of compound flooding within the design process of coastal and urban infrastructure in a non-stationary framework and to explore the potential effects of climate change on these high impact events.

  7. Gender-specific suicide risk factors: a case-control study of individuals with major depressive disorder.

    Science.gov (United States)

    Dalca, Ioana Mioara; McGirr, Alexander; Renaud, Johanne; Turecki, Gustavo

    2013-12-01

    Available information on risk for suicide completion in females is limited and often extrapolated from studies conducted in males. However, the validity of extending to females risk factors identified among male suicide cases is unclear. In this study, we aimed to investigate clinical and behavioral risk factors for suicide among female depressed patients and compare them to similar factors among male depressed patients. We identified 201 suicide completers (160 male and 41 female) who died during an episode of major depressive disorder (MDD). Cases were compared to 127 living patients with MDD (88 male and 39 female). All subjects were characterized for Axis I and II diagnoses using the Structured Clinical Interview for DSM-IV Axis I Disorders and Structured Clinical Interview for DSM-IV Axis II Personality Disorders according to the DSM-IV, as well as behavioral and temperament dimensions using proxy-based interviews. The primary outcome was measures of impulsive and impulsive-aggressive behaviors. Compared to controls, male, but not female suicide cases had higher levels of impulsive aggression (P suicide cases from controls. However, nonimpulsive aggression and impulsive aggression were correlated constructs in males (r = 0.297; P suicide, such as alcohol and substance dependence, cluster B disorders, and elevated hostility and aggression, were replicated in the pooled-sex analyses, and, though not statistically significant in discriminating between suicide cases and controls by gender, maintained strong group differences. Males and females share many risk factors for suicide in MDD, yet alcohol dependence is much more specific though less sensitive among depressed females. Nonimpulsive aggression is part of a diathesis for suicide in females, which is distinct from the well-characterized impulsive aggression that is consistently reported in a portion of male suicide cases. © Copyright 2013 Physicians Postgraduate Press, Inc.

  8. Predictors of major postoperative cardiac complications in a surgical ICU.

    Science.gov (United States)

    Maia, Paula C; Abelha, Fernando J

    2008-03-01

    Cardiovascular complications are associated with increased mortality and morbidity during the postoperative period, resulting in longer hospital stay and higher treatment costs. The aim of this study was to identify predictors of major postoperative cardiac complications. 187 patients undergoing noncardiac surgery, admitted to a surgical intensive care unit (ICU) between November 2004 and April 2005. Variables recorded were age, gender, American Society of Anesthesiologists (ASA) physical status, type and magnitude of surgery, mortality, ICU and hospital length of stay (LOS), Simplified Acute Physiology Score II (SAPS II), cardiac troponin I (cTnI) at postoperative day 0, 1, 2 and 3, history of hypertension, hyperlipidemia, Revised Cardiac Risk Index (RCRI) score, major cardiac events (MCE): acute myocardial infarction (AMI), pulmonary edema (PE), ventricular fibrillation (VF) or primary cardiac arrest (PCA). Correlations between variables and MCE were made by univariate analysis by simple logistic regression with odds ratio (OR) and 95% confidence interval (95% CI). Total of 14 MCE: 9 AMI, 1 VF, 4 PE. Significant risk factors for MCE were high-risk surgery (OR 8.26, 95% CI 1.76-38.85, p = 0.008), RCRI > or = 2 (OR 4.0, 95% CI 1.22-13.16, p = 0.022), admission cTnI (OR 1.46, 95% CI 1.07-1.99, p = 0.018); day 1 cTnI (OR 1.75, 95% CI 1.27-2.41, p = 0.001); day 2 cTnI (OR 2.23, 95% CI 1.24-3.98, p = 0.007), SAPS II (OR 1.08, 95% CI 1.04-1.12, p or = 2, cTnI levels and SAPS II were predictors of postoperative MCE. Patients with MCE had longer ICU stay and higher mortality rate.

  9. Symptomatic menopausal transition and subsequent bipolar disorder among midlife women with major depression: a nationwide longitudinal study.

    Science.gov (United States)

    Chen, Li-Chi; Yang, Albert C; Su, Tung-Ping; Bai, Ya-Mei; Li, Cheng-Ta; Chang, Wen-Han; Chen, Tzeng-Ji; Tsai, Shih-Jen; Chen, Mu-Hong

    2017-06-01

    Previous studies suggested that menopausal transition played an important role in the clinical course of major depression and bipolar disorder. However, the role of symptomatic menopausal transition in diagnostic conversion from major depression to bipolar disorder was still unknown. Using the Taiwan National Health Insurance Research Database, 50,273 midlife women aged between 40 and 60 years in 2002∼2008 with major depression were enrolled in our study and divided into two subgroups based on the presence (n = 21,120) or absence (n = 29,153) of symptomatic menopausal transition. Subjects who had subsequent bipolar disorder during the follow-up were identified. Midlife women with major depression and symptomatic menopausal transition had a higher incidence of the diagnostic conversion to bipolar disorder (7.3 vs. 6.6%, p = 0.003) than those with major depression alone. Cox regression analysis after adjusting for demographic data and psychiatric comorbidities further showed that symptomatic menopausal transition was associated with an increased risk of developing bipolar disorder (HR 1.14, 95% CI 1.07∼1.23) among midlife women with major depression. Sensitivity test after excluding the 1-year and 3-year observation exhibited the consistent findings (HR 1.18, 95% CI 1.09∼1.28; HR 1.20, 95% CI 1.08∼1.34). Midlife women with the dual diagnoses of major depression and symptomatic menopausal transition had an increased risk of the diagnostic conversion to bipolar disorder compared to those with major depression alone. Further studies may be required to investigate the underlying mechanisms among menopausal transition and the diagnostic conversion from major depression to bipolar disorder.

  10. Internet-based control recruitment for a case-control study of major risk factors for stroke in Korea: lessons from the experience.

    Science.gov (United States)

    Park, Jong-Moo; Cho, Yong-Jin; Lee, Kyung Bok; Park, Tai Hwan; Lee, Soo Joo; Han, Moon-Ku; Ko, Youngchai; Lee, Jun; Cha, Jae-Kwan; Lee, Byung-Chul; Yu, Kyung-Ho; Oh, Mi-Sun; Lee, Ji Sung; Lee, Juneyoung; Bae, Hee-Joon

    2014-01-01

    This study aimed to estimate the population-attributable risks (PARs) of 9 major risk factors for stroke in Korea through a case-control study and to test the feasibility and validity of internet-based control recruitment. From April 2008 to September 2009, controls were enrolled via internet after providing consent for participation through a web-based survey. The cases included patients who were admitted to the participating centers due to acute stroke or transient ischemic attack within 7 days of onset during the study period. Each control was age- and sex-matched with 2 cases. Adjusted odd ratios, age-standardized prevalence, and PARs were estimated for the 9 major risk factors using the prevalence of risk factors in the control group and the age and sex characteristics from Korea's national census data. In total, 1041 controls were matched to 2082 stroke cases. Because of a shortage of elderly controls in the internet-based recruitment, 248 controls were recruited off-line. The PARs were 23.44%, 10.95%, 51.32%, and 6.35% for hypertension, diabetes, smoking, and stroke history, respectively. Hypercholesterolemia, atrial fibrillation, obesity, coronary heart disease, and a family history of stroke were not associated with stroke. Comparison with education and religion of the control group with that mentioned in the national census data showed a notable difference. The study results imply that internet-based control recruitment for a case-control study requires careful selection of risk factors with high self-awareness and effective strategies to facilitate the recruitment of elderly participants. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  11. Major histocompatibility complex harbors widespread genotypic variability of non-additive risk of rheumatoid arthritis including epistasis.

    Science.gov (United States)

    Wei, Wen-Hua; Bowes, John; Plant, Darren; Viatte, Sebastien; Yarwood, Annie; Massey, Jonathan; Worthington, Jane; Eyre, Stephen

    2016-04-25

    Genotypic variability based genome-wide association studies (vGWASs) can identify potentially interacting loci without prior knowledge of the interacting factors. We report a two-stage approach to make vGWAS applicable to diseases: firstly using a mixed model approach to partition dichotomous phenotypes into additive risk and non-additive environmental residuals on the liability scale and secondly using the Levene's (Brown-Forsythe) test to assess equality of the residual variances across genotype groups per marker. We found widespread significant (P 5e-05) vGWAS signals within the major histocompatibility complex (MHC) across all three study cohorts of rheumatoid arthritis. We further identified 10 epistatic interactions between the vGWAS signals independent of the MHC additive effects, each with a weak effect but jointly explained 1.9% of phenotypic variance. PTPN22 was also identified in the discovery cohort but replicated in only one independent cohort. Combining the three cohorts boosted power of vGWAS and additionally identified TYK2 and ANKRD55. Both PTPN22 and TYK2 had evidence of interactions reported elsewhere. We conclude that vGWAS can help discover interacting loci for complex diseases but require large samples to find additional signals.

  12. Association between depression and anxiety symptoms and major atherosclerosis risk factors in patients with chest pain

    International Nuclear Information System (INIS)

    Vural, M.; Satiroglu, Oe.; Goeksel, I.; Akbas, B.; Karabay, Oe.

    2007-01-01

    Psychological variables, such as depression and anxiety, are known as independent risk factors for coronary artery disease (CAD), suggesting the interaction of psychological and physiological factors in the development of CAD. In the present study, we analyzed the possible association between depressive and anxiety symptoms and major atherosclerotic risk factors in patients with chest pain warranting coronary angiography. The patients without CAD (n=159) and those with CAD (n=155) were evaluated for the severity of depression and anxiety by the symptom scales; high scores indicate severe symptoms. Age, male/female ratio, prevalence of diabetes mellitus (DM), and depression level were significantly higher in the CAD group. Among a total of 314 patients with chest pain, the mean depression score was higher in patients with DM (16.01±8.12 vs 13.01±9.6, p=0.01) and those with hypercholesterolemia (15.43±9.61 vs 12.53±9.61, p=0.02). The mean anxiety score was also higher in patients with DM (20.81±12.85 vs 16.51±12.09, p=0.008), hypercholesterolemia (20.67±13.11 vs 15.29±11.36, p=0.002), or hypertension (20.74±12.94 vs 14.1±10.8, p=0.001). Thus, DM and hypercholesterolemia are associated with depression and anxiety, while hypertension is only related to anxiety. In contrast, smoking and family history of atherosclerosis are not related to depression and anxiety scores. These results suggest depression and anxiety symptoms may contribute to the development and progression of CAD, especially in patients with DM or hypercholesterolemia. (author)

  13. The Association Between Major Depressive Disorder and Outcomes in Older Veterans Hospitalized With Pneumonia.

    Science.gov (United States)

    DeWaters, Ami L; Chansard, Matthieu; Anzueto, Antonio; Pugh, Mary Jo; Mortensen, Eric M

    2018-01-01

    Major depressive disorder ("depression") has been identified as an independent risk factor for mortality for many comorbid conditions, including heart failure, cancer and stroke. Major depressive disorder has also been linked to immune suppression by generating a chronic inflammatory state. However, the association between major depression and pneumonia has not been examined. The aim of this study was to examine the association between depression and outcomes, including mortality and intensive care unit admission, in Veterans hospitalized with pneumonia. We conducted a retrospective national study using administrative data of patients hospitalized at any Veterans Administration acute care hospital. We included patients ≥65 years old hospitalized with pneumonia from 2002-2012. Depressed patients were further analyzed based on whether they were receiving medications to treat depression. We used generalized linear mixed effect models to examine the association of depression with the outcomes of interest after controlling for potential confounders. Patients with depression had a significantly higher 90-day mortality (odds ratio 1.12, 95% confidence interval 1.07-1.17) compared to patients without depression. Patients with untreated depression had a significantly higher 30-day (1.11, 1.04-1.20) and 90-day (1.20, 1.13-1.28) mortality, as well as significantly higher intensive care unit admission rates (1.12, 1.03-1.21), compared to patients with treated depression. For older veterans hospitalized with pneumonia, a concurrent diagnosis of major depressive disorder, and especially untreated depression, was associated with higher mortality. This highlights that untreated major depressive disorder is an independent risk factor for mortality for patients with pneumonia. Published by Elsevier Inc.

  14. Barrett associated MHC and FOXF1 variants also increase esophageal carcinoma risk

    NARCIS (Netherlands)

    Dura, P.; Veen, E.M. van; Salomon, J.; Morsche, R.H.M. te; Roelofs, H.M.J.; Kristinsson, J.O.; Wobbes, T.; Witteman, B.J.; Tan, A.C.; Drenth, J.P.H.; Peters, W.H.M.

    2013-01-01

    Barrett's esophagus, with gastroesophageal reflux disease and obesity as risk factors, predisposes to esophageal adenocarcinoma (EAC). Recently a British genome wide association study identified two Barrett's esophagus susceptibility loci mapping within the major histocompatibility complex (MHC;

  15. Outcome of intraoperative goal-directed therapy using Vigileo/FloTrac in high-risk patients scheduled for major abdominal surgeries: A prospective randomized trial

    Directory of Open Access Journals (Sweden)

    Mohammed A. Elgendy

    2017-07-01

    Conclusion: The applied protocol for intraoperative GDT provided significant reduction of PO morbidities, ICU and hospital LOS but couldn‘t significantly reduce mortality rates in high risk patients scheduled for major abdominal surgeries.

  16. Cardiovascular Risks Associated with Incident and Prevalent Periodontal Disease

    Science.gov (United States)

    Yu, Yau-Hua; Chasman, Daniel I; Buring, Julie E; Rose, Lynda; Ridker, Paul M

    2014-01-01

    Aim While prevalent periodontal disease associates with cardiovascular risk, little is known about how incident periodontal disease influences future vascular risk. We compared effects of incident versus prevalent periodontal disease in developing major cardiovascular diseases (CVD), myocardial infarction (MI), ischemic stroke and total CVD. Material and Methods In a prospective cohort of 39863 predominantly white women, age ≥ 45 years and free of cardiovascular disease at baseline were followed for an average of 15.7 years. Cox proportional hazard models with time-varying periodontal status (prevalent [18%], incident [7.3%] vs. never [74.7%]) were used to assess future cardiovascular risks. Results Incidence rates of all CVD outcomes were higher in women with prevalent or incident periodontal disease. For women with incident periodontal disease, risk factor adjusted hazard ratios (HRs) were 1.42 (95% CI, 1.14–1.77) for major CVD, 1.72 (1.25–2.38) for MI, 1.41(1.02–1.95) for ischemic stroke, and 1.27(1.06–1.52) for total CVD. For women with prevalent periodontal disease, adjusted HRs were 1.14 (1.00–1.31) for major CVD, 1.27 (1.04–1.56) for MI, 1.12(0.91–1.37) for ischemic stroke, and 1.15(1.03–1.28) for total CVD. Conclusion New cases of periodontal disease, not just those that are pre-existing, place women at significantly elevated risks for future cardiovascular events. PMID:25385537

  17. Report by the Delegate for major risks for 2010; Rapport 2010 du delegue aux risques majeurs

    Energy Technology Data Exchange (ETDEWEB)

    Michel, Laurent [Ministere de l' Ecologie, du Developpement durable, des Transports et du Logement, Grande Arche, Tour Pascal A et B, 92055 La Defense Cedex (France)

    2011-07-01

    The first part of this report comments the major natural and industrial disasters which occurred in 2010 in France (Xynthia tempest, flooding, and forest fires) and in other countries. It also proposes some lessons from these disasters. The second part discusses the evolution towards a resilient society by a combined approach of sustainable development, of cultural good safeguarding, and person protection. It also discusses a prospective approach regarding natural hazards and technological accidents, adapted procedures, governance and land planning, the evolution of information and alarm systems, and emerging risks. The third part addresses the adaptation to natural hazards: frameworks and strategies, actions (regulatory prevention, flooding management, safety of hydraulic works, seismic plan). It assesses the financial and budgetary means brought by the State and its partners, and discusses some perspectives. It addresses the technological risks: legal and regulatory evolutions, safety of hazardous industrial installations, consequences of technological accidents. The next part deals with the control of civilian nuclear installations by the ASN. The last part presents the different involved structures and authorities

  18. Predictors of perioperative major bleeding in patients who interrupt warfarin for an elective surgery or procedure: Analysis of the BRIDGE trial.

    Science.gov (United States)

    Clark, Nathan P; Douketis, James D; Hasselblad, Vic; Schulman, Sam; Kindzelski, Andrei L; Ortel, Thomas L

    2018-01-01

    The use of low-molecular weight heparin bridge therapy during warfarin interruption for elective surgery/procedures increases bleeding. Other predictors of bleeding in this setting are not well described. BRIDGE was a randomized, double-blind, placebo-controlled trial of bridge therapy with dalteparin 100 IU/kg twice daily in patients with atrial fibrillation requiring warfarin interruption. Bleeding outcomes were documented from the time of warfarin interruption until up to 37 days postprocedure. Multiple logistic regression and time-dependent hazard models were used to identify major bleeding predictors. We analyzed 1,813 patients of whom 895 received bridging and 918 received placebo. Median patient age was 72.6 years, and 73.3% were male. Forty-one major bleeding events occurred at a median time of 7.0 days (interquartile range, 4.0-18.0 days) postprocedure. Bridge therapy was a baseline predictor of major bleeding (odds ratio [OR]=2.4, 95% CI: 1.2-4.8), as were a history of renal disease (OR=2.9, 95% CI: 1.4-6.0), and high-bleeding risk procedures (vs low-bleeding risk procedures) (OR=2.9, 95% CI: 1.4-5.9). Perioperative aspirin use (OR=3.6, 95% CI: 1.1-11.9) and postprocedure international normalized ratio >3.0 (OR=2.1, 95% CI: 1.5-3.1) were time-dependent predictors of major bleeding. Major bleeding was most common in the first 10 days compared with 11-37 days postprocedure (OR=3.5, 95% CI: 1.8-6.9). In addition to bridge therapy, perioperative aspirin use, postprocedure international normalized ratio >3.0, a history of renal failure, and having a high-bleeding risk procedure increase the risk of major bleeding around the time of an elective surgery/procedure requiring warfarin interruption. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Association between toll-like receptors expression and major depressive disorder.

    Science.gov (United States)

    Hung, Yi-Yung; Kang, Hong-Yo; Huang, Kai-Wei; Huang, Tiao-Lai

    2014-12-15

    Accumulating evidences suggest that Toll-like receptors (TLRs) were involved in the pathophysiology of major depressive disorder. TLR4 was thought to be associated with major depressive disorder in animal model, but the others were still unknown. In order to examine TLR1-9 mRNA expression levels in peripheral blood and their relationships with the psychopathology of major depressive disorder, 30 patients with major depressive disorder were compared with 29 healthy controls. The 17-item Hamilton Depression Rating Scale (HAMD-17) was used to assess the severity of major depression. The mRNA expression levels of TLRs were examined in parallel with a housekeeping gene using real-time polymerase chain reaction (RT-PCR). Analysis of covariance with age and body mass index adjustment revealed a significantly higher expression of TLR3, 4, 5 and 7 mRNA but lower expression of TLR1 and 6 in patients with major depressive disorder as compared with healthy controls. Multiple linear regression analysis revealed that TLR4 was an independent risk factor relating to severity of major depression. These findings suggest that TLRs, especially TLR4, may be involved in the psychopathology of major depression. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Genome-wide DNA methylation in 1-year-old infants of mothers with major depressive disorder.

    Science.gov (United States)

    Cicchetti, Dante; Hetzel, Susan; Rogosch, Fred A; Handley, Elizabeth D; Toth, Sheree L

    2016-11-01

    A genome-wide methylation study was conducted among a sample of 114 infants (M age = 13.2 months, SD = 1.08) of low-income urban women with (n = 73) and without (n = 41) major depressive disorder. The Illumina HumanMethylation450 BeadChip array with a GenomeStudio Methylation Module and Illumina Custom model were used to conduct differential methylation analyses. Using the 5.0 × 10-7 p value, 2,119 loci were found to be significantly different between infants of depressed and nondepressed mothers. Infants of depressed mothers had greater methylation at low methylation sites (0%-29%) compared to infants of nondepressed mothers. At high levels of methylation (70%-100%), the infants of depressed mothers were predominantly hypomethylated. The mean difference in methylation between the infants of depressed and infants of nondepressed mothers was 5.23%. Disease by biomarker analyses were also conducted using GeneGo MetaCore Software. The results indicated significant cancer-related differences in biomarker networks such as prostatic neoplasms, ovarian and breast neoplasms, and colonic neoplasms. The results of a process networks analysis indicated significant differences in process networks associated with neuronal development and central nervous system functioning, as well as cardiac development between infants of depressed and nondepressed mothers. These findings indicate that early in development, infants of mothers with major depressive disorder evince epigenetic differences relative to infants of well mothers that suggest risk for later adverse health outcomes.

  1. MHD mode evolutions prior to minor and major disruptions in SST-1 plasma

    Energy Technology Data Exchange (ETDEWEB)

    Dhongde, Jasraj; Pradhan, Subrata, E-mail: pradhan@ipr.res.in; Bhandarkar, Manisha

    2017-01-15

    Highlights: • Observation of different regimes of MHD phenomena in SST-1 plasma. • MHD mode (m/n = 1/1, m/n = 2/1) evolutions prior to minor and major disruptions in SST-1 plasma. • MHD mode characteristics such as mode frequency, mode number, island width etc. in different regimes. - Abstract: Steady State Superconducting Tokamak (SST-1) is a medium size Tokamak (R{sub 0} = 1.1 m, a = 0.2 m, B{sub T} = 1.5T, Ip ∼ 110 kA) in operation at the Institute for Plasma Research, India. SST-1 uniquely experiments large aspect ratio (∼5.5) plasma in different operation regimes. In these experiments, repeatable characteristic MHD phenomena have been consistently observed. As the large aspect ratio plasma pulse progresses, these MHD phenomena display minor-major disruptions ably indicated in Mirnov oscillations, Mirnov oscillations with saw teeth and locked modes etc. Even though somewhat similar observations have been found in some other machines, these observations are found for the first time in large aspect ratio plasma of SST-1. This paper elaborates the magnetic field perturbations and mode evolutions due to MHD activities from Mirnov coils (poloidal and toroidal), Soft X-ray diagnostics, ECE diagnostics etc. This work further, for the first time reports quantitatively different regimes of MHD phenomena observed in SST-1 plasma, their details of mode evolutions characteristics as well as the subsequently observed minor, major disruptions supported with the physical explanations. This study will help developing disruption mitigation and avoidance scenarios for having better confinement plasma experiments.

  2. Risk-based approach for bioremediation of fuel hydrocarbons at a major airport

    International Nuclear Information System (INIS)

    Wiedemeier, T.H.; Guest, P.R.; Blicker, B.R.

    1994-01-01

    This paper describes a risk-based approach for bioremediation of fuel-hydrocarbon-contaminated soil and ground water at a major airport in Colorado. In situ bioremediation pilot testing, natural attenuation modeling, and full-scale remedial action planning and implementation for soil and ground water contamination has conducted at four airport fuel farms. The sources of fuel contamination were leaking underground storage tanks (USTs) or pipelines transporting Jet A fuel and aviation gasoline. Continuing sources of contamination were present in several small cells of free-phase product and in fuel residuals trapped within the capillary fringe at depths 15 to 20 feet below ground surface. Bioventing pilot tests were conducted to assess the feasibility of using this technology to remediate contaminated soils. The pilot tests included measurement of initial soil gas chemistry at the site, determination of subsurface permeability, and in situ respiration tests to determine fuel biodegradation rates. A product recovery test was also conducted. ES designed and installed four full-scale bioventing systems to remediate the long-term sources of continuing fuel contamination. Benzene, toluene, ethylbenzene, and xylenes (BTEX) and total petroleum hydrocarbons (TPH) were detected in ground water at concentrations slightly above regulatory guidelines

  3. Major depressive disorder, anxiety disorders, and cardiac biomarkers in subjects at high risk of obstructive sleep apnea.

    Science.gov (United States)

    Einvik, Gunnar; Hrubos-Strøm, Harald; Randby, Anna; Nordhus, Inger Hilde; Somers, Virend K; Omland, Torbjørn; Dammen, Toril

    2011-06-01

    Cardiac biomarkers may be valuable when exploring potential mechanisms for the association between cardiovascular disease and psychiatric disorders. In subjects at increased risk for obstructive sleep apnea, we examined whether major depressive disorder (MDD), anxiety disorders, or the combination of these was associated with circulating C-reactive protein (CRP), cardiac troponin T (cTnT), or heart rate variability (HRV). From the Akershus Sleep Apnea Project, 290 participants were assessed for MDD or any anxiety disorder by a physician using the Structured Clinical Interview for DSM-IV. Fasting blood samples were analyzed with high-sensitivity assays for CRP, cTnT, and HRV calculated from a Holter recording. Age, sex, hypertension, diabetes, hyperlipidemia, obesity, smoking, apnea-hypopnea index, and previous cardiovascular disease were adjusted for. The CRP levels (median [interquartile range], mg/L) were higher in depressive (2.7 [1.1-5.8]) versus nondepressive (1.3 [0.7-3.1], p = .02) and in anxious (2.8 [0.9-5.2]) versus nonanxious (1.3 [0.7-3.1], p = .01). MDD was independently associated with CRP (unstandardized β = 0.387, p = .04), but anxiety was not (unstandardized β = 0.298, p = .09). The CRP level was highest in subjects with comorbid MDD and anxiety (3.4 [1.1-7.8]). The unadjusted and adjusted odds ratios (95% confidence interval) for having measurable cTnT (> 3 ng/L) were 0.49 (0.24-1.07) and 0.92 (0.31-2.67) for MDD versus nondepressive and 0.38 (0.18-0.80) and 0.61 (0.30-2.05) for anxiety versus nonanxiety, respectively. HRV did not vary between groups. Although CRP was increased both in MDD and anxiety disorders, patients with comorbid MDD and anxiety may be particularly prone to increased systemic inflammation. Neither MDD nor anxiety disorders were associated with low-level myocardial damage or HRV.

  4. Age, gender and hypertension as major risk factors in development of subclinical atherosclerosis

    Directory of Open Access Journals (Sweden)

    Ajla Rahimić Ćatić

    2013-04-01

    Full Text Available Introduction: Intima-media thickness (IMT measurement of the common carotid artery (CCA is considered as useful indicator of carotid atherosclerosis. Early detection of atherosclerosis and its associated risk factors is important to prevent stroke and heart diseases. The aim of the present study was to investigate which risk factors are better determinants of subclinical atherosclerosis, measured by common carotidartery intima media thickness (CCA-IMT.Methods: A total of 74 subjects were randomly selected in this cross – sectional study. Information on the patient’s medical history and laboratory fi ndings were obtained from their clinical records. Risk factors relevant to this study were age, gender, cigarette smoking status, diabetes, hypertension and dyslipidemia. Ultrasound scanning of carotid arteries was performed with a 7,5 MHz linear array transducer (GE Voluson730 pro. The highest value of six common carotid artery measurements was taken as the fi nal IMT. Increased CCA-IMT was defi ned when it was > 1 mm.Results: Our data demonstrated higher CCA-IMT values in male patients compared with female patients. Increased CCA-IMT was the most closely related to age (P<0.001, followed by systolic blood pressure (P=0.001, diastolic blood pressure (P=0.003 and glucose blood level (P=0.048.Conclusion: Age, gender and hypertension are the most important risk factors in development of carotid atherosclerosis. Early detection of atherosclerosis among high-risk populations is important in order to prevent stroke and heart diseases, which are leading causes of death worldwide.

  5. Risk assessment of major hazards: Hazardous materials transportation in urban areas

    Energy Technology Data Exchange (ETDEWEB)

    Hubert, Ph; Pages, P

    1988-02-01

    There is no doubt that, thanks to the pioneering studies of the late seventies and the early eighties, a methodology has been made available that allows risk management of hazardous transportation in urban areas. This approach can easily be extended to the management of other similar risks (storages and to some extent natural hazards). The methodology is both technically available and affordable. The insertion within the decision making processes deserves still some efforts. It has be seen that the applications are broad and numerous. They range from route selection to emergency preparedness, with some insights into acceptability considerations. One limit to the use of such studies, aiming to an objective assessment of the risk, is the complexity of the decision problems, where many factors are to be considered, the most subtle being the one linked to acceptability. However, as such studies develop, those factors start to be clarified, and decision makers learn how to use risk indices in this context. So at the present time it can be said that risk analyses are a valuable input into the decision making process in most cases. And, as more experience is acquired the uses are broader. As any technical innovation risk assessment modifies the approaches to the questions it is dealing with. It seems impossible now to treat those kinds of risks as was done ten years ago.

  6. Risk assessment of major hazards: Hazardous materials transportation in urban areas

    International Nuclear Information System (INIS)

    Hubert, Ph.; Pages, P.

