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Sample records for association study confirms

  1. Genome-wide association study of electrocardiographic parameters identifies a new association for PR interval and confirms previously reported associations.

    Science.gov (United States)

    Sano, Motoaki; Kamitsuji, Shigeo; Kamatani, Naoyuki; Hong, Kyung-Won; Han, Bok-Ghee; Kim, Yeonjung; Kim, Jong Wook; Aizawa, Yoshiyasu; Fukuda, Keiichi

    2014-12-15

    Previous reports have described several associations of PR, QRS, QT and heart rate with genomic variations by genome-wide association studies (GWASs). In the present study, we examined the association of ∼2.5 million SNPs from 2994 Japanese healthy volunteers obtained from the JPDSC database with electrocardiographic parameters. We confirmed associations of PR interval, QRS duration and QT interval in individuals of Japanese ancestry with 11 of the 45 SNPs (6 of 20 for QT, 5 of 19 for PR and 0 of 6 for QRS) observed among individuals of European, African and Asian (Indian and Korean) ancestries. Those results indicate that many of the electrocardiographic associations with genes are shared by different ethnic groups including Japanese. Possible novel associations found in this study were validated by Korean data. As a result, we identified a novel association of SNP rs4952632[G] (maps near SLC8A1, sodium-calcium exchanger) (P = 7.595 × 10(-6)) with PR interval in Japanese individuals, and replication testing among Koreans confirmed the association of the same SNP with prolonged PR interval. Meta-analysis of the Japanese and Korean datasets demonstrated highly significant associations of SNP rs4952632[G] with a 2.325-ms (95% CI, 1.693-2.957 ms) longer PR interval per minor allele copy (P = 5.598 × 10(-13)). Cell-type-specific SLC8A1 knockout mice have demonstrated a regulatory role of sodium-calcium exchanger in automaticity and conduction in sinoatrial node, atrium and atrioventricular node. Our findings support a functional role of sodium-calcium exchanger in human atrial and atrioventricular nodal conduction as suggested by genetically modified mouse models. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Sleep in Genetically Confirmed Pantothenate Kinase-Associated Neurodegeneration: A Video-Polysomnographic Study

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    Maria Livia Fantini

    2010-01-01

    Full Text Available Pantothenate kinase-associated neurodegeneration (PKAN is a familial or sporadic disease characterized by extrapyramidal and corticospinal signs with dementia. Patients show iron accumulation in the basal ganglia, with neuronal loss and gliosis. A mutation of pantothenate kinase (PANK2 gene localized on chromosome 20p13 has been described in familiar forms, as well as in sporadic patients. We sought to assess sleep characteristics, including muscle activity during REM sleep, in three patients with PANK2 gene mutation-confirmed diagnosis of PKAN. Sleep architecture was altered in all patients with reduced total time of sleep in two and lack of SWS in one. No significant apnea/hypopnea were detected, and mild PLMS were observed in one patient (PLMS index:10.7/h. In contrast with other neurodegenerative diseases, no REM sleep abnormalities, especially REM sleep behavior disorder, were observed in PKAN patients, and percentage of both REM sleep atonia and phasic EMG activity were within normal ranges. Sleep studies may phenotypically differentiate PKAN from other neurodegenerative disorders.

  3. Association study confirms two susceptibility loci for breast cancer in Chinese Han women.

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    Xu, Minggui; Xu, Yihui; Chen, Mengyun; Li, Yang; Li, Wei; Zhu, Jun; Zhang, Mingjun; Chen, Zhendong; Zhang, Xuejun; Liu, Jianjun; Zhang, Bo

    2016-10-01

    To date, many loci associated with breast cancer have been identified through genome-wide association studies; most of these studies were conducted using populations of European descent. Thus, it is not clear whether these susceptibility loci are also risk factors for Chinese populations. We selected and genotyped 32 single nucleotide polymorphisms (SNPs) using the Sequenom iPLEX platform in a female Chinese cohort of 3036 breast cancer cases and 3036 healthy controls. A total of 23 SNPs passed the quality control test. The associations of these SNPs with disease susceptibility were assessed using logistic regression, adjusting for age. The Bonferroni correction was used to conservatively account for multiple testing, and the threshold for statistical significance was P associated variants within three reported breast cancer susceptibility loci in a Chinese Han population: 5q11.2 (rs16886181, P = 5.29 × 10(-6), OR = 1.19; rs1017226, P = 5.24 × 10(-4), OR = 1.22; rs16886034, P = 2.00 × 10(-3), OR = 1.21; rs16886113, P = 1.24 × 10(-3), OR = 1.20; rs16886364, P = 9.20 × 10(-4), OR = 1.21; rs16886397, P = 1.17 × 10(-3), OR = 1.20; rs16886448, P = 1.62 × 10(-3,)OR = 1.20; and rs2229882, P = 5.14 × 10(-4), OR = 1.31), 5q14.3 (rs421379, P = 2.83 × 10(-13), OR = 1.83), and 10q26.1 (rs35054928, P = 7.73 × 10(-6), OR = 1.18). The 10q26.1 locus was found to be a susceptibility locus for breast cancer in Chinese Han women in our previous studies. 5q11.2 and 5q14.3 are confirmed here for the first time as susceptibility loci for breast cancer in Chinese Han women. This study reports three breast cancer susceptibility loci that were previously identified in European populations and are also risk factors for Chinese populations. This study may extend the genetic basis of breast cancer in Chinese Han women and highlight the contribution of multiple variants of modest effect.

  4. A multicenter study confirms CD226 gene association with systemic sclerosis-related pulmonary fibrosis

    NARCIS (Netherlands)

    Bossini-Castillo, L.; Simeon, C.P.; Beretta, L.; Broen, J.C.A.; Vonk, M.C.; Rios-Fernandez, R.; Espinosa, G.; Carreira, P.; Camps, M.T.; Castillo, M.J.; Gonzalez-Gay, M.A.; Beltran, E.; Carmen Freire, M.; Narvaez, J.; Tolosa, C.; Witte, T.; Kreuter, A.; Schuerwegh, A.J.; Hoffmann-Vold, A.M.; Hesselstrand, R.; Lunardi, C.; Laar, J.M. van; Chee, M.M.; Herrick, A.; Koeleman, B.P.; Denton, C.P.; Fonseca, C.; Radstake, T.R.D.J.; Martin, J.; Spanish Scleroderma, G.

    2012-01-01

    INTRODUCTION: CD226 genetic variants have been associated with a number of autoimmune diseases and recently with systemic sclerosis (SSc). The aim of this study was to test the influence of CD226 loci in SSc susceptibility, clinical phenotypes and autoantibody status in a large multicenter European

  5. Genome-wide association study of celiac disease in North America confirms FRMD4B as new celiac locus.

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    Chad Garner

    Full Text Available We performed a genome-wide association study (GWAS of 1550 North American celiac disease cases and 3084 controls. Twelve SNPs, distributed across four regions (3p21.31, 4q27, 6q15, 6q25, were significantly associated with disease (p-value <1.0×10-7, and a further seven SNPs, across four additional regions (1q24.3, 10p15.1, 6q22.31, 17q21.32 had suggestive evidence (1.0×10-7 < p-value < 1.0×10-6. This study replicated a previous suggestive association within FRMD4B (3p14.1, confirming it as a celiac disease locus. All four regions with significant associations and two regions with suggestive results (1q24.3, 10p15.1 were known disease loci. The 6q22.31 and 10p11.23 regions were not replicated. A total of 410 SNPs distributed across the eight significant and suggestive regions were tested for association with dermatitis herpetiformis and microscopic colitis. Preliminary, suggestive statistical evidence for association with the two traits was found at chromosomes 3p21.31, 6q15, 6q25, 1q24.3 and 10p11.23, with future studies being required to validate the reported associations.

  6. Consistent association between mixed lateral preference and PTSD: confirmation among a national study of 2490 US Army Vietnam veterans.

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    Boscarino, Joseph A; Hoffman, Stuart N

    2007-05-01

    To evaluate the research-based association between mixed lateral preference for handedness and risk for posttraumatic stress disorder (PTSD) in a large-scale sample of US Army Vietnam veterans exposed to war zone stressors. We used a national sample of 2490 male US Army veterans, who completed the Edinburgh Handedness Inventory (EHI), a measure ranging from -100 (pure left-handedness) to +100 (pure right-handedness). We developed several classifications representing levels of mixed laterality: a) an EHI -70 to +70 (EHI 70, moderate mixed); b) an EHI -50 to +50 (EHI 50, consistent mixed); and c) an EHI 0, plus reports of using either hand on > or =50% of the tasks assessed (EHI 0+, extreme mixed). We controlled for intelligence, race, Army entry age, and Army volunteer status, and we assessed the impact of combat exposure. Although all three handedness measures were associated with current PTSD in bivariate analyses, only Edinburgh 0+ was associated with PTSD in the multivariate model (odds ratio (OR) = 2.1; p = .021). However, when we classified handedness by high combat exposure, all three measures were associated with PTSD, with ORs = 2.5, 2.8, and 4.7 for EHI 70, EHI 50, and EHI 0+, respectively (all p < .001). Veterans with mixed laterality and high combat exposure also had significantly increased PTSD symptoms (all p < .001). Our study confirmed findings reported among mostly smaller clinical samples and suggested that mixed lateral preference was associated with PTSD, especially among those individuals exposed to more severe psychological trauma.

  7. Clinical and laboratory associations of severity in a Sri Lankan cohort of patients with serologically confirmed leptospirosis: a prospective study.

    Science.gov (United States)

    Rajapakse, Senaka; Weeratunga, Praveen; Niloofa, M J Roshan; Fernando, Narmada; Rodrigo, Chathuraka; Maduranga, Sachith; de Silva, Nipun Lakshitha; Fernando, Nipun Lakshitha; de Silva, H Janaka; Karunanayake, Lilani; Handunnetti, Shiroma

    2015-11-01

    Leptospirosis results in significant morbidity and mortality. This study elucidates markers of severity in a cohort of Sri Lankan patients. Patients presenting to three healthcare institutions in the Western province of Sri Lanka with leptospirosis serological confirmed by the microscopic agglutination test (MAT) were included. Prospective data regarding demographic, clinical and laboratory parameters was extracted. Univariate associations and subsequent multivariate logistic regression models were constructed. The study included 232 patients, with 68.5% (159) demonstrating severe disease. Significant associations of severe disease at a significance level of p38.8°C on presentation, age >40 years, muscle tenderness, tachycardia on admission, highest white cell count >12 350/mm(3) and 84%, haemoglobin >11.2 g/dL and 33.8% and 70 IU/L and hyponatremia with sodium 70 IU/L (p=0.044; OR 2.639; CI: 1.028-6.774) and hyponatremia leptospirosis. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. A genome-wide association study confirms previously reported loci for type 2 diabetes in Han Chinese.

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    Bin Cui

    Full Text Available BACKGROUND: Genome-wide association study (GWAS has identified more than 30 loci associated with type 2 diabetes (T2D in Caucasians. However, genomic understanding of T2D in Asians, especially Han Chinese, is still limited. METHODS AND PRINCIPAL FINDINGS: A two-stage GWAS was performed in Han Chinese from Mainland China. The discovery stage included 793 T2D cases and 806 healthy controls genotyped using Illumina Human 660- and 610-Quad BeadChips; and the replication stage included two independent case-control populations (a total of 4445 T2D cases and 4458 controls genotyped using TaqMan assay. We validated the associations of KCNQ1 (rs163182, p = 2.085×10(-17, OR 1.28 and C2CD4A/B (rs1370176, p = 3.677×10(-4, OR 1.124; rs1436953, p = 7.753×10(-6, OR 1.141; rs7172432, p = 4.001×10(-5, OR 1.134 in Han Chinese. CONCLUSIONS AND SIGNIFICANCE: Our study represents the first GWAS of T2D with both discovery and replication sample sets recruited from Han Chinese men and women residing in Mainland China. We confirmed the associations of KCNQ1 and C2CD4A/B with T2D, with the latter for the first time being examined in Han Chinese. Arguably, eight more independent loci were replicated in our GWAS.

  9. Genome-wide association study of multiple sclerosis confirms a novel locus at 5p13.1.

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    Fuencisla Matesanz

    Full Text Available Multiple Sclerosis (MS is the most common progressive and disabling neurological condition affecting young adults in the world today. From a genetic point of view, MS is a complex disorder resulting from the combination of genetic and non-genetic factors. We aimed to identify previously unidentified loci conducting a new GWAS of Multiple Sclerosis (MS in a sample of 296 MS cases and 801 controls from the Spanish population. Meta-analysis of our data in combination with previous GWAS was done. A total of 17 GWAS-significant SNPs, corresponding to three different loci were identified:HLA, IL2RA, and 5p13.1. All three have been previously reported as GWAS-significant. We confirmed our observation in 5p13.1 for rs9292777 using two additional independent Spanish samples to make a total of 4912 MS cases and 7498 controls (ORpooled = 0.84; 95%CI: 0.80-0.89; p = 1.36 × 10-9. This SNP differs from the one reported within this locus in a recent GWAS. Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS.

  10. Genome-Wide Association Study of Multiple Sclerosis Confirms a Novel Locus at 5p13.1

    Science.gov (United States)

    Sanna, Serena; Gayán, Javier; Urcelay, Elena; Zara, Ilenia; Pitzalis, Maristella; Cavanillas, María L.; Arroyo, Rafael; Zoledziewska, Magdalena; Marrosu, Marisa; Fernández, Oscar; Leyva, Laura; Alcina, Antonio; Fedetz, Maria; Moreno-Rey, Concha; Velasco, Juan; Real, Luis M.; Ruiz-Peña, Juan Luis; Cucca, Francesco

    2012-01-01

    Multiple Sclerosis (MS) is the most common progressive and disabling neurological condition affecting young adults in the world today. From a genetic point of view, MS is a complex disorder resulting from the combination of genetic and non-genetic factors. We aimed to identify previously unidentified loci conducting a new GWAS of Multiple Sclerosis (MS) in a sample of 296 MS cases and 801 controls from the Spanish population. Meta-analysis of our data in combination with previous GWAS was done. A total of 17 GWAS-significant SNPs, corresponding to three different loci were identified:HLA, IL2RA, and 5p13.1. All three have been previously reported as GWAS-significant. We confirmed our observation in 5p13.1 for rs9292777 using two additional independent Spanish samples to make a total of 4912 MS cases and 7498 controls (ORpooled = 0.84; 95%CI: 0.80–0.89; p = 1.36×10-9). This SNP differs from the one reported within this locus in a recent GWAS. Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS. PMID:22570697

  11. Genome-wide Association Study of Late-Onset Myasthenia Gravis: Confirmation of TNFRSF11A, and Identification of ZBTB10 and Three Distinct HLA Associations.

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    Seldin, Michael F; Alkhairy, Omar K; Lee, Annette T; Lamb, Janine A; Sussman, Jon; Pirskanen-Matell, Ritva; Piehl, Fredrik; Verschuuren, J J G M; Kostera-Pruszczyk, Anna; Szczudlik, Piotr; Mckee, David; Maniaol, Angelina H; Harbo, Hanne F; Lie, Benedicte A; Melms, Arthur; Garchon, Henri-Jean; Willcox, Nicholas; Gregersen, Peter K; Hammarstrom, Lennart

    2015-10-10

    To investigate the genetics of late-onset myasthenia gravis (LOMG), we conducted a genome-wide association study imputation of >6 million SNPs in 532 LOMG cases (anti-acetylcholine receptor (AChR) antibody positive, onset age ≥50 years) and 2,128 controls matched for sex and population substructure. The data confirm reported TNFRSF11A associations [rs4574025, P = 3.9×10(-07), odds ratio (OR) = 1.42] and identify a novel candidate gene, ZBTB10, achieving genome-wide significance (rs6998967, P = 8.9×10(-10), OR = 0.53). Several other SNPs showed suggestive significance including rs2476601 (P = 6.5×10(-06), OR =1.62) encoding the PTPN22 R620W variant noted in early-onset MG (EOMG) and other autoimmune diseases. In contrast, EOMG-associated SNPs in TNIP1 showed no association in LOMG, nor did other loci suggested for EOMG. Many SNPs within the major histocompatibility complex (MHC) region showed strong associations in LOMG, but with smaller effect sizes than in EOMG (highest OR ~2 vs. ~6 in EOMG). Moreover, the strongest associations were in opposite directions from EOMG, including an OR of 0.54 for DQA1*05:01 in LOMG (P = 5.9×10(-12)) vs. 2.82 in EOMG (P = 3.86×10(-45)). Association and conditioning studies for the MHC region showed three distinct and largely independent association peaks for LOMG corresponding to i) MHC class II (highest attenuation when conditioning on DQA1), ii) HLA-A and iii) MHC class III SNPs. Conditioning studies of HLA amino acid residues also suggest potential functional correlates. Together, these findings emphasize the value of subgrouping MG patients for clinical and basic investigations, and imply distinct predisposing mechanisms in LOMG.

  12. Confirmation of the association between high levels of immunoglobulin E food sensitization and eczema in infancy : an international study

    NARCIS (Netherlands)

    Hill, D. J.; Hosking, C. S.; de Benedictis, F. M.; Oranje, A. P.; Diepgen, T. L.; Bauchau, V.

    Background Studies of Australian infants have reported that more than 80% of those with moderate atopic eczema (AE) have high levels of IgE food sensitization (IgE-FS) that are commonly associated with IgE food allergy. Objectives To explore the relationship between high levels of IgE-FS and AE in a

  13. Genome-wide association study in a Lebanese cohort confirms PHACTR1 as a major determinant of coronary artery stenosis.

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    Jörg Hager

    Full Text Available The manifestation of coronary artery disease (CAD follows a well-choreographed series of events that includes damage of arterial endothelial cells and deposition of lipids in the sub-endothelial layers. Genome-wide association studies (GWAS of multiple populations with distinctive genetic and lifestyle backgrounds are a crucial step in understanding global CAD pathophysiology. In this study, we report a GWAS on the genetic basis of arterial stenosis as measured by cardiac catheterization in a Lebanese population. The locus of the phosphatase and actin regulator 1 gene (PHACTR1 showed association with coronary stenosis in a discovery experiment with genome wide data in 1,949 individuals (rs9349379, OR = 1.37, p = 1.57×10(-5. The association was replicated in an additional 2,547 individuals (OR = 1.31, p = 8.85×10(-6, leading to genome-wide significant association in a combined analysis (OR = 1.34, p = 8.02×10(-10. Results from this GWAS support a central role of PHACTR1 in CAD susceptibility irrespective of lifestyle and ethnic divergences. This association provides a plausible component for understanding molecular mechanisms involved in the formation of stenosis in cardiac vessels and a potential drug target against CAD.

  14. Genome-Wide Association Study in a Lebanese Cohort Confirms PHACTR1 as a Major Determinant of Coronary Artery Stenosis

    Science.gov (United States)

    Hager, Jörg; Youhanna, Sonia; Ghassibe-Sabbagh, Michella; Platt, Daniel E.; Abchee, Antoine B.; Romanos, Jihane; Khazen, Georges; Othman, Raed; Badro, Danielle A.; Haber, Marc; Salloum, Angelique K.; Douaihy, Bouchra; Shasha, Nabil; Kabbani, Samer; Sbeite, Hana; Chammas, Elie; el Bayeh, Hamid; Rousseau, Francis; Zelenika, Diana; Gut, Ivo; Lathrop, Mark; Farrall, Martin; Gauguier, Dominique; Zalloua, Pierre A.

    2012-01-01

    The manifestation of coronary artery disease (CAD) follows a well-choreographed series of events that includes damage of arterial endothelial cells and deposition of lipids in the sub-endothelial layers. Genome-wide association studies (GWAS) of multiple populations with distinctive genetic and lifestyle backgrounds are a crucial step in understanding global CAD pathophysiology. In this study, we report a GWAS on the genetic basis of arterial stenosis as measured by cardiac catheterization in a Lebanese population. The locus of the phosphatase and actin regulator 1 gene (PHACTR1) showed association with coronary stenosis in a discovery experiment with genome wide data in 1,949 individuals (rs9349379, OR = 1.37, p = 1.57×10−5). The association was replicated in an additional 2,547 individuals (OR = 1.31, p = 8.85×10−6), leading to genome-wide significant association in a combined analysis (OR = 1.34, p = 8.02×10−10). Results from this GWAS support a central role of PHACTR1 in CAD susceptibility irrespective of lifestyle and ethnic divergences. This association provides a plausible component for understanding molecular mechanisms involved in the formation of stenosis in cardiac vessels and a potential drug target against CAD. PMID:22745674

  15. Genome-Wide Association Study in a Lebanese Cohort Confirms PHACTR1 as a Major Determinant of Coronary Artery Stenosis

    OpenAIRE

    Hager, Jörg; Kamatani, Yoichiro; Cazier, Jean-Baptiste; Youhanna, Sonia; Ghassibe-Sabbagh, Michella; Platt, Daniel E.; Abchee, Antoine B.; Romanos, Jihane; Khazen, Georges; Othman, Raed; Badro, Danielle A; Haber, Marc; Salloum, Angelique K.; Douaihy, Bouchra; Shasha, Nabil

    2012-01-01

    The manifestation of coronary artery disease (CAD) follows a well-choreographed series of events that includes damage of arterial endothelial cells and deposition of lipids in the sub-endothelial layers. Genome-wide association studies (GWAS) of multiple populations with distinctive genetic and lifestyle backgrounds are a crucial step in understanding global CAD pathophysiology. In this study, we report a GWAS on the genetic basis of arterial stenosis as measured by cardiac catheterization in...

  16. Family-based genome-wide association study in Patagonia confirms the association of the DMD locus and cleft lip and palate.

    Science.gov (United States)

    Fonseca, Renata F; de Carvalho, Flávia M; Poletta, Fernando A; Montaner, David; Dopazo, Joaquin; Mereb, Juan C; Moreira, Miguel A M; Seuanez, Hector N; Vieira, Alexandre R; Castilla, Eduardo E; Orioli, Iêda M

    2015-09-01

    The etiology of cleft lip with or without cleft palate (CL±P) is complex and heterogeneous, and multiple genetic and environmental factors are involved. Some candidate genes reported to be associated with oral clefts are located on the X chromosome. At least three genes causing X-linked syndromes [midline 1 (MID1), oral-facial-digital syndrome 1 (OFD1), and dystrophin (DMD)] were previously found to be associated with isolated CL±P. We attempted to confirm the role of X-linked genes in the etiology of isolated CL±P in a South American population through a family-based genome-wide scan. We studied 27 affected children and their mothers, from 26 families, in a Patagonian population with a high prevalence of CL±P. We conducted an exploratory analysis of the X chromosome to identify candidate regions associated with CL±P. Four genomic segments were identified, two of which showed a statistically significant association with CL±P. One is an 11-kb region of Xp21.1 containing the DMD gene, and the other is an intergenic region (8.7 kb; Xp11.4). Our results are consistent with recent data on the involvement of the DMD gene in the etiology of CL±P. The MID1 and OFD1 genes were not included in the four potential CL±P-associated X-chromosome genomic segments. © 2015 Eur J Oral Sci.

  17. Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium

    NARCIS (Netherlands)

    Verhoeven, Virginie J. M.; Hysi, Pirro G.; Saw, Seang-Mei; Vitart, Veronique; Mirshahi, Alireza; Guggenheim, Jeremy A.; Cotch, Mary Frances; Yamashiro, Kenji; Baird, Paul N.; Mackey, David A.; Wojciechowski, Robert; Ikram, M. Kamran; Hewitt, Alex W.; Duggal, Priya; Janmahasatian, Sarayut; Khor, Chiea-Chuen; Fan, Qiao; Zhou, Xin; Young, Terri L.; Tai, E.-Shyong; Goh, Liang-Kee; Li, Yi-Ju; Aung, Tin; Vithana, Eranga; teo, Yik-Ying; Tay, Wanting; Sim, Xueling; Rudan, Igor; Hayward, Caroline; Wright, Alan F.; Polasek, Ozren; Campbell, Harry; Wilson, James F.; Fleck, Brian W.; Nakata, Isao; Yoshimura, Nagahisa; Yamada, Ryo; Matsuda, Fumihiko; Ohno-Matsui, Kyoko; Nag, Abhishek; McMahon, George; St Pourcain, Beate; Lu, Yi; Rahi, Jugnoo S.; Cumberland, Phillippa M.; Bhattacharya, Shomi; Simpson, Claire L.; Atwood, Larry D.; Li, Xiaohui; Raffel, Leslie J.; Murgia, Federico; Portas, Laura; Despriet, Dominiek D. G.; van Koolwijk, Leonieke M. E.; Wolfram, Christian; Lackner, Karl J.; Tönjes, Anke; Mägi, Reedik; Lehtimäki, Terho; Kähönen, Mika; Esko, Tõnu; Metspalu, Andres; Rantanen, Taina; Pärssinen, Olavi; Klein, Barbara E.; Meitinger, Thomas; Spector, Timothy D.; Oostra, Ben A.; Smith, Albert V.; de Jong, Paulus T. V. M.; Hofman, Albert; Amin, Najaf; Karssen, Lennart C.; Rivadeneira, Fernando; Vingerling, Johannes R.; Eiríksdóttir, Guðný; Gudnason, Vilmundur; Döring, Angela; Bettecken, Thomas; Uitterlinden, André G.; Williams, Cathy; Zeller, Tanja; Castagné, Raphaële; Oexle, Konrad; van Duijn, Cornelia M.; Iyengar, Sudha K.; Mitchell, Paul; Wang, Jie Jin; Höhn, René; Pfeiffer, Norbert; Bailey-Wilson, Joan E.; Stambolian, Dwight; Wong, Tien-Yin; Hammond, Christopher J.; Klaver, Caroline C. W.

    2012-01-01

    Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis

  18. Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium

    NARCIS (Netherlands)

    V.J.M. Verhoeven (Virginie); P.G. Hysi (Pirro); S-M. Saw (Seang-Mei); V. Vitart (Veronique); A. Mirshahi (Alireza); J. Guggenheim (Jean); M.F. Cotch (Mary Frances); K. Yamashiro (Kenji); P.N. Baird (Paul); D.A. Mackey (David); R. Wojciechowski (Robert); M.K. Ikram (Kamran); A.W. Hewit (Alex); P. Duggal (Priya); S. Janmahasatian (Sarayut); C.C. Khor; Q. Fan (Qiao); X. Zhou (Xinying); T.L. Young (Terri); E.S. Tai (Shyong); L.-K. Goh; Y.J. Li (Yi); T. Aung (Tin); E.N. Vithana (Eranga); Y.Y. Teo (Yik Ying); W.-T. Tay; X. Sim (Xueling); I. Rudan (Igor); C. Hayward (Caroline); A.F. Wright (Alan); O. Polasek (Ozren); H. Campbell (Harry); J.F. Wilson (James); B. Fleck (Brian); I. Nakata (Isao); N. Yoshimura; R. Yamada (Ryo); F. Matsuda (Fumihiko); K. Ohno-Matsui (Kyoko); A. Nag (Abhishek); G. Mcmahon (George); B. St Pourcain (Beate); Y. Lu (Yi); J.S. Rahi (Jugnoo); P. Cumberland (Phillippa); S. Bhattacharya (Shoumo); C.L. Simpson (Claire); L.D. Atwood (Larry); X. Li (Xiaohui); L.J. Raffel (Leslie); D. Murgia (Daniela); L. Portas (Laura); D.D.G. Despriet (Dominique); L.M.E. van Koolwijk (Leonieke); C. Wolfram (Christian); K.J. Lackner (Karl); A. Tönjes (Anke); R. Mägi (Reedik); T. Lehtimäki (Terho); M. Kähönen (Mika); T. Esko (Tõnu); A. Metspalu (Andres); T. Rantanen (Taina); O. Pärssinen (Olavi); B.E.K. Klein (Barbara); T. Meitinger (Thomas); T.D. Spector (Timothy); B.A. Oostra (Ben); G.D. Smith; P.T.V.M. de Jong (Paulus); A. Hofman (Albert); N. Amin (Najaf); L.C. Karssen (Lennart); F. Rivadeneira Ramirez (Fernando); J.R. Vingerling (Hans); G. Eiriksdottir (Gudny); V. Gudnason (Vilmundur); A. Döring (Angela); T. Bettecken (Thomas); A.G. Uitterlinden (André); C. Williams (Cathy); T. Zeller (Tanja); R. Castagne (Raphaële); K. Oexle (Konrad); C.M. van Duijn (Cornelia); S.K. Iyengar (Sudha); P. Mitchell (Paul); J.J. Wang (Jie Jin); R. Höhn (René); A.F.H. Pfeiffer (Andreas); J.E. Bailey-Wilson (Joan); D.E. Stambolian (Dwight); T.Y. Wong (Tien Yin); C.J. Hammond (Christopher); C.C.W. Klaver (Caroline)

    2012-01-01

    textabstractMyopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and

  19. A replication study confirms the association of dendritic cell immunoreceptor (DCIR polymorphisms with ACPA - negative RA in a large Asian cohort.

    Directory of Open Access Journals (Sweden)

    Jianping Guo

    Full Text Available Dendritic cell immunoreceptor (DCIR has been implicated in development of autoimmune disorders in rodent and DCIR polymorphisms were associated with anti-citrullinated proteins antibodies (ACPA-negative rheumatoid arthritis (RA in Swedish Caucasians. This study was undertaken to further investigate whether DCIR polymorphisms are also risk factors for the development of RA in four Asian populations originated from China and Malaysia.We genotyped two DCIR SNPs rs2377422 and rs10840759 in Han Chinese population (1,193 cases, 1,278 controls, to assess their association with RA. Subsequently, rs2377422 was further genotyped in three independent cohorts of Malaysian-Chinese subjects (MY_Chinese, 254 cases, 206 controls, Malay subjects (MY_ Malay, 515 cases, 986 controls, and Malaysian-Indian subjects (MY_Indian, 378 cases, 285 controls, to seek confirmation of association in various ethnic groups. Meta-analysis was preformed to evaluate the contribution of rs2377422 polymorphisms to the development of ACPA-negative RA in distinct ethnic groups. Finally, we carried out association analysis of rs2377422 polymorphisms with DCIR mRNA expression levels.DCIR rs2377422 was found to be significantly associated with ACPA -negative RA in Han Chinese (OR 1.92, 95% CI 1.27-2.90, P=0.0020. Meta-analysis confirms DCIR rs2377422 as a risk factor for ACPA-negative RA across distinct ethnic groups (OR(overall =1.17, 95% CI 1.06-1.30, P=0.003. The SNP rs2377422 polymorphism showed significant association with DCIR mRNA expression level, i.e. RA-risk CC genotype exhibit a significant increase in the expression of DCIR (P=0.0023, Kruskal-Wallis.Our data provide evidence for association between DCIR rs2377422 and RA in non-Caucasian populations and confirm the influence of DCIR polymorphisms on RA susceptibility, especially on ACPA-negative RA.

  20. Factors associated with child sexual abuse confirmation at forensic examinations.

    Science.gov (United States)

    Silva, Welington Dos Santos; Ribeiro, Filipe Moraes; Guimarães, Gabriel Kamei; Santos, Matheus de Sá Dos; Almeida, Victor Porfírio Dos Santos; Barroso-Junior, Ubirajara de Oliveira

    2018-02-01

    The aim of this study is identify potential factors associated with child sexual abuse confirmation at forensic examinations. The forensic files of children under 12 years of age reporting sexual abuse at the Nina Rodrigues Institute of Forensic Medicine in Salvador, Bahia, Brazil between January 2008 and December 2009 were reviewed. A multivariate analysis was conducted to identify factors associated with finding evidence of sexual abuse in forensic examinations. The proportion of cases confirmed by the forensic physician based on material evidence was 10.4%. Adjusted analysis showed that the variables place of birth, type of abuse reported, family relationship between the child and the perpetrator, and the interval between the reported abuse and the forensic examination were not independently associated with finding forensic evidence of sexual abuse. A report of penetration was associated with a five-fold greater likelihood of confirmation, while the victim being 10-11 years of age was associated with a two-fold of abuse confirmation than younger children. These findings should be taken into consideration when drawing up guidelines for the multidisciplinary evaluation of children suspected of being victims of sexual abuse and in deciding whether to refer the child for forensic examination.

  1. Family-based exome-wide association study of childhood acute lymphoblastic leukemia among Hispanics confirms role of ARID5B in susceptibility.

    Directory of Open Access Journals (Sweden)

    Natalie P Archer

    Full Text Available We conducted an exome-wide association study of childhood acute lymphoblastic leukemia (ALL among Hispanics to confirm and identify novel variants associated with disease risk in this population. We used a case-parent trio study design; unlike more commonly used case-control studies, this study design is ideal for avoiding issues with population stratification bias among this at-risk ethnic group. Using 710 individuals from 323 Guatemalan and US Hispanic families, two inherited SNPs in ARID5B reached genome-wide level significance: rs10821936, RR = 2.31, 95% CI = 1.70-3.14, p = 1.7×10-8 and rs7089424, RR = 2.22, 95% CI = 1.64-3.01, p = 5.2×10-8. Similar results were observed when restricting our analyses to those with the B-ALL subtype: ARID5B rs10821936 RR = 2.22, 95% CI = 1.63-3.02, p = 9.63×10-8 and ARID5B rs7089424 RR = 2.13, 95% CI = 1.57-2.88, p = 2.81×10-7. Notably, effect sizes observed for rs7089424 and rs10821936 in our study were >20% higher than those reported among non-Hispanic white populations in previous genetic association studies. Our results confirmed the role of ARID5B in childhood ALL susceptibility among Hispanics; however, our assessment did not reveal any strong novel inherited genetic risks for acute lymphoblastic leukemia among this ethnic group.

  2. Family-based exome-wide association study of childhood acute lymphoblastic leukemia among Hispanics confirms role of ARID5B in susceptibility.

    Science.gov (United States)

    Archer, Natalie P; Perez-Andreu, Virginia; Stoltze, Ulrik; Scheurer, Michael E; Wilkinson, Anna V; Lin, Ting-Nien; Qian, Maoxiang; Goodings, Charnise; Swartz, Michael D; Ranjit, Nalini; Rabin, Karen R; Peckham-Gregory, Erin C; Plon, Sharon E; de Alarcon, Pedro A; Zabriskie, Ryan C; Antillon-Klussmann, Federico; Najera, Cesar R; Yang, Jun J; Lupo, Philip J

    2017-01-01

    We conducted an exome-wide association study of childhood acute lymphoblastic leukemia (ALL) among Hispanics to confirm and identify novel variants associated with disease risk in this population. We used a case-parent trio study design; unlike more commonly used case-control studies, this study design is ideal for avoiding issues with population stratification bias among this at-risk ethnic group. Using 710 individuals from 323 Guatemalan and US Hispanic families, two inherited SNPs in ARID5B reached genome-wide level significance: rs10821936, RR = 2.31, 95% CI = 1.70-3.14, p = 1.7×10-8 and rs7089424, RR = 2.22, 95% CI = 1.64-3.01, p = 5.2×10-8. Similar results were observed when restricting our analyses to those with the B-ALL subtype: ARID5B rs10821936 RR = 2.22, 95% CI = 1.63-3.02, p = 9.63×10-8 and ARID5B rs7089424 RR = 2.13, 95% CI = 1.57-2.88, p = 2.81×10-7. Notably, effect sizes observed for rs7089424 and rs10821936 in our study were >20% higher than those reported among non-Hispanic white populations in previous genetic association studies. Our results confirmed the role of ARID5B in childhood ALL susceptibility among Hispanics; however, our assessment did not reveal any strong novel inherited genetic risks for acute lymphoblastic leukemia among this ethnic group.

  3. Confirmation of prior evidence of genetic susceptibility to alcoholism in a genome-wide association study of comorbid alcoholism and bipolar disorder.

    Science.gov (United States)

    Lydall, Gregory John; Bass, Nicholas J; McQuillin, Andrew; Lawrence, Jacob; Anjorin, Adebayo; Kandaswamy, Radhika; Pereira, Ana; Guerrini, Irene; Curtis, David; Vine, Anna E; Sklar, Pamela; Purcell, Shaun M; Gurling, Hugh Malcolm Douglas

    2011-12-01

    Alcoholism and affective disorders are both strongly comorbid and heritable. We have investigated the genetic comorbidity between bipolar affective disorder and alcoholism. A genome-wide allelic association study of 506 patients from the University College London bipolar disorder case-control sample and 510 ancestrally matched supernormal controls. One hundred forty-three of the bipolar patients fulfilled the Research Diagnostic Criteria diagnosis of alcoholism. A total of 372 193 single nucleotide polymorphisms (SNPs) were genotyped. Genes previously shown to be associated with alcoholism and addiction phenotypes were then tested for association in the bipolar alcoholic sample using gene-wise permutation tests of all SNPs genotyped within a 50-kb region flanking each gene. Several central nervous system genes showed significant (Palcoholism. The genes implicated, which replicated genes previously shown to be associated with alcoholism were: cadherin 11, collagen type 11 α2, neuromedin U receptor 2, exportin7, and semaphorin-associated protein 5A. The SNPs most strongly implicated in bipolar alcoholism, but, which did not meet conventional genome-wide significance criteria were the insulin-like growth factor-binding protein 7, carboxypeptidase O, cerebellin 2, and the cadherin 12 genes. We have confirmed the role of some genes previously shown to be associated with alcoholism in the comorbid bipolar alcoholism subgroup. In this subgroup, bipolar disorder may lower the threshold for the phenotypic expression of these alcoholism susceptibility genes. We also show that some genes may independently increase susceptibility to affective disorder and alcoholism.

  4. Genome-wide association study confirms lung cancer susceptibility loci on chromosomes 5p15 and 15q25 in an African-American population.

    Science.gov (United States)

    Zanetti, Krista A; Wang, Zhaoming; Aldrich, Melinda; Amos, Christopher I; Blot, William J; Bowman, Elise D; Burdette, Laurie; Cai, Qiuyin; Caporaso, Neil; Chung, Charles C; Gillanders, Elizabeth M; Haiman, Christopher A; Hansen, Helen M; Henderson, Brian E; Kolonel, Laurence N; Marchand, Loic Le; Li, Shengchao; McNeill, Lorna Haughton; Ryan, Bríd M; Schwartz, Ann G; Sison, Jennette D; Spitz, Margaret R; Tucker, Margaret; Wenzlaff, Angela S; Wiencke, John K; Wilkens, Lynne; Wrensch, Margaret R; Wu, Xifeng; Zheng, Wei; Zhou, Weiyin; Christiani, David; Palmer, Julie R; Penning, Trevor M; Rieber, Alyssa G; Rosenberg, Lynn; Ruiz-Narvaez, Edward A; Su, Li; Vachani, Anil; Wei, Yongyue; Whitehead, Alexander S; Chanock, Stephen J; Harris, Curtis C

    2016-08-01

    Genome-wide association studies (GWAS) of lung cancer have identified regions of common genetic variation with lung cancer risk in Europeans who smoke and never-smoking Asian women. This study aimed to conduct a GWAS in African Americans, who have higher rates of lung cancer despite smoking fewer cigarettes per day when compared with Caucasians. This population provides a different genetic architecture based on underlying African ancestry allowing the identification of new regions and exploration of known regions for finer mapping. We genotyped 1,024,001 SNPs in 1737 cases and 3602 controls in stage 1, followed by a replication phase of 20 SNPs (p<1.51×10(-5)) in an independent set of 866 cases and 796 controls in stage 2. In the combined analysis, we confirmed two loci to be associated with lung cancer that achieved the threshold of genome-wide significance: 15q25.1 marked by rs2036527 (p=1.3×10(-9); OR=1.32; 95% CI=1.20-1.44) near CHRNA5, and 5p15.33 marked by rs2853677 (p=2.8×10(-9); OR=1.28; 95% CI=1.18-1.39) near TERT. The association with rs2853677 is driven by the adenocarcinoma subtype of lung cancer (p=1.3×10(-8); OR=1.37; 95% CI=1.23-1.54). No SNPs reached genome-wide significance for either of the main effect models examining smoking - cigarettes per day and current or former smoker. Our study was powered to identify strong risk loci for lung cancer in African Americans; we confirmed results previously reported in African Americans and other populations for two loci near plausible candidate genes, CHRNA5 and TERT, on 15q25.1 and 5p15.33 respectively, are associated with lung cancer. Additional work is required to map and understand the biological underpinnings of the strong association of these loci with lung cancer risk in African Americans. Published by Elsevier Ireland Ltd.

  5. Genome-wide association study confirms lung cancer susceptibility loci on chromosome 5p15 and 15q25 in an African-American population

    Science.gov (United States)

    Zanetti, Krista A.; Wang, Zhaoming; Aldrich, Melinda; Amos, Christopher I.; Blot, William J.; Bowman, Elise D.; Burdette, Laurie; Cai, Quiyin; Caporaso, Neil; Chung, Charles C.; Gillanders, Elizabeth M.; Haiman, Christopher A.; Hansen, Helen M.; Henderson, Brian E.; Kolonel, Laurence N.; Le Marchand, Loic; Li, Shengchao; McNeill, Lorna Haughton; Ryan, Bríd M.; Schwartz, Ann G.; Sison, Jennette D.; Spitz, Margaret R.; Tucker, Margaret; Wenzlaff, Angela S.; Wiencke, John K.; Wilkens, Lynne; Wrensch, Margaret R.; Wu, Xifeng; Zheng, Wei; Zhou, Weiyin; Christiani, David; Palmer, Julie R.; Penning, Trevor M.; Rieber, Alyssa G.; Rosenberg, Lynn; Ruiz-Narvaez, Edward A.; Su, Li; Vachani, Anil; Wei, Yongyue; Whitehead, Alexander S.; Chanock, Stephen J.; Harris, Curtis C.

    2016-01-01

    Objectives Genome-wide association studies (GWAS) of lung cancer have identified regions of common genetic variation with lung cancer risk in Europeans who smoke and never-smoking Asian women. This study aimed to conduct a GWAS in African Americans, who have higher rates of lung cancer despite smoking fewer cigarettes per day when compared with Caucasians. This population provides a different genetic architecture based on underlying African ancestry allowing the identification of new regions and exploration of known regions for finer mapping. Materials and Methods We genotyped 1,024,001 SNPs in 1737 cases and 3602 controls in stage 1, followed by a replication phase of 20 SNPs (p<1.51×10−5) in an independent set of 866 cases and 796 controls in stage 2. Results and Conclusion In the combined analysis, we confirmed two loci to be associated with lung cancer that achieved the threshold of genome-wide significance: 15q25.1 marked by rs2036527 (p = 1.3 × 10−9; OR = 1.32; 95% CI = 1.20–1.44) near CHRNA5, and 5p15.33 marked by rs2853677 (p = 2.8 × 10−9; OR = 1.28; 95% CI = 1.18–1.39) near TERT. The association with rs2853677 is driven by the adenocarcinoma subtype of lung cancer (p = 1.3 × 10−8; OR = 1.37; 95% CI = 1.23–1.54). No SNPs reached genome-wide significance for either of the main effect models examining smoking - cigarettes per day and current or former smoker. Our study was powered to identify strong risk loci for lung cancer in African Americans; we confirmed results previously reported in African Americans and other populations for two loci near plausible candidate genes, CHRNA5 and TERT, on 15q25.1 and 5p15.33 respectively, are associated with lung cancer. Additional work is required to map and understand the biological underpinnings of the strong association of these loci with lung cancer risk in African Americans. PMID:27393504

  6. A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort

    NARCIS (Netherlands)

    Bossini-Castillo, L.; Broen, J.C.; Simeon, C.P.; Beretta, L.; Vonk, M.C.; Ortego-Centeno, N.; Espinosa, G.; Carreira, P.; Camps, M.T.; Navarrete, N.; Gonzalez-Escribano, M.F.; Vicente-Rabaneda, E.; Rodriguez, L.; Tolosa, C.; Roman-Ivorra, J.A.; Gomez-Gracia, I.; Garcia-Hernandez, F.J.; Castellvi, I.; Gallego, M.; Fernandez-Nebro, A.; Garcia-Portales, R.; Egurbide, M.V.; Fonollosa, V.; Pena, P.G. de la; Pros, A.; Gonzalez-Gay, M.A.; Hesselstrand, R.; Riemekasten, G.; Witte, T.J.M. de; Coenen, M.J.H.; Koeleman, B.P.; Houssiau, F.; Smith, V.; Keyser, F. de; Westhovens, R.; Langhe, E. De; Voskuyl, A.E.; Schuerwegh, A.J.; Chee, M.M.; Madhok, R.; Shiels, P.; Fonseca, C.; Denton, C.; Claes, K.; Padykov, L.; Nordin, A.; Palm, O.; Lie, B.A.; Airo, P.; Scorza, R.; Laar, J.M. van; Hunzelmann, N.; Kreuter, A.; Herrick, A.; Worthington, J.; Radstake, T.R.D.J.; Martin, J.; Rueda, B.

    2011-01-01

    OBJECTIVES: The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features. METHODS: A total of 8 European populations of Caucasian ancestry were included, comprising 3014 patients with SSc and 3125 healthy controls. Four

  7. Replication Study Confirms the Association of the Common rs1800629 Variant of the TNF Gene with Postmenopausal Osteoporosis Susceptibility in the Han Chinese Population.

    Science.gov (United States)

    Jin, Xiaona; Zhou, Baozhen; Zhang, Dangfeng

    2018-02-26

    Previous studies have suggested that tumor necrosis factor a (TNF-a), encoded by TNF gene, can increase osteoclast formation, and that specific alleles of the TNF gene are associated with postmenopausal osteoporosis susceptibility in some populations; however, the exact molecular mechanism remains unknown. To investigate the potential association of nineteen polymorphisms of the TNF gene with postmenopausal osteoporosis and bone mineral density (BMD) traits in a sample of 1288 postmenopausal women from the Han Chinese population. A total of 437 postmenopausal osteoporosis patients and 851 unrelated age-matched healthy women were recruited in the study. Single marker and haplotype based analyses were conducted to evaluate the association of nineteen single nucleotide polymorphisms (SNPs) in both patient and control groups. The SNP rs1800629 was identified as being highly significantly associated with postmenopausal osteoporosis after accounting for age and body mass index (p = 0.000087). In addition, the GG genotype of this SNP was associated with significantly lower measures of femoral neck BMD and lumbar spine BMD. Moreover, haplotype based analyses suggested significant association signals between the haplotype block, including rs1800629 with postmenopausal osteoporosis (p osteoporosis and BMD in the female Han Chinese population. Additional sequencing-based studies are needed to investigate the genetic architecture of this genomic region and its relationship with osteoporosis-related phenotypes.

  8. Association between stillbirth and risk factors known at pregnancy confirmation.

    Science.gov (United States)

    2011-12-14

    Stillbirths account for almost half of US deaths from 20 weeks' gestation to 1 year of life. Most large studies of risk factors for stillbirth use vital statistics with limited data. To determine the relation between stillbirths and risk factors that could be ascertained at the start of pregnancy, particularly the contribution of these factors to racial disparities. Multisite population-based case-control study conducted between March 2006 and September 2008. Fifty-nine US tertiary care and community hospitals, with access to at least 90% of deliveries within 5 catchment areas defined by state and county lines, enrolled residents with deliveries of 1 or more stillborn fetuses and a representative sample of deliveries of only live-born infants, oversampled for those at less than 32 weeks' gestation and those of African descent. Stillbirth. Analysis included 614 case and 1816 control deliveries. In multivariate analyses, the following factors were independently associated with stillbirth: non-Hispanic black race/ethnicity (23.1% stillbirths, 11.2% live births) (vs non-Hispanic whites; adjusted odds ratio [AOR], 2.12 [95% CI, 1.41-3.20]); previous stillbirth (6.7% stillbirths, 1.4% live births); nulliparity with (10.5% stillbirths, 5.2% live births) and without (34.0% stillbirths, 29.7% live births) previous losses at fewer than 20 weeks' gestation (vs multiparity without stillbirth or previous losses; AOR, 5.91 [95% CI, 3.18-11.00]; AOR, 3.13 [95% CI, 2.06-4.75]; and AOR, 1.98 [95% CI, 1.51-2.60], respectively); diabetes (5.6% stillbirths, 1.6% live births) (vs no diabetes; AOR, 2.50 [95% CI, 1.39-4.48]); maternal age 40 years or older (4.5% stillbirths, 2.1% live births) (vs age 20-34 years; AOR, 2.41 [95% CI, 1.24-4.70]); maternal AB blood type (4.9% stillbirths, 3.0% live births) (vs type O; AOR, 1.96 [95% CI, 1.16-3.30]); history of drug addiction (4.5% stillbirths, 2.1% live births) (vs never use; AOR, 2.08 [95% CI, 1.12-3.88]); smoking during the 3 months prior

  9. NIH study confirms risk factors for male breast cancer

    Science.gov (United States)

    Pooled data from studies of about 2,400 men with breast cancer and 52,000 men without breast cancer confirmed that risk factors for male breast cancer include obesity, a rare genetic condition called Klinefelter syndrome, and gynecomastia.

  10. Exploring Selective Exposure and Confirmation Bias as Processes Underlying Employee Work Happiness: An Intervention Study

    Science.gov (United States)

    Williams, Paige; Kern, Margaret L.; Waters, Lea

    2016-01-01

    Employee psychological capital (PsyCap), perceptions of organizational virtue (OV), and work happiness have been shown to be associated within and over time. This study examines selective exposure and confirmation bias as potential processes underlying PsyCap, OV, and work happiness associations. As part of a quasi-experimental study design, school staff (N = 69) completed surveys at three time points. After the first assessment, some staff (n = 51) completed a positive psychology training intervention. Results of descriptive statistics, correlation, and regression analyses on the intervention group provide some support for selective exposure and confirmation bias as explanatory mechanisms. In focusing on the processes through which employee attitudes may influence work happiness this study advances theoretical understanding, specifically of selective exposure and confirmation bias in a field study context. PMID:27378978

  11. Association between Apolipoprotein E genotype and cerebral palsy is not confirmed in a Caucasian population.

    Science.gov (United States)

    McMichael, Gai L; Gibson, Catherine S; Goldwater, Paul N; Haan, Eric A; Priest, Kevin; Dekker, Gustaaf A; MacLennan, Alastair H

    2008-11-01

    Apolipoprotein E (APOE) plays a significant role in lipid metabolism and has been implicated in the growth and repair of injured neurons. Two small studies have suggested an association between APOE genotype and cerebral palsy. We investigated if APOE genotype is associated with an increased risk for cerebral palsy, influences the type of cerebral palsy or interacts with prenatal viral infection to influence risk of cerebral palsy. The population-based case-control study comprised newborn screening cards of 443 Caucasian patients with cerebral palsy and 883 Caucasian matched controls. APOE genotyping was performed on DNA extracted from dried blood spots. Allelic and genotypic frequencies did not differ between cases and controls and combined frequencies were 0.10 (epsilon2), 0.76 (epsilon3), 0.14 (epsilon4), 0.03 (epsilon2/epsilon2), 0.10 (epsilon2/epsilon3), 0.03 (epsilon2/epsilon4), 0.02 (epsilon4/epsilon4), 0.21 (epsilon3/epsilon4), 0.61 (epsilon3/epsilon3). APOE genotype was correlated with cerebral palsy, type of cerebral palsy, gestation at birth and the presence of viral nucleic acids detected in previous work. Analysis by gestational age (all gestational ages, >/=37, 32-36 and <32 weeks) and type of cerebral palsy (all types, diplegia, hemiplegia and quadriplegia) showed no association between APOE genotype and cerebral palsy in this Caucasian population. An association between prenatal viral infection, APOE genotype and cerebral palsy was not demonstrated. These results did not confirm an association between APOE genotype, cerebral palsy, type of cerebral palsy and prenatal infection in a Caucasian population. Given the low frequency of APOE epsilon2 and some of the heterozygote and homozygote combinations in this study, a larger study is assessing this further.

  12. Failure to confirm association between RGS4 haplotypes and schizophrenia in Caucasians.

    Science.gov (United States)

    Sobell, Janet L; Richard, Christian; Wirshing, Donna A; Heston, Leonard L

    2005-11-05

    The regulator of G-protein signaling (RGS) and RGS-like proteins are a diverse family of over 30 molecules that function as GTPase activating proteins for Galpha subunits of the Gq and Gi families of heterotrimeric guanine nucleotide-binding proteins (G proteins). By accelerating GTPase activity, RGS proteins drive G proteins into their inactive GDP-bound forms. G-protein coupled dopamine, metabotropic glutamate, and other neurotransmitter receptors can be modulated by RGS4, the predominant form in brain. The recent finding of decreased RGS4 mRNA expression in post-mortem brains from schizophrenic patients, coupled with the map position of RGS4 to a region previously linked to schizophrenia, as well as other biological data, prompted the investigation of the gene as a disease candidate. Multiple family-based and case-control association studies have been conducted, with modest and conflicting support for particular single nucleotide polymorphism (SNP) markers and SNP marker haplotypes. The present case-control analysis of 568 patients and 689 controls, one of the largest single studies to date, failed to confirm support for association of particular RGS4 SNP alleles, or for association of any particular four, three, or two SNP haplotype. (c) 2005 Wiley-Liss, Inc.

  13. Tracers confirm downward mixing of Tyrrhenian Sea upper waters associated with the Eastern Mediterranean Transient

    Directory of Open Access Journals (Sweden)

    W. Roether

    2011-01-01

    Full Text Available Observations of tritium and 3He in the Tyrrhenian Sea, 1987–2009, confirm the enhanced vertical mixing of intermediate waters into the deep waters that has been noted and associated with the Eastern Mediterranean Transient in previous studies. Our evidence for the mixing rests on increasing tracer concentrations in the Tyrrhenian deep waters, accompanied by decreases in the upper waters, which are supplied from the Eastern Mediterranean. The downward transfer is particularly evident between 1987 and 1997. Later on, information partly rests on increasing tritium-3He ages; here we correct the observed 3He for contributions released from the ocean floor. The Tyrrhenian tracer distributions are fully compatible with data upstream of the Sicily Strait and in the Western Mediterranean. The tracer data show that mixing reached to the bottom and confirm a cyclonic nature of the deep water circulation in the Tyrrhenian. They furthermore indicate that horizontal homogenization of the deep waters occurs on a time scale of roughly 5 years. Various features point to a reduced impact of Western Mediterranean Deep Water (WMDW in the Tyrrhenian during the enhanced-mixing period. This is an important finding because it implies less upward mixing of WMDW, which has been named a major process to enable the WMDW to leave the Mediterranean via the Gibraltar Strait. On the other hand, the TDW outflow for several years represented a major influx of enhanced salinity and density waters into the deep-water range of the Western Mediterranean.

  14. A genome-wide SNP-association study confirms a sequence variant (g.66493737C>T in the equine myostatin (MSTN gene as the most powerful predictor of optimum racing distance for Thoroughbred racehorses

    Directory of Open Access Journals (Sweden)

    Whiston Ronan

    2010-10-01

    Full Text Available Abstract Background Thoroughbred horses have been selected for traits contributing to speed and stamina for centuries. It is widely recognized that inherited variation in physical and physiological characteristics is responsible for variation in individual aptitude for race distance, and that muscle phenotypes in particular are important. Results A genome-wide SNP-association study for optimum racing distance was performed using the EquineSNP50 Bead Chip genotyping array in a cohort of n = 118 elite Thoroughbred racehorses divergent for race distance aptitude. In a cohort-based association test we evaluated genotypic variation at 40,977 SNPs between horses suited to short distance (≤ 8 f and middle-long distance (> 8 f races. The most significant SNP was located on chromosome 18: BIEC2-417495 ~690 kb from the gene encoding myostatin (MSTN [Punadj. = 6.96 × 10-6]. Considering best race distance as a quantitative phenotype, a peak of association on chromosome 18 (chr18:65809482-67545806 comprising eight SNPs encompassing a 1.7 Mb region was observed. Again, similar to the cohort-based analysis, the most significant SNP was BIEC2-417495 (Punadj. = 1.61 × 10-9; PBonf. = 6.58 × 10-5. In a candidate gene study we have previously reported a SNP (g.66493737C>T in MSTN associated with best race distance in Thoroughbreds; however, its functional and genome-wide relevance were uncertain. Additional re-sequencing in the flanking regions of the MSTN gene revealed four novel 3' UTR SNPs and a 227 bp SINE insertion polymorphism in the 5' UTR promoter sequence. Linkage disequilibrium was highest between g.66493737C>T and BIEC2-417495 (r2 = 0.86. Conclusions Comparative association tests consistently demonstrated the g.66493737C>T SNP as the superior variant in the prediction of distance aptitude in racehorses (g.66493737C>T, P = 1.02 × 10-10; BIEC2-417495, Punadj. = 1.61 × 10-9. Functional investigations will be required to determine whether this

  15. A genome-wide SNP-association study confirms a sequence variant (g.66493737C>T) in the equine myostatin (MSTN) gene as the most powerful predictor of optimum racing distance for Thoroughbred racehorses.