    1988-02-01

    There is no doubt that, thanks to the pioneering studies of the late seventies and the early eighties, a methodology has been made available that allows risk management of hazardous transportation in urban areas. This approach can easily be extended to the management of other similar risks (storages and to some extent natural hazards). The methodology is both technically available and affordable. The insertion within the decision making processes deserves still some efforts. It has be seen that the applications are broad and numerous. They range from route selection to emergency preparedness, with some insights into acceptability considerations. One limit to the use of such studies, aiming to an objective assessment of the risk, is the complexity of the decision problems, where many factors are to be considered, the most subtle being the one linked to acceptability. However, as such studies develop, those factors start to be clarified, and decision makers learn how to use risk indices in this context. So at the present time it can be said that risk analyses are a valuable input into the decision making process in most cases. And, as more experience is acquired the uses are broader. As any technical innovation risk assessment modifies the approaches to the questions it is dealing with. It seems impossible now to treat those kinds of risks as was done ten years ago

  7. Apolipoprotein E e4 allele does not increase the risk of early postoperative delirium after major surgery.

    Science.gov (United States)

    Abelha, Fernando José; Fernandes, Vera; Botelho, Miguela; Santos, Patricia; Santos, Alice; Machado, J C; Barros, Henrique

    2012-02-01

    BACKGROUND: A relationship between patients with a genetic predisposition to and those who develop postoperative delirium has not been yet determined. The aim of this study was to determine whether there is an association between apolipoprotein E epsilon 4 allele (APOE4) and delirium after major surgery. METHODS: Of 230 intensive care patients admitted to the post anesthesia care unit (PACU) over a period of 3 months, 173 were enrolled in the study. Patients' demographics and intra- and postoperative data were collected. Patients were followed for the development of delirium using the Intensive Care Delirium Screening Checklist, and DNA was obtained at PACU admission to determine apolipoprotein E genotype. RESULTS: Fifteen percent of patients developed delirium after surgery. Twenty-four patients had one copy of APOE4. The presence of APOE4 was not associated with an increased risk of early postoperative delirium (4% vs. 17%; P = 0.088). The presence of APOE4 was not associated with differences in any studied variables. Multivariate analysis identified age [odds ratio (OR) 9.3, 95% confidence interval (CI) 2.0-43.0, P = 0.004 for age ≥65 years), congestive heart disease (OR 6.2, 95% CI 2.0-19.3, P = 0.002), and emergency surgery (OR 59.7, 95% CI 6.7-530.5, P < 0.001) as independent predictors for development of delirium. The Simplified Acute Physiology Score II (SAPS II) and The Acute Physiology and Chronic Health Evaluation II (APACHE II) were significantly higher in patients with delirium (P < 0.001 and 0.008, respectively). Hospital mortality rates of these patients was higher and they had a longer median PACU stay. CONCLUSIONS: Apolipoprotein e4 carrier status was not associated with an increased risk for early postoperative delirium. Age, congestive heart failure, and emergency surgery were independent risk factors for the development of delirium after major surgery.

  8. Differential Effects of Intraoperative Positive End-expiratory Pressure (PEEP) on Respiratory Outcome in Major Abdominal Surgery Versus Craniotomy

    DEFF Research Database (Denmark)

    de Jong, Myrthe A C; Ladha, Karim S; Melo, Marcos F Vidal

    2015-01-01

    OBJECTIVES: In this study, we examined whether (1) positive end-expiratory pressure (PEEP) has a protective effect on the risk of major postoperative respiratory complications in a cohort of patients undergoing major abdominal surgeries and craniotomies, and (2) the effect of PEEP is differed......: Within the entire study population (major abdominal surgeries and craniotomies), we found an association between application of PEEP ≥5 cmH2O and a decreased risk of postoperative respiratory complications compared with PEEP 5 cmH2O was associated with a significant lower...... undergoing major abdominal surgery. Our data suggest that default mechanical ventilator settings should include PEEP of 5-10 cmH2O during major abdominal surgery....

  9. Lower Frequency of HLA-DRB1 Type 1 Diabetes Risk Alleles in Pediatric Patients with MODY.

    Science.gov (United States)

    Urrutia, Inés; Martínez, Rosa; López-Euba, Tamara; Velayos, Teresa; Martínez de LaPiscina, Idoia; Bilbao, José Ramón; Rica, Itxaso; Castaño, Luis

    2017-01-01

    The aim of this study was to determine the frequency of susceptible HLA-DRB1 alleles for type 1 diabetes in a cohort of pediatric patients with a confirmed genetic diagnosis of MODY. 160 families with a proband diagnosed with type 1 diabetes and 74 families with a molecular diagnosis of MODY (61 GCK-MODY and 13 HNF1A-MODY) were categorized at high definition for HLA-DRB1 locus. According to the presence or absence of the susceptible HLA-DRB1 alleles for type 1 diabetes, we considered three different HLA-DRB1 genotypes: 0 risk alleles (no DR3 no DR4); 1 risk allele (DR3 or DR4); 2 risk alleles (DR3 and/or DR4). Compared with type 1 diabetes, patients with MODY carried higher frequency of 0 risk alleles, OR 22.7 (95% CI: 10.7-48.6) and lower frequency of 1 or 2 risk alleles, OR 0.53 (95% CI: 0.29-0.96) and OR 0.06 (95% CI: 0.02-0.18), respectively. The frequency of HLA-DRB1 risk alleles for type 1 diabetes is significantly lower in patients with MODY. In children and adolescents with diabetes, the presence of 2 risk alleles (DR3 and/or DR4) reduces the probability of MODY diagnosis, whereas the lack of risk alleles increases it. Therefore, we might consider that HLA-DRB1 provides additional information for the selection of patients with high probability of monogenic diabetes.

  10. Lower Frequency of HLA-DRB1 Type 1 Diabetes Risk Alleles in Pediatric Patients with MODY.

    Directory of Open Access Journals (Sweden)

    Inés Urrutia

    Full Text Available The aim of this study was to determine the frequency of susceptible HLA-DRB1 alleles for type 1 diabetes in a cohort of pediatric patients with a confirmed genetic diagnosis of MODY.160 families with a proband diagnosed with type 1 diabetes and 74 families with a molecular diagnosis of MODY (61 GCK-MODY and 13 HNF1A-MODY were categorized at high definition for HLA-DRB1 locus. According to the presence or absence of the susceptible HLA-DRB1 alleles for type 1 diabetes, we considered three different HLA-DRB1 genotypes: 0 risk alleles (no DR3 no DR4; 1 risk allele (DR3 or DR4; 2 risk alleles (DR3 and/or DR4.Compared with type 1 diabetes, patients with MODY carried higher frequency of 0 risk alleles, OR 22.7 (95% CI: 10.7-48.6 and lower frequency of 1 or 2 risk alleles, OR 0.53 (95% CI: 0.29-0.96 and OR 0.06 (95% CI: 0.02-0.18, respectively.The frequency of HLA-DRB1 risk alleles for type 1 diabetes is significantly lower in patients with MODY. In children and adolescents with diabetes, the presence of 2 risk alleles (DR3 and/or DR4 reduces the probability of MODY diagnosis, whereas the lack of risk alleles increases it. Therefore, we might consider that HLA-DRB1 provides additional information for the selection of patients with high probability of monogenic diabetes.

  11. MAJOR-MERGER GALAXY PAIRS IN THE COSMOS FIELD—MASS-DEPENDENT MERGER RATE EVOLUTION SINCE z = 1

    International Nuclear Information System (INIS)

    Xu, C. Kevin; Zhao, Yinghe; Gao, Y.; Scoville, N.; Capak, P.; Drory, N.

    2012-01-01

    We present results of a statistical study of the cosmic evolution of the mass-dependent major-merger rate since z = 1. A stellar mass limited sample of close major-merger pairs (the CPAIR sample) was selected from the archive of the COSMOS survey. Pair fractions at different redshifts derived using the CPAIR sample and a local K-band-selected pair sample show no significant variations with stellar mass. The pair fraction exhibits moderately strong cosmic evolution, with the best-fitting function of f pair = 10 –1.88(±0.03) (1 + z) 2.2(±0.2) . The best-fitting function for the merger rate is R mg (Gyr –1 ) = 0.053 × (M star /10 10.7 M ☉ ) 0.3 (1 + z) 2.2 /(1 + z/8). This rate implies that galaxies of M star ∼ 10 10 -10 11.5 M ☉ have undergone ∼0.5-1.5 major mergers since z = 1. Our results show that, for massive galaxies (M star ≥ 10 10.5 M ☉ ) at z ≤ 1, major mergers involving star-forming galaxies (i.e., wet and mixed mergers) can account for the formation of both ellipticals and red quiescent galaxies (RQGs). On the other hand, major mergers cannot be responsible for the formation of most low mass ellipticals and RQGs of M star ∼ 10.3 M ☉ . Our quantitative estimates indicate that major mergers have significant impact on the stellar mass assembly of the most massive galaxies (M star ≥ 10 11.3 M ☉ ), but for less massive galaxies the stellar mass assembly is dominated by the star formation. Comparison with the mass-dependent (ultra)luminous infrared galaxies ((U)LIRG) rates suggests that the frequency of major-merger events is comparable to or higher than that of (U)LIRGs.

  12. A Successful ED Fall Risk Program Using the KINDER 1 Fall RiskAssessment Tool.

    Science.gov (United States)

    Townsend, Ann B; Valle-Ortiz, Marisol; Sansweet, Tracy

    2016-11-01

    Emergency nurses did not perform falls risk assessments routinely on our ED patients; the instrument used was aimed at inpatients. We identified a need to revise fall assessment practices specific to our emergency department. The purpose of the performance improvement project was to reduce ED falls and evaluate the use of an ED-specific fall risk tool, the KINDER 1 Fall Risk Assessment. The plan was to establish fall risk assessment practices at point of ED entry and to decrease total falls. We retrospectively reviewed ED fall data for each quarter of 2013, which included risk assessments scores, the total number of falls, and the circumstances of each fall. Using Kotter's framework to guide a successful change process, we implemented the KINDER 1 to assess fall risk. During the first 4 weeks of the project, 937 patients (27%) were identified as high risk for falls using the KINDER 1. During the subsequent 3 quarters, the total number of falls decreased; reported falls without injuries dropped from 0.21 to 0.07 per 1000 patients, and falls with injuries were reduced from 0.21 to 0.0 per 1000 patients. The results of this project represented a valuable step toward achieving our goal to keep ED patients safe from injuries as a result of falls. The findings add to the body of nursing knowledge on the application of clinical-based performance improvement projects to improve patient outcomes and to provide data on the use of the KINDER 1 tool, which has not been extensively tested. Copyright © 2016 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.

  13. Association between regulator of telomere elongation helicase1 (RTEL1) gene and HAPE risk

    Science.gov (United States)

    Rong, Hao; He, Xue; Zhu, Linhao; Zhu, Xikai; Kang, Longli; Wang, Li; He, Yongjun; Yuan, Dongya; Jin, Tianbo

    2017-01-01

    Abstract High altitude pulmonary edema (HAPE) is a paradigm of pulmonary edema. Mutations in regulator of telomere elongation helicase1 (RTEL1) represent an important contributor to risk for pulmonary fibrosis. However, little information is found about the association between RTEL1 and HAPE risk. The present study was undertaken to tentatively explore the potential relation between single-nucleotide polymorphisms (SNPs) in RTEL1 and HAPE risk in Chinese Han population. A total of 265 HAPE patients and 303 healthy controls were included in our case-control study. Four SNPs in RTEL1 were selected and genotyped using the Sequenom MassARRAY method. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by unconditional logistic regression with adjustment for gender and age. All P values were Bonferroni corrected, and statistical significance was set at P RTEL1 and a decreased risk HAPE in the Chinese population. The results need further confirmation. PMID:28953687

  14. Association between alcohol dehydrogenase 1C gene *1/*2 polymorphism and pancreatitis risk: a meta-analysis.

    Science.gov (United States)

    Fang, F; Pan, J; Su, G H; Xu, L X; Li, G; Li, Z H; Zhao, H; Wang, J

    2015-11-30

    Numerous studies have focused on the relationship be-tween alcohol dehydrogenase 1C gene (ADH1C) *1/*2 polymorphism (Ile350Val, rs698, also known as ADH1C *1/*2) and pancreatitis risk, but the results have been inconsistent. Thus, we conducted a meta-anal-ysis to more precisely estimate this association. Relevant publications were searched in several widely used databases and 9 eligible studies were included in the meta-analysis. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Significant associations between ADH1C *1/*2 poly-morphism and pancreatitis risk were observed in both overall meta-analysis for 12 vs 22 (OR = 1.53, 95%CI = 1.12-2.10) and 11 + 12 vs 22 (OR = 1.44, 95%CI = 1.07-1.95), and the chronic alcoholic pancre-atitis subgroup for 12 vs 22 (OR = 1.64, 95%CI = 1.17-2.29) and 11 + 12 vs 22 (OR = 1.53, 95%CI = 1.11-2.11). Significant pancreatitis risk variation was also detected in Caucasians for 11 + 12 vs 22 (OR = 1.45, 95%CI = 1.07-1.98). In conclusion, the ADH1C *1/*2 polymorphism is likely associated with pancreatitis risk, particularly chronic alcoholic pancreatitis risk, with the *1 allele functioning as a risk factor.

  15. The impact of a massive transfusion protocol (1:1:1) on major hepatic injuries: does it increase abdominal wall closure rates?

    Science.gov (United States)

    Ball, Chad G; Dente, Christopher J; Shaz, Beth; Wyrzykowski, Amy D; Nicholas, Jeffrey M; Kirkpatrick, Andrew W; Feliciano, David V

    2013-10-01

    Massive transfusion protocols (MTPs) using high plasma and platelet ratios for exsanguinating trauma patients are increasingly popular. Major liver injuries often require massive resuscitations and immediate hemorrhage control. Current published literature describes outcomes among patients with mixed patterns of injury. We sought to identify the effects of an MTP on patients with major liver trauma. Patients with grade 3, 4 or 5 liver injuries who required a massive blood component transfusion were analyzed. We compared patients with high plasma:red blood cell:platelet ratio (1:1:1) transfusions (2007-2009) with patients injured before the creation of an institutional MTP (2005-2007). Among 60 patients with major hepatic injuries, 35 (58%) underwent resuscitation after the implementation of an MTP. Patient and injury characteristics were similar between cohorts. Implementation of the MTP significantly improved plasma: red blood cell:platelet ratios and decreased crystalloid fluid resuscitation (p = 0.026). Rapid improvement in early acidosis and coagulopathy was superior with an MTP (p = 0.009). More patients in the MTP group also underwent primary abdominal fascial closure during their hospital stay (p = 0.021). This was most evident with grade 4 injuries (89% vs. 14%). The mean time to fascial closure was 4.2 days. The overall survival rate for all major liver injuries was not affected by an MTP (p = 0.61). The implementation of a formal MTP using high plasma and platelet ratios resulted in a substantial increase in abdominal wall approximation. This occurred concurrently to a decrease in the delivered volume of crystalloid fluid.

  16. What characteristics of primary anxiety disorders predict subsequent major depressive disorder?

    Science.gov (United States)

    Bittner, Antje; Goodwin, Renee D; Wittchen, Hans-Ulrich; Beesdo, Katja; Höfler, Michael; Lieb, Roselind

    2004-05-01

    The goal of this study was to examine the associations between specific anxiety disorders and the risk of major depressive disorder and to explore the role of various clinical characteristics of anxiety disorders in these relationships using a prospective, longitudinal design. The data are from a 4-year prospective, longitudinal community study, which included both baseline and follow-up survey data on 2548 adolescents and young adults aged 14 to 24 years at baseline. DSM-IV diagnoses were made using the Munich-Composite International Diagnostic Interview. The presence at baseline of any anxiety disorder (odds ratio [OR] = 2.2 [95% CI = 1.6 to 3.2]) and each of the anxiety disorders (specific phobia, OR = 1.9 [95% CI = 1.3 to 2.8]; social phobia, OR = 2.9 [95% CI = 1.7 to 4.8]; agoraphobia, OR = 3.1 [95% CI = 1.4 to 6.7]; panic disorder, OR = 3.4 [95% CI = 1.2 to 9.0]; generalized anxiety disorder, OR = 4.5 [95% CI = 1.9 to 10.3]) was associated with a significantly (p depressive disorder. These associations remained significant after we adjusted for mental disorders occurring prior to the onset of the anxiety disorder, with the exception of the panic disorder association. The following clinical characteristics of anxiety disorders were associated with a significantly (p depressive disorder: more than 1 anxiety disorder, severe impairment due to the anxiety disorder, and comorbid panic attacks. In the final model, which included all clinical characteristics, severe impairment remained the only clinical characteristic that was an independent predictor of the development of major depressive disorder (OR = 2.2 [95% CI = 1.0 to 4.4]). Our findings suggest that anxiety disorders are risk factors for the first onset of major depressive disorder. Although a number of clinical characteristics of anxiety disorders appear to play a role in the association between anxiety disorders and depression, severe impairment is the strongest predictor of major depressive disorder.

  17. Genetic polymorphisms of GSTM1, GSTT1, and GSTP1 with prostate cancer risk: a meta-analysis of 57 studies.

    Directory of Open Access Journals (Sweden)

    Mancheng Gong

    Full Text Available BACKGROUND AND OBJECTIVES: The GSTM1, GSTT1 and GSTP1 polymorphisms might be involved in inactivation of procarcinogens that contribute to the genesis and progression of cancers. However, studies investigating the association between GSTM1, GSTT1 or GSTP1 polymorphisms and prostate cancer (PCa risk report conflicting results, therefore, we conducted a meta-analysis to re-examine the controversy. METHODS: Published literature from PubMed, Embase, Google Scholar and China National Knowledge Infrastructure (CNKI were searched (updated to June 2, 2012. According to our inclusion criteria, studies that observed the association between GSTM1, GSTT1 or GSTP1 polymorphisms and PCa risk were included. The principal outcome measure was the odds ratio (OR with 95% confidence interval (CI for the risk of PCa associated with GSTM1, GSTT1 and GSTP1 polymorphisms. RESULTS: Fifty-seven studies involving 11313 cases and 12934 controls were recruited. The overall OR, which was 1.2854 (95% CI = 1.1405-1.4487, revealed a significant risk of PCa and GSTM1 null genotype, and the similar results were observed when stratified by ethnicity and control source. Further, the more important is that the present study first reported the high risks of PCa for people who with dual null genotype of GSTM1 and GSTT1 (OR = 1.4353, 95% CI = 1.0345-1.9913, or who with GSTT1 null genotype and GSTP1 A131G polymorphism (OR = 1.7335, 95% CI = 1.1067-2.7152. But no association was determined between GSTT1 null genotype (OR = 1.102, 95% CI = 0.9596-1.2655 or GSTP1 A131G polymorphism (OR = 1.0845, 95% CI = 0.96-1.2251 and the PCa risk. CONCLUSIONS: Our meta-analysis suggested that the people with GSTM1 null genotype, with dual null genotype of GSTM1 and GSTT1, or with GSTT1 null genotype and GSTP1 A131G polymorphism are associated with high risks of PCa, but no association was found between GSTT1 null genotype or GSTP1 A131G polymorphism and the risk of

  18. Major Management Challenges and Program Risks. Department of Labor

    National Research Council Canada - National Science Library

    2001-01-01

    This report addresses the major performance and accountability challenges facing the Department of Labor as it seeks to promote the welfare and economic security of the nations work force and ensure...

  19. Risk in Science Instruction. The Realist and Constructivist Paradigms of Risk

    Science.gov (United States)

    Hansen, Julia; Hammann, Marcus

    2017-11-01

    Risk is always present in people's lives: diseases, new technologies, socio-scientific issues (SSIs) such as climate change, and advances in medicine—to name just a few examples—all carry risks. To be able to navigate risks in everyday life, as well as to participate in social debate on risk-related issues, students need to develop risk competence. Science education can be a powerful tool in supporting students' risk competence, which is an important component of scientific literacy. As there are different definitions of risk within the scientific community, the aims of this article are (1) to review the literature on two major theoretical frameworks for conceptualising risk, the realist, and the constructivist paradigms of risk and (2) to connect both in order to suggest a working definition of what can be understood as risk competence in science instruction.

  20. Pharmacogenetics-based warfarin dosing algorithm decreases time to stable anticoagulation and the risk of major hemorrhage: an updated meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Wang, Zhi-Quan; Zhang, Rui; Zhang, Peng-Pai; Liu, Xiao-Hong; Sun, Jian; Wang, Jun; Feng, Xiang-Fei; Lu, Qiu-Fen; Li, Yi-Gang

    2015-04-01

    Warfarin is yet the most widely used oral anticoagulant for thromboembolic diseases, despite the recently emerged novel anticoagulants. However, difficulty in maintaining stable dose within the therapeutic range and subsequent serious adverse effects markedly limited its use in clinical practice. Pharmacogenetics-based warfarin dosing algorithm is a recently emerged strategy to predict the initial and maintaining dose of warfarin. However, whether this algorithm is superior over conventional clinically guided dosing algorithm remains controversial. We made a comparison of pharmacogenetics-based versus clinically guided dosing algorithm by an updated meta-analysis. We searched OVID MEDLINE, EMBASE, and the Cochrane Library for relevant citations. The primary outcome was the percentage of time in therapeutic range. The secondary outcomes were time to stable therapeutic dose and the risks of adverse events including all-cause mortality, thromboembolic events, total bleedings, and major bleedings. Eleven randomized controlled trials with 2639 participants were included. Our pooled estimates indicated that pharmacogenetics-based dosing algorithm did not improve percentage of time in therapeutic range [weighted mean difference, 4.26; 95% confidence interval (CI), -0.50 to 9.01; P = 0.08], but it significantly shortened the time to stable therapeutic dose (weighted mean difference, -8.67; 95% CI, -11.86 to -5.49; P pharmacogenetics-based algorithm significantly reduced the risk of major bleedings (odds ratio, 0.48; 95% CI, 0.23 to 0.98; P = 0.04), but it did not reduce the risks of all-cause mortality, total bleedings, or thromboembolic events. Our results suggest that pharmacogenetics-based warfarin dosing algorithm significantly improves the efficiency of International Normalized Ratio correction and reduces the risk of major hemorrhage.

  1. Measurement of mean cardiac dose for various breast irradiation techniques and corresponding risk of major cardiovascular event.

    Directory of Open Access Journals (Sweden)

    Tomas Rodrigo Merino Lara

    2014-10-01

    Full Text Available After breast conserving surgery, early stage breast cancer patients are currently treated with a wide range of radiation techniques including whole breast irradiation (WBI, accelerated partial breast irradiation (APBI using high dose rate (HDR brachytherapy, or 3D conformal radiotherapy (3D-CRT. This study compares the mean heart’s doses for a left breast irradiated with different breast techniques.An anthropomorphic Rando phantom was modified with gelatin-based breast of different sizes and tumors located medially or laterally. The breasts were treated with WBI, 3D-CRT or HDR APBI. The heart’s mean doses were measured with Gafchromic films and controlled with optically stimulated luminescent dosimeters (OSLDs. Following the model reported by Darby (16, major cardiac were estimated assuming a linear risk increase with the mean dose to the heart of 7.4% per gray.Whole breast irradiation lead to the highest mean heart dose (2.99 Gy compared to 3D-CRT APBI, (0.51 Gy, multicatheter (1.58 Gy and balloon HDR (2.17 Gy for a medially located tumor. This translated into long-term coronary event increases of 22%, 3.8%, 11.7%, and 16% respectively. The sensitivity analysis showed that the tumor location had almost no effect on the mean heart dose for 3D-CRT APBI and a minimal impact for HDR APBI. For WBI large breast size and set-up errors lead to sharp increases of the mean heart dose. Its value reached 10.79 Gy for women with large breast and a set-up error of 1.5 cm. Such a high value could increase the risk of having long-term coronary events by 80%.Comparison among different irradiation techniques demonstrates that 3D-CRT APBI appears the safest one with less probability of having cardiovascular events in the future. A sensitivity analysis showed that WBI is the most challenging technique for patients with large breasts or when significant set-up errors are anticipated. In those cases additional heart shielding techniques are required.

  2. Previously known and newly diagnosed atrial fibrillation: a major risk indicator after a myocardial infarction complicated by heart failure or left ventricular dysfunction

    DEFF Research Database (Denmark)

    Køber, Lars; Swedberg, Karl; McMurray, John J V

    2006-01-01

    AIMS: To characterize the relationship between known and newly diagnosed atrial fibrillation (AF) and the risk of death and major cardiovascular (CV) events in patients with acute myocardial infarction (MI) complicated by heart failure (HF) and/or left ventricular systolic dysfunction (LVSD). MET...

  3. ITS1 locus: a major determinant of genetic diversity of Plantago spp. (plantaginaceae)

    International Nuclear Information System (INIS)

    Altantestseg, K.; Baatartsogt, O.; Enkhchimeg, V.

    2018-01-01

    By this study, ITS (Internal Transcribed Spacer) regions in the nuclear DNA of 10 Plantago samples collected from Mongolia (5 samples) and Vietnam (5 samples) were sequenced and constructed Maximum Parsimony (MP) and Neighbor-Joining (NJ) phylogenetic trees for establishing the genetic relationship. The results showed that 10 samples belonged to 2 species (7 Plantago major and 3 Plantago depressa). The length of sequences ranged from 632 to 644 bp (ITS1 ranged from 210-222 bp, 5.8S was 162 bp, and ITS2 259 - 261 bp). The ITS1 region was highly variable among the sequences whereas ITS2 and 5.8S regions were more conservative. The MP and NJ trees apparently separated P. major and P. depressa into 2 different groups, supported with high bootstrap values. P. depressa was first time reported in Mongolia. The results highlighted that ITS sequences could distinguish P. major and P. depressa, which is certainly important for pharmacist to use crude drugs derived from Plantago. (author)

  4. Outcome of patients with major depressive disorder after serious suicide attempt.

    Science.gov (United States)

    Suominen, Kirsi; Haukka, Jari; Valtonen, Hanna M; Lönnqvist, Jouko

    2009-10-01

    To investigate the outcome of subjects with major depressive disorder after serious suicide attempt and to examine the effect of psychotic symptoms on their outcome. The study population included all individuals aged 16 years or older in Finland who were hospitalized with ICD-10 diagnoses of major depressive disorder and attempted suicide from 1996 to 2003 (N = 1,820). The main outcome measures were completed suicides, overall mortality, and repeated suicide attempts during drug treatment versus no treatment. During the 4-year follow-up period, 13% of patients died, 6% completed suicide, and 31% made a repeat suicide attempt. Subjects with major depression with psychotic features completed suicide more often than subjects without psychotic features during the follow-up (hazard ratio [HR] 3.32; 95% CI, 1.95 - 5.67). Antidepressant treatment reduced all-cause mortality by 24% (HR 0.74; 95% CI, 0.56 - 0.97) but did not reduce suicide mortality (HR 1.06; 95% CI, 0.71 - 1.58). Psychotic symptoms during major depressive episode increase the risk of completed suicide after serious suicide attempt. The quality of treatment for major depression with psychotic features after attempted suicide should be improved to prevent suicide. Copyright 2009 Physicians Postgraduate Press, Inc.

  5. Endometriosis: a high-risk population for major chronic diseases?

    Science.gov (United States)

    Kvaskoff, Marina; Mu, Fan; Terry, Kathryn L.; Harris, Holly R.; Poole, Elizabeth M.; Farland, Leslie; Missmer, Stacey A.

    2015-01-01

    BACKGROUND Despite an estimated prevalence of 10% in women, the etiology of endometriosis remains poorly understood. Over recent decades, endometriosis has been associated with risk of several chronic diseases, such as cancer, autoimmune diseases, asthma/atopic diseases and cardiovascular diseases. A deeper understanding of these associations is needed as they may provide new leads into the causes or consequences of endometriosis. This review summarizes the available epidemiological findings on the associations between endometriosis and other chronic diseases and discusses hypotheses for underlying mechanisms, potential sources of bias and methodological complexities. METHODS We performed a comprehensive search of the PubMed/Medline and ISI Web of Knowledge databases for all studies reporting on the associations between endometriosis and other diseases published in English through to May 2014, using numerous search terms. We additionally examined the reference lists of all identified papers to capture any additional articles that were not identified through computer searches. RESULTS We identified 21 studies on the associations between endometriosis and ovarian cancer, 14 for breast cancer, 8 for endometrial cancer, 4 for cervical cancer, 12 for cutaneous melanoma and 3 for non-Hodgkin's lymphoma, as well as 9 on the links between endometriosis and autoimmune diseases, 6 on the links with asthma and atopic diseases, and 4 on the links with cardiovascular diseases. Endometriosis patients were reported to be at higher risk of ovarian and breast cancers, cutaneous melanoma, asthma, and some autoimmune, cardiovascular and atopic diseases, and at decreased risk of cervical cancer. CONCLUSIONS Increasing evidence suggests that endometriosis patients are at higher risk of several chronic diseases. Although the underlying mechanisms are not yet understood, the available data to date suggest that endometriosis is not harmless with respects to women's long-term health. If

  6. Risk factors for congenital anomalies in high risk pregnant women: A ...

    African Journals Online (AJOL)

    The major CAs observed were Central Nervous System (CNS) followed by renal anomalies. Maternal age (≤25 years, OR =1.42, p= 0.002), paternal age (<30 years, OR =1.51, p< 0.001), consanguinity (OR =1.39, p= 0.012) and primi gravida (OR= 3.40, p<0.001) were identified as risk factors for HRP women with fetal CAs ...