    Science.gov (United States)

    Hill, Emmeline W; McGivney, Beatrice A; Gu, Jingjing; Whiston, Ronan; Machugh, David E

    2010-10-11

    Thoroughbred horses have been selected for traits contributing to speed and stamina for centuries. It is widely recognized that inherited variation in physical and physiological characteristics is responsible for variation in individual aptitude for race distance, and that muscle phenotypes in particular are important. A genome-wide SNP-association study for optimum racing distance was performed using the EquineSNP50 Bead Chip genotyping array in a cohort of n = 118 elite Thoroughbred racehorses divergent for race distance aptitude. In a cohort-based association test we evaluated genotypic variation at 40,977 SNPs between horses suited to short distance (≤ 8 f) and middle-long distance (> 8 f) races. The most significant SNP was located on chromosome 18: BIEC2-417495 ~690 kb from the gene encoding myostatin (MSTN) [P(unadj.) = 6.96 x 10⁻⁶]. Considering best race distance as a quantitative phenotype, a peak of association on chromosome 18 (chr18:65809482-67545806) comprising eight SNPs encompassing a 1.7 Mb region was observed. Again, similar to the cohort-based analysis, the most significant SNP was BIEC2-417495 (P(unadj.) = 1.61 x 10⁻⁹; P(Bonf.) = 6.58 x 10⁻⁵). In a candidate gene study we have previously reported a SNP (g.66493737C>T) in MSTN associated with best race distance in Thoroughbreds; however, its functional and genome-wide relevance were uncertain. Additional re-sequencing in the flanking regions of the MSTN gene revealed four novel 3' UTR SNPs and a 227 bp SINE insertion polymorphism in the 5' UTR promoter sequence. Linkage disequilibrium was highest between g.66493737C>T and BIEC2-417495 (r² = 0.86). Comparative association tests consistently demonstrated the g.66493737C>T SNP as the superior variant in the prediction of distance aptitude in racehorses (g.66493737C>T, P = 1.02 x 10⁻¹⁰; BIEC2-417495, P(unadj.) = 1.61 x 10⁻⁹). Functional investigations will be required to determine whether this polymorphism affects putative

  16. Confirmed case of levamisole-associated multifocal inflammatory leukoencephalopathy in a cocaine user.

    Science.gov (United States)

    Vitt, Jeffrey R; Brown, Ethan G; Chow, Daniel S; Josephson, S Andrew

    2017-04-15

    Levamisole is a common adulterant in cocaine and has previously been associated with a variety of serious complications including multifocal inflammatory leukoencephalopathy (MIL). There have been several reports of MIL in patients taking cocaine and, though suspected, the presence of levamisole was not confirmed. We present a case of a 63-year-old woman presenting with stupor and spastic quadraparesis found to have urine positive for cocaine and levamisole. An MRI brain revealed innumerable FLAIR hyperintensities with restricted diffusion and incomplete ring-enhancement. This is the first case to confirm the presence of levamisole in a patient with MIL associated with cocaine use. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Antimicrobial Resistance and Antimicrobial Use Associated with Laboratory-Confirmed Cases of Campylobacter Infection in Two Health Units in Ontario

    Directory of Open Access Journals (Sweden)

    Anne E Deckert

    2013-01-01

    Full Text Available AIM: A population-based study was conducted over a two-year period in the Perth District (PD and Wellington-Dufferin-Guelph (WDG health units in Ontario to document antimicrobial resistance and antimicrobial use associated with clinical cases of laboratory-confirmed campylobacteriosis.

  18. Perivenous demyelination: association with clinically defined acute disseminated encephalomyelitis and comparison with pathologically confirmed multiple sclerosis.

    Science.gov (United States)

    Young, Nathan P; Weinshenker, Brian G; Parisi, Joseph E; Scheithauer, B; Giannini, C; Roemer, Shanu F; Thomsen, Kristine M; Mandrekar, Jayawant N; Erickson, Bradley J; Lucchinetti, Claudia F

    2010-02-01

    Distinction between acute disseminated encephalomyelitis and acute multiple sclerosis is often clinically difficult. Perivenous demyelination is the pathological hallmark of acute disseminated encephalomyelitis, whereas confluent demyelination is the hallmark of acute multiple sclerosis. We investigated whether perivenous demyelination versus confluent demyelination distinguishes acute disseminated encephalomyelitis from multiple sclerosis. Patients with perivenous demyelination (n = 13; median age 43 years, range 5-67) on brain biopsy and/or autopsy, ascertained retrospectively, were compared with a cohort with confluent demyelination only (n = 91; 84% multiple sclerosis, 16% isolated syndrome at follow-up; median age 39 years, range 10-69). Clinical presentation, course and the International Paediatric Multiple Sclerosis Study Group clinical criteria for acute disseminated encephalomyelitis were assessed in both cohorts. Among the perivenous demyelination cohort, 10 patients had only perivenous demyelination and three also had confluent demyelination. All but one patient with perivenous demyelination only had a monophasic course, whereas two of three with both types had a relapsing course. The perivenous demyelination cohort was more likely than the confluent demyelination cohort to present with encephalopathy (P acute disseminated encephalomyelitis (perivenous demyelination), but misdiagnosed acute disseminated encephalomyelitis among 9% of patients with confluent demyelination and multiple sclerosis diagnosis at last follow-up. Perivenous demyelination is associated with meningoencephalopathic presentations and a monophasic course. Depressed level of consciousness is a more specific clinical criterion for pathologically confirmed acute disseminated encephalomyelitis than encephalopathy, which over-diagnosed acute disseminated encephalomyelitis among multiple sclerosis patients. A distinct pattern of cortical microglial activation without cortical demyelination

  19. Data on association between QRS duration on prehospital ECG and mortality in patients with confirmed STEMI

    DEFF Research Database (Denmark)

    Hansen, Rikke; Frydland, Martin; Møller-Helgestad, Ole Kristian

    2017-01-01

    Data presented in this article relates to the research article entitled “Association between QRS duration on prehospital ECG and mortality in patients with suspected STEMI” (Hansen et al., in press) [1]. Data on the prognostic effect of automatically recoded QRS duration on prehospital ECG...... and presence of classic left and right bundle branch block in 1777 consecutive patients with confirmed ST segment elevation AMI is presented. Multivariable analysis, suggested that QRS duration >111 ms, left bundle branch block and right bundle branch block were independent predictors of 30 days all...

  20. Data on association between QRS duration on prehospital ECG and mortality in patients with confirmed STEMI

    Directory of Open Access Journals (Sweden)

    Rikke Hansen

    2017-12-01

    Full Text Available Data presented in this article relates to the research article entitled “Association between QRS duration on prehospital ECG and mortality in patients with suspected STEMI” (Hansen et al., in press [1].Data on the prognostic effect of automatically recoded QRS duration on prehospital ECG and presence of classic left and right bundle branch block in 1777 consecutive patients with confirmed ST segment elevation AMI is presented. Multivariable analysis, suggested that QRS duration >111 ms, left bundle branch block and right bundle branch block were independent predictors of 30 days all-cause mortality. For interpretation and discussion of these data, refer to the research article referenced above.

  1. Antimicrobial resistance and antimicrobial use associated with laboratory-confirmed cases of Campylobacter infection in two health units in Ontario

    OpenAIRE

    Deckert, Anne E; Reid-Smith, Richard J.; Tamblyn, Susan E; Larry Morrell; Patrick Seliske; Jamieson, Frances B.; Rebecca Irwin; Dewey, Catherine E.; Patrick Boerlin; McEwen, Scott A.

    2013-01-01

    AIM: A population-based study was conducted over a two-year period in the Perth District (PD) and Wellington-Dufferin-Guelph (WDG) health units in Ontario to document antimicrobial resistance and antimicrobial use associated with clinical cases of laboratory-confirmed campylobacteriosis.METHODS: Etest (bioMérieux SA, France) was used to determine the minimum inhibitory concentration of amoxicillin/clavulanic acid, ampicillin, chloramphenicol, ciprofloxacin (CIP), clindamycin, erythromycin (ER...

  2. Confirmation of genetic variants associated with lethal prostate cancer in a cohort of men from hereditary prostate cancer families.

    Science.gov (United States)

    Karyadi, Danielle M; Zhao, Shanshan; He, Qianchuan; McIntosh, Laura; Wright, Jonathan L; Ostrander, Elaine A; Feng, Ziding; Stanford, Janet L

    2015-05-01

    Germline genetic variants have been suggested as prognostic biomarkers for identifying patients at high risk for lethal prostate cancer (PCa). Validation studies have confirmed the association of several single nucleotide polymorphisms (SNPs) with fatal PCa, but whether these variants affect PCa-specific mortality (PCSM) in patients with an inherited predisposition to PCa, based on familial history, is unknown. For this study, a cohort of 957 PCa patients from 270 hereditary prostate cancer families of European ancestry was genotyped for a panel of 22 PCSM-associated SNPs. Death certificates were reviewed to confirm cause of death. Mixed-effect Cox proportional hazards models were used to assess survival according to genotypes, accounting for relatedness and clinicopathological factors. Within this cohort, 98 PCa deaths were confirmed over an average follow-up period of 12.7 years after diagnosis. Variant allele carriers for three SNPs had significantly altered risk for PCSM [rs635261 at RNASEL, hazard ratio (HR), 0.35, 95% CI, 0.18-0.66; p = 0.002; rs915927 in XRCC1, HR, 1.91, 95% CI, 1.21-3.02; p = 0.009; and rs2494750 at AKT1, HR, 0.45, 95% CI, 0.23-0.90; p = 0.016). These results confirm the association of genetic variation in three genes with PCa lethality in a cohort of men with an inherited susceptibility to the disease and provide validation evidence that germline SNPs provide prognostic information for PCa patients. Development of a panel of germline biomarkers with clinical utility for distinguishing patients at detection who have an increased risk for fatal PCa is warranted. © 2014 UICC.

  3. Multiple Novel Prostate Cancer Predisposition Loci Confirmed by an International Study: The PRACTICAL Consortium

    Science.gov (United States)

    Kote-Jarai, Zsofia; Easton, Douglas F.; Stanford, Janet L.; Ostrander, Elaine A.; Schleutker, Johanna; Ingles, Sue A.; Schaid, Daniel; Thibodeau, Stephen; Dörk, Thilo; Neal, David; Cox, Angela; Maier, Christiane; Vogel, Walter; Guy, Michelle; Muir, Kenneth; Lophatananon, Artitaya; Kedda, Mary-Anne; Spurdle, Amanda; Steginga, Suzanne; John, Esther M.; Giles, Graham; Hopper, John; Chappuis, Pierre O.; Hutter, Pierre; Foulkes, William D.; Hamel, Nancy; Salinas, Claudia A.; Koopmeiners, Joseph S.; Karyadi, Danielle M.; Johanneson, Bo; Wahlfors, Tiina; Tammela, Teuvo L.; Stern, Mariana C.; Corral, Roman; McDonnell, Shannon K.; Schürmann, Peter; Meyer, Andreas; Kuefer, Rainer; Leongamornlert, Daniel A.; Tymrakiewicz, Malgorzata; Liu, Jo-fen; O'Mara, Tracy; Gardiner, R.A. (Frank); Aitken, Joanne; Joshi, Amit D.; Severi, Gianluca; English, Dallas R.; Southey, Melissa; Edwards, Stephen M.; Amin Al Olama, Ali; Eeles, Rosalind A.

    2009-01-01

    A recent genome-wide association study found that genetic variants on chromosomes 3, 6, 7, 10, 11, 19 and X were associated with prostate cancer risk. We evaluated the most significant single-nucleotide polymorphisms (SNP) in these loci using a worldwide consortium of 13 groups (PRACTICAL). Blood DNA from 7,370 prostate cancer cases and 5,742 male controls was analyzed by genotyping assays. Odds ratios (OR) associated with each genotype were estimated using unconditional logistic regression. Six of the seven SNPs showed clear evidence of association with prostate cancer (P = 0.0007-P = 10−17). For each of these six SNPs, the estimated per-allele OR was similar to those previously reported and ranged from 1.12 to 1.29. One SNP on 3p12 (rs2660753) showed a weaker association than previously reported [per-allele OR, 1.08 (95% confidence interval, 1.00-1.16; P = 0.06) versus 1.18 (95% confidence interval, 1.06-1.31)]. The combined risks associated with each pair of SNPs were consistent with a multiplicative risk model. Under this model, and in combination with previously reported SNPs on 8q and 17q, these loci explain 16% of the familial risk of the disease, and men in the top 10% of the risk distribution have a 2.1-fold increased risk relative to general population rates. This study provides strong confirmation of these susceptibility loci in multiple populations and shows that they make an important contribution to prostate cancer risk prediction. PMID:18708398

  4. Premenstrual spotting of ≥2 days is strongly associated with histologically confirmed endometriosis in women with infertility.

    Science.gov (United States)

    Heitmann, Ryan J; Langan, Kelly L; Huang, Raywin R; Chow, Gregory E; Burney, Richard O

    2014-10-01

    The purpose of this study was to assess the prevalence of endometriosis in women with premenstrual spotting and to determine the predictive value of this symptom in the diagnosis of endometriosis. We conducted a retrospective cohort study of 80 consecutive women who presented to the infertility clinic for evaluation and who subsequently underwent laparoscopic assessment for infertility with or without pelvic pain. Our main outcome measure was the presence or absence of histologically confirmed endometriosis in women with and without premenstrual spotting. Endometriosis was significantly more prevalent in subfertile women who reported premenstrual spotting for ≥2 days relative to women without this symptom (89% [34/38 women] vs 26% [11/42 women]; P women with infertility, premenstrual spotting of ≥2 days was associated strongly with histologically confirmed endometriosis and a better predictor than dysmenorrhea or dyspareunia of finding endometriosis at laparoscopy. Premenstrual spotting of at least 2 days was also associated strongly with both higher stage disease and the red vesicular peritoneal endometriosis phenotype. Published by Elsevier Inc.

  5. Confirmation that a deletion in the POMC gene is associated with body weight of Labrador Retriever dogs.

    Science.gov (United States)

    Mankowska, M; Krzeminska, P; Graczyk, M; Switonski, M

    2017-06-01

    A 14-bp deletion present in the proopiomelanocortin (POMC) gene of Labrador and Flat Coat Retrievers (FCR), but absent in POMC of other breeds, disrupts the β-MSH and β-endorphin coding sequences. This deletion was recently reported as strongly associated with increased body weight and obesity. We searched for this mutation in a cohort of 272 dogs, representing four breeds with a known predisposition to obesity (Labrador and Golden Retrievers, Beagle, and Cocker Spaniel) and, as expected, we found it only in Labradors. Further, we confirmed the association between the deletion variant and body weight of Labradors but not with a 5-point body condition score (BCS). We suspect that the deletion variant in our cohort may act as a recessive allele, unlike the previous study, which suggested its additive effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Influence of Malnutrition on Adverse Outcome in Children with Confirmed or Probable Viral Encephalitis: A Prospective Observational Study

    Directory of Open Access Journals (Sweden)

    Priyanka Singh

    2015-01-01

    Full Text Available A prospective observational study was conducted in a tertiary care teaching hospital from August 2008 to August 2009 to explore the independent predictors of adverse outcome in the patients with confirmed/probable viral encephalitis. The primary outcome variable was the incidence of adverse outcomes defined as death or severe neurological deficit such as loss of speech, motor deficits, behavioural problems, blindness, and cognitive impairment. Patients with confirmed or probable viral encephalitis were classified into two groups based on their Z-score of weight-for-age as per WHO growth charts. Group I. Patients with confirmed or probable viral encephalitis with weight-for-age (W/A Z-scores below −2SD were classified as undernourished. Group II. Patients with confirmed or probable viral encephalitis were classified as having normal nutritional status (weight-for-age Z-score >−2SD. A total of 114 patients were classified as confirmed or probable viral encephalitis based on detailed investigations. On multivariate logistic regression, undernutrition (adjusted OR: 5.05; 95% CI: 1.92 to 13.44 and requirement of ventilation (adjusted OR: 6.75; 95% CI: 3.63 to 77.34 were independent predictors of adverse outcomes in these patients. Thus, the results from our study highlight that the association between undernutrition and adverse outcome could be extended to the patients with confirmed/probable viral encephalitis.

  7. HIV-associated benign lymphoepithelial cysts of the parotid glands confirmed by HIV-1 p24 antigen immunostaining.

    Science.gov (United States)

    Sekikawa, Yoshiyuki; Hongo, Igen

    2017-09-28

    Approximately 1%-10% of patients with HIV infection have been reported to have salivary gland enlargement. Parotid swelling in patients with HIV is often associated with salivary gland disease, including benign lymphoepithelial cysts (BLECs). The presence of BLEC can serve as an indicator of HIV infection, and the diagnosis of HIV-associated BLEC is usually based on clinical course, HIV confirmatory blood testing, such as western blot or viral detection, and imaging studies, but not on biopsies or immunostaining. To exclude other diseases such as tuberculosis and malignant lymphoma and to further improve the diagnostic accuracy of BLEC, the detection of the HIV-1 p24 antigen by immunohistochemistry is a useful diagnostic method. We report a case of a 65-year-old Japanese man with swelling of the parotid glands and HIV-associated BLEC confirmed via HIV-1 p24 immunohistochemical staining. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. Associations between multiple indoor environmental factors and clinically confirmed allergic disease in early childhood

    DEFF Research Database (Denmark)

    Callesen, Mette Buhl; Bekö, Gabriel; Weschler, Charles J.

    2012-01-01

    rhinoconjunctivitis or atopic dermatitis). The same physician conducted a clinical examination of all the 500 children including structured interview on allergic heredity, clinical and medical history. Specific s-IgE against inhalant and food allergens was determined. The homes were investigated by inspectors...... was clinically diagnosed in 5.1%, rhinoconjunctivitis in 5.1% and atopic dermatitis in 11.0%. Air change rates were below the recommended 0.5 in 56% of all the homes. Air change rates were higher among children asthma/rhinoconjunctivitis (P ... and allergic disease were found. Conclusion: Air change rates were insufficient in the majority of the homes, and low rates were associated with higher concentrations of HDM allergens and sensitization in children with asthma. Asthma was associated with higher levels of nicotine and phthalates in dust. Pet...

  9. Interphase cytogenetics of multicentric renal cell tumours confirm associations of specific aberrations with defined cytomorphologies

    OpenAIRE

    Amo-Takyi, B K; Mittermayer, C; G?nther, K; Handt, S

    2000-01-01

    To demonstrate associations of certain chromosomal aberrations with defined renal cell tumour (RCT) subtypes, we analysed 239 tumour nephrectomy cases for specimens with multicentric tumours. Chromosomal in situ hybridization was then performed on 15 cases with 34 foci (16 conventional renal cell carcinomas (RCCs), and 18 papillary RCTs (11 carcinomas and seven adenomas) for specific chromosomal aberrations, using ?-satellite probes for chromosomes 3, 7 or 17. Particular preference was given ...

  10. A confirmed case of toxic shock syndrome associated with the use of a menstrual cup.

    Science.gov (United States)

    Mitchell, Michael A; Bisch, Steve; Arntfield, Shannon; Hosseini-Moghaddam, Seyed M

    2015-01-01

    Menstrual cups have been reported to be an acceptable substitute for tampons. These flexible cups have also been reported to provide a sustainable solution to menstrual management, with modest cost savings and no significant health risk. The present article documents the first case of toxic shock syndrome associated with the use of a menstrual cup in a woman 37 years of age, using a menstrual cup for the first time. Toxic shock syndrome and the literature on menstrual cups is reviewed and a possible mechanism for the development of toxic shock syndrome in the patient is described.

  11. A Confirmed Case of Toxic Shock Syndrome Associated with the Use of a Menstrual Cup

    OpenAIRE

    Michael A Mitchell; Steve Bisch; Shannon Arntfield; Seyed M Hosseini-Moghaddam

    2015-01-01

    Menstrual cups have been reported to be an acceptable substitute for tampons. These flexible cups have also been reported to provide a sustainable solution to menstrual management, with modest cost savings and no significant health risk. The present article documents the first case of toxic shock syndrome associated with the use of a menstrual cup in a woman 37 years of age, using a menstrual cup for the first time. Toxic shock syndrome and the literature on menstrual cups is reviewed and a p...

  12. A confirmed case of toxic shock syndrome associated with the use of a menstrual cup

    Science.gov (United States)

    Mitchell, Michael A; Bisch, Steve; Arntfield, Shannon; Hosseini-Moghaddam, Seyed M

    2015-01-01

    Menstrual cups have been reported to be an acceptable substitute for tampons. These flexible cups have also been reported to provide a sustainable solution to menstrual management, with modest cost savings and no significant health risk. The present article documents the first case of toxic shock syndrome associated with the use of a menstrual cup in a woman 37 years of age, using a menstrual cup for the first time. Toxic shock syndrome and the literature on menstrual cups is reviewed and a possible mechanism for the development of toxic shock syndrome in the patient is described. PMID:26361491

  13. Rivaroxaban for treatment of suspected or confirmed heparin-induced thrombocytopenia study.

    Science.gov (United States)

    Linkins, L A; Warkentin, T E; Pai, M; Shivakumar, S; Manji, R A; Wells, P S; Wu, C; Nazi, I; Crowther, M A

    2016-06-01

    Essentials Heparin-induced thrombocytopenia (HIT) is a thrombogenic condition that is difficult to treat. We evaluated rivaroxaban as a treatment option in patients with suspected or confirmed HIT. One patient had recurrent thrombosis and 9/10 patients with thrombocytopenia had platelet recovery. Rivaroxaban may be an effective and safe treatment option for HIT. Background Rivaroxaban is a direct oral anti-Xa inhibitor that has the potential to greatly simplify treatment of heparin-induced thrombocytopenia (HIT). Objectives To evaluate the efficacy and safety of rivaroxaban in this patient population, we conducted a multicenter, single-arm, prospective cohort study of patients with suspected or confirmed HIT. Patients/Methods Twenty-two consecutive adults with suspected or confirmed HIT received rivaroxaban 15 mg bid until a local HIT assay result was available. Participants with a positive local assay result continued rivaroxaban 15 mg bid until platelet recovery (or until day 21 if they had acute thrombosis at study entry), then stepped down to rivaroxaban 20 mg daily until day 30. Results and Conclusions The primary outcome measure, incidence of new symptomatic, objectively-confirmed venous and arterial thromboembolism at 30 days, occurred in one HIT-positive participant (4.5%; 95% confidence interval [CI], 0-23.5%) and one HIT-positive participant required limb amputation despite platelet recovery. Platelet recovery was achieved in nine out of 10 HIT-positive patients with thrombocytopenia. Rivaroxaban appears to be effective for treating patients with confirmed HIT, although the small number of patients enrolled limits precision. © 2016 International Society on Thrombosis and Haemostasis.

  14. Intensive care nursing students' perceptions of simulation for learning confirming communication skills: A descriptive qualitative study.

    Science.gov (United States)

    Karlsen, Marte-Marie Wallander; Gabrielsen, Anita Kristin; Falch, Anne Lise; Stubberud, Dag-Gunnar

    2017-10-01

    The aim of this study was to explore intensive care nursing students experiences with confirming communication skills training in a simulation-based environment. The study has a qualitative, exploratory and descriptive design. The participants were students in a post-graduate program in intensive care nursing, that had attended a one day confirming communication course. Three focus group interviews lasting between 60 and 80min were conducted with 14 participants. The interviews were transcribed verbatim. Thematic analysis was performed, using Braun & Clark's seven steps. The analysis resulted in three main themes: "awareness", "ice-breaker" and "challenging learning environment". The participants felt that it was a challenge to see themselves on the video-recordings afterwards, however receiving feedback resulted in better self-confidence in mastering complex communication. The main finding of the study is that the students reported improved communication skills after the confirming communication course. However; it is uncertain how these skills can be transferred to clinical practice improving patient outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Onychomycosis: a critical study of techniques and criteria for confirming the etiologic significance of nondermatophytes.

    Science.gov (United States)

    Summerbell, Richard C; Cooper, Elizabeth; Bunn, Ursula; Jamieson, Frances; Gupta, Aditya K

    2005-02-01

    Nondermatophytic filamentous fungi (NDF) other than Scytalidium species are variously said to cause between 0 and 50% of all toenail onychomycoses, though most estimates are in the 2-5% range. Due to the difficulty of obtaining 'gold standard' control data for comparison, the accuracy of many laboratory evaluation processes used to deal with potential NDF onychomycoses has never been rigorously measured, thus allowing use of differing interpretations of the significance of cultures. To allow valid comparison of these procedures and interpretations, a large series of patients who declined treatment were sampled on multiple occasions from all apparently onychomycotic toenails until adequate certainty had been attained that all etiologic agents had been isolated and, where necessary, confirmed as etiologic via consistent repeated isolation. This information was used to evaluate results that had been obtained in the initial direct microscopy and culture studies for the same patient population, as such results are strongly relied on in routine diagnosis. Direct microscopy (KOH) was found to be 73.8% sensitive for dermatophytes and 67.2% sensitive for proven etiologic NDF (difference not significant). Culture of the initial specimen coincidentally had a sensitivity of 74.6% for both fungal groups. KOH and culture in tandem were 83.9% sensitive for indicating fungal etiology based on the first specimen. Different evaluative frameworks currently used to interpret NDF isolations were contrasted. The 'classic' evaluation procedure, in which all NDF considered etiologic must be isolated from at least two successive nail specimens, at least one of which must be microscopic positive for compatible fungal filaments, had a sensitivity of 59.5% but a specificity of 100% for true NDF infections and mixed NDF/dermatophyte infections. The most widely used 'simple association' evaluation criterion, in which NDF outgrowth is considered etiologic whenever direct microscopy is positive

  16. Factors Associated with Pneumonia-caused Death in Older Adults with Autopsy-confirmed Dementia.

    Science.gov (United States)

    Manabe, Toshie; Mizukami, Katsuyoshi; Akatsu, Hiroyasu; Hashizume, Yoshio; Ohkubo, Takayoshi; Kudo, Koichiro; Hizawa, Nobuyuki

    2017-01-01

    Objective A better understanding of risk factors for pneumonia-caused death may help to improve the clinical management of dementia. Methods A retrospective observational study was conducted by reviewing the medical charts and autopsy reports of 204 patients who were admitted to hospital, underwent a post-mortem examination, and who were neuropathologically diagnosed with dementia. The risk factors for pneumonia-caused death were examined both as underlying and immediate causes of death using logistic regression models. Results A high frequency of pneumonia-caused death was observed both in underlying- (37.3%) and immediate- (44.1%) cause of death, but varied according to the subtypes of dementia. The factors related to pneumonia-caused death (underlying) were subtypes of dementia; Alzheimer's disease (odds ratio [OR], 2.891; 95% confidence interval [CI], 1.459-5.730); argyrophilic grain disease (OR, 3.148; 95% CI, 0.937-10.577); and progressive supranuclear palsy (OR, 34.921; 95% CI, 3.826-318.775), dysphagia (OR, 2.045; 95% CI, 1.047-3.994), diabetes mellitus (OR, 3.084; 95% CI, 1.180-8.061) and conversely related with heart failure (OR, 0.149; 95% CI, 0.026-0.861). Factors relating to pneumonia-caused death (immediate) were incidence of pneumonia during hospitalizations (OR, 32.579; 95%CI, 4.308-246.370), gender-male (OR, 2.060; 95% CI, 1.098-3.864), and conversely related with malignant neoplasm (OR, 0.220; 95% CI, 0.058-0.840). Conclusion The different factors relating to the pneumonia-caused death were evaluated depending on whether pneumonia was the underlying- or immediate-cause of death. Strengthening clinical management on dysphagia and diabetes mellitus, and preventing incidence of pneumonia during hospitalization appear to be the important for the terminal stage of hospitalized patients with dementia.

  17. Sonographic Identification of Tube Thoracostomy Study (SITTS: Confirmation of Intrathoracic Placement

    Directory of Open Access Journals (Sweden)

    Jamie A. Jenkins

    2012-09-01

    Full Text Available Introduction: Thoracostomy tubes (TT are commonly placed in the management of surgical, emergency, and trauma patients and chest radiographs (CXR and computed tomography (CT are performed to confirm placement. Ultrasound (US has not previously been used as a means to confirm intrathoracic placement of chest tubes. This study involves a novel application of US to demonstrate chest tubes passing through the pleural line, thus confirming intrathoracic placement.Methods: This was an observational proof-of-concept study using a convenience sample of patients with TTs at a tertiary-care university hospital. Bedside US was performed by the primary investigatorusing first the low-frequency (5–1 MHz followed by the high-frequency (10–5 MHz transducers, in both 2-dimensional gray-scale and M-modes in a uniform manner. The TTs were identified in transverse and longitudinal views by starting at the skin entry point and scanning to where the TT passed the pleural line, entering the intrathoracic region. All US images were reviewed by US fellowship-trained emergency physicians. CXRs and CTs were used as the standard for confirmation ofTT placement.Results: Seventeen patients with a total of 21 TTs were enrolled. TTs were visualized entering the intrathoracic space in 100% of cases. They were subjectively best visualized with the high-frequency (10–5 MHz linear transducer. Sixteen TTs were evaluated using M-mode. TTs produced a distinct pattern on M-mode.Conclusion: Bedside US can visualize the TT and its entrance into the thoracic cavity and it can distinguish it from the pleural line by a characteristic M-mode pattern. This is best visualized with the high-frequency (10–5 MHz linear transducer. [West J Emerg Med. 2012;13(4:305–311.

  18. Confirmation test for hysteroscopic sterilization: a descriptive study of patient tolerability and impressions

    Directory of Open Access Journals (Sweden)

    Chapa HO

    2013-03-01

    Full Text Available Hector O Chapa, Gonzalo VenegasDepartment of Obstetrics and Gynecology, Methodist Medical and Women’s Specialty Center, Dallas, TX, USABackground: This retrospective descriptive study describes patient follow-up and tolerability of the post-hysteroscopic sterilization confirmation test.Methods: Recruitment for the original sterilization procedure was from January 2008 to March 2009; subsequent confirmation test (hysterosalpingogram capture was from March 2008 to July 2009. Patients were given a 10 cm visual analog pain scale during the hysteroscopic sterilization procedure, and took the scale with them as a take-home sheet. Following hysterosalpingography (HSG, patients received a follow-up phone call within 24 hours, and were asked to rate their pain during the hysterosalpingogram as well as during the first 2 hours following the test.Results: Eighty-nine hysteroscopic sterilizations were performed under local paracervical block and oral nonsteroidal medication. The median immediate post-sterilization visual analog pain score was 1.9 (range 1.7–2.1, 95% confidence interval [CI] 1.3–1.5. Of the 89 sterilization procedures, 79% (n = 70 patients underwent a confirmation test using HSG. Ten percent (n = 7 of the hysterosalpinograms were performed at least 3 months after sterilization (mean 17 [range 14–20] weeks. Median intratest visual analog pain score overall (n = 70 was 1.8 (range 1.6–1.9, 95% CI 1.5–1.9. Following the test, the median visual analog pain score was 1.7 (range 1.6–1.9, 95% CI 1.4–0.18. Of the 70 patients who participated in visual analog pain score capture, 64 had a paper copy of the scale had six had it via email. Of the 19 who did not complete hysterosalpinography, five were lost to follow-up. Reasons given by the remaining 14 for noncompliance with hysterosalpinography were: a busy schedule/childcare issues (62%, fear of the test (13%, trust in the sterilization procedure alone (13%, and forgetting the

  19. Confirmation of association of the macrophage migration inhibitory factor gene with systemic sclerosis in a large European population

    NARCIS (Netherlands)

    Bossini-Castillo, L.; Simeon, C.P.; Beretta, L.; Vonk, M.C.; Callejas-Rubio, J.L.; Espinosa, G.; Carreira, P.; Camps, M.T.; Rodriguez-Rodriguez, L.; Rodriguez-Carballeira, M.; Garcia-Hernandez, F.J.; Lopez-Longo, F.J.; Hernandez-Hernandez, V.; Saez-Comet, L.; Egurbide, M.V.; Hesselstrand, R.; Nordin, A.; Hoffmann-Vold, A.M.; Vanthuyne, M.; Smith, V.; Langhe, E. De; Kreuter, A.; Riemekasten, G.; Witte, T.J.M. de; Hunzelmann, N.; Voskuyl, A.E.; Schuerwegh, A.J.; Lunardi, C.; Airo, P.; Scorza, R.; Shiels, P.; Laar, J.M. van; Fonseca, C.; Denton, C.; Herrick, A.; Worthington, J.; Koeleman, B.P.; Rueda, B.; Radstake, T.R.D.J.; Martin, J.

    2011-01-01

    Objectives. The aim of this study was to confirm the implication of macrophage migration inhibitory factor (MIF) gene in SSc susceptibility or clinical phenotypes in a large European population. Methods. A total of 3800 SSc patients and 4282 healthy controls of white Caucasian ancestry from eight

  20. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47

    DEFF Research Database (Denmark)

    Anderson, Carl A; Boucher, Gabrielle; Lees, Charlie W

    2011-01-01

    Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association s...

  1. Genome-wide association analysis confirms and extends the association of SLC2A9 with serum uric acid levels to Mexican Americans

    Directory of Open Access Journals (Sweden)

    Venkata Saroja eVoruganti

    2013-12-01

    Full Text Available Increased serum uric acid (SUA is a risk factor for gout and renal and cardiovascular disease. The purpose of this study was to identify genetic factors that affect the variation in SUA in 632 Mexican Americans participants of the San Antonio Family Heart Study (SAFHS. A genome-wide association analysis was performed using the Illumina Human Hap 550K single nucleotide polymorphism (SNP microarray. We used a linear regression-based association test under an additive model of allelic effect, while accounting for non-independence among family members via a kinship variance component. All analyses were performed in the software package SOLAR. SNPs rs6832439, rs13131257 and rs737267 in solute carrier protein 2 family, member 9 (SLC2A9 were associated with SUA at genome-wide significance (p <1.3×10-7. The minor alleles of these SNPs had frequencies of 36.2%, 36.2%, and 38.2 %, respectively, and were associated with decreasing SUA levels. All of these SNPs were located in introns 3-7 of SLC2A9, the location of the previously reported associations in European populations. When analyzed for association with cardiovascular-renal disease risk factors, conditional on SLC2A9 SNPs strongly associated with SUA, significant associations were found for SLC2A9 SNPs with BMI, body weight and waist circumference (p < 1.4 x 10-3 and suggestive associations with albumin-creatinine ratio and total antioxidant status. The SLC2A9 gene encodes an urate transporter that has considerable influence on variation in SUA. In addition to the primary association locus, suggestive evidence (p<1.9×10-6 for joint linkage/association was found at a previously-reported urate quantitative trait locus (Logarithm of odds score = 3.6 on 3p26.3. In summary, our GWAS extends and confirms the association of SLC2A9 with SUA for the first time in a Mexican American cohort and also shows for the first time its association with cardiovascular-renal disease risk factors.

  2. Effects of delayed-release dimethyl fumarate on MRI measures in the phase 3 CONFIRM study.

    Science.gov (United States)

    Miller, David H; Fox, Robert J; Phillips, J Theodore; Hutchinson, Michael; Havrdova, Eva; Kita, Mariko; Wheeler-Kingshott, Claudia A M; Tozer, Daniel J; MacManus, David G; Yousry, Tarek A; Goodsell, Mary; Yang, Minhua; Zhang, Ray; Viglietta, Vissia; Dawson, Katherine T

    2015-03-17

    To evaluate the effects of oral delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) on MRI lesion activity and load, atrophy, and magnetization transfer ratio (MTR) measures from the Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis (CONFIRM) study. CONFIRM was a 2-year, placebo-controlled study of the efficacy and safety of DMF 240 mg twice (BID) or 3 times daily (TID) in 1,417 patients with relapsing-remitting multiple sclerosis (RRMS); subcutaneous glatiramer acetate 20 mg once daily was included as an active reference comparator. The number and volume of T2-hyperintense, T1-hypointense, and gadolinium-enhancing (Gd+) lesions, as well as whole brain volume and MTR, were assessed in 681 patients (MRI cohort). DMF BID and TID produced significant and consistent reductions vs placebo in the number of new or enlarging T2-hyperintense lesions and new nonenhancing T1-hypointense lesions after 1 and 2 years of treatment and in the number of Gd+ lesions at week 24, year 1, and year 2. Lesion volumes were also significantly reduced. Reductions in brain atrophy and MTR changes with DMF relative to placebo did not reach statistical significance. The robust effects on MRI active lesion counts and total lesion volume in patients with RRMS demonstrate the ability of DMF to exert beneficial effects on inflammatory lesion activity in multiple sclerosis, and support DMF therapy as a valuable new treatment option in RRMS. This study provides Class I evidence of reduction in brain lesion number and volume, as assessed by MRI, over 2 years of delayed-release DMF treatment. © 2015 American Academy of Neurology.

  3. Confirmation of emergence of mutations associated with atovaquone-proguanil resistance in unexposed Plasmodium falciparum isolates from Africa.

    Science.gov (United States)

    Happi, Christian T; Gbotosho, Grace O; Folarin, Onikepe A; Milner, Danny; Sarr, Ousmane; Sowunmi, Akintunde; Kyle, Dennis E; Milhous, Wilbur K; Wirth, Dyann F; Oduola, Ayoade M J

    2006-10-04

    In vitro and in vivo resistance of Plasmodium falciparum to atovaquone or atovaquone-proguanil hydrochloride combination has been associated to two point mutations in the parasite cytochrome b (cytb) gene (Tyr268Ser and Tyr268Asn). However, little is known about the prevalence of codon-268 mutations in natural populations of P. falciparum without previous exposure to the drug in Africa. The prevalence of codon-268 mutations in the cytb gene of African P. falciparum isolates from Nigeria, Malawi and Senegal, where atovaquone-proguanil has not been introduced for treatment of malaria was assessed. Genotyping of the cytb gene in isolates of P. falciparum was performed by PCR-restriction fragment length polymorphism and confirmed by sequencing. 295 samples from Nigeria (111), Malawi (91) and Senegal (93) were successfully analyzed for detection of either mutant Tyr268Ser or Tyr268Asn. No case of Ser268 or Asn268 was detected in cytb gene of parasites from Malawi or Senegal. However, Asn268 was detected in five out of 111 (4.5%) unexposed P. falciparum isolates from Nigeria. In addition, one out of these five mutant Asn268 isolates showed an additional cytb mutation leading to a Pro266Thr substitution inside the ubiquinone reduction site. No Tyr268Ser mutation is found in cytb of P. falciparum isolates from Nigeria, Malawi or Senegal. This study reports for the first time cytb Tyr268Asn mutation in unexposed P. falciparum isolates from Nigeria. The emergence in Africa of P. falciparum isolates with cytb Tyr268Asn mutation is a matter of serious concern. Continuous monitoring of atovaquone-proguanil resistant P. falciparum in Africa is warranted for the rational use of this new antimalarial drug, especially in non-immune travelers.

  4. Antimicrobial resistance and antimicrobial use associated with laboratory-confirmed cases of Campylobacter infection in two health units in Ontario.

    Science.gov (United States)

    Deckert, Anne E; Reid-Smith, Richard J; Tamblyn, Susan E; Morrell, Larry; Seliske, Patrick; Jamieson, Frances B; Irwin, Rebecca; Dewey, Catherine E; Boerlin, Patrick; McEwen, Scott A

    2013-01-01

    A population-based study was conducted over a two-year period in the Perth District (PD) and Wellington-Dufferin-Guelph (WDG) health units in Ontario to document antimicrobial resistance and antimicrobial use associated with clinical cases of laboratory-confirmed campylobacteriosis. Etest (bioMérieux SA, France) was used to determine the minimum inhibitory concentration of amoxicillin/clavulanic acid, ampicillin, chloramphenicol, ciprofloxacin (CIP), clindamycin, erythromycin (ERY), gentamicin, nalidixic acid and tetracycline. Data regarding antimicrobial use were collected from 250 cases. Of the 250 cases, 165 (65.7%) reported staying home or being hospitalized due to campylobacteriosis. Fifty-four per cent of cases (135 of 249) reported taking antimicrobials to treat campylobacteriosis. In 115 cases (51.1%), fecal culture results were not used for treatment decisions because they were not available before the initiation of antimicrobial treatment and/or they were not available before the cessation of symptoms. Of the 250 cases, 124 (49.6%) had available Campylobacter isolates, of which 66 (53.2%) were resistant to at least one of the antimicrobials tested. No resistance to ampicillin, chloramphenicol or gentamicin was found in these isolates. Six isolates (4.8%) were resistant to CIP. Two isolates (1.6%) were resistant to ERY; however, no isolates were resistant to both CIP and ERY. Prudent use practices should be promoted among physicians to reduce the use of antimicrobials for the treatment of gastroenteritis in general and campylobacteriosis in particular, as well as to minimize the future development of resistance to these antimicrobials in Campylobacter species.

  5. Sexual behavior of gender-dysphoric individuals before gender-confirming interventions: a European multicenter study.

    Science.gov (United States)

    Cerwenka, Susanne; Nieder, Timo O; Cohen-Kettenis, Peggy; De Cuypere, Griet; Haraldsen, Ira R Hebold; Kreukels, Baudewijntje P C; Richter-Appelt, Hertha

    2014-01-01

    A transsexual course of development that starts before puberty (early onset) or during or after puberty, respectively (late onset), may lead to diverse challenges in coping with sexual activity. The authors explored the sexual behavior of 380 adult male-to-female and female-to-male individuals diagnosed according to DSM-IV-TR criteria who had not yet undergone gender-confirming interventions. Data originated from the European Network for the Investigation of Gender Incongruence Initiative, conducted in Belgium, Germany, The Netherlands, and Norway. Information on outcome variables was collected using self-administered questionnaires at first clinical presentation. Compared with late-onset male-to-females, early-onset individuals tended to show sexual attraction toward males more frequently (50.5%), involve genitals less frequently in partner-related sexual activity, and consider penile sensations and orgasm as more negative. Early-onset female-to-males predominantly reported sexual attraction toward females (84.0%), whereas those with a late-onset more frequently showed other sexual attractions (41.7%). The study (a) shows that early- and late-onset male-to-females differ considerably with regard to coping strategies involving their body during sexual relations and (b) reveals initial insights into developmental pathways of late-onset female-to-males.

  6. Repository performance confirmation.

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, Francis D.

    2011-09-01

    Repository performance confirmation links the technical bases of repository science and societal acceptance. This paper explores the myriad aspects of what has been labeled performance confirmation in U.S. programs, which involves monitoring as a collection of distinct activities combining technical and social significance in radioactive waste management. This paper is divided into four parts: (1) A distinction is drawn between performance confirmation monitoring and other testing and monitoring objectives; (2) A case study illustrates confirmation activities integrated within a long-term testing and monitoring strategy for Yucca Mountain; (3) A case study reviews compliance monitoring developed and implemented for the Waste Isolation Pilot Plant; and (4) An approach for developing, evaluating and implementing the next generation of performance confirmation monitoring is presented. International interest in repository monitoring is exhibited by the European Commission Seventh Framework Programme 'Monitoring Developments for Safe Repository Operation and Staged Closure' (MoDeRn) Project. The MoDeRn partners are considering the role of monitoring in a phased approach to the geological disposal of radioactive waste. As repository plans advance in different countries, the need to consider monitoring strategies within a controlled framework has become more apparent. The MoDeRn project pulls together technical and societal experts to assimilate a common understanding of a process that could be followed to develop a monitoring program. A fundamental consideration is the differentiation of confirmation monitoring from the many other testing and monitoring activities. Recently, the license application for Yucca Mountain provided a case study including a technical process for meeting regulatory requirements to confirm repository performance as well as considerations related to the preservation of retrievability. The performance confirmation plan developed as part

  7. Polarisation confirmed

    CERN Multimedia

    Anaïs Schaeffer

    2014-01-01

    The polarisation of photons emitted in the decay of a bottom quark into a strange quark, as predicted by the Standard Model, has just been observed for the first time by the LHCb collaboration. More detailed research is still required to determine the value of this polarisation with precision.   In this LHCb event, K, π and γ are emitted from a B+ → K+π-π+γ decay. This was investigated by the LHCb collaboration in order to study the photon (γ) polarisation.   If we imagine that photons are like little spinning tops which spin around an axis aligned with their direction of propagation, we can identify two types of photons. Those that are “right-handed” turn in the same direction as a corkscrew, and those that are “left-handed” turn in the opposite direction. If for a large number of decays of a given type we can observe an imbalance between the production of right-han...

  8. Association of the apolipoprotein E {epsilon}4 allele with clinical subtypes of autopsy-confirmed Alzheimer`s Disease

    Energy Technology Data Exchange (ETDEWEB)

    Zubenko, G.S.; Stiffler, S.; Kopp, U. [Univ. of Pittsburgh School of Medicine, PA (United States)] [and others

    1994-09-15

    Consistent with previous reports, we observed a significant association of the APOE {epsilon}4 allele with Alzheimer`s Disease (AD) in a series of 91 autopsy-confirmed cases. The {epsilon}4 allele frequency was higher in cases with a family history of AD-like dementia (0.54 {+-} 0.07), although the {epsilon}4 allele frequency in the AD cases with a negative family history (0.38 {+-} 0.05) remained significantly greater than that for the non-AD control group (0.13 {+-} 0.03). A similar increase in {epsilon}4 allele frequency (0.54 {+-} 0.07) was observed in the AD cases with amyloid angiopathy, compared to those who did not have amyloid angiopathy (0.35 {+-} 0.04). Contrary to previous reports, no effect of the dosage of the {epsilon}4 allele was found on the age of onset of dementia among the AD cases and, contrary to reports suggesting an association of {epsilon}4 and atherosclerosis, the {epsilon}4 allele frequency was similar in cases with or without concurrent brain infarcts. Modest but consistent correlations were observed between the dosage of {epsilon}4 alleles and the cortical density of senile plaques, but not neurofibrillary tangles. The last finding suggests that the pathogenic events mediated by the {epsilon}4 allele may be more directly involved in the formation of senile plaques, the identifying lesions in AD, than neurofibrillary tangles. A robust association of both the presence of an {epsilon}4 allele and a family history of AD-like dementia with concurrent amyloid angiopathy occurred within our sample of AD cases. This association arose from an interaction of the {epsilon}4 allele with a separate familial factor for which a family history of dementia served as a surrogate. These results suggest that amyloid angiopathy may be a common or central feature of a form of familial AD that is associated with the transmission of the APOE {epsilon}4 allele. 22 refs., 2 figs., 5 tabs.

  9. Systematic study of subcellular localization of Arabidopsis PPR proteins confirms a massive targeting to organelles.

    Science.gov (United States)

    Colcombet, Jean; Lopez-Obando, Mauricio; Heurtevin, Laure; Bernard, Clément; Martin, Karine; Berthomé, Richard; Lurin, Claire

    2013-01-01

    Four hundred and fifty-eight genes coding for PentatricoPeptide Repeat (PPR) proteins are annotated in the Arabidopsis thaliana genome. Over the past 10 years, numerous reports have shown that many of these proteins function in organelles to target specific transcripts and are involved in post-transcriptional regulation. Therefore, they are thought to be important players in the coordination between nuclear and organelle genome expression. Only four of these proteins have been described to be addressed outside organelles, indicating that some PPRs could function in post-transcriptional regulations of nuclear genes. In this work, we updated and improved our current knowledge on the localization of PPR proteins of Arabidopsis within the plant cell. We particularly investigated the subcellular localization of 166 PPR proteins whose targeting predictions were ambiguous, using a combination of high-throughput cloning and microscopy. Through systematic localization experiments and data integration, we confirmed that PPR proteins are largely targeted to organelles and showed that dual targeting to both the mitochondria and plastid occurs more frequently than expected. These results allow us to speculate that dual-targeted PPR proteins could be important for the fine coordination of gene expressions in both organelles.

  10. Combinations of newly confirmed Glioma-Associated loci link regions on chromosomes 1 and 9 to increased disease risk

    Directory of Open Access Journals (Sweden)

    Hung Jui-Hung

    2011-08-01

    Full Text Available Abstract Background Glioblastoma multiforme (GBM tends to occur between the ages of 45 and 70. This relatively early onset and its poor prognosis make the impact of GBM on public health far greater than would be suggested by its relatively low frequency. Tissue and blood samples have now been collected for a number of populations, and predisposing alleles have been sought by several different genome-wide association (GWA studies. The Cancer Genome Atlas (TCGA at NIH has also collected a considerable amount of data. Because of the low concordance between the results obtained using different populations, only 14 predisposing single nucleotide polymorphism (SNP candidates in five genomic regions have been replicated in two or more studies. The purpose of this paper is to present an improved approach to biomarker identification. Methods Association analysis was performed with control of population stratifications using the EIGENSTRAT package, under the null hypothesis of "no association between GBM and control SNP genotypes," based on an additive inheritance model. Genes that are strongly correlated with identified SNPs were determined by linkage disequilibrium (LD or expression quantitative trait locus (eQTL analysis. A new approach that combines meta-analysis and pathway enrichment analysis identified additional genes. Results (i A meta-analysis of SNP data from TCGA and the Adult Glioma Study identifies 12 predisposing SNP candidates, seven of which are reported for the first time. These SNPs fall in five genomic regions (5p15.33, 9p21.3, 1p21.2, 3q26.2 and 7p15.3, three of which have not been previously reported. (ii 25 genes are strongly correlated with these 12 SNPs, eight of which are known to be cancer-associated. (iii The relative risk for GBM is highest for risk allele combinations on chromosomes 1 and 9. (iv A combined meta-analysis/pathway analysis identified an additional four genes. All of these have been identified as cancer

  11. Confirmation bias in studies of nestmate recognition: a cautionary note for research into the behaviour of animals.

    Directory of Open Access Journals (Sweden)

    Ellen van Wilgenburg

    Full Text Available Confirmation bias is a tendency of people to interpret information in a way that confirms their expectations. A long recognized phenomenon in human psychology, confirmation bias can distort the results of a study and thus reduce its reliability. While confirmation bias can be avoided by conducting studies blind to treatment groups, this practice is not always used. Surprisingly, this is true of research in animal behaviour, and the extent to which confirmation bias influences research outcomes in this field is rarely investigated. Here we conducted a meta-analysis, using studies on nestmate recognition in ants, to compare the outcomes of studies that were conducted blind with those that were not. Nestmate recognition studies typically perform intra- and inter colony aggression assays, with the a priori expectation that there should be little or no aggression among nestmates. Aggressive interactions between ants can include subtle behaviours such as mandible flaring and recoil, which can be hard to quantify, making these types of assays prone to confirmation bias. Our survey revealed that only 29% of our sample of 79 studies were conducted blind. These studies were more likely to report aggression among nestmates if they were conducted blind (73% than if they were not (21%. Moreover, we found that the effect size between nestmate and non-nestmate treatment means is significantly lower in experiments conducted blind than those in which colony identity is known (1.38 versus 2.76. We discuss the implications of the impact of confirmation bias for research that attempts to obtain quantitative synthesises of data from different studies.

  12. Associations between selected allergens, phthalates, nicotine, polycyclic aromatic hydrocarbons, and bedroom ventilation and clinically confirmed asthma, rhinoconjunctivitis, and atopic dermatitis in preschool children.

    Science.gov (United States)

    Callesen, M; Bekö, G; Weschler, C J; Sigsgaard, T; Jensen, T K; Clausen, G; Toftum, J; Norberg, L A; Høst, A

    2014-04-01

    Previous studies, often using data from questionnaires, have reported associations between various characteristics of indoor environments and allergic disease. The aim of this study has been to investigate possible associations between objectively assessed indoor environmental factors and clinically confirmed asthma, rhinoconjunctivitis, and atopic dermatitis. The study is a cross-sectional case-control study of 500 children aged 3-5 years from Odense, Denmark. The 200 cases had at least two parentally reported allergic diseases, while the 300 controls were randomly selected from 2835 participating families. A single physician conducted clinical examinations of all 500 children. Children from the initially random control group with clinically confirmed allergic disease were subsequently excluded from the control group and admitted in the case group, leaving 242 in the healthy control group. For most children, specific IgE's against various allergens were determined. In parallel, dust samples were collected and air change rates were measured in the children's bedrooms. The dust samples were analyzed for phthalate esters, polycyclic aromatic hydrocarbons (PAH), nicotine, and various allergens. Among children diagnosed with asthma, concentrations of nicotine were higher (P allergens were lower (P controls; air change rates were lower for those sensitized (specific IgE+) compared with those not sensitized (specific IgE-, P allergens were higher for specific IgE+ cases compared with healthy controls (P allergens in dust and current wheeze. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Confirming mental health care in acute psychiatric wards, as narrated by persons experiencing psychotic illness: an interview study.

    Science.gov (United States)

    Sebergsen, Karina; Norberg, Astrid; Talseth, Anne-Grethe

    2016-01-01

    It is important that mental health nurses meet the safety, security and care needs of persons suffering from psychotic illness to enhance these persons' likelihood of feeling better during their time in acute psychiatric wards. Certain persons in care describe nurses' mental health care as positive, whereas others report negative experiences and express a desire for improvements. There is limited research on how persons with psychotic illness experience nurses' mental health care acts and how such acts help these persons feel better. Therefore, the aim of this study was to explore, describe and understand how the mental health nurses in acute psychiatric wards provide care that helps persons who experienced psychotic illness to feel better, as narrated by these persons. This study had a qualitative design; 12 persons participated in qualitative interviews. The interviews were transcribed, content analysed and interpreted using Martin Buber's concept of confirmation. The results of this study show three categories of confirming mental health care that describe what helped the participants to feel better step-by-step: first, being confirmed as a person experiencing psychotic illness in need of endurance; second, being confirmed as a person experiencing psychotic illness in need of decreased psychotic symptoms; and third, being confirmed as a person experiencing psychotic illness in need of support in daily life. The underlying meaning of the categories and of subcategories were interpreted and formulated as the theme; confirming mental health care to persons experiencing psychotic illness. Confirming mental health care acts seem to help persons to feel better in a step-wise manner during psychotic illness. Nurses' openness and sensitivity to the changing care needs of persons who suffer from psychotic illness create moments of confirmation within caring acts that concretely help the persons to feel better and that may enhance their health. The results show the

  14. Clinical pharmacological studies in children: From exploratory towards confirmation driven methodology.

    Science.gov (United States)

    Allegaert, Karel

    2012-08-08

    Just like children are not small adults, pediatric studies are not just subgroup-adult studies. Clinical pharmacology aims to predict these effects based on drug, population and/or patient-specific pharmacokinetics (concentration-time profiles) and -dynamics (concentration-effect profile). The most essential characteristics of childhood are growth and maturation. Both phenomena are most prominent during infancy making the claim that "an infant is not just a small child" as relevant compared to the paradigm that "a child is not just a small adult". From a clinical pharmacology perspective, the consequence of such a dynamic setting is extensive variability throughout childhood in both the pharmacokinetics and pharmacodynamics. Trial design probably has impact on recruitment to an even greater extent compared to adult studies. In general, if a study is designed well, with a clear clinical question with which parents and children can identify, they are likely to consider participation. Open communication with all stakeholders involved will most likely result in ethically correct, practically feasible, scientifically sound, and economical reasonable studies to provide children with the appropriate treatment. From an academic perspective, feasibility, relevance, applicability and costs of clinical pharmacological studies in children can be significantly improved by new sampling concepts (e.g., saliva, urine, dried spot blood) and the systematic introduction of already known information into the trial design through model based pediatric drug development, that mainly affect feasibility of pharmacokinetic studies. In contrast, for the pharmacodynamic part of pediatric studies, development and validation of population specific biomarkers or robust outcome variables is urgently needed.

  15. Clinical pharmacological studies in children: From exploratory towards confirmation driven methodology

    OpenAIRE

    Allegaert, Karel

    2012-01-01

    Just like children are not small adults, pediatric studies are not just subgroup-adult studies. Clinical pharmacology aims to predict these effects based on drug, population and/or patient-specific pharmacokinetics (concentration-time profiles) and -dynamics (concentration-effect profile). The most essential characteristics of childhood are growth and maturation. Both phenomena are most prominent during infancy making the claim that “an infant is not just a small child” as relevant compared t...

  16. Follow up of patients with signs and symptoms of polyneuropathy not confirmed by electrophysiological studies

    NARCIS (Netherlands)

    Rosenberg, NR; Slotema, CW; Hoogendijk, JE

    The outcome and final diagnoses of patients with symptoms and/or signs suggestive of polyneuropathy, but with normal electrophysiological studies, were investigated. All patients who presented at the outpatient clinic between 1993 and 1998 with signs and symptoms suggestive of polyneuropathy, but in

  17. Risk factors for fatality among confirmed adult dengue inpatients in Singapore: a matched case-control study.

    Directory of Open Access Journals (Sweden)

    Tun-Linn Thein

    Full Text Available OBJECTIVES: To identify demographic, clinical and laboratory risk factors for death due to dengue fever in adult patients in Singapore. METHODS: Multi-center retrospective study of hospitalized adult patients with confirmed dengue fever in Singapore between 1 January 2004 and 31 December 2008. Non-fatal controls were selected by matching age and year of infection with fatal cases. World Health Organization 1997, 2009 criteria were applied to define dengue hemorrhagic fever (DHF, warning signs and severe dengue. Statistical significance was assessed by conditional logistic regression modeling. RESULTS: Significantly more fatal cases than matched controls had pre-existing co-morbid conditions, and presented with abdominal pain/tenderness. Median pulse rates were significantly higher while myalgia was significantly less frequent in cases. . Fatal cases also had higher leucocyte counts, platelet counts, serum sodium, potassium, urea, creatine and bilirubin levels on admission compared to controls. There was no statistical significant difference between the prevalence of DHF and hematocrit level among cases and controls. Multivariate analysis showed myalgia and leucocyte count at presentation were independent predictors of fatality (adjusted odds ratios 0.09 and 2.94 respectively. None of the controls was admitted to intensive care unit (ICU or given blood transfusion, while 71.4% and 28.6% of fatal cases received ICU admission and blood transfusion. CONCLUSIONS: Absence of myalgia and leucocytosis on admission were independently associated with fatality in our matched case-control study. Fatalities were also commonly associated with co-morbidities and clinicians should be alarmed if dengue patients fulfilled severe dengue case definition on admission.

  18. The association between self-reported versus nicotine metabolite-confirmed smoking status and coronary artery calcification.

    Science.gov (United States)

    Kim, Byung Jin; Han, Ji Min; Kang, Jung Gyu; Kim, Bum Soo; Kang, Jin Ho

    2017-10-03

    There are no data comparing the relationship between coronary artery calcification and self-reported and cotinine-verified smoking. This study was carried out to evaluate the relationship between coronary artery calcium (CAC) and urinary cotinine or self-reported smoking status in Korean adults. Study participants included 22 797 individuals (19 181 men; mean age±SD 39.2±7.1 years) who were enrolled in the Kangbuk Samsung Health Study and Kangbuk Samsung Cohort Study between 2011 and 2013, and who had urinary cotinine and CAC measurements. Cotinine-verified current smokers were defined as having a urinary cotinine level of above 50 ng/ml. The prevalence of never smokers, former smokers, and current smokers according to the self-reported questionnaires was 44.6, 24.2, and 31.2%, respectively, and that of cotinine-verified current smokers was 30.2%. The prevalence of the presence of CAC in self-reported current smokers was higher than that in self-reported never/former smokers (13.7 vs. 10.2%, P<0.001), and that in cotinine-verified current smokers was higher than that in cotinine-verified never smokers (14.0 vs. 10.2%, P<0.001). A multivariate logistic regression model adjusted for the variables with univariate relationships showed that self-reported former smokers and current smokers had significantly increased odds ratio (OR) for the presence of CAC compared with self-reported never smokers [OR (95% confidence interval): 1.20 (1.03-1.40) in former smokers and 1.29 (1.11-1.50) in current smokers]. Cotinine-verified current smokers also showed a significant association with the presence of CAC [1.23 (1.12-1.35)]. Furthermore, log-transformed cotinine levels increased the OR for the presence of CAC [1.03 (1.01-1.05)]. This study is the first large cohort study to show that both self-reported and cotinine-verified smoking is associated independently with the presence of CAC in Korean adults.

  19. Confirmed enterovirus encephalitis with associated steroid-responsive acute disseminated encephalomyelitis: an overlapping infection and inflammation syndrome.

    Science.gov (United States)

    Pillai, Sekhar; Tantsis, Esther; Prelog, Kristina; Ramanathan, Sudarshini; Webster, Richard; Ouvrier, Robert A; Kesson, Alison; Brilot, Fabienne; Dale, Russell C

    2015-03-01

    Inflammatory disorders of the central nervous system have generally been separated into infectious or immune-mediated aetiologies. However, there are emerging examples of confirmed infectious viral infection of the brain followed by secondary inflammation or autoimmunity that is amenable to immune suppressive therapies. We report four children with confirmed enterovirus encephalitis (CSF enterovirus PCR positivity), who had MRI evidence of inflammatory demyelination compatible with ADEM. Two patients had a monophasic course, whereas two had a biphasic course. Serum myelin oligodendrocyte glycoprotein antibodies were negative in two tested patients, although all patients had mirrored CSF and serum oligoclonal bands. All four patients only improved with introduction of immune therapy (corticosteroids in three, corticosteroid and intravenous immunoglobulin in one). These cases provide a further example of the overlap between CNS infection and immune mediated CNS disease. Randomised controlled trials investigating immune therapies in encephalitis are required. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  20. Use of bedside abdominal ultrasound to confirm intestinal motility in neonates with gastroschisis: A feasibility study.

    Science.gov (United States)

    Gurien, Lori A; Wyrick, Deidre L; Dassinger, Melvin S; Burford, Jeffrey M; Mehl, Steven C; Saylors, Marie E; Smith, Samuel D

    2017-05-01

    Optimal timing to begin feeds in neonates with gastroschisis remains unclear. We examined if bedside abdominal ultrasound for intestinal motility is a feasible tool to detect return of bowel function in neonates with gastroschisis. Neonates born with uncomplicated gastroschisis who underwent closure received daily ultrasound exams. Full motility was defined as peristalsis seen in all quadrants. Average length of time between abdominal wall closure and start of enteral feeds, full ultrasound motility, and clinical characteristics was compared using Student's t-tests. Seventeen patients were enrolled. No differences were found between motility on ultrasound and bowel movements, gastric residuals, or nonbilious residuals. Mean time to enteral feeds (11.82days) was significantly delayed compared to documentation of full motility on ultrasound (8.94days; p=0.012), consistent bowel movements (8.41days; p=0.006), low gastric residuals (9.47days; p<0.001), and nonbilious residuals (9.18days; p<0.001). In the single subject in which feeds were started before full motility was seen on ultrasound, feeds were subsequently discontinued because of emesis. Bedside abdominal ultrasound provides real-time evidence regarding intestinal motility and is a feasible tool to detect return of bowel function in neonates with gastroschisis. Future studies are needed to determine if abdominal ultrasound can shorten time to start of enteral feeds. III (diagnosis: nonconsecutive study). Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Serological surveillance studies confirm the Rift Valley fever virus free status in South Korea.

    Science.gov (United States)

    Kim, Hyun Joo; Park, Jee-Yong; Jeoung, Hye-Young; Yeh, Jung-Yong; Cho, Yun-Sang; Choi, Jeong-Soo; Lee, Ji-Youn; Cho, In-Soo; Yoo, Han-Sang

    2015-10-01

    Rift Valley fever is a mosquito-borne zoonotic disease of domestic ruminants. This disease causes abortions in pregnant animals, and it has a high mortality rate in newborn animals. Recently, a Rift Valley fever virus (RVFV) outbreak in the Arabian Peninsula increased its potential spread to new regions worldwide. In non-endemic or disease-free countries, early detection and surveillance are important for preventing the introduction of RVFV. In this study, a serological surveillance was conducted to detect antibodies against RVFV. A total of 2382 serum samples from goats and cattle were randomly collected from nine areas in South Korea from 2011 to 2013. These samples were tested for antibodies against RVFV, using commercial ELISA kits. None of the goats and cattle were positive for antibodies against RVFV. This finding suggests that this disease is not present in South Korea, and furthermore presents the evidence of the RVFV-free status of this country.

  2. Ultrasound-Guided Superior Hypogastric Plexus Block: A Cadaveric Feasibility Study with Fluoroscopic Confirmation.

    Science.gov (United States)

    Gofeld, Michael; Lee, Chuan-Whei

    2017-02-01

    Plancarte first described a fluoroscopy-guided superior hypogastric plexus block to manage pelvic pain in 1990. Modifications have since been described using different imaging modalities. Ultrasound-guided approach has been described in a clinical outcome study. However, the accuracy of an ultrasound-guided method has never been validated by alternative imaging. We conducted an experiment aiming to develop ultrasound-guided superior hypogastric plexus block using human cadavers in the supine position. Final needle position and spread of a radiopaque contrast was verified by fluoroscopy, a standard imaging tool. The needle approach to the L5 vertebral body was performed in the short axis as has been recommended. Injection of radiopaque contrast revealed unilateral and cephalad spread to the L5/S1 disk. Additional transabdominal long-axis scanning of the lumbosacral segment was and the needle trajectory was modified to aim for the apex of the L5/S1 disk. Bilateral spread was achieved by strict midline placement of the needle tip and real-time observation of injection. The modified ultrasound-guided technique resulted in a similar spread of injectate as the traditional fluoroscopy-guided technique that in a clinical scenario would offer complete block of the superior hypogastric plexus. © 2016 World Institute of Pain.

  3. Optical coherence tomography study of experimental anterior ischemic optic neuropathy and histologic confirmation.

    Science.gov (United States)

    Ho, Joyce K; Stanford, Madison P; Shariati, Mohammad A; Dalal, Roopa; Liao, Yaping Joyce

    2013-09-05

    The optic nerve is part of the central nervous system, and interruption of this pathway due to ischemia typically results in optic atrophy and loss of retinal ganglion cells. In this study, we assessed in vivo retinal changes following murine anterior ischemic optic neuropathy (AION) by using spectral-domain optical coherence tomography (SD-OCT) and compared these anatomic measurements to that of histology. We induced ischemia at the optic disc via laser-activated photochemical thrombosis, performed serial SD-OCT and manual segmentation of the retinal layers to measure the ganglion cell complex (GCC) and total retinal thickness, and correlated these measurements with that of histology. There was impaired perfusion and leakage at the optic disc on fluorescein angiography immediately after AION and severe swelling and distortion of the peripapillary retina on day-1. We used SD-OCT to quantify the changes in retinal thickness following experimental AION, which revealed significant thickening of the GCC on day-1 after ischemia followed by gradual thinning that plateaued by week-3. Thickness of the peripapillary sensory retina was also increased on day-1 and thinned chronically. This pattern of acute retinal swelling and chronic thinning on SD-OCT correlated well with changes seen in histology and corresponded to loss of retinal ganglion layer cells after ischemia. This was a serial SD-OCT quantification of acute and chronic changes following experimental AION, which revealed changes in the GCC similar to that of human AION, but over a time frame of weeks rather than months.

  4. Ureaplasma parvum and Mycoplasma genitalium are found to be significantly associated with microscopy-confirmed urethritis in a routine genitourinary medicine setting.

    Science.gov (United States)

    Cox, Ciara; McKenna, James P; Watt, Alison P; Coyle, Peter V

    2016-09-01

    Inflammation of the urethra defined by an excess of polymorphonuclear leukocytes in the absence of sexually transmitted Chlamydia trachomatis and Neisseria gonorrhoeae is called non-chlamydial non-gonococcal urethritis (NCNGU). Although Mycoplasma genitalium is now recognised as causing a sexually transmitted infection, the clinical significance of the other Mollicute species is less clear. This study used specific real-time quantitative polymerase chain reaction assays to detect and quantify four Mollicute species, M. genitalium, M. hominis, Ureaplasma urealyticum and U. parvum, in urine specimens from men with and without NCNGU. A total of 165 urine specimens from male patients attending a genitourinary medicine clinic were eligible for the study, with microscopy-confirmed (≥5 polymorphonuclear leukocytes in urethral swab) NCNGU in 75 (45.5%) and non-confirmed NCNGU in 90 (54.5%). Chi-squared statistical analysis indicated a significantly higher prevalence of U. parvum (17.3% vs. 5.6%; p = 0.03) and M. genitalium (12% vs. 0%; p < 0.001) in NCNGU. In a subset analysis, M. genitalium was also significantly (p = 0.03) higher in men who have sex with men (MSM; 13.5%) compared to non-MSM (3.1%). No significant associations were reported for U. urealyticum and M. hominis In conclusion, this study supports a clinically significant role in NGNCU for both U. parvum and M. genitalium. © The Author(s) 2015.

  5. Confirming nasogastric tube placement: Is the colorimeter as sensitive and specific as X-ray? A diagnostic accuracy study.

    Science.gov (United States)

    Mordiffi, Siti Zubaidah; Goh, Mien Li; Phua, Jason; Chan, Yiong-Huak

    2016-09-01

    The effect of delivering enteral nutrition or medications via a nasogastric tube that is inadvertently located in the tracheobronchial tract can cause respiratory complications. Although radiographic examination is accepted as the gold standard for confirming the position of patients' enteral tubes, it is costly, involves risks of radiation, and is not failsafe. Studies using carbon dioxide sensors to detect inadvertent nasogastric tube placements have been conducted in intensive care settings. However, none involved patients in general wards. The objective of this study was to ascertain the diagnostic measure of colorimeter, with radiographic examination as the reference standard, to confirm the location of nasogastric tubes in patients. A prospective observational study of a diagnostic test. This study was conducted in the general wards of an approximately 1100-bed acute care tertiary hospital of an Academic Medical Center in Singapore. Adult patients with nasogastric tubes admitted to the general wards were recruited into the study. The colorimeter was attached to the nasogastric tube to detect for the presence of carbon dioxide, suggestive of a tracheobronchial placement. The exact location of the nasogastric tube was subsequently confirmed by a radiographic examination. A total of 192 tests were undertaken. The colorimeter detected carbon dioxide in 29 tested nasogastric tubes, of which radiographic examination confirmed that four tubes were located in the tracheobronchial tract. The colorimeter failed to detect carbon dioxide in one nasogastric tube that was located in the tracheobronchial tract, thus, demonstrating a sensitivity of 0.80 [95% CI (0.376, 0.964)]. The colorimeter detected absence of carbon dioxide in 163 tested nasogastric tubes in which radiographic examination confirmed 160 gastrointestinal and one tracheobronchial placements, demonstrating a specificity of 0.865 [95% CI (0.808, 0.907)]. The colorimeter detected one tracheobronchial

  6. Factors associated with colposcopy-histopathology confirmed cervical intraepithelial neoplasia among HIV-infected women from Rio De Janeiro, Brazil.

    Directory of Open Access Journals (Sweden)

    Angela Cristina Vasconcelos de Andrade

    Full Text Available INTRODUCTION: Despite the availability of preventive strategies (screening tests and vaccines, cervical cancer continues to impose a significant health burden in low- and medium-resourced countries. HIV-infected women are at increased risk for infection with human papillomavirus (HPV and thus development of cervical squamous intraepithelial neoplasia (CIN. METHODS: Study participants included HIV-infected women enrolling the prospective open cohort of Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation (IPEC/FIOCRUZ. At cohort entry, women were subjected to conventional Papanicolaou test, HPV-DNA test and colposcopy; lesions suspicious for CIN were biopsied. Histopathology report was based on directed biopsy or on specimens obtained by excision of the transformation zone or cervical conization. Poisson regression modeling was used to assess factors associated with CIN2+ diagnosis. RESULTS: The median age of the 366 HIV-infected women included in the study was 34 years (interquartile range: 28-41 years. The prevalence of CIN1, CIN2 and CIN3 were 20.0%, 3.5%, and 2.2%, respectively. One woman was found to have cervical cancer. The prevalence of CIN2+ was 6.0%. Factors associated with CIN2+ diagnosis in the multivariate model were age < years compared to ≥ 35 years (aPR  =  3.22 95%CI 1.23-8.39, current tobacco use (aPR  =  3.69 95%CI 1.54-8.78, nadir CD4 T-cell count <350 cells/mm3 when compared to ≥ 350 cells/mm3 (aPR  =  6.03 95%CI 1.50-24.3 and concomitant diagnosis of vulvar and/or vaginal intraepithelial lesion (aPR  =  2.68 95%CI 0.99-7.24. DISCUSSION: Increased survival through wide-spread use of highly active antiretroviral therapy might allow for the development of cervical cancer. In Brazil, limited cytology screening and gynecological care adds further complexity to the HIV-HPV co-infection problem. Integrated HIV care and cervical cancer prevention programs are needed for the prevention of cervical

  7. A Study of A B3R Converter Based PCU, to Confirm the Flexibility and Performance of the Converter Topology

    OpenAIRE

    Mache Erik; Koch Michael

    2017-01-01

    The main objective of this activity was to study the B3R converter [1] and to confirm its flexibility and performance (mainly efficiency and mass reduction) versus solutions that is implemented in a satellite PCU. For details see [2] ESTEC SOW. An architecture with centralised regulated bus, single battery and centralised solar array was selected for this study. Project Plan: - Study, design and development of an evaluation prototype, based on the B3R topology (including protections ...

  8. Autopsy-confirmed Alzheimer's disease versus clinically diagnosed Alzheimer's disease in the Cache County Study on Memory and Aging: a comparison of quantitative MRI and neuropsychological findings.

    Science.gov (United States)

    Fearing, Michael A; Bigler, Erin D; Norton, Maria; Tschanz, Jo Ann; Hulette, Christine; Leslie, Carol; Welsh-Bohmer, Kathleen

    2007-07-01

    Atrophy of specific, regional, and generalized brain structures occurs as a result of the Alzheimer's disease (AD) process. Comparing AD patients with histopathological confirmation of the disease at autopsy to those without autopsy but who were clinically diagnosed using the same antemortem criteria will provide further evidence of the utility and accuracy of neuropsychological assessments at the time of diagnosis, as well as the efficacy of quantitative magnetic resonance imaging (qMRI) in demonstrating gross neuropathological changes associated with the disease. The Cache County Study of Aging provides a unique opportunity to determine how closely AD subjects with only the clinical diagnosis match similarly diagnosed AD subjects but with postmortem confirmation of the disease. qMRI volumes of various brain structures, as well as neuropsychological outcome measures from an expanded battery, were obtained in 31 autopsy-confirmed AD subjects and 45 clinically diagnosed AD subjects. Of the various qMRI variables examined, only total temporal lobe volume was different, where those with postmortem confirmation had reduced volume. No significant differences between the two groups were found with any of the neuropsychological outcome measures. These findings confirm the similarity in neuroimaging and neuropsychological assessment findings between those with just the clinical diagnosis of AD and those with an autopsy-confirmed diagnosis in the moderate-to-severe stage of the disease at the time of diagnosis.

  9. Students' Perceived Understanding: An Alternative Measure and Its Associations with Perceived Teacher Confirmation, Verbal Aggressiveness, and Credibility

    Science.gov (United States)

    Schrodt, Paul; Finn, Amber N.

    2011-01-01

    Given recent questions regarding the construct validity of Cahn and Shulman's Feelings of Understanding/Misunderstanding scale, two studies were conducted to develop a low-inference, behavioral measure of students' perceived understanding in the college classroom. In Study One (N = 265), a pilot inventory was developed to measure students'…

  10. Confirmation of HLA class II independent type 1 diabetes associations in the major histocompatibility complex including HLA-B and HLA-A

    Science.gov (United States)

    Howson, J. M. M.; Walker, N. M.; Clayton, D.; Todd, J. A.

    2009-01-01

    Aim Until recently, human leucocyte antigen (HLA) class II-independent associations with type 1 diabetes (T1D) in the Major Histocompatibility Complex (MHC) region were not adequately characterized owing to insufficient map coverage, inadequate statistical approaches and strong linkage disequilibrium spanning the entire MHC. Here we test for HLA class II-independent associations in the MHC using fine mapping data generated by the Type 1 Diabetes Genetics Consortium (T1DGC). Methods We have applied recursive partitioning to the modelling of the class II loci and used stepwise conditional logistic regression to test ~1534 loci between 29 and 34 Mb on chromosome 6p21, typed in 2240 affected sibpair (ASP) families. Results Preliminary analyses confirm that HLA-B (at 31.4 Mb), HLA-A (at 30.0 Mb) are associated with T1D independently of the class II genes HLA-DRB1 and HLA-DQB1 (P = 6.0 × 10−17 and 8.8 × 10−13, respectively). In addition, a second class II region of association containing the single-nucleotide polymorphism (SNP), rs439121, and the class II locus HLA-DPB1, was identified as a T1D susceptibility effect which is independent of HLA-DRB1, HLA-DQB1 and HLA-B (P = 9.2 × 10−8). A younger age-at-diagnosis of T1D was found for HLA-B*39 (P = 7.6 × 10−6), and HLA-B*38 was protective for T1D. Conclusions These analyses in the T1DGC families replicate our results obtained previously in ~2000 cases and controls and 850 families. Taking both studies together, there is evidence for four T1D-associated regions at 30.0 Mb (HLA-A), 31.4 Mb (HLA-B), 32.5 Mb (rs9268831/HLA-DRA) and 33.2 Mb (rs439121/HLA-DPB1) that are independent of HLA-DRB1/HLA-DQB1. Neither study found evidence of independent associations at HLA-C, HLA-DQA1 loci nor in the UBD/MAS1L or ITPR3 gene regions. These studies show that to find true class II-independent effects, large, well-powered sample collections are required and be genotyped with a dense map of markers. In addition, a robust

  11. A Longitudinal Study of Motivations Before and Psychosexual Outcomes After Genital Gender-Confirming Surgery in Transmen.

    Science.gov (United States)

    van de Grift, Tim C; Pigot, Garry L S; Boudhan, Siham; Elfering, Lian; Kreukels, Baudewijntje P C; Gijs, Luk A C L; Buncamper, Marlon E; Özer, Müjde; van der Sluis, Wouter; Meuleman, Eric J H; Bouman, Mark-Bram; Mullender, Margriet G

    2017-12-01

    Genital dissatisfaction is an important reason for transmen to undergo genital gender-confirming surgery (GCS; phalloplasty or metoidioplasty). However, little is known about motives for choosing specific techniques, how transmen benefit postoperatively, and whether psychosexual outcomes improve. To evaluate motivations for and psychosexual outcomes after GCS. A longitudinal study of 21 transmen at least 1 year after GCS was conducted. Participants were recruited through their surgeon. Data were collected when they applied for surgery and at least 1 year after surgery. Data collection included semistructured questionnaires on motivations for surgery, postoperative experiences, and standardized measures of psychological symptoms, body image, self-esteem, sexuality, and quality of life (pre- and postoperative). Information on surgical complications and corrections was retrieved from medical records. Most participants underwent phalloplasty with urethral lengthening using a radial forearm flap. Although problematic voiding symptoms were prevalent, many participants were satisfied with their penile function. The strongest motivations to pursue penile surgery were confirmation of one's identity (100%), enabling sexual intercourse (78%), and voiding while standing (74%). No significant differences between postoperative and reference values were observed for standardized measures. After surgery, transmen were more sexually active (masturbation and with a partner) and used their genitals more frequently during sex compared with before surgery (31-78%). The present study provides input for preoperative decision making: (i) main motives for surgery include identity confirmation, voiding, and sexuality, (ii) surgery can result in more sexual activity and genital involvement during sex, although some distress can remain, but (iii) complications and voiding symptoms are prevalent. Study strengths include its longitudinal design and the novelty of the studied outcomes. The main

  12. Human cystic echinococcosis in Turkey: a preliminary study on DNA polymorphisms of hydatid cysts removed from confirmed patients.

    Science.gov (United States)

    Orsten, Serra; Boufana, Belgees; Ciftci, Turkmen; Akinci, Devrim; Karaagaoglu, Ergun; Ozkuyumcu, Cumhur; Casulli, Adriano; Akhan, Okan

    2018-02-23

    Cystic echinococcosis caused by the larval stages of Echinococcus granulosus sensu lato s.l is endemic in Turkey with a high public health impact particularly in rural areas. The aim of this study was to investigate the genetic variation and population structure of E. granulosus s.s using metacestode isolates removed from surgically confirmed patients originating from several regions in Turkey and to investigate the occurrence of autochthonous transmission. Using DNA extracted from a total of 46 human-derived CE isolates, we successfully analysed an 827-bp fragment within the cox1 mitochondrial gene and confirmed the causative agent of human cystic echinococcosis in patients included in this study to be Echinococcus granulosus s.s (G1 and G3 genotypes). The haplotype parsimony network consisted of 28 haplotypes arranged within three main clusters and the neutrality indices were both negative and significant indicating negative selection or population expansion. The assessment carried out in this study using GenBank nucleotide sequence data from Turkey for sheep and cattle hosts demonstrated the importance of autochthonous transmission with sheep, cattle and humans harbouring the same haplotypes. Further studies are required to investigate the biological significance, if any, of E. granulosus s.s haplotypes and the genetic variability of CE from human patients using longer nucleotide sequences and a larger sample set.

  13. Confirmation of a Campylobacteriosis Outbreak Associated with Chicken Liver Pâté Using PFGE and WGS.

    Science.gov (United States)

    Lahti, E; Löfdahl, M; Ågren, J; Hansson, I; Olsson Engvall, E

    2017-02-01

    In May 2012, an outbreak of campylobacteriosis occurred in southern Sweden at a wedding reception affecting 44 persons. A total of 17 cases were notified (13 were culture positive for Campylobacter spp.). Epidemiological investigation suspected chicken liver pâté as the source of infection. The liver pâté had been deliberately undercooked, lightly fried to keep the right texture and mixed with spices. Campylobacter isolates from six cases as well as three Campylobacter isolates from chicken flocks previously raised by the producer delivering the liver were subtyped using pulsed-field gel electrophoresis and whole-genome sequencing. Indistinguishable PFGE profiles were identified among five human and one chicken C. jejuni isolates as well among the two C. coli isolates, one from a human case and one from a chicken. WGS supported the PFGE findings; the six C. jejuni isolates belonged to one cluster. All these six isolates were of MLST type ST 50 (ST-CC 21). This study highlights the importance of a combination of strict biosecurity at the flock-level as well as adequate cooking of chicken liver to prevent transmission of Campylobacter to humans. © 2016 Blackwell Verlag GmbH.

  14. Stable cystatin C serum levels confirm normal renal function in patients with dronedarone-associated increase in serum creatinine.

    Science.gov (United States)

    Duncker, David; Oswald, Hanno; Gardiwal, Ajmal; Lüsebrink, Ulrich; König, Thorben; Schreyer, Hendrik; Klein, Gunnar

    2013-03-01

    Dronedarone is a new antiarrhythmic drug for patients with nonpermanent atrial fibrillation (AF). A relatively consistent finding in all trials studying dronedarone was a moderate but significant elevation of serum creatinine. Since dronedarone competes for the same organic cation transporter in the distal renal tubule with creatinine, serum creatinine and its derived estimated glomerular filtration rate might not reflect true renal function in patients on dronedarone. We therefore investigated alternative markers for renal function in these patients. We prospectively included 20 patients with nonpermanent AF in whom dronedarone 400 mg twice daily was started. Patients had normal renal function and serum creatinine; serum cystatin C and creatinine clearance were measured before treatment and 10 and 90 days after treatment started. Mean serum creatinine level for all 20 patients at baseline (day 0) was 84.55 ± 12.14 and 87.8 ± 17.59 µmol/L on day 10. This slight increase in all patients was not significant. Patients were now divided into the predefined groups of "increased creatinine" (increase in serum creatinine level > 1 standard deviation) and "not increased creatinine." Patients with increased creatinine levels (n = 5) showed a significant elevation of serum creatinine levels from day 0 to day 10 (82.4 ± 9.18 to 104.4 ± 12.74 µmol/L; P = .003), whereas change in serum creatinine levels in the not increased creatinine group (n = 15) was not significant. Serum cystatin C levels remained stable in both of these groups (increased creatinine group: 0.76 ± 0.08 to 0.78 ± 0.08 mg/L; P = .65; not increased creatinine group: 0.77 ± 0.108 to 0.77 ± 0.107 mg/L; P = .906). In conclusion, cystatin C represents an easily available and reliable biomarker for estimation of true renal function in patients on dronedarone treatment.

  15. Dose confirmation studies for monepantel, an amino-acetonitrile derivative, against fourth stage gastro-intestinal nematode larvae infecting sheep.

    Science.gov (United States)

    Hosking, B C; Dobson, D P; Stein, P A; Kaminsky, R; Bapst, B; Mosimann, D; Mason, P C; Seewald, W; Strehlau, G; Sager, H

    2009-03-23

    Monepantel is the first compound from the recently discovered amino-acetonitrile derivative (AAD) class of anthelmintics to be developed for use in sheep. Nine dose confirmation studies were conducted in Australia, New Zealand and Switzerland to confirm the minimum therapeutic oral dose of monepantel to control fourth stage (L4) gastro-intestinal nematode larvae in sheep (target species were Haemonchus contortus, Teladorsagia (Ostertagia) circumcincta, Teladorsagia trifurcata, Trichostrongylus axei, Trichostrongylus colubriformis, Trichostrongylus vitrinus, Cooperia curticei, Cooperia oncophora, Nematodirusbattus, Nematodirusfilicollis, Nematodirus spathiger, Chabertia ovina and Oesophagostomum venulosum). In each study, sheep infected with a defined selection of the target nematodes were treated with 2.5mg monepantel/kg liveweight. Following euthanasia and worm counting, efficacy was calculated against worm counts from untreated control groups. The results demonstrate high (95 or =90%) in some studies. Efficacy was demonstrated against L4 stages of nematodes known to be resistant to either benzimidazole and/or levamisole anthelmintics (macrocyclic lactone resistant isolates were not available for testing). The broad-spectrum activity of monepantel against L4 larvae of common gastro-intestinal nematodes in sheep and its favorable safety profile represents a significant advance in the treatment of parasitic gastro-enteritis in this animal species. No adverse effects related to treatment with monepantel were observed.

  16. Clinical and radiological characteristics of 17 Chinese patients with pathology confirmed tumefactive demyelinating diseases: follow-up study.

    Science.gov (United States)

    Yao, Jiarui; Huang, Dehui; Gui, Qiuping; Chen, Xiaolei; Lou, Xin; Wu, Lei; Cheng, Chen; Li, Jie; Wu, Weiping

    2015-01-15

    Tumefactive demyelinating disease is a rare inflammatory demyelinating disease (IDD) of the central nervous system (CNS). The literature lacks a clear and consistent description of the clinical and radiological spectrum of this disorder, and few Chinese cases have been studied. Here we report 17 Chinese patients, with pathology confirmed CNS IDD, who had distinct clinical and imaging features from those in previous reports. Median age at onset was 47 years, with a female to male ratio of 1.1:1. Multifocal lesions were present in nine cases (53%) on their pre-biopsy magnetic resonance imagings (MRIs), with locations predominantly involving periventricular white matter (41%), subcortical white matter (41%), juxtacortical regions (41%), and cortical gray matter (35%). Moderate to severe perilesional edema and/or mass effect were present in 35% of cases. A variety of enhancement patterns were observed; most were heterogeneous, including ring-like, patchy, venular-like, nodular, punctate, and diffuse in a decreased frequency. Perilesional restriction on diffusion-weighted images (DWI) were evident in 70% cases. Clinical course prior to biopsy was a first neurological event in 82% cases. During a median follow-up of 4.1 years, 76% of cases remained as isolated demyelinating syndrome, and 70% experienced a total or near-total recovery regardless of whether they received immunotherapy. Further studies are needed, especially concerning series with pathological confirmation and long-term follow-up information. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. A bias-reducing pathway enrichment analysis of genome-wide association data confirmed association of the MHC region with schizophrenia.

    LENUS (Irish Health Repository)

    Jia, Peilin

    2012-02-01

    After the recent successes of genome-wide association studies (GWAS), one key challenge is to identify genetic variants that might have a significant joint effect on complex diseases but have failed to be identified individually due to weak to moderate marginal effect. One popular and effective approach is gene set based analysis, which investigates the joint effect of multiple functionally related genes (eg, pathways). However, a typical gene set analysis method is biased towards long genes, a problem that is especially severe in psychiatric diseases.

  18. A study to confirm the reliability and construct validity of an organisational citizenship behaviour measure on a South African sample

    Directory of Open Access Journals (Sweden)

    Bright Mahembe

    2015-02-01

    Full Text Available Orientation: Organisational citizenship behaviour, or extra-role behaviours, are essential outcomes for the health functioning of organisations.Research purpose: The primary goal of the study was to validate the Organisational Citizenship Behaviour Scale (OCBS developed by Podsakoff, Mackenzie, Moorman and Fetter (1990 on a South African sample. Motivation for the study: Organisational citizenship behaviour is one of the important workplace outcomes. A psychometrically sound instrument is therefore required. Research design, approach and method: The sample consisted of 503 employees from the educational sector in the Eastern and Western Cape Provinces of South Africa. The OCBS was used to measure organisational citizenship behaviour.Main findings: High levels of reliability were found for the OCBS sub-scales. The first and second-order measurement models of the OCBS showed good fit. A competing one-factor model did not show good model fit. In terms of discriminant validity four of the five subdimensions correlated highly.Practical/managerial implications: Although the OCBS demonstrated some sound reliability coefficients and reasonable construct validity, the discriminant validity of four of the subscales raise some questions which future studies should confirm. The use of the instrument should help to continue to measure the much-needed extra-role behaviours that mirror an employee’s interest in the success of the organisation. Contribution/value-add: The study contributes to the requirements of the Employment Equity Act (No. 55 of 1998 and the Amended Employment Equity Act of South Africa (Republic of South Africa, 1998; 2014. This promotes the use of reliable and valid instruments in South Africa by confirming the psychometric properties of the OCBS.

  19. Confirmed Beliefs or False Assumptions? A Study of Home Stay Experiences in the French Study Abroad Context

    Science.gov (United States)

    Diao, Wenhao; Freed, Barbara; Smith, Leigh

    2011-01-01

    The past 20 years have witnessed enormous growth in a diverse array of studies which explore the linguistic impact of study abroad (SA) experiences. During this period a multitude of research projects have investigated SLA/L2 learning in SA, in a number of different languages (Russian, Japanese, French, Spanish, English), utilizing diverse…

  20. Long-term urinary dysfunction after mesorectal excision: a prospective study with intraoperative electrophysiological confirmation of nerve preservation.

    Science.gov (United States)

    Kneist, W; Junginger, T

    2007-11-01

    Bladder dysfunctions are well-recognized complications after nerve-sparing mesorectal excision for rectal cancer. This study sought to symptomatically analyze the extent of recovery from major and minor urinary symptoms in patients with signs of bladder denervation. Sixty-two patients with mesorectal excision for rectal cancer were investigated prospectively. Pelvic autonomic nerve preservation (PANP) was assessed macroscopically and with the aid of intraoperative electrical stimulation of pelvic autonomic nerves (INS). Bladder function was evaluated with the International Prostate Symptom Score (IPSS) and the Quality of life index (Qol). Median follow-up was 20 months (range 3-40 months). Forty-six patients with INS-confirmed preservation of parasympathetic nerves remained unchanged in early and long-term urinary function (IPSS: median 1; range 0-24 and Qol 0; range 0-5). In 15 patients without confirmation of PANP (unilaterally or bilaterally) on INS, voiding function was significantly more impaired postoperatively (IPSS: median 10; range 0-25 and Qol 3; range 0-6) and at long-term follow-up (IPSS: median 9; range 0-25 and Qol 3; range 0-6) (p<0.001). Voiding function was improved in 4 of 10 patients with major and minor symptoms. In 5 of 6 patients with long-term bladder dysfunction INS assessed parasympathetic nerve damage unilaterally (3/5) and bilaterally (2/5). Long-term voiding disturbance after mesorectal excision was found to be a serious complication. INS while monitoring intravesical pressure is a valuable aid in predicting long-term bladder function after TME. The device may serve a secondary preventive function in enabling the initiation of early urologic therapy.

  1. Flow confirmation study for central venous port in oncologic outpatient undergoing chemotherapy: Evaluation of suspected system-related mechanical complications

    Energy Technology Data Exchange (ETDEWEB)

    Sofue, Keitaro, E-mail: ksofue@ncc.go.jp [Divisions of Diagnostic Radiology, National Cancer Center Hospital (Japan); Department of Radiology, Kobe University, Graduate School of Medicine (Japan); Arai, Yasuaki; Takeuchi, Yoshito [Divisions of Diagnostic Radiology, National Cancer Center Hospital (Japan); Sugimura, Kazuro [Department of Radiology, Kobe University, Graduate School of Medicine (Japan)

    2013-11-01

    Purpose: To evaluate the efficacy and outcome of a flow confirmation study (FCS) in oncologic outpatients undergoing chemotherapy suspected of a central venous port (CVP) system-related mechanical complication. Materials and methods: A total of 66 patients (27 men, 39 women; mean age, 60 years) received FCS for the following reasons: prolonged infusion time during chemotherapy (n = 32), inability to inject saline fluid (n = 15), lateral neck and/or back pain (n = 6), subcutaneous extravasation of anticancer drug (n = 5), arm swelling (n = 4), and inability to puncture the port (n = 4). FCS consisted of examining the position of CVP, potential secondary shifts or fractures, and integrity of the system using contrast material through the port. Results: Of the 66 patients, 43 had an abnormal finding uncovered by FCS. The most frequent abnormal findings was catheter kinking (n = 22). Explantation and reimplantation of the CVP system was required in 21 of the 66 patients. Remaining 45 patients were able continue using the CVP system after the FCS without any system malfunction. Conclusion: FCS was effective for evaluating CVP system-related mechanical complications and was useful for deciding whether CVP system explantation and reimplantation was required.

  2. Clinical characterization of acute and convalescent illness of confirmed chikungunya cases from Chiapas, S. Mexico: A cross sectional study.

    Directory of Open Access Journals (Sweden)

    Rogelio Danis-Lozano

    Full Text Available The emerging chikungunya virus (CHIKV, is an arbovirus causing intense outbreaks in North America. The situation in Mexico is alarming, and CHIKV threatens to spread further throughout North America. Clinical and biological features of CHIKF outbreaks in Mexico have not been well described; thus, we conducted a cross sectional study of a CHIKV outbreak in Chiapas, Southern Mexico to further characterize these features.We collected blood samples from patients suspected of having chikungunya fever (CHIKF who presented to Clinical Hospital ISSSTE Dr. Roberto Nettel in Tapachula, Chiapas, Mexico. In addition to the clinical examination, real-time polymerase chain reaction (PCR standardized for the Asian Chikungunya lineage and/or enzyme-linked immunosorbent assay for immunoglobulin M (IgM were used to confirm CHIKV diagnosis. Of a total of 850 patients who presented with probably CHIKV at Hospital "Dr. Roberto Nettel", 112 probable CHIKF cases were enrolled in this study from November 2014- June 2015, of which 95 patients (84.8% were CHIKV positive and 17 were negative (15.2%. Of these 95 CHIKV positive patients, 62 were positive by real-time reverse transcriptase PCR (+qRT-PCR; and 33 were seropositive to +IgM with a negative qRT-PCR. The most frequent symptoms reported were fever (100%, headache (82.3%, polyarthralgia (72.1%, and exanthem (82.3%. Biological abnormalities observed during CHIKV infection were lymphopenia (41.1%, leukopenia (51.6%, elevated transaminases (30.5%-46.3% and high LDH (46.3% and CRP (60.0%.Clinical and biological data obtained from this study is providing more useful information for benchmarking purposes with outbreaks from different parts of the world and would be helpful for better patient care and treatment.

  3. Body odor attractiveness as a cue of impending ovulation in women: evidence from a study using hormone-confirmed ovulation.

    Science.gov (United States)

    Gildersleeve, Kelly A; Haselton, Martie G; Larson, Christina M; Pillsworth, Elizabeth G

    2012-02-01

    Scent communication plays a central role in the mating behavior of many nonhuman mammals but has often been overlooked in the study of human mating. However, a growing body of evidence suggests that men may perceive women's high-fertility body scents (collected near ovulation) as more attractive than their low-fertility body scents. The present study provides a methodologically rigorous replication of this finding, while also examining several novel questions. Women collected samples of their natural body scent twice--once on a low-fertility day and once on a high-fertility day of the ovulatory cycle. Tests of luteinizing hormone confirmed that women experienced ovulation within two days of their high-fertility session. Men smelled each woman's high- and low-fertility scent samples and completed discrimination and preference tasks. At above-chance levels, men accurately discriminated between women's high- and low-fertility scent samples (61%) and chose women's high-fertility scent samples as more attractive than their low-fertility scent samples (56%). Men also rated each scent sample on sexiness, pleasantness, and intensity, and estimated the physical attractiveness of the woman who had provided the sample. Multilevel modeling revealed that, when high- and low-fertility scent samples were easier to discriminate from each other, high-fertility scent samples received even more favorable ratings compared with low-fertility scent samples. This study builds on a growing body of evidence indicating that men are attracted to cues of impending ovulation in women and raises the intriguing question of whether women's cycling hormones influence men's attraction and sexual approach behavior. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Clinical characterization of acute and convalescent illness of confirmed chikungunya cases from Chiapas, S. Mexico: A cross sectional study.

    Science.gov (United States)

    Danis-Lozano, Rogelio; Díaz-González, Esteban Eduardo; Trujillo-Murillo, Karina Del Carmen; Caballero-Sosa, Sandra; Sepúlveda-Delgado, Jesús; Malo-García, Iliana Rosalía; Canseco-Ávila, Luis Miguel; Salgado-Corsantes, Luis Manuel; Domínguez-Arrevillaga, Sergio; Torres-Zapata, Raúl; Gómez-Cruz, Omar; Fernández-Salas, Ildefonso

    2017-01-01

    The emerging chikungunya virus (CHIKV), is an arbovirus causing intense outbreaks in North America. The situation in Mexico is alarming, and CHIKV threatens to spread further throughout North America. Clinical and biological features of CHIKF outbreaks in Mexico have not been well described; thus, we conducted a cross sectional study of a CHIKV outbreak in Chiapas, Southern Mexico to further characterize these features. We collected blood samples from patients suspected of having chikungunya fever (CHIKF) who presented to Clinical Hospital ISSSTE Dr. Roberto Nettel in Tapachula, Chiapas, Mexico. In addition to the clinical examination, real-time polymerase chain reaction (PCR) standardized for the Asian Chikungunya lineage and/or enzyme-linked immunosorbent assay for immunoglobulin M (IgM) were used to confirm CHIKV diagnosis. Of a total of 850 patients who presented with probably CHIKV at Hospital "Dr. Roberto Nettel", 112 probable CHIKF cases were enrolled in this study from November 2014- June 2015, of which 95 patients (84.8%) were CHIKV positive and 17 were negative (15.2%). Of these 95 CHIKV positive patients, 62 were positive by real-time reverse transcriptase PCR (+qRT-PCR); and 33 were seropositive to +IgM with a negative qRT-PCR. The most frequent symptoms reported were fever (100%), headache (82.3%), polyarthralgia (72.1%), and exanthem (82.3%). Biological abnormalities observed during CHIKV infection were lymphopenia (41.1%), leukopenia (51.6%), elevated transaminases (30.5%-46.3%) and high LDH (46.3%) and CRP (60.0%). Clinical and biological data obtained from this study is providing more useful information for benchmarking purposes with outbreaks from different parts of the world and would be helpful for better patient care and treatment.

  5. Control of antioxidant supplementation through interview is not appropriate in oxidative-stress sport studies: Analytical confirmation should be required.

    Science.gov (United States)

    Barranco-Ruiz, Yaira; Aragón-Vela, Jeronimo; Casals, Cristina; Martínez-Amat, Antonio; Casuso, Rafael A; Huertas, Jesus R

    2017-01-01

    Controlling antioxidant supplementation in athletes involved in studies related to oxidative stress and muscle damage is the key to ensure results. The aim of this study was to confirm through high-performance liquid chromatography (HPLC) analysis whether well-trained individuals lied during a personal interview when asked if they were taking supplements with antioxidants, and how this could affect oxidative stress, muscle damage, and antioxidant response. A total of 94 men, well trained in endurance sports, volunteered in this study. They denied taking any antioxidant supplementation at initial interview. After a HPLC analysis, abnormal α-tocopherol concentrations were detected, probably due to a hidden antioxidant supplementation. Participants were classified into two groups: no evidence of antioxidant supplementation (NS group = α-tocopherol values antioxidant supplementation (S group = α-tocopherol values >80 nmol/mL; n = 19). Lipid peroxidation, muscle damage, antioxidant enzyme activity, and nonenzymatic antioxidant content were analyzed according to this classification. Statistical comparisons were performed using Student's t test. The α-tocopherol concentrations were significantly higher in the S group than in the NS group (MD = 725.01 ± 39.01 nmol/mL; P = 0.001). The S group showed a trend toward lower hydroperoxides than the NS group (MD = 1.19 ± 0.72 nmol/mL; P = 0.071). The S group showed significantly lower catalase activity than the NS group (MD = 0.10 ± 0.02-seg-1 mg-1; P antioxidant supplementation in a personal interview, as they showed high plasmatic α-tocopherol concentrations after HPLC verification. Catalase activity seems to be affected by high α-tocopherol plasma levels. Therefore, we strongly recommend the HPLC analysis as a necessary tool to verify the antioxidant intake and preserve results in studies linking oxidative stress and sport. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Failure to confirm allelic and haplotypic association between markers at the chromosome 6p22.3 dystrobrevin-binding protein 1 (DTNBP1 locus and schizophrenia

    Directory of Open Access Journals (Sweden)

    Kirwin Simon

    2007-09-01

    Full Text Available Abstract Background Previous linkage and association studies may have implicated the Dystrobrevin-binding protein 1 (DTNBP1 gene locus or a gene in linkage disequilibrium with DTNBP1 on chromosome 6p22.3 in genetic susceptibility to schizophrenia. Methods We used the case control design to test for of allelic and haplotypic association with schizophrenia in a sample of four hundred and fifty research subjects with schizophrenia and four hundred and fifty ancestrally matched supernormal controls. We genotyped the SNP markers previously found to be significantly associated with schizophrenia in the original study and also other markers found to be positive in subsequent studies. Results We could find no evidence of allelic, genotypic or haplotypic association with schizophrenia in our UK sample. Conclusion The results suggest that the DTNBP1 gene contribution to schizophrenia must be rare or absent in our sample. The discrepant allelic association results in previous studies of association between DTNBP1 and schizophrenia could be due population admixture. However, even positive studies of European populations do not show any consistent DTNBP1 alleles or haplotypes associated with schizophrenia. Further research is needed to resolve these issues. The possible confounding of linkage with association in family samples already showing linkage at 6p22.3 might be revealed by testing genes closely linked to DTNBP1 for allelic association and by restricting family based tests of association to only one case per family.

  7. Multi-frequency study of the newly confirmed supernova remnant MCSNR J0512-6707 in the Large Magellanic Cloud

    Science.gov (United States)

    Kavanagh, P. J.; Sasaki, M.; Bozzetto, L. M.; Points, S. D.; Filipović, M. D.; Maggi, P.; Haberl, F.; Crawford, E. J.

    2015-11-01

    Aims: We present a multi-frequency study of the supernova remnant MCSNR J0512-6707 in the Large Magellanic Cloud. Methods: We used new data from XMM-Newton to characterise the X-ray emission and data from the Australian Telescope Compact Array, the Magellanic Cloud Emission Line Survey, and Spitzer to gain a picture of the environment into which the remnant is expanding. We performed a morphological study, determined radio polarisation and magnetic field orientation, and performed an X-ray spectral analysis. Results: We estimated the remnant's size to be 24.9 ( ± 1.5) × 21.9 ( ± 1.5) pc, with the major axis rotated ~29° east of north. Radio polarisation images at 3 cm and 6 cm indicate a higher degree of polarisation in the northwest and southeast tangentially oriented to the SNR shock front, indicative of an SNR compressing the magnetic field threading the interstellar medium. The X-ray spectrum is unusual as it requires a soft (~0.2 keV) collisional ionisation equilibrium thermal plasma of interstellar medium abundance, in addition to a harder component. Using our fit results and the Sedov dynamical model, we showed that the thermal emission is not consistent with a Sedov remnant. We suggested that the thermal X-rays can be explained by MCSNR J0512-6707 having initially evolved into a wind-blown cavity and is now interacting with the surrounding dense shell. The origin of the hard component remains unclear. We could not determine the supernova type from the X-ray spectrum. Indirect evidence for the type is found in the study of the local stellar population and star formation history in the literature, which suggests a core-collapse origin. Conclusions: MCSNR J0512-6707 likely resulted from the core-collapse of high mass progenitor which carved a low density cavity into its surrounding medium, with the soft X-rays resulting from the impact of the blast wave with the surrounding shell. The unusual hard X-ray component requires deeper and higher spatial

  8. Lidocaine response rate in aEEG-confirmed neonatal seizures: Retrospective study of 413 full-term and preterm infants.

    Science.gov (United States)

    Weeke, Lauren C; Toet, Mona C; van Rooij, Linda G M; Groenendaal, Floris; Boylan, Geraldine B; Pressler, Ronit M; Hellström-Westas, Lena; van den Broek, Marcel P H; de Vries, Linda S

    2016-02-01

    To investigate the seizure response rate to lidocaine in a large cohort of infants who received lidocaine as second- or third-line antiepileptic drug (AED) for neonatal seizures. Full-term (n = 319) and preterm (n = 94) infants, who received lidocaine for neonatal seizures confirmed on amplitude-integrated EEG (aEEG), were studied retrospectively (January 1992-December 2012). Based on aEEG findings, the response was defined as good (>4 h no seizures, no need for rescue medication); intermediate (0-2 h no seizures, but rescue medication needed after 2-4 h); or no clear response (rescue medication needed Lidocaine had a good or intermediate effect in 71.4%. The response rate was significantly lower in preterm (55.3%) than in full-term infants (76.1%, p lidocaine was significantly better than midazolam as second-line AED (21.4% vs. 12.7%, p = 0.049), and there was a trend for a higher response rate as third-line AED (67.6% vs. 57%, p = 0.086). Both lidocaine and midazolam had a higher response rate as third-line AED than as second-line AED (p lidocaine were the following: higher gestational age, longer time between start of first seizure and administration of lidocaine, lidocaine as third-line AED, use of new lidocaine regimens, diagnosis of stroke, use of digital aEEG, and hypothermia. Multivariable analysis of seizure response to lidocaine included lidocaine as second- or third-line AED and seizure etiology. Seizure response to lidocaine was seen in ~70%. The response rate was influenced by gestational age, underlying etiology, and timing of administration. Lidocaine had a significantly higher response rate than midazolam as second-line AED, and there was a trend for a higher response rate as third-line AED. Both lidocaine and midazolam had a higher response rate as third-line compared to second-line AED, which could be due to a pharmacologic synergistic mechanism between the two drugs. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

  9. First confirmed case of Clostridium difficile-associated diarrhea in foals in Brazil Primeiro relato de diarreia associada à Clostridium difficile em potros no Brasil

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    Rodrigo Otávio Silveira Silva

    2012-03-01

    Full Text Available Despite of the substantial role of Clostridium difficile in causing diarrhea and colitis in foals, there have been no confirmed diagnoses of disease caused by this bacteria in Brazil. In this paper, we describe confirmed cases of colitis caused by C. difficile in two foals in Brazil. Two five-month-old foals with a five-day history of diarrhea after antibiotic treatment for a respiratory disease were treated at the Veterinary Hospital of the Universidade Federal de Minas Gerais. C. difficile A/B toxins were detected, and toxigenic strains of C. difficile were isolated from the foals' feces. The treatment was based on fluid therapy and antibiotics (metronidazole and ceftiofur, and the animals experienced a gradual recovery. The association between the medical history, clinical signs, laboratory exam results and therapeutic success confirmed the diagnosis of C. difficile-associated diarrhea. The present report raises the possibility that C. difficile is also a pathogen in equines in Brazil and highlights the need for up to date routine laboratory protocols for the diagnosis of this disease.Apesar da importância de Clostridium difficile como agente causador de diarreia e colite em potros, inexistem relatos confirmados de tal doença no Brasil. O objetivo deste trabalho foi descrever dois casos confirmados de diarreia causados por C. difficile em potros, ocorridos em Minas Gerais, Brasil. Os animais, com cinco meses de idade, foram encaminhados ao Hospital Veterinário da Universidade Federal de Minas Gerais (UFMG com histórico de cinco dias de diarreia após antibioticoterapia com penicilina para uma possível pneumonia. Ambos os animais foram positivos para detecção das toxinas A/B de C. difficile e isolados toxigênicas de C. difficile foram isoladas de amostras de fezes. Os animais apresentaram melhora gradual com o tratamento baseado em metronidazol e fluidoterapia e receberam alta após sete dias. A associação do quadro clínico, exames

  10. Pneumonia tuberculosa: um estudo de 59 casos confirmados microbiologicamente Tuberculous pneumonia: a study of 59 microbiologically confirmed cases

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    Jose Moreira

    2011-04-01

    consistent with fistula between a lymph node and a bronchus. RESULTS: Of the 59 patients studied, 43 (73% were between 20 and 50 years of age, 31 (53% were male, and 28 (47% were Black. The most common symptoms were cough (in 100%, fever (in 88%, expectoration (in 81%, and weight loss (in 40%. Comorbidities were reported in 35 cases (59%, the most common being HIV infection (in 20% and diabetes (in 15%. On chest X-rays, consolidation was observed, predominantly in the upper lobes (in 68%. The diagnostic confirmation (identification of AFB was made through the sputum smear microscopy in the majority of the cases and by bronchoscopy (BAL examination or bronchial biopsy in the remainder. Bronchial lesions were clearly indicative or suggestive of fistula in three cases and five cases, respectively. CONCLUSIONS: Tuberculous pneumonia presents as acute respiratory infection, initiating with a dry cough that is followed by fever. Chest X-rays show alveolar consolidation. In most cases, tuberculous pneumonia was accompanied by at least one comorbid condition, the most common being HIV infection, and the etiological diagnosis was made through sputum smear microscopy for AFB. Bronchoscopy findings were indicative of bronchial fistula in eight cases (13%.

  11. Confirmation and fine-mapping of a major QTL for resistance to infectious pancreatic necrosis in Atlantic salmon (Salmo salar: population-level associations between markers and trait

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    Moen Thomas

    2009-08-01

    multi-marker haplotypes. One four-marker haplotype was found to be the best predictor of QTL alleles, and was successfully used to deduce genotypes of the underlying polymorphism in 72% of the parents of the next generation within a breeding nucleus. A highly significant population-level correlation was found between deduced alleles at the underlying polymorphism and survival of offspring groups in the fry challenge test, parents with the three deduced genotypes (QQ, Qq, qq having mean offspring mortality rates of 0.13, 0.32, and 0.49, respectively. The frequency of the high-resistance allele (Q in the population was estimated to be 0.30. Apart from this major QTL, one other experiment-wise significant QTL for IPN-resistance was detected, located on linkage group 4. Conclusion The QTL confirmed in this study represents a case of a major gene explaining the bulk of genetic variation for a presumed complex trait. QTL genotypes were deduced within most parents of the 2005 generation of a major breeding company, providing a solid framework for linkage-based MAS within the whole population in subsequent generations. Since haplotype-trait associations valid at the population level were found, there is also a potential for MAS based on linkage disequilibrium (LD. However, in order to use MAS across many generations without reassessment of linkage phases between markers and the underlying polymorphism, the QTL needs to be positioned with even greater accuracy. This will require higher marker densities than are currently available.