  7. The framing of two major flood episodes in the Irish print news media: Implications for societal adaptation to living with flood risk.

    Science.gov (United States)

    Devitt, Catherine; O'Neill, Eoin

    2017-10-01

    Societal adaptation to flooding is a critical component of contemporary flood policy. Using content analysis, this article identifies how two major flooding episodes (2009 and 2014) are framed in the Irish broadsheet news media. The article considers the extent to which these frames reflect shifts in contemporary flood policy away from protection towards risk management, and the possible implications for adaptation to living with flood risk. Frames help us make sense of the social world, and within the media, framing is an essential tool for communication. Five frames were identified: flood resistance and structural defences, politicisation of flood risk, citizen as risk manager, citizen as victim and emerging trade-offs. These frames suggest that public debates on flood management do not fully reflect shifts in contemporary flood policy, with negative implications for the direction of societal adaptation. Greater discussion is required on the influence of the media on achieving policy objectives.

  8. [Is a patient's knowledge of cardiovascular risk factors better after the occurrence of a major ischemic event? Survey of 135 cases and 260 controls].

    Science.gov (United States)

    Lensel, A-S; Lermusiaux, P; Boileau, C; Feugier, P; Sérusclat, A; Zerbib, Y; Ninet, J

    2013-12-01

    We hypothezised that patients (cases) who are hospitalized for a major ischemic event--myocardial infarction, stroke, decompensation of peripheral arterial disease--acquire better knowledge than a control population--atheromatous patients without a major ischemic event, patients consulting for a vein disease or a diabetes evaluation, and accompanists--about cardiovascular risk factors (smoking, hypertension, diabetes, dyslipidemia, obesity) and have a better understanding of the usefulness of making changes in their lifestyle (quit smoking, regular exercise, Mediterranean diet, low salt diet, weight control, diabetes care). A questionnaire was proposed at vascular surgery consultations and vascular and cardiac functional explorations, at the M Pavillon of the Édouard-Herriot hospital, Lyon, France. In five months, 395 questionnaires (135 cases and 260 controls) were analyzed. The global knowledge score was statistically higher for cases than for controls (cases 3.23±1.81; controls 2.77±2.03; P=0.037). Cases did not abide by monitoring and dietary rules better, except as regards the management of diabetes. Regular physical activity was statistically more prevalent among controls than among cases. Cases mainly received their information from their doctors (general practitioner for 59% of controls and 78% of cases, cardiologist for 25% of controls and 57% of cases) while controls got their information more through magazines or advertising. Our results show that after a major ischemic event, cases' knowledge of risk factors is better than the rest of the population without improved rules lifestyle changes. This suggests the usefulness of evaluating a therapeutic education program for atheromatous disease. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  9. Perioperative bleeding and blood transfusion are major risk factors for venous thromboembolism following bariatric surgery.

    Science.gov (United States)

    Nielsen, Alexander W; Helm, Melissa C; Kindel, Tammy; Higgins, Rana; Lak, Kathleen; Helmen, Zachary M; Gould, Jon C

    2018-05-01

    Morbidly obese patients are at increased risk for venous thromboembolism (VTE) after bariatric surgery. Perioperative chemoprophylaxis is used routinely with bariatric surgery to decrease the risk of VTE. When bleeding occurs, routine chemoprophylaxis is often withheld due to concerns about inciting another bleeding event. We sought to evaluate the relationship between perioperative bleeding and postoperative VTE in bariatric surgery. The American College of Surgeons-National Surgical Quality Improvement Program (NSQIP) dataset between 2012 and 2014 was queried to identify patients who underwent bariatric surgery. Gastric bypass (n = 28,145), sleeve gastrectomy (n = 30,080), bariatric revision (n = 324), and biliopancreatic diversion procedures (n = 492) were included. Univariate and multivariate regressions were used to determine perioperative factors predictive of postoperative VTE within 30 days in patients who experience a bleeding complication necessitating transfusion. The rate of bleeding necessitating transfusion was 1.3%. Bleeding was significantly more likely to occur in gastric bypass compared to sleeve gastrectomy (1.6 vs. 1.0%) (p surgeries, increased age, length of stay, operative time, and comorbidities including hypertension, dyspnea with moderate exertion, partially dependent functional status, bleeding disorder, transfusion prior to surgery, ASA class III/IV, and metabolic syndrome increased the perioperative bleeding risk (p Bariatric surgery patients who receive postoperative blood transfusion are at a significantly increased risk for VTE. The etiology of VTE in those who are transfused is likely multifactorial and possibly related to withholding chemoprophylaxis and the potential of a hypercoagulable state induced by the transfusion. In those who bleed, consideration should be given to reinitiating chemoprophylaxis when safe, extending treatment after discharge, and screening ultrasound.

  10. Redundant Notch1 and Notch2 signaling is necessary for IFNγ secretion by T helper 1 cells during infection with Leishmania major.

    Directory of Open Access Journals (Sweden)

    Floriane Auderset

    Full Text Available The protective immune response to intracellular parasites involves in most cases the differentiation of IFNγ-secreting CD4(+ T helper (Th 1 cells. Notch receptors regulate cell differentiation during development but their implication in the polarization of peripheral CD4(+ T helper 1 cells is not well understood. Of the four Notch receptors, only Notch1 (N1 and Notch2 (N2 are expressed on activated CD4(+ T cells. To investigate the role of Notch in Th1 cell differentiation following parasite infection, mice with T cell-specific gene ablation of N1, N2 or both (N1N2(ΔCD4Cre were infected with the protozoan parasite Leishmania major. N1N2(ΔCD4Cre mice, on the C57BL/6 L. major-resistant genetic background, developed unhealing lesions and uncontrolled parasitemia. Susceptibility correlated with impaired secretion of IFNγ by draining lymph node CD4(+ T cells and increased secretion of the IL-5 and IL-13 Th2 cytokines. Mice with single inactivation of N1 or N2 in their T cells were resistant to infection and developed a protective Th1 immune response, showing that CD4(+ T cell expression of N1 or N2 is redundant in driving Th1 differentiation. Furthermore, we show that Notch signaling is required for the secretion of IFNγ by Th1 cells. This effect is independent of CSL/RBP-Jκ, the major effector of Notch receptors, since L. major-infected mice with a RBP-Jκ deletion in their T cells were able to develop IFNγ-secreting Th1 cells, kill parasites and heal their lesions. Collectively, we demonstrate here a crucial role for RBP-Jκ-independent Notch signaling in the differentiation of a functional Th1 immune response following L. major infection.

  11. Atherogenic Dyslipidemia and Residual Cardiovascular Risk in Statin-Treated Patients

    DEFF Research Database (Denmark)

    Sirimarco, Gaia; Labreuche, Julien; Bruckert, Eric

    2014-01-01

    BACKGROUND AND PURPOSE: Treatment with statins reduces the rate of cardiovascular events in high-risk patients, but residual risk persists. At least part of that risk may be attributable to atherogenic dyslipidemia characterized by low high-density lipoprotein cholesterol (≤40 mg/dL) and high......% of subjects in PERFORM and 9% in SPARCL had atherogenic dyslipidemia after ≥3 months on start statin therapy. After a follow-up of 2.3 years (PERFORM) and 4.9 years (SPARCL), a major cardiovascular event occurred in 1123 and 485 patients in the 2 trials, respectively. The risk of major cardiovascular events...... was higher in subjects with versus those without atherogenic dyslipidemia in both PERFORM (hazard ratio, 1.36; 95% confidence interval, 1.14-1.63) and SPARCL (hazard ratio, 1.40; 95% confidence interval, 1.06-1.85). The association was attenuated after multivariable adjustment (hazard ratio, 1.23; 95...

  12. Genetic polymorphism of interleukin-1A (IL-1A), IL-1B, and IL-1 receptor antagonist (IL-1RN) and prostate cancer risk.

    Science.gov (United States)

    Xu, Hua; Ding, Qiang; Jiang, Hao-Wen

    2014-01-01

    We aimed to investigate the associations between polymorphisms of interleukin-1A (IL-1A), IL-1B, and IL-1 receptor antagonist (IL-1RN) and prostate cancer (PCa) risk. A comprehensive search for articles of MEDLINE and EMBASE databases and bibliographies of retrieved articles published up to August 3, 2014 was performed. Methodological quality assessment of the trials was based on a standard quality scoring system. The meta-analysis was performed using STATA 12.0. We included 9 studies (1 study for IL-1A, 5 studies for IL-1B, and 3 studies for IL-1RN), and significant association was found between polymorphisms of IL-1B-511 (rs16944) as well as IL-1B-31 (rs1143627) and PCa risk. IL-1B-511 (rs16944) polymorphism was significantly associated with PCa risk in homozygote and recessive models, as well as allele contrast (TT vs CC: OR, 0.74; 95%CI, 0.58-0.94; P=0.012; TT vs TC+CC; OR, 0.79; 95%CI, 0.63-0.98; P=0.033; T vs C: OR, 0.86; 95%CI, 0.77-0.96; P=0.008). The association between IL-1B-31 (rs1143627) polymorphism and PCa risk was weakly significant under a heterozygote model (OR, 1.35; 95%CI, 1.00-1.80; P=0.047). Sequence variants in IL-1B-511 (rs16944) and IL-1B-31 (rs1143627) are significantly associated with PCa risk, which provides additional novel evidence that proinflammatory cytokines and inflammation play an important role in the etiology of PCa.

  13. Dementia, post-traumatic stress disorder and major depressive disorder: a review of the mental health risk factors for dementia in the military veteran population.

    Science.gov (United States)

    Rafferty, L A; Cawkill, P E; Stevelink, S A M; Greenberg, K; Greenberg, N

    2018-07-01

    Dementia is currently incurable, irreversible and a major cause of disability for the world's older population. The association between mental health difficulties, such as post-traumatic stress disorder (PTSD) and major depressive disorder (MDD), and dementia has a long history within the civilian population. Despite the increased importance of this link within the military veteran population, who suffer a greater propensity of mental health difficulties and consist largely of over 65s, attention is only recently being paid to the salience of such an association for this group. This paper aims to explore the relationship between PTSD and MDD with dementia within the military veteran population. A systematic review was conducted on articles from 1990 to July 2016 on MEDLINE, EMBASE, EBSCO and Web of Science electronic databases with an update conducted in February 2017. Six empirical studies were identified from the review, the majority of which originated from the USA. Five of the studies asserted that veterans with a diagnosis of either PTSD or MDD are at a significantly greater risk of developing dementia than 'healthy' controls. The final study, conducted in Australia, found only a small, but non-significant, correlation between earlier MDD and future dementia, but no concurrent correlation. While causality cannot be determined, it is likely that PTSD and depressive disorders are related to an increased risk of dementia in military veterans. Potential pathological explanations and risk factors are reviewed and the clinical and neuroscience implications of these findings are explored.

  14. Selective isolation and differentiation of a stromal population of human embryonic stem cells with osteogenic potential

    DEFF Research Database (Denmark)

    Harkness, Linda M; Mahmood, Amer; Ditzel, Nicholas

    2011-01-01

    cultured in osteogenic differentiation media, up regulation of osteoblastic lineage markers (DLX5, MSX2, RUNX2, SPARC, ALP, COL1a1, BGLAP, IBSP, DCN, LOX-L4) and production of in vitro mineralized matrix was detected. hESC-stromal cells loaded on a carrier and implanted either subcutaneously...... or in a critical size calvarial defect in immune deficient mice for 10weeks, resulted in new bone formation and partial repair of the calvarial defect. In conclusion, hESC-stromal can be isolated from hESC cultures and represent a good source for obtaining cells with osteogenic differentiation potential suitable...

  15. Cancer risks for MLH1 and MSH2 mutation carriers

    OpenAIRE

    Dowty, James G.; Win, Aung K.; Buchanan, Daniel D.; Lindor, Noralane M.; Macrae, Finlay A.; Clendenning, Mark; Antill, Yoland C.; Thibodeau, Stephen N.; Casey, Graham; Gallinger, Steve; Le Marchand, Loic; Newcomb, Polly A.; Haile, Robert W.; Young, Graeme P.; James, Paul A.

    2013-01-01

    We studied 17,576 members of 166 MLH1 and 224 MSH2 mutation-carrying families from the Colon Cancer Family Registry. Average cumulative risks of colorectal cancer (CRC), endometrial cancer (EC) and other cancers for carriers were estimated using modified segregation analysis conditioned on ascertainment criteria. Heterogeneity in risks was investigated using a polygenic risk modifier. Average CRC cumulative risks to age 70 years (95% confidence intervals) for MLH1 and MSH2 mutation carriers, ...

  16. Interbirth interval is associated with childhood type 1 diabetes risk

    DEFF Research Database (Denmark)

    Cardwell, Chris R; Svensson, Jannet; Waldhoer, Thomas

    2012-01-01

    to calculate pooled odds ratios (ORs) and investigate heterogeneity between studies. Overall, 2,787 children with type 1 diabetes were included. There was a reduction in the risk of childhood type 1 diabetes in children born to mothers after interbirth intervals...... of childhood type 1 diabetes has not been investigated. A secondary analysis of 14 published observational studies of perinatal risk factors for type 1 diabetes was conducted. Risk estimates of diabetes by category of interbirth interval were calculated for each study. Random effects models were used...

  17. Major depressive disorder, panic disorder, and post-traumatic stress disorder in Korean subway drivers.

    Science.gov (United States)

    Kim, Hyoung-Ryoul; Yim, Hyeon Woo; Jo, Sun-Jin; Choi, Bongkyoo; Jeong, Seung Hee; Lee, Kang Sook; Park, Jong-Ik; Chang, Sung Man

    2013-05-01

    The purposes of this study are to investigate the prevalence of major depressive disorder, panic disorder, and post-traumatic stress disorder (PTSD) in Korean subway drivers, and find the association between these disorders and the drivers' person-under-train (PUT) experiences. A total of 826 subway drivers who participated in a cross-sectional work and health survey were included for this study. The Korean version of the Composite International Diagnostic Interview 2.1 was applied to assess major depressive disorder, panic disorder, and PTSD. The date of PUT, whether victim died, and how many PUTs the drivers experienced were asked using a structured questionnaire. The standardized prevalence ratios (SPRs) for lifetime prevalence of panic disorder and PTSD in subway drivers were 13.3 (95 % confidence interval [CI] 6.6-22.4) and 2.1 (95 % CI 1.1-3.4), respectively. In lifetime prevalence, after adjusting for age, education, income, and working career, the drivers who experienced PUT had significantly higher risks for panic disorder (odds ratio [OR] = 4.2, 95 % CI 1.2-16.6) and PTSD (OR = 4.4, 95 % CI 1.3-16.4). In 1-year prevalence, the drivers who experienced PUT had a significantly higher risk for PTSD (OR = 11.7, 95 % CI 1.9-225.8). There was no significant value of SPR and OR in major depressive disorder. This study suggests that Korean subway drivers are at higher risk for panic disorder and PTSD compared to the general population, and PUT experience is associated with panic disorder and PTSD. Drivers who have experienced PUT should be treated quickly, sympathetically, and sensitively by a psychological professional and their colleagues, so they can return to work soon.

  18. Urbanization and traffic related exposures as risk factors for Schizophrenia

    DEFF Research Database (Denmark)

    Pedersen, Carsten Bøcker; Mortensen, Preben Bo

    2006-01-01

    : The geographical distance from place of residence to nearest major road had a significant effect. The highest risk was found in children living 500-1000 metres from nearest major road (RR=1.30 (95% Confidence Interval: 1.17-1.44). However, when we accounted for the degree of urbanization, the geographical distance...... that traffic related exposures affect schizophrenia risk and that this potential effect is responsible for the urban-rural differences. The geographical distance from place of residence to nearest major road was used as a proxy variable for traffic related exposures. We used a large population-based sample......BACKGROUND: Urban birth or upbringing increase schizophrenia risk. Though unknown, the causes of these urban-rural differences have been hypothesized to include, e.g., infections, diet, toxic exposures, social class, or an artefact due to selective migration. METHODS: We investigated the hypothesis...

  19. The interplay between alcohol consumption, oral hygiene, ALDH2 and ADH1B in the risk of head and neck cancer.

    Science.gov (United States)

    Tsai, Sen-Tien; Wong, Tung-Yiu; Ou, Chun-Yen; Fang, Sheen-Yie; Chen, Ken-Chung; Hsiao, Jenn-Ren; Huang, Cheng-Chih; Lee, Wei-Ting; Lo, Hung-I; Huang, Jehn-Shyun; Wu, Jiunn-Liang; Yen, Chia-Jui; Hsueh, Wei-Ting; Wu, Yuan-Hua; Yang, Ming-Wei; Lin, Forn-Chia; Chang, Jang-Yang; Chang, Kwang-Yu; Wu, Shang-Yin; Liao, Hsiao-Chen; Lin, Chen-Lin; Wang, Yi-Hui; Weng, Ya-Ling; Yang, Han-Chien; Chang, Jeffrey S

    2014-11-15

    Alcohol consumption is an established risk factor for head and neck cancer (HNC). The major carcinogen from alcohol is acetaldehyde, which may be produced by humans or by oral microorganisms through the metabolism of ethanol. To account for the different sources of acetaldehyde production, the current study examined the interplay between alcohol consumption, oral hygiene (as a proxy measure for the growth of oral microorganisms), and alcohol-metabolizing genes (ADH1B and ALDH2) in the risk of HNC. We found that both the fast (*2/*2) and the slow (*1/*1+ *1/*2) ADH1B genotypes increased the risk of HNC due to alcohol consumption, and this association differed according to the slow/non-functional ALDH2 genotypes (*1/*2+ *2/*2) or poor oral hygiene. In persons with the fast ADH1B genotype, the HNC risk associated with alcohol drinking was increased for those with the slow/non-functional ALDH2 genotypes. For those with the slow ADH1B genotypes, oral hygiene appeared to play an important role; the highest magnitude of an increased HNC risk in alcohol drinkers occurred among those with the worst oral hygiene. This is the first study to show that the association between alcohol drinking and HNC risk may be modified by the interplay between genetic polymorphisms of ADH1B and ALDH2 and oral hygiene. Although it is important to promote abstinence from or reduction of alcohol drinking to decrease the occurrence of HNC, improving oral hygiene practices may provide additional benefit. © 2014 UICC.

  20. Major incidents in rural areas: managing a pandemic A/H1N1/2009 cluster.

    Science.gov (United States)

    Stark, Cameron; Garman, Elaine; McMenamin, Jim; McCormick, Duncan; Oates, Ken

    2010-01-01

    Pandemic Influenza (A/H1N1/2009) caused worldwide concern because of its potential to spread rapidly in human populations. In Scotland, Government policy had been to seek to contain the spread of the virus for as long as possible in order to allow time for service preparations, and for vaccine development and supply. The first major Scottish outbreak of pandemic A/H1N1/2009 was in the rural area of Cowal and Bute. After two initial cases were identified, contact tracing found a cluster of cases associated with a football supporters' bus. Within 3 weeks, 130 cases had been identified in the area. Rapid provision of treatment doses of anti-viral medication to cases and prophylactic treatment of asymptomatic close contacts, advice on self-isolation and, where required, interruption of transmission by temporary school closure, were successful in containing the outbreak. Pre-existing Major Incident and Pandemic Flu plans were used and adapted to the particular circumstances of the outbreak and the area. Supporting operational decision-making as close to the cases as possible allowed for speed and flexibility of response. Contact tracing and tracking of cases and results was performed by specialist public health staff who were geographically removed from the cases. This was possible because of effective use of existing telephone conferencing facilities, clarity of roles, and frequent communication among staff working on all areas of the response. Basing the work on established plans, staff experience of rural areas and rural service provision was successful.

  1. Evaluation of Polygenic Risk Scores for Breast and Ovarian Cancer Risk Prediction in BRCA1 and BRCA2 Mutation Carriers

    Science.gov (United States)

    Kuchenbaecker, Karoline B.; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Soucy, Penny; Healey, Sue; Dennis, Joe; Lush, Michael; Robson, Mark; Spurdle, Amanda B.; Ramus, Susan J.; Mavaddat, Nasim; Terry, Mary Beth; Neuhausen, Susan L.; Hamann, Ute; Southey, Melissa; John, Esther M.; Chung, Wendy K.; Daly, Mary B.; Buys, Saundra S.; Goldgar, David E.; Dorfling, Cecilia M.; van Rensburg, Elizabeth J.; Ding, Yuan Chun; Ejlertsen, Bent; Gerdes, Anne-Marie; Hansen, Thomas V. O.; Slager, Susan; Hallberg, Emily; Benitez, Javier; Osorio, Ana; Cohen, Nancy; Lawler, William; Weitzel, Jeffrey N.; Peterlongo, Paolo; Pensotti, Valeria; Dolcetti, Riccardo; Barile, Monica; Bonanni, Bernardo; Azzollini, Jacopo; Manoukian, Siranoush; Peissel, Bernard; Radice, Paolo; Savarese, Antonella; Papi, Laura; Giannini, Giuseppe; Fostira, Florentia; Konstantopoulou, Irene; Adlard, Julian; Brewer, Carole; Cook, Jackie; Davidson, Rosemarie; Eccles, Diana; Eeles, Ros; Ellis, Steve; Frost, Debra; Hodgson, Shirley; Izatt, Louise; Lalloo, Fiona; Ong, Kai-ren; Godwin, Andrew K.; Arnold, Norbert; Dworniczak, Bernd; Engel, Christoph; Gehrig, Andrea; Hahnen, Eric; Hauke, Jan; Kast, Karin; Meindl, Alfons; Niederacher, Dieter; Schmutzler, Rita Katharina; Varon-Mateeva, Raymonda; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Barjhoux, Laure; Collonge-Rame, Marie-Agnès; Elan, Camille; Golmard, Lisa; Barouk-Simonet, Emmanuelle; Lesueur, Fabienne; Mazoyer, Sylvie; Sokolowska, Joanna; Stoppa-Lyonnet, Dominique; Isaacs, Claudine; Claes, Kathleen B. M.; Poppe, Bruce; de la Hoya, Miguel; Garcia-Barberan, Vanesa; Aittomäki, Kristiina; Nevanlinna, Heli; Ausems, Margreet G. E. M.; de Lange, J. L.; Gómez Garcia, Encarna B.; Hogervorst, Frans B. L.; Kets, Carolien M.; Meijers-Heijboer, Hanne E. J.; Oosterwijk, Jan C.; Rookus, Matti A.; van Asperen, Christi J.; van den Ouweland, Ans M. W.; van Doorn, Helena C.; van Os, Theo A. M.; Kwong, Ava; Olah, Edith; Diez, Orland; Brunet, Joan; Lazaro, Conxi; Teulé, Alex; Gronwald, Jacek; Jakubowska, Anna; Kaczmarek, Katarzyna; Lubinski, Jan; Sukiennicki, Grzegorz; Barkardottir, Rosa B.; Chiquette, Jocelyne; Agata, Simona; Montagna, Marco; Teixeira, Manuel R.; Park, Sue Kyung; Olswold, Curtis; Tischkowitz, Marc; Foretova, Lenka; Gaddam, Pragna; Vijai, Joseph; Pfeiler, Georg; Rappaport-Fuerhauser, Christine; Singer, Christian F.; Tea, Muy-Kheng M.; Greene, Mark H.; Loud, Jennifer T.; Rennert, Gad; Imyanitov, Evgeny N.; Hulick, Peter J.; Hays, John L.; Piedmonte, Marion; Rodriguez, Gustavo C.; Martyn, Julie; Glendon, Gord; Mulligan, Anna Marie; Andrulis, Irene L.; Toland, Amanda Ewart; Jensen, Uffe Birk; Kruse, Torben A.; Pedersen, Inge Sokilde; Thomassen, Mads; Caligo, Maria A.; Teo, Soo-Hwang; Berger, Raanan; Friedman, Eitan; Laitman, Yael; Arver, Brita; Borg, Ake; Ehrencrona, Hans; Rantala, Johanna; Olopade, Olufunmilayo I.; Ganz, Patricia A.; Nussbaum, Robert L.; Bradbury, Angela R.; Domchek, Susan M.; Nathanson, Katherine L.; Arun, Banu K.; James, Paul; Karlan, Beth Y.; Lester, Jenny; Simard, Jacques; Pharoah, Paul D. P.; Offit, Kenneth; Couch, Fergus J.; Chenevix-Trench, Georgia; Easton, Douglas F.

    2017-01-01

    Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]–positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2×10−53). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2×10−20). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management. PMID

  2. Review of the flood risk management system in Germany after the major flood in 2013

    Directory of Open Access Journals (Sweden)

    Annegret H. Thieken

    2016-06-01

    Full Text Available Widespread flooding in June 2013 caused damage costs of €6 to 8 billion in Germany, and awoke many memories of the floods in August 2002, which resulted in total damage of €11.6 billion and hence was the most expensive natural hazard event in Germany up to now. The event of 2002 does, however, also mark a reorientation toward an integrated flood risk management system in Germany. Therefore, the flood of 2013 offered the opportunity to review how the measures that politics, administration, and civil society have implemented since 2002 helped to cope with the flood and what still needs to be done to achieve effective and more integrated flood risk management. The review highlights considerable improvements on many levels, in particular (1 an increased consideration of flood hazards in spatial planning and urban development, (2 comprehensive property-level mitigation and preparedness measures, (3 more effective flood warnings and improved coordination of disaster response, and (4 a more targeted maintenance of flood defense systems. In 2013, this led to more effective flood management and to a reduction of damage. Nevertheless, important aspects remain unclear and need to be clarified. This particularly holds for balanced and coordinated strategies for reducing and overcoming the impacts of flooding in large catchments, cross-border and interdisciplinary cooperation, the role of the general public in the different phases of flood risk management, as well as a transparent risk transfer system. Recurring flood events reveal that flood risk management is a continuous task. Hence, risk drivers, such as climate change, land-use changes, economic developments, or demographic change and the resultant risks must be investigated at regular intervals, and risk reduction strategies and processes must be reassessed as well as adapted and implemented in a dialogue with all stakeholders.

  3. Major cardiovascular risk factors in Latin America: a comparison with the United States. The Latin American Consortium of Studies in Obesity (LASO.

    Directory of Open Access Journals (Sweden)

    J Jaime Miranda

    Full Text Available Limited knowledge on the prevalence and distribution of risk factors impairs the planning and implementation of cardiovascular prevention programs in the Latin American and Caribbean (LAC region.Prevalence of hypertension, diabetes mellitus, abnormal lipoprotein levels, obesity, and smoking were estimated from individual-level patient data pooled from population-based surveys (1998-2007, n=31,009 from eight LAC countries and from a national survey of the United States (US population (1999-2004 Age and gender specific prevalence were estimated and age-gender adjusted comparisons between both populations were conducted. Prevalence of diabetes mellitus, hypertension, and low high-density lipoprotein (HDL-cholesterol in LAC were 5% (95% confidence interval [95% CI]: 3.4, 7.9, 20.2% (95% CI: 12.5, 31, and 53.3% (95% CI: 47, 63.4, respectively. Compared to LAC region's average, the prevalence of each risk factor tended to be lower in Peru and higher in Chile. LAC women had higher prevalence of obesity and low HDL-cholesterol than men. Obesity, hypercholesterolemia, and hypertriglyceridemia were more prevalent in the US population than in LAC population (31 vs. 16.1%, 16.8 vs. 8.9%, and 36.2 vs. 26.5%, respectively. However, the prevalence of low HDL-cholesterol was higher in LAC than in the US (53.3 vs. 33.7%.Major cardiovascular risk factors are highly prevalent in LAC region, in particular low HDL-cholesterol. In addition, marked differences do exist in this prevalence profile between LAC and the US. The observed patterns of obesity-related risk factors and their current and future impact on the burden of cardiovascular diseases remain to be explained.

  4. Risk of cardiovascular disease and total mortality in adults with type 1 diabetes: Scottish registry linkage study.

    Directory of Open Access Journals (Sweden)

    Shona J Livingstone

    Full Text Available Randomized controlled trials have shown the importance of tight glucose control in type 1 diabetes (T1DM, but few recent studies have evaluated the risk of cardiovascular disease (CVD and all-cause mortality among adults with T1DM. We evaluated these risks in adults with T1DM compared with the non-diabetic population in a nationwide study from Scotland and examined control of CVD risk factors in those with T1DM.The Scottish Care Information-Diabetes Collaboration database was used to identify all people registered with T1DM and aged ≥20 years in 2005-2007 and to provide risk factor data. Major CVD events and deaths were obtained from the national hospital admissions database and death register. The age-adjusted incidence rate ratio (IRR for CVD and mortality in T1DM (n = 21,789 versus the non-diabetic population (3.96 million was estimated using Poisson regression. The age-adjusted IRR for first CVD event associated with T1DM versus the non-diabetic population was higher in women (3.0: 95% CI 2.4-3.8, p<0.001 than men (2.3: 2.0-2.7, p<0.001 while the IRR for all-cause mortality associated with T1DM was comparable at 2.6 (2.2-3.0, p<0.001 in men and 2.7 (2.2-3.4, p<0.001 in women. Between 2005-2007, among individuals with T1DM, 34 of 123 deaths among 10,173 who were <40 years and 37 of 907 deaths among 12,739 who were ≥40 years had an underlying cause of death of coma or diabetic ketoacidosis. Among individuals 60-69 years, approximately three extra deaths per 100 per year occurred among men with T1DM (28.51/1,000 person years at risk, and two per 100 per year for women (17.99/1,000 person years at risk. 28% of those with T1DM were current smokers, 13% achieved target HbA(1c of <7% and 37% had very poor (≥9% glycaemic control. Among those aged ≥40, 37% had blood pressures above even conservative targets (≥140/90 mmHg and 39% of those ≥40 years were not on a statin. Although many of these risk factors were comparable to those

  5. Prevalence, Incidence, and Residual Risks for Transfusion Transmitted HIV-1/2 Infection among Chinese Blood Donors

    Science.gov (United States)

    Wang, Jingxing; Liu, Jing; Yao, Fuzhu; Wen, Guoxin; Li, Julin; Huang, Yi; Lv, Yunlai; Wen, Xiuqiong; Wright, David; Yu, Qilu; Guo, Nan; Ness, Paul; Shan, Hua

    2012-01-01

    Background There is little data on HIV prevalence, incidence or residual risks for transfusion transmitted HIV infection among Chinese blood donors. Methods Donations from five Chinese blood centers in 2008–2010 were screened using two rounds of ELISA testing for anti-HIV-1/2. A reactive result in either or both rounds led to Western Blot confirmatory testing. HIV prevalence and demographic correlates among first time donors, incidence rate and demographic correlates among repeat donors were examined. Weighted multivariable logistic regression analysis examined correlates of HIV confirmatory status among first time donors. Residual risks for transfusion transmitted HIV infection were evaluated based on incidence among repeat donors. Results Among 821,320 donations, 40% came from repeat donors.1,837 (0.34%) first time and 577 (0.17%) repeat donations screened reactive for anti-HIV-1/2, among which 1,310 and 419 were tested by Western Blot. 233 (17.7%) first time and 44 (10.5%) repeat donations were confirmed positive. Estimated prevalence was 66 infections per 100,000 (95% CI: 59–74) first time donors. Estimated incidence was 9/100,000 (95% CI: 7–12) person-years among repeat donors. Weighted multivariable logistic regression analysis indicate that first time donors 26–45 years old were 1.6–1.8 times likely to be HIV positive than those 25 years and younger. Donors with some college or above education were less likely to be HIV positive than those with middle school education, ORs ranging from 0.35 to 0.60. Minority were 1.6 times likely to be HIV positive than Han majority donors (OR: 1.6; CI: 1.2–2.1). No difference in prevalence was found between gender. Current HIV TTI residual risk was 5.4 (1.2–12.5) infections per million whole blood donations. Conclusion Despite the declining HIV epidemic China, estimated residual risks for transfusion transmitted HIV infection are still high, highlighting the potential blood safety yield of NAT implementation

  6. Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores.

    Science.gov (United States)

    Lecarpentier, Julie; Silvestri, Valentina; Kuchenbaecker, Karoline B; Barrowdale, Daniel; Dennis, Joe; McGuffog, Lesley; Soucy, Penny; Leslie, Goska; Rizzolo, Piera; Navazio, Anna Sara; Valentini, Virginia; Zelli, Veronica; Lee, Andrew; Amin Al Olama, Ali; Tyrer, Jonathan P; Southey, Melissa; John, Esther M; Conner, Thomas A; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Steele, Linda; Ding, Yuan Chun; Neuhausen, Susan L; Hansen, Thomas V O; Osorio, Ana; Weitzel, Jeffrey N; Toss, Angela; Medici, Veronica; Cortesi, Laura; Zanna, Ines; Palli, Domenico; Radice, Paolo; Manoukian, Siranoush; Peissel, Bernard; Azzollini, Jacopo; Viel, Alessandra; Cini, Giulia; Damante, Giuseppe; Tommasi, Stefania; Peterlongo, Paolo; Fostira, Florentia; Hamann, Ute; Evans, D Gareth; Henderson, Alex; Brewer, Carole; Eccles, Diana; Cook, Jackie; Ong, Kai-Ren; Walker, Lisa; Side, Lucy E; Porteous, Mary E; Davidson, Rosemarie; Hodgson, Shirley; Frost, Debra; Adlard, Julian; Izatt, Louise; Eeles, Ros; Ellis, Steve; Tischkowitz, Marc; Godwin, Andrew K; Meindl, Alfons; Gehrig, Andrea; Dworniczak, Bernd; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Hahnen, Eric; Hauke, Jan; Rhiem, Kerstin; Kast, Karin; Arnold, Norbert; Ditsch, Nina; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Wand, Dorothea; Lasset, Christine; Stoppa-Lyonnet, Dominique; Belotti, Muriel; Damiola, Francesca; Barjhoux, Laure; Mazoyer, Sylvie; Van Heetvelde, Mattias; Poppe, Bruce; De Leeneer, Kim; Claes, Kathleen B M; de la Hoya, Miguel; Garcia-Barberan, Vanesa; Caldes, Trinidad; Perez Segura, Pedro; Kiiski, Johanna I; Aittomäki, Kristiina; Khan, Sofia; Nevanlinna, Heli; van Asperen, Christi J; Vaszko, Tibor; Kasler, Miklos; Olah, Edith; Balmaña, Judith; Gutiérrez-Enríquez, Sara; Diez, Orland; Teulé, Alex; Izquierdo, Angel; Darder, Esther; Brunet, Joan; Del Valle, Jesús; Feliubadalo, Lidia; Pujana, Miquel Angel; Lazaro, Conxi; Arason, Adalgeir; Agnarsson, Bjarni A; Johannsson, Oskar Th; Barkardottir, Rosa B; Alducci, Elisa; Tognazzo, Silvia; Montagna, Marco; Teixeira, Manuel R; Pinto, Pedro; Spurdle, Amanda B; Holland, Helene; Lee, Jong Won; Lee, Min Hyuk; Lee, Jihyoun; Kim, Sung-Won; Kang, Eunyoung; Kim, Zisun; Sharma, Priyanka; Rebbeck, Timothy R; Vijai, Joseph; Robson, Mark; Lincoln, Anne; Musinsky, Jacob; Gaddam, Pragna; Tan, Yen Y; Berger, Andreas; Singer, Christian F; Loud, Jennifer T; Greene, Mark H; Mulligan, Anna Marie; Glendon, Gord; Andrulis, Irene L; Toland, Amanda Ewart; Senter, Leigha; Bojesen, Anders; Nielsen, Henriette Roed; Skytte, Anne-Bine; Sunde, Lone; Jensen, Uffe Birk; Pedersen, Inge Sokilde; Krogh, Lotte; Kruse, Torben A; Caligo, Maria A; Yoon, Sook-Yee; Teo, Soo-Hwang; von Wachenfeldt, Anna; Huo, Dezheng; Nielsen, Sarah M; Olopade, Olufunmilayo I; Nathanson, Katherine L; Domchek, Susan M; Lorenchick, Christa; Jankowitz, Rachel C; Campbell, Ian; James, Paul; Mitchell, Gillian; Orr, Nick; Park, Sue Kyung; Thomassen, Mads; Offit, Kenneth; Couch, Fergus J; Simard, Jacques; Easton, Douglas F; Chenevix-Trench, Georgia; Schmutzler, Rita K; Antoniou, Antonis C; Ottini, Laura

    2017-07-10

    Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigated-for the first time to our knowledge-associations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/ 2 mutations and implications for cancer risk prediction. Materials and Methods We genotyped 1,802 male carriers of BRCA1/2 mutations from the Consortium of Investigators of Modifiers of BRCA1/2 by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of BRCA1/2 mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights. Results In male carriers of BRCA1/2 mutations, PRS that was based on 88 female breast cancer susceptibility variants was associated with breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19 to 1.56; P = 8.6 × 10 -6 ). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95% CI, 1.35 to 1.81; P = 3.2 × 10 -9 ). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7% to 26% for carriers of BRCA1 mutations and from 19% to 61% for carriers of BRCA2 mutations, respectively. Conclusion PRSs may provide informative cancer risk stratification for male carriers of BRCA1/2 mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management.

  7. Smoking and Pregnancy — A Review on the First Major Environmental Risk Factor of the Unborn

    Directory of Open Access Journals (Sweden)

    Mathias Mund

    2013-11-01

    Full Text Available Smoking cigarettes throughout pregnancy is one of the single most important avoidable causes of adverse pregnancy outcomes and it represents the first major environmental risk of the unborn. If compared with other risk factors in the perinatal period, exposure to tobacco smoke is considered to be amongst the most harmful and it is associated with high rates of long and short term morbidity and mortality for mother and child. A variety of adverse pregnancy outcomes are linked with cigarette consumption before and during pregnancy. Maternal prenatal cigarette smoke disturbs the equilibrium among the oxidant and antioxidant system, has negative impact on the genetic and cellular level of both mother and fetus and causes a large quantity of diseases in the unborn child. These smoking-induced damages for the unborn offspring manifest themselves at various times in life and for most only a very limited range of causal treatment exists. Education, support and assistance are of high importance to decrease maternal and fetal morbidity and mortality, as there are few other avoidable factors which influence a child’s health that profoundly throughout its life. It is imperative that smoking control should be seen as a public health priority.

  8. A lifestyle intervention program for successfully addressing major cardiometabolic risks in persons with SCI: a three-subject case series.

    Science.gov (United States)

    Bigford, Gregory E; Mendez, Armando J; Betancourt, Luisa; Burns-Drecq, Patricia; Backus, Deborah; Nash, Mark S

    2017-01-01

    This study is a prospective case series analyzing the effects of a comprehensive lifestyle intervention program in three patients with chronic paraplegia having major risks for the cardiometabolic syndrome (CMS). Individuals underwent an intense 6-month program of circuit resistance exercise, nutrition using a Mediterranean diet and behavioral support, followed by a 6-month extension (maintenance) phase involving minimal support. The primary goal was a 7% reduction of body mass. Other outcomes analyzed insulin resistance using the HOMA-IR model, and plasma levels of fasting triglycerides and high-density lipoprotein cholesterol. All participants achieved the goal for 7% reduction of body mass and maintained the loss after the MP. Improvements were observed in 2/3 subjects for HOMA-IR and high-density lipoprotein cholesterol. All participants improved their risk for plasma triglycerides. We conclude, in a three-person case series of persons with chronic paraplegia, a lifestyle intervention program involving circuit resistance training, a calorie-restrictive Mediterranean-style diet and behavioral support, results in clinically significant loss of body mass and effectively reduced component risks for CMS and diabetes. These results were for the most part maintained after a 6-month MP involving minimal supervision.

  9. Variants of ST8SIA1 are associated with risk of developing multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Seema Husain

    Full Text Available Multiple sclerosis (MS is an inflammatory demyelinating disease of the central nervous system of unknown etiology with both genetic and environmental factors playing a role in susceptibility. To date, the HLA DR15/DQ6 haplotype within the major histocompatibility complex on chromosome 6p, is the strongest genetic risk factor associated with MS susceptibility. Additional alleles of IL7 and IL2 have been identified as risk factors for MS with small effect. Here we present two independent studies supporting an allelic association of MS with polymorphisms in the ST8SIA1 gene, located on chromosome 12p12 and encoding ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1. The initial association was made in a single three-generation family where a single-nucleotide polymorphism (SNP rs4762896, was segregating together with HLA DR15/DQ6 in MS patients. A study of 274 family trios (affected child and both unaffected parents from Australia validated the association of ST8SIA1 in individuals with MS, showing transmission disequilibrium of the paternal alleles for three additional SNPs, namely rs704219, rs2041906, and rs1558793, with p = 0.001, p = 0.01 and p = 0.01 respectively. These findings implicate ST8SIA1 as a possible novel susceptibility gene for MS.

  10. A case-control study of gallstones: a major risk factor for biliary tract cancer.

    Science.gov (United States)

    Kato, I; Kato, K; Akai, S; Tominaga, S

    1990-01-01

    Because of the strong association between gallstones and biliary tract cancer, we conducted a case-control study of gallstones at Niigata Cancer Center Hospital. Eighty-six cases with gallstones (33 males and 53 females) and 116 hospital controls (56 males and 60 females) were surveyed by means of a self-administered questionnaire. Gallstones were categorized into cholesterol stones (25 cases) and pigment stones (30 cases) based on the appearance of the stones. In multivariate analyses based on an unconditional logistic regression model, the risk of total gallstones was positively associated with a taste for salty food (relative risk (RR) = 2.31, 95% confidence interval (CI): 1.10-4.84), an intake of lettuce and cabbage (RR = 2.98, 95% CI: 1.47-6.06) and a family history of biliary diseases (RR = 5.63, 95% CI: 1.76-17.95), and inversely associated with an intake of salted and dried fish (RR = 0.16, 95% CI: 0.04-0.64). When analyzed by type of stones, cholesterol stones were associated with a taste for oily food (RR = 3.87, 95% CI: 1.36-11.03) and pigment stones were positively associated with professional or administrative occupation (RR = 4.74, 95% CI: 1.35-16.68) and inversely associated with a taste for less greasy food (RR = 0.28, 95% CI: 0.10-0.83). Some of these results are consistent with the results of our previous study on biliary tract cancer.

  11. A significantly joint effect between arsenic and occupational exposures and risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2 on risk of urothelial carcinoma

    International Nuclear Information System (INIS)

    Wang, Y.-H.; Yeh, S.-D.; Shen, K.-H.; Shen, Cheng-Huang; Juang, G.-D.; Hsu, L.-I; Chiou, H.-Y.; Chen, C.-J.

    2009-01-01

    Cigarette smoking, arsenic and occupational exposures are well-known risk factors for the development of urothelial carcinoma (UC). Therefore, the aim of this study is to investigate whether the effect of cigarette smoking, alcohol consumption, arsenic and occupational exposures on risk of UC could be modified by genetic polymorphisms of cytochrome P450 2E1 and glutathione S-transferase omega. A hospital-based case-control study consisted of 520 histologically confirmed UC cases, and 520 age- and gender-matched cancer-free controls were carried out from September 1998 to December 2007. Genotyping of CYP2E1, GSTO1 and GSTO2 was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Subjects with both of cigarette smoking and alcohol consumption have a significantly increased UC risk (odds ratio [OR] = 2.9; 95% confidence interval [CI] = 1.9-4.4). Significantly increased UC risks of 1.5 and 1.9 were found for study subjects with high arsenic exposure and those who have been exposed to two or more occupational exposures, respectively. A significantly increased UC risk of 3.9 was observed in study subjects with H2-H2 diplotype of GSTO1 and GSTO2. The significantly highest UC risk of 9.0 was found for those with all environmental risk factors of cigarette smoking, alcohol consumption, arsenic and occupational exposures and two or more risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2. Our findings suggest that a significantly joint effect of cigarette smoking, alcohol consumption, arsenic and occupational exposures and risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2 on risk of UC was found.

  12. HABP2 p.G534E variant in patients with family history of thyroid and breast cancer

    DEFF Research Database (Denmark)

    Pinheiro, Maísa; Drigo, Sandra Aparecida; Tonhosolo, Renata

    2017-01-01

    Familial Papillary Thyroid Carcinoma (PTC) has been described as a hereditary predisposition cancer syndrome associated with mutations in candidate genes including HABP2. Two of 20 probands from families with history of PTC and breast carcinoma (BC) were evaluated by whole exome sequencing (WES...... familial PTC cases. Genes potentially associated with deregulation of the extracellular matrix organization pathway (CTSB, TNXB, COL4A3, COL16A1, COL24A1, COL5A2, NID1, LOXL2, MMP11, TRIM24 and MUSK) and DNA repair function (NBN and MSH2) were detected by WES, suggesting that other cancer-associated genes...

  13. Quantifying Cardiometabolic Risk Using Modifiable Non–Self-Reported Risk Factors

    Science.gov (United States)

    Marino, Miguel; Li, Yi; Pencina, Michael J.; D’Agostino, Ralph B.; Berkman, Lisa F.; Buxton, Orfeu M.

    2014-01-01

    Background Sensitive general cardiometabolic risk assessment tools of modifiable risk factors would be helpful and practical in a range of primary prevention interventions or for preventive health maintenance. Purpose To develop and validate a cumulative general cardiometabolic risk score that focuses on non–self-reported modifiable risk factors such as glycosylated hemoglobin (HbA1c) and BMI so as to be sensitive to small changes across a span of major modifiable risk factors, which may not individually cross clinical cut off points for risk categories. Methods We prospectively followed 2,359 cardiovascular disease (CVD)-free subjects from the Framingham offspring cohort over a 14–year follow-up. Baseline (fifth offspring examination cycle) included HbA1c and cholesterol measurements. Gender–specific Cox proportional hazards models were considered to evaluate the effects of non–self-reported modifiable risk factors (blood pressure, total cholesterol, high–density lipoprotein cholesterol, smoking, BMI, and HbA1c) on general CVD risk. We constructed 10–year general cardiometabolic risk score functions and evaluated its predictive performance in 2012–2013. Results HbA1c was significantly related to general CVD risk. The proposed cardiometabolic general CVD risk model showed good predictive performance as determined by cross-validated discrimination (male C-index=0.703, 95% CI=0.668, 0.734; female C-index=0.762, 95% CI=0.726, 0.801) and calibration (lack-of-fit χ2=9.05 [p=0.338] and 12.54 [p=0.128] for men and women, respectively). Conclusions This study presents a risk factor algorithm that provides a convenient and informative way to quantify cardiometabolic risk based on modifiable risk factors that can motivate an individual’s commitment to prevention and intervention. PMID:24951039

  14. Quantifying cardiometabolic risk using modifiable non-self-reported risk factors.

    Science.gov (United States)

    Marino, Miguel; Li, Yi; Pencina, Michael J; D'Agostino, Ralph B; Berkman, Lisa F; Buxton, Orfeu M

    2014-08-01

    Sensitive general cardiometabolic risk assessment tools of modifiable risk factors would be helpful and practical in a range of primary prevention interventions or for preventive health maintenance. To develop and validate a cumulative general cardiometabolic risk score that focuses on non-self-reported modifiable risk factors such as glycosylated hemoglobin (HbA1c) and BMI so as to be sensitive to small changes across a span of major modifiable risk factors, which may not individually cross clinical cut-off points for risk categories. We prospectively followed 2,359 cardiovascular disease (CVD)-free subjects from the Framingham offspring cohort over a 14-year follow-up. Baseline (fifth offspring examination cycle) included HbA1c and cholesterol measurements. Gender-specific Cox proportional hazards models were considered to evaluate the effects of non-self-reported modifiable risk factors (blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking, BMI, and HbA1c) on general CVD risk. We constructed 10-year general cardiometabolic risk score functions and evaluated its predictive performance in 2012-2013. HbA1c was significantly related to general CVD risk. The proposed cardiometabolic general CVD risk model showed good predictive performance as determined by cross-validated discrimination (male C-index=0.703, 95% CI=0.668, 0.734; female C-index=0.762, 95% CI=0.726, 0.801) and calibration (lack-of-fit chi-square=9.05 [p=0.338] and 12.54 [p=0.128] for men and women, respectively). This study presents a risk factor algorithm that provides a convenient and informative way to quantify cardiometabolic risk on the basis of modifiable risk factors that can motivate an individual's commitment to prevention and intervention. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  15. Risk assessment terminology: risk communication part 1

    Directory of Open Access Journals (Sweden)

    Gaetano Liuzzo

    2016-03-01

    Full Text Available The paper describes the terminology of risk communication in the view of food safety: the theory of stakeholders, the citizens’ involvement and the community interest and consultation are reported. Different aspects of risk communication (public communication, scientific uncertainty, trust, care, consensus and crisis communication are discussed.

  16. Residual sleep disturbance and risk of relapse during the continuation/maintenance phase treatment of major depressive disorder with the selective serotonin reuptake inhibitor fluoxetine

    Directory of Open Access Journals (Sweden)

    McGrath Patrick J

    2010-02-01

    Full Text Available Abstract Background Relapse of major depressive disorder (MDD is a common clinical problem. This study was designed to determine whether residual sleep disturbance (insomnia and hypersomnia predict risk of relapse during the continuation and maintenance treatment of MDD. Methods A total of 570 patients with MDD were treated with open-label, flexible dose fluoxetine (range 20 to 60 mg; mean dose = 45.8 mg/day; SD = 15.1 for 12 weeks. Under double blind conditions, 262 patients who achieved clinical response were randomly assigned to continue fluoxetine or to switch to placebo for 52 weeks or until relapse. Residual sleep disturbance during the baseline visit of the double-blind phase was assessed using items 4, 5, 6 (insomnia and 22, 23, 24 (hypersomnia of the Hamilton Depression Rating Scale (HDRS. Survival analysis was utilized to determine the effect of residual sleep disturbance on risk of relapse. Results The severities of early (P > 0.05, middle (P > 0.05, late (P > 0.05, or total (P > 0.05 residual insomnia were not found to significantly predict risk of relapse during continuation and maintenance-phase treatment. Similarly, the severities of early bedtime (P > 0.05, oversleeping (P > 0.05, napping (P > 0.05, or total (P > 0.05 residual hypersomnia were not found to significantly predict risk of relapse during continuation and maintenance-phase treatment. Conclusion The present study did not identify the severity of residual sleep disturbance among fluoxetine responders to predict risk of MDD relapse. The size of our sample may have precluded us from identifying more modest effects of residual sleep disturbance on the risk of relapse in MDD patients. Future studies are needed to further explore the relationship between residual sleep disturbance and relapse in MDD. Trial Registration ClinicalTrials.gov Identifier: NCT00427128

  17. Cardiovascular risk-factor knowledge and risk perception among HIV-infected adults.

    Science.gov (United States)

    Cioe, Patricia A; Crawford, Sybil L; Stein, Michael D

    2014-01-01

    Cardiovascular disease (CVD) has emerged as a major cause of morbidity and mortality in HIV-infected adults. Research in noninfected populations has suggested that knowledge of CVD risk factors significantly influences perceptions of risk. This cross-sectional study describes CVD risk factor knowledge and risk perception in HIV-infected adults. We recruited 130 HIV-infected adults (mean age = 48 years, 62% male, 56% current smokers, mean years since HIV diagnosis, 14.7). The mean CVD risk factor knowledge score was fairly high. However, controlling for age, CVD risk factor knowledge was not predictive of perceived risk [F(1, 117) = 0.13, p > .05]. Estimated risk and perceived risk were weakly but significantly correlated; r (126) = .24, p = .01. HIV-infected adults are at increased risk for CVD. Despite having adequate risk-factor knowledge, CVD risk perception was inaccurate. Improving risk perception and developing CVD risk reduction interventions for this population are imperative. Copyright © 2014 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

  18. Risk prediction models for major adverse cardiac event (MACE) following percutaneous coronary intervention (PCI): A review

    Science.gov (United States)

    Manan, Norhafizah A.; Abidin, Basir

    2015-02-01

    Five percent of patients who went through Percutaneous Coronary Intervention (PCI) experienced Major Adverse Cardiac Events (MACE) after PCI procedure. Risk prediction of MACE following a PCI procedure therefore is helpful. This work describes a review of such prediction models currently in use. Literature search was done on PubMed and SCOPUS database. Thirty literatures were found but only 4 studies were chosen based on the data used, design, and outcome of the study. Particular emphasis was given and commented on the study design, population, sample size, modeling method, predictors, outcomes, discrimination and calibration of the model. All the models had acceptable discrimination ability (C-statistics >0.7) and good calibration (Hosmer-Lameshow P-value >0.05). Most common model used was multivariate logistic regression and most popular predictor was age.

  19. Association of major depression and diabetes in medically indigent Puerto Rican adults.

    Science.gov (United States)

    Disdier-Flores, Orville M

    2010-03-01

    Studies have found that major depression and diabetes mellitus are strongly associated. The main goal of this study was to evaluate the association between major depression and diabetes in a large medically indigent population of Puerto Rican adults living on the island. A secondary database analysis through a cross-sectional design was used for this study. Participants were selected from the Puerto Rico Commonwealth Health Plan database, beneficiaries of the public health sector. Adult's subjects with at least one claim during 2002 were included. The final sample consisted of 1,026,625 adult insured. The International Classification of Diseases (ICD-9) was used for disease classifications. The prevalence of diabetes was 14.6% in subjects with major depression and 9.7% for those without major depression (POR 1.59, p diabetes appears to be significantly higher in Puerto Rican adults with major depression compared to those without this psychiatric disorder. Longitudinal prospective studies and randomized controlled trials are needed to shed light on the temporal or causal relationship and to test whether effective prevention and treatment can reduce the risk of developing diabetes.

  20. Risk in pediatric anesthesia.

    Science.gov (United States)

    Paterson, Neil; Waterhouse, Peter

    2011-08-01

    Risk in pediatric anesthesia can be conveniently classified as minor or major. Major morbidity includes cardiac arrest, brain damage and death. Minor morbidity can be assessed by clinical audits with small patient samples. Major morbidity is rare. It is best assessed by very large clinical studies and by review of closed malpractice claims. Both minor and major morbidity occur most commonly in infants and children under three, especially those with severe co-morbidities. Knowledge of risk profiles in pediatric anesthesia is a starting point for the reduction of risk. © 2010 Blackwell Publishing Ltd.

  1. Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor.

    Science.gov (United States)

    Tenenbaum, Alexander; Klempfner, Robert; Fisman, Enrique Z

    2014-12-04

    The existence of an independent association between elevated triglyceride (TG) levels, cardiovascular (CV) risk and mortality has been largely controversial. The main difficulty in isolating the effect of hypertriglyceridemia on CV risk is the fact that elevated triglyceride levels are commonly associated with concomitant changes in high density lipoprotein (HDL), low density lipoprotein (LDL) and other lipoproteins. As a result of this problem and in disregard of the real biological role of TG, its significance as a plausible therapeutic target was unfoundedly underestimated for many years. However, taking epidemiological data together, both moderate and severe hypertriglyceridaemia are associated with a substantially increased long term total mortality and CV risk. Plasma TG levels partially reflect the concentration of the triglyceride-carrying lipoproteins (TRL): very low density lipoprotein (VLDL), chylomicrons and their remnants. Furthermore, hypertriglyceridemia commonly leads to reduction in HDL and increase in atherogenic small dense LDL levels. TG may also stimulate atherogenesis by mechanisms, such excessive free fatty acids (FFA) release, production of proinflammatory cytokines, fibrinogen, coagulation factors and impairment of fibrinolysis. Genetic studies strongly support hypertriglyceridemia and high concentrations of TRL as causal risk factors for CV disease. The most common forms of hypertriglyceridemia are related to overweight and sedentary life style, which in turn lead to insulin resistance, metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM). Intensive lifestyle therapy is the main initial treatment of hypertriglyceridemia. Statins are a cornerstone of the modern lipids-modifying therapy. If the primary goal is to lower TG levels, fibrates (bezafibrate and fenofibrate for monotherapy, and in combination with statin; gemfibrozil only for monotherapy) could be the preferable drugs. Also ezetimibe has mild positive effects in lowering TG

  2. Membrane omega-3 Fatty Acid deficiency as a preventable risk factor for comorbid coronary heart disease in major depressive disorder.