  12. Confirmation and fine-mapping of a major QTL for resistance to infectious pancreatic necrosis in Atlantic salmon (Salmo salar): population-level associations between markers and trait

    Science.gov (United States)

    Moen, Thomas; Baranski, Matthew; Sonesson, Anna K; Kjøglum, Sissel

    2009-01-01

    . One four-marker haplotype was found to be the best predictor of QTL alleles, and was successfully used to deduce genotypes of the underlying polymorphism in 72% of the parents of the next generation within a breeding nucleus. A highly significant population-level correlation was found between deduced alleles at the underlying polymorphism and survival of offspring groups in the fry challenge test, parents with the three deduced genotypes (QQ, Qq, qq) having mean offspring mortality rates of 0.13, 0.32, and 0.49, respectively. The frequency of the high-resistance allele (Q) in the population was estimated to be 0.30. Apart from this major QTL, one other experiment-wise significant QTL for IPN-resistance was detected, located on linkage group 4. Conclusion The QTL confirmed in this study represents a case of a major gene explaining the bulk of genetic variation for a presumed complex trait. QTL genotypes were deduced within most parents of the 2005 generation of a major breeding company, providing a solid framework for linkage-based MAS within the whole population in subsequent generations. Since haplotype-trait associations valid at the population level were found, there is also a potential for MAS based on linkage disequilibrium (LD). However, in order to use MAS across many generations without reassessment of linkage phases between markers and the underlying polymorphism, the QTL needs to be positioned with even greater accuracy. This will require higher marker densities than are currently available. PMID:19664221

  13. Gene susceptibility identification in a longitudinal study confirms new loci in the development of chronic obstructive pulmonary disease and influences lung function decline.

    Science.gov (United States)

    Xie, Jungang; Wu, Hongxu; Xu, Yuzhu; Wu, Xiaojie; Liu, Xue; Shang, Jin; Zhao, Jianping; Zhao, Junling; Wang, Jianmiao; Dela Cruz, Charles S; Xiong, Weining; Xu, Yongjian

    2015-04-18

    To identify COPD associated gene susceptibility and lung function in a longitudinal cohort including COPD and subjects who were at risk for developing COPD, and to replicate this in two cross-sectional and longitudinal populations in Chinese Han population. Three cohorts were recruited in this study, including an 18-year follow-up population (306 COPD and 743 control subjects) in one village in 1992 and it changed to 409 COPD and 611 controls in 2010, a 2 year follow-up study in another village (374 COPD and 377 controls) and another 2 year follow-up one in a city (541 COPD and 560 controls) in 2010. Sixteen candidate single nucleotide polymorphisms (SNPs) were selected for genotyping. Among them, 5SNPs in or near HHIP, 1SNP in IREB2 and 1SNP in FAM13A were previously reported to be associated with COPD susceptibility or lung function decline. And another 9SNPs were selected from HapMap website as HHIP tags. In 2010, totaling 1,324 COPD patients and 1,548 healthy controls were finally included in our genetic susceptibility analyses. We identified two new regions showing an association with COPD susceptibility in the Human Hedgehog interacting protein (HHIP) rs11100865 and rs7654947, and we confirmed that the family with sequence similarity 13 member A gene (FAM13A) rs7671167 was associated with the development of COPD in Chinese Han population. And the HHIP rs7654947 and FAM13A rs7671167 were associated with lung function decline, and this result was replicated in other two populations. These results suggest an important role of the HHIP and FAM13A regions as genetic risk factors for COPD development and lung function decline in Chinese Han population. Future research on these genes should focus on the molecular mechanisms of these genes on developing COPD and creating therapies to alleviate reduced lung function.

  14. Morphological and genetic barcoding study confirming the first Stegastes variabilis (Castelnau, 1855 report in the Mediterranean Sea

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    A. VELLA

    2015-10-01

    Full Text Available This paper presents morphometric and genetic barcoding analyses of the first record of the Cocoa Damselfish, Stegastes variabilis in the Mediterranean Sea. A single specimen was captured from Senglea waterfront, Malta (Central Mediterranean on the 15th of September 2013. The species is non-indigenous in the Mediterranean, as it is native to the tropical Western Atlantic. Apart from undertaking identification through meristics and morphometric measurements of the specimen, genetic analyss of the 3410 bp mtDNA genes were carried out to confirm the species' identity. The latter was useful given that the genus Stegastes is known to be composed of morphologically very similar species, with variable colour patterns.

  15. Metal–organic framework thin films with well-controlled growth directions confirmed by x-ray study

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    Kazuya Otsubo

    2014-12-01

    Full Text Available Metal–organic frameworks (MOFs have attracted the attention of a variety of researchers because of their structural diversity and designability, and their varied physical properties based on their uniform microporosity. While MOFs are interesting as bulk materials, future applications in functional nanomaterials will require the use of MOFs as thin films, and to achieve this, several thin-film fabrication techniques have been developed. These techniques have provided rational design of a variety of MOF thin films; however, oriented crystal growth of a MOF thin film, which is mainly confirmed by X-ray diffraction, remains a challenge that should be addressed. In this article, we review thin-film fabrications and characterizations, and structural features of MOF thin films with perfect crystalline orientation.

  16. Confirmation of high cytokine clearance by hemofiltration with a cellulose triacetate membrane with large pores: an in vivo study.

    Science.gov (United States)

    Delanaye, P; Lambermont, B; Dogné, J-M; Dubois, B; Ghuysen, A; Janssen, N; Desaive, T; Kolh, P; D'Orio, V; Krzesinski, J-M

    2006-10-01

    To confirm in vivo the hypothesis that hemofiltration with a large pore membrane can achieve significant cytokine clearance. We used a well-known animal model of endotoxinic shock (0.5 mg/kg of lipopolysaccharide from Escherichia Coli over a period of 30 mins). Six pigs were hemofiltrated for 3 hours with a large pore membrane (78 A pore, 80 kDa cut off) (Sureflux FH 70, Nipro, Osaka, Japan). The ultrafiltration rate was 45 ml/kg/min. Samples were taken from arterial, venous line and in the ultrafiltrate at T120 and T240. We measured concentrations of interleukin 6, interleukin 10 and albumin. At T120 and T240, the IL-6 clearances were 22 +/- 7 and 15 +/- 3 ml/min, respectively. The IL-6 sieving coefficients were 0.97 and 0.7 at T120 and T240, respectively. At T120 and T240, the IL-10 clearances were 14 +/- 4 and 10 +/- 7 ml/min, respectively. The sieving coefficients were 0.63 and 0.45 at T120 and T240, respectively. The concentrations of IL-6 and IL-10 were the same at T0 and T240. At T60 and T240, the plasmatic albumin concentrations were 24 +/- 4 g/L and 23 +/- 4 g/L, respectively (p = 0.13). In this animal model of endotoxinic shock, we confirm the high cytokine clearance observed when hemofiltration is applied to a large pore membrane. The loss of albumin seems negligible. The impact of such clearances on hemodynamic stability and survival remains to be proved.

  17. Molecular characterization of a 12q22-q24 deletion associated with congenital deafness: confirmation and refinement of the DFNA25 locus.

    Science.gov (United States)

    Petek, Erwin; Windpassinger, Christian; Mach, Monika; Rauter, Ludwig; Scherer, Stephen W; Wagner, Klaus; Kroisel, Peter M

    2003-03-01

    The DFNA25 locus for autosomal dominant nonsyndromic hereditary hearing loss has been mapped to 12q21-q24 by linkage analysis. A de novo deletion in a six-year-old boy with congenital hearing loss as well as mental and motor retardation now provides independent confirmation of this genetic localization and narrows the critical interval to 13 cM in the 12q22-q24.1 region. Mapping of the deletion was performed using fluorescence in situ hybridization (FISH) analysis with region-specific yeast artificial chromosome (YAC) clones. Ten YACs 929_e_4, 959_c_3, 746_h_7, 817_h_10, 886_a_6, 916_h_9, 969_c_12, 747_e_2, 812_h_12, and 959_f_8 were absent from one chromosome 12 from the patient. Molecular analyses of eight polymorphic markers helped to narrow down the breakpoints and demonstrated that the derivative chromosome 12 is of paternal origin. Several known genes including ATP2A2, UBE3B, and VR-OAC that map in the 12q22-q24.1 region are included in the deletion. These results provide evidence that haploinsufficiency for a gene or genes in 12q22-q24.1 is associated with autosomal dominant deafness. Copyright 2003 Wiley-Liss, Inc.

  18. User Coupled Confirmation Drilling Program case study: City of Alamosa, Colorado, Alamosa No. 1 geothermal test well

    Energy Technology Data Exchange (ETDEWEB)

    Zeisloft, J.; Sibbett, B.S.

    1985-08-01

    A 7118 ft (2170 m) deep geothermal test well was drilled on the south edge of the city of Alamosa, Colorado as part of the Department of Energy's User Coupled Confirmation Drilling Program. The project was selected on the bases of a potential direct heat geothermal resource within the Rio Grande rift graben and resource users in Alamosa. The well site was selected on the hypothesis of a buried horst along which deep thermal fluids might be rising. In addition, there were city wells that were anomalous in temperature and the location was convenient to potential application. The Alamosa No. 1 penetrated 2000 ft (610 m) of fine clastic rocks over 4000 ft (1219 m) of volcaniclastic rock resting on precambrian crystalline rock at a depth of 6370 ft (1942 m). Due to poor hole conditions, geophysical logs were not run. The stabilized bottom hole temperature was 223/sup 0/F (106/sup 0/C) with a gradient of 2.6/sup 0/F/100 ft (47/sup 0/C/km). Limited testing indicated a very low production capacity. 16 refs., 6 figs.

  19. CERN confirms LHC schedule

    CERN Multimedia

    2003-01-01

    The CERN Council held its 125th session on 20 June. Highlights of the meeting included confirmation that the LHC is on schedule for a 2007 start-up, and the announcement of a new organizational structure in 2004.

  20. Confirmation of an Association Between Single Nucleotide Polymorphisms in the VDR Gene With Respiratory Syncytial Virus Related Disease in South African Children

    NARCIS (Netherlands)

    Kresfelder, T. L.; Janssen, R.; Bont, L.; Venter, M.

    2011-01-01

    Respiratory syncytial virus is a leading cause of lower respiratory tract infection in infants. Disease severity has been linked to host immune responses and polymorphisms in genes associated with innate immunity. A large-scale genetics study of single nucleotide polymorphisms (SNPs) in children in

  1. Robust physical methods that enrich genomic regions identical by descent for linkage studies: confirmation of a locus for osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Cohen Nadine

    2009-03-01

    Full Text Available Abstract Background The monogenic disease osteogenesis imperfecta (OI is due to single mutations in either of the collagen genes ColA1 or ColA2, but within the same family a given mutation is accompanied by a wide range of disease severity. Although this phenotypic variability implies the existence of modifier gene variants, genome wide scanning of DNA from OI patients has not been reported. Promising genome wide marker-independent physical methods for identifying disease-related loci have lacked robustness for widespread applicability. Therefore we sought to improve these methods and demonstrate their performance to identify known and novel loci relevant to OI. Results We have improved methods for enriching regions of identity-by-descent (IBD shared between related, afflicted individuals. The extent of enrichment exceeds 10- to 50-fold for some loci. The efficiency of the new process is shown by confirmation of the identification of the Col1A2 locus in osteogenesis imperfecta patients from Amish families. Moreover the analysis revealed additional candidate linkage loci that may harbour modifier genes for OI; a locus on chromosome 1q includes COX-2, a gene implicated in osteogenesis. Conclusion Technology for physical enrichment of IBD loci is now robust and applicable for finding genes for monogenic diseases and genes for complex diseases. The data support the further investigation of genetic loci other than collagen gene loci to identify genes affecting the clinical expression of osteogenesis imperfecta. The discrimination of IBD mapping will be enhanced when the IBD enrichment procedure is coupled with deep resequencing.

  2. Association analysis of 29,956 individuals confirms that a low-frequency variant at CCND2 halves the risk of type 2 diabetes by enhancing insulin secretion

    DEFF Research Database (Denmark)

    Yaghootkar, Hanieh; Stancáková, Alena; Freathy, Rachel M

    2015-01-01

    × 10(-9); n = 13,927), but the association of the variant with BMI (β = 0.36 kg/m(2); P = 0.02; n = 24,807), estimated in four population-based samples, was less than in the original publication where the effect estimate was biased by analyzing case subjects with type 2 diabetes and control subjects......A recent study identified a low-frequency variant at CCND2 associated with lower risk of type 2 diabetes, enhanced insulin response to a glucose challenge, higher height, and, paradoxically, higher BMI. We aimed to replicate the strength and effect size of these associations in independent samples...... and to assess the underlying mechanism. We genotyped the variant in 29,956 individuals and tested its association with type 2 diabetes and related traits. The low-frequency allele was associated with a lower risk of type 2 diabetes (OR 0.53; P = 2 × 10(-13); 6,647 case vs. 12,645 control subjects), higher...

  3. A Study of A B3R Converter Based PCU, to Confirm the Flexibility and Performance of the Converter Topology

    Directory of Open Access Journals (Sweden)

    Mache Erik

    2017-01-01

    - Conclude the study by comparing the achieved performances (including efficiency and mass versus current solutions implemented on a satellite PCU. Summary of the pros and cons of the use of the B3R concept.

  4. Confirmation of the pathogenicity of a mutation p.G337C in the COL1A2 gene associated with osteogenesis imperfecta

    Science.gov (United States)

    Jia, Mingrui; Shi, Ranran; Zhao, Xuli; Fu, Zhijian; Bai, Zhijing; Sun, Tao; Zhao, Xuejun; Wang, Wenbo; Xu, Chao; Yan, Fang

    2017-01-01

    Abstract Mutation analysis as the gold standard is particularly important in diagnosis of osteogenesis imperfecta (OI) and it may be preventable upon early diagnosis. In this study, we aimed to analyze the clinical and genetic materials of an OI pedigree as well as to confirm the deleterious property of the mutation. A pedigree with OI was identified. All family members received careful clinical examinations and blood was drawn for genetic analyses. Genes implicated in OI were screened for mutation. The function and structure of the mutant protein were predicted using bioinformatics analysis. The proband, a 9-month fetus, showed abnormal sonographic images. Disproportionately short and triangular face with blue sclera was noticed at birth. She can barely walk and suffered multiple fractures till 2-year old. Her mother appeared small stature, frequent fractures, blue sclera, and deformity of extremities. A heterozygous missense mutation c.1009G>T (p.G337C) in the COL1A2 gene was identified in her mother and her. Bioinformatics analysis showed p.G337 was well-conserved among multiple species and the mutation probably changed the structure and damaged the function of collagen. We suggest that the mutation p.G337C in the COL1A2 gene is pathogenic for OI by affecting the protein structure and the function of collagen. PMID:28953610

  5. [Dissecting cellulitis of the scalp: a retrospective study of 7 cases confirming the efficacy of oral isotretinoin].

    Science.gov (United States)

    Koudoukpo, C; Abdennader, S; Cavelier-Balloy, B; Gasnier, C; Yédomon, H

    2014-01-01

    Dissecting cellulitis of the scalp (DCS) is a rare and long-standing disease and its aetiopathogenesis remains unclear. Various therapeutic alternatives exist. We attempted to assess the efficacy of oral isotretinoin in a series of patients. Seven cases of DCS followed and treated by one of the authors at the Sabouraud Centre in the Saint-Louis Hospital between 2007 and 2013 were retrospectively studied and the efficacy of oral isotretinoin was evaluated. The seven patients included were males aged between 22 and 39 years, with alopecic nodules on the occiput (two cases) or the top of the vertex (five cases). Most patients were given oral isotretinoin at a dosage of 0.75mg/kg/day for at least nine months. The outcome was satisfactory with complete healing of the lesions and good regrowth in all cases. Follow-up after recovery lasted between 16 and 42 months. Based on published studies and the results of the present study, oral isotretinoin at a dose of 0.75mg/kg/day may be proposed as first-line treatment for DCS. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  6. Path Integral Monte Carlo Study Confirms a Highly Ordered Snowball in 4He Nanodroplets Doped with an Ar+ Ion

    Science.gov (United States)

    Tramonto, F.; Salvestrini, P.; Nava, M.; Galli, D. E.

    2015-07-01

    By means of the Path Integral Monte Carlo method, we have performed a detailed microscopic study of 4He nanodroplets doped with an argon ion, Ar, at K. We have computed density profiles, energies, dissociation energies, and characterized the local order around the ion for nanodroplets with a number of 4He atoms ranging from 10 to 64 and also 128. We have found the formation of a stable solid structure around the ion, a "snowball", consisting of three concentric shells in which the 4He atoms are placed at the vertices of platonic solids: the first inner shell is an icosahedron (12 atoms); the second one is a dodecahedron with 20 atoms placed on the faces of the icosahedron of the first shell; the third shell is again an icosahedron composed of 12 atoms placed on the faces of the dodecahedron of the second shell. The "magic numbers" implied by this structure, 12, 32, and 44 helium atoms, have been observed in a recent experimental study (Bartl et al., J Phys Chem A 118:8050, 2014) of these complexes; the dissociation energy curve computed in the present work shows jumps in correspondence with those found in the nanodroplets abundance distribution measured in that experiment, strengthening the agreement between theory and experiment. The same structures were predicted in Galli et al. (J Phys Chem A 115:7300, 2011) in a study regarding Na+@4He when ; a comparison between Ar+@4He and Na+@4He complexes is also presented.

  7. Abnormal regional activity and functional connectivity in resting-state brain networks associated with etiology confirmed unilateral pulsatile tinnitus in the early stage of disease.

    Science.gov (United States)

    Lv, Han; Zhao, Pengfei; Liu, Zhaohui; Li, Rui; Zhang, Ling; Wang, Peng; Yan, Fei; Liu, Liheng; Wang, Guopeng; Zeng, Rong; Li, Ting; Dong, Cheng; Gong, Shusheng; Wang, Zhenchang

    2017-03-01

    Abnormal neural activities can be revealed by resting-state functional magnetic resonance imaging (rs-fMRI) using analyses of the regional activity and functional connectivity (FC) of the networks in the brain. This study was designed to demonstrate the functional network alterations in the patients with pulsatile tinnitus (PT). In this study, we recruited 45 patients with unilateral PT in the early stage of disease (less than 48 months of disease duration) and 45 normal controls. We used regional homogeneity (ReHo) and seed-based FC computational methods to reveal resting-state brain activity features associated with pulsatile tinnitus. Compared with healthy controls, PT patients showed regional abnormalities mainly in the left middle occipital gyrus (MOG), posterior cingulate gyrus (PCC), precuneus and right anterior insula (AI). When these regions were defined as seeds, we demonstrated widespread modification of interaction between the auditory and non-auditory networks. The auditory network was positively connected with the cognitive control network (CCN), which may associate with tinnitus related distress. Both altered regional activity and changed FC were found in the visual network. The modification of interactions of higher order networks were mainly found in the DMN, CCN and limbic networks. Functional connectivity between the left MOG and left parahippocampal gyrus could also be an index to reflect the disease duration. This study helped us gain a better understanding of the characteristics of neural network modifications in patients with pulsatile tinnitus. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Family-based association analysis confirms the role of the chromosome 9q21.32 locus in the susceptibility of diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Marcus G Pezzolesi

    Full Text Available A genome-wide association scan of type 1 diabetic patients from the GoKinD collections previously identified four novel diabetic nephropathy susceptibility loci that have subsequently been shown to be associated with diabetic nephropathy in unrelated patients with type 2 diabetes. To expand these findings, we examined whether single nucleotide polymorphisms (SNPs at these susceptibility loci were associated with diabetic nephropathy in patients from the Joslin Study of Genetics of Nephropathy in Type 2 Diabetes Family Collection. Six SNPs across the four loci identified in the GoKinD collections and 7 haplotype tagging SNPs, were genotyped in 66 extended families of European ancestry. Pedigrees from this collection contained an average of 18.5 members, including 2 to 14 members with type 2 diabetes. Among diabetic family members, the 9q21.32 locus approached statistical significance with advanced diabetic nephropathy (P = 0.037 [adjusted P = 0.222]. When we expanded our definition of diabetic nephropathy to include individuals with high microalbuminuria, the strength of this association improved significantly (P = 1.42×10(-3 [adjusted P = 0.009]. This same locus also trended toward statistical significance with variation in urinary albumin excretion in family members with type 2 diabetes (P = 0.032 [adjusted P = 0.192] and in analyses expanded to include all relatives (P = 0.019 [adjusted P = 0.114]. These data increase support that SNPs identified in the GoKinD collections on chromosome 9q21.32 are true diabetic nephropathy susceptibility loci.

  9. A clinically confirmed family history for early myocardial infarction is associated with increased risk of obesity, insulin resistance and metabolic syndrome.

    Science.gov (United States)

    Magnusson, Martin; Burri, Philippe; Melander, Olle

    2012-05-01

    The risk factor pattern underlying a parental history of myocardial infarction (MI) is incompletely understood. We examined whether a parental history of clinically verified early MI may promote development of insulin resistance, obesity and the metabolic syndrome (MetS). One hundred and seventy-four offspring to patients with clinically verified MI before 60 years of age in the population-based prospective Malmo Diet and Cancer (MDC) study were recruited (positive parental history). As controls, we included 174 offspring of MDC participants without MI during 14 years of follow-up in the MDC (negative parental history). MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines, obesity as BMI greater than 30  kg/m and insulin resistance as the top quartile of homeostasis model assessment index in the 348 included offspring (mean age 44 years, 49% women). The odds ratio, 95% confidence interval, for MetS in positive parental history as compared with negative parental history was 2.05, 1.06-4.00 (P = 0.034) after adjustment for age, sex, low-density lipoprotein cholesterol (LDL) and smoking. positive parental history was also independently associated with obesity 2.50, 1.34-4.66 (P = 0.003), abdominal obesity 2.01, 1.21-3.33 (P = 0.007) and insulin resistance 1.97, 1.14-3.40 (P = 0.014), whereas there was no association with LDL and smoking. All of these relationships were stronger in men than in women. Parental history of clinically verified early MI is associated with MetS, obesity and insulin resistance rather than with traditional cardiovascular disease risk factors such as LDL and smoking, suggesting that primary preventive interventions targeted at weight reduction and improvement of insulin sensitivity may be particularly beneficial in this subset of the population.

  10. Effects of BG-12 (dimethyl fumarate) on health-related quality of life in patients with relapsing-remitting multiple sclerosis: findings from the CONFIRM study.

    Science.gov (United States)

    Kita, Mariko; Fox, Robert J; Phillips, J Theodore; Hutchinson, Michael; Havrdova, Eva; Sarda, Sujata P; Agarwal, Sonalee; Kong, Jessica; Zhang, Annie; Viglietta, Vissia; Sheikh, Sarah I; Seidman, Emily; Dawson, Katherine T

    2014-02-01

    Multiple sclerosis (MS) has a significant impact on health-related quality of life (HRQoL) with symptoms adversely affecting many aspects of everyday living. BG-12 (dimethyl fumarate) demonstrated significant efficacy in the phase III studies DEFINE and CONFIRM in patients with relapsing-remitting MS. In CONFIRM, HRQoL was worse in patients with greater disability at baseline, and who relapsed during the study, and improved with BG-12 treatment. Mean Short Form-36 Physical Component Summary scores for BG-12 increased over 2 years and scores for placebo decreased. Coupled with clinical and neuroradiological benefits, these HRQoL results further support BG-12 as an effective oral treatment for relapsing MS.

  11. A descriptive study of biological and psychosocial factors associated ...

    African Journals Online (AJOL)

    Conclusion: This study supports previous findings that a significant association exists between maternal and childhood obesity. The association between BMI and psychotropic medication, nutritional intake and eating habits, and level of physical activity could not be confirmed in our study. The study results were limited by ...

  12. Confirmation and Fine Mapping of a Major QTL for Aflatoxin Resistance in Maize Using a Combination of Linkage and Association Mapping

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2016-09-01

    Full Text Available Maize grain contamination with aflatoxin from Aspergillus flavus (A. flavus is a serious health hazard to animals and humans. To map the quantitative trait loci (QTLs associated with resistance to A. flavus, we employed a powerful approach that differs from previous methods in one important way: it combines the advantages of the genome-wide association analysis (GWAS and traditional linkage mapping analysis. Linkage mapping was performed using 228 recombinant inbred lines (RILs, and a highly significant QTL that affected aflatoxin accumulation, qAA8, was mapped. This QTL spanned approximately 7 centi-Morgan (cM on chromosome 8. The confidence interval was too large for positional cloning of the causal gene. To refine this QTL, GWAS was performed with 558,629 single nucleotide polymorphisms (SNPs in an association population comprising 437 maize inbred lines. Twenty-five significantly associated SNPs were identified, most of which co-localised with qAA8 and explained 6.7% to 26.8% of the phenotypic variation observed. Based on the rapid linkage disequilibrium (LD and the high density of SNPs in the association population, qAA8 was further localised to a smaller genomic region of approximately 1500 bp. A high-resolution map of the qAA8 region will be useful towards a marker-assisted selection (MAS of A. flavus resistance and a characterisation of the causal gene.

  13. Clinical and Epidemiologic Characteristics of Hospitalized Patients with Laboratory-Confirmed Respiratory Syncytial Virus Infection in Eastern China between 2009 and 2013: A Retrospective Study.

    Science.gov (United States)

    Cui, Dawei; Feng, Luzhao; Chen, Yu; Lai, Shengjie; Zhang, Zike; Yu, Fei; Zheng, Shufa; Li, Zhongjie; Yu, Hongjie

    2016-01-01

    Respiratory syncytial virus (RSV) is a leading cause of morbidity and mortality worldwide in children aged acute lower respiratory infections (ALRIs). However, few studies regarding the epidemiology of hospitalizations for RSV infection have been performed previously in China. Here, we aimed to describe the clinical and epidemiologic characteristics of hospitalized patients with laboratory-confirmed RSV infection in eastern China. Active surveillance for hospitalized ALRI patients using a broad case definition based on symptoms was performed from 2009-2013 in 12 sentinel hospitals in eastern China. Clinical and epidemiologic data pertaining to hospitalized patients of all ages with laboratory-confirmed RSV infection by PCR assay were collected and analyzed in this study. From 2009 to 2013, 1046 hospitalized patients with laboratory-confirmed RSV infection were enrolled in this study, and 14.7% of patients had subtype A, 24.2% of patients had subtype B, 23.8% of patients with subtype not performed, and 37.3% of patients had RSV coinfections with other viruses. RSV and influenza coinfections (33.3%) were the most common coinfections noted in this study. Moreover, young children aged infections. In contrast, older adults aged ≥60 years (1.1%, 12/1046) represented the lowest proportion of patients with RSV infections among enrolled patients. The peak RSV infection period occurred mainly during autumn and winter, and 57% and 66% of patients exhibited symptoms such as fever (body temperature ≥38°C) and cough separately. Additionally, only a small number of patients were treated with broad-spectrum antiviral drugs, and most of patients were treated with antimicrobial drugs that were not appropriate for RSV infection. RSV is a leading viral pathogen and a common cause of viral infection in young children aged <5 years with ALRIs in eastern China. Effective vaccines and antiviral agents targeting RSV are needed to mitigate its large public health impact.

  14. ARPES studies of the inverse perovskite Ca3PbO : Experimental confirmation of a candidate 3D Dirac fermion system

    Science.gov (United States)

    Obata, Yukiko; Yukawa, Ryu; Horiba, Koji; Kumigashira, Hiroshi; Toda, Yoshitake; Matsuishi, Satoru; Hosono, Hideo

    2017-10-01

    We investigate the band structure of the inverse perovskite Ca3PbO , a candidate three-dimensional (3D) Dirac fermion material, through soft x-ray angle-resolved photoemission spectroscopy. Conelike band dispersions are observed for Ca3PbO , in close agreement with the predictions of electronic structure calculations. We further demonstrate that chemical substitution of Bi for Pb is effective in tuning the Fermi level of Ca3PbO while leaving its electronic structure intact. Our study confirms that the inverse perovskite family provides a promising platform for the exploration of 3D Dirac fermion systems.

  15. Clinical efficacy of BG-12 (dimethyl fumarate) in patients with relapsing-remitting multiple sclerosis: subgroup analyses of the CONFIRM study.

    LENUS (Irish Health Repository)

    Hutchinson, Michael

    2013-09-01

    In the phase 3, randomized, placebo-controlled and active reference (glatiramer acetate) comparator CONFIRM study in patients with relapsing-remitting multiple sclerosis, oral BG-12 (dimethyl fumarate) reduced the annualized relapse rate (ARR; primary endpoint), as well as the proportion of patients relapsed, magnetic resonance imaging lesion activity, and confirmed disability progression, compared with placebo. We investigated the clinical efficacy of BG-12 240 mg twice daily (BID) and three times daily (TID) in patient subgroups stratified according to baseline demographic and disease characteristics including gender, age, relapse history, McDonald criteria, treatment history, Expanded Disability Status Scale score, T2 lesion volume, and gadolinium-enhancing lesions. BG-12 treatment demonstrated generally consistent benefits on relapse-related outcomes across patient subgroups, reflecting the positive findings in the overall CONFIRM study population. Treatment with BG-12 BID and TID reduced the ARR and the proportion of patients relapsed at 2 years compared with placebo in all subgroups analyzed. Reductions in ARR with BG-12 BID versus placebo ranged from 34% [rate ratio 0.664 (95% confidence interval 0.422-1.043)] to 53% [0.466 (0.313-0.694)] and from 13% [0.870 (0.551-1.373)] to 67% [0.334 (0.226-0.493)] with BG-12 TID versus placebo. Treatment with glatiramer acetate reduced the ARR and the proportion of patients relapsed at 2 years compared with placebo in most patient subgroups. The results of these analyses indicate that treatment with BG-12 is effective on relapses across a broad range of patients with relapsing-remitting multiple sclerosis with varied demographic and disease characteristics.

  16. Confirmation and Extension of Association of Blood Lead with Attention-Deficit/Hyperactivity Disorder (ADHD) and ADHD Symptom Domains at Population-Typical Exposure Levels

    Science.gov (United States)

    Nigg, Joel T.; Nikolas, Molly; Mark Knottnerus, G.; Cavanagh, Kevin; Friderici, Karen

    2010-01-01

    Background: Recent studies have suggested that child attention-deficit/hyperactivity disorder (ADHD) and its symptom domains are related to blood lead level, even at background exposure levels typical in western countries. However, recent studies disagreed as to whether lead was related to inattention or hyperactivity-impulsivity within the ADHD…

  17. Opinion dynamics with confirmation bias.

    Directory of Open Access Journals (Sweden)

    Armen E Allahverdyan

    Full Text Available Confirmation bias is the tendency to acquire or evaluate new information in a way that is consistent with one's preexisting beliefs. It is omnipresent in psychology, economics, and even scientific practices. Prior theoretical research of this phenomenon has mainly focused on its economic implications possibly missing its potential connections with broader notions of cognitive science.We formulate a (non-Bayesian model for revising subjective probabilistic opinion of a confirmationally-biased agent in the light of a persuasive opinion. The revision rule ensures that the agent does not react to persuasion that is either far from his current opinion or coincides with it. We demonstrate that the model accounts for the basic phenomenology of the social judgment theory, and allows to study various phenomena such as cognitive dissonance and boomerang effect. The model also displays the order of presentation effect-when consecutively exposed to two opinions, the preference is given to the last opinion (recency or the first opinion (primacy -and relates recency to confirmation bias. Finally, we study the model in the case of repeated persuasion and analyze its convergence properties.The standard Bayesian approach to probabilistic opinion revision is inadequate for describing the observed phenomenology of persuasion process. The simple non-Bayesian model proposed here does agree with this phenomenology and is capable of reproducing a spectrum of effects observed in psychology: primacy-recency phenomenon, boomerang effect and cognitive dissonance. We point out several limitations of the model that should motivate its future development.

  18. Opinion dynamics with confirmation bias.

    Science.gov (United States)

    Allahverdyan, Armen E; Galstyan, Aram

    2014-01-01

    Confirmation bias is the tendency to acquire or evaluate new information in a way that is consistent with one's preexisting beliefs. It is omnipresent in psychology, economics, and even scientific practices. Prior theoretical research of this phenomenon has mainly focused on its economic implications possibly missing its potential connections with broader notions of cognitive science. We formulate a (non-Bayesian) model for revising subjective probabilistic opinion of a confirmationally-biased agent in the light of a persuasive opinion. The revision rule ensures that the agent does not react to persuasion that is either far from his current opinion or coincides with it. We demonstrate that the model accounts for the basic phenomenology of the social judgment theory, and allows to study various phenomena such as cognitive dissonance and boomerang effect. The model also displays the order of presentation effect-when consecutively exposed to two opinions, the preference is given to the last opinion (recency) or the first opinion (primacy) -and relates recency to confirmation bias. Finally, we study the model in the case of repeated persuasion and analyze its convergence properties. The standard Bayesian approach to probabilistic opinion revision is inadequate for describing the observed phenomenology of persuasion process. The simple non-Bayesian model proposed here does agree with this phenomenology and is capable of reproducing a spectrum of effects observed in psychology: primacy-recency phenomenon, boomerang effect and cognitive dissonance. We point out several limitations of the model that should motivate its future development.

  19. Medication-wide association studies

    NARCIS (Netherlands)

    P.B. Ryan (Patrick); D. Madigan (David); P.E. Stang (Paul); M.J. Schuemie (Martijn); G. Hripcsak (G.)

    2013-01-01

    textabstractUndiscovered side effects of drugs can have a profound effect on the health of the nation, and electronic health-care databases offer opportunities to speed up the discovery of these side effects. We applied a "medication-wide association study" approach that combined multivariate

  20. Opinion Dynamics with Confirmation Bias

    Science.gov (United States)

    Allahverdyan, Armen E.; Galstyan, Aram

    2014-01-01

    Background Confirmation bias is the tendency to acquire or evaluate new information in a way that is consistent with one's preexisting beliefs. It is omnipresent in psychology, economics, and even scientific practices. Prior theoretical research of this phenomenon has mainly focused on its economic implications possibly missing its potential connections with broader notions of cognitive science. Methodology/Principal Findings We formulate a (non-Bayesian) model for revising subjective probabilistic opinion of a confirmationally-biased agent in the light of a persuasive opinion. The revision rule ensures that the agent does not react to persuasion that is either far from his current opinion or coincides with it. We demonstrate that the model accounts for the basic phenomenology of the social judgment theory, and allows to study various phenomena such as cognitive dissonance and boomerang effect. The model also displays the order of presentation effect–when consecutively exposed to two opinions, the preference is given to the last opinion (recency) or the first opinion (primacy) –and relates recency to confirmation bias. Finally, we study the model in the case of repeated persuasion and analyze its convergence properties. Conclusions The standard Bayesian approach to probabilistic opinion revision is inadequate for describing the observed phenomenology of persuasion process. The simple non-Bayesian model proposed here does agree with this phenomenology and is capable of reproducing a spectrum of effects observed in psychology: primacy-recency phenomenon, boomerang effect and cognitive dissonance. We point out several limitations of the model that should motivate its future development. PMID:25007078

  1. Evidence of activation of the Nrf2 pathway in multiple sclerosis patients treated with delayed-release dimethyl fumarate in the Phase 3 DEFINE and CONFIRM studies.

    Science.gov (United States)

    Gopal, Sreeja; Mikulskis, Alvydas; Gold, Ralf; Fox, Robert J; Dawson, Katherine T; Amaravadi, Lakshmi

    2017-12-01

    Delayed-release dimethyl fumarate (DMF) is an approved oral treatment for relapsing forms of multiple sclerosis (MS). Preclinical studies demonstrated that DMF activated the nuclear factor E2-related factor 2 (Nrf2) pathway. DMF and its primary metabolite monomethyl fumarate (MMF) were also shown to promote cytoprotection of cultured central nervous system (CNS) cells via the Nrf2 pathway. To investigate the activation of Nrf2 pathway following ex vivo stimulation of human peripheral blood mononuclear cells (PBMCs) with DMF or MMF, and in DMF-treated patients from two Phase 3 relapsing MS studies DEFINE and CONFIRM. Transcription of Nrf2 target genes NADPH:quinone oxidoreductase-1 (NQO1) and heme-oxygenase-1 (HO1) was measured using Taqman® assays. RNA samples were isolated from ex vivo-stimulated PBMCs and from whole blood samples of 200 patients each from placebo, twice daily (BID) and three times daily (TID) treatments. DMF and MMF induced NQO1 and HO1 gene expression in ex vivo-stimulated PBMCs, DMF being the more potent inducer. Induction of NQO1 occurred at lower DMF concentrations compared to that of HO1. In DMF-treated patients, a statistically significant induction of NQO1 was observed relative to baseline and compared to placebo. No statistical significance was reached for HO1 induction. These data provide the first evidence of Nrf2 pathway activation from two large pivotal Phase 3 studies of DMF-treated MS patients.

  2. Self-reported dietary supplement use is confirmed by biological markers in the Norwegian Mother and Child Cohort Study (MoBa).

    Science.gov (United States)

    Brantsaeter, Anne Lise; Haugen, Margaretha; Hagve, Tor-Arne; Aksnes, Lage; Rasmussen, Salka E; Julshamn, Kåre; Alexander, Jan; Meltzer, Helle Margrete

    2007-01-01

    A food frequency questionnaire (FFQ) and a database for dietary supplements were developed for use in the Norwegian Mother and Child Cohort Study (MoBa). The aim of the present study was to investigate the relation between reported use and biomarkers in supplement and non-supplement users and to validate self-reported intake of dietary supplements in mid pregnancy. 120 women were recruited from MoBa, and 119 subjects completed the MoBa FFQ and a 4-day weighed food diary. Information on supplement use was collected by both methods. Venous blood specimens and 24-hour urine samples were obtained for measurement of dietary biomarkers. Biomarker concentration/excretion and intake differed significantly between supplement and non-supplement users for vitamin D, carotenoids, folate, the n-6/n-3 fatty acid ratio and iodine (p < 0.05 for all variables). Flavonoid excretion was higher in flavonoid-supplement users (p < 0.05). Significant correlations between total dietary intake (food and supplements) and biomarker concentration/excretion were found for vitamin D (r = 0.45, p < 0.001), folate (r = 0.26, p = 0.005), the n-6/n-3 fatty acid ratio (r = 0.36, p < 0.001) and iodine (r = 0.42, p < 0.001). The biochemical indicators examined in this study confirmed differences in self-reported micronutrient intake between supplement and non-supplement users for vitamin D, beta-carotene, folate, n-3 fatty acids, flavonoids and iodine. Copyright 2007 S. Karger AG, Basel.

  3. Human leptospirosis in Seychelles: A prospective study confirms the heavy burden of the disease but suggests that rats are not the main reservoir.

    Directory of Open Access Journals (Sweden)

    Leon Biscornet

    2017-08-01

    Full Text Available Leptospirosis is a bacterial zoonosis caused by pathogenic Leptospira for which rats are considered as the main reservoir. Disease incidence is higher in tropical countries, especially in insular ecosystems. Our objectives were to determine the current burden of leptospirosis in Seychelles, a country ranking first worldwide according to historical data, to establish epidemiological links between animal reservoirs and human disease, and to identify drivers of transmission.A total of 223 patients with acute febrile symptoms of unknown origin were enrolled in a 12-months prospective study and tested for leptospirosis through real-time PCR, IgM ELISA and MAT. In addition, 739 rats trapped throughout the main island were investigated for Leptospira renal carriage. All molecularly confirmed positive samples were further genotyped.A total of 51 patients fulfilled the biological criteria of acute leptospirosis, corresponding to an annual incidence of 54.6 (95% CI 40.7-71.8 per 100,000 inhabitants. Leptospira carriage in Rattus spp. was overall low (7.7% but dramatically higher in Rattus norvegicus (52.9% than in Rattus rattus (4.4%. Leptospira interrogans was the only detected species in both humans and rats, and was represented by three distinct Sequence Types (STs. Two were novel STs identified in two thirds of acute human cases while noteworthily absent from rats.This study shows that human leptospirosis still represents a heavy disease burden in Seychelles. Genotype data suggests that rats are actually not the main reservoir for human disease. We highlight a rather limited efficacy of preventive measures so far implemented in Seychelles. This could result from ineffective control measures of excreting animal populations, possibly due to a misidentification of the main contaminating reservoir(s. Altogether, presented data stimulate the exploration of alternative reservoir animal hosts.

  4. Human leptospirosis in Seychelles: A prospective study confirms the heavy burden of the disease but suggests that rats are not the main reservoir

    Science.gov (United States)

    Biscornet, Leon; Dellagi, Koussay; Pagès, Frédéric; Bibi, Jastin; de Comarmond, Jeanine; Mélade, Julien; Govinden, Graham; Tirant, Maria; Gomard, Yann; Guernier, Vanina; Lagadec, Erwan; Mélanie, Jimmy; Rocamora, Gérard; Le Minter, Gildas; Jaubert, Julien; Mavingui, Patrick

    2017-01-01

    Background Leptospirosis is a bacterial zoonosis caused by pathogenic Leptospira for which rats are considered as the main reservoir. Disease incidence is higher in tropical countries, especially in insular ecosystems. Our objectives were to determine the current burden of leptospirosis in Seychelles, a country ranking first worldwide according to historical data, to establish epidemiological links between animal reservoirs and human disease, and to identify drivers of transmission. Methods A total of 223 patients with acute febrile symptoms of unknown origin were enrolled in a 12-months prospective study and tested for leptospirosis through real-time PCR, IgM ELISA and MAT. In addition, 739 rats trapped throughout the main island were investigated for Leptospira renal carriage. All molecularly confirmed positive samples were further genotyped. Results A total of 51 patients fulfilled the biological criteria of acute leptospirosis, corresponding to an annual incidence of 54.6 (95% CI 40.7–71.8) per 100,000 inhabitants. Leptospira carriage in Rattus spp. was overall low (7.7%) but dramatically higher in Rattus norvegicus (52.9%) than in Rattus rattus (4.4%). Leptospira interrogans was the only detected species in both humans and rats, and was represented by three distinct Sequence Types (STs). Two were novel STs identified in two thirds of acute human cases while noteworthily absent from rats. Conclusions This study shows that human leptospirosis still represents a heavy disease burden in Seychelles. Genotype data suggests that rats are actually not the main reservoir for human disease. We highlight a rather limited efficacy of preventive measures so far implemented in Seychelles. This could result from ineffective control measures of excreting animal populations, possibly due to a misidentification of the main contaminating reservoir(s). Altogether, presented data stimulate the exploration of alternative reservoir animal hosts. PMID:28846678

  5. Human leptospirosis in Seychelles: A prospective study confirms the heavy burden of the disease but suggests that rats are not the main reservoir.

    Science.gov (United States)

    Biscornet, Leon; Dellagi, Koussay; Pagès, Frédéric; Bibi, Jastin; de Comarmond, Jeanine; Mélade, Julien; Govinden, Graham; Tirant, Maria; Gomard, Yann; Guernier, Vanina; Lagadec, Erwan; Mélanie, Jimmy; Rocamora, Gérard; Le Minter, Gildas; Jaubert, Julien; Mavingui, Patrick; Tortosa, Pablo

    2017-08-01

    Leptospirosis is a bacterial zoonosis caused by pathogenic Leptospira for which rats are considered as the main reservoir. Disease incidence is higher in tropical countries, especially in insular ecosystems. Our objectives were to determine the current burden of leptospirosis in Seychelles, a country ranking first worldwide according to historical data, to establish epidemiological links between animal reservoirs and human disease, and to identify drivers of transmission. A total of 223 patients with acute febrile symptoms of unknown origin were enrolled in a 12-months prospective study and tested for leptospirosis through real-time PCR, IgM ELISA and MAT. In addition, 739 rats trapped throughout the main island were investigated for Leptospira renal carriage. All molecularly confirmed positive samples were further genotyped. A total of 51 patients fulfilled the biological criteria of acute leptospirosis, corresponding to an annual incidence of 54.6 (95% CI 40.7-71.8) per 100,000 inhabitants. Leptospira carriage in Rattus spp. was overall low (7.7%) but dramatically higher in Rattus norvegicus (52.9%) than in Rattus rattus (4.4%). Leptospira interrogans was the only detected species in both humans and rats, and was represented by three distinct Sequence Types (STs). Two were novel STs identified in two thirds of acute human cases while noteworthily absent from rats. This study shows that human leptospirosis still represents a heavy disease burden in Seychelles. Genotype data suggests that rats are actually not the main reservoir for human disease. We highlight a rather limited efficacy of preventive measures so far implemented in Seychelles. This could result from ineffective control measures of excreting animal populations, possibly due to a misidentification of the main contaminating reservoir(s). Altogether, presented data stimulate the exploration of alternative reservoir animal hosts.

  6. Metastatic colorectal adenocarcinoma in cervicovaginal cytology specimens confirmed by immunocytochemical stains on liquid base specimens: Two study cases with review of the literature

    Directory of Open Access Journals (Sweden)

    Muhammad Zulfiqar

    2013-01-01

    Full Text Available Only a few cases of adenocarcinoma (ACA metastatic to the female lower genital tract diagnosed on cervicovaginal Pap smear have been reported during the past several decades. Both conventional and liquid based cytology (LBC have limited sensitivity and specificity in diagnosing metastatic disease and immunocytochemical (ICC staining may be needed for confirming the diagnosis. We present two cases of metastatic colorectal ACA diagnosed on cervicovaginal ThinPrep (TP Pap smears, with one confirmed by ICC staining method. Recognition of extra-uterine malignancy in the cervicovaginal cytology specimen is critical for the disease diagnosis, prognosis, and the treatment. ICC staining performed on the residual LBC specimen is an important methodology to confirm the diagnosis.

  7. Physiological studies in heterozygous calcium sensing receptor (CaSR gene-ablated mice confirm that the CaSR regulates calcitonin release in vivo

    Directory of Open Access Journals (Sweden)

    Kovacs Christopher S

    2004-04-01

    Full Text Available Abstract Background The calcium sensing receptor (CaSR regulates serum calcium by suppressing secretion of parathyroid hormone; it also regulates renal tubular calcium excretion. Inactivating mutations of CaSR raise serum calcium and reduce urine calcium excretion. Thyroid C-cells (which make calcitonin express CaSR and may, therefore, be regulated by it. Since calcium stimulates release of calcitonin, the higher blood calcium caused by inactivation of CaSR should increase serum calcitonin, unless CaSR mutations alter the responsiveness of calcitonin to calcium. To demonstrate regulatory effects of CaSR on calcitonin release, we studied calcitonin responsiveness to calcium in normal and CaSR heterozygous-ablated (Casr+/- mice. Casr+/- mice have hypercalcemia and hypocalciuria, and live normal life spans. Each mouse received either 500 μl of normal saline or one of two doses of elemental calcium (500 μmol/kg or 5 mmol/kg by intraperitoneal injection. Ionized calcium was measured at baseline and 10 minutes, and serum calcitonin was measured on the 10 minute sample. Results At baseline, Casr+/- mice had a higher blood calcium, and in response to the two doses of elemental calcium, had greater increments and peak levels of ionized calcium than their wild type littermates. Despite significantly higher ionized calcium levels, the calcitonin levels of Casr+/- mice were consistently lower than wild type at any ionized calcium level, indicating that the dose-response curve of calcitonin to increases in ionized calcium had been significantly blunted or shifted to the right in Casr+/- mice. Conclusions These results confirm that the CaSR is a physiological regulator of calcitonin; therefore, in response to increases in ionized calcium, the CaSR inhibits parathyroid hormone secretion and stimulates calcitonin secretion.

  8. Prospective study of p-[{sup 123}I]iodo-L-phenylalanine and SPECT for the evaluation of newly diagnosed cerebral lesions: specific confirmation of glioma

    Energy Technology Data Exchange (ETDEWEB)

    Hellwig, Dirk; Schaefer, Andrea; Farmakis, Georgios; Grgic, Aleksandar; Kirsch, Carl-Martin [Saarland University Medical Center, Department of Nuclear Medicine, Homburg/Saar (Germany); Ketter, Ralf; Moringlane, Jean R.; Steudel, Wolf-Ingo [Saarland University Medical Center, Department of Neurosurgery, Homburg (Germany); Romeike, Bernd F.M. [Saarland University Medical Center, Institute of Neuropathology, Homburg (Germany); Friedrich-Schiller-University, Department of Neuropathology, Jena (Germany); Samnick, Samuel [Saarland University Medical Center, Department of Nuclear Medicine, Homburg/Saar (Germany); University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany)

    2010-12-15

    The differentiation between gliomas, metastases and gliotic or inflammatory lesions by imaging techniques remains a challenge. Gliomas frequently exhibit increased uptake of radiolabelled amino acids and are thus amenable to PET or SPECT imaging. Recently, p-[{sup 123}I]iodo-L-phenylalanine (IPA) was validated for the visualization of glioma by SPECT and received orphan drug status. Here we investigated its diagnostic performance for differentiating indeterminate brain lesions. This prospective open study included 67 patients with newly diagnosed brain lesions suspicious for glioma (34 without and 33 with contrast enhancement in the MRI scan). Patients received 250 MBq IPA intravenously after overnight fasting. SPECT images at 30 min and 3 h post-injection were iteratively reconstructed and visually interpreted after image fusion with an MRI brain scan (fluid-attenuated inversion recovery sequence or T1-weighted contrast-enhanced image). Findings were correlated with results of stereotactic or open biopsies or serial imaging. Twenty-seven low-grade (2 WHO I, 25 WHO II) and 24 high-grade gliomas (1 WHO III, 23 WHO IV), 3 metastases originating from lung cancer as well as 13 non-neoplastic lesions were proven. All non-neoplastic lesions and all metastases were negative with IPA SPECT. Forty gliomas were true-positive (TP) and 11 false-negative (FN) findings (8 WHO II, 1 WHO III, 2 WHO IV) occurred. There were no false-positive (FP) findings. For the differentiation of primary brain tumours and non-neoplastic lesions, sensitivity and specificity were 78 and 100%. In 34 lesions without contrast enhancement in MRI, IPA SPECT resulted in 17 TP, 8 true-negative, 9 FN and no FP findings (sensitivity 65%, specificity 100%). In patients with suspected glioma, IPA SPECT shows a high specificity, but especially in low-grade gliomas FN findings may occur. Due to the high positive predictive value a positive finding allows a suspected glioma to be confirmed. (orig.)

  9. A randomized, placebo-controlled, double-blind study to confirm the reversal of hepatorenal syndrome type 1 with terlipressin: the REVERSE trial design

    Directory of Open Access Journals (Sweden)

    Boyer TD

    2012-07-01

    Full Text Available Thomas D Boyer,1 Joseph J Medicis,2 Stephen Chris Pappas,3 Jim Potenziano,2 Khuramm Jamil21Department of Medicine, University of Arizona College of Medicine, Tucson, AZ, USA; 2Research and Development, Ikaria, Hampton, NJ, USA; 3Orphan Therapeutics, Lebanon, NJ, USABackground: Hepatorenal syndrome (HRS is a rare disorder of marked renal dysfunction in patients with cirrhosis, ascites, and portal hypertension. Type 1 HRS is a rapidly progressive acute kidney injury that develops shortly after a precipitating event, followed by a deterioration of function of other organs (eg, heart, brain, liver, adrenal glands. Presently, no approved drug therapies exist for HRS type 1 in the USA, Canada, or Australia. Given the rarity of this condition and the existing unmet medical need for treatment, the US Food and Drug Administration granted orphan drug and fast-track designations for terlipressin. The objective of the REVERSE trial was to determine the efficacy and safety of intravenous terlipressin compared with placebo in the treatment of adults with HRS type 1 who were also receiving intravenous albumin.Methods: 180 subjects with HRS type 1 were enrolled at 65 investigational sites located in the USA and ten sites in Canada. Patients were randomized in a 1:1 ratio to treatment with either intravenous terlipressin administered every 6 hours or placebo for up to 14 days. The primary efficacy measure was confirmed HRS reversal, defined as the percentage of patients with two serum creatinine values of ≤1.5 mg/dL at least 48 hours apart, on treatment, and without intervening renal replacement therapy or liver transplantation. Other efficacy measures included change in renal function as reflected in serum creatinine levels, fractional excretion of sodium, recurrence of HRS type 1, transplant-free, dialysis-free, and overall survival.Discussion: Data from this pivotal study are intended to demonstrate whether terlipressin is effective in reversing HRS type 1

  10. Studying risk factors associated with Human Leptospirosis

    Directory of Open Access Journals (Sweden)

    Ramachandra Kamath

    2014-01-01

    Full Text Available Background: Leptospirosis is one of the most under diagnosed and underreported disease in both developed and developing countries including India. It is established that environmental conditions and occupational habit of the individuals put them at risk of acquiring disease, which varies from community to community. Various seroprevalence studies across the world have documented emerging situation of this neglected tropical disease, but limited have probed to identify the risk factors, especially in India. Objectives: The objective of this study was to identify the environmental and occupational risk factors associated with the disease in Udupi District. Materials and Methods: This population-based case-control study was carried out in Udupi, a District in Southern India from April 2012 until August 2012. Udupi is considered to be endemic for Leptospirosis and reported 116 confirmed cases in the year 2011. Seventy of 116 laboratory confirmed cases and 140 sex matched neighborhood healthy controls participated in the study. A predesigned, semi-structured and validated questionnaire was used for data collection through house to house visit and observations were noted about environmental conditions. Univariate analysis followed by multivariate analysis (back ward conditional logistic regression was performed by using STATA version 9.2 (StataCorp, College Station, TX, USA to identify potential risk factors. Results: Occupational factors such as outdoor activities (matched odds ratio [OR] of 3.95, 95% confidence interval [CI]: 1.19-13.0, presence of cut or wound at body parts during work (matched OR: 4.88, CI: 1.83-13.02 and environmental factors such as contact with rodents through using the food materials ate by rat (matched OR: 4.29, CI: 1.45-12.73 and contact with soil or water contaminated with urine of rat (matched OR: 4.58, CI: 1.43-14.67 were the risk factors identified to be associated with disease. Conclusion: Leptospirosis is still

  11. Genomic and genotoxic responses to controlled weathered-oil exposures confirm and extend field studies on impacts of the Deepwater Horizon oil spill on native killifish.

    Directory of Open Access Journals (Sweden)

    Whitney Pilcher

    Full Text Available To understand the ecotoxicological impacts of the Deepwater Horizon oil spill, field studies provide a context for ecological realism but laboratory-based studies offer power for connecting biological effects with specific causes. As a complement to field studies, we characterized genome-wide gene expression responses of Gulf killifish (Fundulus grandis to oil-contaminated waters in controlled laboratory exposures. Transcriptional responses to the highest concentrations of oiled water in the laboratory were predictive of field-observed responses that coincided with the timing and location of major oiling. The transcriptional response to the low concentration (∼ 10-fold lower than the high concentration was distinct from the high concentration and was not predictive of major oiling in the field. The high concentration response was characterized by activation of the molecular signaling pathway that facilitates oil metabolism and oil toxicity. The high concentration also induced DNA damage. The low concentration invoked expression of genes that may support a compensatory response, including genes associated with regulation of transcription, cell cycle progression, RNA processing, DNA damage, and apoptosis. We conclude that the gene expression response detected in the field was a robust indicator of exposure to the toxic components of contaminating oil, that animals in the field were exposed to relatively high concentrations that are especially damaging to early life stages, and that such exposures can damage DNA.