    Science.gov (United States)

    McNamara, Robert K

    2009-01-01

    Major depression disorder (MDD) significantly increases the risk for coronary heart disease (CHD) which is a leading cause of mortality in patients with MDD. Moreover, depression is frequently observed in a subset of patients following acute coronary syndrome (ACS) and increases risk for mortality. Here evidence implicating omega-3 (n-3) fatty acid deficiency in the pathoaetiology of CHD and MDD is reviewed, and the hypothesis that n-3 fatty acid deficiency is a preventable risk factor for CHD comorbidity in MDD patients is evaluated. This hypothesis is supported by cross-national and cross-sectional epidemiological surveys finding an inverse correlation between n-3 fatty acid status and prevalence rates of both CHD and MDD, prospective studies finding that lower dietary or membrane EPA+DHA levels increase risk for both MDD and CHD, case-control studies finding that the n-3 fatty acid status of MDD patients places them at high risk for emergent CHD morbidity and mortality, meta-analyses of controlled n-3 fatty acid intervention studies finding significant advantage over placebo for reducing depression symptom severity in MDD patients, and for secondary prevention of cardiac events in CHD patients, findings that n-3 fatty acid status is inversely correlated with other documented CHD risk factors, and patients diagnosed with MDD after ACS exhibit significantly lower n-3 fatty acid status compared with nondepressed ACS patients. This body of evidence provides strong support for future studies to evaluate the effects of increasing dietary n-3 fatty acid status on CHD comorbidity and mortality in MDD patients.

  3. Outcomes of influenza A(H1N1)pdm09 virus infection

    DEFF Research Database (Denmark)

    Lynfield, Ruth; Davey, Richard; Dwyer, Dominic E

    2014-01-01

    BACKGROUND: Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited. In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were...

  4. Minerals in thalassaemia major patients: An overview.

    Science.gov (United States)

    Ozturk, Zeynep; Genc, Gizem Esra; Gumuslu, Saadet

    2017-05-01

    Thalassaemia major (TM) is a hereditary blood disease characterised by reduced or absent production of beta globin chains. Erythrocyte transfusions are given to raise the haemoglobin level in patients with thalassaemia major. However, transfusions have been related to increased risk of iron overload and tissue damage related to excess iron. Both elevated oxidative stress due to iron overload and increased hemolysis lead to over utilisation of minerals required for antioxidant enzymes activities. Iron chelators have been used to prevent iron overload in thalassaemia major patients, but these chelators have the possibility of removing minerals from the body. Thalassaemia patients are more at risk for mineral deficiency because of increased oxidative stress and iron chelation therapies. Growth and maturational delay, cardiomyopathy, endocrinopathies and osteoporosis are the complications of thalassaemia. Minerals may play a particular role to prevent these complications. In the current review, we provide an overview of minerals including zinc (Zn), copper (Cu), selenium (Se), magnesium (Mg) and calcium (Ca) in thalassaemia major patients. We, also, underline that some complications of thalassaemia can be caused by an increased need for minerals or lack of the minerals. Copyright © 2017 Elsevier GmbH. All rights reserved.

  5. Myastenia and risk of cancer

    DEFF Research Database (Denmark)

    Pedersen, Emil Arnspang; Pottegård, Anton; Hallas, Jesper

    2014-01-01

    BACKGROUND AND PURPOSE: To evaluate the association between having non-thymoma myasthenia and the risk of extra-thymic cancer in a population-based setting. METHODS: A nationwide case-control study was conducted in Denmark based on medical registries. The study included all cases with a first time...... diagnosis of cancer during 2000-2009. Each case was matched by birth year and gender with eight population controls using risk set sampling. Subjects with myasthenia were identified through a validated register-based algorithm. Conditional logistic regression was used to compute crude and adjusted odds...... risk of overall cancer (OR 1.1; 95% CI 0.9-1.4). Adjusted ORs for major cancer sites were also close to unity, whereas an elevated risk of lymphomas was observed (OR 2.0; 95% CI 0.8-5.5). Early-onset myasthenia was associated with a slightly increased OR for overall cancer (1.5; 95% CI 1...

  6. Feasibility and early outcome of high-dose-rate Ir-192 brachytherapy as monotherapy in two fractions within 1 day for high-/very high-risk prostate cancer.

    Science.gov (United States)

    Ashida, Shingo; Yamasaki, Ichiro; Tamura, Kenji; Shimamoto, Tsutomu; Inoue, Keiji; Kariya, Shinji; Kobayashi, Kana; Yamagami, Takuji; Shuin, Taro

    2016-05-01

    The aim of the present study was to evaluate the feasibility and preliminary outcomes of high-dose-rate (HDR)-brachytherapy as a monotherapy in two fractions within 1 day for localized prostate cancer, including high-/very high-risk cases. Among the 68 patients treated with HDR monotherapy between July 2011 and December 2014, 65 had a minimal follow-up of 12 months without adjuvant androgen deprivation therapy and were enrolled in the present study [42/65 (64.6%) exhibited high-/very high-risk diseases]. HDR monotherapy was performed in two fractions with a minimal interval of 6 h and the prescribed dose was 13.5 Gy (×2). Adverse events (AEs) were assessed using Common Terminology Criteria for Adverse Events (version 4; http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40), and biochemical failure was assessed by the Phoenix definition. The median follow-up time was 30.1 months. The majority of patients had Grade 0-1 acute AEs. Four patients (6.2%) exhibited urinary retention, requiring a Foley catheter. Grade 3 acute AEs occurred at a frequency of 3.1% and hematuria at 1.5%. The majority of patients also exhibited Grade 0-1 chronic AEs. Grade 3 chronic AEs occurred at a frequency of 1.5% and urethral stricture at 1.5%, for which endoscopic treatment was indicated. Acute and chronic gastrointestinal AEs were uncommon, and no Grade 3 or above AEs developed. Biochemical failure occurred in 4 patients who all exhibited high-/very high-risk diseases. Kaplan-Meier estimated that 3 year biochemical failure-free survival was 91.6% overall and 88.0% in high-/very high-risk cases. The present two-fraction 1 day HDR monotherapy is feasible with minimal AEs and achieved acceptable biochemical control of localized prostate cancer, including high-/very high-risk cases, although long-term follow-up is required.

  7. Genetic polymorphisms of GSTO2, GSTM1, and GSTT1 and risk of gastric cancer.

    Science.gov (United States)

    Masoudi, Mohammad; Saadat, Iraj; Omidvari, Shahpour; Saadat, Mostafa

    2009-04-01

    The glutathione S-transferases (GSTs) are a superfamily of proteins that participates in detoxification. The GSTs were dividing into several classes including omega (GSTO), micro (GSTM) and theta (GSTT) classes. In human GSTO2, GSTM1, and GSTT1 are polymorphic. In order to study whether GSTO2, GSTM1, and GSTT1 polymorphisms are associated with increased gastric cancer risk in Iranian patients, the present case-control study was done. Genomic DNA was extracted from peripheral blood of 67 gastric cancer patients and 134 control subjects. The genotyping was performed using PCR-based method. The possible association of gastric cancer with the GSTO2 N142D polymorphism was estimated with assuming additive, dominant, and recessive effect of the variant 142D allele. To investigate whether profiles of GST genotypes are associated with the risk of gastric cancer, we used unconditional logistic regression analysis. The GSTO2 142D allele in additive, dominant and recessive models was not associated with the risk. Because GSTM1, GSTT1, and GSTO2 genes belong to low-penetrance genes which might be involved in the carcinogenesis, patients and controls without family of cancer in first-degree relatives were also analyzes separately. To investigate whether profiles of GST genotypes are associated with the risk of gastric cancer, we used unconditional logistic regression analysis with GSTM1, GSTT1, and GSTO2 genotypes as predictor factors. The GSTO2 DD genotype was associated with decreased risk as compared to GSTO2 NN genotype (OR = 0.21, 95% CI: 0.05-0.92, P = 0.038). Present findings show that GSTO2 DD genotype decreases the risk of gastric cancer in individuals without history of cancer in their first-degree relatives.

  8. Combustion modeling and kinetic rate calculations for a stoichiometric cyclohexane flame. 1. Major reaction pathways.

    Science.gov (United States)

    Zhang, Hongzhi R; Huynh, Lam K; Kungwan, Nawee; Yang, Zhiwei; Zhang, Shaowen

    2007-05-17

    The Utah Surrogate Mechanism was extended in order to model a stoichiometric premixed cyclohexane flame (P = 30 Torr). Generic rates were assigned to reaction classes of hydrogen abstraction, beta scission, and isomerization, and the resulting mechanism was found to be adequate in describing the combustion chemistry of cyclohexane. Satisfactory results were obtained in comparison with the experimental data of oxygen, major products and important intermediates, which include major soot precursors of C2-C5 unsaturated species. Measured concentrations of immediate products of fuel decomposition were also successfully reproduced. For example, the maximum concentrations of benzene and 1,3-butadiene, two major fuel decomposition products via competing pathways, were predicted within 10% of the measured values. Ring-opening reactions compete with those of cascading dehydrogenation for the decomposition of the conjugate cyclohexyl radical. The major ring-opening pathways produce 1-buten-4-yl radical, molecular ethylene, and 1,3-butadiene. The butadiene species is formed via beta scission after a 1-4 internal hydrogen migration of 1-hexen-6-yl radical. Cascading dehydrogenation also makes an important contribution to the fuel decomposition and provides the exclusive formation pathway of benzene. Benzene formation routes via combination of C2-C4 hydrocarbon fragments were found to be insignificant under current flame conditions, inferred by the later concentration peak of fulvene, in comparison with benzene, because the analogous species series for benzene formation via dehydrogenation was found to be precursors with regard to parent species of fulvene.

  9. Operative risk and preoperative hematocrit in bypass graft surgery: Role of gender and blood transfusion.

    Science.gov (United States)

    Ad, Niv; Holmes, Sari D; Massimiano, Paul S; Spiegelstein, Dan; Shuman, Deborah J; Pritchard, Graciela; Halpin, Linda

    2015-01-01

    The association between lower preoperative hematocrit (Hct) and risk for morbidity/mortality after cardiac surgery is well established. We examined whether the impact of low preoperative Hct on outcome is modified by blood transfusion and operative risk in women and men undergoing nonemergent CABG surgery. Patients having nonemergent, first-time, isolated CABG were included (N=2757). Logistic regressions assessed effect of hematocrit on major perioperative morbidity/mortality separately by males (n=2232) and females (n=525). Mean age was 63.2±10.1years, preoperative hematocrit was 38.9±4.8%, and STS risk score was 1.3±1.8%. Blood transfusion was more likely in female patients (26% vs. 12%, Ptransfusion in males and females, whereas older age (OR=1.03, P=0.017) also predicted transfusion in females. Major morbidity was also more likely in female patients (12% vs. 7%, Pblood transfusion was the only predictive factor for major morbidity in females (OR=4.56, Pblood transfusion (OR=9.22, Pblood transfusion and major morbidities after nonemergent CABG. Traditional factors that have been found to predict outcomes, such as hematocrit and STS risk, were related only to major morbidity in male patients. However, blood transfusion negatively impacted major outcome after nonemergent CABG surgery across all STS risk levels in both genders. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Symptoms of major depressive disorder subsequent to child maltreatment: Examining change across multiple levels of analysis to identify transdiagnostic risk pathways.

    Science.gov (United States)

    Shenk, Chad E; Griffin, Amanda M; O'Donnell, Kieran J

    2015-11-01

    Major depressive disorder (MDD) is a prevalent psychiatric condition in the child maltreatment population. However, not all children who have been maltreated will develop MDD or MDD symptoms, suggesting the presence of unique risk pathways that explain how certain children develop MDD symptoms when others do not. The current study tested several candidate risk pathways to MDD symptoms following child maltreatment: neuroendocrine, autonomic, affective, and emotion regulation. Female adolescents (N = 110; age range = 14-19) were recruited into a substantiated child maltreatment or comparison condition and completed a laboratory stressor, saliva samples, and measures of emotion regulation, negative affect, and MDD symptoms. MDD symptoms were reassessed 18 months later. Mediational modeling revealed that emotion regulation was the only significant indirect effect of the relationship between child maltreatment and subsequent MDD symptoms, demonstrating that children exposed to maltreatment had greater difficulties managing affective states that in turn led to more severe MDD symptoms. These results highlight the importance of emotion dysregulation as a central risk pathway to MDD following child maltreatment. Areas of future research and implications for optimizing prevention and clinical intervention through the direct targeting of transdiagnostic risk pathways are discussed.

  11. Association between RTEL1, PHLDB1, and TREH Polymorphisms and Glioblastoma Risk: A Case-Control Study.

    Science.gov (United States)

    Yang, Bo; Heng, Liang; Du, Shuli; Yang, Hua; Jin, Tianbo; Lang, Hongjun; Li, Shanqu

    2015-07-09

    Glioblastoma (GBM) is a highly invasive, aggressive, and incurable brain tumor. Genetic factors play important roles in GBM risk. The aim of this study was to elucidate the influence of gene polymorphism on GBM susceptibility. In this case-control study, we included 72 GBM patients and 320 healthy controls to analyze the association between 29 single-nucleotide polymorphisms and GBM cancer risk in the Chinese Han population. The single-nucleotide polymorphisms were determined by Sequenom MassARRAY RS1000 and statistical analysis was performed using SPSS software and SNPStats software. Using the χ(2) test, we found that rs2297440 and rs6010620 in RTEL1 increased risk of GBM. In the recessive model, we also found that the genotypes "CC" of rs2297440 and "GG" of rs6010620 in RTEL1 significantly increased GBM risk. The variant TT genotype of TREH rs17748 and the variant TT genotype of PHLDB1 rs498872 decreased GBM risk in the recessive model. We also found that the TREH rs17748 variant C allele showed an increased risk in males in the dominant model. Our results suggest a significant association between the RETL1, TREH, and PHLDB1 genes and GBM development in the Han Chinese population.

  12. Two-year prospective study of major depressive disorder in HIV-infected men.

    Science.gov (United States)

    Atkinson, J Hampton; Heaton, Robert K; Patterson, Thomas L; Wolfson, Tanya; Deutsch, Reena; Brown, Stephen J; Summers, J; Sciolla, A; Gutierrez, R; Ellis, Ronald J; Abramson, Ian; Hesselink, John R; McCutchan, J Allen; Grant, Igor

    2008-06-01

    The risks and factors contributing to major depressive episodes in HIV infection remain unclear. This 2-year prospective study compared cumulative rates and predictors of a major depressive episode in HIV-infected (HIV+) men (N=297) and uninfected (HIV-) risk-group controls (N=90). By design participants at entry were without current major depression, substance dependence or major anxiety disorder. Standardized neuromedical, neuropsychological, neuroimaging, life events, and psychiatric assessments (Structured Clinical Interview for DSM III-R) were conducted semi-annually for those with AIDS, and annually for all others. Lifetime prevalence of major depression or other psychiatric disorder did not differ at baseline between HIV+ men and controls. On a two-year follow-up those with symptomatic HIV disease were significantly more likely to experience a major depressive episode than were asymptomatic HIV+ individuals and HIV-controls (pdepression. After baseline disease stage and medical variables associated with HIV infection were controlled, a lifetime history of major depression, or of lifetime psychiatric comorbidity (two or more psychiatric disorders), predicted subsequent major depressive episode (pdepressive episode. Research cohort of men examined before era of widespread use of advanced anti-HIV therapies. Symptomatic HIV disease, but not HIV infection itself, increases intermediate-term risk of major depression. Prior psychiatric history most strongly predicted future vulnerability.

  13. Clinical and Surgical Factors Associated With Increased Epilepsy Risk in Children With Hydrocephalus.

    Science.gov (United States)

    Tully, Hannah M; Kukull, Walter A; Mueller, Beth A

    2016-06-01

    Children with hydrocephalus are at risk for epilepsy both due to their underlying condition and as a consequence of surgical treatment; however, the relative contributions of these factors remain unknown. The authors sought to characterize epilepsy among children with infancy-onset hydrocephalus and to examine the risks of epilepsy associated with hydrocephalus subtype and with factors related to surgical treatment. We conducted a longitudinal cohort study of all children with infancy-onset hydrocephalus treated at a major regional children's hospital during 2002 to 2012, with follow-up to ascertain risk factors and epilepsy outcome through April 2015. Poisson regression was used to calculate adjusted risk ratios and 95% confidence intervals for associations. Among 379 children with hydrocephalus, 86 (23%) developed epilepsy (mean onset age = 2.7 years), almost one fifth of whom had a history of infantile spasms. Relative to spina bifida-associated hydrocephalus, children with other major hydrocephalus subtypes had fourfold higher risks of developing epilepsy. Among children who underwent surgery, surgical infection doubled the risk of epilepsy (risk ratio = 2.0, 95% confidence interval = 1.4 to 3.0). Epilepsy was associated with surgical failure for intracranial reasons but not extracranial reasons (risk ratio = 1.7, 95% confidence interval = 1.1 to 2.7; risk ratio = 1.1, 95% confidence interval = 0.7 to 1.9, respectively). Epilepsy is common among children with hydrocephalus. Compared with children with spina bifida-associated hydrocephalus, children with other major hydrocephalus subtypes have a markedly increased risk of epilepsy. Surgical infection doubles the risk of epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Prediction of Major Vascular Events after Stroke

    DEFF Research Database (Denmark)

    Ovbiagele, Bruce; Goldstein, Larry B.; Amarenco, Pierre

    2014-01-01

    BACKGROUND: Identifying patients with recent stroke or transient ischemic attack (TIA) at high risk of major vascular events (MVEs; stroke, myocardial infarction, or vascular death) may help optimize the intensity of secondary preventive interventions. We evaluated the relationships between...... the baseline Framingham Coronary Risk Score (FCRS) and a novel risk prediction model and with the occurrence of MVEs after stroke or TIA in subjects enrolled in the Stroke Prevention by Aggressive Reduction in Cholesterol Level (SPARCL) trial. METHODS: Data from the 4731 subjects enrolled in the SPARCL study...... were analyzed. Hazard ratios (HRs) from Cox regression models were used to determine the risk of subsequent MVEs based on the FCRS predicting 20% or more 10-year coronary heart disease risk. The novel risk model was derived based on multivariable modeling with backward selection. Model discrimination...

  15. Gender Differences in Major Dietary Patterns and Their Relationship with Cardio-Metabolic Risk Factors in a Year before Coronary Artery Bypass Grafting (CABG) Surgery Period.

    Science.gov (United States)

    Abbasalizad Farhangi, Mahdieh; Ataie-Jafari, Asal; Najafi, Mahdi; Sarami Foroushani, Gholamreza; Mohajeri Tehrani, Mohammad Reza; Jahangiry, Leila

    2016-07-01

    Previous studies reported the association between dietary patterns and prevalence of diabetes, cardiovascular disease and other chronic disease. However, there are no studies reporting major dietary patterns in patients awaiting coronary artery bypass graft surgery (CABG). The aim of this study was to obtain the major dietary patterns and their association with demographic, dietary factors and biochemical parameters in these patients. This was a cross-sectional study on 454 patients aged 35 - 80 years as candidates of CABG and hospitalized in the Tehran Heart Center. Anthropometric and demographic characteristics were obtained from all participants and a 138-item semi-quantitative food frequency questionnaire (FFQ) was used to evaluate dietary patterns by factor analysis. Biochemical parameters including HbA1c, serum lipids, hematocrit (HCT), albumin, creatinine and CRP were assessed by commercial laboratory methods. Five major dietary patterns, including: healthy, intermediate, neo-traditional, western and semi-Mediterranean patterns were extracted. Top quartile of healthy pattern was associated with higher educational attainment and lower serum low-density lipoprotein cholesterol (LDL), and total cholesterol (TC) in men, as well as  higher high-density lipoprotein cholesterol (HDL) concentrations in women (P habits, as well as the lower prevalence of diabetes, hyperlipidemia and hypertension (P eating patterns were associated with lower cardio-metabolic risk factors.

  16. The interrelation between premenstrual syndrome and major depression: Results from a population-based sample

    Directory of Open Access Journals (Sweden)

    Weiss Carine

    2011-10-01

    Full Text Available Abstract Background Research about the relationship between premenstrual syndrome (PMS and major depression is limited. This study examined the relationship between moderate to severe PMS and major depression in a population-based sample of women of reproductive age. The objectives of the study were to assess the association between premenstrual syndrome and major depression, to analyse how PMS and major depression differ and to characterise the group of women who report both PMS and major depression. Methods Data were obtained from the Swiss Health Survey 2007. Included in the analysis was data from women under the age of 55 without hysterectomy and who answered the questions on PMS symptoms. The population-based sample consisted of 3518 women. Weighted prevalence rates were calculated and relative risk ratios for PMS, major depression and women who reported both PMS and major depression, were calculated with logistic multinominal logit regression. Results The prevalence of major depression was 11.3% in women screening positive for moderate PMS and 24.6% in women screening positive for severe PMS. Compared to women without any of these conditions, women who reported moderate to severe alcohol consumption had a lower risk for PMS. Women reporting use of antidepressants, and use of oral contraceptives had a higher risk for major depression compared to women without any of these conditions. Women reporting work dissatisfaction had a higher risk for PMS. A higher relative risk to report both PMS and major depression compared to women without PMS or major depression was related to factors such as high psychological distress, low mastery, psychotropic drug consumption, and low self-rated health. Conclusions The results suggested that women who suffer from both PMS and major depression are more impaired compared to women with only one disorder. The results further indicated that PMS and major depression are different disorders that can, however, co-occur.

  17. Major Cardiovascular Risk Factors in Latin America: A Comparison with the United States. The Latin American Consortium of Studies in Obesity (LASO)

    Science.gov (United States)

    Chirinos, Julio A.; Gómez, Luis F.; Perel, Pablo; Pichardo, Rafael; González, Angel; Sánchez, José R.; Ferreccio, Catterina; Aguilera, Ximena; Silva, Eglé; Oróstegui, Myriam; Medina-Lezama, Josefina; Pérez, Cynthia M.; Suárez, Erick; Ortiz, Ana P.; Rosero, Luis; Schapochnik, Noberto; Ortiz, Zulma; Ferrante, Daniel; Casas, Juan P.

    2013-01-01

    Background Limited knowledge on the prevalence and distribution of risk factors impairs the planning and implementation of cardiovascular prevention programs in the Latin American and Caribbean (LAC) region. Methods and Findings Prevalence of hypertension, diabetes mellitus, abnormal lipoprotein levels, obesity, and smoking were estimated from individual-level patient data pooled from population-based surveys (1998–2007, n = 31,009) from eight LAC countries and from a national survey of the United States (US) population (1999–2004) Age and gender specific prevalence were estimated and age-gender adjusted comparisons between both populations were conducted. Prevalence of diabetes mellitus, hypertension, and low high-density lipoprotein (HDL)-cholesterol in LAC were 5% (95% confidence interval [95% CI]: 3.4, 7.9), 20.2% (95% CI: 12.5, 31), and 53.3% (95% CI: 47, 63.4), respectively. Compared to LAC region’s average, the prevalence of each risk factor tended to be lower in Peru and higher in Chile. LAC women had higher prevalence of obesity and low HDL-cholesterol than men. Obesity, hypercholesterolemia, and hypertriglyceridemia were more prevalent in the US population than in LAC population (31 vs. 16.1%, 16.8 vs. 8.9%, and 36.2 vs. 26.5%, respectively). However, the prevalence of low HDL-cholesterol was higher in LAC than in the US (53.3 vs. 33.7%). Conclusions Major cardiovascular risk factors are highly prevalent in LAC region, in particular low HDL-cholesterol. In addition, marked differences do exist in this prevalence profile between LAC and the US. The observed patterns of obesity-related risk factors and their current and future impact on the burden of cardiovascular diseases remain to be explained. PMID:23349785

  18. The interleukin 1 beta (IL1B) gene is associated with failure to achieve remission and impaired emotion processing in major depression.

    Science.gov (United States)

    Baune, Bernhard T; Dannlowski, Udo; Domschke, Katharina; Janssen, Debbie G A; Jordan, Margaret A; Ohrmann, Patricia; Bauer, Jochen; Biros, Erik; Arolt, Volker; Kugel, Harald; Baxter, Alan G; Suslow, Thomas

    2010-03-15

    Accumulating evidence suggests the involvement of inflammatory processes and cytokines in particular in the pathophysiology of major depression (MDD) and resistance to antidepressant treatment. Furthermore, amygdala and anterior cingulate cortex (ACC) responsiveness to emotional stimuli has been suggested as a predictor of treatment response. This study investigated the association between genetic variants of the interleukin 1 beta (IL1B) gene and amygdala and ACC responsiveness to emotional stimuli and response to antidepressant treatment. In this analysis, 256 Caucasian patients with MDD (145 women, 111 men) were genotyped for variants rs16944, rs1143643, and rs1143634 in the IL1B gene (2q14). Response to antidepressant treatment over 6 weeks was defined as remission (50% decrease on Hamilton Rating Scale for Depression-21-question). Brain activity under visual presentation of emotional faces was assessed in a subsample of 32 depressed patients by means of functional magnetic resonance imaging at 3 T. Pharmacogenetic analyses show significant associations of the GG genotypes of single nucleotide polymorphisms (SNPs) rs16944 (odds ratio = 1.74; 95% confidence interval 1.2-4.3) and rs1143643 (odds ratio = 3.1; 95% confidence interval 1.3-7.8) (compared with the AA genotype) with nonremission after 6 weeks. The imaging analyses show that the number of G-alleles in both SNPs (rs16944 and rs1143643) was associated with reduced responsiveness of the amygdala and ACC to emotional stimulation. The present study suggests a negative effect of the IL1B gene on pharmacological response and amygdala and ACC function involving the same genotypes of two SNPs (rs16944, rs116343), which taken together increase the risk of nonremission over 6 weeks of antidepressant treatment in MDD. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  19. Genetic polymorphisms in CYP1A1, GSTM1, GSTP1 and GSTT1 metabolic genes and risk of lung cancer in Asturias

    International Nuclear Information System (INIS)

    López-Cima, M Felicitas; Álvarez-Avellón, Sara M; Pascual, Teresa; Fernández-Somoano, Ana; Tardón, Adonina

    2012-01-01

    Metabolic genes have been associated with the function of metabolizing and detoxifying environmental carcinogens. Polymorphisms present in these genes could lead to changes in their metabolizing and detoxifying ability and thus may contribute to individual susceptibility to different types of cancer. We investigated if the individual and/or combined modifying effects of the CYP1A1 MspI T6235C, GSTM1 present/null, GSTT1 present/null and GSTP1 Ile105Val polymorphisms are related to the risk of developing lung cancer in relation to tobacco consumption and occupation in Asturias, Northern Spain. A hospital-based case–control study (CAPUA Study) was designed including 789 lung cancer patients and 789 control subjects matched in ethnicity, age, sex, and hospital. Genotypes were determined by PCR or PCR-RFLP. Individual and combination effects were analysed using an unconditional logistic regression adjusting for age, pack-years, family history of any cancer and occupation. No statistically significant main effects were observed for the carcinogen metabolism genes in relation to lung cancer risk. In addition, the analysis did not reveal any significant gene-gene, gene-tobacco smoking or gene-occupational exposure interactions relative to lung cancer susceptibility. Lastly, no significant gene-gene combination effects were observed. These results suggest that genetic polymorphisms in the CYP1A1, GSTM1, GSTT1 and GSTP1 metabolic genes were not significantly associated with lung cancer risk in the current study. The results of the analysis of gene-gene interactions of CYP1A1 MspI T6235C, GSTM1 present/null, GSTT1 present/null and GSTP1 Ile105Val polymorphisms in lung cancer risk indicate that these genes do not interact in lung cancer development

  20. Gender Differences in Somatic Symptoms and Current Suicidal Risk in Outpatients with Major Depressive Disorder.

    Science.gov (United States)

    Jeon, Hong Jin; Woo, Jong-Min; Kim, Hyo-Jin; Fava, Maurizio; Mischoulon, David; Cho, Seong Jin; Chang, Sung Man; Park, Doo-Heum; Kim, Jong Woo; Yoo, Ikki; Heo, Jung-Yoon; Hong, Jin Pyo

    2016-11-01

    Although somatic symptoms are common complaints of patients with major depressive disorder (MDD), their associations with suicide are still unclear. A total of 811 MDD outpatients of aged between 18 to 64 years were enrolled nationwide in Korea with the suicidality module of the Mini-International Neuropsychiatric Interview (MINI) and the Depression and Somatic Symptom Scale (DSSS). On stepwise regression analysis, current suicidality scores were most strongly associated with chest pain in men, and neck or shoulder pain in women. Severe chest pain was associated with higher current suicidality scores in men than in women, whereas severe neck or shoulder pain showed no significant differences between the genders. In conclusion, MDD patients of both sexes with suicidal ideation showed significantly more frequent and severe somatic symptoms than those without. Current suicidal risk was associated with chest pain in men, and neck or shoulder pain in women. We suggest that clinicians pay attention to patients' somatic symptoms in real world practice.

  1. Clinical features and risk factors for post-partum depression in a large cohort of Chinese women with recurrent major depressive disorder.

    Science.gov (United States)

    Tian, Tian; Li, Yihan; Xie, Dong; Shen, Yifeng; Ren, Jianer; Wu, Wenyuan; Guan, Chengbin; Zhang, Zhen; Zhang, Danning; Gao, Chengge; Zhang, Xiaoming; Wu, Jinbo; Deng, Hong; Wang, Gang; Zhang, Yunshu; Shao, Yun; Rong, Han; Gan, Zhaoyu; Sun, Yan; Hu, Bin; Pan, Jiyang; Li, Yi; Sun, Shufan; Song, Libo; Fan, Xuesheng; Li, Yi; Zhao, Xiaochuan; Yang, Bin; Lv, Luxian; Chen, Yunchun; Wang, Xiaoli; Ning, Yuping; Shi, Shenxun; Chen, Yiping; Kendler, Kenneth S; Flint, Jonathan; Tian, Hongjun

    2012-02-01

    Post partum depression (PPD) is relatively common in China but its clinical characteristics and risk factors have not been studied. We set out to investigate whether known risk factors for PPD could be found in Chinese women. A case control design was used to determine the impact of known risk factors for PPD in a cohort of 1970 Chinese women with recurrent DSM-IV major depressive disorder (MDD). In a within-case design we examined the risk factors for PPD in patients with recurrent MDD. We compared the clinical features of MDD in cases with PPD to those without MDD. Odds ratios were calculated using logistic and ordinal regression. Lower occupational and educational statuses increased the risk of PPD, as did a history of pre-menstrual symptoms, stressful life events and elevated levels of the personality trait of neuroticism. Patients with PPD and MDD were more likely to experience a comorbid anxiety disorder, had a younger age of onset of MDD, have higher levels of neuroticism and dysthymia. Results obtained in this clinical sample may not be applicable to PPD within the community. Data were obtained retrospectively and we do not know whether the correlations we observe have the same causes as those operating in other populations. Our results are consistent with the hypothesis that the despite cultural differences between Chinese and Western women, the phenomenology and risk factors for PPD are very similar. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Long noncoding RNA expression in peripheral blood mononuclear cells and suicide risk in Chinese patients with major depressive disorder.

    Science.gov (United States)

    Cui, Xuelian; Niu, Wei; Kong, Lingming; He, Mingjun; Jiang, Kunhong; Chen, Shengdong; Zhong, Aifang; Li, Wanshuai; Lu, Jim; Zhang, Liyi

    2017-06-01

    WHO stated that nearly one million people commit suicide every year worldly, and 40% of the suicide completer suffered from depression. The primary aim of this study was to explore the association between long noncoding RNAs (lncRNAs) expression in peripheral blood mononuclear cells (PBMCs) and suicide risk of patients with major depressive disorder (MDD). Using Human LncRNA 3.0 microarray profiling which includes 30,586 human lncRNAs and RT-PCR, six down-regulated lncRNAs were identified differentially expressed in MDD patients. According to suicidal ideation and suicidal attempt, the suicide risk of MDD patients was classified into suicidal ideation versus no suicidal ideation groups, and past attempt versus no past attempt groups, respectively. The expression of six lncRNAs in MDD patients and controls were examined by RT-PCR. The expression of six lncRNAs had significant differences between no suicidal ideation, suicidal ideation, and controls; corresponding lncRNAs associated with suicidal attempt had remarkable differences between no past attempt, past attempt, and controls. Additionally, only the expression of lncRNAs in suicidal ideation group and past attempt group markedly declined compared with controls. This study indicated that the expression of six down-regulated lncRNAs had a negative association with suicide risk in MDD patients, and the expression of lncRNAs in PBMCs could have the potential to help clinician judge the suicide risk of MDD patients to provide timely treatment and prevent suicide.

  3. Dopamine D1 receptor gene variation modulates opioid dependence risk by affecting transition to addiction.

    Directory of Open Access Journals (Sweden)

    Feng Zhu

    Full Text Available Dopamine D1 receptor (DRD1 modulates opioid reinforcement, reward, and opioid-induced neuroadaptation. We propose that DRD1 polymorphism affects susceptibility to opioid dependence (OD, the efficiency of transition to OD, and opioid-induced pleasure response. We analyzed potential association between seven DRD1 polymorphisms with the following traits: duration of transition from the first use to dependence (DTFUD, subjective pleasure responses to opioid on first use and post-dependence use, and OD risk in 425 Chinese with OD and 514 healthy controls. DTFUD and level of pleasure responses were examined using a semi-structured interview. The DTFUD of opioid addicts ranged from 5 days to 11 years. Most addicts (64.0% reported non-comfortable response upon first opioid use, while after dependence, most addicts (53.0% felt strong opioid-induced pleasure. Survival analysis revealed a correlation of prolonged DTFUD with the minor allele-carrying genotypes of DRD1 rs4532 (hazard ratios (HR = 0.694; p = 0.001 and rs686 (HR = 0.681, p = 0.0003. Binary logistic regression indicated that rs10063995 GT genotype (vs. GG+TT, OR = 0.261 could predict decreased pleasure response to first-time use and the minor alleles of rs686 (OR = 0.535 and rs4532 (OR = 0.537 could predict decreased post-dependence pleasure. Moreover, rs686 minor allele was associated with a decreased risk for rapid transition from initial use to dependence (DTFUD≤30 days; OR = 0.603 or post-dependence euphoria (OR = 0.603 relative to major allele. In conclusion, DRD1 rs686 minor allele decreases the OD risk by prolonging the transition to dependence and attenuating opioid-induced pleasure in Chinese.

  4. Night shift fatigue among anaesthesia trainees at a major metropolitan teaching hospital.

    Science.gov (United States)

    Lancman, B M

    2016-05-01

    Night shifts expose anaesthesia trainees to the risk of fatigue and, potentially, fatigue-related performance impairment. This study examined the workload, fatigue and coping strategies of anaesthesia trainees during night shifts. A blinded survey-based study was undertaken at a major single centre metropolitan teaching hospital in Australia. All ten anaesthesia trainees who worked night shifts participated. The survey collected data on duration of night shifts, workload, and sleep patterns. Fatigue was assessed using the Karolinska Sleepiness Scale (KSS). There were 93 night shifts generating data out of a potential 165. Trainees tended to sleep an increasing amount before their shift as the nights progressed from 1 to 5. Night 1 was identified as an 'at risk' night due to the amount of time spent awake before arriving at work (32% awake for U+003E8 hours); on all other nights trainees were most likely to have slept 6-8 hours. The KSS demonstrated an increase in sleepiness of 3 to 4 points on the scale from commencement to conclusion of a night shift. The Night 1 conclusion sleepiness was markedly worse than any other night with 42% falling into an 'at-risk' category. The findings demonstrate fatigue and inadequate sleep in anaesthesia trainees during night shifts in a major metropolitan teaching hospital. The data obtained may help administrators prepare safer rosters, and junior staff develop improved strategies to reduce the likelihood of fatigue.

  5. Major Accidents (Gray Swans) Likelihood Modeling Using Accident Precursors and Approximate Reasoning.

    Science.gov (United States)

    Khakzad, Nima; Khan, Faisal; Amyotte, Paul

    2015-07-01

    Compared to the remarkable progress in risk analysis of normal accidents, the risk analysis of major accidents has not been so well-established, partly due to the complexity of such accidents and partly due to low probabilities involved. The issue of low probabilities normally arises from the scarcity of major accidents' relevant data since such accidents are few and far between. In this work, knowing that major accidents are frequently preceded by accident precursors, a novel precursor-based methodology has been developed for likelihood modeling of major accidents in critical infrastructures based on a unique combination of accident precursor data, information theory, and approximate reasoning. For this purpose, we have introduced an innovative application of information analysis to identify the most informative near accident of a major accident. The observed data of the near accident were then used to establish predictive scenarios to foresee the occurrence of the major accident. We verified the methodology using offshore blowouts in the Gulf of Mexico, and then demonstrated its application to dam breaches in the United Sates. © 2015 Society for Risk Analysis.

  6. Epidemiology of major depressive disorder

    NARCIS (Netherlands)

    Stegenga, B.T.

    2011-01-01

    Major depressive disorder (MDD) is a serious health problem and will be the second leading cause of burden of disease worldwide by 2030. To be able to prevent MDD, insight into risk factors for the onset of MDD is of clear importance. On the other hand, if onset of MDD has occurred, one may argue

  7. Risk factors for recurrent spontaneous epistaxis.

    Science.gov (United States)

    Abrich, Victor; Brozek, Annabelle; Boyle, Timothy R; Chyou, Po-Huang; Yale, Steven H

    2014-12-01

    To identify risk factors associated with spontaneous recurrent epistaxis. This was a retrospective cohort study assessing patients in the Marshfield Clinic system diagnosed as having epistaxis between January 1, 1991, and January 1, 2011. There were 461 cases with at least 2 episodes of spontaneous epistaxis within 3 years and 912 controls with only 1 episode in the same time frame. More than 50 potential risk factors were investigated, including demographic features, substance use, nasal anatomical abnormalities, nasal infectious and inflammatory processes, medical comorbidities, medications, and laboratory values. A Cox proportional hazards regression modeling approach was used to calculate hazard ratios of epistaxis recurrence. Traditional risk factors for epistaxis, including nasal perforation, nasal septum deviation, rhinitis, sinusitis, and upper respiratory tract infection, did not increase the risk of recurrence. Significant risk factors for recurrent epistaxis included congestive heart failure, diabetes mellitus, hypertension, and a history of anemia. Warfarin use increased the risk of recurrence, independent of international normalized ratio. Aspirin and clopidogrel were not found to increase the risk of recurrence. Few major adverse cardiovascular events were observed within 30 days of the first epistaxis event. Congestive heart failure is an underappreciated risk factor for recurrent epistaxis. Hypertension and diabetes mellitus may induce atherosclerotic changes in the nasal vessels, making them friable and more at risk for bleeding. Patients with recurrent epistaxis may also be more susceptible to developing anemia. Physicians should promote antiplatelet and antithrombotic medication adherence despite an increased propensity for recurrent epistaxis to prevent major adverse cardiovascular events. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  8. A Single IGF1 Allele Is a Major Determinant of Small Size in Dogs

    Science.gov (United States)

    Sutter, Nathan B.; Bustamante, Carlos D.; Chase, Kevin; Gray, Melissa M.; Zhao, Keyan; Zhu, Lan; Padhukasahasram, Badri; Karlins, Eric; Davis, Sean; Jones, Paul G.; Quignon, Pascale; Johnson, Gary S.; Parker, Heidi G.; Fretwell, Neale; Mosher, Dana S.; Lawler, Dennis F.; Satyaraj, Ebenezer; Nordborg, Magnus; Lark, K. Gordon; Wayne, Robert K.; Ostrander, Elaine A.

    2009-01-01

    The domestic dog exhibits greater diversity in body size than any other terrestrial vertebrate. We used a strategy that exploits the breed structure of dogs to investigate the genetic basis of size. First, through a genome-wide scan, we identified a major quantitative trait locus (QTL) on chromosome 15 influencing size variation within a single breed. Second, we examined genetic variation in the 15-megabase interval surrounding the QTL in small and giant breeds and found marked evidence for a selective sweep spanning a single gene (IGF1), encoding insulin-like growth factor 1. A single IGF1 single-nucleotide polymorphism haplotype is common to all small breeds and nearly absent from giant breeds, suggesting that the same causal sequence variant is a major contributor to body size in all small dogs. PMID:17412960

  9. Variation in the γ-glutamyltransferase 1 gene and risk of chronic pancreatitis.

    Science.gov (United States)

    Brand, Harrison; Diergaarde, Brenda; O'Connell, Michael R; Whitcomb, David C; Brand, Randall E

    2013-07-01

    Individuals with chronic pancreatitis are at increased risk for pancreatic cancer. We hypothesized that genetic variation in the γ-glutamyltransferase 1 (GGT1) gene, which was recently reported associated with pancreatic cancer risk in a genome-wide association study, is also associated with risk of chronic pancreatitis. Associations between common polymorphisms in GGT1 and chronic pancreatitis were evaluated using data and samples from the North American Pancreatitis Study 2. Patients (n = 496) and control subjects (n = 465) were genotyped for 4 single-nucleotide polymorphisms: rs4820599, rs2017869, rs8135987, and rs5751901. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CI) for chronic pancreatitis risk were calculated using multiple logistic regression models. Interactions with cigarette smoking and alcohol use were explored. Single-nucleotide polymorphisms rs8135987 and rs4820599 were both statistically significantly associated with risk of chronic pancreatitis; compared with common allele homozygotes, individuals with at least 1 minor allele were at increased risk (rs8135987: OR, 1.36; 95% CI, 1.03-1.80 [P(trend) = 0.01]; rs4820599: OR, 1.39; 95% CI, 1.04-1.84 [P(trend) = 0.0]; adjusted for age, sex, race, smoking status, and alcohol use). No significant interactions with cigarette smoking and alcohol use were observed. Our results suggest that common variation in the GGT1 gene may also affect risk of chronic pancreatitis.

  10. Major risk from rapid, large-volume landslides in Europe (EU Project RUNOUT)

    Science.gov (United States)

    Kilburn, Christopher R. J.; Pasuto, Alessandro

    2003-08-01

    Project RUNOUT has investigated methods for reducing the risk from large-volume landslides in Europe, especially those involving rapid rates of emplacement. Using field data from five test sites (Bad Goisern and Köfels in Austria, Tessina and Vajont in Italy, and the Barranco de Tirajana in Gran Canaria, Spain), the studies have developed (1) techniques for applying geomorphological investigations and optical remote sensing to map landslides and their evolution; (2) analytical, numerical, and cellular automata models for the emplacement of sturzstroms and debris flows; (3) a brittle-failure model for forecasting catastrophic slope failure; (4) new strategies for integrating large-area Global Positioning System (GPS) arrays with local geodetic monitoring networks; (5) methods for raising public awareness of landslide hazards; and (6) Geographic Information System (GIS)-based databases for the test areas. The results highlight the importance of multidisciplinary studies of landslide hazards, combining subjects as diverse as geology and geomorphology, remote sensing, geodesy, fluid dynamics, and social profiling. They have also identified key goals for an improved understanding of the physical processes that govern landslide collapse and runout, as well as for designing strategies for raising public awareness of landslide hazards and for implementing appropriate land management policies for reducing landslide risk.

  11. [Control of major cardiovascular risk factors of ischemic heart disease in secondary prevention in Aragón: COCINA study].

    Science.gov (United States)

    Cucalon Arenal, J M; Buisac Ramón, C; Marin Ibáñez, A; Castan Ruiz, S; Blay Cortes, M G; Barrasa Villar, J I

    2016-01-01

    Ischemic heart disease remains a leading cause of death in Spain. According to the American Heart Association/American College of Cardiology (AHA/ACC) and European national societies, secondary prevention for these patients consists of control of major cardiovascular risk factors (CVRF) and suitable lifestyle habits. To determine the degree of control of CVRF in the Aragonese population in secondary prevention. Cross-sectional study of a sample of 705 patients of Aragon who had suffered a cardiac event, selected opportunistically in consultations of family physicians participating in the 3 provinces of Aragon. The study was conducted in the second half of 2012. To measure the degree of control of different FRVC and lifestyle habits in this population. Anthropometric, different cardiovascular risk factors, treatment and lifestyle. 58% of men and 52% of women met criteria for monitoring of measured variables. The best result was obtained with smoking cessation and the worst with BMI. Hypertension, Dyslipidemia and Diabetes Mellitus achieve poor control results. The results show that the degree of control of CVRF is still low, especially in variables such as dyslipidemia and Diabetes Mellitus. Only 16.5% of control patients met criteria given the pharmacologically-modifiable cardiovascular risk factors. Copyright © 2015 SEHLELHA. Published by Elsevier España, S.L.U. All rights reserved.

  12. Does thromboprophylaxis prevent venous thromboembolism after major orthopedic surgery?

    Directory of Open Access Journals (Sweden)

    Evrim Eylem Akpinar

    2013-06-01

    Full Text Available OBJECTIVE: Pulmonary embolism (PE is an important complication of major orthopedic surgery. The aim of this study was to evaluate the incidence of venous thromboembolism (VTE and factors influencing the development of VTE in patients undergoing major orthopedic surgery in a university hospital. METHODS: Patients who underwent major orthopedic surgery (hip arthroplasty, knee arthroplasty, or femur fracture repair between February of 2006 and June of 2012 were retrospectively included in the study. The incidences of PE and deep vein thrombosis (DVT were evaluated, as were the factors influencing their development, such as type of operation, age, and comorbidities. RESULTS: We reviewed the medical records of 1,306 patients. The proportions of knee arthroplasty, hip arthroplasty, and femur fracture repair were 63.4%, 29.9%, and 6.7%, respectively. The cumulative incidence of PE and DVT in patients undergoing major orthopedic surgery was 1.99% and 2.22%, respectively. Most of the patients presented with PE and DVT (61.5% and 72.4%, respectively within the first 72 h after surgery. Patients undergoing femur fracture repair, those aged ≥ 65 years, and bedridden patients were at a higher risk for developing VTE. CONCLUSIONS: Our results show that VTE was a significant complication of major orthopedic surgery, despite the use of thromboprophylaxis. Clinicians should be aware of VTE, especially during the perioperative period and in bedridden, elderly patients (≥ 65 years of age.

  13. Increased Risk of HIV-1 Transmission in Pregnancy: A Prospective Study among African HIV-1 Serodiscordant Couples

    Science.gov (United States)

    MUGO, Nelly R.; HEFFRON, Renee; DONNELL, Deborah; WALD, Anna; WERE, Edwin O.; REES, Helen; CELUM, Connie; KIARIE, James N.; COHEN, Craig R.; KAYINTEKORE, Kayitesi; BAETEN, Jared M.

    2011-01-01

    Background Physiologic and behavioral changes during pregnancy may alter HIV-1 susceptibility and infectiousness. Prospective studies exploring pregnancy and HIV-1 acquisition risk in women have found inconsistent results. No study has explored the effect of pregnancy on HIV-1 transmission risk from HIV-1 infected women to male partners. Methods In a prospective study of African HIV-1 serodiscordant couples, we evaluated the relationship between pregnancy and the risk of 1) HIV-1 acquisition among women and 2) HIV-1 transmission from women to men. Results 3321 HIV-1 serodiscordant couples were enrolled, 1085 (32.7%) with HIV-1 susceptible female partners and 2236 (67.3%) with susceptible male partners. HIV-1 incidence in women was 7.35 versus 3.01 per 100 person-years during pregnant and non-pregnant periods (hazard ratio [HR] 2.34, 95% confidence interval [CI] 1.33–4.09). This effect was attenuated and not statistically significant after adjusting for sexual behavior and other confounding factors (adjusted HR 1.71, 95% CI 0.93–3.12). HIV-1 incidence in male partners of infected women was 3.46 versus 1.58 per 100 person-years when their partners were pregnant versus not pregnant (HR 2.31, 95% CI 1.22–4.39). This effect was not attenuated in adjusted analysis (adjusted HR 2.47, 95% CI 1.26–4.85). Conclusions HIV-1 risk increased two-fold during pregnancy. Elevated risk of HIV-1 acquisition in pregnant women appeared in part to be explained by behavioral and other factors. This is the first study to show pregnancy increased the risk of female-to-male HIV-1 transmission, which may reflect biological changes of pregnancy that could increase HIV-1 infectiousness. PMID:21785321

  14. Disordered Eating Behaviors and Food Addiction among Nutrition Major College Students.

    Science.gov (United States)

    Yu, Zhiping; Tan, Michael

    2016-10-26

    Evidence of whether nutrition students are free from food-related issues or at higher risk for eating disorders is inconsistent. This study aimed to assess disordered eating behaviors and food addiction among nutrition and non-nutrition major college students. Students ( n = 967, ages 18-25, female 72.7%, white 74.8%) enrolled at a public university completed online demographic characteristics surveys and validated questionnaires measuring specific disordered eating behaviors. Academic major category differences were compared. Additionally, high risk participants were assessed by weight status and academic year. Overall, 10% of respondents were a high level of concern for developing eating disorders. About 10.3% of respondents met criteria for food addiction. In addition, 4.5% of respondents had co-occurrence of eating disorder risk and food addiction risk out of total respondents. There were no significant differences in level of concern for developing an eating disorder, eating subscales, or food addiction among academic majors. The percentage of high risk participants was lower in the underweight/normal weight group than in the overweight/obese group in health-related non-nutrition major students but not in nutrition students. Early screening, increasing awareness, and promoting healthy eating habits could be potential strategies to help treat and prevent the development of disorders or associated health conditions in nutrition as well as non-nutrition students.

  15. Disordered Eating Behaviors and Food Addiction among Nutrition Major College Students

    Science.gov (United States)

    Yu, Zhiping; Tan, Michael

    2016-01-01

    Evidence of whether nutrition students are free from food-related issues or at higher risk for eating disorders is inconsistent. This study aimed to assess disordered eating behaviors and food addiction among nutrition and non-nutrition major college students. Students (n = 967, ages 18–25, female 72.7%, white 74.8%) enrolled at a public university completed online demographic characteristics surveys and validated questionnaires measuring specific disordered eating behaviors. Academic major category differences were compared. Additionally, high risk participants were assessed by weight status and academic year. Overall, 10% of respondents were a high level of concern for developing eating disorders. About 10.3% of respondents met criteria for food addiction. In addition, 4.5% of respondents had co-occurrence of eating disorder risk and food addiction risk out of total respondents. There were no significant differences in level of concern for developing an eating disorder, eating subscales, or food addiction among academic majors. The percentage of high risk participants was lower in the underweight/normal weight group than in the overweight/obese group in health-related non-nutrition major students but not in nutrition students. Early screening, increasing awareness, and promoting healthy eating habits could be potential strategies to help treat and prevent the development of disorders or associated health conditions in nutrition as well as non-nutrition students. PMID:27792162

  16. Disordered Eating Behaviors and Food Addiction among Nutrition Major College Students

    Directory of Open Access Journals (Sweden)

    Zhiping Yu

    2016-10-01

    Full Text Available Evidence of whether nutrition students are free from food-related issues or at higher risk for eating disorders is inconsistent. This study aimed to assess disordered eating behaviors and food addiction among nutrition and non-nutrition major college students. Students (n = 967, ages 18–25, female 72.7%, white 74.8% enrolled at a public university completed online demographic characteristics surveys and validated questionnaires measuring specific disordered eating behaviors. Academic major category differences were compared. Additionally, high risk participants were assessed by weight status and academic year. Overall, 10% of respondents were a high level of concern for developing eating disorders. About 10.3% of respondents met criteria for food addiction. In addition, 4.5% of respondents had co-occurrence of eating disorder risk and food addiction risk out of total respondents. There were no significant differences in level of concern for developing an eating disorder, eating subscales, or food addiction among academic majors. The percentage of high risk participants was lower in the underweight/normal weight group than in the overweight/obese group in health-related non-nutrition major students but not in nutrition students. Early screening, increasing awareness, and promoting healthy eating habits could be potential strategies to help treat and prevent the development of disorders or associated health conditions in nutrition as well as non-nutrition students.

  17. Behavior is a major determinant of predation risk in zooplankton

    DEFF Research Database (Denmark)

    Almeda, Rodrigo; van Someren Gréve, Hans; Kiørboe, Thomas

    2017-01-01

    as prey for different predatory copepods. Copepods with “active” feeding behaviors (feeding-current and cruising feeders) showed significantly higher mortality from predation (~2–8 times) than similarly sized copepods with low motility feeding behavior (ambush feeders). Copepod males, which have a more...... active motile behavior than females (mate-seeking behavior), suffered a higher predation mortality than females in most of the experiments. However, the predation risk for mate-searching behavior in copepods varied depending on feeding behavior with ambush feeders consistently having the greatest......Zooplankton exhibit different small-scale motile behaviors related to feeding and mating activities. These different motile behaviors may result in different levels of predation risk, which may partially determine the structure of planktonic communities. Here, we experimentally determined predation...

  18. HVAC fault tree analysis for WIPP integrated risk assessment

    International Nuclear Information System (INIS)

    Kirby, P.; Iacovino, J.

    1990-01-01

    In order to evaluate the public health risk from operation of the Waste Isolation Pilot Plant (WIPP) due to potential radioactive releases, a probabilistic risk assessment of waste handling operations was conducted. One major aspect of this risk assessment involved fault tree analysis of the plant heating, ventilation, and air conditioning (HVAC) systems, which comprise the final barrier between waste handling operations and the environment. 1 refs., 1 tab

  19. Prelabor Cesarean Section and Risk of Childhood Type 1 Diabetes

    DEFF Research Database (Denmark)

    Clausen, Tine Dalsgaard; Bergholt, Thomas; Eriksson, Frank

    2016-01-01

    BACKGROUND: Unfavorable conditions associated with cesarean section may influence the risk of type 1 diabetes in offspring, but results from studies are conflicting. We aimed to evaluate the association between prelabor cesarean section and risk of childhood type 1 diabetes. METHODS: A Danish...... nationwide cohort study followed all singletons born during 1982-2010. Five national registers provided information on mode of delivery, outcome, and confounders. The risk of childhood type 1 diabetes with onset before the age of 15 years was assessed by Cox regression. A total of 1,760,336 singletons...... contributed 20,436,684 person-years, during which 4,400 were diagnosed with childhood type 1 diabetes. RESULTS: The hazard ratio for childhood type 1 diabetes was increased in children delivered by prelabor cesarean section compared with vaginal delivery when adjusted for year of birth, parity, sex, parental...

  20. Leishmania major Infection Activates NF-κB and Interferon Regulatory Factors 1 and 8 in Human Dendritic Cells▿

    Science.gov (United States)

    Jayakumar, Asha; Donovan, Michael J.; Tripathi, Vinita; Ramalho-Ortigao, Marcelo; McDowell, Mary Ann

    2008-01-01

    The salient feature of dendritic cells (DC) is the initiation of appropriate adaptive immune responses by discriminating between pathogens. Using a prototypic model of intracellular infection, we previously showed that Leishmania major parasites prime human DC for efficient interleukin-12 (IL-12) secretion. L. major infection is associated with self-limiting cutaneous disease and powerful immunity. In stark contrast, the causative agent of visceral leishmaniasis, Leishmania donovani, does not prime human DC for IL-12 production. Here, we report that DC priming by L. major infection results in the early activation of NF-κB transcription factors and the up-regulation and nuclear translocation of interferon regulatory factor 1 (IRF-1) and IRF-8. The inhibition of NF-κB activation by the pretreatment of DC with caffeic acid phenethyl ester blocks L. major-induced IRF-1 and IRF-8 activation and IL-12 expression. We further demonstrate that IRF-1 and IRF-8 obtained from L. major-infected human DC specifically bind to their consensus binding sites on the IL-12p35 promoter, indicating that L. major infection either directly stimulates a signaling cascade or induces an autocrine pathway that activates IRF-1 and IRF-8, ultimately resulting in IL-12 transcription. PMID:18316378

  1. Genetic variation in CYP19A1 and risk of breast cancer and fibrocystic breast conditions among women in Shanghai, China.

    Science.gov (United States)

    Chen, Chu; Sakoda, Lori C; Doherty, Jennifer A; Loomis, Melissa M; Fish, Sherianne; Ray, Roberta M; Lin, Ming Gang; Fan, Wenhong; Zhao, Lue Ping; Gao, Dao Li; Stalsberg, Helge; Feng, Ziding; Thomas, David B

    2008-12-01

    CYP19A1 encodes for aromatase, which irreversibly converts androgens to estrogens; variation in this gene may affect individual susceptibility to breast cancer and other sex hormone-dependent outcomes. In a case-control study nested within a breast self-examination trial conducted in China, we examined whether CYP19A1 polymorphisms (rs1870049, rs1004982, rs28566535, rs936306, rs11636639, rs767199, rs4775936, rs11575899, rs10046, and rs4646) were associated with risk of breast cancer and fibrocystic breast conditions. Cases were diagnosed with breast cancer (n = 614) or fibrocystic breast conditions (n = 465) during 1989 to 2000. Controls were free of breast disease during the same period (n = 879). Presence of proliferative changes within the extratumoral tissue of women with breast cancer and the lesions of women with fibrocystic conditions only was assessed. None of the polymorphisms were associated with overall risk of breast cancer or fibrocystic breast conditions. Differences in breast cancer risk, however, were observed by proliferation status. The risk of breast cancer with (but not without) proliferative fibrocystic conditions was increased among women homozygous for the minor allele of rs1004982 (C), rs28566535 (C), rs936306 (T), and rs4775936 (C) relative to those homozygous for the major allele [age-adjusted odds ratios (95% confidence intervals), 2.19 (1.24-3.85), 2.20 (1.27-3.82), 1.94 (1.13-3.30), and 1.95 (1.07-3.58), respectively]. Also, haplotypes inferred using all polymorphisms were not associated with overall risk of either outcome, although some block-specific haplotypes were associated with an increased risk of breast cancer with concurrent proliferative fibrocystic conditions. Our findings suggest that CYP19A1 variation may enhance breast cancer development in some women, but further confirmation is warranted.

  2. Eielson Air Force Base OU-1 baseline risk assessment

    International Nuclear Information System (INIS)

    Jarvis, M.T.; Jarvis, T.T.; Van Houten, N.C.; Lewis, R.E.