  12. Preoperative Quantitative MR Tractography Compared with Visual Tract Evaluation in Patients with Neuropathologically Confirmed Gliomas Grades II and III: A Prospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Anna F. Delgado

    2016-01-01

    Full Text Available Background and Purpose. Low-grade gliomas show infiltrative growth in white matter tracts. Diffusion tensor tractography can noninvasively assess white matter tracts. The aim was to preoperatively assess tumor growth in white matter tracts using quantitative MR tractography (3T. The hypothesis was that suspected infiltrated tracts would have altered diffusional properties in infiltrated tract segments compared to noninfiltrated tracts. Materials and Methods. Forty-eight patients with suspected low-grade glioma were included after written informed consent and underwent preoperative diffusion tensor imaging in this prospective review-board approved study. Major white matter tracts in both hemispheres were tracked, segmented, and visually assessed for tumor involvement in thirty-four patients with gliomas grade II or III (astrocytomas or oligodendrogliomas on postoperative neuropathological evaluation. Relative fractional anisotropy (rFA and mean diffusivity (rMD in tract segments were calculated and compared with visual evaluation and neuropathological diagnosis. Results. Tract segment infiltration on visual evaluation was associated with a lower rFA and high rMD in a majority of evaluated tract segments (89% and 78%, resp.. Grade II and grade III gliomas had similar infiltrating behavior. Conclusion. Quantitative MR tractography corresponds to visual evaluation of suspected tract infiltration. It may be useful for an objective preoperative evaluation of tract segment involvement.

  13. Influenza vaccine effectiveness in preventing hospitalizations with laboratory-confirmed influenza in Greece during the 2014-2015 season: A test-negative study.

    Science.gov (United States)

    Lytras, Theodore; Kossyvakis, Athanasios; Melidou, Angeliki; Andreopoulou, Anastasia; Exindari, Maria; Gioula, Georgia; Kalliaropoulos, Antonios; Tryfinopoulou, Kyriaki; Pogka, Vasiliki; Spala, Georgia; Malisiovas, Nikolaos; Mentis, Andreas

    2016-11-01

    The 2014-2015 influenza season was marked by circulation of antigenically drifted A/H3N2 strains, raising the possibility of low seasonal influenza Vaccine Effectiveness (VE). We assessed VE against hospitalization with laboratory-confirmed influenza for the 2014-2015 season, using routine surveillance data. Non-sentinel swab samples from Greek hospital inpatients were tested for influenza by RT-PCR in three laboratories, covering the entire country. We estimated VE using a test-negative design. Out of 883 patients with known vaccination status, 161 (18.2%) were vaccinated, and 392/883 patients (44.4%) tested positive for influenza, of whom 162 (41.3%) had type B and 151 (38.5%) had A/H3N2. Adjusted VE was 31.6% (95%CI: 2.9-51.8%) against any influenza, 46.8%, 95%CI: 12.5-67.6%) against type B and -1.9%, 95%CI: -69.5 to 38.7%) against A/H3N2. VE against non-ICU hospitalization appeared to be higher, but the difference did not reach statistical significance. Circulating A/H3N2 viruses showed substantial antigenic drift, while about half of the type B strains were similar to the vaccine strain. Despite the antigenic drift of the A/H3N2 strains, the vaccine still offered substantial protection against hospitalization with laboratory-confirmed influenza, mostly due to a surge in type B influenza late in the season. Vaccine coverage was low, even among groups targeted for vaccination, and considerable effort should be made to improve it. J. Med. Virol. 88:1896-1904, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Performance Confirmation Data Aquisition System

    Energy Technology Data Exchange (ETDEWEB)

    D.W. Markman

    2000-10-27

    The purpose of this analysis is to identify and analyze concepts for the acquisition of data in support of the Performance Confirmation (PC) program at the potential subsurface nuclear waste repository at Yucca Mountain. The scope and primary objectives of this analysis are to: (1) Review the criteria for design as presented in the Performance Confirmation Data Acquisition/Monitoring System Description Document, by way of the Input Transmittal, Performance Confirmation Input Criteria (CRWMS M&O 1999c). (2) Identify and describe existing and potential new trends in data acquisition system software and hardware that would support the PC plan. The data acquisition software and hardware will support the field instruments and equipment that will be installed for the observation and perimeter drift borehole monitoring, and in-situ monitoring within the emplacement drifts. The exhaust air monitoring requirements will be supported by a data communication network interface with the ventilation monitoring system database. (3) Identify the concepts and features that a data acquisition system should have in order to support the PC process and its activities. (4) Based on PC monitoring needs and available technologies, further develop concepts of a potential data acquisition system network in support of the PC program and the Site Recommendation and License Application.

  15. Genomic and genotoxic responses to controlled weathered-oil exposures confirm and extend field studies on impacts of the Deepwater Horizon oil spill on native killifish

    National Research Council Canada - National Science Library

    Pilcher, Whitney; Miles, Scott; Tang, Song; Mayer, Greg; Whitehead, Andrew

    2014-01-01

    To understand the ecotoxicological impacts of the Deepwater Horizon oil spill, field studies provide a context for ecological realism but laboratory-based studies offer power for connecting biological...

  16. Confirmation of shutdown cooling effects

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Kotaro, E-mail: ksato@nelted.co.jp; Tabuchi, Masato; Sugimura, Naoki; Tatsumi, Masahiro [Nuclear Engineering, Limited, 1-3-7 Tosabori Nishi-ku, Osaka-shi, Osaka 550-0001 (Japan)

    2015-12-31

    After the Fukushima accidents, all nuclear power plants in Japan have gradually stopped their operations and have long periods of shutdown. During those periods, reactivity of fuels continues to change significantly especially for high-burnup UO{sub 2} fuels and MOX fuels due to radioactive decays. It is necessary to consider these isotopic changes precisely, to predict neutronics characteristics accurately. In this paper, shutdown cooling (SDC) effects of UO{sub 2} and MOX fuels that have unusual operation histories are confirmed by the advanced lattice code, AEGIS. The calculation results show that the effects need to be considered even after nuclear power plants come back to normal operation.

  17. Constructing, Confirming, and Contesting Icons

    DEFF Research Database (Denmark)

    Mortensen, Mette

    2017-01-01

    to their reception as they help shape and delimit the publics and discourses surrounding visual icons. This article draws on existing research on visual icons and appropriations to develop a theoretical framework for how appropriations construct, confirm and contest icons and how personification constitutes the main...... link between icons and their appropriations. Three sets of appropriations are analyzed of the iconic imagery of Alan Kurdi, the refugee boy drowning in the Mediterranean in 2015. First, the numerous appropriations circulated under the Twitter hashtag #humanitywashedashore. Based on genre analysis...

  18. UV-visible marker confirms that environmental persistence of Clostridium difficile spores in toilets of patients with C. difficile-associated diarrhea is associated with lack of compliance with cleaning protocol.

    Directory of Open Access Journals (Sweden)

    Papetti Selena

    2008-05-01

    Full Text Available Abstract Background An ultraviolet visible marker (UVM was used to assess the cleaning compliance of housekeeping staff for toilets in a tertiary healthcare setting. Methods The UVM was applied to the toilets of patients who were on isolation precautions due to Clostridium difficile-associated diarrhea (CDAD as well as for patients who were not on isolation precautions. Cleaning was visually scored using a numeric system where 0, 1, 2, and 3 represented; no, light, moderate or heavy residual UVM. Rodac plates containing CDMN selective agar were used to test for the presence of C. difficile on the surfaces of patient's toilets. Results Despite twice daily cleaning for the toilets of patients who were on CDAD isolation precautions, the average cleaning score was 1.23 whereas the average cleaning score for toilets of patients not on isolation precautions was 0.9. Even with optimal cleaning (UVM score of 0 C. difficile was detected from 33% of the samples taken from toilets of patients with CDAD (4% detection in toilet samples from patients who had diarrhea not due to CDAD. Conclusion Our data demonstrated the value of UVM for monitoring the compliance of housekeeping staff with the facility's toilet cleaning protocol. In addition to providing good physical cleaning action, agents with some sporicidal activity against C. difficile may be needed to effectively reduce the environmental reservoir.

  19. Self-reported dietary supplement use is confirmed by biological markers in the Norwegian Mother and Child Cohort Study (MoBa)

    DEFF Research Database (Denmark)

    Brantsæter, Anne Lise; Haugen, Margaretha; Hagve, Tor-Arne

    2007-01-01

    Background/ Aims: A food frequency questionnaire ( FFQ) and a database for dietary supplements were developed for use in the Norwegian Mother and Child Cohort Study ( MoBa). The aim of the present study was to investigate the relation between reported use and biomarkers in supplement and nonsuppl...

  20. Antibiotic prescribing practices for patients with fever in the transition from presumptive treatment of malaria to 'confirm and treat' in Zambia: a cross-sectional study.

    Science.gov (United States)

    Ndhlovu, Micky; Nkhama, Emmy; Miller, John M; Hamer, Davidson H

    2015-12-01

    To evaluate antibiotic use among patients presenting to primary healthcare facilities with febrile illness in Zambia. We analysed data from a 2011 nationwide cross-sectional health facility survey of routine malaria case management in Zambia. Patient consultation observation and medical record charts were used to calculate the proportion of febrile patients who were prescribed antibiotics, stratified by symptoms, health workers' diagnosis and malaria test results. Logistic regression was used to identify factors affecting antibiotic prescribing behaviour. Of 872 patients presenting with fever, 651 (74.6%) were tested for malaria. Among those tested, 608 (93.4%) had analysable results; 230 (37.8%) had positive results. Antibiotics were prescribed to 69/230 (30.0%), 247/378 (65.3%) and 132/221 (59.7%) of those who tested positive, negative and those 'not tested', respectively. Furthermore, antibiotics were prescribed to 36/59 (61.0%) and 242/322 (75.1%) of those diagnosed with diarrhoea and upper respiratory tract infection (URTI), respectively. Among patients prescribed any antibiotic, concurrent antimalarial prescribing occurred in 66/69 (95.6%), 32/247 (12.9%) and 19/132 (14.4%) for those with positive results, negative results and 'not tested', respectively. Respiratory symptoms, diagnosis of URTI, malaria or skin disease and level of health care in the health delivery system were associated with antibiotic prescribing. Testing positive for malaria or receiving a malaria diagnosis was associated with reduced antibiotic prescribing, while testing negative, not being tested or a diagnosis of URTI resulted in higher rates of antibiotic prescribing. There is a need for improving diagnostic capacity for non-malaria causes of febrile illness at healthcare delivery points and limiting antibiotic use to patients with definite bacterial infections. © 2015 John Wiley & Sons Ltd.

  1. Use of fine needle aspirate from peripheral nerves of pure-neural leprosy for cytology and PCR to confirm the diagnosis: A pilot study

    Directory of Open Access Journals (Sweden)

    Abu Hena Hasanoor Reja

    2013-01-01

    Full Text Available Background: The diagnosis of pure neural leprosy (PNL remained subjective because of over-dependence of clinical expertise and a lack of simple yet reliable diagnostic tool. The criteria for diagnosis, proposed by Jardim et al., are not routinely done by clinicians in developing country as it involves invasive nerve biopsy and sophisticated anti-PGL-1 detection. We conducted a study using fine needle aspiration cytology (FNAC coupled with Ziehl Neelsen staining (ZN staining and Multiplex- Polymerase Chain Reaction (PCR specific for M. leprae for an objective diagnosis of pure neural leprosy (PNL, which may be simpler and yet reliable. Aim: The aim of the study is to couple FNAC with ZN staining and multiplex PCR to diagnose pure neural leprosy patients rapidly, in simpler and yet reliable way. Methods: Thirteen patients of PNL as diagnosed by two independent consultants were included as case, and 5 patients other than PNL were taken as control in the study. Fine needle aspiration was done on the affected nerve, and aspirates were evaluated for cytology, ZN staining and multiplex- PCR. Results: Out of the 13 cases where fine needle aspiration was done, M. leprae could be elicited in the nerve tissue aspirates in 5 cases (38.4% with the help of conventional acid-fast staining and 11 cases (84.6% with the help of multiplex PCR. On cytological examination of the aspirates, only 3 (23% cases showed specific epithelioid cells, whereas 8 (61.5% cases showed non-specific inflammation, and 2 (15.3% cases had no inflammatory cells. Conclusion: Our study demonstrates that in the field of laboratory diagnosis of PNL cases, FNAC in combination with ZN staining for acid-fast bacilli (AFB and Multiplex-PCR can provide a rapid and definitive diagnosis for the majority of PNL cases. FNAC is a less-invasive, outdoor-based and simpler technique than invasive nerve biopsy procedure. Thus, this study may enlighten the future path for easy and reliable diagnosis of

  2. Influence of demographics on clinical outcome of dengue: a cross-sectional study of 6703 confirmed cases in Vitória, Espírito Santo State, Brazil.

    Science.gov (United States)

    Vicente, C R; Cerutti Junior, C; Fröschl, G; Romano, C M; Cabidelle, A S A; Herbinger, K-H

    2017-01-01

    Dengue presents a wide clinical spectrum of signs and symptoms, with characteristics of the host potentially influencing the disease evolution. Therefore, the purpose of this study was to evaluate the influence of gender and age on dengue clinical outcomes in a recent outbreak situation in Brazil, applying a cross-sectional design and including 6703 dengue cases with laboratory confirmation, occurring in Vitória, Espírito Santo State, Brazil, between 2007 and 2013. Data were obtained from the Information System for Notifiable Diseases. Overall, 11·3% of the sample presented with severe dengue, which affected 13·0% of males, 10·0% of females, 8·8% of children, 12·5% of adolescents, 10·5% of adults and 15·5% of the elderly. Age was higher in the severe dengue group (P = 0·03). Severe dengue was associated with males and the elderly (P dengue cases, taking into consideration host factors like age. These findings also suggest the elderly and children as priority groups for immunization in a future implementation of a vaccine.

  3. Performance confirmation data acquisition system

    Energy Technology Data Exchange (ETDEWEB)

    McAffee, D.A.; Raczka, N.T. [Yucca Mountain Project, Las Vegas, NV (United States)

    1997-12-31

    As part of the Viability Assessment (VA) work, this QAP-3-9 document presents and evaluates a comprehensive set of viable concepts for collecting Performance Confirmation (PC) related data. The concepts include: monitoring subsurface repository air temperatures, humidity levels and gaseous emissions via the subsurface ventilation systems, and monitoring the repository geo-technical parameters and rock mass from bore-holes located along the perimeter main drifts and throughout a series of human-rated Observation Drifts to be located in a plane 25 meters above the plane of the emplacement drifts. A key element of this document is the development and analysis of a purposed multi-purpose Remote Inspection Gantry that would provide direct, real-time visual, thermal, and radiological monitoring of conditions inside operational emplacement drifts and close-up observations of in-situ Waste Packages. Preliminary finite-element analyses are presented that indicate the technological feasibility of operating an inspection gantry inside the operational emplacement drifts for short inspection missions lasting 2--3 hours. Overall reliability, availability, and maintainability of the PC data collection concepts are discussed. Preliminary concepts for PC data collection network are also provided.

  4. Estimation of arterial input by a noninvasive image derived method in brain H215O PET study: confirmation of arterial location using MR angiography.

    Science.gov (United States)

    Islam, Muhammad Muinul; Tsujikawa, Tetsuya; Mori, Tetsuya; Kiyono, Yasushi; Okazawa, Hidehiko

    2017-03-31

    A noninvasive method to estimate input function directly from H215O brain PET data for measurement of cerebral blood flow (CBF) was proposed in this study. The image derived input function (IDIF) method extracted the time-activity curves (TAC) of the major cerebral arteries at the skull base from the dynamic PET data. The extracted primordial IDIF showed almost the same radioactivity as the arterial input function (AIF) from sampled blood at the plateau part in the later phase, but significantly lower radioactivity in the initial arterial phase compared with that of AIF-TAC. To correct the initial part of the IDIF, a dispersion function was applied and two constants for the correction were determined by fitting with the individual AIF in 15 patients with unilateral arterial stenoocclusive lesions. The area under the curves (AUC) from the two input functions showed good agreement with the mean AUCIDIF/ AUCAIF ratio of 0.92 ± 0.09. The final products of CBF and arterial-to-capillary vascular volume (V0) obtained from the IDIF and AIF showed no difference, and had with high correlation coefficients. Creative Commons Attribution license.

  5. Extended Follow-up Confirms Early Vaccine-Enhanced Risk of HIV Acquisition and Demonstrates Waning Effect Over Time Among Participants in a Randomized Trial of Recombinant Adenovirus HIV Vaccine (Step Study)

    Science.gov (United States)

    Duerr, Ann; Huang, Yunda; Buchbinder, Susan; Coombs, Robert W.; Sanchez, Jorge; del Rio, Carlos; Casapia, Martin; Santiago, Steven; Gilbert, Peter; Corey, Lawrence; Robertson, Michael N.

    2012-01-01

    Background. The Step Study tested whether an adenovirus serotype 5 (Ad5)–vectored human immunodeficiency virus (HIV) vaccine could prevent HIV acquisition and/or reduce viral load set-point after infection. At the first interim analysis, nonefficacy criteria were met. Vaccinations were halted; participants were unblinded. In post hoc analyses, more HIV infections occurred in vaccinees vs placebo recipients in men who had Ad5-neutralizing antibodies and/or were uncircumcised. Follow-up was extended to assess relative risk of HIV acquisition in vaccinees vs placebo recipients over time. Methods. We used Cox proportional hazard models for analyses of vaccine effect on HIV acquisition and vaccine effect modifiers, and nonparametric and semiparametric methods for analysis of constancy of relative risk over time. Results. One hundred seventy-two of 1836 men were infected. The adjusted vaccinees vs placebo recipients hazard ratio (HR) for all follow-up time was 1.40 (95% confidence interval [CI], 1.03–1.92; P = .03). Vaccine effect differed by baseline Ad5 or circumcision status during first 18 months, but neither was significant for all follow-up time. The HR among uncircumcised and/or Ad5-seropositive men waned with time since vaccination. No significant vaccine-associated risk was seen among circumcised, Ad5-negative men (HR, 0.97; P = 1.0) over all follow-up time. Conclusions. The vaccine-associated risk seen in interim analysis was confirmed but waned with time from vaccination. Clinical Trials Registration. NCT00095576. PMID:22561365

  6. Orbital apocrine hidrocystoma with immunohistochemical confirmation

    Directory of Open Access Journals (Sweden)

    Eduardo Damous Feijó

    2016-06-01

    Full Text Available ABSTRACT The authors report the first case in Brazilian literature of orbital apocrine hidrocystoma with immunohistochemistry confirmation. The tumor had been growing slowly and progressively, there was no history of impaired vision, diplopia, watering, discharge, or prior trauma. There was no proptosis and extraocular mobility was normal. The radiologic study by orbital computerized tomography revealed an extraconal nodule, with partially defined limits, with cystic and solid areas in the superomedial right orbit. An anterior orbitotomy, with full excision of the tumor was performed. A histopathology examination revealed apocrine hidrocystoma and immunohistochemistry confirmed the diagnosis. After surgery, the patient had total remission of symptoms.

  7. Knee-ligament injuries associated with leg fractures. Prospective study.

    Science.gov (United States)

    Matić, A; Kasić, M; Hudolin, I

    1992-09-01

    It has been proved in 25-35% of the cases that knee-ligament injuries are associated with fracture of the femoral diaphysis. No such association has been confirmed between leg fractures and knee ligaments. In order to find out if this is a coincidence, a prospective study was conducted on 229 patients who had undergone operations for leg fractures at various locations and of variable intensity. It was established in 41 cases (17.34%) that the leg fracture was associated with knee-ligament injuries, resulting in joint instability. A significantly higher percentage of associated ligament lesions was found in open fractures as opposed to closed leg fractures. The examination was carried out with the patient under general or block anesthesia. On the basis of what was established it is recommended that the knee be examined clinically in all leg osteosynthesis cases.

  8. Genetic association studies in lumbar disc degeneration

    DEFF Research Database (Denmark)

    Eskola, Pasi J; Lemmelä, Susanna; Kjaer, Per

    2012-01-01

    Low back pain is associated with lumbar disc degeneration, which is mainly due to genetic predisposition. The objective of this study was to perform a systematic review to evaluate genetic association studies in lumbar disc degeneration as defined on magnetic resonance imaging (MRI) in humans....

  9. One-step 3D-TV-hysterosalpingo-foam-sonography (3D-TV-HyFoSy) confirmation test for Essure® follow-up: a multicenter study.

    Science.gov (United States)

    Zizolfi, Brunella; Lazzeri, Lucia; Franchini, Mario; Di Spiezio Sardo, Attilio; Nappi, Carmine; Piccione, Emilio; Exacoustos, Caterina

    2017-01-09

    To evaluate the feasibility and accuracy of a three-dimensional-transvaginal-hysterosalpingo-contrast-sonography using the new dedicated contrast-enhanced gel foam (3D-TV-HyFoSy) to assess the position of the tubal sterilization Essure® devices and consequent tubal occlusion in patients who underwent Essure® hysteroscopic tubal sterilization. This multicenter study was prospectively conducted from June 2012 to July 2014 in four italian centers and included 50 women who underwent hysteroscopic Essure® microinsert placement, for a total of 95 tubes. Insertion of the microinserts was performed in outpatient setting following standard procedure recommendations. All patients underwent 3D-TV-HyFoSy and hysterosalpingography (HSG) about 3 months to 3 months and 2 weeks after the procedure. The devices' positions were first seen on 3D- transvaginal sonography (TVS) and classified according to specific criteria in 4 positions. Then a hysterosalpingo-contrast-sonography (HyCoSy) with 3D technique and ExEm® Foam gel as ultrasound contrast agent (HyFoSy) was performed to confirm tubal occlusion by the absence of contrast agent within the tubes and/or around the ovaries. To evaluate the feasibility of 3D-TV-HyFoSy, consecutive volume acquisitions were performed while injecting the gel foam. After sonographic evaluation all women underwent HSG to assess as standard methodology the success of sterilization. Side effects and pain evoked during and after 3D- TV-HyFoSy and HSG, using a 10-point numeric pain rating scale (NRS), were also evaluated. At 3D-TVS, 10 devices (10.5%) were in position "A", 2 (2.1%) in position"B", 59 (62.1%) in position "C", 24 (25.2%) in position"D". During 3D-HyFoSy, we observed tubal occlusion in 89 out of 95 tubes (93.7%). In the 6 cases in which the passage of the contrast was observed, one device (16.7%) was in position "B", one device (16.7%) in position "D"and four devices (66.7%) were found to lie in position "C". Tubal patency was confirmed at

  10. Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes.

    Science.gov (United States)

    Teumer, Alexander; Tin, Adrienne; Sorice, Rossella; Gorski, Mathias; Yeo, Nan Cher; Chu, Audrey Y; Li, Man; Li, Yong; Mijatovic, Vladan; Ko, Yi-An; Taliun, Daniel; Luciani, Alessandro; Chen, Ming-Huei; Yang, Qiong; Foster, Meredith C; Olden, Matthias; Hiraki, Linda T; Tayo, Bamidele O; Fuchsberger, Christian; Dieffenbach, Aida Karina; Shuldiner, Alan R; Smith, Albert V; Zappa, Allison M; Lupo, Antonio; Kollerits, Barbara; Ponte, Belen; Stengel, Bénédicte; Krämer, Bernhard K; Paulweber, Bernhard; Mitchell, Braxton D; Hayward, Caroline; Helmer, Catherine; Meisinger, Christa; Gieger, Christian; Shaffer, Christian M; Müller, Christian; Langenberg, Claudia; Ackermann, Daniel; Siscovick, David; Boerwinkle, Eric; Kronenberg, Florian; Ehret, Georg B; Homuth, Georg; Waeber, Gerard; Navis, Gerjan; Gambaro, Giovanni; Malerba, Giovanni; Eiriksdottir, Gudny; Li, Guo; Wichmann, H Erich; Grallert, Harald; Wallaschofski, Henri; Völzke, Henry; Brenner, Herrmann; Kramer, Holly; Mateo Leach, I; Rudan, Igor; Hillege, Hans L; Beckmann, Jacques S; Lambert, Jean Charles; Luan, Jian'an; Zhao, Jing Hua; Chalmers, John; Coresh, Josef; Denny, Joshua C; Butterbach, Katja; Launer, Lenore J; Ferrucci, Luigi; Kedenko, Lyudmyla; Haun, Margot; Metzger, Marie; Woodward, Mark; Hoffman, Matthew J; Nauck, Matthias; Waldenberger, Melanie; Pruijm, Menno; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Wareham, Nicholas J; Endlich, Nicole; Soranzo, Nicole; Polasek, Ozren; van der Harst, Pim; Pramstaller, Peter Paul; Vollenweider, Peter; Wild, Philipp S; Gansevoort, Ron T; Rettig, Rainer; Biffar, Reiner; Carroll, Robert J; Katz, Ronit; Loos, Ruth J F; Hwang, Shih-Jen; Coassin, Stefan; Bergmann, Sven; Rosas, Sylvia E; Stracke, Sylvia; Harris, Tamara B; Corre, Tanguy; Zeller, Tanja; Illig, Thomas; Aspelund, Thor; Tanaka, Toshiko; Lendeckel, Uwe; Völker, Uwe; Gudnason, Vilmundur; Chouraki, Vincent; Koenig, Wolfgang; Kutalik, Zoltan; O'Connell, Jeffrey R; Parsa, Afshin; Heid, Iris M; Paterson, Andrew D; de Boer, Ian H; Devuyst, Olivier; Lazar, Jozef; Endlich, Karlhans; Susztak, Katalin; Tremblay, Johanne; Hamet, Pavel; Jacob, Howard J; Böger, Carsten A; Fox, Caroline S; Pattaro, Cristian; Köttgen, Anna

    2016-03-01

    Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 × 10(-7)) and 13% for RAB38/CTSC (P = 5.8 × 10(-7)). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  11. A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation.

    Directory of Open Access Journals (Sweden)

    Jiali Han

    2008-05-01

    Full Text Available We conducted a multi-stage genome-wide association study of natural hair color in more than 10,000 men and women of European ancestry from the United States and Australia. An initial analysis of 528,173 single nucleotide polymorphisms (SNPs genotyped on 2,287 women identified IRF4 and SLC24A4 as loci highly associated with hair color, along with three other regions encompassing known pigmentation genes. We confirmed these associations in 7,028 individuals from three additional studies. Across these four studies, SLC24A4 rs12896399 and IRF4 rs12203592 showed strong associations with hair color, with p = 6.0x10(-62 and p = 7.46x10(-127, respectively. The IRF4 SNP was also associated with skin color (p = 6.2x10(-14, eye color (p = 6.1x10(-13, and skin tanning response to sunlight (p = 3.9x10(-89. A multivariable analysis pooling data from the initial GWAS and an additional 1,440 individuals suggested that the association between rs12203592 and hair color was independent of rs1540771, a SNP between the IRF4 and EXOC2 genes previously found to be associated with hair color. After adjustment for rs12203592, the association between rs1540771 and hair color was not significant (p = 0.52. One variant in the MATP gene was associated with hair color. A variant in the HERC2 gene upstream of the OCA2 gene showed the strongest and independent association with hair color compared with other SNPs in this region, including three previously reported SNPs. The signals detected in a region around the MC1R gene were explained by MC1R red hair color alleles. Our results suggest that the IRF4 and SLC24A4 loci are associated with human hair color and skin pigmentation.

  12. A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation.

    Science.gov (United States)

    Han, Jiali; Kraft, Peter; Nan, Hongmei; Guo, Qun; Chen, Constance; Qureshi, Abrar; Hankinson, Susan E; Hu, Frank B; Duffy, David L; Zhao, Zhen Zhen; Martin, Nicholas G; Montgomery, Grant W; Hayward, Nicholas K; Thomas, Gilles; Hoover, Robert N; Chanock, Stephen; Hunter, David J

    2008-05-16

    We conducted a multi-stage genome-wide association study of natural hair color in more than 10,000 men and women of European ancestry from the United States and Australia. An initial analysis of 528,173 single nucleotide polymorphisms (SNPs) genotyped on 2,287 women identified IRF4 and SLC24A4 as loci highly associated with hair color, along with three other regions encompassing known pigmentation genes. We confirmed these associations in 7,028 individuals from three additional studies. Across these four studies, SLC24A4 rs12896399 and IRF4 rs12203592 showed strong associations with hair color, with p = 6.0x10(-62) and p = 7.46x10(-127), respectively. The IRF4 SNP was also associated with skin color (p = 6.2x10(-14)), eye color (p = 6.1x10(-13)), and skin tanning response to sunlight (p = 3.9x10(-89)). A multivariable analysis pooling data from the initial GWAS and an additional 1,440 individuals suggested that the association between rs12203592 and hair color was independent of rs1540771, a SNP between the IRF4 and EXOC2 genes previously found to be associated with hair color. After adjustment for rs12203592, the association between rs1540771 and hair color was not significant (p = 0.52). One variant in the MATP gene was associated with hair color. A variant in the HERC2 gene upstream of the OCA2 gene showed the strongest and independent association with hair color compared with other SNPs in this region, including three previously reported SNPs. The signals detected in a region around the MC1R gene were explained by MC1R red hair color alleles. Our results suggest that the IRF4 and SLC24A4 loci are associated with human hair color and skin pigmentation.

  13. Behavioral confirmation of everyday sadism.

    Science.gov (United States)

    Buckels, Erin E; Jones, Daniel N; Paulhus, Delroy L

    2013-11-01

    Past research on socially aversive personalities has focused on subclinical psychopathy, subclinical narcissism, and Machiavellianism-the "Dark Triad" of personality. In the research reported here, we evaluated whether an everyday form of sadism should be added to that list. Acts of apparent cruelty were captured using two laboratory procedures, and we showed that such behavior could be predicted with two measures of sadistic personality. Study 1 featured a bug-killing paradigm. As expected, sadists volunteered to kill bugs at greater rates than did nonsadists. Study 2 examined willingness to harm an innocent victim. When aggression was easy, sadism and Dark Triad measures predicted unprovoked aggression. However, only sadists were willing to work for the opportunity to hurt an innocent person. In both studies, sadism emerged as an independent predictor of behavior reflecting an appetite for cruelty. Together, these findings support the construct validity of everyday sadism and its incorporation into a new "Dark Tetrad" of personality.

  14. Confirmation of Essure placement using transvaginal ultrasound.

    Science.gov (United States)

    Veersema, Sebastiaan; Vleugels, Michel; Koks, Caroline; Thurkow, Andreas; van der Vaart, Huub; Brölmann, Hans

    2011-01-01

    To evaluate the protocol for confirmation of satisfactory Essure placement using transvaginal ultrasound. Prospective multicenter cohort study (Canadian Task Force classification II-2). Outpatient departments of 4 teaching hospitals in the Netherlands. Eleven hundred forty-five women who underwent hysteroscopic sterilization using the Essure device between March 2005 and December 2007. Transvaginal ultrasound examination 12 weeks after uncomplicated successful bilateral placement or as indicated according to the transvaginal ultrasound protocol after 4 weeks, and hysterosalpingography (HSG) at 12 weeks to confirm correct placement of the device after 3 months. The rate of successful placement was 88.4% initially. In 164 women (15%), successful placement was confirmed at HSG according the protocol. In 9 patients (0.84%), incorrect position of the device was observed at HSG. The cumulative pregnancy rate after 18 months was 3.85 per thousand women. Transvaginal ultrasound should be the first diagnostic test used to confirm the adequacy of hysteroscopic Essure sterilization because it is minimally invasive, averts ionizing radiation, and does not decrease the effectiveness of the Essure procedure. Copyright © 2011 AAGL. Published by Elsevier Inc. All rights reserved.

  15. Two-stage genome-wide association study identifies a novel susceptibility locus associated with melanoma.

    Science.gov (United States)

    Ransohoff, Katherine J; Wu, Wenting; Cho, Hyunje G; Chahal, Harvind C; Lin, Yuan; Dai, Hong-Ji; Amos, Christopher I; Lee, Jeffrey E; Tang, Jean Y; Hinds, David A; Han, Jiali; Wei, Qingyi; Sarin, Kavita Y

    2017-03-14

    Genome-wide association studies have identified 21 susceptibility loci associated with melanoma. These loci implicate genes affecting pigmentation, nevus count, telomere maintenance, and DNA repair in melanoma risk. Here, we report the results of a two-stage genome-wide association study of melanoma. The stage 1 discovery phase consisted of 4,842 self-reported melanoma cases and 286,565 controls of European ancestry from the 23andMe research cohort and the stage 2 replication phase consisted of 1,804 melanoma cases and 1,026 controls from the University of Texas M.D. Anderson Cancer Center. We performed a combined meta-analysis totaling 6,628 melanoma cases and 287,591 controls. Our study replicates 20 of 21 previously known melanoma-loci and confirms the association of the telomerase reverse transcriptase, TERT, with melanoma susceptibility at genome-wide significance. In addition, we uncover a novel polymorphism, rs187843643 (OR = 1.96; 95% CI = [1.54, 2.48]; P = 3.53 x 10-8), associated with melanoma. The SNP rs187842643 lies within a noncoding RNA 177kb downstream of BASP1 (brain associated protein-1). We find that BASP1 expression is suppressed in melanoma as compared with benign nevi, providing additional evidence for a putative role in melanoma pathogenesis.

  16. Study of obesity associated proopiomelanocortin gene polymorphism

    African Journals Online (AJOL)

    Study of obesity associated proopiomelanocortin gene polymorphism: Relation to metabolic profile and eating habits in a sample of obese Egyptian children and ... Polymorphisms in the POMC gene locus are associated with obesity phenotypes. Aim: To ... Keywords: Childhood obesity; POMC gene; Metabolic syndrome ...

  17. Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes

    Science.gov (United States)

    Tin, Adrienne; Sorice, Rossella; Gorski, Mathias; Yeo, Nan Cher; Chu, Audrey Y.; Li, Man; Li, Yong; Mijatovic, Vladan; Ko, Yi-An; Taliun, Daniel; Luciani, Alessandro; Chen, Ming-Huei; Yang, Qiong; Foster, Meredith C.; Olden, Matthias; Hiraki, Linda T.; Tayo, Bamidele O.; Fuchsberger, Christian; Dieffenbach, Aida Karina; Shuldiner, Alan R.; Smith, Albert V.; Zappa, Allison M.; Lupo, Antonio; Kollerits, Barbara; Ponte, Belen; Stengel, Bénédicte; Krämer, Bernhard K.; Paulweber, Bernhard; Mitchell, Braxton D.; Hayward, Caroline; Helmer, Catherine; Meisinger, Christa; Gieger, Christian; Shaffer, Christian M.; Müller, Christian; Langenberg, Claudia; Ackermann, Daniel; Siscovick, David; Boerwinkle, Eric; Kronenberg, Florian; Ehret, Georg B.; Homuth, Georg; Waeber, Gerard; Navis, Gerjan; Gambaro, Giovanni; Malerba, Giovanni; Eiriksdottir, Gudny; Li, Guo; Wichmann, H. Erich; Grallert, Harald; Wallaschofski, Henri; Völzke, Henry; Brenner, Herrmann; Kramer, Holly; Leach, I. Mateo; Rudan, Igor; Hillege, Hans L.; Beckmann, Jacques S.; Lambert, Jean Charles; Luan, Jian'an; Zhao, Jing Hua; Chalmers, John; Coresh, Josef; Denny, Joshua C.; Butterbach, Katja; Launer, Lenore J.; Ferrucci, Luigi; Kedenko, Lyudmyla; Haun, Margot; Metzger, Marie; Woodward, Mark; Hoffman, Matthew J.; Nauck, Matthias; Waldenberger, Melanie; Pruijm, Menno; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Wareham, Nicholas J.; Endlich, Nicole; Soranzo, Nicole; Polasek, Ozren; van der Harst, Pim; Pramstaller, Peter Paul; Vollenweider, Peter; Wild, Philipp S.; Gansevoort, Ron T.; Rettig, Rainer; Biffar, Reiner; Carroll, Robert J.; Katz, Ronit; Loos, Ruth J.F.; Hwang, Shih-Jen; Coassin, Stefan; Bergmann, Sven; Rosas, Sylvia E.; Stracke, Sylvia; Harris, Tamara B.; Corre, Tanguy; Zeller, Tanja; Illig, Thomas; Aspelund, Thor; Tanaka, Toshiko; Lendeckel, Uwe; Völker, Uwe; Gudnason, Vilmundur; Chouraki, Vincent; Koenig, Wolfgang; Kutalik, Zoltan; O'Connell, Jeffrey R.; Parsa, Afshin; Heid, Iris M.; Paterson, Andrew D.; de Boer, Ian H.; Devuyst, Olivier; Lazar, Jozef; Endlich, Karlhans; Susztak, Katalin; Tremblay, Johanne; Hamet, Pavel; Jacob, Howard J.; Böger, Carsten A.

    2016-01-01

    Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10−10). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 × 10–7) and 13% for RAB38/CTSC (P = 5.8 × 10−7). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria. PMID:26631737

  18. Analysis of radiographically confirmed blunt-mechanism facial fractures.

    Science.gov (United States)

    Mundinger, Gerhard S; Dorafshar, Amir H; Gilson, Marta M; Mithani, Suhail K; Kelamis, Joseph A; Christy, Michael R; Manson, Paul N; Rodriguez, Eduardo D

    2014-01-01

    Facial fractures resulting from blunt-mechanism trauma, although common, have been infrequently evaluated in large studies that do not include confirmation of fractures based on author review of available patient radiographic studies. An 8-year review (1998-2006) of the R Adams Cowley Shock Trauma Registry was performed with institutional review board approval. Patients diagnosed with blunt-mechanism facial fractures were identified by the International Classification of Diseases, Ninth Revision (ICD-9) codes and their facial fractures confirmed by author review of computed tomographic scans. Individual fractures were classified and grouped according to the facial thirds. Intra- and interreader variability was calculated, and confirmed fracture patterns were compared to fracture patterns listed by ICD-9 codes. Concomitant injuries and demographic data were additionally evaluated. Four thousand three hundred ninety-eight patients with 8127 fractures were identified. Intra- and interreader variability was 2% and 7%, respectively. ICD-9 coding misdiagnosed 12.5% of all fractures. Eighty-two percent of patients sustained associated injuries, including basilar skull fractures (7.6%) and cervical spine fractures (6.6%). 1.1% had at least one fracture in each facial third (panfacial fracture pattern). Significant relationships were found between demographic parameters, concomitant injuries, specific fractures, and fracture patterns. Studies investigating facial fractures should report fracture patterns confirmed by author review of available radiographic imaging. Large retrospective data sets containing confirmed fractures and capable of addressing rare fracture patterns can be compiled with low inter- and intrauser variability, and are useful for generating mechanistic hypotheses suitable for evaluation in prospective series or by directed biomechanical studies.

  19. Poor replication validity of biomedical association studies reported by newspapers.

    Directory of Open Access Journals (Sweden)

    Estelle Dumas-Mallet

    Full Text Available To investigate the replication validity of biomedical association studies covered by newspapers.We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking and a non-lifestyle category (e.g. genetic risk. Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses.Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8% and subsequent (58/600 9.7% lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1% than subsequent ones (45/3718 1.2%. Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48 than subsequent ones (29/45 and than lifestyle studies (31/63. Psychiatric studies covered by newspapers were less often confirmed (10/38 than the neurological (26/41 or somatic (40/77 ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim.Journalists preferentially cover initial findings

  20. Poor replication validity of biomedical association studies reported by newspapers.

    Science.gov (United States)

    Dumas-Mallet, Estelle; Smith, Andy; Boraud, Thomas; Gonon, François

    2017-01-01

    To investigate the replication validity of biomedical association studies covered by newspapers. We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking) and a non-lifestyle category (e.g. genetic risk). Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses. Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies) and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8%) and subsequent (58/600 9.7%) lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1%) than subsequent ones (45/3718 1.2%). Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48) than subsequent ones (29/45) and than lifestyle studies (31/63). Psychiatric studies covered by newspapers were less often confirmed (10/38) than the neurological (26/41) or somatic (40/77) ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim. Journalists preferentially cover initial findings

  1. Poor replication validity of biomedical association studies reported by newspapers

    Science.gov (United States)

    Smith, Andy; Boraud, Thomas; Gonon, François

    2017-01-01

    Objective To investigate the replication validity of biomedical association studies covered by newspapers. Methods We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking) and a non-lifestyle category (e.g. genetic risk). Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses. Results Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies) and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8%) and subsequent (58/600 9.7%) lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1%) than subsequent ones (45/3718 1.2%). Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48) than subsequent ones (29/45) and than lifestyle studies (31/63). Psychiatric studies covered by newspapers were less often confirmed (10/38) than the neurological (26/41) or somatic (40/77) ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim. Conclusion Journalists

  2. Confirmation of the Most Distant Quasar

    Science.gov (United States)

    Tilvi, Vithal

    2017-08-01

    We propose for 8-orbit G141 grism observations to confirm the AGN nature of a z=7.51 galaxy, currently the most distant quasar candidate identified via NV line detection using deep G102 grism observations. The AGN evidence is further supported by a weak line detection in the ground-based MOSFIRE spectrum. Here we request grism observations to better understand the physical processes occurring in this unique galaxy, and confirm its AGN nature via additional lines: CIV, HeII and CIII. Detection of CIV alone will unambiguously confirm its AGN nature. Currently, WFC3 grism is the most efficient instrument for observing these lines as our recent work shows that the flux loss from ground-based slit-spectrographs is significant (>4x) compared with the grism measurements. Furthermore, the CIII line falls on to a bright atmospheric line making it nearly impossible to observe from the ground. Confirmation of the AGN nature of our target will be a tremendous achievement because this discovery implies that the black hole accretion was already in place within the first few million years after the big bang. This also means that at least some fraction of Lyman-break selected galaxies host AGNs, which can enhance the escape of ionizing radiation and thus contribute to the reionization of the intergalactic medium (IGM). Currently there are no observations of faint quasars, M(UV)>-23.2 mag, at z>7. Our proposed observations will push the discoveries to fainter limits, which consequently will start building an excellent base-sample for James Webb Space Telescope for studying the physical nature of sources responsible for reionizing the universe.

  3. Genetic associations with neuroendocrine tumor risk: results from a genome-wide association study.

    Science.gov (United States)

    Du, Yeting; Ter-Minassian, Monica; Brais, Lauren; Brooks, Nichole; Waldron, Amanda; Chan, Jennifer A; Lin, Xihong; Kraft, Peter; Christiani, David C; Kulke, Matthew H

    2016-08-01

    The etiology of neuroendocrine tumors remains poorly defined. Although neuroendocrine tumors are in some cases associated with inherited genetic syndromes, such syndromes are rare. The majority of neuroendocrine tumors are thought to be sporadic. We performed a genome-wide association study (GWAS) to identify potential genetic risk factors for sporadic neuroendocrine tumors. Using germline DNA from blood specimens, we genotyped 909,622 SNPs using the Affymetrix 6.0 GeneChip, in a cohort comprising 832 neuroendocrine tumor cases from Dana-Farber Cancer Institute and Massachusetts General Hospital and 4542 controls from the Harvard School of Public Health. An additional 241 controls from Dana-Farber Cancer Institute were used for quality control. We assessed risk associations in the overall cohort, and in neuroendocrine tumor subgroups. We identified no potential risk associations in the cohort overall. In the small intestine neuroendocrine tumor subgroup, comprising 293 cases, we identified risk associations with three SNPs on chromosome 12, all in strong LD. The three SNPs are located upstream of ELK3, a transcription factor implicated in angiogenesis. We did not identify clear risk associations in the bronchial or pancreatic neuroendocrine subgroups. This large-scale study provides initial evidence that presumed sporadic small intestine neuroendocrine tumors may have a genetic etiology. Our results provide a basis for further exploring the role of genes implicated in this analysis, and for replication studies to confirm the observed associations. Additional studies to evaluate potential genetic risk factors for sporadic pancreatic and bronchial neuroendocrine tumors are warranted. © 2016 Society for Endocrinology.

  4. Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study

    DEFF Research Database (Denmark)

    Song, Honglin; Ramus, Susan J; Kjaer, Susanne Krüger

    2009-01-01

    cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95% CI 1...... ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case-control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially......Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive...

  5. Association study between methylenetetrahydrofolate reductase gene polymorphisms and Graves' disease.

    Science.gov (United States)

    Mao, Renfang; Fan, Yihui; Zuo, Lulu; Geng, Dongfeng; Meng, Fantao; Zhu, Jing; Li, Qiang; Qiao, Hong; Jin, Yan; Bai, Jing; Fu, Songbin

    2010-10-01

    5,10-Methylenetetrahydrofolate reductase (MTHFR) catalyzes the metabolism of folate and nucleotides, which are essential for DNA synthesis and methylation. It is highly polymorphic, and its variant genotypes result in lower enzymatic activity and higher plasma homocysteine. Previous studies have provided evidence that a high prevalence of MTHFR gene polymorphisms is frequently detected in patients with autoimmune disease, suggesting a novel genetic association with autoimmune disorders. However, the genetic association between MTHFR and Graves' disease (GD), one of the most common autoimmune diseases, has not been studied. Here, we designed a clinic-based case-control study including 199 GD cases and 235 healthy controls to examine the associations between three common MTHFR polymorphisms (i.e., C677T, A1298C, and G1793A) and GD. Surprisingly, logistic regression analysis shows MTHFR 677CT + TT genotypes are associated with an approximately 42% reduction in the risk of GD in women (adjusted OR = 0.58, 95% CI = 0.3-0.9), compared to the CC genotype, indicating a significant protective effect of 677CT + TT genotypes. Our result provides epidemiological evidence that MTHFR mutation (C677T) protects women from GD. The protective effect, possibly obtained by influencing DNA methylation, should be confirmed in a large number of cohorts. Copyright © 2010 John Wiley & Sons, Ltd.

  6. Associative Visual Agnosia: A Case Study

    OpenAIRE

    A. Charnallet; Carbonnel, S.; David, D.; Moreaud, O.

    2008-01-01

    We report a case of massive associative visual agnosia. In the light of current theories of identification and semantic knowledge organization, a deficit involving both levels of structural description system and visual semantics must be assumed to explain the case. We suggest, in line with a previous case study [1], an alternative account in the framework of (non abstractive) episodic models of memory [4].

  7. Associative visual agnosia: a case study.

    Science.gov (United States)

    Charnallet, A; Carbonnel, S; David, D; Moreaud, O

    2008-01-01

    We report a case of massive associative visual agnosia. In the light of current theories of identification and semantic knowledge organization, a deficit involving both levels of structural description system and visual semantics must be assumed to explain the case. We suggest, in line with a previous case study, an alternative account in the framework of (non abstractive) episodic models of memory.

  8. Study of obesity associated proopiomelanocortin gene polymorphism

    African Journals Online (AJOL)

    Farida El-Baz Mohamed

    2016-03-10

    Mar 10, 2016 ... Study of obesity associated proopiomelanocortin ... Binge Eating Disorder (BED) by The Diagnostic and Statistical Manual of Mental Disorders, Fifth ... Cases were compared to fifty age-, sex- and pubertal stage-matched healthy non obese children and adolescents as a control group. The work was carried ...

  9. Understanding Salesforce Behavior using Genetic Association Studies

    NARCIS (Netherlands)

    W.E. van den Berg (Wouter)

    2014-01-01

    markdownabstract__Abstract__ Using genetic association studies, this thesis aims to investigate the drivers of successful customer-salesperson interactions in a context where knowledge development has become crucial to the value creation process. Central to this thesis is the developing role of

  10. An association study between polymorphism of alcohol ...

    African Journals Online (AJOL)

    Jane

    2011-09-28

    Sep 28, 2011 ... We wanted to determine the association between alcohol addiction and ethanol metabolizing genes and neurotransmitter related genes. MATERIALS AND METHODS. Study population. A total of 332 DNA samples from unrelated Chinese Han population in Yunnan region were obtained (214 controls and ...

  11. Chapter 11: Genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    William S Bush

    Full Text Available Genome-wide association studies (GWAS have evolved over the last ten years into a powerful tool for investigating the genetic architecture of human disease. In this work, we review the key concepts underlying GWAS, including the architecture of common diseases, the structure of common human genetic variation, technologies for capturing genetic information, study designs, and the statistical methods used for data analysis. We also look forward to the future beyond GWAS.

  12. The Multispot rapid HIV-1/HIV-2 differentiation assay is comparable with the Western blot and an immunofluorescence assay at confirming HIV infection in a prospective study in three regions of the United States.

    Science.gov (United States)

    Pandori, Mark W; Westheimer, Emily; Gay, Cindy; Moss, Nicholas; Fu, Jie; Hightow-Weidman, Lisa B; Craw, Jason; Hall, Laura; Giancotti, Francesca R; Mak, Mae Ling; Madayag, Carmela; Tsoi, Benjamin; Louie, Brian; Patel, Pragna; Owen, S Michele; Peters, Philip J

    2013-12-01

    A new HIV diagnostic algorithm has been proposed which replaces the use of the HIV-1 Western blot and HIV-1 immunofluorescence assays (IFA) as the supplemental test with an HIV-1/HIV-2 antibody differentiation assay. To compare an FDA-approved HIV-1/HIV-2 antibody differentiation test (Multispot) as a confirmatory test with the HIV-1 Western blot and IFA. Participants were screened with an HIV-1/HIV-2 combination Antigen/Antibody (Ag/Ab) screening assay. Specimens with repeatedly reactive results were tested with Multispot and either Western blot or IFA. Specimens with discordant screening and confirmatory results were resolved with HIV-1 RNA testing. Individuals (37,876) were screened for HIV infection and 654 (1.7%) had a repeatedly reactive Ag/Ab assay result. On Multispot, 554 (84.7%) were HIV-1 reactive, 0 (0%) were HIV-2 reactive, 1 (0.2%) was reactive for both HIV-1 and HIV-2 (undifferentiated), 9 (1.4%) were HIV-1 indeterminate, and 90 (13.8%) were non-reactive. HIV-1 RNA was detected in 47/90 Multispot non-reactive (52.2%) specimens. Among specimens confirmed to have HIV infection (true positives), Multispot and Western blot detected HIV-1 antibody in a similar proportion of cases (93.7% vs. 94.4% respectively) while Multispot and IFA also detected HIV-1 antibody in a similar proportion of cases (84.5% vs. 83.4% respectively). In this study, Multispot confirmed HIV infections at a similar proportion to Western blot and IFA. Multispot, Western blot, and IFA, however, did not confirm all of the reactive Ag/Ab assay results and underscores the importance of HIV NAT testing to resolve discordant screening and confirmatory results. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Epigenome-Wide Association Study of Wellbeing.

    Science.gov (United States)

    Baselmans, Bart M L; van Dongen, Jenny; Nivard, Michel G; Lin, Bochao D; Zilhão, Nuno R; Boomsma, Dorret I; Bartels, Meike

    2015-12-01

    Wellbeing (WB) is a major topic of research across several scientific disciplines, partly driven by its strong association with psychological and mental health. Twin-family studies have found that both genotype and environment play an important role in explaining the variance in WB. Epigenetic mechanisms, such as DNA methylation, regulate gene expression, and may mediate genetic and environmental effects on WB. Here, for the first time, we apply an epigenome-wide association study (EWAS) approach to identify differentially methylated sites associated with individual differences in WB. Subjects were part of the longitudinal survey studies of the Netherlands Twin Register (NTR) and participated in the NTR biobank project between 2002 and 2011. WB was assessed by a short inventory that measures satisfaction with life (SAT). DNA methylation was measured in whole blood by the Illumina Infinium HumanMethylation450 BeadChip (HM450k array) and the association between WB and DNA methylation level was tested at 411,169 autosomal sites. Two sites (cg10845147, p = 1.51 * 10(-8) and cg01940273, p = 2.34 * 10(-8)) reached genome-wide significance following Bonferonni correction. Four more sites (cg03329539, p = 2.76* 10(-7); cg09716613, p = 3.23 * 10(-7); cg04387347, p = 3.95 * 10(-7); and cg02290168, p = 5.23 * 10(-7)) were considered to be genome-wide significant when applying the widely used criterion of a FDR q value system categories among higher-ranking methylation sites. Overall, these results provide a first insight into the epigenetic mechanisms associated with WB and lay the foundations for future work aiming to unravel the biological mechanisms underlying a complex trait like WB.

  14. Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22

    NARCIS (Netherlands)

    Evangelou, Evangelos; Valdes, Ana M.; Kerkhof, Hanneke J. M.; Styrkarsdottir, Unnur; Zhu, YanYan; Meulenbelt, Ingrid; Lories, Rik J.; Karassa, Fotini B.; Tylzanowski, Przemko; Bos, Steffan D.; Akune, Toru; Arden, Nigel K.; Carr, Andrew; Chapman, Kay; Cupples, L. Adrienne; Dai, Jin; Deloukas, Panos; Doherty, Michael; Doherty, Sally; Engstrom, Gunnar; Gonzalez, Antonio; Halldorsson, Bjarni V.; Hammond, Christina L.; Hart, Deborah J.; Helgadottir, Hafdis; Hofman, Albert; Ikegawa, Shiro; Ingvarsson, Thorvaldur; Jiang, Qing; Jonsson, Helgi; Kaprio, Jaakko; Kawaguchi, Hiroshi; Kisand, Kalle; Kloppenburg, Margreet; Kujala, Urho M.; Lohmander, L. Stefan; Loughlin, John; Luyten, Frank P.; Mabuchi, Akihiko; McCaskie, Andrew; Nakajima, Masahiro; Nilsson, Peter M.; Nishida, Nao; Ollier, William E. R.; Panoutsopoulou, Kalliope; van de Putte, Tom; Ralston, Stuart H.; Rivadeneira, Fernado; Saarela, Janna; Schulte-Merker, Stefan; Shi, Dongquan; Slagboom, P. Eline; Sudo, Akihiro; Tamm, Agu; Tamm, Ann; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Tsezou, Aspasia; Wallis, Gillian A.; Wilkinson, J. Mark; Yoshimura, Noriko; Zeggini, Eleftheria; Zhai, Guangju; Zhang, Feng; Jonsdottir, Ingileif; Uitterlinden, Andre G.; Felson, David T.; van Meurs, Joyce B.; Stefansson, Kari; Ioannidis, John P. A.; Spector, Timothy D.

    Objectives Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in older people. It is characterised by changes in joint structure, including degeneration of the articular cartilage, and its aetiology is multifactorial with a

  15. Pathway analysis comparison using Crohn's disease genome wide association studies.

    Science.gov (United States)

    Ballard, David; Abraham, Clara; Cho, Judy; Zhao, Hongyu

    2010-06-28

    The use of biological annotation such as genes and pathways in the analysis of gene expression data has aided the identification of genes for follow-up studies and suggested functional information to uncharacterized genes. Several studies have applied similar methods to genome wide association studies and identified a number of disease related pathways. However, many questions remain on how to best approach this problem, such as whether there is a need to obtain a score to summarize association evidence at the gene level, and whether a pathway, dominated by just a few highly significant genes, is of interest. We evaluated the performance of two pathway-based methods (Random Set, and Binomial approximation to the hypergeometric test) based on their applications to three data sets of Crohn's disease. We consider both the disease status as a phenotype as well as the residuals after conditioning on IL23R, a known Crohn's related gene, as a phenotype. Our results show that Random Set method has the most power to identify disease related pathways. We confirm previously reported disease related pathways and provide evidence for IL-2 Receptor Beta Chain in T cell Activation and IL-9 signaling as Crohn's disease associated pathways. Our results highlight the need to apply powerful gene score methods prior to pathway enrichment tests, and that controlling for genes that attain genome wide significance enable further biological insight.

  16. Pathway analysis comparison using Crohn's disease genome wide association studies

    Directory of Open Access Journals (Sweden)

    Cho Judy

    2010-06-01

    Full Text Available Abstract Background The use of biological annotation such as genes and pathways in the analysis of gene expression data has aided the identification of genes for follow-up studies and suggested functional information to uncharacterized genes. Several studies have applied similar methods to genome wide association studies and identified a number of disease related pathways. However, many questions remain on how to best approach this problem, such as whether there is a need to obtain a score to summarize association evidence at the gene level, and whether a pathway, dominated by just a few highly significant genes, is of interest. Methods We evaluated the performance of two pathway-based methods (Random Set, and Binomial approximation to the hypergeometric test based on their applications to three data sets of Crohn's disease. We consider both the disease status as a phenotype as well as the residuals after conditioning on IL23R, a known Crohn's related gene, as a phenotype. Results Our results show that Random Set method has the most power to identify disease related pathways. We confirm previously reported disease related pathways and provide evidence for IL-2 Receptor Beta Chain in T cell Activation and IL-9 signaling as Crohn's disease associated pathways. Conclusions Our results highlight the need to apply powerful gene score methods prior to pathway enrichment tests, and that controlling for genes that attain genome wide significance enable further biological insight.