    1993-09-01

    This Baseline Risk Assessment report is the second volume in a set of three volumes for operable Unit 1 (OU-1). The companion documents contain the Remedial Investigation and the Feasibility Study. Operable Unit 1 (OU-1) is one of several groups of hazardous waste sites located at Eielson Air Force Base (AFB) near Fairbanks, Alaska. The operable units at Eielson are typically characterized by petroleum, oil, lubricant/solvent contamination, and by the presence of organics floating at the water table. In 1989 and 1990, firms under contract to the Air Force conducted field studies to gather information about the extent of chemical contamination in soil, groundwater, and soil air pore space (soil gas) at the site. This report documents the results of a baseline risk assessment, which uses the 1989 and 1991 site characterization database to quantify the potential human health risk associated with past Base industrial activities in the vicinity of OU-1. Background data collected in 1992 were also used in the preparation of this report

  3. Allele variants of HLA II genes DRB1 and DQB1 regarding risk for type 1 diabetes mellitus in population of Bashkortostan

    Directory of Open Access Journals (Sweden)

    Shamilevna Avzaletdinova

    2012-09-01

    Full Text Available Aims. To estimate significance of HLA II DRB1 and DRB2 allele variants for development of type 1 diabetes mellitus (T1DM in Bashkortostanpopulation (ethnical Russians, Tatar, Bashkir. Materials and methods. We analyzed DNA of 323 patients with T1DM and 683 healthy controls. DNA was derived from venous bloodsamples by phenol-chloroform extraction. DRB1 and DQB1 gene typing was performed by PCR method. Amplification products wereidentified with electrophoresis on a 1% agarose gel. Statistica for Windows v6.0 and MS Excel 98 software were applied for statisticalprocessing of acquired data. Results. Common markers of high risk for T1DM were found to be DRB1*04, DRB1*17, genotype DRB1*04/*17. On the contrary,lower risk was associated with DRB1*15 allele. In ethnical Russians lower risk of T1DM is also determined by DRB1*11 allele andDRB1*01 in Tatars. Predisposition by DQB1-alleles in Russians and Bashkir realizes only within DRB1*04/*17 genotype. However,in Tatar subpopulation DQB1*0302 is an independent risk marker of T1DM development. Conclusion. Common low risk markers for all three ethnic groups are DQB1*0301, DQB1*0602-08 alleles. Their presence negates riskof disease in all studied subpopulations even within DRB1*04/*17-genotype.

  4. Fast/Major and Slow/Minor pairings in J.S. Bach's Well Tempered Clavier Books 1 and 2

    Directory of Open Access Journals (Sweden)

    Katelyn Horn

    2012-07-01

    Full Text Available Some studies have found that subjects give higher preference ratings and clearer emotional descriptions to pieces with the tempo/mode pairs fast/major and slow/minor. If these findings are true, one might expect to find a predominance of fast/major and slow/minor pairings in musical literature. This study looks for just such a trend in the canonical work of J.S. Bach’s Well Tempered Clavier. Books 1 and 2 together contain 24 Major Preludes, 24 Minor Preludes, 24 Major Fugues and 24 Minor Fugues. We use four different measurements of fast/slow tempo based both on elements within the musical notation as well as the interpretive markings of four different music editors: 1. Attacks Per Beat (APB – measures the number of subdivisions of each piece 2. Attacks Per Minute (APM – is the APB of a piece multiplied by the editor’s metronome marking 3. Time Signature Distribution and 4. Editor’s Tempo Distribution. We find a significant amount of fast/major and slow/minor pairings in Book 1 but not in Book 2.

  5. Impacts of climate change and climate extremes on major crops productivity in China at a global warming of 1.5 and 2.0 °C

    Science.gov (United States)

    Chen, Yi; Zhang, Zhao; Tao, Fulu

    2018-05-01

    A new temperature goal of holding the increase in global average temperature well below 2 °C above pre-industrial levels and pursuing efforts to limit the temperature increase to 1.5 °C above pre-industrial levels has been established in the Paris Agreement, which calls for an understanding of climate risk under 1.5 and 2.0 °C warming scenarios. Here, we evaluated the effects of climate change on growth and productivity of three major crops (i.e. maize, wheat, rice) in China during 2106-2115 in warming scenarios of 1.5 and 2.0 °C using a method of ensemble simulation with well-validated Model to capture the Crop-Weather relationship over a Large Area (MCWLA) family crop models, their 10 sets of optimal crop model parameters and 70 climate projections from four global climate models. We presented the spatial patterns of changes in crop growth duration, crop yield, impacts of heat and drought stress, as well as crop yield variability and the probability of crop yield decrease. Results showed that climate change would have major negative impacts on crop production, particularly for wheat in north China, rice in south China and maize across the major cultivation areas, due to a decrease in crop growth duration and an increase in extreme events. By contrast, with moderate increases in temperature, solar radiation, precipitation and atmospheric CO2 concentration, agricultural climate resources such as light and thermal resources could be ameliorated, which would enhance canopy photosynthesis and consequently biomass accumulations and yields. The moderate climate change would slightly worsen the maize growth environment but would result in a much more appropriate growth environment for wheat and rice. As a result, wheat, rice and maize yields would change by +3.9 (+8.6), +4.1 (+9.4) and +0.2 % (-1.7 %), respectively, in a warming scenario of 1.5 °C (2.0 °C). In general, the warming scenarios would bring more opportunities than risks for crop development and food

  6. Fibrinogen, viscosity, and white blood cell count are major risk factors for ischemic heart disease. The Caerphilly and Speedwell collaborative heart disease studies.

    Science.gov (United States)

    Yarnell, J W; Baker, I A; Sweetnam, P M; Bainton, D; O'Brien, J R; Whitehead, P J; Elwood, P C

    1991-03-01

    Recent studies have suggested that hemostatic factors and white blood cell count are predictive of ischemic heart disease (IHD). The relations of fibrinogen, viscosity, and white blood cell count to the incidence of IHD in the Caerphilly and Speedwell prospective studies are described. The two studies have a common core protocol and are based on a combined cohort of 4,860 middle-aged men from the general population. The first follow-up was at a nearly constant interval of 5.1 years in Caerphilly and 3.2 years in Speedwell; 251 major IHD events had occurred. Age-adjusted relative odds of IHD for men in the top 20% of the distribution compared with the bottom 20% were 4.1 (95% confidence interval, 2.6-6.5) for fibrinogen, 4.5 (95% confidence interval, 2.8-7.4) for viscosity, and 3.2 (95% confidence interval, 2.0-4.9) for white blood cell count. Associations with IHD were similar in men who had never smoked, exsmokers, and current smokers, and the results suggest that at least part of the effect of smoking on IHD is mediated through fibrinogen, viscosity, and white blood cell count. Multivariate analysis shows that white blood cell count is an independent risk factor for IHD as is either fibrinogen or viscosity, or possibly both. Jointly, these three variables significantly improve the fit of a logistic regression model containing all the main conventional risk factors. Further, a model including age, smoking habits, fibrinogen, viscosity, and white blood cell count predicts IHD as well as one in which the three hemostatic/rheological variables are replaced by total cholesterol, diastolic pressure, and body mass index. Jointly, fibrinogen, viscosity, and white blood cell count are important risk factors for IHD.

  7. External Validation of the Adult Spinal Deformity (ASD) Frailty Index (ASD-FI) in the Scoli-RISK-1 Patient Database.

    Science.gov (United States)

    Miller, Emily K; Lenke, Lawrence G; Neuman, Brian J; Sciubba, Daniel M; Kebaish, Khaled M; Smith, Justin S; Qiu, Yong; Dahl, Benny T; Pellisé, Ferran; Matsuyama, Yukihiro; Carreon, Leah Y; Fehlings, Michael G; Cheung, Kenneth M; Lewis, Stephen; Dekutoski, Mark B; Schwab, Frank J; Boachie-Adjei, Oheneba; Mehdian, Hossein; Bess, Shay; Shaffrey, Christopher I; Ames, Christopher P

    2018-05-14

    Analysis of a prospective multicenter database. To assess the ability of the recently created Adult Spinal Deformity (ASD) Frailty Index (ASD-FI) to predict odds of major complications and length of hospital stay for patients who had more severe preoperative deformity and underwent more invasive ASD surgery compared with patients in the database used to create the index. Accurate preoperative estimates of risk are necessary given the high complication rates currently associated with ASD surgery. Patients were enrolled by participating institutions in Europe, Asia, and North America from 2009 to 2011. ASD-FI scores were used to classify 267 patients as not frail (NF) (0.5). Multivariable logistic regression, adjusted for preoperative and surgical covariates such as operative time and blood loss, was performed to determine the relationship between ASD-FI category and incidence of major complications, overall incidence of complications, and length of hospital stay. The mean ASD-FI score was 0.3 (range, 0-0.7). We categorized 105 patients as NF, 103 as frail, and 59 as SF. The adjusted odds of developing a major complication were higher for SF patients (odds ratio = 4.4; 95% CI 2.0, 9.9) compared with NF patients. After adjusting for covariates, length of hospital stay for SF patients increased by 19% (95% CI 1.4%, 39%) compared with NF patients. The odds of developing a major complication or having increased length of stay were similar between frail and NF patients. Greater patient frailty, as measured by the ASD-FI, is associated with a longer hospital stay and greater risk of major complications among patients who have severe preoperative deformity and undergo invasive surgical procedures. 2.

  8. Risk-benefit assessment of cold-smoked salmon: microbial risk versus nutritional benefit

    DEFF Research Database (Denmark)

    Berjia, Firew Lemma; Hoekstra, Jeljer; Andersen, Rikke

    2012-01-01

    Heart Disease (CHD) mortality and stroke, as well as enhanced cognitive (IQ) development of unborns following maternal intake, are identified as the main health benefits of omega-3 fatty acid from CSS. Contrary, risk of meningitis, septicemia and abortion/stillborn are identified as a major health risk......The objective of the study is to perform an integrated analysis of microbiological risks and nutritional benefits in a fish product, Cold Smoked Salmon (CSS). Literature study identified the major health risks and benefits in connection with CSS consumption. The reduction of the risk of Coronary...

  9. Minor Electrocardiographic ST-T Change and Risk of Stroke in the General Japanese Population.

    Science.gov (United States)

    Ishikawa, Joji; Hirose, Hideo; Schwartz, Joseph E; Ishikawa, Shizukiyo

    2018-06-25

    Minor ST-T changes are frequently observed on the electrocardiogram (ECG), but the risk of stroke associated with such changes is unclear.Methods and Results:In 10,642 subjects from the Japanese general population, we evaluated minor and major ST-T changes (major ST depression ≥0.1 mV) on ECGs obtained at annual health examinations. At baseline, minor ST-T changes were found in 10.7% of the subjects and 0.5% had major ST-T changes. Minor ST-T changes were associated with older age, female gender, higher systolic blood pressure, presence of hyperlipidemia, and use of antihypertensive medication. There were 375 stroke events during the follow-up period (128.7±28.1 months). In all subjects, minor ST-T changes (HR, 2.10; 95% CI: 1.57-2.81) and major ST-T changes (HR, 8.64; 95% CI: 4.44-16.82) were associated with an increased risk of stroke, but the stroke risk associated with minor ST-T changes had borderline significance after adjustment for conventional risk factors (P=0.055). In subgroup analysis, the risk of stroke was significantly associated with minor ST-T changes in subjects who had hyperlipidemia (HR, 1.75; 95% CI: 1.15-2.67) compared to those without hyperlipidemia (HR, 1.01; 95% CI: 0.64-1.59; P for interaction=0.016), even after adjustment for ECG-diagnosed left ventricular hypertrophy. Minor ST-T changes were particularly associated with a higher risk of stroke in subjects with hyperlipidemia and this association was independent of electrocardiographic left ventricular hypertrophy.

  10. Class II HLA interactions modulate genetic risk for multiple sclerosis

    Science.gov (United States)

    Dilthey, Alexander T; Xifara, Dionysia K; Ban, Maria; Shah, Tejas S; Patsopoulos, Nikolaos A; Alfredsson, Lars; Anderson, Carl A; Attfield, Katherine E; Baranzini, Sergio E; Barrett, Jeffrey; Binder, Thomas M C; Booth, David; Buck, Dorothea; Celius, Elisabeth G; Cotsapas, Chris; D’Alfonso, Sandra; Dendrou, Calliope A; Donnelly, Peter; Dubois, Bénédicte; Fontaine, Bertrand; Fugger, Lars; Goris, An; Gourraud, Pierre-Antoine; Graetz, Christiane; Hemmer, Bernhard; Hillert, Jan; Kockum, Ingrid; Leslie, Stephen; Lill, Christina M; Martinelli-Boneschi, Filippo; Oksenberg, Jorge R; Olsson, Tomas; Oturai, Annette; Saarela, Janna; Søndergaard, Helle Bach; Spurkland, Anne; Taylor, Bruce; Winkelmann, Juliane; Zipp, Frauke; Haines, Jonathan L; Pericak-Vance, Margaret A; Spencer, Chris C A; Stewart, Graeme; Hafler, David A; Ivinson, Adrian J; Harbo, Hanne F; Hauser, Stephen L; De Jager, Philip L; Compston, Alastair; McCauley, Jacob L; Sawcer, Stephen; McVean, Gil

    2016-01-01

    Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and class I protective alleles (HLA-A*02:01, HLA-B*44:02, HLA-B*38:01 and HLA-B*55:01), we find evidence for two interactions involving pairs of class II alleles: HLA-DQA1*01:01–HLA-DRB1*15:01 and HLA-DQB1*03:01–HLA-DQB1*03:02. We find no evidence for interactions between classical HLA alleles and non-HLA risk-associated variants and estimate a minimal effect of polygenic epistasis in modulating major risk alleles. PMID:26343388

  11. Risk factors for coronary heart disease in the white comm.unity ...

    African Journals Online (AJOL)

    major risk factors showed that 35,1% (age and sex adjusted) had at least one major risk factor at the higher level (level A) and 33,8% (age and sex adjusted) ... in a number of other countries with a high CHD mor- ... Afrikaans-speaking community in the south-western ... in an average week; (viI) physical activity both at work.

  12. Radiation risks in pregnancy

    International Nuclear Information System (INIS)

    Mossman, K.L.; Hill, L.T.

    1982-01-01

    A major contraindication of radiodiagnostic procedures is pregnancy. Approximately 1% of all pregnant women are given abdominal x-rays during the first trimester of pregnancy. Evaluation of radiation exposure should involve consideration of the types of examinations performed and when performed, as well as radiation dose and risk estimation. This information is then weighed against other possible risks of the pregnancy as well as personal factors. In the authors' experiences, radiation exposures usually result in doses to the embryo of less than 5 cGy (rad); the resulting radiation risks are usually small compared with other risks of pregnancy. Procedures to minimize diagnostic x-ray exposure of the fetus are also discussed

  13. Cancer risk in MLH1, MSH2 and MSH6 mutation carriers; different risk profiles may influence clinical management

    Directory of Open Access Journals (Sweden)

    Ramsoekh Dewkoemar

    2009-12-01

    Full Text Available Abstract Background Lynch syndrome (LS is associated with a high risk for colorectal cancer (CRC and extracolonic malignancies, such as endometrial carcinoma (EC. The risk is dependent of the affected mismatch repair gene. The aim of the present study was to calculate the cumulative risk of LS related cancers in proven MLH1, MSH2 and MSH6 mutation carriers. Methods The studypopulation consisted out of 67 proven LS families. Clinical information including mutation status and tumour diagnosis was collected. Cumulative risks were calculated and compared using Kaplan Meier survival analysis. Results MSH6 mutation carriers, both males and females had the lowest risk for developing CRC at age 70 years, 54% and 30% respectively and the age of onset was delayed by 3-5 years in males. With respect to endometrial carcinoma, female MSH6 mutation carriers had the highest risk at age 70 years (61% compared to MLH1 (25% and MSH2 (49%. Also, the age of EC onset was delayed by 5-10 years in comparison with MLH1 and MSH2. Conclusions Although the cumulative lifetime risk of LS related cancer is similar, MLH1, MSH2 and MSH6 mutations seem to cause distinguishable cancer risk profiles. Female MSH6 mutation carriers have a lower CRC risk and a higher risk for developing endometrial carcinoma. As a consequence, surveillance colonoscopy starting at age 30 years instead of 20-25 years is more suitable. Also, prophylactic hysterectomy may be more indicated in female MSH6 mutation carriers compared to MLH1 and MSH2 mutation carriers.

  14. Mitochondrial Haplogroups Modify the Effect of Diabetes Duration and HbA1c on Proliferative Diabetic Retinopathy Risk in Patients With Type 2 Diabetes.

    Science.gov (United States)

    Mitchell, Sabrina L; Neininger, Abigail C; Bruce, Carleigh N; Chocron, Isaac M; Bregman, Jana A; Estopinal, Christopher B; Muhammad, Ayesha; Umfress, Allison C; Jarrell, Kelli L; Warden, Cassandra; Harlow, Paula A; Wellons, Melissa; Samuels, David C; Brantley, Milam A

    2017-12-01

    We previously demonstrated an association between European mitochondrial haplogroups and proliferative diabetic retinopathy (PDR). The purpose of this study was to determine how the relationship between these haplogroups and both diabetes duration and hyperglycemia, two major risk factors for diabetic retinopathy (DR), affect PDR prevalence. Our population consisted of patients with type 2 diabetes with (n = 377) and without (n = 480) DR. A Kruskal-Wallis test was used to compare diabetes duration and hemoglobin A1c (HbA1c) among mitochondrial haplogroups. Logistic regressions were performed to investigate diabetes duration and HbA1c as risk factors for PDR in the context of European mitochondrial haplogroups. Neither diabetes duration nor HbA1c differed among mitochondrial haplogroups. Among DR patients from haplogroup H, longer diabetes duration and increasing HbA1c were significant risk factors for PDR (P = 0.0001 and P = 0.011, respectively). Neither diabetes duration nor HbA1c was a significant risk factor for PDR in DR patients from haplogroup UK. European mitochondrial haplogroups modify the effects of diabetes duration and HbA1c on PDR risk in patients with type 2 diabetes. In our patient population, longer diabetes duration and higher HbA1c increased PDR risk in patients from haplogroup H, but did not affect PDR risk in patients from haplogroup UK. This relationship has not been previously demonstrated and may explain, in part, why some patients with nonproliferative DR develop PDR and others do not, despite similar diabetes duration and glycemic control.

  15. Polymorphisms in GSTT1, GSTM1, NAT1 and NAT2 genes and bladder cancer risk in men and women

    International Nuclear Information System (INIS)

    McGrath, Monica; Michaud, Dominique; De Vivo, Immaculata

    2006-01-01

    Cigarette smoking is an established risk factor for bladder cancer. Epidemiological and biological data suggest that genetic polymorphisms in activating and detoxifying enzymes may play a role in determining an individual's susceptibility to bladder cancer in particular when in combination with specific environmental exposures such as cigarette smoking. N-acetyltransferase (NAT) enzymes, NAT1 and NAT2, are involved in the activation and detoxification of tobacco smoke constituents. Polymorphisms in these genes alter the ability of these enzymes to metabolize carcinogens, as certain allelic combinations result in a slow or rapid acetylation phenotype. Glutathione S-transferases (GSTs) also detoxify tobacco smoke constituents, and polymorphisms within the GSTM1 and GSTT1 genes can result in a complete lack of enzyme activity. We assessed the association between common polymorphisms identified in the GSTM1, GSTT1, NAT1, and NAT2 genes and the risk of bladder cancer in two nested case-control studies within the Nurses' Health Study (n = 78 female cases, 234 female controls) and the Health Professionals' Follow-up Study (n = 139 male cases, 293 male controls). We also evaluated whether cigarette smoking modified the associations of the genotypes and bladder cancer risk in men and women. Overall, we observed no statistically significant associations between the polymorphisms and bladder cancer risk among men and women, although given our sample size, we had limited power to detect small to moderate effects. There was however the suggestion of an increased risk among female ever smokers with the NAT2 slow genotype and an increased risk in male never smokers with the GSTM1 null genotype. In summary, these prospective results are consistent with previous literature supporting associations between bladder cancer and the NAT2 slow acetylation and the GSTM1 null genotypes

  16. Vanillin Suppresses Cell Motility by Inhibiting STAT3-Mediated HIF-1α mRNA Expression in Malignant Melanoma Cells.

    Science.gov (United States)

    Park, Eun-Ji; Lee, Yoon-Mi; Oh, Taek-In; Kim, Byeong Mo; Lim, Beong-Ou; Lim, Ji-Hong

    2017-03-01

    Recent studies have shown that vanillin has anti-cancer, anti-mutagenic, and anti-metastatic activity; however, the precise molecular mechanism whereby vanillin inhibits metastasis and cancer progression is not fully elucidated. In this study, we examined whether vanillin has anti-cancer and anti-metastatic activities via inhibition of hypoxia-inducible factor-1α (HIF-1α) in A2058 and A375 human malignant melanoma cells. Immunoblotting and quantitative real time (RT)-PCR analysis revealed that vanillin down-regulates HIF-1α protein accumulation and the transcripts of HIF-1α target genes related to cancer metastasis including fibronectin 1 ( FN1 ), lysyl oxidase-like 2 ( LOXL2 ), and urokinase plasminogen activator receptor ( uPAR ). It was also found that vanillin significantly suppresses HIF-1α mRNA expression and de novo HIF-1α protein synthesis. To understand the suppressive mechanism of vanillin on HIF-1α expression, chromatin immunoprecipitation was performed. Consequently, it was found that vanillin causes inhibition of promoter occupancy by signal transducer and activator of transcription 3 (STAT3), but not nuclear factor-κB (NF-κB), on HIF1A . Furthermore, an in vitro migration assay revealed that the motility of melanoma cells stimulated by hypoxia was attenuated by vanillin treatment. In conclusion, we demonstrate that vanillin might be a potential anti-metastatic agent that suppresses metastatic gene expression and migration activity under hypoxia via the STAT3-HIF-1α signaling pathway.

  17. Measurement of serum amyloid A1 (SAA1), a major isotype of acute phase SAA.

    Science.gov (United States)

    Xu, Yuanyuan; Yamada, Toshiyuki; Satoh, Takahiko; Okuda, Yasuaki

    2006-01-01

    Serum amyloid A (SAA), a plasma precursor of reactive amyloid deposits, is a multigene product. SAA1 and SAA2, with primary structures that are 93% identical (98 of 104 amino acids), behave as acute phase proteins, as demonstrated by their increasing levels in plasma. Heretofore, it has been understood that SAA1 predominates and functions as an isotype in plasma. However, accurate measurements differentiating the two isotypes have not been reported. In this study, using monoclonal antibodies specific for SAA1, we developed an enzyme-linked immunosorbent assay (ELISA) for SAA1. The levels and ratios of SAA1 in total SAA (TSAA) were investigated in healthy subjects and patients with rheumatoid arthritis (RA). The SAA1/TSAA ratio was 74 +/- 12% and 77 +/- 12% in healthy subjects and RA patients, respectively. In RA patients, the ratios were not influenced by SAA1 genotype, which has been proposed to affect plasma SAA values. The kinetics of SAA1 in inflamed patients undergoing hemodialysis was found to be parallel with total SAA and C-reactive protein. Finally, this study confirmed that SAA1 is a major isotype of acute phase SAA and may determine total SAA values. This specific assay could be used in the evaluation of SAA behavior in several clinical conditions.

  18. Factors associated with nocturnal hypoglycemia in at-risk adolescents and young adults with type 1 diabetes.

    Science.gov (United States)

    Wilson, Darrell M; Calhoun, Peter M; Maahs, David M; Chase, H Peter; Messer, Laurel; Buckingham, Bruce A; Aye, Tandy; Clinton, Paula K; Hramiak, Irene; Kollman, Craig; Beck, Roy W

    2015-06-01

    Hypoglycemia remains an impediment to good glycemic control, with nocturnal hypoglycemia being particularly dangerous. Information on major contributors to nocturnal hypoglycemia remains critical for understanding and mitigating risk. Continuous glucose monitoring (CGM) data for 855 nights were studied, generated by 45 subjects 15-45 years of age with hemoglobin A1c (HbA1c) levels of ≤8.0% who participated in a larger randomized study. Factors assessed for potential association with nocturnal hypoglycemia (CGM measurement of <60 mg/dL for ≥30 min) included bedtime blood glucose (BG), exercise intensity, bedtime snack, insulin on board, day of the week, previous daytime hypoglycemia, age, gender, HbA1c level, diabetes duration, daily basal insulin, and daily insulin dose. Hypoglycemia occurred during 221 of 885 (25%) nights and was more frequent with younger age (P<0.001), lower HbA1c levels (P=0.006), medium/high-intensity exercise during the preceding day (P=0.003), and the occurrence of antecedent daytime hypoglycemia (P=0.001). There was a trend for lower bedtime BG levels to be associated with more frequent nocturnal hypoglycemia (P=0.10). Bedtime snack, before bedtime insulin bolus, weekend versus weekday, gender, and daily basal and bolus insulin were not associated with nocturnal hypoglycemia. Awareness that HbA1c level, exercise, bedtime BG level, and daytime hypoglycemia are all modifiable factors associated with nocturnal hypoglycemia may help patients and providers decrease the risk of hypoglycemia at night. Risk for nocturnal hypoglycemia increased in a linear fashion across the range of variables, with no clear-cut thresholds to guide clinicians or patients for any particular night.

  19. Use of an ACE inhibitor or angiotensin receptor blocker is a major risk factor for dehydration requiring readmission in the setting of a new ileostomy.

    Science.gov (United States)

    Charak, Gregory; Kuritzkes, Benjamin A; Al-Mazrou, Ahmed; Suradkar, Kunal; Valizadeh, Neda; Lee-Kong, Steven A; Feingold, Daniel L; Pappou, Emmanouil P

    2018-03-01

    Diverting ileostomies help prevent major complications related to anastomoses after colorectal resection but can cause metabolic derangement and hypovolemia, leading to readmission. This paper aims to determine whether angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) use increased the risk of readmission, or readmission specifically for dehydration after new ileostomy creation. Retrospective analysis of patients undergoing diverting ileostomy at a tertiary-care hospital, 2009-2015. Primary outcome was 60-day readmission for dehydration; secondary outcomes included 60-day readmission for any cause, or for infection obstruction. Ninety-nine patients underwent diverting ileostomy creation, 59% with a primary diagnosis of colorectal cancer. The 60-day readmission rate was 36% (n = 36). Of readmitted patients, 39% (n = 14) were admitted for dehydration. Other readmission reasons were infection (33%) and obstruction (3%). The majority (64%, n = 9) of patients readmitted for dehydration were taking either an ACEi or an ARB. Compared to patients not readmitted for dehydration, those who were readmitted for dehydration were more likely to be on an ACEi or an ARB (11/85, 13% vs. 9/14, 64%). After controlling for covariates, ACEi or ARB use was significantly associated with risk of readmission (p readmission for dehydration. ACEi and ARB use is a significant risk factor for readmission for dehydration following diverting ileostomy creation. Consideration should be given to withholding these medications after ileostomy creation to reduce this risk.

  20. Exposure to polycyclic aromatic hydrocarbons in atmospheric PM1.0 of urban environments: Carcinogenic and mutagenic respiratory health risk by age groups.

    Science.gov (United States)

    Agudelo-Castañeda, Dayana M; Teixeira, Elba C; Schneider, Ismael L; Lara, Sheila Rincón; Silva, Luis F O

    2017-05-01

    We investigated the carcinogenic and mutagenic respiratory health risks related to the exposure to atmospheric PAHs in an urban area. Our study focused in the association of these pollutants and their possible effect in human health, principally respiratory and circulatory diseases. Also, we determined a relationship between the inhalation risk of PAHs and meteorological conditions. We validated the hypothesis that in winter PAHs with high molecular weight associated to submicron particles (PM 1 ) may increase exposure risk, especially for respiratory diseases, bronchitis and pneumonia diseases. Moreover, in our study we verified the relationship between diseases and several carcinogenic PAHs (Ind, BbkF, DahA, BaP, and BghiP). These individual PAHs contributed the most to the potential risk of exposure for inhalation of PM 1.0 . Even at lower ambient concentrations of BaP and DahA in comparison with individual concentrations of other PAHs associated to PM 1.0 . Mainly, research suggests to include carcinogenic and mutagenic PAHs in future studies of environmental health risk due to their capacity to associate to PM 10 . Such carcinogenic and mutagenic PAHs are likely to provide the majority of the human exposure, since they originate from dense traffic urban areas were humans congregate. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. The impact of chronic kidney disease as a predictor of major cardiac events in patients with no evidence of coronary artery disease

    International Nuclear Information System (INIS)

    Furuhashi, Tatsuhiko; Moroi, Masao; Joki, Nobuhiko; Hase, Hiroki; Masai, Hirofumi; Kunimasa, Taeko; Nakazato, Ryo; Fukuda, Hiroshi; Sugi, Kaoru

    2010-01-01

    Normal stress myocardial perfusion images (MPI) generally show good prognosis for cardiovascular events. However, chronic kidney disease (CKD) is one of the important risk factors for coronary artery disease (CAD), and the interpretation of normal stress MPI has not been well established in CKD patients with no evidence of CAD. The purpose of this study was to evaluate the long-term prognostic value of stress MPI in CKD patients with no evidence of myocardial ischemia or infarction. Patients who had no history but were suspected of CAD and had normal stress MPI (n=307, male=208, age=67 years, CKD/non-CKD=46/261) were followed-up for 4.5 years. CKD was defined as a glomerular filtration ratio of 2 and/or persistent proteinuria. Cardiac death, non-fatal myocardial infarction, and unstable angina requiring hospitalization were defined as major cardiac events. Major cardiac events were observed in 3 of 261 (1.1%) non-CKD patients and 6 of 46 (13%) CKD patients (p<0.001, with log-rank test). CKD was an independent risk factor for major cardiac events (hazard ratio=13.1, p<0.001, multivariate Cox regression analysis). Normal stress MPI does not always promise a good prognosis for major cardiac events. Even in patients with no evidence of CAD from stress MPI, CKD can be an independent and significant risk factor for major cardiac events. (author)

  2. Major Electrocardiographic Abnormalities According to the Minnesota Coding System Among Brazilian Adults (from the ELSA-Brasil Cohort Study).