  17. Genome-Wide Association Studies of Cancer

    Science.gov (United States)

    Stadler, Zsofia K.; Thom, Peter; Robson, Mark E.; Weitzel, Jeffrey N.; Kauff, Noah D.; Hurley, Karen E.; Devlin, Vincent; Gold, Bert; Klein, Robert J.; Offit, Kenneth

    2010-01-01

    Knowledge of the inherited risk for cancer is an important component of preventive oncology. In addition to well-established syndromes of cancer predisposition, much remains to be discovered about the genetic variation underlying susceptibility to common malignancies. Increased knowledge about the human genome and advances in genotyping technology have made possible genome-wide association studies (GWAS) of human diseases. These studies have identified many important regions of genetic variation associated with an increased risk for human traits and diseases including cancer. Understanding the principles, major findings, and limitations of GWAS is becoming increasingly important for oncologists as dissemination of genomic risk tests directly to consumers is already occurring through commercial companies. GWAS have contributed to our understanding of the genetic basis of cancer and will shed light on biologic pathways and possible new strategies for targeted prevention. To date, however, the clinical utility of GWAS-derived risk markers remains limited. PMID:20585100

  18. Associative Visual Agnosia: A Case Study

    Directory of Open Access Journals (Sweden)

    A. Charnallet

    2008-01-01

    Full Text Available We report a case of massive associative visual agnosia. In the light of current theories of identification and semantic knowledge organization, a deficit involving both levels of structural description system and visual semantics must be assumed to explain the case. We suggest, in line with a previous case study [1], an alternative account in the framework of (non abstractive episodic models of memory [4].

  19. Microorganisms associated particulate matter: a preliminary study.

    Science.gov (United States)

    Alghamdi, Mansour A; Shamy, Magdy; Redal, Maria Ana; Khoder, Mamdouh; Awad, Abdel Hameed; Elserougy, Safaa

    2014-05-01

    This study aims to determine the microbiological quality of particulate matter (PM) in an urban area in Jeddah, Saudi Arabia, during December 2012 to April 2013. This was achieved by the determination of airborne bacteria, fungi, and actinobacteria associated PM10 and PM2.5, as well as their relationships with gaseous pollutants, O3, SO2 and NO2, and meteorological factors (T°C, RH% and Ws). High volume samplers with PM10 and PM2.5 selective sizes, and glass fiber filters were used to collect PM10 and PM2.5, respectively. The filters were suspended in buffer phosphate and aliquots were spread plated onto the surfaces of trypticase soy agar, malt extract agar, and starch casein agar media for counting of bacteria, fungi and actinobacteria-associated PM, respectively. PM10 and PM2.5 concentrations averaged 159.9 μg/m(3) and 60 μg/m(3), respectively, with the ratio of PM2.5/PM10 averaged ~0.4. The concentrations of O3, SO2 and NO2 averaged 35.73 μg/m(3), 38.1μg/m(3) and 52.5 μg/m(3), respectively. Fungi and actinobacteria associated PM were found in lower concentrations than bacteria. The sum of microbial loads was higher in PM10 than PM2.5, however a significant correlation (r=0.57, P ≤ 0.05) was found between the sum of microbial loads associated PM10 and PM2.5. Aspergillus fumigatus and Aspergillus niger were the common fungal types associated PM. Temperature significantly correlated with both PM10 (r=0.44), and PM2.5 (r=0.5). Significant negative correlations were found between O3 and PM2.5 (r=-0.47), and between SO2 with PM10 (r=-0.48). Wind speed positively correlated with airborne microorganisms associated PM. The regression model showed that the inverse PM2.5 concentration (1/PM2.5) was a significant determinant of fungal count associated PM. Chemical processes and environmental factors could affect properties of PM and in turn its biological quality. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Proteomic studies associated with Parkinson's disease.

    Science.gov (United States)

    Kasap, Murat; Akpinar, Gurler; Kanli, Aylin

    2017-03-01

    Parkinson's disease (PD) is an insidious disorder affecting more than 1-2% of the population over the age of 65. Understanding the etiology of PD may create opportunities for developing new treatments. Genomic and transcriptomic studies are useful, but do not provide evidence for the actual status of the disease. Conversely, proteomic studies deal with proteins, which are real time players, and can hence provide information on the dynamic nature of the affected cells. The number of publications relating to the proteomics of PD is vast. Therefore, there is a need to evaluate the current proteomics literature and establish the connections between the past and the present to foresee the future. Areas covered: PubMed and Web of Science were used to retrieve the literature associated with PD proteomics. Studies using human samples, model organisms and cell lines were selected and reviewed to highlight their contributions to PD. Expert commentary: The proteomic studies associated with PD achieved only limited success in facilitating disease diagnosis, monitoring and progression. A global system biology approach using new models is needed. Future research should integrate the findings of proteomics with other omics data to facilitate both early diagnosis and the treatment of PD.

  1. Gastroschisis and associated defects: an international study.

    LENUS (Irish Health Repository)

    Mastroiacovo, Pierpaolo

    2007-04-01

    Our objective was to evaluate the frequency and type of malformations associated with gastroschisis in a large pool of international data, to identify malformation patterns, and to evaluate the role of maternal age in non-isolated cases. Case-by-case information from 24 registries, all members of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), were evaluated. After the exclusion of other abdominal wall defects cases were classified as: (a) isolated; (b) recognizable syndrome, chromosomal or not; (c) multiple congenital anomalies (MCA). Our results showed that out of 3,322 total cases 469 non-isolated cases were registered (14.1%): 41 chromosomal syndromes, 24 other syndromes, and 404 MCA. Among MCA four groups of anomalies were most frequent: CNS (4.5%), cardio-vascular (2.5%), limb (2.2%), and kidney anomalies (1.9%). No similar patterns emerged except two patterns resembling limb-body wall complex and OEIS. In both of them the gastroschisis could be however misclassified. Chromosomal trisomies and possibly non-syndromic MCA are associated with an older maternal age more than isolated cases. On consideration of our data and the most valid studies published in the literature, the best estimate of the proportion of gastroschisis associated with major unrelated defects is about 10%, with a few cases associated to recognizable syndromes. Recognized syndromes with gastroschisis seem to be so exceptional that the well documented and validated cases are worth being published as interesting case report. An appropriate case definition in etiological studies should include only isolated gastroschisis after an appropriate definition of isolated and non-isolated cases and a thorough case-by-case review.

  2. An efficient synthesis of a rationally designed 1,5 disubstituted imidazole AT1 Angiotensin II receptor antagonist: reorientation of imidazole pharmacophore groups in losartan reserves high receptor affinity and confirms docking studies

    Science.gov (United States)

    Agelis, George; Roumelioti, Panagiota; Resvani, Amalia; Durdagi, Serdar; Androutsou, Maria-Eleni; Kelaidonis, Konstantinos; Vlahakos, Demetrios; Mavromoustakos, Thomas; Matsoukas, John

    2010-09-01

    A new 1,5 disubstituted imidazole AT1 Angiotensin II (AII) receptor antagonist related to losartan with reversion of butyl and hydroxymethyl groups at the 2-, 5-positions of the imidazole ring was synthesized and evaluated for its antagonist activity ( V8). In vitro results indicated that the reorientation of butyl and hydroxymethyl groups on the imidazole template of losartan retained high binding affinity to the AT1 receptor concluding that the spacing of the substituents at the 2,5- positions is of primary importance. The docking studies are confirmed by binding assay results which clearly show a comparable binding score of the designed compound V8 with that of the prototype losartan. An efficient, regioselective and cost effective synthesis renders the new compound as an attractive candidate for advanced toxicological evaluation and a drug against hypertension.

  3. Confirming a case of ball lightening production

    Energy Technology Data Exchange (ETDEWEB)

    Balyberdin, V.V.

    1975-01-01

    Model confirmation of ball lightening production was carried out on a three-cascade unit having a working voltage of 150 kV in an air atmosphere at a pressure of 730 to 750 mg Hg std. with C-shaped bending of the lightening drawoff. The electrical discharge parameters were held constant as follows: maximum current amplitude of 7 kA, oscillatory period of the quenched discharge of 6.5 x 10/sup -6/ sec, and energy used up in the unit approximately 2.2 k joules. Moving pictures are presented of the generation of one long luminous bundle displaced from a solid with a velocity up to 240 m/sec, whose luminosity was observed over a period of approximately 3 x 10/sup -3/ sec. Analysis of the experimental results showed that the appearance of plasma bundles is associated with the development of turbulent flows of a low-temperature plasma near the tip of a solid. (SJR)

  4. Use of urinary pregnanediol 3-glucuronide to confirm ovulation.

    Science.gov (United States)

    Ecochard, R; Leiva, R; Bouchard, T; Boehringer, H; Direito, A; Mariani, A; Fehring, R

    2013-10-01

    Urinary hormonal markers may assist in increasing the efficacy of Fertility Awareness Based Methods (FABM). This study uses urinary pregnanediol-3a-glucuronide (PDG) testing to more accurately identify the infertile phase of the menstrual cycle in the setting of FABM. Secondary analysis of an observational and simulation study, multicentre, European study. The study includes 107 women and tracks daily first morning urine (FMU), observed the changes in cervical mucus discharge, and ultrasonography to identify the day of ovulation over 326 menstrual cycles. The following three scenarios were tested: (A) use of the daily pregnandiol-3a-glucuronide (PDG) test alone; (B) use of the PDG test after the first positive urine luteinizing hormone (LH) kit result; (C) use of the PDG test after the disappearance of fertile type mucus. Two models were used: (1) one day of PDG positivity; or (2) waiting for three days of PDG positivity before declaring infertility. After the first positivity of a LH test or the end of fertile mucus, three consecutive days of PDG testing over a threshold of 5μg/mL resulted in a 100% specificity for ovulation confirmation. They were respectively associated an identification of an average of 6.1 and 7.6 recognized infertile days. The results demonstrate a clinical scenario with 100% specificity for ovulation confirmation and provide the theoretical background for a future development of a competitive lateral flow assay for the detection of PDG in the urine. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Symptomatic, Magnetic Resonance Imaging-Confirmed Cervical Disk Herniation Patients: A Comparative-Effectiveness Prospective Observational Study of 2 Age- and Sex-Matched Cohorts Treated With Either Imaging-Guided Indirect Cervical Nerve Root Injections or Spinal Manipulative Therapy.

    Science.gov (United States)

    Peterson, Cynthia K; Pfirrmann, Christian W A; Hodler, Jürg; Leemann, Serafin; Schmid, Christof; Anklin, Bernard; Humphreys, B Kim

    2016-01-01

    The purpose of this study was to compare the outcomes of overall improvement, pain reduction, and treatment costs in matched patients with symptomatic, magnetic resonance imaging-confirmed cervical disk herniations treated with either spinal manipulative therapy (SMT) or imaging-guided cervical nerve root injection blocks (CNRI). This prospective cohort comparative-effectiveness study included 104 patients with magnetic resonance imaging-confirmed symptomatic cervical disk herniation. Fifty-two patients treated with CNRI were age and sex matched with 52 patients treated with SMT. Baseline numerical rating scale (NRS) pain data were collected. Three months after treatment, NRS pain levels were recorded and overall "improvement" was assessed using the Patient Global Impression of Change scale. Only responses "much better" or "better" were considered "improved." The proportion of patients "improved" was calculated for each treatment method and compared using the χ(2) test. The NRS and NRS change scores for the 2 groups were compared at baseline and 3 months using the unpaired t test. Acute and subacute/chronic patients in the 2 groups were compared for "improvement" using the χ(2) test. "Improvement" was reported in 86.5% of SMT patients and 49.0% of CNRI patients (P = .0001). Significantly more CNRI patients were in the subacute/chronic category (77%) compared with SMT patients (46%). A significant difference between the proportion of subacute/chronic CNRI patients (37.5%) and SMT patients (78.3%) reporting "improvement" was noted (P = .002). Subacute/chronic patients treated with SMT were significantly more likely to report relevant "improvement" compared with CNRI patients. There was no difference in outcomes when comparing acute patients only. Copyright © 2016 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

  6. Lipid nanotechnologies for structural studies of membrane-associated proteins.

    Science.gov (United States)

    Stoilova-McPhie, Svetla; Grushin, Kirill; Dalm, Daniela; Miller, Jaimy

    2014-11-01

    We present a methodology of lipid nanotubes (LNT) and nanodisks technologies optimized in our laboratory for structural studies of membrane-associated proteins at close to physiological conditions. The application of these lipid nanotechnologies for structure determination by cryo-electron microscopy (cryo-EM) is fundamental for understanding and modulating their function. The LNTs in our studies are single bilayer galactosylceramide based nanotubes of ∼20 nm inner diameter and a few microns in length, that self-assemble in aqueous solutions. The lipid nanodisks (NDs) are self-assembled discoid lipid bilayers of ∼10 nm diameter, which are stabilized in aqueous solutions by a belt of amphipathic helical scaffold proteins. By combining LNT and ND technologies, we can examine structurally how the membrane curvature and lipid composition modulates the function of the membrane-associated proteins. As proof of principle, we have engineered these lipid nanotechnologies to mimic the activated platelet's phosphtaidylserine rich membrane and have successfully assembled functional membrane-bound coagulation factor VIII in vitro for structure determination by cryo-EM. The macromolecular organization of the proteins bound to ND and LNT are further defined by fitting the known atomic structures within the calculated three-dimensional maps. The combination of LNT and ND technologies offers a means to control the design and assembly of a wide range of functional membrane-associated proteins and complexes for structural studies by cryo-EM. The presented results confirm the suitability of the developed methodology for studying the functional structure of membrane-associated proteins, such as the coagulation factors, at a close to physiological environment. © 2014 Wiley Periodicals, Inc.

  7. Study of the association between blood types and breast cancer among Isfahanian women with breast cancer

    OpenAIRE

    Amir Hossein Mirlohi Flavarjani; Behnood Hedayatpour; Nasrollah Bashardoost; Sayed Mohammad Nourian

    2014-01-01

    Background: Previous studies suggest a possible association between ABO blood group and the risk of breast cancer. The aim of this study is to investigate the presence of a possible association between breast cancer and blood groups ABO and Rh. Materials and Methods: 549 women including 173 cases and 376 controls were selected. The case group included patients with breast cancer and the cancer diagnosis was confirmed for all of them. The control group included women with no reports of bre...

  8. Catapult current sheet relaxation model confirmed by THEMIS observations

    Science.gov (United States)

    Machida, S.; Miyashita, Y.; Ieda, A.; Nose, M.; Angelopoulos, V.; McFadden, J. P.

    2014-12-01

    In this study, we show the result of superposed epoch analysis on the THEMIS probe data during the period from November, 2007 to April, 2009 by setting the origin of time axis to the substorm onset determined by Nishimura with THEMIS all sky imager (THEMS/ASI) data (http://www.atmos.ucla.edu/~toshi/files/paper/Toshi_THEMIS_GBO_list_distribution.xls). We confirmed the presence of earthward flows which can be associated with north-south auroral streamers during the substorm growth phase. At around X = -12 Earth radii (Re), the northward magnetic field and its elevation angle decreased markedly approximately 4 min before substorm onset. A northward magnetic-field increase associated with pre-onset earthward flows was found at around X = -17Re. This variation indicates the occurrence of the local depolarization. Interestingly, in the region earthwards of X = -18Re, earthward flows in the central plasma sheet (CPS) reduced significantly about 3min before substorm onset. However, the earthward flows enhanced again at t = -60 sec in the region around X = -14 Re, and they moved toward the Earth. At t = 0, the dipolarization of the magnetic field started at X ~ -10 Re, and simultaneously the magnetic reconnection started at X ~ -20 Re. Synthesizing these results, we can confirm the validity of our catapult current sheet relaxation model.

  9. Funding Alert Subscribe Confirmation | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Thank you. Please check your email ( ) to confirm your subscription to the IDRC Funding Alerts. Please note: the link in your confirmation email is valid for 3 days, so please reply promptly. We fund researchers driving global change. Careers · Contact Us · Subscribe · Unsubscribe · Site map. Follow us; Facebook · Twitter ...

  10. A Multinational Arab Genome-Wide Association Study Identifies New Genetic Associations for Rheumatoid Arthritis.

    Science.gov (United States)

    Saxena, Richa; Plenge, Robert M; Bjonnes, Andrew C; Dashti, Hassan S; Okada, Yukinori; Gad El Haq, Wessam; Hammoudeh, Mohammed; Al Emadi, Samar; Masri, Basel K; Halabi, Hussein; Badsha, Humeira; Uthman, Imad W; Margolin, Lauren; Gupta, Namrata; Mahfoud, Ziyad R; Kapiri, Marianthi; Dargham, Soha R; Aranki, Grace; Kazkaz, Layla A; Arayssi, Thurayya

    2017-05-01

    Genetic factors underlying susceptibility to rheumatoid arthritis (RA) in Arab populations are largely unknown. This genome-wide association study (GWAS) was undertaken to explore the generalizability of previously reported RA loci to Arab subjects and to discover new Arab-specific genetic loci. The Genetics of Rheumatoid Arthritis in Some Arab States Study was designed to examine the genetics and clinical features of RA patients from Jordan, the Kingdom of Saudi Arabia, Lebanon, Qatar, and the United Arab Emirates. In total, >7 million single-nucleotide polymorphisms (SNPs) were tested for association with RA overall and with seropositive or seronegative RA in 511 RA cases and 352 healthy controls. In addition, replication of 15 signals was attempted in 283 RA cases and 221 healthy controls. A genetic risk score of 68 known RA SNPs was also examined in this study population. Three loci (HLA region, intergenic 5q13, and 17p13 at SMTNL2/GGT6) reached genome-wide significance in the analyses of association with RA and with seropositive RA, and for all 3 loci, evidence of independent replication was demonstrated. Consistent with the findings in European and East Asian populations, the association of RA with HLA-DRB1 amino acid position 11 conferred the strongest effect (P = 4.8 × 10(-16) ), and a weighted genetic risk score of previously associated RA loci was found to be associated with RA (P = 3.41 × 10(-5) ) and with seropositive RA (P = 1.48 × 10(-6) ) in this population. In addition, 2 novel associations specific to Arab populations were found at the 5q13 and 17p13 loci. This first RA GWAS in Arab populations confirms that established HLA-region and known RA risk alleles contribute strongly to the risk and severity of disease in some Arab groups, suggesting that the genetic architecture of RA is similar across ethnic groups. Moreover, this study identified 2 novel RA risk loci in Arabs, offering further population-specific insights into the

  11. Genetically Confirmed Familial Hypercholesterolemia in Patients With Acute Coronary Syndrome.

    Science.gov (United States)

    Amor-Salamanca, Almudena; Castillo, Sergio; Gonzalez-Vioque, Emiliano; Dominguez, Fernando; Quintana, Lucía; Lluís-Ganella, Carla; Escudier, Juan Manuel; Ortega, Javier; Lara-Pezzi, Enrique; Alonso-Pulpon, Luis; Garcia-Pavia, Pablo

    2017-10-03

    Genetic screening programs in unselected individuals with increased levels of low-density lipoprotein cholesterol (LDL-C) have shown modest results in identifying individuals with familial hypercholesterolemia (FH). This study assessed the prevalence of genetically confirmed FH in patients with acute coronary syndrome (ACS) and compared the diagnostic performance of FH clinical criteria versus FH genetic testing. Genetic study of 7 genes (LDLR, APOB, PCSK9, APOE, STAP1, LDLRAP1, and LIPA) associated with FH and 12 common alleles associated with polygenic hypercholesterolemia was performed in 103 patients with ACS, age ≤65 years, and LDL-C levels ≥160 mg/dl. Dutch Lipid Clinic (DLC) and Simon Broome (SB) FH clinical criteria were also applied. The prevalence of genetically confirmed FH was 8.7% (95% confidence interval [CI]: 4.3% to 16.4%; n = 9); 29% (95% CI: 18.5% to 42.1%; n = 18) of patients without FH variants had a score highly suggestive of polygenic hypercholesterolemia. The prevalence of probable to definite FH according to DLC criteria was 27.2% (95% CI: 19.1% to 37.0%; n = 28), whereas SB criteria identified 27.2% of patients (95% CI: 19.1% to 37.0%; n = 28) with possible to definite FH. DLC and SB algorithms failed to diagnose 4 (44%) and 3 (33%) patients with genetically confirmed FH, respectively. Cascade genetic testing in first-degree relatives identified 6 additional individuals with FH. The prevalence of genetically confirmed FH in patients with ACS age ≤65 years and with LDL-C levels ≥160 mg/dl is high (approximately 9%). FH clinical algorithms do not accurately classify patients with FH. Genetic testing should be advocated in young patients with ACS and high LDL-C levels to allow prompt identification of patients with FH and relatives at risk. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  12. 3. A Cross-sectional Study on Factors Associated With Perforated ...

    African Journals Online (AJOL)

    Esem

    and 57.2% of patients had symptoms lasting 24 hours or less. Furthermore, the commonest blood group was group O+(33.2%),with 40% confirming history of use of NSAIDs. 57% were regular alcohol. A Cross-sectional Study on Factors Associated With. Perforated Peptic Ulcer Disease in Adults Presenting to UTH, Lusaka.

  13. Analyzes of genome-wide association follow-up study for calving traits in dairy cattle

    DEFF Research Database (Denmark)

    Höglund, Johanna Karolina; Guldbrandtsen, Bernt; Lund, Mogens Sandø

    2012-01-01

    incorporated or weighted in selection decisions or further studied for causal gene. In dairy cattle progeny testing scheme new data is routinely accumulated which can be used to validate previously discovered associations. However, the data is not an independent sample and the sample size may not be sufficient......,039 respectively. A total of 424 SNP-trait combinations on 22 chromosomes showed genome-wide significant association involving 284 unique SNPs in the COMB dataset. In the REF data set 101 associations (73 unique SNPs) and in the VAL 24 associations (18 unique SNPs) were found genome-wide significant Sixty......-eight percent of the SNPs in the REF dataset could be confirmed in the VAL dataset. Out of 469 unique SNPs showing chromosome-wide significant association with calving traits in the REF dataset 321 could be confirmed in the VAL dataset at P

  14. Yin-Cold or Yang-Heat Syndrome Type of Traditional Chinese Medicine Was Associated with the Epidermal Growth Factor Receptor Gene Status in Non-Small Cell Lung Cancer Patients: Confirmation of a TCM Concept

    Directory of Open Access Journals (Sweden)

    Yan-juan Zhu

    2017-01-01

    Full Text Available Traditional Chinese Medicine (TCM therapies should be tailored according to the different syndrome types. In order to identify the relationship between the TCM Yin-cold (YC or Yang-heat (YH syndrome types and the EGFR gene status, we prospectively studied 310 NSCLC patients. TCM YH or YC was diagnosed by three TCM experts. TCM symptoms and signs were entered into a binary cluster analysis. The relationships between the EGFR gene status, YH or YC syndrome types, and classification by cluster analysis were analyzed using the chi-square test and multivariate logistic regression. In the 299 patients who had their EGFR gene tested, 45.24% YC (76/168 and 25.95% YH (34/131 patients had EGFR mutations (p=0.001. Among the 292 patients entered into the cluster analysis, 132 were classified into group A, with signs and symptoms similar to YC, whereas 160 group B patients were similar to YH. In the 281 patients with EGFR tested, 45.67% group A (58/127 and 28.57% group B patients (44/154 had EGFR mutations (p=0.003. The EGFR status was independently correlated with TCM syndrome type and classification by cluster analysis on multivariate logistic regression. NSCLC patients with YC were more likely to have EGFR gene mutations.

  15. Brain expression genome-wide association study (eGWAS identifies human disease-associated variants.

    Directory of Open Access Journals (Sweden)

    Fanggeng Zou

    Full Text Available Genetic variants that modify brain gene expression may also influence risk for human diseases. We measured expression levels of 24,526 transcripts in brain samples from the cerebellum and temporal cortex of autopsied subjects with Alzheimer's disease (AD, cerebellar n=197, temporal cortex n=202 and with other brain pathologies (non-AD, cerebellar n=177, temporal cortex n=197. We conducted an expression genome-wide association study (eGWAS using 213,528 cisSNPs within ± 100 kb of the tested transcripts. We identified 2,980 cerebellar cisSNP/transcript level associations (2,596 unique cisSNPs significant in both ADs and non-ADs (q<0.05, p=7.70 × 10(-5-1.67 × 10(-82. Of these, 2,089 were also significant in the temporal cortex (p=1.85 × 10(-5-1.70 × 10(-141. The top cerebellar cisSNPs had 2.4-fold enrichment for human disease-associated variants (p<10(-6. We identified novel cisSNP/transcript associations for human disease-associated variants, including progressive supranuclear palsy SLCO1A2/rs11568563, Parkinson's disease (PD MMRN1/rs6532197, Paget's disease OPTN/rs1561570; and we confirmed others, including PD MAPT/rs242557, systemic lupus erythematosus and ulcerative colitis IRF5/rs4728142, and type 1 diabetes mellitus RPS26/rs1701704. In our eGWAS, there was 2.9-3.3 fold enrichment (p<10(-6 of significant cisSNPs with suggestive AD-risk association (p<10(-3 in the Alzheimer's Disease Genetics Consortium GWAS. These results demonstrate the significant contributions of genetic factors to human brain gene expression, which are reliably detected across different brain regions and pathologies. The significant enrichment of brain cisSNPs among disease-associated variants advocates gene expression changes as a mechanism for many central nervous system (CNS and non-CNS diseases. Combined assessment of expression and disease GWAS may provide complementary information in discovery of human disease variants with functional implications. Our findings

  16. Phenome-Wide Association Study of Rheumatoid Arthritis Subgroups Identifies Association Between Seronegative Disease and Fibromyalgia.

    Science.gov (United States)

    Doss, Jayanth; Mo, Huan; Carroll, Robert J; Crofford, Leslie J; Denny, Joshua C

    2017-02-01

    The differences between seronegative and seropositive rheumatoid arthritis (RA) have not been widely reported. We performed electronic health record (EHR)-based phenome-wide association studies (PheWAS) to identify disease associations in seropositive and seronegative RA. A validated algorithm identified RA subjects from the de-identified version of the Vanderbilt University Medical Center EHR. Serotypes were determined by rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) values. We tested EHR-derived phenotypes using PheWAS comparing seropositive RA and seronegative RA, yielding disease associations. PheWAS was also performed in RF-positive versus RF-negative subjects and ACPA-positive versus ACPA-negative subjects. Following PheWAS, select phenotypes were then manually reviewed, and fibromyalgia was specifically evaluated using a validated algorithm. A total of 2,199 RA individuals with either RF or ACPA testing were identified. Of these, 1,382 patients (63%) were classified as seropositive. Seronegative RA was associated with myalgia and myositis (odds ratio [OR] 2.1, P = 3.7 × 10-10 ) and back pain. A manual review of the health record showed that among subjects coded for Myalgia and Myositis, ∼80% had fibromyalgia. Follow-up with a specific EHR algorithm for fibromyalgia confirmed that seronegative RA was associated with fibromyalgia (OR 1.8, P = 4.0 × 10-6 ). Seropositive RA was associated with chronic airway obstruction (OR 2.2, P = 1.4 × 10-4 ) and tobacco use (OR 2.2, P = 7.0 × 10-4 ). This PheWAS of RA patients identifies a strong association between seronegativity and fibromyalgia. It also affirms relationships between seropositivity and chronic airway obstruction and between seropositivity and tobacco use. These findings demonstrate the utility of the PheWAS approach to discover novel phenotype associations within different subgroups of a disease. © 2016, American College of Rheumatology.

  17. Typhoid fever: clinical diagnosis versus laboratory confirmation.

    Science.gov (United States)

    Ngwu, B A; Agbo, J A

    2003-01-01

    Recently there has been an increase in the clinically diagnosed typhoid fever in various parts of Nigeria with subsequent increase in public fear of possible epidemics of the disease. In this study the accuracy of clinically diagnosed typhoid fever were investigated. Blood and stool specimens from 260 patients clinically diagnosed typhoid fever were investigated using Widal test and bacteriological culture methods respectively. One hundred and thirty-four (51.5%) of the cases investigated were positive and that there was a significant difference (P clinically diagnosed and bacteriologically confirmed typhoid fever cases. Causative organisms were Salmonella typhi 46 (34.3%); S paratyphi B 34 (25.4%); S paratyphi A 24 (17.9%); S paratyphi C 20 (14.9%); other Salmonella spp 10 (7.5%). Young adults and males were predominantely affected. Most of the clinically diagnosed typhoid cases were misdiagnosis and the hue and cry by the general public on the epidemic of typhoid fever could not be justified. It is recommended that careful detailed history taking, meticulous clinical examination and prompt bacteriological culturing of specimens from suspected typhoid cases will improve the accuracy of clinically diagnosed typhoid fever.

  18. Metabolome-wide association study identified the association between a circulating polyunsaturated fatty acids variant rs174548 and lung cancer.

    Science.gov (United States)

    Wang, Cheng; Qin, Na; Zhu, Meng; Chen, Minjian; Xie, Kaipeng; Cheng, Yang; Dai, Juncheng; Liu, Jia; Xia, Yankai; Ma, Hongxia; Jin, Guangfu; Amos, Christopher I; Hu, Zhibin; Lin, Dongxin; Shen, Hongbing

    2017-10-26

    Quantitative trait loci (QTLs) are widely used as instruments to infer causal risk factors of diseases based on the idea of mendelian randomization. Plasma metabolites can serve as risk factors of cancer, and the heritability of many circulating metabolites was high. We conducted a metabolome-wide association study (MWAS) to systematically investigate the effects of genetic variants on metabolites and lung cancer based on published genome-wide association study (GWASs) and metabolic-QTL (mQTL) study. Then we confirmed the results by subsequent genetic and metabolic validations and inferred the causal relationship between identified metabolites and lung cancer through genetic variant(s). We firstly identified six polyunsaturated fatty acids (PUFAs) represented by rs174548-linked haplotype were significantly associated with lung cancer risk in a Chinese GWAS (2311 cases and 3077 controls). Rs174548 was further confirmed to be associated with lung cancer in 13 821 Europeans and 18 471 Asians (ORmeta = 0.87, Pmeta = 1.76 × 10-15) and the effect was much stronger in females (Pinteraction = 6.00 × 10-4). We next validated rs174548-plasma PUFA association in 253 Chinese subjects (β = -0.57, P = 1.68 × 10-3). Rs174548 was also found associated with FADS1 (the major fatty acid desaturase of identified PUFAs) expression in liver tissues. Taken together, we found that rs174548 was associated with both PUFAs and lung cancer. Because rs174548 was the only mQTL variant of PUFAs reported by previous GWASs and explained a large proportion of heritability, we proposed that plasma PUFAs could be causally associated with lung cancer based on the idea of mendelian randomization. These findings provide a diet-related risk factor and may have important implications for prevention on lung cancer. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Outcomes from magnetic resonance imaging-confirmed symptomatic cervical disk herniation patients treated with high-velocity, low-amplitude spinal manipulative therapy: a prospective cohort study with 3-month follow-up.

    Science.gov (United States)

    Peterson, Cynthia K; Schmid, Christof; Leemann, Serafin; Anklin, Bernard; Humphreys, B Kim

    2013-10-01

    The purpose of this study was to investigate outcomes of patients with cervical radiculopathy from cervical disk herniation (CDH) who are treated with spinal manipulative therapy. Adult Swiss patients with neck pain and dermatomal arm pain; sensory, motor, or reflex changes corresponding to the involved nerve root; and at least 1 positive orthopaedic test for cervical radiculopathy were included. Magnetic resonance imaging-confirmed CDH linked with symptoms was required. Baseline data included 2 pain numeric rating scales (NRSs), for neck and arm, and the Neck Disability Index (NDI). At 2 weeks, 1 month, and 3 months after initial consultation, patients were contacted by telephone, and the NDI, NRSs, and patient's global impression of change data were collected. High-velocity, low-amplitude spinal manipulations were administered by experienced doctors of chiropractic. The proportion of patients responding "better" or "much better" on the patient's global impression of change scale was calculated. Pretreatment and posttreatment NRSs and NDIs were compared using the Wilcoxon test. Acute vs subacute/chronic patients' NRSs and NDIs were compared using the Mann-Whitney U test. Fifty patients were included. At 2 weeks, 55.3% were "improved," 68.9% at 1 month and 85.7% at 3 months. Statistically significant decreases in neck pain, arm pain, and NDI scores were noted at 1 and 3 months compared with baseline scores (P manipulative therapy, reported significant improvement with no adverse events. © 2013. Published by National University of Health Sciences All rights reserved.

  20. Hierarchical Naive Bayes for genetic association studies.

    Science.gov (United States)

    Malovini, Alberto; Barbarini, Nicola; Bellazzi, Riccardo; de Michelis, Francesca

    2012-01-01

    Genome Wide Association Studies represent powerful approaches that aim at disentangling the genetic and molecular mechanisms underlying complex traits. The usual "one-SNP-at-the-time" testing strategy cannot capture the multi-factorial nature of this kind of disorders. We propose a Hierarchical Naïve Bayes classification model for taking into account associations in SNPs data characterized by Linkage Disequilibrium. Validation shows that our model reaches classification performances superior to those obtained by the standard Naïve Bayes classifier for simulated and real datasets. In the Hierarchical Naïve Bayes implemented, the SNPs mapping to the same region of Linkage Disequilibrium are considered as "details" or "replicates" of the locus, each contributing to the overall effect of the region on the phenotype. A latent variable for each block, which models the "population" of correlated SNPs, can be then used to summarize the available information. The classification is thus performed relying on the latent variables conditional probability distributions and on the SNPs data available. The developed methodology has been tested on simulated datasets, each composed by 300 cases, 300 controls and a variable number of SNPs. Our approach has been also applied to two real datasets on the genetic bases of Type 1 Diabetes and Type 2 Diabetes generated by the Wellcome Trust Case Control Consortium. The approach proposed in this paper, called Hierarchical Naïve Bayes, allows dealing with classification of examples for which genetic information of structurally correlated SNPs are available. It improves the Naïve Bayes performances by properly handling the within-loci variability.

  1. Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI Study.

    Directory of Open Access Journals (Sweden)

    Toshiko Tanaka

    2009-01-01

    Full Text Available Polyunsaturated fatty acids (PUFA have a role in many physiological processes, including energy production, modulation of inflammation, and maintenance of cell membrane integrity. High plasma PUFA concentrations have been shown to have beneficial effects on cardiovascular disease and mortality. To identify genetic contributors of plasma PUFA concentrations, we conducted a genome-wide association study of plasma levels of six omega-3 and omega-6 fatty acids in 1,075 participants in the InCHIANTI study on aging. The strongest evidence for association was observed in a region of chromosome 11 that encodes three fatty acid desaturases (FADS1, FADS2, FADS3. The SNP with the most significant association was rs174537 near FADS1 in the analysis of arachidonic acid (AA; p = 5.95 x 10(-46. Minor allele homozygotes had lower AA compared to the major allele homozygotes and rs174537 accounted for 18.6% of the additive variance in AA concentrations. This SNP was also associated with levels of eicosadienoic acid (EDA; p = 6.78 x 10(-9 and eicosapentanoic acid (EPA; p = 1.07 x 10(-14. Participants carrying the allele associated with higher AA, EDA, and EPA also had higher low-density lipoprotein (LDL-C and total cholesterol levels. Outside the FADS gene cluster, the strongest region of association mapped to chromosome 6 in the region encoding an elongase of very long fatty acids 2 (ELOVL2. In this region, association was observed with EPA (rs953413; p = 1.1 x 10(-6. The effects of rs174537 were confirmed in an independent sample of 1,076 subjects participating in the GOLDN study. The ELOVL2 SNP was associated with docosapentanoic and DHA but not with EPA in GOLDN. These findings show that polymorphisms of genes encoding enzymes in the metabolism of PUFA contribute to plasma concentrations of fatty acids.

  2. GWAS and admixture mapping identify different asthma-associated loci in Latinos: The GALA II Study

    Science.gov (United States)

    Galanter, Joshua M; Gignoux, Christopher R; Torgerson, Dara G; Roth, Lindsey A; Eng, Celeste; Oh, Sam S; Nguyen, Elizabeth A; Drake, Katherine A; Huntsman, Scott; Hu, Donglei; Sen, Saunak; Davis, Adam; Farber, Harold J.; Avila, Pedro C.; Brigino-Buenaventura, Emerita; LeNoir, Michael A.; Meade, Kelley; Serebrisky, Denise; Borrell, Luisa N; Rodríguez-Cintrón, William; Estrada, Andres Moreno; Mendoza, Karla Sandoval; Winkler, Cheryl A.; Klitz, William; Romieu, Isabelle; London, Stephanie J.; Gilliland, Frank; Martinez, Fernando; Bustamante, Carlos; Williams, L Keoki; Kumar, Rajesh; Rodríguez-Santana, José R.; Burchard, and Esteban G.

    2013-01-01

    Background Asthma is a complex disease with both genetic and environmental causes. Genome-wide association studies of asthma have mostly involved European populations and replication of positive associations has been inconsistent. Objective To identify asthma-associated genes in a large Latino population with genome-wide association analysis and admixture mapping. Methods Latino children with asthma (n = 1,893) and healthy controls (n = 1,881) were recruited from five sites in the United States: Puerto Rico, New York, Chicago, Houston, and the San Francisco Bay Area. Subjects were genotyped on an Affymetrix World Array IV chip. We performed genome-wide association and admixture mapping to identify asthma-associated loci. Results We identified a significant association between ancestry and asthma at 6p21 (lowest p-value: rs2523924, p < 5 × 10−6). This association replicates in a meta-analysis of the EVE Asthma Consortium (p = 0.01). Fine mapping of the region in this study and the EVE Asthma Consortium suggests an association between PSORS1C1 and asthma. We confirmed the strong allelic association between the 17q21 asthma in Latinos (IKZF3, lowest p-value: rs90792, OR: 0.67, 95% CI 0.61 – 0.75, p = 6 × 10−13) and replicated associations in several genes that had previously been associated with asthma in genome-wide association studies. Conclusions Admixture mapping and genome-wide association are complementary techniques that provide evidence for multiple asthma-associated loci in Latinos. Admixture mapping identifies a novel locus on 6p21 that replicates in a meta-analysis of several Latino populations, while genome-wide association confirms the previously identified locus on 17q21. PMID:24406073

  3. Outcomes of acute and chronic patients with magnetic resonance imaging-confirmed symptomatic lumbar disc herniations receiving high-velocity, low-amplitude, spinal manipulative therapy: a prospective observational cohort study with one-year follow-up.

    Science.gov (United States)

    Leemann, Serafin; Peterson, Cynthia K; Schmid, Christof; Anklin, Bernard; Humphreys, B Kim

    2014-01-01

    The purposes of this study were to evaluate patients with low-back pain (LBP) and leg pain due to magnetic resonance imaging-confirmed disc herniation who are treated with high-velocity, low-amplitude spinal manipulation in terms of their short-, medium-, and long-term outcomes of self-reported global impression of change and pain levels at various time points up to 1 year and to determine if outcomes differ between acute and chronic patients using a prospective, cohort design. This prospective cohort outcomes study includes 148 patients (between ages of 18 and 65 years) with LBP, leg pain, and physical examination abnormalities with concordant lumbar disc herniations. Baseline numerical rating scale (NRS) data for LBP, leg pain, and the Oswestry questionnaire were obtained. The specific lumbar spinal manipulation was dependent upon whether the disc herniation was intraforaminal or paramedian as seen on the magnetic resonance images and was performed by a doctor of chiropractic. Outcomes included the patient's global impression of change scale for overall improvement, the NRS for LBP, leg pain, and the Oswestry questionnaire at 2 weeks, 1, 3, and 6 months, and 1 year after the first treatment. The proportion of patients reporting "improvement" on the patient's global impression of change scale was calculated for all patients and acute vs chronic patients. Pretreatment and posttreatment NRS scores were compared using the paired t test. Baseline and follow-up Oswestry scores were compared using the Wilcoxon test. Numerical rating scale and Oswestry scores for acute vs chronic patients were compared using the unpaired t test for NRS scores and the Mann-Whitney U test for Oswestry scores. Logistic regression analysis compared baseline variables with "improvement." Significant improvement for all outcomes at all time points was reported (P manipulation reported clinically relevant improvement. Copyright © 2014 National University of Health Sciences. Published by Mosby

  4. Autism and genetics: Clinical approach and association study with two markers of HRAS gene

    Energy Technology Data Exchange (ETDEWEB)

    Herault, J.; Petit, E.; Cherpi, C. [Laboratoire de Biochimie Medicale, Tours (France)] [and others

    1995-08-14

    Twin studies and familial aggregation studies indicate that genetic factors could play a role in infantile autism. In an earlier study, we identified a possible positive association between autism and a c-Harvey-ras (HRAS) oncogene marker at the 3{prime} end of the coding region. In an attempt to confirm this finding, we studied a larger population, well-characterized clinically and genetically. We report a positive association between autism and two HRAS markers, the 3{prime} marker used in the initial study and an additional marker in exon 1. 46 refs., 1 fig., 2 tabs.

  5. 'Smoking genes': a genetic association study.

    Directory of Open Access Journals (Sweden)

    Zoraida Verde

    Full Text Available Some controversy exists on the specific genetic variants that are associated with nicotine dependence and smoking-related phenotypes. The purpose of this study was to analyse the association of smoking status and smoking-related phenotypes (included nicotine dependence with 17 candidate genetic variants: CYP2A6*1×2, CYP2A6*2 (1799T>A [rs1801272], CYP2A6*9 (-48T>G [rs28399433], CYP2A6*12, CYP2A13*2 (3375C>T [rs8192789], CYP2A13*3 (7520C>G, CYP2A13*4 (579G>A, CYP2A13*7 (578C>T [rs72552266], CYP2B6*4 (785A>G, CYP2B6*9 (516G>T, CHRNA3 546C>T [rs578776], CHRNA5 1192G>A [rs16969968], CNR1 3764C>G [rs6928499], DRD2-ANKK1 2137G>A (Taq1A [rs1800497], 5HTT LPR, HTR2A -1438A>G [rs6311] and OPRM1 118A>G [rs1799971]. We studied the genotypes of the aforementioned polymorphisms in a cohort of Spanish smokers (cases, N = 126 and ethnically matched never smokers (controls, N = 80. The results showed significant between-group differences for CYP2A6*2 and CYP2A6*12 (both PA (Taq1A polymorphisms was 3.60 (95%CI: 1.75, 7.44 and 2.63 (95%CI: 1.41, 4.89 respectively. Compared with the wild-type genotype, the OR for being a non-smoker in carriers of the minor CYP2A6*2 allele was 1.80 (95%CI: 1.24, 2.65. We found a significant genotype effect (all P≤0.017 for the following smoking-related phenotypes: (i cigarettes smoked per day and CYP2A13*3; (ii pack years smoked and CYP2A6*2, CYP2A6*1×2, CYP2A13*7, CYP2B6*4 and DRD2-ANKK1 2137G>A (Taq1A; (iii nicotine dependence (assessed with the Fagestrom test and CYP2A6*9. Overall, our results suggest that genetic variants potentially involved in nicotine metabolization (mainly, CYP2A6 polymorphisms are those showing the strongest association with smoking-related phenotypes, as opposed to genetic variants influencing the brain effects of nicotine, e.g., through nicotinic acetylcholine (CHRNA5, serotoninergic (HTR2A, opioid (OPRM1 or cannabinoid receptors (CNR1.

  6. Fetal and maternal candidate single nucleotide polymorphism associations with cerebral palsy: a case-control study.

    Science.gov (United States)

    O'Callaghan, Michael E; Maclennan, Alastair H; Gibson, Catherine S; McMichael, Gai L; Haan, Eric A; Broadbent, Jessica L; Goldwater, Paul N; Painter, Jodie N; Montgomery, Grant W; Dekker, Gus A

    2012-02-01

    Previous studies have suggested associations between certain genetic variants and susceptibility to cerebral palsy (CP). This study was designed to assess established and novel maternal and child genetic and epidemiologic risk factors for CP along with their interactions. DNA from 587 case and 1154 control mother-child pairs was analyzed. A panel of 35 candidate single nucleotide polymorphisms (SNPs) were examined and included SNPs in genes associated with (1) thrombophilia, (2) inflammation, and (3) risk factors for CP (eg, preterm birth). Comparisons were specified a priori and made by using a χ(2) test. There were 40 fetal and 28 maternal associations with CP when analyzed by CP subtype, gestational age, genotypes of apolipoprotein E, and haplotypes of mannose-binding-lectin. After Bonferroni correction for multiple testing, no fetal or maternal candidate SNP was associated with CP or its subtypes. Only fetal carriage of prothrombin gene mutation remained marginally associated with hemiplegia in term infants born to mothers with a reported infection during pregnancy. Odds ratio directions of fetal SNP associations were compared with previously reported studies and confirmed no trend toward association. Except for the prothrombin gene mutation, individual maternal and fetal SNPs in our candidate panel were not found to be associated with CP outcome. Past reported SNP associations with CP were not confirmed, possibly reflecting type I error from small numbers and multiple testing in the original reports.

  7. Disentangling pooled triad genotypes for association studies.

    Science.gov (United States)

    Shi, Min; Umbach, David M; Weinberg, Clarice R

    2014-09-01

    Association studies that genotype affected offspring and their parents (triads) offer robustness to genetic population structure while enabling assessments of maternal effects, parent-of-origin effects, and gene-by-environment interaction. We propose case-parents designs that use pooled DNA specimens to make economical use of limited available specimens. One can markedly reduce the number of genotyping assays required by randomly partitioning the case-parent triads into pooling sets of h triads each and creating three pools from every pooling set, one pool each for mothers, fathers, and offspring. Maximum-likelihood estimation of relative risk parameters proceeds via log-linear modeling using the expectation-maximization algorithm. The approach can assess offspring and maternal genetic effects and accommodate genotyping errors and missing genotypes. We compare the power of our proposed analysis for testing offspring and maternal genetic effects to that based on a difference approach and that of the gold standard based on individual genotypes, under a range of allele frequencies, missing parent proportions, and genotyping error rates. Power calculations show that the pooling strategies cause only modest reductions in power if genotyping errors are low, while reducing genotyping costs and conserving limited specimens. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  8. Multiple sclerosis genetics: Results from meta-analyses of candidate-gene association studies.

    Science.gov (United States)

    Tizaoui, Kalthoum

    2017-11-02

    As a complex disease, multiple sclerosis (MS) susceptibility implicates many genetic and environmental factors. Usually, individual genetic association studies have several limitations, and results are specific to the population of study. The Meta-analysis approach has been proposed to resolve these limitations and to increase the power of statistical analyses. In this review, we summarize results from meta-analyses of candidate genes of MS. Using the keywords: multiple sclerosis, genetic polymorphism and meta-analysis, we searched electronic databases (PubMed, Embase and Web of Sciences) for published meta-analyses until May 2017. Meta-analyses confirmed the association of polymorphisms in fifteen candidate genes with MS disease. However, polymorphisms in fourteen genes showed none significant association. Results outlined the importance of confirmed genes to understand signaling pathways in MS disease and shed light on their utility to develop new drugs targets. Copyright © 2017. Published by Elsevier Ltd.

  9. High Throughput Analytical Techniques for the Determination and Confirmation of Residues of 653 Multiclass Pesticides and Chemical Pollutants in Tea by GC/MS, GC/MS/MS, and LC/MS/MS: Collaborative Study, First Action 2014.09.

    Science.gov (United States)

    Pang, Guo-Fang; Fan, Chun-Lin; Cao, Yan-Zhong; Yan, Fang; Li, Yan; Kang, Jian; Chen, Hui; Chang, Qiao-Ying

    2015-01-01

    collaborative study were excluded from further analysis and interpretation. The results presented are therefore the 6638 analytical results obtained from the 29 remaining laboratories, which included 1977 results generated by GC/MS, 1704 results by GC/MS/MS, and 2957 results by LC/MS/MS. It was determined after application of the Grubbs and Dixon tests for outliers to the data sets that there were 65 outlier results from the 1977 GC/MS results (3.3%), 65 outlier results from the 1704 GC/MS/MS results (3.8%), and 57 outlier results out of 2957 LC/MS/MS results (1.9%), representing 0.98, 0.98, and 0.86%, respectively, of the 6638 results generated in the study. Analysis with the AOAC statistical software package also confirmed that the method is rugged, and average recovery, average concentration, RSDr, RSDR, and HorRat values all meet recovery and reproducibility criteria for use in multiple laboratories. The Study Director is recommending this method for adoption as an AOAC First Action Official MethodSM.

  10. Experimental confirmation of Lenz’s law

    Science.gov (United States)

    Mayer, V. V.; Varaksina, E. I.

    2017-11-01

    The paper presents a series of experiments that demonstrate the phenomenon of electromagnetic induction. These make it possible to determine the direction of the induced current and so confirm Lenz’s Law. The simple experiments can be reproduced in a school laboratory and can be recommended for students’ project activity.

  11. escherichia coli serotypes confirmed in experimental mammary ...

    African Journals Online (AJOL)

    DJFLEX

    SEROTYPES CONFIRMED IN EXPERIMENTAL MAMMARY GLAND. INFECTIONS. P. A. AKPAN AND ... 037, 02a and 109) in mammary glands of experimental cows (cow 105, 107 and 102 respectively). Pathogenicity of the E. coli which ..... Akpan, P. A and Ikpeme, E. U., 2005. pathology of. Experimental Escherichia Coli ...

  12. Confirmed and Potential Sources of Legionella Reviewed.

    Science.gov (United States)

    van Heijnsbergen, Eri; Schalk, Johanna A C; Euser, Sjoerd M; Brandsema, Petra S; den Boer, Jeroen W; de Roda Husman, Ana Maria

    2015-04-21

    Legionella bacteria are ubiquitous in natural matrices and man-made systems. However, it is not always clear if these reservoirs can act as source of infection resulting in cases of Legionnaires' disease. This review provides an overview of reservoirs of Legionella reported in the literature, other than drinking water distribution systems. Levels of evidence were developed to discriminate between potential and confirmed sources of Legionella. A total of 17 systems and matrices could be classified as confirmed sources of Legionella. Many other man-made systems or natural matrices were not classified as a confirmed source, since either no patients were linked to these reservoirs or the supporting evidence was weak. However, these systems or matrices could play an important role in the transmission of infectious Legionella bacteria; they might not yet be considered in source investigations, resulting in an underestimation of their importance. To optimize source investigations it is important to have knowledge about all the (potential) sources of Legionella. Further research is needed to unravel what the contribution is of each confirmed source, and possibly also potential sources, to the LD disease burden.

  13. Manned in Situ Confirmation of Lunar Ice

    Science.gov (United States)

    Gerené, S. P. B.; Hummeling, R. W. J.; Ockels, W. J.

    A study is performed to investigate the feasibility of a manned expedition to the Moon using the European Ariane-5 launcher. The primary objective of this lunar mission is to confirm the presence of water at the South-Pole craters. It is believed that these permanently shadowed craters contain water in the form of ice. Secondary objective is to perform lunar surface science and making a first step towards a lunar outpost. Early results show that a minimum of two Ariane-5 launches is required. In this `two Ariane' scenario the first launch will bring a Lunar Landing Vehicle (LLV) into low lunar orbit. The second will launch two astronauts in a Crew Transfer Vehicle into a rendez- vous trajectory with the LLV. Arrived at the Moon, the astronauts will enter the LLV, undock from the CTV and land at the designated site located near the rim of the South-Pole Shackleton crater. The transfer strategy for both spacecraft will be the so-called direct transfer, taking about four days. At arrival the LLV will start mapping the landing site at a ground resolution of one meter. As a consequence of the polar orbit, the CTV has to arrive fourteen days later and surface operations can take about twelve days, accumulating in a total mission-duration of 36 days. 32 days for the CTV and 22 days for the LLV. In case a `two Ariane' flight does not posses sufficient capabilities also a `three Ariane' scenario is developed, in which the LLV is split-up into two stages and launched separately. These two will dock at the Moon forming a descent stage and an ascent stage. The third launch will be a CTV. During surface operations, astronauts will set up a solar power unit, install the sample retrieval system and carry out surface science. Samples of the crater floor will be retrieved by means of a probe or robot guided along a cable suspended over the crater rim. Also, this paper shows the way in which European astronauts can be brought to the Moon for other future missions, like the

  14. Sequence imputation of HPV16 genomes for genetic association studies.

    Directory of Open Access Journals (Sweden)

    Benjamin Smith

    Full Text Available Human Papillomavirus type 16 (HPV16 causes over half of all cervical cancer and some HPV16 variants are more oncogenic than others. The genetic basis for the extraordinary oncogenic properties of HPV16 compared to other HPVs is unknown. In addition, we neither know which nucleotides vary across and within HPV types and lineages, nor which of the single nucleotide polymorphisms (SNPs determine oncogenicity.A reference set of 62 HPV16 complete genome sequences was established and used to examine patterns of evolutionary relatedness amongst variants using a pairwise identity heatmap and HPV16 phylogeny. A BLAST-based algorithm was developed to impute complete genome data from partial sequence information using the reference database. To interrogate the oncogenic risk of determined and imputed HPV16 SNPs, odds-ratios for each SNP were calculated in a case-control viral genome-wide association study (VWAS using biopsy confirmed high-grade cervix neoplasia and self-limited HPV16 infections from Guanacaste, Costa Rica.HPV16 variants display evolutionarily stable lineages that contain conserved diagnostic SNPs. The imputation algorithm indicated that an average of 97.5±1.03% of SNPs could be accurately imputed. The VWAS revealed specific HPV16 viral SNPs associated with variant lineages and elevated odds ratios; however, individual causal SNPs could not be distinguished with certainty due to the nature of HPV evolution.Conserved and lineage-specific SNPs can be imputed with a high degree of accuracy from limited viral polymorphic data due to the lack of recombination and the stochastic mechanism of variation accumulation in the HPV genome. However, to determine the role of novel variants or non-lineage-specific SNPs by VWAS will require direct sequence analysis. The investigation of patterns of genetic variation and the identification of diagnostic SNPs for lineages of HPV16 variants provides a valuable resource for future studies of HPV16

  15. Genetics in psychiatry: common variant association studies

    Directory of Open Access Journals (Sweden)

    Buxbaum Joseph D

    2010-03-01

    Full Text Available Abstract Many psychiatric conditions and traits are associated with significant heritability. Genetic risk for psychiatric conditions encompass rare variants, identified due to major effect, as well as common variants, the latter analyzed by association analyses. We review guidelines for common variant association analyses, undertaking after assessing evidence of heritability. We highlight the importance of: suitably large sample sizes; an experimental design that controls for ancestry; careful data cleaning; correction for multiple testing; small P values for positive findings; assessment of effect size for positive findings; and, inclusion of an independent replication sample. We also note the importance of a critical discussion of any prior findings, biological follow-up where possible, and a means of accessing the raw data.

  16. Confirmation of bistable stellar differential rotation profiles

    Science.gov (United States)

    Käpylä, P. J.; Käpylä, M. J.; Brandenburg, A.

    2014-10-01

    Context. Solar-like differential rotation is characterized by a rapidly rotating equator and slower poles. However, theoretical models and numerical simulations can also result in a slower equator and faster poles when the overall rotation is slow. Aims: We study the critical rotational influence under which differential rotation flips from solar-like (fast equator, slow poles) to an anti-solar one (slow equator, fast poles). We also estimate the non-diffusive (Λ effect) and diffusive (turbulent viscosity) contributions to the Reynolds stress. Methods: We present the results of three-dimensional numerical simulations of mildly turbulent convection in spherical wedge geometry. Here we apply a fully compressible setup which would suffer from a prohibitive time step constraint if the real solar luminosity was used. To avoid this problem while still representing the same rotational influence on the flow as in the Sun, we increase the luminosity by a factor of roughly 106 and the rotation rate by a factor of 102. We regulate the convective velocities by varying the amount of heat transported by thermal conduction, turbulent diffusion, and resolved convection. Results: Increasing the efficiency of resolved convection leads to a reduction of the rotational influence on the flow and a sharp transition from solar-like to anti-solar differential rotation for Coriolis numbers around 1.3. We confirm the recent finding of a large-scale flow bistability: contrasted with running the models from an initial condition with unprescribed differential rotation, the initialization of the model with certain kind of rotation profile sustains the solution over a wider parameter range. The anti-solar profiles are found to be more stable against perturbations in the level of convective turbulent velocity than the solar-type solutions. Conclusions: Our results may have implications for real stars that start their lives as rapid rotators implying solar-like rotation in the early main

  17. Padrões dermatoscópicos do molusco contagioso: estudo de 211 lesões confirmadas por exame histopatológico Dermoscopic patterns of molluscum contagiosum: a study of 211 lesions confirmed by histopathology

    Directory of Open Access Journals (Sweden)

    Mayra Ianhez

    2011-02-01

    Full Text Available FUNDAMENTOS: Embora de fácil diagnóstico, o molusco contagioso pode apresentar-se como lesões inflamadas, únicas ou pequenas de difícil diagnóstico. OBJETIVO: Descrever características dermatoscópicas do molusco contagioso e comparar achados do exame clínico e dermatoscópico. MÉTODOS: Avaliou-se clínica e dermatoscopicamente lesões confirmadas pela histopatologia em 57 pacientes. RESULTADOS: Nos exames clínico e dermatoscópico de 211 lesões, foram visualizados orifícios em 50,24% e 96,68% das lesões e vasos em 6,16% e 89,10% delas, respectivamente. Os padrões vasculares encontrados em 188 lesões que apresentaram vasos à dermatoscopia foram coroa (72,34%, radial (54,25% e puntiforme (20,21%. Metade das 188 lesões apresentou padrão vascular combinado, sendo o padrão em flor (novo padrão vascular responsável por 19,68%. Foram identificados mais orifícios e vasos no exame dermatoscópico que no clínico, inclusive naquelas com inflamação, eczema perilesional e de tamanho pequeno. Vasos puntiformes relacionaram-se com inflamação, escoriação e eczema perilesional. CONCLUSÕES: A dermatoscopia das lesões de molusco mostrou-se superior ao exame dermatológico mesmo quando seu diagnóstico clínico torna-se difícil. A presença de orifícios, vasos e padrões vasculares específicos auxilia no seu diagnóstico e na diferenciação de outras lesões de pele.BACKGROUNDS: Although easily diagnosed, molluscum contagiosum may present as a single lesion or as several small, inflamed lesions of difficult diagnosis. OBJECTIVE: To describe the dermoscopic characteristics of molluscum contagiosum and to compare the findings from clinical examination and dermoscopy. METHODS: Histopathologically confirmed lesions were evaluated clinically and dermoscopically in 57 patients. RESULTS: At clinical examination and dermoscopy of 211 lesions, orifices were visualized in 50.24% and 96.68% of the lesions, and vessels in 6.16% and 89

  18. Exploratory investigation of genetic associations with basal cell carcinoma risk: genome-wide association study in Jeju Island, Korea.

    Science.gov (United States)

    Yun, Byung Min; Song, Jung-Kook; Lee, Ji-Young

    2014-01-01

    Little is known about the genetic associations with Basal cell carcinoma (BCC) risk in non-Caucasian populations, in which BCC is rare, as in Korea. We here conducted a pilot genome-wide association study (GWAS) in 12 patients and 48 standard controls. A total of 263,511 SNPs were analyzed with the Illumina HumanOmni1 Quad v1.0 DNA Analysis BeadChip for cases and Korean HapMap 570K for controls. SNP-based analyses, based on the allele genetic model with adjustment for sex and age showed suggestive associations with BCC risk for 6 SNPs with a P-value (P associations were not statistically significant after Bonferroni correction: rs1040503, rs2216491, rs13407683, rs4751072, rs9891263, and rs1368474. In addition, results from gene-based analyses showed suggestive associations with BCC risk for 33 candidate genes with a P-value (P associations with BCC (P > 0.05), likely due to the smaller sample size. Although this was a small-scale negative study, to our knowledge, we have conducted the first GWAS for BCC risk in an Asian population. Further large studies in non-Caucasian populations are required to achieve statistical significance and confirm these findings.

  19. Interferometric confirmation of `water fountain' candidates

    Science.gov (United States)

    Gómez, José F.; Suárez, Olga; Rizzo, J. Ricardo; Uscanga, Lucero; Walsh, Andrew; Miranda, Luis F.; Bendjoya, Philippe

    2017-06-01

    Water fountain stars (WFs) are evolved objects with water masers tracing high-velocity jets (up to several hundreds of km s-1). They could represent one of the first manifestations of collimated mass-loss in evolved objects and thus be a key to understanding the shaping mechanisms of planetary nebulae. Only 13 objects had been confirmed so far as WFs with interferometer observations. We present new observations with the Australia Telescope Compact Array and archival observations with the Very Large Array of four objects that are considered to be WF candidates, mainly based on single-dish observations. We confirm IRAS 17291-2147 and IRAS 18596+0315 (OH 37.1-0.8) as bona fide members of the WF class, with high-velocity water maser emission consistent with tracing bipolar jets. We argue that IRAS 15544-5332 has been wrongly considered as a WF in previous works, since we see no evidence in our data nor in the literature that this object harbours high-velocity water maser emission. In the case of IRAS 19067+0811, we did not detect any water maser emission, so its confirmation as a WF is still pending. With the result of this work, there are 15 objects that can be considered confirmed WFs. We speculate that there is no significant physical difference between WFs and obscured post-AGB stars in general. The absence of high-velocity water maser emission in some obscured post-AGB stars could be attributed to a variability or orientation effect.

  20. Effect of delayed-release dimethyl fumarate on no evidence of disease activity in relapsing-remitting multiple sclerosis: integrated analysis of the phase III DEFINE and CONFIRM studies.

    Science.gov (United States)

    Havrdova, E; Giovannoni, G; Gold, R; Fox, R J; Kappos, L; Phillips, J Theodore; Okwuokenye, M; Marantz, J L

    2017-05-01

    Significant effects on clinical/neuroradiological disease activity have been reported in patients with relapsing-remitting multiple sclerosis treated with delayed-release dimethyl fumarate (DMF) in phase III DEFINE/CONFIRM trials. We conducted a post hoc analysis of integrated data from DEFINE/CONFIRM to evaluate the effect of DMF on achieving no evidence of disease activity (NEDA) in patients with relapsing-remitting multiple sclerosis. The analysis included patients randomized to DMF 240 mg twice daily, placebo or glatiramer acetate (CONFIRM only) for ≤2 years. A time-to-event method was used to estimate the percentage of patients achieving NEDA. Clinical NEDA (no relapses/no 12-week confirmed disability progression) was analysed in the intention-to-treat (ITT) population. Neuroradiological (no new/newly enlarging T2 hyperintense lesions/no gadolinium-enhancing lesions) and overall NEDA (clinical and neuroradiological NEDA) were analysed in the magnetic resonance imaging (MRI) cohort. The ITT and MRI populations comprised 1540 and 692 patients, respectively. The percentage of patients with clinical NEDA (ITT population) and neuroradiological NEDA (MRI cohort) was higher with DMF versus placebo over 2 years [clinical NEDA: 38.9% relative reduction; hazard ratio (HR), 0.61; 95% confidence interval (CI), 0.52-0.72; P < 0.0001; neuroradiological NEDA: 40.0% relative reduction; HR, 0.60; 95% CI, 0.49-0.73; P < 0.0001]. The percentage of patients achieving overall NEDA (MRI cohort) was also higher with DMF (26%) versus placebo (12%) over 2 years, with a relative risk reduction of 42.7% (HR, 0.57; 95% CI, 0.48-0.69; P < 0.0001). A significantly higher percentage of patients treated with DMF achieved NEDA status over 2 years compared with placebo. © 2017 Biogen. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

  1. CT features of intrapulmonary lymph nodes confirmed by cytology.

    Science.gov (United States)

    Shaham, Dorith; Vazquez, Madeline; Bogot, Naama R; Henschke, Claudia I; Yankelevitz, David F

    2010-01-01

    We retrospectively assessed the computed tomography features of intrapulmonary lymph nodes confirmed by cytology in 18 patients. The median size of the lymph nodes was 5.8 mm (range=3.3-8.5 mm). All were below the carina, and only one nodule, which was associated with an interlobar fissure, was over 20 mm from the chest wall. The nodules were oval, round, triangular, or trapezoidal; had sharply defined borders; were solid and homogenous; and were without calcification. Six nodules (33.3%) had a discrete thin tag extending to the pleura. Intrapulmonary lymph nodes can reliably be confirmed by fine needle aspiration with cytological diagnosis.

  2. Pathological Confirmation of Optic Neuropathy in Familial Dysautonomia.

    Science.gov (United States)

    Mendoza-Santiesteban, Carlos E; Palma, Jose-Alberto; Hedges, Thomas R; Laver, Nora V; Farhat, Nada; Norcliffe-Kaufmann, Lucy; Kaufmann, Horacio

    2017-03-01

    Clinical data suggest that optic neuropathy and retinal ganglion cell loss are the main cause of visual decline in patients with familial dysautonomia, but this has not previously been confirmed by pathological analyses. We studied retinas and optic nerves in 6 eyes from 3 affected patients obtained at autopsy. Analyses included routine neurohistology and immunohistochemistry for neurofilaments, cytochrome c oxidase (COX), and melanopsin-containing ganglion cells. We observed profound axon loss in the temporal portions of optic nerves with relative preservation in the nasal portions; this correlated with clinical and optical coherence tomography findings in 1 patient. Retinal ganglion cell layers were markedly reduced in the central retina, whereas melanopsin-containing ganglion cells were relatively spared. COX staining was reduced in the temporal portions of the optic nerve indicating reduced mitochondrial density. Axonal swelling with degenerating lysosomes and mitochondria were observed by electron microscopy. These findings support the concept that there is a specific optic neuropathy and retinopathy in patients with familial dysautonomia similar to that seen in other optic neuropathies with mitochondrial dysfunction. This raises the possibility that defective expression of the IkB kinase complex-associated protein (IKAP) resulting from mutations in IKBKAP affects mitochondrial function in the metabolism-dependent retinal parvocellular ganglion cells in this condition. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

  3. Feedback that confirms reward expectation triggers auditory cortex activity.

    Science.gov (United States)

    Weis, Tina; Brechmann, André; Puschmann, Sebastian; Thiel, Christiane M

    2013-10-01

    Associative learning studies have shown that the anticipation of reward and punishment shapes the representation of sensory stimuli, which is further modulated by dopamine. Less is known about whether and how reward delivery activates sensory cortices and the role of dopamine at that time point of learning. We used an appetitive instrumental learning task in which participants had to learn that a specific class of frequency-modulated tones predicted a monetary reward following fast and correct responses in a succeeding reaction time task. These fMRI data were previously analyzed regarding the effect of reward anticipation, but here we focused on neural activity to the reward outcome relative to the reward expectation and tested whether such activation in the reward reception phase is modulated by L-DOPA. We analyzed neural responses at the time point of reward outcome under three different conditions: 1) when a reward was expected and received, 2) when a reward was expected but not received, and 3) when a reward was not expected and not received. Neural activity in auditory cortex was enhanced during feedback delivery either when an expected reward was received or when the expectation of obtaining no reward was correct. This differential neural activity in auditory cortex was only seen in subjects who learned the reward association and not under dopaminergic modulation. Our data provide evidence that auditory cortices are active at the time point of reward outcome. However, responses are not dependent on the reward itself but on whether the outcome confirmed the subject's expectations.

  4. Stereotype confirmation concerns predict dropout from cognitive behavioral therapy for social anxiety disorder.

    Science.gov (United States)

    Johnson, Suzanne; Price, Matthew; Mehta, Natasha; Anderson, Page L

    2014-08-19

    There are high attrition rates observed in efficacy studies for social anxiety disorder, and research has not identified consistent nor theoretically meaningful predictors of dropout. Pre-treatment symptom severity and demographic factors, such as age and gender, are sometimes predictive of dropout. The current study examines a theoretically meaningful predictor of attrition based on experiences associated with social group membership rather than differences between social group categories--fear of confirming stereotypes. This is a secondary data analysis of a randomized controlled trial comparing two cognitive behavioral treatments for social anxiety disorder: virtual reality exposure therapy and exposure group therapy. Participants (N = 74) with a primary diagnosis of social anxiety disorder who were eligible to participate in the parent study and who self-identified as either "African American" (n = 31) or "Caucasian" (n = 43) completed standardized self-report measures of stereotype confirmation concerns (SCC) and social anxiety symptoms as part of a pre-treatment assessment battery. Hierarchical logistic regression showed that greater stereotype confirmation concerns were associated with higher dropout from therapy--race, age, gender, and pre-treatment symptom severity were not. Group treatment also was associated with higher dropout. These findings urge further research on theoretically meaningful predictors of attrition and highlight the importance of addressing cultural variables, such as the experience of stereotype confirmation concerns, during treatment of social anxiety to minimize dropout from therapy.

  5. The Danish Association for Science and Technology Studies

    DEFF Research Database (Denmark)

    A presentation of the Danish Association for Science and Technology Studies (DASTS). Organization, experiences, challenges and future developments.......A presentation of the Danish Association for Science and Technology Studies (DASTS). Organization, experiences, challenges and future developments....

  6. Genome-wide association study of sporadic brain arteriovenous malformations

    NARCIS (Netherlands)

    Weinsheimer, S.; Bendjilali, N.; Nelson, J.; Guo, D.E.; Zaroff, J.G.; Sidney, S.; McCulloch, C.E.; Salman, R. Al-Shahi; Berg, J.N.; Koeleman, B.P.C.; Simon, M.; Bostroem, A.; Fontanella, M.; Sturiale, C.L.; Pola, R.; Puca, A.; Lawton, M.T.; Young, W.L.; Pawlikowska, L.; Klijn, C.J.M.; Kim, H.

    2016-01-01

    BACKGROUND: The pathogenesis of sporadic brain arteriovenous malformations (BAVMs) remains unknown, but studies suggest a genetic component. We estimated the heritability of sporadic BAVM and performed a genome-wide association study (GWAS) to investigate association of common single nucleotide

  7. Association study of nonsynonymous single nucleotide polymorphisms in schizophrenia

    DEFF Research Database (Denmark)

    Carrera, Noa; Arrojo, Manuel; Sanjuán, Julio

    2012-01-01

    Genome-wide association studies using several hundred thousand anonymous markers present limited statistical power. Alternatively, association studies restricted to common nonsynonymous single nucleotide polymorphisms (nsSNPs) have the advantage of strongly reducing the multiple testing problem, ...

  8. Genome-wide Association Study and Admixture Mapping Reveal New Loci Associated with Total IgE Levels in Latinos

    Science.gov (United States)

    Pino-Yanes, Maria; Gignoux, Christopher R.; Galanter, Joshua M.; Levin, Albert M.; Campbell, Catarina D.; Eng, Celeste; Huntsman, Scott; Nishimura, Katherine K.; Gourraud, Pierre-Antoine; Mohajeri, Kiana; O'Roak, Brian J.; Hu, Donglei; Mathias, Rasika A.; Nguyen, Elizabeth A.; Roth, Lindsey A.; Padhukasahasram, Badri; Moreno-Estrada, Andres; Sandoval, Karla; Winkler, Cheryl A.; Lurmann, Fred; Davis, Adam; Farber, Harold J.; Meade, Kelley; Avila, Pedro C.; Serebrisky, Denise; Chapela, Rocio; Ford, Jean G.; Lenoir, Michael A.; Thyne, Shannon M.; Brigino-Buenaventura, Emerita; Borrell, Luisa N.; Rodriguez-Cintron, William; Sen, Saunak; Kumar, Rajesh; Rodriguez-Santana, Jose R.; Bustamante, Carlos D.; Martinez, Fernando D.; Raby, Benjamin A.; Weiss, Scott T.; Nicolae, Dan L.; Ober, Carole; Meyers, Deborah A.; Bleecker, Eugene R.; Mack, Steven J.; Hernandez, Ryan D.; Eichler, Evan E.; Barnes, Kathleen C.; Williams, L. Keoki; Torgerson, Dara G.; Burchard, Esteban G.

    2014-01-01

    Background Immunoglobulin E (IgE) is a key mediator of allergic inflammation and is frequently elevated in allergic disorders. Objective To identify genetic variants associated with IgE levels in Latinos. Methods We performed a genome-wide association study (GWAS) and admixture mapping of total IgE levels in 3,334 Latinos from the Genes-environments & Admixture in Latino Americans (GALA II) study. Replication was evaluated in 454 Latinos, 1,564 European Americans, and 3,187 African Americans from independent studies. Results We confirmed associations of six genes identified by previous GWAS and identified a novel genome-wide significant association of a polymorphism in ZNF365 with total IgE (rs200076616, p=2.3x10−8). We next identified four admixture mapping peaks (6p21.32-p22.1, 13p22-31, 14q23.2, and 22q13.1) where local African, European, and/or Native American ancestry was significantly associated with IgE levels. The most significant peak was 6p21.32-p22.1, where Native American ancestry was associated with lower levels of IgE (p=4.95x10−8). All but 22q13.1 were replicated in an independent sample of Latinos, and two of the peaks were replicated in African Americans (6p21.32-p22.1 and 14q23.2). Fine mapping of 6p21.32-p22.1 identified six genome-wide significant single nucleotide polymorphisms in Latinos, two of which replicated in European Americans. Another SNP was peak-wide significant within 14q23.2 in African Americans (rs1741099, p=3.7x10−6), and replicated in non-African American samples (p=0.011). Conclusion We confirmed genetic associations at six genes, and identified novel associations within ZNF365, HLA-DQA1, and 14q23.2. Our results highlight the importance of studying diverse, multi-ethnic populations to uncover novel loci associated with total IgE levels. PMID:25488688

  9. Preliminary Analysis of Remote Monitoring & Robotic Concepts for Performance Confirmation

    Energy Technology Data Exchange (ETDEWEB)

    D.A. McAffee

    1997-02-18

    As defined in 10 CFR Part 60.2, Performance Confirmation is the ''program of tests, experiments and analyses which is conducted to evaluate the accuracy and adequacy of the information used to determine with reasonable assurance that the performance objectives for the period after permanent closure will be met''. The overall Performance Confirmation program begins during site characterization and continues up to repository closure. The main purpose of this document is to develop, explore and analyze initial concepts for using remotely operated and robotic systems in gathering repository performance information during Performance Confirmation. This analysis focuses primarily on possible Performance Confirmation related applications within the emplacement drifts after waste packages have been emplaced (post-emplacement) and before permanent closure of the repository (preclosure). This will be a period of time lasting approximately 100 years and basically coincides with the Caretaker phase of the project. This analysis also examines, to a lesser extent, some applications related to Caretaker operations. A previous report examined remote handling and robotic technologies that could be employed during the waste package emplacement phase of the project (Reference 5.1). This analysis is being prepared to provide an early investigation of possible design concepts and technical challenges associated with developing remote systems for monitoring and inspecting activities during Performance Confirmation. The writing of this analysis preceded formal development of Performance Confirmation functional requirements and program plans and therefore examines, in part, the fundamental Performance Confirmation monitoring needs and operating conditions. The scope and primary objectives of this analysis are to: (1) Describe the operating environment and conditions expected in the emplacement drifts during the preclosure period. (Presented in Section 7.2). (2

  10. [Empirical antimicrobial therapy in ICU admitted patients. Influence of microbiological confirmation on the length of treatment].

    Science.gov (United States)

    Nuvials, Xavier; Arnau, Elena; Serra, Joaquim; Alcaraz, Rosa; Caballero, Jesús; Laborda, César; Pérez, Marcos; Larrosa, M Nieves; Palomar, Mercedes

    2014-12-01

    Introduction. Most patients admitted to the Intensive Care Units (ICU) receive antimicrobial treatment. A proper therapeutic strategy may be useful in decreasing inappropriate empirical antibiotic treatments. When the infection is not microbiologically confirmed, the antimicrobial streamlining may be difficult. Nevertheless, there is scant information about the influence of the microbiological confirmation of the infections on empirical antimicrobial treatment duration. Method. Post-hoc analysis of prospective data (ENVIN-UCI register) and observational study of patients admitted (> 24 hours) in a medico-surgical ICU, through the three-months annual surveillance interval for a period of ten years, receiving antimicrobial treatment for treating an infection. Demographic, infection and microbiological data were collected as well as empirical antimicrobial treatment and causes of adaptation. The main goal was to establish the influence of microbiological confirmation on empirical antimicrobial treatment duration. Results. During the study period 1,526 patients were included, 1,260 infections were diagnosed and an empirical antibiotic treatment was started in 1,754 cases. Infections were microbiologically confirmed in 1,073 (62.2%) of the empirical antibiotic treatment. In 593 (55.3%) cases, the antimicrobial treatment was considered appropriate. The main cause of treatment adaptation in the microbiologically confirmed infections was streamlining (39%). The microbiological confirmation of the infection was not associated with significantly shorter empirical antibiotic treatments (6.6 ± 5.2 VS. 6.8 ± 4.5 days). Conclusion. The microbiological confirmation of infections in patients admitted to UCI was associated with a higher reduction of antimicrobial spectrum, although had no effect on the length of empirical antimicrobial therapy.

  11. The efficacy of feeding tubes: confirmation and loss.

    Science.gov (United States)

    Taylor, Stephen J; McWilliam, Helen; Allan, Kaylee; Hocking, Paul

    Around 5% of hospital patients require enteral tube feeding, yet its efficacy and costs are poorly understood. The authors examined radio-opacity, reason for repeat X-ray and overall cost in consecutive patients having tubes confirmed by X-ray when using polyvinylchloride (PVC) Ryles tubes versus CORFLO® (CORTRAK Medsystems) polyurethane tubes (PUTs); and confirmation method and reason for tube loss over an enteral episode. Despite higher PUT cost, because more Ryles tubes required re-X-ray ± radio-contrast injection (0% compared with 26%, p=0.029), overall cost was almost identical (Corflo: £54.2 vs Ryles: £54.6). Confirmation of tube position by X-ray remains more common than pH (51% compared with 45%) and tube loss is mostly as a result of inadvertent patient removal (54%). These studies show that: a) when using X-ray confirmation, PUTs and PVC Ryles tube cost is similar; b) despite pH being taught as first-line confirmation, X-ray remains the most common method therefore PUT use may further reduce cost when staff and outcome costs are included. In addition, more reliable and repeatable bedside confirmation methods are required; c) most tube loss is potentially preventable by use of nasal bridles. Larger studies are required to establish baseline data on problems and cost-effectiveness of enteral tube feeding before intervention trials.

  12. Troubleshooting Requests e-mail Confirmation

    CERN Multimedia

    TS Department

    2004-01-01

    In an ongoing effort to improve quality of the repair requests, a new e-mail confirmation automatic system will be implemented starting from the 21st October. All repair requests transmitted to the TCR (72201) or the FM Helpdesk (77777) will be confirmed in an e-mail to the requestor, provided that the latter has a valid e-mail address in the HR database. The e-mail will contain a reference number, a brief description of the problem, the location and a contact where more information can be obtained. A second e-mail will be sent when the processing of the repair request is finished. We hope that this initiative will improve the transparency and quality of our service. Helpdesk Troubleshooting Requests (reminder) We remind you that all the repair requests and other communication concerning the CERN machine buildings have to be transmitted to the TCR via 72201, whereas the ones concerning tertiary buildings are handled directly by the FM helpdesk under the phone number 77777, i.e. problems on systems and equ...

  13. Genome-wide association study identifies the GLDC/IL33 locus associated with survival of osteosarcoma patients.

    Science.gov (United States)

    Koster, Roelof; Panagiotou, Orestis A; Wheeler, William A; Karlins, Eric; Gastier-Foster, Julie M; Caminada de Toledo, Silvia Regina; Petrilli, Antonio S; Flanagan, Adrienne M; Tirabosco, Roberto; Andrulis, Irene L; Wunder, Jay S; Gokgoz, Nalan; Patiño-Garcia, Ana; Lecanda, Fernando; Serra, Massimo; Hattinger, Claudia; Picci, Piero; Scotlandi, Katia; Thomas, David M; Ballinger, Mandy L; Gorlick, Richard; Barkauskas, Donald A; Spector, Logan G; Tucker, Margaret; Belynda, D Hicks; Yeager, Meredith; Hoover, Robert N; Wacholder, Sholom; Chanock, Stephen J; Savage, Sharon A; Mirabello, Lisa

    2017-12-06

    Survival rates for osteosarcoma, the most common primary bone cancer, have changed little over the past three decades and are particularly low for patients with metastatic disease. We conducted a multi-institutional genome-wide association study (GWAS) to identify germline genetic variants associated with overall survival in 632 patients with osteosarcoma, including 523 patients of European ancestry and 109 from Brazil. We conducted a time-to-event analysis and estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards models, with and without adjustment for metastatic disease. The results were combined across the European and Brazilian case sets using a random-effects meta-analysis. The strongest association after meta-analysis was for rs3765555 at 9p24.1, which was inversely associated with overall survival (HR = 1.76; 95% CI 1.41-2.18, p = 4.84 × 10-7 ). After imputation across this region, the combined analysis identified two SNPs that reached genome-wide significance. The strongest single association was with rs55933544 (HR = 1.9; 95% CI 1.5-2.4; p = 1.3 × 10-8 ), which localizes to the GLDC gene, adjacent to the IL33 gene and was consistent across both the European and Brazilian case sets. Using publicly available data, the risk allele was associated with lower expression of IL33 and low expression of IL33 was associated with poor survival in an independent set of patients with osteosarcoma. In conclusion, we have identified the GLDC/IL33 locus on chromosome 9p24.1 as associated with overall survival in patients with osteosarcoma. Further studies are needed to confirm this association and shed light on the biological underpinnings of this susceptibility locus. © 2017 UICC.

  14. Sciatica: Detection and Confirmation by New Method

    Science.gov (United States)

    Nadkarni, Sunil

    2014-01-01

    We need to overcome limitations of present assessment and also integrate newer research in our work about sciatica. Inflammation induces changes in the DRG and nerve root. It sensitizes the axons. Nociceptor is a unique axon. It is pseudo unipolar: both its ends, central and peripheral, behave in similar fashion. The nerve in periphery which carries these axons may selectively become sensitive to mechanical pressure--“mechanosensitized,” as we coin the phrase. Many pain questionnaires are used and are effective in identifying neuropathic pain solely on basis of descriptors but they do not directly physically correlate nerve root and pain. A thorough neurological evaluation is always needed. Physical examination is not direct pain assessment but testing mobility of nerve root and its effect on pain generation. There is a dogmatic dominance of dermatomes in assessment of leg pain. They are unreliable. Images may not correlate with symptoms and pathology in about 28% of cases. Electrophysiology may be normal in purely inflamed nerve root. Palpation may help in such inflammatory setting to refine our assessment further. Confirmation of sciatica is done by selective nerve root block (SNRB) today but it is fraught with several complications and needs elaborate inpatient and operating room set up. We have used the unique property of the pseudo unipolar axon that both its ends have similar functional properties and so inject along its peripheral end sodium channel blockers to block the basic cause of the mechanosensitization namely upregulated sodium channels in the root or DRG. Thus using palpation we may be able to detect symptomatic nerve in stage of inflammation and with distal end injection, along same inflamed nerve we may be able to abolish and so confirm sciatica. Discussions of sciatica pain diagnosis tend to immediately shift and centre on the affected disc rather than the nerve. Theoretically it may be possible to detect the affected nerve by palpating the

  15. Histopathology confirms white-nose syndrome in bats in Europe

    Science.gov (United States)

    Pikula, J.; Bandouchova, H.; Novotny, L.; Meteyer, C.U.; Zukal, J.; Irwin, N.R.; Zima, J.; Martinkova, N.

    2012-01-01

    White-nose syndrome, associated with the fungal skin infection geomycosis, caused regional population collapse in bats in North America. Our results, based on histopathology, show the presence of white-nose syndrome in Europe. Dermatohistopathology on two bats (Myotis myotis) found dead in March 2010 with geomycosis in the Czech Republic had characteristics resembling Geomyces destructans infection in bats confirmed with white-nose syndrome in US hibernacula. In addition, a live M. myotis, biopsied for histopathology during hibernation in April 2011, had typical fungal infection with cupping erosion and invasion of muzzle skin diagnostic for white-nose syndrome and conidiospores identical to G. destructans that were genetically confirmed as G. destructans. ?? Wildlife Disease Association 2012.

  16. An association study between polymorphism of alcohol ...

    African Journals Online (AJOL)

    The aim of this study was to identify the genetic risk factors which include alcohol metabolizing genes and neurotransmitter related genes for alcoholism in Yunnan Han population. Eight allelic variants of five genes were genotyped from 332 Yunnan Han individuals (including 118 alcohol-dependent patients (DSM-IV ...

  17. The first confirmed case of Diphyllobothrium latum in Brazil

    OpenAIRE

    FLN Santos; LB de Faro

    2005-01-01

    Diphyllobothriasis is an infection of the small intestine by the broad tapeworm Diphyllobothrium sp. The associated symptomatology is nonspecific, but megaloblastic anemia is a well-described complication. Although the infection is common in temperate regions, descriptions in South America have so far been limited to Chile, Peru, and a few cases in Argentina. This paper presents the first confirmed Brazilian case of diphyllobothriasis. A 29-years-old woman living in Salvador (state of Bahia) ...

  18. A study of diabetes associated oral manifestations

    Directory of Open Access Journals (Sweden)

    T Shanmugam Kathiresan

    2017-01-01

    Full Text Available Aim: The aim of this work was to determine the frequency of oral changes in diabetic patients and to study the relationship between periodontal disease and diabetes mellitus. Materials and Methods: The study sample consisted of 440 known diabetic patients between the age group of 20–80 years, of which 212 were males and 228 were females. One hundred and six patients were below 40 years, 138 patients between 41 and 50 years, 97 in 51–60 years, and 99 above 60 years of age. Data were statistically analyzed by Student's t-test. Results: Nearly 57% of the patients showed a Russell's Periodontal Index score of 2–4.9, which suggested an established periodontal disease. Risk factors for the people above the age of 40 years to develop diabetes were 76%. Conclusion: The frequency of oral manifestations in diabetic patients was significantly high, hence showing a relationship of gingival and periodontal diseases with diabetes mellitus.

  19. A refined study of FCRL genes from a genome-wide association study for Graves' disease.

    Directory of Open Access Journals (Sweden)

    Shuang-Xia Zhao

    Full Text Available To pinpoint the exact location of the etiological variant/s present at 1q21.1 harboring FCRL1-5 and CD5L genes, we carried out a refined association study in the entire FCRL region in 1,536 patients with Graves' disease (GD and 1,516 sex-matched controls by imputation analysis, logistic regression, and cis-eQTL analysis. Among 516 SNPs with P<0.05 in the initial GWAS scan, the strongest signals associated with GD and correlated to FCRL3 expression were located at a cluster of SNPs including rs7528684 and rs3761959. And the allele-specific effects for rs3761959 and rs7528684 on FCRL3 expression level revealed that the risk alleles A of rs3761959 and C of rs7528684 were correlated with the elevated expression level of FCRL3 whether in PBMCs or its subsets, especially in CD19(+ B cells and CD8(+ T subsets. Next, the combined analysis with 5,300 GD cases and 4,916 control individuals confirmed FCRL3 was a susceptibility gene of GD in Chinese Han populations, and rs3761959 and rs7528684 met the genome-wide association significance level (P(combined = 2.27×10(-12 and 7.11×10(-13, respectively. Moreover, the haplotypes with the risk allele A of rs3761959 and risk allele C of rs7528684 were associated with GD risk. Finally, our epigenetic analysis suggested the disease-associated C allele of rs7528684 increased affinity for NF-KB transcription factor. Above data indicated that FCRL3 gene and its proxy SNP rs7528684 may be involved in the pathogenesis of GD by excessive inhibiting B cell receptor signaling and the impairment of suppressing function of Tregs.

  20. CCNA Cisco Certified Network Associate Study Guide

    CERN Document Server

    Lammle, Todd

    2011-01-01

    Learn from the Best - Cisco Networking Authority Todd LammleWritten by Cisco networking authority Todd Lammle, this comprehensive guide has been completely updated to reflect the latest CCNA 640-802 exam. Todd's straightforward style provides lively examples, hands on and written labs, easy-to-understand analogies, and real-world scenarios that will not only help you prepare for the exam, but also give you a solid foundation as a Cisco networking professional.This Study Guide teaches you how toDescribe how a network worksConfigure, verify and troubleshoot a switch with VLANs and interswitch co

  1. Genome-wide association study of multiplex schizophrenia pedigrees

    DEFF Research Database (Denmark)

    Levinson, Douglas F; Shi, Jianxin; Wang, Kai

    2012-01-01

    The authors used a genome-wide association study (GWAS) of multiply affected families to investigate the association of schizophrenia to common single-nucleotide polymorphisms (SNPs) and rare copy number variants (CNVs).......The authors used a genome-wide association study (GWAS) of multiply affected families to investigate the association of schizophrenia to common single-nucleotide polymorphisms (SNPs) and rare copy number variants (CNVs)....

  2. TANK 50 BATCH 0 SALTSTONE FORMULATION CONFIRMATION

    Energy Technology Data Exchange (ETDEWEB)

    Langton, C.

    2006-06-05

    Savannah River National Laboratory (SRNL) personnel were requested to confirm the Tank 50 Batch 0 grout formulation per Technical Task Request, SSF-TTR-2006-0001 (task 1 of 2) [1]. Earlier Batch 0 formulation testing used a Tank 50 sample collected in September 2005 and is described elsewhere [2]. The current testing was performed using a sample of Tank 50 waste collected in May 2006. This work was performed according to the Technical Task and Quality Assurance Plan (TT/QAP), WSRC-RP-2006-00594 [3]. The salt solution collected from Tank 50 in May 2006 contained approximately 3 weight percent more solids than the sample collected in September 2005. The insoluble solids took longer to settle in the new sample which was interpreted as indicating finer particles in the current sample. The saltstone formulation developed for the September 2005 Tank 50 Batch 0 sample was confirmed for the May 2006 sample with one minor exception. Saltstone prepared with the Tank 50 sample collected in May 2006 required 1.5 times more Daratard 17 set retarding admixture than the saltstone prepared with the September In addition, a sample prepared with lower shear mixing (stirring with a spatula) had a higher plastic viscosity (57 cP) than samples made with higher shear mixing in a blender (23cP). The static gel times of the saltstone slurries made with low shear mixing were also shorter ({approx}32 minutes) than those for comparable samples made in the blender ({approx}47 minutes). The addition of the various waste streams (ETP, HEU-HCAN, and GPE-HCAN) to Tank 50 from September 2005 to May 2006 has increased the amount of set retarder, Daratard 17, required for processing saltstone slurries through the Saltstone facility. If these streams are continued to be added to Tank 50, the quantity of admixtures required to maintain the same processing conditions for the Saltstone facility will probably change and additional testing is recommended to reconfirm the Tank 50 Saltstone formulation.

  3. Association studies of lung function in mice.

    Science.gov (United States)

    Ganguly, K; Schulz, H

    2008-07-01

    Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide and an accelerating decline of lung function is the earliest and a major indicator of the onset of COPD. Therefore it has become necessary to understand the genetic basis of this complex physiological trait in order to determine the potential susceptibility factors of this disease. REINHARD et al (2005) performed the genome wide linkage analysis study with inbred mice having extremely divergent lung function (C3H/HeJ versus JF1/Msf) and identified multiple Quantitative Trait Loci (QTLs) on mouse chromosomes (mCh) 5, 15, 17, and 19 with Logarithm of odd (LOD) scores > or = 4. Significant linkages to total lung capacity (TLC) were detected on mCh 15 and 17, to dead space volume (VD) and lung compliance (C(L)) on mCh 5 and 15, to C(L) on mCh 19, and to diffusing capacity for CO (D(co)) on mCh 15 and 17. Several of the mouse chromosomal regions identified were syntenic to human chromosomal regions identified with linkage to FEV1 (forced expiratory volume-1 second), FVC (forced vital capacity), or FEV1/FVC in separate studies. Using a systematic approach of expression QTL (e-QTL) strategy and exon-wise sequencing of suggested candidate genes followed by predicted protein structure and property, GANGULY et al (2007) recently proposed four candidate genes for lung function in mice. They are superoxide dismutase 3, extracellular [SOD3; mCh 5: V(D)], trefoil factor 2 (TFF2; mCh 17: TLC and D(co)), ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2; mCh 15:TLC and C(L)), and relaxin 1 (RLN1; mCh 19; CL and CL/TLC). As a part of functional validation, gene-targeted Sod3-/- mice were detected with increased conducting airway volume (V(D)/TLC) compared with strain-matched control Sod3+/+ mice, consistent with the QTL on mCh 5. Findings with gene-targeted mice suggested that SOD3 is a contributing factor defining the complex trait of conducting airway volume. The human variation in

  4. Further palaeomagnetic confirmation of the magellanes orocline

    Science.gov (United States)

    Burns, K. L.; Rickard, M. J.; Belbin, L.; Chamalaun, F.

    1980-03-01

    Palaeomagnetic determinations for Jurassic volcanics and a Cretaceous quartz—dolerite sill at three localities around the arcuate Patagonia'n Cordillera show that a bending of 40° to 27° has occurred. Since the structural bend is 90° it is probable that the Mesozoic arc was originally curved. Cainozoic dykes and sills at Lago San Martin in the northwardtrending belt and Sierra Valdivieso in the eastward-trending belt have the same magnetic directions and were intruded after bending. These results essentially confirm the palaeomagnetic determinations of Dalziel et al., (1973a) and further suggest that the collapse of the marginal sea during the Late Cretaceous orogenesis resulted in greater bending in the outer arc than in the inner arc. The orocline must have formed during the Andean orogeny between 80 m.y. and 21 m.y. ago and was accompanied by folding and thrusting. New K—Ar dates for the Dientes de Navarino Sill (105 m.y.), basalt at Isla Carlos in the Straits of Magellan (21 m.y.) and diorite and andesite sills at Lago San Martin (14 m.y.) are also presented.

  5. Confirmation of ETI: initial organizational response

    Science.gov (United States)

    Harrison, Albert A.

    2003-08-01

    Perhaps the most crucial responses to the confirmation of extraterrestrial intelligence will come from organizations, rather than from individual people. Among the key organizations that will help shape humanity's response are political institutions such as the US Congress, administrative bodies such as the US Department of State, security agencies, the military, professional societies, and the media. Although popular culture and individual beliefs will affect organizational performance, organizational reactions will depend also on organizational cultures and traditions, administrative structures, communication patterns, decision-making processes, and the actions of other organizations. Prompt and effective responses may be blocked by sociopolitical constraints, jurisdictional disputes, cumbersome structures and procedures, stresses that frequently slow and distort information processing, and potentially counterproductive efforts to maintain positive organizational images. Efforts undertaken by governmental agencies will be hampered by public perceptions of low credibility. Foresight and advance preparation are among the steps that organizations may take to prepare for contact, but conservative values, skepticism towards SETI, and competing organizational priorities make serious preparation unlikely.

  6. Hemithyroidectomy in a horse with confirmed hyperthyroidism.

    Science.gov (United States)

    Alberts, M K; McCann, J P; Woods, P R

    2000-10-01

    A 23-year-old Quarter Horse gelding was admitted to the hospital because of cachexia and hyperactive behavior of 1 year's duration. At admission the horse was severely emaciated, tachycardic with a grade V/VI diastolic murmur, pyrexic, polydipsic, enophthalmic, and alopecic. The right lobe of the thyroid gland was noticeably larger than typical. The horse was also hyperexcitable and had a ravenous appetite. A presumptive diagnosis of hyperthyroidism was made on the basis of clinical signs and high plasma thyroid hormone concentrations. Confirmation of the diagnosis was made on the basis of results of a triiodothyronine-suppression test. Following endocrine testing, the affected portion of the thyroid gland was removed and identified histologically as an adenoma. Return or plasma thyroid hormone concentrations to reference range values and resolution of the clinical signs of disease following hemithyroidectomy provided further conformation of the diagnosis. On the basis of finding in this horse, it appears that horses with hyperthyroidism may be successfully treated by hemithyroidectomy.

  7. Magnetic resonance tomography in confirmed multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Uhlenbrock, D.; Dickmann, E.; Beyer, H.K.; Gehlen, W.

    1985-03-01

    The authors report on 21 cases of confirmed multiple sclerosis examined by both CT and magnetic resonance tomography. To safeguard the results, strict criteria were applied in accordance with the suggestions made by neurological work teams. Pathological lesions were seen in 20 patients; the MR image did not reveal anything abnormal in one case. On the average, 10.3 lesions were seen in the MR tomogram, whereas CT images showed on the average only 2.1 foci. The size and number of lesions in the MR tomogram were independent of the duration of the disease, the presented clinical symptoms, or the type of treatment at the time of examination. Evidently the sensitivity of MR tomography is very high in MS patients, but it has not yet been clarified to what extent this applies also to the specificity. Further research is mandatory. First experiences made by us show that lesions of a similar kind can also occur in diseases such as malignant lymphoma involving the brain, in vitamin B 12 deficiency syndrome, or encephalitis, and can become manifest in the MR tomogram.

  8. Candidate pathway-based genome-wide association studies identify novel associations of genomic variants in the complement system associated with coronary artery disease.

    Science.gov (United States)

    Xu, Chengqi; Yang, Qin; Xiong, Hongbo; Wang, Longfei; Cai, Jianping; Wang, Fan; Li, Sisi; Chen, Jing; Wang, Chuchu; Wang, Dan; Xiong, Xin; Wang, Pengyun; Zhao, Yuanyuan; Wang, Xiaojing; Huang, Yufeng; Chen, Shanshan; Yin, Dan; Li, Xiuchun; Liu, Ying; Liu, Jinqiu; Wang, Jingjing; Li, Hui; Ke, Tie; Ren, Xiang; Wu, Yanxia; Wu, Gang; Wan, Jing; Zhang, Rongfeng; Wu, Tangchun; Wang, Junhan; Xia, Yunlong; Yang, Yanzong; Cheng, Xiang; Liao, Yuhua; Chen, Qiuyun; Zhou, Yanhong; He, Qing; Tu, Xin; Wang, Qing K

    2014-12-01

    Genomic variants identified by genome-wide association studies (GWAS) explain associated with CAD, we developed a candidate pathway-based GWAS by integrating expression quantitative loci analysis and mining of GWAS data with variants in a candidate pathway. Mining of GWAS data was performed to analyze variants in 32 complement system genes for positive association with CAD. Functional variants in genes showing positive association were then identified by searching existing expression quantitative loci databases and validated by real-time reverse transcription polymerase chain reaction. A follow-up case-control design was then used to determine whether the functional variants are associated with CAD in 2 independent GeneID Chinese populations. Candidate pathway-based GWAS identified positive association between variants in C3AR1 and C6 and CAD. Two functional variants, rs7842 in C3AR1 and rs4400166 in C6, were found to be associated with expression levels of C3AR1 and C6, respectively. Significant association was identified between rs7842 and CAD (P=3.99×10(-6); odds ratio, 1.47) and between rs4400166 and CAD (P=9.30×10(-3); odds ratio, 1.24) in the validation cohort. The significant findings were confirmed in the replication cohort (P=1.53×10(-5); odds ratio, 1.37 for rs7842; P=8.41×10(-3); odds ratio, 1.21 for rs4400166). Integration of GWAS with biological pathways and expression quantitative loci is effective in identifying new risk variants for CAD. Functional variants increasing C3AR1 and C6 expression were shown to confer significant risk of CAD for the first time. © 2014 American Heart Association, Inc.

  9. Racial athletic stereotype confirmation in college football recruiting.

    Science.gov (United States)

    Thomas, Grant; Good, Jessica J; Gross, Alexi R

    2015-01-01

    The present study tested real-world racial stereotype use in the context of college athletic recruiting. Stereotype confirmation suggests that observers use stereotypes as hypotheses and interpret relevant evidence in a biased way that confirms their stereotypes. Shifting standards suggest that the evaluative standard to which we hold a target changes as a function of their group membership. We examined whether stereotype confirmation and shifting standards effects would be seen in college football coaches during recruiting. College football coaches evaluated a Black or White player on several attributes and made both zero- and non-zero-sum allocations. Results suggested that coaches used the evidence presented to develop biased subjective evaluations of the players based on race while still maintaining equivalent objective evaluations. Coaches also allocated greater overall resources to the Black recruit than the White recruit.

  10. Narrative Skills Following Early Confirmation of Permanent Childhood Hearing Impairment

    Science.gov (United States)

    Worsfold, Sarah; Mahon, Merle; Yuen, Ho Ming; Kennedy, Colin

    2010-01-01

    Aim: The aim of this study was to compare spoken language production in children with permanent childhood hearing impairment (PCHI) whose PCHI was confirmed either early or late. Method: Audio-taped spoken narrative was assessed for syntax, phonology, morphology, and narrative in transcripts from a population-based sample of 89 children (49 males,…

  11. Sample size computation for association studies using case–parents ...

    Indian Academy of Sciences (India)

    sample size for case–control association studies is discussed. Materials and methods. Parameter settings. We consider a candidate locus with two alleles A and a where. A is putatively associated with the disease status (increasing. Keywords. sample size; association tests; genotype relative risk; power; autism. Journal of ...

  12. Immunohistochemical study of hepatic fibropoiesis associated with canine visceral leishmaniasis.

    Science.gov (United States)

    Madeira, Igor M V M; Pereira, Debora M O; Sousa, Aline A; Vilela, Cesar A; Amorim, Izabela F G; Caliari, Marcelo V; Souza, Carolina C; Tafuri, Wagner L

    2016-04-01

    Hepatic fibropoiesis has been confirmed in canine visceral leishmaniasis. In fibrotic disease, hepatic stellate cells (HSC) play an important role in fibropoiesis, undergoing activation by TGF-β to acquire characteristics of myofibroblasts. These cells show extensive capacity for proliferation, motility, contractility, collagen synthesis and extracellular matrix component synthesis. The aim of this work was to identify markers of HSC activation in 10 symptomatic and 10 asymptomatic dogs naturally infected with Leishmania (Leishmania) infantum. Eight uninfected dogs were used as controls. Alpha-actin (α-SMA), vimentin and cytokeratin were investigated by immunohistochemistry as HSC markers. The cytokine TGF-β in tissue was also evaluated by immunohistochemistry. All infected dogs showed higher numbers of reticular fibres than controls. Fibropoiesis found in infected dogs was always associated with the presence of parasites and chronic granulomatous hepatitis. Positive correlation was found among fibropoiesis, parasite tissue load and expression of α-SMA. There was no correlation between fibropoiesis, vimentin and cytokeratin markers. The expression of cytokine TGF-β was higher in infected dogs than in controls, but not significantly different between symptomatic and asymptomatic dogs. These results confirm previous work describing the intense hepatic fibropoiesis in dogs naturally infected with Leishmania infantum, but now associated them with overexpression of TGF-β, where α-SMA may be a superior marker for activated HSC cells in CVL. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

  13. Association of C-Reactive Protein With Bacterial and Respiratory Syncytial Virus-Associated Pneumonia Among Children Aged <5 Years in the PERCH Study.

    Science.gov (United States)

    Higdon, Melissa M; Le, Tham; O'Brien, Katherine L; Murdoch, David R; Prosperi, Christine; Baggett, Henry C; Brooks, W Abdullah; Feikin, Daniel R; Hammitt, Laura L; Howie, Stephen R C; Kotloff, Karen L; Levine, Orin S; Scott, J Anthony G; Thea, Donald M; Awori, Juliet O; Baillie, Vicky L; Cascio, Stephanie; Chuananon, Somchai; DeLuca, Andrea N; Driscoll, Amanda J; Ebruke, Bernard E; Endtz, Hubert P; Kaewpan, Anek; Kahn, Geoff; Karani, Angela; Karron, Ruth A; Moore, David P; Park, Daniel E; Rahman, Mohammed Ziaur; Salaudeen, Rasheed; Seidenberg, Phil; Somwe, Somwe Wa; Sylla, Mamadou; Tapia, Milagritos D; Zeger, Scott L; Deloria Knoll, Maria; Madhi, Shabir A

    2017-06-15

    Lack of a gold standard for identifying bacterial and viral etiologies of pneumonia has limited evaluation of C-reactive protein (CRP) for identifying bacterial pneumonia. We evaluated the sensitivity and specificity of CRP for identifying bacterial vs respiratory syncytial virus (RSV) pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) multicenter case-control study. We measured serum CRP levels in cases with World Health Organization-defined severe or very severe pneumonia and a subset of community controls. We evaluated the sensitivity and specificity of elevated CRP for "confirmed" bacterial pneumonia (positive blood culture or positive lung aspirate or pleural fluid culture or polymerase chain reaction [PCR]) compared to "RSV pneumonia" (nasopharyngeal/oropharyngeal or induced sputum PCR-positive without confirmed/suspected bacterial pneumonia). Receiver operating characteristic (ROC) curves were constructed to assess the performance of elevated CRP in distinguishing these cases. Among 601 human immunodeficiency virus (HIV)-negative tested controls, 3% had CRP ≥40 mg/L. Among 119 HIV-negative cases with confirmed bacterial pneumonia, 77% had CRP ≥40 mg/L compared with 17% of 556 RSV pneumonia cases. The ROC analysis produced an area under the curve of 0.87, indicating very good discrimination; a cut-point of 37.1 mg/L best discriminated confirmed bacterial pneumonia (sensitivity 77%) from RSV pneumonia (specificity 82%). CRP ≥100 mg/L substantially improved specificity over CRP ≥40 mg/L, though at a loss to sensitivity. Elevated CRP was positively associated with confirmed bacterial pneumonia and negatively associated with RSV pneumonia in PERCH. CRP may be useful for distinguishing bacterial from RSV-associated pneumonia, although its role in discriminating against other respiratory viral-associated pneumonia needs further study.

  14. Hindsight and confirmation biases in an exercise in telepathy.

    Science.gov (United States)

    Rudski, Jeffrey M

    2002-12-01

    Belief in the paranormal or claims of paranormal experiences may be, at least in part, associated with systematic cognitive biases. 48 undergraduate college students engaged in an exercise in telepathy in which the color of cards was 'sent' to them by the experimenter under two conditions. In a Hindsight-possible condition, participants recorded whether their choice was correct following the revelation of the color. In the Control condition participants committed to a particular response by writing it down before receiving feedback, thus eliminating ability to alter retrospectively what 'was known all along'. Consistent with a hindsight bias, participants performed significantly better under the Hindsight-possible condition. Moreover, a statisically significant correlation was found between paranormal belief assessed on Tobacyk's 1988 Revised Paranormal Belief Scale in the Hindsight-possible but not in the Control condition, suggesting a confirmation bias. Results are discussed in terms of interactions between hindsight and confirmation biases and how they might relate to paranormal beliefs.

  15. Confirming the Lanchestrian linear-logarithmic model of attrition

    Energy Technology Data Exchange (ETDEWEB)

    Hartley, D.S. III.

    1990-12-01

    This paper is the fourth in a series of reports on the breakthrough research in historical validation of attrition in conflict. Significant defense policy decisions, including weapons acquisition and arms reduction, are based in part on models of conflict. Most of these models are driven by their attrition algorithms, usually forms of the Lanchester square and linear laws. None of these algorithms have been validated. The results of this paper confirm the results of earlier papers, using a large database of historical results. The homogeneous linear-logarithmic Lanchestrian attrition model is validated to the extent possible with current initial and final force size data and is consistent with the Iwo Jima data. A particular differential linear-logarithmic model is described that fits the data very well. A version of Helmbold's victory predicting parameter is also confirmed, with an associated probability function. 37 refs., 73 figs., 68 tabs.

  16. Theory of chaotic orbital variations confirmed by Cretaceous geological evidence.

    Science.gov (United States)

    Ma, Chao; Meyers, Stephen R; Sageman, Bradley B

    2017-02-22

    Variations in the Earth's orbit and spin vector are a primary control on insolation and climate; their recognition in the geological record has revolutionized our understanding of palaeoclimate dynamics, and has catalysed improvements in the accuracy and precision of the geological timescale. Yet the secular evolution of the planetary orbits beyond 50 million years ago remains highly uncertain, and the chaotic dynamical nature of the Solar System predicted by theoretical models has yet to be rigorously confirmed by well constrained (radioisotopically calibrated and anchored) geological data. Here we present geological evidence for a chaotic resonance transition associated with interactions between the orbits of Mars and the Earth, using an integrated radioisotopic and astronomical timescale from the Cretaceous Western Interior Basin of what is now North America. This analysis confirms the predicted chaotic dynamical behaviour of the Solar System, and provides a constraint for refining numerical solutions for insolation, which will enable a more precise and accurate geological timescale to be produced.

  17. Predominance and association risk of Blastocystis hominis subtype I in colorectal cancer: a case control study.

    Science.gov (United States)

    Mohamed, Amr Mohamed; Ahmed, Mona Abdelfattah; Ahmed, Sabah Abdelghany; Al-Semany, Sherif Ahmed; Alghamdi, Saad Saed; Zaglool, Dina Abdulla

    2017-01-01

    Blastocystis, a genetically diverse intestinal parasite with controversial pathogenic potential, has increasingly been incriminated for diarrheal illness in immunocompromised individuals including colorectal cancer (CRC) patients. The aim of the current study was to assess the possible association between Blastocystis infection and CRC condition in Makkah, Saudi Arabia (KSA). Stool samples were collected from 80 non-cancer (NC) and 138 cancer subjects including 74 CRC patients and 64 patients with other cancers outside gastrointestinal tract (COGT). Molecularly confirmed Blastocystis isolates were genetically grouped and subtyped using multiplex polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) and sequence-tagged site primers-based PCR (PCR-STS), respectively. Blastocystis hominis were confirmed in 29.7, 25 and 15% among CRC, COGT and NC patients, respectively. Obtained Blastocystis isolates were initially categorized into 2 groups (A and C), which were subsequently subtyped into 3 different subtypes; subtype-I (38%), subtype-II (44%) and subtype-V (22%). Interestingly, subtype-I was the most predominantly detected subtype (54.5%) among CRC patients with a significant association risk (COR 7.548; 95% CI: 1.629-34.987; P = 0.004). To the best of our knowledge, the current study is the first to provide genetic insights on the prevalence of Blastocystis hominis among CRC patients in Makkah, KSA. Moreover, the study suggests for a possible association between subtype-I of Blastocystis hominis and CRC, which could indicate a potential influence of Blastocystis on CRC condition. Further studies are required to confirm this association risk and to investigate the possible underlying mechanism of postulated carcinogenic influence of Blastocystis hominis subtype-I.

  18. The Canadian Association for the Study of International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The Canadian Association for the Study of International Development (CASID) was founded in 1989 to provide a forum for Canadian scholars, policymakers, and civil society to meet and exchange views. It is the only Canadian learned society devoted to the study of international development. The Association's journal, the ...