    Science.gov (United States)

    Pinto-Filho, Marcelo M; Brant, Luisa C C; Foppa, Murilo; Garcia-Silva, Kaiser B; Mendes de Oliveira, Rackel Aguiar; de Jesus Mendes da Fonseca, Maria; Alvim, Sheila; Lotufo, Paulo A; Mill, José G; Barreto, Sandhi M; Macfarlane, Peter W; Ribeiro, Antonio L P

    2017-06-15

    The electrocardiogram is a simple and useful clinical tool; nevertheless, few studies have evaluated the prevalence of electrocardiographic abnormalities in the Latin American population. This study aims to evaluate the major electrocardiographic abnormalities according to the Minnesota coding system in Brazilian adults, stratified by gender, age, race, and cardiovascular risk factors. Data from 14,424 adults (45.8% men, age 35 to 74 years) were obtained at baseline of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), according to standardized protocol. The electrocardiogram were obtained with the Burdick Atria 6100 machine, stored on Pyramis System, automatically coded according to the Minnesota coding system by the Glasgow University software and then manually revised. Major abnormalities were more prevalent in men than women (11.3% and 7.9%, p <0.001). These differences were consistent through the different age groups, race, and number of cardiovascular risk factors. Electrocardiographic major abnormalities were more prevalent in black participants for both men (black: 15.1%, mixed: 10.4%, white: 11.1%, p = 0.001) and women (black: 10%, mixed: 7.6%, white: 7.2%, p = 0.004). In conclusion, in this large sample of Brazilian adults, the prevalence of major electrocardiographic abnormalities was higher among men, the elderly, black, and among people with more cardiovascular risk factors. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. 17 CFR 1.64 - Composition of various self-regulatory organization governing boards and major disciplinary...

    Science.gov (United States)

    2010-04-01

    ... ACT Miscellaneous § 1.64 Composition of various self-regulatory organization governing boards and major disciplinary committees. (a) Definitions. For purposes of this section: (1) Self-regulatory organization means “self-regulatory organization” as defined in § 1.3(ee), not including a “clearing...

  4. Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.

    Science.gov (United States)

    Power, Robert A; Tansey, Katherine E; Buttenschøn, Henriette Nørmølle; Cohen-Woods, Sarah; Bigdeli, Tim; Hall, Lynsey S; Kutalik, Zoltán; Lee, S Hong; Ripke, Stephan; Steinberg, Stacy; Teumer, Alexander; Viktorin, Alexander; Wray, Naomi R; Arolt, Volker; Baune, Bernard T; Boomsma, Dorret I; Børglum, Anders D; Byrne, Enda M; Castelao, Enrique; Craddock, Nick; Craig, Ian W; Dannlowski, Udo; Deary, Ian J; Degenhardt, Franziska; Forstner, Andreas J; Gordon, Scott D; Grabe, Hans J; Grove, Jakob; Hamilton, Steven P; Hayward, Caroline; Heath, Andrew C; Hocking, Lynne J; Homuth, Georg; Hottenga, Jouke J; Kloiber, Stefan; Krogh, Jesper; Landén, Mikael; Lang, Maren; Levinson, Douglas F; Lichtenstein, Paul; Lucae, Susanne; MacIntyre, Donald J; Madden, Pamela; Magnusson, Patrik K E; Martin, Nicholas G; McIntosh, Andrew M; Middeldorp, Christel M; Milaneschi, Yuri; Montgomery, Grant W; Mors, Ole; Müller-Myhsok, Bertram; Nyholt, Dale R; Oskarsson, Hogni; Owen, Michael J; Padmanabhan, Sandosh; Penninx, Brenda W J H; Pergadia, Michele L; Porteous, David J; Potash, James B; Preisig, Martin; Rivera, Margarita; Shi, Jianxin; Shyn, Stanley I; Sigurdsson, Engilbert; Smit, Johannes H; Smith, Blair H; Stefansson, Hreinn; Stefansson, Kari; Strohmaier, Jana; Sullivan, Patrick F; Thomson, Pippa; Thorgeirsson, Thorgeir E; Van der Auwera, Sandra; Weissman, Myrna M; Breen, Gerome; Lewis, Cathryn M

    2017-02-15

    Major depressive disorder (MDD) is a disabling mood disorder, and despite a known heritable component, a large meta-analysis of genome-wide association studies revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age at onset in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by age at onset. Discovery case-control genome-wide association studies were performed where cases were stratified using increasing/decreasing age-at-onset cutoffs; significant single nucleotide polymorphisms were tested in nine independent replication samples, giving a total sample of 22,158 cases and 133,749 control subjects for subsetting. Polygenic score analysis was used to examine whether differences in shared genetic risk exists between earlier and adult-onset MDD with commonly comorbid disorders of schizophrenia, bipolar disorder, Alzheimer's disease, and coronary artery disease. We identified one replicated genome-wide significant locus associated with adult-onset (>27 years) MDD (rs7647854, odds ratio: 1.16, 95% confidence interval: 1.11-1.21, p = 5.2 × 10 -11 ). Using polygenic score analyses, we show that earlier-onset MDD is genetically more similar to schizophrenia and bipolar disorder than adult-onset MDD. We demonstrate that using additional phenotype data previously collected by genetic studies to tackle phenotypic heterogeneity in MDD can successfully lead to the discovery of genetic risk factor despite reduced sample size. Furthermore, our results suggest that the genetic susceptibility to MDD differs between adult- and earlier-onset MDD, with earlier-onset cases having a greater genetic overlap with schizophrenia and bipolar disorder. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  5. Reducing sexual risk behavior among high-risk couples in Northern India.

    Science.gov (United States)

    Jones, Deborah; Bagga, Rashmi; Nehra, Ritu; Deepika; Sethi, Sunil; Walia, Kamini; Kumar, Mahendra; Villar-Loubet, Olga; Lopez, Maria; Weiss, Stephen M

    2013-09-01

    With a population of 1.1 billion, India is considered to be a country in which effective prevention interventions could contain the development of a human immunodeficiency virus (HIV) epidemic. Heterosexual transmission accounts for 85 % of the extant HIV infections. This study sought to assess the feasibility of conducting a group, culturally tailored behavioral intervention and its impact on sexual barrier use, self-efficacy, knowledge, conflict resolution, and coping among high-risk heterosexual couples in Northern India. This pilot study was conducted at the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India from February 2008 to January 2009. Thirty sexually active high-risk couples were drawn from a convenience sample of PGIMER patients attending infectious disease and family planning clinics. Couples participated in 1 month of three weekly gender-concordant behavioral intervention groups and were individually administered assessments preintervention and post-intervention. The intervention was tailored to the Northern Indian context and addressed sexual barrier use, human immunodeficiency virus (HIV)/sexually transmitted infection transmission, and cognitive behavioral skill building focusing on sexual negotiation and communication. The participants had a mean age of 32 years (men) and 29 years (women), and the majority had at least 10 years of education. At baseline, the majority reported inconsistent condom use (knowledge, and women increased their use of positive coping tactics. The results highlight the potential to successfully utilize a group intervention to discuss sensitive issues such as sexual risk behavior among both men and women. Strategies to improve condom use and communication without increasing intimate partner violence in high-risk couples may be an important adjunct to preventing the development of a generalized epidemic in India.

  6. Risk uncertainty analysis methods for NUREG-1150

    International Nuclear Information System (INIS)

    Benjamin, A.S.; Boyd, G.J.

    1987-01-01

    Evaluation and display of risk uncertainties for NUREG-1150 constitute a principal focus of the Severe Accident Risk Rebaselining/Risk Reduction Program (SARRP). Some of the principal objectives of the uncertainty evaluation are: (1) to provide a quantitative estimate that reflects, for those areas considered, a credible and realistic range of uncertainty in risk; (2) to rank the various sources of uncertainty with respect to their importance for various measures of risk; and (3) to characterize the state of understanding of each aspect of the risk assessment for which major uncertainties exist. This paper describes the methods developed to fulfill these objectives

  7. District file of major risks for the Moselle district: B6 - The nuclear risk; B7 - The risk related to radioactive material transport

    International Nuclear Information System (INIS)

    2013-10-01

    A first document addresses the nuclear risk with some generalities (definition, occurrence, consequences for people and for the environment with an indication of exposure thresholds, presentation of individual safety directives), a discussion of the nuclear risk level in the district (history, contamination threats, preventive actions for the Cattenom nuclear plant, existence of a triple barrier for radioactive product containment, other factors aimed at nuclear safety, urban development control, control of nuclear activities, information, rescue organisation, map of concerned communes). The second document addresses the risk related to radioactive material transport with some generalities (definition, occurrence, consequences for persons and goods, individual safety directive in case of road or railway accident), a more detailed analysis of the risk in the district (situation of the radioactive material transport in the district, risk history, human and environmental stakes, preventive actions, radiation protection safety challenges, safety factors, control of transports, rescue organisation)

  8. Risk of depressive disorder following disasters and military deployment

    DEFF Research Database (Denmark)

    Bonde, J. P.; Utzon-Frank, Nicolai; Bertelsen, M.

    2016-01-01

    BACKGROUND: Numerous studies describe the occurrence of post-traumatic stress disorder following disasters, but less is known about the risk of major depression. AIMS: To review the risk of depressive disorder in people surviving disasters and in soldiers returning from military deployment. METHOD.......30-3.98), technological disaster OR = 1.44 (95% CI 1.21-1.70), terrorist acts OR = 1.80 (95% CI 1.38-2.34) and military combat OR = 1.60 (95% CI 1.09-2.35). In a subset of ten high-quality studies OR was 1.41 (95% CI 1.06-1.87). CONCLUSIONS: Disasters and combat experience substantially increase the risk of depression...

  9. THE MAJOR AND MINOR GALAXY MERGER RATES AT z < 1.5

    International Nuclear Information System (INIS)

    Lotz, Jennifer M.; Jonsson, Patrik; Cox, T. J.; Croton, Darren; Primack, Joel R.; Somerville, Rachel S.; Stewart, Kyle

    2011-01-01

    Calculating the galaxy merger rate requires both a census of galaxies identified as merger candidates and a cosmologically averaged 'observability' timescale (T obs (z)) for identifying galaxy mergers. While many have counted galaxy mergers using a variety of techniques, (T obs (z)) for these techniques have been poorly constrained. We address this problem by calibrating three merger rate estimators with a suite of hydrodynamic merger simulations and three galaxy formation models. We estimate (T obs (z)) for (1) close galaxy pairs with a range of projected separations, (2) the morphology indicator G – M 20 , and (3) the morphology indicator asymmetry A. Then, we apply these timescales to the observed merger fractions at z +3.0±1.1 ) than samples selected with constant stellar mass or passively evolving luminosity (∝(1 + z) +0.1±0.4 ). We calculate the minor merger rate (1:4 sat /M primary ∼ 20 . The implied minor merger rate is ∼3 times the major merger rate at z ∼ 0.7 and shows little evolution with redshift.

  10. CYP1B1 expression, a potential risk factor for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Goth-Goldstein, Regine; Erdmann, Christine A.; Russell, Marion

    2001-05-31

    CYP1B1 expression in non-tumor breast tissue from breast cancer patients and cancer-free individuals was determined to test the hypothesis that high CYP1B1 expression is a risk factor for breast cancer. Large interindividual variations in CYP1B1 expression were found with CYP1B1 levels notably higher in breast cancer patients than cancer-free individuals. The results indicate that CYP1B1 might play a role in breast cancer either through increased PAH activation or through metabolism of endogenous estrogen to a carcinogenic derivative.

  11. The effect of interpersonal psychotherapy and other psychodynamic therapies versus 'treatment as usual' in patients with major depressive disorder.

    Science.gov (United States)

    Jakobsen, Janus Christian; Hansen, Jane Lindschou; Simonsen, Erik; Gluud, Christian

    2011-04-27

    Major depressive disorder afflicts an estimated 17% of individuals during their lifetimes at tremendous suffering and costs. Interpersonal psychotherapy and other psychodynamic therapies may be effective interventions for major depressive disorder, but the effects have only had limited assessment in systematic reviews. Cochrane systematic review methodology with meta-analysis and trial sequential analysis of randomized trials comparing the effect of psychodynamic therapies versus 'treatment as usual' for major depressive disorder. To be included the participants had to be older than 17 years with a primary diagnosis of major depressive disorder. Altogether, we included six trials randomizing a total of 648 participants. Five trials assessed 'interpersonal psychotherapy' and only one trial assessed 'psychodynamic psychotherapy'. All six trials had high risk of bias. Meta-analysis on all six trials showed that the psychodynamic interventions significantly reduced depressive symptoms on the 17-item Hamilton Rating Scale for Depression (mean difference -3.12 (95% confidence interval -4.39 to -1.86;Pinterpersonal psychotherapy or psychodynamic therapy compared with 'treatment as usual' for patients with major depressive disorder. The potential beneficial effect seems small and effects on major outcomes are unknown. Randomized trials with low risk of systematic errors and low risk of random errors are needed.

  12. Sex Differences in the Effect of Type 2 Diabetes on Major Cardiovascular Diseases: Results from a Population-Based Study in Italy

    Directory of Open Access Journals (Sweden)

    Paola Ballotari

    2017-01-01

    Full Text Available The aim of the study is to assess sex difference in association between type 2 diabetes and incidence of major cardiovascular events, that is, myocardial infarction, stroke, and heart failure, using information retrieved by diabetes register. The inhabitants of Reggio Emilia (Italy aged 30–84 were followed during 2012–2014. Incidence rate ratios and 95% confidence intervals were calculated using multivariate Poisson model. The age- and sex-specific event rates were graphed. Subjects with type 2 diabetes had an excess risk compared to their counterparts without diabetes for all the three major cardiovascular events. The excess risk is similar in women and men for stroke (1.8 times and heart failure (2.7 times, while for myocardial infarction, the excess risk in women is greater than the one observed in men (IRR 2.58, 95% CI 2.22–3.00 and IRR 1.78, 95% CI 1.60–2.00, resp.; P of interaction <0.0001. Women had always a lesser risk than men, but in case of myocardial infarction, the women with type 2 diabetes lost part of advantage gained by women free of diabetes (IRR 0.61, 95% CI 0.53–0.72 and IRR 0.36, 95% CI 0.33–0.39, resp.. In women with type 2 diabetes, the risk of major cardiovascular events is anticipated by 20–30 years, while in men it is by 15–20.

  13. Sex Differences in the Effect of Type 2 Diabetes on Major Cardiovascular Diseases: Results from a Population-Based Study in Italy

    Science.gov (United States)

    Greci, Marina; Manicardi, Valeria

    2017-01-01

    The aim of the study is to assess sex difference in association between type 2 diabetes and incidence of major cardiovascular events, that is, myocardial infarction, stroke, and heart failure, using information retrieved by diabetes register. The inhabitants of Reggio Emilia (Italy) aged 30–84 were followed during 2012–2014. Incidence rate ratios and 95% confidence intervals were calculated using multivariate Poisson model. The age- and sex-specific event rates were graphed. Subjects with type 2 diabetes had an excess risk compared to their counterparts without diabetes for all the three major cardiovascular events. The excess risk is similar in women and men for stroke (1.8 times) and heart failure (2.7 times), while for myocardial infarction, the excess risk in women is greater than the one observed in men (IRR 2.58, 95% CI 2.22–3.00 and IRR 1.78, 95% CI 1.60–2.00, resp.; P of interaction < 0.0001). Women had always a lesser risk than men, but in case of myocardial infarction, the women with type 2 diabetes lost part of advantage gained by women free of diabetes (IRR 0.61, 95% CI 0.53–0.72 and IRR 0.36, 95% CI 0.33–0.39, resp.). In women with type 2 diabetes, the risk of major cardiovascular events is anticipated by 20–30 years, while in men it is by 15–20. PMID:28316624

  14. Suicide risk in a representative sample of people receiving HIV care: Time to target most-at-risk populations (ANRS VESPA2 French national survey).

    Science.gov (United States)

    Carrieri, Maria Patrizia; Marcellin, Fabienne; Fressard, Lisa; Préau, Marie; Sagaon-Teyssier, Luis; Suzan-Monti, Marie; Guagliardo, Valérie; Mora, Marion; Roux, Perrine; Dray-Spira, Rosemary; Spire, Bruno

    2017-01-01

    Suicide risk is high among people living with HIV (PLHIV). This study aimed to identify major correlates of suicide risk in a representative sample of PLHIV in France, in order to help target individuals who would benefit from suicide risk screening and psychiatric care. The ANRS VESPA2 cross-sectional survey (April 2011-January 2012) collected socio-demographic, medical and behavioral data from 3,022 PLHIV recruited in 73 French HIV hospital departments. The study sample comprised the 2,973 participants with available self-reported data on suicide risk (defined as having either thought about and planned to commit suicide during the previous 12 months or attempted suicide during the same period of time) and medical data on comorbidities. Weighted Poisson models adjusted for HCV co-infection and significant clinical variables were used to estimate the relationship between suicide risk and HIV transmission groups, experience with HIV disease and other psychosocial factors. Suicide risk was reported by 6.3% of PLHIV in the study sample. After adjustment for HIV immunological status and HCV co-infection, women (IRR [95%CI]:1.93 [1.17; 3.19]) and men who have sex with men (MSM) (1.97 [1.22; 3.19]) had a higher suicide risk than the rest of the sample. Moreover, the number of discrimination-related social contexts reported (1.39 [1.19; 1.61]), homelessness (4.87 [1.82; 13.02]), and reporting a feeling of loneliness (4.62 [3.06; 6.97]) were major predictors of suicide risk. Reducing the burden of precarious social conditions and discrimination is an important lever for preventing suicide risk among PLHIV in France. Comprehensive care models involving peer/community social interventions targeted at women and MSM need to be implemented to lower the risk of suicide in these specific subgroups of PLHIV.

  15. Suicide risk in a representative sample of people receiving HIV care: Time to target most-at-risk populations (ANRS VESPA2 French national survey.

    Directory of Open Access Journals (Sweden)

    Maria Patrizia Carrieri

    Full Text Available Suicide risk is high among people living with HIV (PLHIV. This study aimed to identify major correlates of suicide risk in a representative sample of PLHIV in France, in order to help target individuals who would benefit from suicide risk screening and psychiatric care.The ANRS VESPA2 cross-sectional survey (April 2011-January 2012 collected socio-demographic, medical and behavioral data from 3,022 PLHIV recruited in 73 French HIV hospital departments. The study sample comprised the 2,973 participants with available self-reported data on suicide risk (defined as having either thought about and planned to commit suicide during the previous 12 months or attempted suicide during the same period of time and medical data on comorbidities. Weighted Poisson models adjusted for HCV co-infection and significant clinical variables were used to estimate the relationship between suicide risk and HIV transmission groups, experience with HIV disease and other psychosocial factors.Suicide risk was reported by 6.3% of PLHIV in the study sample. After adjustment for HIV immunological status and HCV co-infection, women (IRR [95%CI]:1.93 [1.17; 3.19] and men who have sex with men (MSM (1.97 [1.22; 3.19] had a higher suicide risk than the rest of the sample. Moreover, the number of discrimination-related social contexts reported (1.39 [1.19; 1.61], homelessness (4.87 [1.82; 13.02], and reporting a feeling of loneliness (4.62 [3.06; 6.97] were major predictors of suicide risk.Reducing the burden of precarious social conditions and discrimination is an important lever for preventing suicide risk among PLHIV in France. Comprehensive care models involving peer/community social interventions targeted at women and MSM need to be implemented to lower the risk of suicide in these specific subgroups of PLHIV.

  16. The drone as an additional risk factor due to conditions not provided for in radiological safety at major events

    International Nuclear Information System (INIS)

    Oliveira, Gilberto de Jesus

    2015-01-01

    Major international events are potential targets of terrorist actions, seeking instant publicity that events of this magnitude provide, with the intention of causing terror and disseminate its power to a large number of people worldwide. In this context, the critical analysis of additional risk factor linked to procedures and protocols adopted on radiation safety is important. The possibility of unforeseen situations of risk, especially those resulting from the current global technological development, is a fact. Radioactive material can be used in this type of terrorism in a wide range of devices and illicit trafficking of this material is a reality that worries the International Atomic Energy Agency. In the current technological development scenario of the world, the potential occurrence of terrorist acts using drones combined with radioactive material dispersal devices, is real. The recent history of drones incidents presents cases where, despite not having been necessarily terrorist motivation, their circumstances and characteristics favor the occurrence of malicious acts. This paper proposes to alert the need of updating the current security protocols, considering the potential association of this technology with radioactive dispersal devices. (author)

  17. PRKCDBP (CAVIN3) and CRY2 associate with major depressive disorder.

    Science.gov (United States)

    Kovanen, Leena; Donner, Kati; Kaunisto, Mari; Partonen, Timo

    2017-01-01

    Dysfunctions in the intrinsic clocks are suggested in patients with depressive disorders. The cryptochrome circadian clocks 1 and 2 (CRY1 and CRY2) proteins modulate circadian rhythms in a cell and influence emotional reactions and mood in an individual. The protein kinase C delta binding protein (PRKCDBP, or CAVIN3), similar to the serum deprivation response protein (SDPR, or CAVIN2), reduces metabolic stability of the PER2-CRY2 transcription factor complex that plays a role in the circadian rhythm synchronization. Our aim was to study SDPR, PRKCDBP, CRY1 and CRY2 genetic variants in depressive disorders. The sample included 5910 Finnish individuals assessed with the Munich-Composite International Diagnostic Interview (M-CIDI) in year 2000. In year 2011, 3424 individuals were assessed again. After genotype quality control, there were 383 subjects with major depressive disorder, 166 with dysthymia, and 479 with depressive disorders (major depressive disorder, dysthymia or both), and 4154 healthy controls. A total of 48 single-nucleotide polymorphisms from SDPR, PRKCDBP, CRY1 and CRY2 genes were analyzed using logistic regression models controlling for age and gender. The earlier reported association of CRY2 variants with dysthymia was confirmed and extended to major depressive disorder (qdepressive disorders (q=0.02) and with major depressive disorder in specific (q=0.007) were found. The number of cases was moderate and coverage of PRKCDB was limited. CRY2 and PRKCDBP variants may be risk factors of major depressive disorder and provide information for diagnosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Polycystic ovary syndrome: a major unrecognized cardiovascular risk factor in women.

    Science.gov (United States)

    Alexander, Carolyn J; Tangchitnob, Edward P; Lepor, Norman E

    2009-01-01

    The prevalence of polycystic ovary syndrome (PCOS) is estimated to be nearly 10% among reproductive-age women. PCOS may represent the largest underappreciated segment of the female population at risk of cardiovascular disease. Clinicians providing care to women of childbearing age must recognize the presenting clues, including irregular menses, hirsutism, alopecia, hyperandrogenemia, and obesity. The pathophysiology of PCOS is complex, involving the hypothalamus-pituitary-ovarian axis, ovarian theca cell hyperplasia, hyperinsulinemia, and a multitude of other cytokine- and adipocyte-driven factors. Cardiac risk factors associated with PCOS have public health implications and should drive early screening and intervention measures. There are no consensus guidelines regarding screening for cardiovascular disease in patients with PCOS. Fasting lipid profiles and glucose examinations should be performed regularly. Carotid intimal medial thickness examinations should begin at age 30 years, and coronary calcium screening should begin at age 45 years. Treatment of the associated cardiovascular risk factors, including insulin resistance, hypertension, and dyslipidemia, should be incorporated into the routine PCOS patient wellness care program.

  19. Risk for Congenital Malformation With H1N1 Influenza Vaccine: A Cohort Study With Sibling Analysis.

    Science.gov (United States)

    Ludvigsson, Jonas F; Ström, Peter; Lundholm, Cecilia; Cnattingius, Sven; Ekbom, Anders; Örtqvist, Åke; Feltelius, Nils; Granath, Fredrik; Stephansson, Olof

    2016-12-20

    Earlier studies reporting varying risk estimates for congenital malformation in offspring of mothers undergoing vaccination against H1N1 influenza during pregnancy did not consider the potential role of confounding by familial (genetic and shared environmental) factors. To evaluate an association between maternal H1N1 vaccination during pregnancy and offspring malformation, with familial factors taken into account. Population-based prospective study. Sweden. Liveborn offspring born between 1 October 2009 and 1 October 2011 to mothers receiving monovalent AS03-adjuvanted H1N1 influenza vaccine (Pandemrix [GlaxoSmithKline]) during pregnancy. A total of 40 983 offspring were prenatally exposed to the vaccine, 14 385 were exposed within the first trimester (14 weeks), and 7502 were exposed during the first 8 weeks of pregnancy. Exposed offspring were compared with 197 588 unexposed offspring. Corresponding risks in exposed versus unexposed siblings were also estimated. Congenital malformation, with subanalyses for congenital heart disease, oral cleft, and limb deficiency. Congenital malformation was observed in 2037 (4.97%) exposed offspring and 9443 (4.78%) unexposed offspring. Adjusted risk for congenital malformation was 4.98% in exposed offspring versus 4.96% in unexposed offspring (risk difference, 0.02% [95% CI, -0.26% to 0.30%]). The corresponding risk differences were 0.16% (CI, -0.23% to 0.56%) for vaccination during the first trimester and 0.10% (CI, -0.41% to 0.62%) for vaccination in the first 8 weeks. Using siblings as comparators yielded no statistically significant risk differences. The study was based on live births, and the possibility that data on miscarriage or induced abortion could have influenced the findings cannot be ruled out. Study power was limited in analyses of specific malformations. When intrafamilial factors were taken into consideration, H1N1 vaccination during pregnancy did not seem to be linked to overall congenital malformation in

  20. Risk factors for postoperative complications in robotic general surgery.

    Science.gov (United States)

    Fantola, Giovanni; Brunaud, Laurent; Nguyen-Thi, Phi-Linh; Germain, Adeline; Ayav, Ahmet; Bresler, Laurent

    2017-03-01

    The feasibility and safety of robotically assisted procedures in general surgery have been reported from various groups worldwide. Because postoperative complications may lead to longer hospital stays and higher costs overall, analysis of risk factors for postoperative surgical complications in this subset of patients is clinically relevant. The goal of this study was to identify risk factors for postoperative morbidity after robotic surgical procedures in general surgery. We performed an observational monocentric retrospective study. All consecutive robotic surgical procedures from November 2001 to December 2013 were included. One thousand consecutive general surgery patients met the inclusion criteria. The mean overall postoperative morbidity and major postoperative morbidity (Clavien >III) rates were 20.4 and 6 %, respectively. This included a conversion rate of 4.4 %, reoperation rate of 4.5 %, and mortality rate of 0.2 %. Multivariate analysis showed that ASA score >3 [OR 1.7; 95 % CI (1.2-2.4)], hematocrit value surgery [OR 1.5; 95 % CI (1-2)], advanced dissection [OR 5.8; 95 % CI (3.1-10.6)], and multiquadrant surgery [OR 2.5; 95 % CI (1.7-3.8)] remained independent risk factors for overall postoperative morbidity. It also showed that advanced dissection [OR 4.4; 95 % CI (1.9-9.6)] and multiquadrant surgery [OR 4.4; 95 % CI (2.3-8.5)] remained independent risk factors for major postoperative morbidity (Clavien >III). This study identifies independent risk factors for postoperative overall and major morbidity in robotic general surgery. Because these factors independently impacted postoperative complications, we believe they could be taken into account in future studies comparing conventional versus robot-assisted laparoscopic procedures in general surgery.