  19. X Chromosome-wide Association Study Identifies a Susceptibility Locus for Inflammatory Bowel Disease in Koreans.

    Science.gov (United States)

    Lee, Ho-Su; Oh, Hyunjung; Yang, Suk-Kyun; Baek, Jiwon; Jung, Seulgi; Hong, Myunghee; Kim, Kyung Mo; Shin, Hyoung Doo; Kim, Kyung-Jo; Park, Sang Hyoung; Ye, Byong Duk; Han, Buhm; Song, Kyuyoung

    2017-07-01

    Genome-wide association studies of inflammatory bowel disease identified > 200 susceptibility loci only in autosomes. This study aimed to identify inflammatory bowel disease susceptibility loci on the X chromosome. We performed an X chromosome-wide association study in Korean patients with inflammatory bowel disease. We analysed X chromosome data from our recent genome-wide association studies, including 1505 cases [922 Crohn's disease and 583 ulcerative colitis] and 4041 controls during the discovery phase, followed by replication in additional 1989 cases [993 Crohn's disease, 996 ulcerative colitis] and 3491 controls. Sex-related differential effects of single nucleotide polymorphisms on disease were also evaluated. We confirmed a significant association of a previously reported inflammatory bowel disease susceptibility locus at chromosome Xq26.3 [CD40LG-ARHGEF6; odds ratio, 1.22; 95% confidence interval, 1.16-1.28; combined p = 3.79 × 10-15]. This locus accounted for 0.18% and 0.12% of genetic variance in Crohn's disease and ulcerative colitis, respectively, and increased the total autosomal chromosome genetic variance from 6.65% to 6.83% and from 5.47% to 5.59% for Crohn's disease and ulcerative colitis risk, respectively, in the Korean population. Sex-stratified analyses did not reveal sex-related differences in effect sizes. We confirmed the association of rs2427870 at the CD40LG-ARHGEF6 locus with an inflammatory bowel disease through an X chromosome-wide association study in a Korean population. Our data suggest that the CD40LG-ARHGEF6 locus on the X chromosome might play a role in inflammatory bowel disease pathogenesis in the Korean population.

  20. Genome-wide association study of serum selenium concentrations

    DEFF Research Database (Denmark)

    Gong, Jian; Hsu, Li; Harrison, Tabitha

    2013-01-01

    Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated this ...

  1. Echocardiography Findings in Clinically Confirmed Congenital ...

    African Journals Online (AJOL)

    Background: Congenital rubella syndrome (CRS) is known to affect thousands of children in the developing world because rubella vaccination is not available routinely in most of these countries. Among its many manifestations only congenital heart disease is life threatening. This study was undertaken to ascertain the ...

  2. Non-replication study of a genome-wide association study for hypertension and blood pressure in African Americans

    Directory of Open Access Journals (Sweden)

    Kidambi Srividya

    2012-04-01

    Full Text Available Abstract Background A recent genome wide association study in 1017 African Americans identified several single nucleotide polymorphisms that reached genome-wide significance for systolic blood pressure. We attempted to replicate these findings in an independent sample of 2474 unrelated African Americans in the Milwaukee metropolitan area; 53% were women and 47% were hypertensives. Methods We evaluated sixteen top associated SNPs from the above genome wide association study for hypertension as a binary trait or blood pressure as a continuous trait. In addition, we evaluated eight single nucleotide polymorphisms located in two genes (STK-39 and CDH-13 found to be associated with systolic and diastolic blood pressures by other genome wide association studies in European and Amish populations. TaqMan MGB-based chemistry with fluorescent probes was used for genotyping. We had an adequate sample size (80% power to detect an effect size of 1.2-2.0 for all the single nucleotide polymorphisms for hypertension as a binary trait, and 1% variance in blood pressure as a continuous trait. Quantitative trait analyses were performed both by excluding and also by including subjects on anti-hypertensive therapy (after adjustments were made for anti-hypertensive medications. Results For all 24 SNPs, no statistically significant differences were noted in the minor allele frequencies between cases and controls. One SNP (rs2146204 showed borderline association (p = 0.006 with hypertension status using recessive model and systolic blood pressure (p = 0.02, but was not significant after adjusting for multiple comparisons. In quantitative trait analyses, among normotensives only, rs12748299 was associated with SBP (p = 0.002. In addition, several nominally significant associations were noted with SBP and DBP among normotensives but none were statistically significant. Conclusions This study highlights the importance of replication to confirm the validity of genome wide

  3. Multicenter dizygotic twin cohort study confirms two linkage susceptibility loci for body mass index at 3q29 and 7q36 and identifies three further potential novel loci

    DEFF Research Database (Denmark)

    Kettunen, J; Perola, M; Martin, N G

    2009-01-01

    OBJECTIVE: To identify common loci and potential genetic variants affecting body mass index (BMI, kg m(-2)) in study populations originating from Europe. DESIGN: We combined genome-wide linkage scans of six cohorts from Australia, Denmark, Finland, the Netherlands, Sweden and the United Kingdom...

  4. Breast Cancer Association with Cytomegalo Virus-A Tertiary Center Case-Control Study.

    Science.gov (United States)

    Surendran, Anilkumar; Chisthi, Meer M

    2017-12-18

    Cytomegalo virus is a ubiquitous virus often associated with congenital infections. Some studied have claimed an association between infection with this virus and development of breast cancer. The aim of this prospective research was to study the difference in Cytomegalo virus sero-positivity among patients with breast cancer and benign breast diseases, and thereby to prove any association. This was a hospital based Case-Control study conducted at the General Surgery wards of our hospital, a tertiary level public sector health care institution. This study was done on 130 patients with breast swellings who underwent surgical excision of their lumps over a 1-year period. Patients with histologically proven malignancies were selected as cases while proven benign cases were deemed to be the controls. IgG and IgM antibodies to Cytomegalo virus were checked in the patients from both groups. All of the studied patients turned out to be positive for Immunoglobulin G against Cytomegalo virus while all the patients were found to be negative for Immunoglobulin M. There was no difference in the antibody titers among the benign and malignant cases in the study. Logistic regression calculation was also carried out including the study parameters and other known risk factors. We conclude that there is no association between Cytomegalo virus sero-positivity and breast cancer. Another conclusion is that the studied adult population has been exposed to Cytomegalo virus in some point of their lives. Further studies of a larger magnitude are essential to confirm our results.

  5. Stroke-induced immunodepression and dysphagia independently predict stroke-associated pneumonia - The PREDICT study.

    Science.gov (United States)

    Hoffmann, Sarah; Harms, Hendrik; Ulm, Lena; Nabavi, Darius G; Mackert, Bruno-Marcel; Schmehl, Ingo; Jungehulsing, Gerhard J; Montaner, Joan; Bustamante, Alejandro; Hermans, Marcella; Hamilton, Frank; Göhler, Jos; Malzahn, Uwe; Malsch, Carolin; Heuschmann, Peter U; Meisel, Christian; Meisel, Andreas

    2017-12-01

    Stroke-associated pneumonia is a frequent complication after stroke associated with poor outcome. Dysphagia is a known risk factor for stroke-associated pneumonia but accumulating evidence suggests that stroke induces an immunodepressive state increasing susceptibility for stroke-associated pneumonia. We aimed to confirm that stroke-induced immunodepression syndrome is associated with stroke-associated pneumonia independently from dysphagia by investigating the predictive properties of monocytic HLA-DR expression as a marker of immunodepression as well as biomarkers for inflammation (interleukin-6) and infection (lipopolysaccharide-binding protein). This was a prospective, multicenter study with 11 study sites in Germany and Spain, including 486 patients with acute ischemic stroke. Daily screening for stroke-associated pneumonia, dysphagia and biomarkers was performed. Frequency of stroke-associated pneumonia was 5.2%. Dysphagia and decreased monocytic HLA-DR were independent predictors for stroke-associated pneumonia in multivariable regression analysis. Proportion of pneumonia ranged between 0.9% in the higher monocytic HLA-DR quartile (≥21,876 mAb/cell) and 8.5% in the lower quartile (≤12,369 mAb/cell). In the presence of dysphagia, proportion of pneumonia increased to 5.9% and 18.8%, respectively. Patients without dysphagia and normal monocytic HLA-DR expression had no stroke-associated pneumonia risk. We demonstrate that dysphagia and stroke-induced immunodepression syndrome are independent risk factors for stroke-associated pneumonia. Screening for immunodepression and dysphagia might be useful for identifying patients at high risk for stroke-associated pneumonia.

  6. What is the probability of replicating a statistically significant association in genome-wide association studies?

    Science.gov (United States)

    Jiang, Wei; Xue, Jing-Hao; Yu, Weichuan

    2017-11-01

    The goal of genome-wide association studies (GWASs) is to discover genetic variants associated with diseases/traits. Replication is a common validation method in GWASs. We regard an association as true finding when it shows significance in both primary and replication studies. A question worth pondering is what is the probability of a primary association (i.e. a statistically significant association in the primary study) being validated in the replication study? This article systematically reviews the answers to this question from different points of view. As Bayesian methods can help us integrate out the uncertainty about the underlying effect of the primary association, we will mainly focus on the Bayesian view in this article. We refer the Bayesian replication probability as the replication rate (RR). We further describe an estimation method for RR, which makes use of the summary statistics from the primary study. We can use the estimated RR to determine the sample size of the replication study and to check the consistency between the results of the primary study and those of the replication study. We describe an R-package to estimate and apply RR in GWASs. Simulation and real data experiments show that the estimated RR has good prediction and calibration performance. We also use these data to demonstrate the usefulness of RR. The R-package is available at http://bioinformatics.ust.hk/RRate.html. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci

    Science.gov (United States)

    Stahl, Eli A.; Raychaudhuri, Soumya; Remmers, Elaine F.; Xie, Gang; Eyre, Stephen; Thomson, Brian P.; Li, Yonghong; Kurreeman, Fina A. S.; Zhernakova, Alexandra; Hinks, Anne; Guiducci, Candace; Chen, Robert; Alfredsson, Lars; Amos, Christopher I.; Ardlie, Kristin G.; Barton, Anne; Bowes, John; Brouwer, Elisabeth; Burtt, Noel P.; Catanese, Joseph J.; Coblyn, Jonathan; Coenen, Marieke JH; Costenbader, Karen H.; Criswell, Lindsey A.; Crusius, J. Bart A.; Cui, Jing; de Bakker, Paul I.W.; De Jager, Phillip L.; Ding, Bo; Emery, Paul; Flynn, Edward; Harrison, Pille; Hocking, Lynne J.; Huizinga, Tom W. J.; Kastner, Daniel L.; Ke, Xiayi; Lee, Annette T.; Liu, Xiangdong; Martin, Paul; Morgan, Ann W.; Padyukov, Leonid; Posthumus, Marcel D.; Radstake, Timothy RDJ; Reid, David M.; Seielstad, Mark; Seldin, Michael F.; Shadick, Nancy A.; Steer, Sophia; Tak, Paul P.; Thomson, Wendy; van der Helm-van Mil, Annette H. M.; van der Horst-Bruinsma, Irene E.; van der Schoot, C. Ellen; van Riel, Piet LCM; Weinblatt, Michael E.; Wilson, Anthony G.; Wolbink, Gert Jan; Wordsworth, Paul; Wijmenga, Cisca; Karlson, Elizabeth W.; Toes, Rene E. M.; de Vries, Niek; Begovich, Ann B.; Worthington, Jane; Siminovitch, Katherine A.; Gregersen, Peter K.; Klareskog, Lars; Plenge, Robert M.

    2014-01-01

    To identify novel genetic risk factors for rheumatoid arthritis (RA), we conducted a genome-wide association study (GWAS) meta-analysis of 5,539 autoantibody positive RA cases and 20,169 controls of European descent, followed by replication in an independent set of 6,768 RA cases and 8,806 controls. Of 34 SNPs selected for replication, 7 novel RA risk alleles were identified at genome-wide significance (P<5×10−8) in analysis of all 41,282 samples. The associated SNPs are near genes of known immune function, including IL6ST, SPRED2, RBPJ, CCR6, IRF5, and PXK. We also refined the risk alleles at two established RA risk loci (IL2RA and CCL21) and confirmed the association at AFF3. These new associations bring the total number of confirmed RA risk loci to 31 among individuals of European ancestry. An additional 11 SNPs replicated at P<0.05, many of which are validated autoimmune risk alleles, suggesting that most represent bona fide RA risk alleles. PMID:20453842

  8. A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese.

    Directory of Open Access Journals (Sweden)

    Fuu-Jen Tsai

    2010-02-01

    Full Text Available To investigate the underlying mechanisms of T2D pathogenesis, we looked for diabetes susceptibility genes that increase the risk of type 2 diabetes (T2D in a Han Chinese population. A two-stage genome-wide association (GWA study was conducted, in which 995 patients and 894 controls were genotyped using the Illumina HumanHap550-Duo BeadChip for the first genome scan stage. This was further replicated in 1,803 patients and 1,473 controls in stage 2. We found two loci not previously associated with diabetes susceptibility in and around the genes protein tyrosine phosphatase receptor type D (PTPRD (P = 8.54x10(-10; odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.36-1.82, and serine racemase (SRR (P = 3.06x10(-9; OR = 1.28; 95% CI = 1.18-1.39. We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65x10(-10; OR = 1.29, 95% CI = 1.19-1.40. By identifying two novel genetic susceptibility loci in a Han Chinese population and confirming the involvement of KCNQ1, which was previously reported to be associated with T2D in Japanese and European descent populations, our results may lead to a better understanding of differences in the molecular pathogenesis of T2D among various populations.

  9. Long-term prognostic impact of CT-Leaman score in patients with non-obstructive CAD: Results from the COronary CT Angiography EvaluatioN For Clinical Outcomes InteRnational Multicenter (CONFIRM) study.

    Science.gov (United States)

    Andreini, Daniele; Pontone, Gianluca; Mushtaq, Saima; Gransar, Heidi; Conte, Edoardo; Bartorelli, Antonio L; Pepi, Mauro; Opolski, Maksymilian P; Ó Hartaigh, Bríain; Berman, Daniel S; Budoff, Matthew J; Achenbach, Stephan; Al-Mallah, Mouaz; Cademartiri, Filippo; Callister, Tracy Q; Chang, Hyuk-Jae; Chinnaiyan, Kavitha; Chow, Benjamin J W; Cury, Ricardo; Delago, Augustin; Hadamitzky, Martin; Hausleiter, Joerg; Feuchtner, Gudrun; Kim, Yong-Jin; Kaufmann, Philipp A; Leipsic, Jonathon; Lin, Fay Y; Maffei, Erica; Raff, Gilbert; Shaw, Leslee J; Villines, Todd C; Dunning, Allison; Marques, Hugo; Rubinshtein, Ronen; Hindoyan, Niree; Gomez, Millie; Min, James K

    2017-03-15

    Non-obstructive coronary artery disease (CAD) identified by coronary computed tomography angiography (CCTA) demonstrated prognostic value. CT-adapted Leaman score (CT-LeSc) showed to improve the prognostic stratification. Aim of the study was to evaluate the capability of CT-LeSc to assess long-term prognosis of patients with non-obstructive (CAD). From 17 centers, we enrolled 2402 patients without prior CAD history who underwent CCTA that showed non-obstructive CAD and provided complete information on plaque composition. Patients were divided into a group without CAD and a group with non-obstructive CAD (CAD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Earthquake Model Confirms Traffic Jams Caused by Tiredness

    OpenAIRE

    Jarai-Szabo, Ferenc; Neda, Zoltan

    2011-01-01

    A simple one-dimensional spring-block model elaborated for the idealized single-lane highway traffic reveals the causes for the emergence of traffic jams. Based on the stop-time statistics of one car in the row, an order parameter is defined and studied. By extensive computer simulations, the parameter space of the model is explored, analyzed and interpreted. Existence of a free a and congested flow phases is confirmed and the transition between them is analyzed.

  11. Novel Loci Associated with Usual Sleep Duration: The CHARGE Consortium Genome-Wide Association Study

    Science.gov (United States)

    Gottlieb, Daniel J.; Hek, Karin; Chen, Ting-hsu; Watson, Nathaniel F.; Eiriksdottir, Gudny; Byrne, Enda M.; Cornelis, Marilyn; Warby, Simon C.; Bandinelli, Stefania; Cherkas, Lynn; Evans, Daniel S.; Grabe, Hans J.; Lahti, Jari; Li, Man; Lehtimäki, Terho; Lumley, Thomas; Marciante, Kristin D.; Pérusse, Louis; Psaty, Bruce M.; Robbins, John; Tranah, Gregory J.; Vink, Jacqueline M.; Wilk, Jemma B.; Stafford, Jeanette M.; Bellis, Claire; Biffar, Reiner; Bouchard, Claude; Cade, Brian; Curhan, Gary C.; Eriksson, Johan G.; Ewert, Ralf; Ferrucci, Luigi; Fülöp, Tibor; Gehrman, Philip R.; Goodloe, Robert; Harris, Tamara B.; Heath, Andrew C.; Hernandez, Dena; Hofman, Albert; Hottenga, Jouke-Jan; Hunter, David J.; Jensen, Majken K.; Johnson, Andrew D.; Kähönen, Mika; Kao, Linda; Kraft, Peter; Larkin, Emma K.; Lauderdale, Diane S.; Luik, Annemarie I.; Medici, Marco; Montgomery, Grant W.; Palotie, Aarno; Patel, Sanjay R.; Pistis, Giorgio; Porcu, Eleonora; Quaye, Lydia; Raitakari, Olli; Redline, Susan; Rimm, Eric B.; Rotter, Jerome I.; Smith, Albert V.; Spector, Tim D.; Teumer, Alexander; Uitterlinden, André G.; Vohl, Marie-Claude; Widen, Elisabeth; Willemsen, Gonneke; Young, Terry; Zhang, Xiaoling; Liu, Yongmei; Blangero, John; Boomsma, Dorret I.; Gudnason, Vilmundur; Hu, Frank; Mangino, Massimo; Martin, Nicholas G.; O’Connor, George T.; Stone, Katie L.; Tanaka, Toshiko; Viikari, Jorma; Gharib, Sina A.; Punjabi, Naresh M.; Räikkönen, Katri; Völzke, Henry; Mignot, Emmanuel; Tiemeier, Henning

    2015-01-01

    Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study of usual sleep duration was conducted using 18 population-based cohorts totaling 47,180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35–80 kb upstream from the thyroid-specific transcription factor PAX8 (lowest p=1.1 ×10−9). This finding was replicated in an African-American sample of 4771 individuals (lowest p=9.3 × 10−4). The strongest combined association was at rs1823125 (p=1.5 × 10−10, minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 minutes longer per night. The alleles associated with longer sleep duration were associated in previous genome-wide association studies with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease. PMID:25469926

  12. A systematic analysis of the association studies between CASP8 ...

    Indian Academy of Sciences (India)

    However, in Australia, Finland, Spain, Sweden and U.S., there is no significant association between CASP8 D302H and breast cancer risk (Figure 3). No heterogeneity was found between groups or between studies. Hence, the association between CASP8 D302H and breast cancer risk may be country variable. Previously ...

  13. A Discovery Genome-Wide Association Study of Entrepreneurship

    Science.gov (United States)

    Quaye, Lydia; Nicolaou, Nicos; Shane, Scott; Mangino, Massimo

    2012-01-01

    To identify specific genetic variants influencing the phenotype of entrepreneurship, we conducted a genome-wide association study (GWAS) with 3,933 Caucasian females from the TwinsUK Adult Twin Registry. Following stringent genotype quality control, GWAF (genome-wide association analyses for family data) software was used to assess the association…

  14. Genome-Wide Association Study of Down Syndrome-Associated Atrioventricular Septal Defects

    National Research Council Canada - National Science Library

    Ramachandran, Dhanya; Zeng, Zhen; Locke, Adam E; Mulle, Jennifer G; Bean, Lora J H; Rosser, Tracie C; Dooley, Kenneth J; Cua, Clifford L; Capone, George T; Reeves, Roger H; Maslen, Cheryl L; Cutler, David J; Feingold, Eleanor; Sherman, Stephanie L; Zwick, Michael E

    2015-01-01

    .... We performed a genome-wide association study using logistic regression analysis on 452 individuals with Down syndrome, consisting of 210 cases with complete atrioventricular septal defects and 242...

  15. Robust ranks of true associations in genome-wide case-control association studies.

    Science.gov (United States)

    Zheng, Gang; Joo, Jungnam; Lin, Jing-Ping; Stylianou, Mario; Waclawiw, Myron A; Geller, Nancy L

    2007-01-01

    In whole-genome association studies, at the first stage, all markers are tested for association and their test statistics or p-values are ranked. At the second stage, some most significant markers are further analyzed by more powerful statistical methods. This helps reduce the number of hypotheses to be corrected for in multiple testing. Ranks of true associations in genome-wide scans using a single test statistic have been studied. In a case-control design for association, the trend test has been proposed. However, three different trend tests, optimal for the recessive, additive, and dominant models, respectively, are available for each marker. Because the true genetic model is unknown, we rank markers based on multiple test statistics or test statistics robust to model mis-specification. We studied this problem with application to Problem 3 of Genetic Analysis Workshop 15. An independent simulation study was also conducted to further evaluate the proposed procedure.

  16. Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes

    OpenAIRE

    Teumer, Alexander; Tin, Adrienne; Sorice, Rossella; Gorski, Mathias; Yeo, Nan Cher; Chu, Audrey Y; Li, Man; Li, Yong; Mijatovic, Vladan; KO, Yi-An; Taliun, Daniel; Luciani, Alessandro; Chen, Ming-Huei; Yang, Qiong; Foster, Meredith C.

    2015-01-01

    Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies...

  17. Progress of genome-wide association studies of ankylosing spondylitis

    Science.gov (United States)

    Li, Zhixiu; Brown, Matthew A

    2017-01-01

    Ankylosing spondylitis (AS) is an immune-mediated arthritis which primarily affects the spine and sacroiliac joints. Significant progress has been made in discovery of genetic associations with AS by genome-wide association studies (GWAS) over past decade. These findings have uncovered novel pathways involved pathogenesis of the disease and have led to introduction of novel therapeutic treatments for AS. In this Review, we discuss the genetic variations associated with AS identified by GWAS, the major pathways revealed by these AS-associated variations and critical cell types involved in AS development. PMID:29333268

  18. Confirmation study of the effectiveness of prospect techniques for geothermal resources. Deep-seated geothermal resources survey report (Fiscal year 1994); 1994 nendo chinetsu tansa gijutsu nado kensho chosa. Shinbu chinetsu shigen chosa hokokusho

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-03-01

    Drilling and survey of deep geothermal exploration wells were conducted to grasp the existing situation of deep geothermal resource and the whole image of geothermal systems in the area where geothermal resource was already developed. In the drilling work in fiscal 1994, 4000m-class rigs and the top drive system were planned to be used for drilling of 12-1/4 inch wells, but 9-5/8 inch liners were used for drilling down to depths of 2550m or deeper since the amount of lost circulation is large and the withdrawal of devices may be very difficult. And in 8-1/2 inch wells, the well was drilled down to a depth of 2950m. As to the deep resistivity exploration technology using electromagnetic method, studies were made of a multiple-frequency array induction logging (MAIL) method, a vertical electromagnetic profiling (VEMP) method, a joint analysis method, etc. Concerning the synthetic fluid inclusion logging technology, containers were lowered into the well and a comparison was made between data of the homogenization temperature analysis of the formed fluid inclusion and those of the temperature log analysis. With relation to the making of deep geothermal structural models, revision was made according to the determination of depths of Miocene formations, Pre-tertiary formations, and the Kakkonda granite. 65 refs., 268 figs., 79 tabs.

  19. Genome-Wide Association Studies of Multiple Keratinocyte Cancers

    Science.gov (United States)

    Verkouteren, Joris A. C.; Hofman, Albert; Uitterlinden, André G.; Kraft, Peter; Turman, Constance; Han, Jiali; Cho, Eunyoung; Murabito, Joanne M.; Levy, Daniel; Qureshi, Abrar A.; Nijsten, Tamar

    2017-01-01

    There is strong evidence for a role of environmental risk factors involved in susceptibility to develop multiple keratinocyte cancers (mKCs), but whether genes are also involved in mKCs susceptibility has not been thoroughly investigated. We investigated whether single nucleotide polymorphisms (SNPs) are associated with susceptibility for mKCs. A genome-wide association study (GWAS) of 1,666 cases with mKCs and 1,950 cases with single KC (sKCs; controls) from Harvard cohorts (the Nurses' Health Study [NHS], NHS II, and the Health Professionals Follow-Up Study) and the Framingham Heart Study was carried-out using over 8 million SNPs (stage-1). We sought to replicate the most significant statistical associations (p-value≤ 5.5x10-6) in an independent cohort of 574 mKCs and 872 sKCs from the Rotterdam Study. In the discovery stage, 40 SNPs with suggestive associations (p-value ≤5.5x10-6) were identified, with eight independent SNPs tagging all 40 SNPs. The most significant SNP was located at chromosome 9 (rs7468390; p-value = 3.92x10-7). In stage-2, none of these SNPs replicated and only two of them were associated with mKCs in the same direction in the combined meta-analysis. We tested the associations for 19 previously reported basal cell carcinoma-related SNPs (candidate gene association analysis), and found that rs1805007 (MC1R locus) was significantly associated with risk of mKCs (p-value = 2.80x10-4). Although the suggestive SNPs with susceptibility for mKCs were not replicated, we found that previously identified BCC variants may also be associated with mKC, which the most significant association (rs1805007) located at the MC1R gene. PMID:28081215

  20. Genome-Wide Association Studies of Multiple Keratinocyte Cancers.

    Directory of Open Access Journals (Sweden)

    Luba M Pardo

    Full Text Available There is strong evidence for a role of environmental risk factors involved in susceptibility to develop multiple keratinocyte cancers (mKCs, but whether genes are also involved in mKCs susceptibility has not been thoroughly investigated. We investigated whether single nucleotide polymorphisms (SNPs are associated with susceptibility for mKCs. A genome-wide association study (GWAS of 1,666 cases with mKCs and 1,950 cases with single KC (sKCs; controls from Harvard cohorts (the Nurses' Health Study [NHS], NHS II, and the Health Professionals Follow-Up Study and the Framingham Heart Study was carried-out using over 8 million SNPs (stage-1. We sought to replicate the most significant statistical associations (p-value≤ 5.5x10-6 in an independent cohort of 574 mKCs and 872 sKCs from the Rotterdam Study. In the discovery stage, 40 SNPs with suggestive associations (p-value ≤5.5x10-6 were identified, with eight independent SNPs tagging all 40 SNPs. The most significant SNP was located at chromosome 9 (rs7468390; p-value = 3.92x10-7. In stage-2, none of these SNPs replicated and only two of them were associated with mKCs in the same direction in the combined meta-analysis. We tested the associations for 19 previously reported basal cell carcinoma-related SNPs (candidate gene association analysis, and found that rs1805007 (MC1R locus was significantly associated with risk of mKCs (p-value = 2.80x10-4. Although the suggestive SNPs with susceptibility for mKCs were not replicated, we found that previously identified BCC variants may also be associated with mKC, which the most significant association (rs1805007 located at the MC1R gene.

  1. Association between erectile dysfunction and chronic periodontitis: A clinical study

    Directory of Open Access Journals (Sweden)

    Ranjit Singh Uppal

    2014-01-01

    Conclusion: It may be concluded that chronic periodontitis and ED are associated with each other. However, further large scale studies with confounder analysis and longitudinal follow-up are warranted to explore the link between these two diseases.

  2. Genome-wide association study identifies novel locus for neuroticism and shows polygenic association with Major Depressive Disorder

    Science.gov (United States)

    de Moor, Marleen H.M.; van den Berg, Stéphanie M.; Verweij, Karin J.H.; Krueger, Robert F.; Luciano, Michelle; Vasquez, Alejandro Arias; Matteson, Lindsay K.; Derringer, Jaime; Esko, Tõnu; Amin, Najaf; Gordon, Scott D.; Hansell, Narelle K.; Hart, Amy B.; Seppälä, Ilkka; Huffman, Jennifer E.; Konte, Bettina; Lahti, Jari; Lee, Minyoung; Miller, Mike; Nutile, Teresa; Tanaka, Toshiko; Teumer, Alexander; Viktorin, Alexander; Wedenoja, Juho; Abecasis, Goncalo R.; Adkins, Daniel E.; Agrawal, Arpana; Allik, Jüri; Appel, Katja; Bigdeli, Timothy B.; Busonero, Fabio; Campbell, Harry; Costa, Paul T.; Smith, George Davey; Davies, Gail; de Wit, Harriet; Ding, Jun; Engelhardt, Barbara E.; Eriksson, Johan G.; Fedko, Iryna O.; Ferrucci, Luigi; Franke, Barbara; Giegling, Ina; Grucza, Richard; Hartmann, Annette M.; Heath, Andrew C.; Heinonen, Kati; Henders, Anjali K.; Homuth, Georg; Hottenga, Jouke-Jan; Janzing, Joost; Jokela, Markus; Karlsson, Robert; Kemp, John P.; Kirkpatrick, Matthew G.; Latvala, Antti; Lehtimäki, Terho; Liewald, David C.; Madden, Pamela A.F.; Magri, Chiara; Magnusson, Patrik K.E.; Marten, Jonathan; Maschio, Andrea; Medland, Sarah E.; Mihailov, Evelin; Milaneschi, Yuri; Montgomery, Grant W.; Nauck, Matthias; Ouwens, Klaasjan G.; Palotie, Aarno; Pettersson, Erik; Polasek, Ozren; Qian, Yong; Pulkki-Råback, Laura; Raitakari, Olli T.; Realo, Anu; Rose, Richard J.; Ruggiero, Daniela; Schmidt, Carsten O.; Slutske, Wendy S.; Sorice, Rossella; Starr, John M.; Pourcain, Beate St; Sutin, Angelina R.; Timpson, Nicholas J.; Trochet, Holly; Vermeulen, Sita; Vuoksimaa, Eero; Widen, Elisabeth; Wouda, Jasper; Wright, Margaret J.; Zgaga, Lina; Scotland, Generation; Porteous, David; Minelli, Alessandra; Palmer, Abraham A.; Rujescu, Dan; Ciullo, Marina; Hayward, Caroline; Rudan, Igor; Metspalu, Andres; Kaprio, Jaakko; Deary, Ian J.; Räikkönen, Katri; Wilson, James F.; Keltikangas-Järvinen, Liisa; Bierut, Laura J.; Hettema, John M.; Grabe, Hans J.; van Duijn, Cornelia M.; Evans, David M.; Schlessinger, David; Pedersen, Nancy L.; Terracciano, Antonio; McGue, Matt; Penninx, Brenda W.J.H.; Martin, Nicholas G.; Boomsma, Dorret I.

    2015-01-01

    shows that neuroticism is influenced by many genetic variants of small effect that are either common or tagged by common variants. These genetic variants also influence MDD. Future studies should confirm the role of the MAGI1 locus for neuroticism, and further investigate the association of MAGI1 and the polygenic association to a range of other psychiatric disorders that are phenotypically correlated with neuroticism. PMID:25993607

  3. Rh factor is associated with individual radiosensitivity: A cytogenetic study

    OpenAIRE

    Khosravifarsani, Meysam; Monfared, Ali Shabestani; Borzoueisileh, Sajad

    2016-01-01

    Introduction Radiosensitivity is an inherent trait, associated with a raised reaction to ionizing radiation on the human body. In radiotherapy and radiation protection fields, individualization of the patient?s treatment is one of the main topics. With the goal of determining biomarkers capable of anticipating normal tissue side reactions, we studied the association between the Rh factor and radiosensitivity. Methods This experimental study was carried out from January to June 2014 among 50 n...

  4. Genome-wide association study of clinical dimensions of schizophrenia

    DEFF Research Database (Denmark)

    Fanous, Ayman H; Zhou, Baiyu; Aggen, Steven H

    2012-01-01

    Multiple sources of evidence suggest that genetic factors influence variation in clinical features of schizophrenia. The authors present the first genome-wide association study (GWAS) of dimensional symptom scores among individuals with schizophrenia.......Multiple sources of evidence suggest that genetic factors influence variation in clinical features of schizophrenia. The authors present the first genome-wide association study (GWAS) of dimensional symptom scores among individuals with schizophrenia....

  5. Genome-wide association study of sporadic brain arteriovenous malformations

    OpenAIRE

    Weinsheimer, Shantel; Bendjilali, Nasrine; Nelson, Jeffrey; Guo, Diana E; Zaroff, Jonathan G.; Sidney, Stephen; McCulloch, Charles E.; Al-Shahi Salman, Rustam; Berg, Jonathan N; Bobby P. C. Koeleman; Simon, Matthias; Bostroem, Azize; Fontanella, Marco; Sturiale, Carmelo L; Pola, Roberto

    2016-01-01

    BACKGROUND: The pathogenesis of sporadic brain arteriovenous malformations (BAVMs) remains unknown, but studies suggest a genetic component. We estimated the heritability of sporadic BAVM and performed a genome-wide association study (GWAS) to investigate association of common single nucleotide polymorphisms (SNPs) with risk of sporadic BAVM in the international, multicentre Genetics of Arteriovenous Malformation (GEN-AVM) consortium.METHODS: The Caucasian discovery cohort included 515 BAVM c...

  6. Leveraging the HapMap Correlation Structure in Association Studies

    OpenAIRE

    Zaitlen, Noah; Kang, Hyun Min; Eskin, Eleazar; Halperin, Eran

    2007-01-01

    Recent high-throughput genotyping technologies, such as the Affymetrix 500k array and the Illumina HumanHap 550 beadchip, have driven down the costs of association studies and have enabled the measurement of single-nucleotide polymorphism (SNP) allele frequency differences between case and control populations on a genomewide scale. A key aspect in the efficiency of association studies is the notion of “indirect association,” where only a subset of SNPs are collected to serve as proxies for th...

  7. [Genome-wide association study of bronchial asthma in the Volga-Ural region of Russia].

    Science.gov (United States)

    Karunas, A S; Iunusbaev, B B; Fedorova, Iu Iu; Gimalova, G F; Ramazanova, N N; Gur'eva, L L; Mukhtarova, L A; Zagidullin, Sh Z; Etkina, E I; Khusnutdinova, E K

    2011-01-01

    Bronchial asthma is a chronic inflammatory respiratory disease that is caused by the complex interaction of environmental influences and genetic susceptibility. The first genome-wide association study of bronchial asthma discovered a significant association between SNPs within 17q12-21 genomic region and childhood bronchial asthma in individuals of European descent. Association with this genomic region was then replicated in a number of independent samples of European and Asian descent. Here we report results of the first genome-wide association study of bronchial asthma in the Volga-Ural region of Russia. The present study includes 358 unrelated patients with physician-diagnosed bronchial asthma and 369 disease-free control subjects of different ethnic origin (Russians, Tatars and Bashkirs). Genotyping of DNA samples was carried out using the Illumina Human610 quad array as a part of GABRIEL project (contract from the EC No LSHB-CT-2006-018996). After QC filtering procedures, a final set of 550915 SNPs genotyped in 330 cases and 348 controls was tested for association with bronchial asthma. Five markers on chromosome 17q12-21 showed statistically significant association with bronchial asthma (p < or = 4.79 x 10(-7)). SNP rs7216389 with the strongest evidence for association (p = 1.01 x 10(-7)) is located within the first intron of the GSDMB gene. Evidence for association was stronger with childhood-onset asthma (p = 1.97 x 10(-6) for SNP rs7216389) compared to late-onset asthma (p = 1.8 x 10(-4) for SNP rs7216389). Our replication study using three SNPs within GSDMB gene confirmed association with only childhood-onset asthma. In summary, these results suggest an important role for genetic variants within 17q12-q21 region in the development of bronchial asthma in the Volga-Ural region of Russia.

  8. A study on the mixed jaw lesions associated with teeth

    Energy Technology Data Exchange (ETDEWEB)

    Nah, Kyung Soo [Dept. of Dental Radiology, College of Dentistry, Pusan National University, Pusan (Korea, Republic of)

    2000-03-15

    1. Retrospectively evaluate the accuracy of tentative diagnosis or impression from the clinico-radiographic materials of jaw lesions which showed mixed lesions associated with teeth. 2. To observe the diagnostic importance of the calcified part of the lesions which appear as radiopaque areas. 14 cases of jaw lesions which showed mixed lesions associated with teeth were reviewed. These lesions were mostly diagnosed as adenomatoid odontogenic tumors (6 cases) or calcifying odontogenic cysts with (4 cases) or without odontomas (4 cases). The calcified elements of the lesions which demonstrated various sizes and patterns of radiopaque shadows resembled odontoid tissues in some cases but could not be defined in some other cases radiographically. The final histopathologic diagnosis confirmed adenomatoid odontogenic tumors in 4 of the 6 cases. The remaining 2 cases turned out to be odontoma and ameloblastic fibroodontoma. The 4 cases of calcifying odontogenic cysts with odontomas were correct in 3 cases but remaining 1 case was just odontoma. The 4 cases of calcifying odontogenic cysts were proved to be odontogenic keratocyst, calcified peripheral fibroma, unicystic ameloblastoma and squamous cell carcinoma. The diagnostic accuracy of the adenomatoid odontogenic tumors and calcifying odontogenic cysts were high when the lesions show typical appearance. The calcifications which show radiopaque areas could be odontomas or dystrophic calficifations or remnants of bone fragments from resorption.

  9. Genome-wide association studies for multiple diseases of the German Shepherd Dog.

    Science.gov (United States)

    Tsai, Kate L; Noorai, Rooksana E; Starr-Moss, Alison N; Quignon, Pascale; Rinz, Caitlin J; Ostrander, Elaine A; Steiner, Jörg M; Murphy, Keith E; Clark, Leigh Anne

    2012-02-01

    The German Shepherd Dog (GSD) is a popular working and companion breed for which over 50 hereditary diseases have been documented. Herein, SNP profiles for 197 GSDs were generated using the Affymetrix v2 canine SNP array for a genome-wide association study to identify loci associated with four diseases: pituitary dwarfism, degenerative myelopathy (DM), congenital megaesophagus (ME), and pancreatic acinar atrophy (PAA). A locus on Chr 9 is strongly associated with pituitary dwarfism and is proximal to a plausible candidate gene, LHX3. Results for DM confirm a major locus encompassing SOD1, in which an associated point mutation was previously identified, but do not suggest modifier loci. Several SNPs on Chr 12 are associated with ME and a 4.7 Mb haplotype block is present in affected dogs. Analysis of additional ME cases for a SNP within the haplotype provides further support for this association. Results for PAA indicate more complex genetic underpinnings. Several regions on multiple chromosomes reach genome-wide significance. However, no major locus is apparent and only two associated haplotype blocks, on Chrs 7 and 12 are observed. These data suggest that PAA may be governed by multiple loci with small effects, or it may be a heterogeneous disorder.

  10. Association between spicy food consumption and lipid profiles in adults: a nationwide population-based study.

    Science.gov (United States)

    Xue, Yong; He, Tingchao; Yu, Kai; Zhao, Ai; Zheng, Wei; Zhang, Yumei; Zhu, Baoli

    2017-07-01

    CVD remains the leading cause of mortality worldwide, with abnormal lipid metabolism as a major risk factor. The aim of this study was to investigate associations between spicy food consumption and serum lipids in Chinese adults. Data were extracted from the 2009 phase of the China Health and Nutrition Survey, consisting of 6774 apparently healthy Chinese adults aged 18-65 years. The frequency of consumption and degree of pungency of spicy food were self-reported, and regular spicy food consumption was assessed using three consecutive 24-h recalls. Total cholesterol, TAG, LDL-cholesterol and HDL-cholesterol in fasting serum were measured. Multilevel mixed-effects models were constructed to estimate associations between spicy food consumption and serum lipid profiles. The results showed that the frequency and the average amount of spicy food intake were both inversely associated with LDL-cholesterol and LDL-cholesterol:HDL-cholesterol ratio (all P for trendfood (≥5 times/week) and who consumed spicy food perceived as moderate in pungency were significantly higher than those who did not (both Pfood intake and the degree of pungency in spicy food were positively associated with TAG (all P for trendfood consumption was inversely associated with serum cholesterol and positively associated with serum TAG, and additional studies are needed to confirm the findings as well as to elucidate the potential roles of spicy food consumption in lipid metabolism.

  11. Visual Confirmation (VICON) of Takeoff Clearance Signal System Impact Study.

    Science.gov (United States)

    1980-11-01

    Throughput, THOG THI IEAYTtAI 1SICAI Simulation, Sampling Techniques wMPORMAION 5SsIlVIC. SPAMO.euLD. P9. Ammoty C,hLuMO..EA..s-W . "awfoc .1aeis.ea W"" FE2...solution to airport surface traffic problems . VICON consists of a cluster of three green lights located on the left side of the runway at each...overall solution to airport surface traffic problems . VICON consists of a cluster of three green lights located on the left side of the runway at each

  12. Computer tomographic and angiographic studies of histologically confirmed intrahepatic masses

    Energy Technology Data Exchange (ETDEWEB)

    Janson, R.; Lackner, K.; Paquet, K.J.; Thelen, M.; Thurn, P.

    1980-06-01

    The computer tomographic and angiographic findings in 53 patients with intrahepatic masses were compared. The histological findings show that 17 were due to echinococcus, 12 were due to hepatic carcinoma, ten were metastases, five patients had focal nodular hyperplasia, three an alveolar echinococcus and there were three cases with an haemangioma of the liver and a further three liver abscesses. Computer tomography proved superior in peripherally situated lesions, and in those in the left lobe of the liver. Arteriography was better at demonstrating lesions below 2 cm in size, particularly vascular tumours. As a pre-operative measure, angiography is to be preferred since it is able to demonstrate anatomic anomalies and variations in the blood supply, as well as invasion of the portal vein or of the inferior vena cava.

  13. Epigenome-wide association studies identify DNA methylation associated with kidney function.

    Science.gov (United States)

    Chu, Audrey Y; Tin, Adrienne; Schlosser, Pascal; Ko, Yi-An; Qiu, Chengxiang; Yao, Chen; Joehanes, Roby; Grams, Morgan E; Liang, Liming; Gluck, Caroline A; Liu, Chunyu; Coresh, Josef; Hwang, Shih-Jen; Levy, Daniel; Boerwinkle, Eric; Pankow, James S; Yang, Qiong; Fornage, Myriam; Fox, Caroline S; Susztak, Katalin; Köttgen, Anna

    2017-11-03

    Chronic kidney disease (CKD) is defined by reduced estimated glomerular filtration rate (eGFR). Previous genetic studies have implicated regulatory mechanisms contributing to CKD. Here we present epigenome-wide association studies of eGFR and CKD using whole-blood DNA methylation of 2264 ARIC Study and 2595 Framingham Heart Study participants to identify epigenetic signatures of kidney function. Of 19 CpG sites significantly associated (P < 1e-07) with eGFR/CKD and replicated, five also associate with renal fibrosis in biopsies from CKD patients and show concordant DNA methylation changes in kidney cortex. Lead CpGs at PTPN6/PHB2, ANKRD11, and TNRC18 map to active enhancers in kidney cortex. At PTPN6/PHB2 cg19942083, methylation in kidney cortex associates with lower renal PTPN6 expression, higher eGFR, and less renal fibrosis. The regions containing the 243 eGFR-associated (P < 1e-05) CpGs are significantly enriched for transcription factor binding sites of EBF1, EP300, and CEBPB (P < 5e-6). Our findings highlight kidney function associated epigenetic variation.

  14. A genome wide association study identifies common variants associated with lipid levels in the Chinese population.

    Directory of Open Access Journals (Sweden)

    Li Zhou

    Full Text Available Plasma lipid levels are important risk factors for cardiovascular disease and are influenced by genetic and environmental factors. Recent genome wide association studies (GWAS have identified several lipid-associated loci, but these loci have been identified primarily in European populations. In order to identify genetic markers for lipid levels in a Chinese population and analyze the heterogeneity between Europeans and Asians, especially Chinese, we performed a meta-analysis of two genome wide association studies on four common lipid traits including total cholesterol (TC, triglycerides (TG, low-density lipoprotein cholesterol (LDL and high-density lipoprotein cholesterol (HDL in a Han Chinese population totaling 3,451 healthy subjects. Replication was performed in an additional 8,830 subjects of Han Chinese ethnicity. We replicated eight loci associated with lipid levels previously reported in a European population. The loci genome wide significantly associated with TC were near DOCK7, HMGCR and ABO; those genome wide significantly associated with TG were near APOA1/C3/A4/A5 and LPL; those genome wide significantly associated with LDL were near HMGCR, ABO and TOMM40; and those genome wide significantly associated with HDL were near LPL, LIPC and CETP. In addition, an additive genotype score of eight SNPs representing the eight loci that were found to be associated with lipid levels was associated with higher TC, TG and LDL levels (P = 5.52 × 10(-16, 1.38 × 10(-6 and 5.59 × 10(-9, respectively. These findings suggest the cumulative effects of multiple genetic loci on plasma lipid levels. Comparisons with previous GWAS of lipids highlight heterogeneity in allele frequency and in effect size for some loci between Chinese and European populations. The results from our GWAS provided comprehensive and convincing evidence of the genetic determinants of plasma lipid levels in a Chinese population.

  15. Depression and Associated Factors in the Elderly Cadres in Fuzhou, China: A Community-based Study

    Directory of Open Access Journals (Sweden)

    Lan Cong

    2015-03-01

    Conclusion: Depression is common among Chinese elderly cadres. Our results confirmed that late-life depression remains complex, and lack of social engagement and low family support were associated with increased risk of GD.

  16. Neutrophil Gelatinase Associated Lipocalin (NGAL) in Leptospirosis Acute Kidney Injury: A Multicenter Study in Thailand.

    Science.gov (United States)

    Srisawat, Nattachai; Praditpornsilpa, Kearkiat; Patarakul, Kanitha; Techapornrung, Malee; Daraswang, Tinnapop; Sukmark, Theerapon; Khositrangsikun, Kamol; Fakthongyoo, Apinya; Oranrigsupak, Petchdee; Praderm, Laksamon; Suwattanasilpa, Ummarit; Peerapornratana, Sadudee; Loahaveeravat, Passisd; Suwachittanont, Nattachai; Wirotwan, Thaksa-on; Phonork, Chayanat; Kumpunya, Sarinya; Tiranathanagul, Khajohn; Chirathaworn, Chintana; Eiam-ong, Somchai; Tungsanga, Kriang; Sitprija, Visith; Kellum, John A; Townamchai, Natavudh

    2015-01-01

    AKI is one of the most serious complications of leptospirosis, an important zoonosis in the tropics. Recently, NGAL, one of the novel AKI biomarkers, is extensively studied in various specific settings such as sepsis, cardiac surgery, and radiocontrast nephropathy. In this multicenter study, we aimed to study the role of NGAL as an early marker and an outcome predictor of leptospirosis associated AKI. Patients who presented with clinical suspiciousness of leptospirosis were prospectively enrolled in 9 centers from August 2012 to November 2014. The first day of enrollment was the first day of clinical suspicious leptospirosis. Blood and urine samples were serially collected on the first three days and day 7 after enrollment. We used three standard techniques (microscopic agglutination test, direct culture, and PCR technique) to confirm the diagnosis of leptospirosis. KDIGO criteria were used for AKI diagnosis. Recovery was defined as alive and not requiring dialysis during hospitalization or maintaining maximum KDIGO stage at hospital discharge. Of the 221 recruited cases, 113 cases were leptospirosis confirmed cases. Thirty seven percent developed AKI. Median uNGAL and pNGAL levels in those developing AKI were significantly higher than in patients not developing AKI [253.8 (631.4) vs 24.1 (49.6) ng/ml, p leptospirosis associated AKI. However, both of them did not show the potential role to be the predictor of renal recovery in this specific setting.

  17. Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study.

    Science.gov (United States)

    Gottlieb, D J; Hek, K; Chen, T-H; Watson, N F; Eiriksdottir, G; Byrne, E M; Cornelis, M; Warby, S C; Bandinelli, S; Cherkas, L; Evans, D S; Grabe, H J; Lahti, J; Li, M; Lehtimäki, T; Lumley, T; Marciante, K D; Pérusse, L; Psaty, B M; Robbins, J; Tranah, G J; Vink, J M; Wilk, J B; Stafford, J M; Bellis, C; Biffar, R; Bouchard, C; Cade, B; Curhan, G C; Eriksson, J G; Ewert, R; Ferrucci, L; Fülöp, T; Gehrman, P R; Goodloe, R; Harris, T B; Heath, A C; Hernandez, D; Hofman, A; Hottenga, J-J; Hunter, D J; Jensen, M K; Johnson, A D; Kähönen, M; Kao, L; Kraft, P; Larkin, E K; Lauderdale, D S; Luik, A I; Medici, M; Montgomery, G W; Palotie, A; Patel, S R; Pistis, G; Porcu, E; Quaye, L; Raitakari, O; Redline, S; Rimm, E B; Rotter, J I; Smith, A V; Spector, T D; Teumer, A; Uitterlinden, A G; Vohl, M-C; Widen, E; Willemsen, G; Young, T; Zhang, X; Liu, Y; Blangero, J; Boomsma, D I; Gudnason, V; Hu, F; Mangino, M; Martin, N G; O'Connor, G T; Stone, K L; Tanaka, T; Viikari, J; Gharib, S A; Punjabi, N M; Räikkönen, K; Völzke, H; Mignot, E; Tiemeier, H

    2015-10-01

    Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.

  18. The Ghostly Novae of Spirits: Candidates, Confirmations, and Classifications

    Science.gov (United States)

    Corgan, David William

    2015-08-01

    The SPIRITS (SPitzer InfraRed Intensive Transients Survey) project has surveyed 242 galaxies across multiple epochs for over a year, searching for gap transient and variable star activity. To date, a wealth of candidate objects has been discovered in the warm Spitzer data being used, with the current total at 1426 individual detections. The discovery, confirmation, follow-up, and comparison to prediction rates of these candidates is presented. Employing subjective detection methods, discussed herein, individual discovery to group confirmation rates were found to be less than 3.6%. Photometric confirmation with correlated team instruments left 53 sources of interest remaining for further study. These targets ranged across 30 different galaxies including IC2163, Messier 101, and NGC3198. Follow-up ground observations in the 1.2, 1.6, and 2.2 µm wavelengths with the legacy 2MASS instrument at MLOF (Mount Lemmon Observing Facility) are highlighted. The data reduction process which has evolved to improve detections by ~.6mag is also detailed. These results are supplemented by SPIRITS team input from a variety of world-class infrared facilities to produce overall nova candidate characteristics, which are included. In some cases this extends to light curves from confirmed and observed novae to depths of ~20mag, while in others it is restricted to limiting magnitudes of ~18 at sight of occurrence (the true “ghosts” of SPIRITS). Candidate novae have been separated into classes where data allows, including the possible discovery of a new variable type coined SMIRTS (Super Massive InfraRed TransientS), and probable members of the elusive Luminous Red Novae category. Finally, comparison of numerical survey results to nova prediction rates is undertaken and results presented. Where deviations from luminosity curve fittings occur, such as in the overly active M81 and IC0342 galaxies, possible causes are proposed.

  19. Sleep quality is associated with weight loss maintenance status: the MedWeight study.

    Science.gov (United States)

    Yannakoulia, M; Anastasiou, C A; Karfopoulou, E; Pehlivanidis, A; Panagiotakos, D B; Vgontzas, A

    2017-06-01

    Sleep duration and quality have been associated with many health outcomes, including weight management. We aimed to investigate the effect of self-reported sleep duration and quality on weight loss maintenance in participants of the MedWeight study, a registry of individuals that lost at least 10% of body weight in the past and either maintained the loss (maintainers: weight maintenance of at least 10% of initial weight loss) or regained it (regainers: weight ≥95% of their maximum body weight). Study participants included 528 volunteers (61% women). Sleep quantity referred to the reported duration of nocturnal sleep, as well as the frequency of mid-day naps during the last month. Sleep quality was assessed through the Athens Insomnia Scale (AIS). Reported sleep quantity was associated with weight maintenance status, but the association became non-significant when the AIS score entered the model. In specific, AIS was inversely associated with the likelihood of being a maintainer (OR=0.89 per AIS unit, 95% CI: 0.81 - 0.98), even after adjusting for potential confounders. Sex-specific analysis revealed that the association between the AIS score and maintenance status was evident in men but not in women. Future studies are needed to confirm these results in other population groups and reveal underlying mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Association Between Migraine and Dry Eye Disease: A Nationwide Population-Based Study.

    Science.gov (United States)

    Yang, Soonwon; Kim, Woojun; Kim, Hyun Seung; Na, Kyung-Sun

    2017-06-01

    Despite the possible association between migraine and dry eye disease (DED), there are only a few studies investigating this link in a relatively limited number of patients. Therefore, we have analyzed the relationship between migraine and DED in the Korean population. This population-based cross-sectional study included 14 329 adults participating in the fifth annual Korea National Health and Nutrition Examination Survey from 2010 to 2012. Migraine, DED diagnosis, and DED symptoms were assessed using questionnaires and surveys. Data were analyzed using logistic regression to determine the association of migraine with DED while controlling for demographic, lifestyle, and medical factors. Individuals with migraine were more likely to report a DED diagnosis (14.4% vs. 8.2%, p migraine and DED diagnosis was significant after adjustments (OR, 1.577; 95% CI, 1.340-1.855). The association between migraine and DED symptoms showed a similar pattern (OR, 1.304; 95%CI, 1.151-1.502). Although a causal relationship was not revealed, we found that patients who had a lifetime history of migraine were more likely to suffer from DED than individuals who did not present with headaches; this association may require confirmation. Large prospective cohort studies are required to evaluate the association between migraine and DED, as well as the influence of DED treatment on the frequency and severity of migraine attacks.

  1. Association between serum CA 19-9 and metabolic syndrome: A cross-sectional study.

    Science.gov (United States)

    Du, Rui; Cheng, Di; Lin, Lin; Sun, Jichao; Peng, Kui; Xu, Yu; Xu, Min; Chen, Yuhong; Bi, Yufang; Wang, Weiqing; Lu, Jieli; Ning, Guang

    2017-11-01

    Increasing evidence suggests that serum CA 19-9 is associated with abnormal glucose metabolism. However, data on the association between CA 19-9 and metabolic syndrome is limited. The aim of the present study was to investigate the association between serum CA 19-9 and metabolic syndrome. A cross-sectional study was conducted on 3641 participants aged ≥40 years from the Songnan Community, Baoshan District in Shanghai, China. Logistic regression analysis was used to evaluate the association between serum CA 19-9 and metabolic syndrome. Multivariate logistic regression analysis showed that compared with participants in the first tertile of serum CA 19-9, those in the second and third tertiles had increased odds ratios (OR) for prevalent metabolic syndrome (multivariate adjusted OR 1.46 [95% confidence interval {CI} 1.11-1.92] and 1.51 [95% CI 1.14-1.98]; P trend  = 0.005). In addition, participants with elevated serum CA 19-9 (≥37 U/mL) had an increased risk of prevalent metabolic syndrome compared with those with serum CA 19-9 metabolic syndrome. In order to confirm this association and identify potential mechanisms, prospective cohort and mechanic studies should be performed. © 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  2. Use of diuretics is associated with reduced risk of Alzheimer's disease: the Cache County Study.

    Science.gov (United States)

    Chuang, Yi-Fang; Breitner, John C S; Chiu, Yen-Ling; Khachaturian, Ara; Hayden, Kathleen; Corcoran, Chris; Tschanz, JoAnn; Norton, Maria; Munger, Ron; Welsh-Bohmer, Kathleen; Zandi, Peter P

    2014-11-01

    Although the use of antihypertensive medications has been associated with reduced risk of Alzheimer's disease (AD), it remains unclear which class provides the most benefit. The Cache County Study of Memory Health and Aging is a prospective longitudinal cohort study of dementing illnesses among the elderly population of Cache County, Utah. Using waves I to IV data of the Cache County Study, 3417 participants had a mean of 7.1 years of follow-up. Time-varying use of antihypertensive medications including different class of diuretics, angiotensin converting enzyme inhibitors, β-blockers, and calcium channel blockers was used to predict the incidence of AD using Cox proportional hazards analyses. During follow-up, 325 AD cases were ascertained with a total of 23,590 person-years. Use of any antihypertensive medication was associated with lower incidence of AD (adjusted hazard ratio [aHR], 0.77; 95% confidence interval [CI], 0.61-0.97). Among different classes of antihypertensive medications, thiazide (aHR, 0.7; 95% CI, 0.53-0.93), and potassium-sparing diuretics (aHR, 0.69; 95% CI, 0.48-0.99) were associated with the greatest reduction of AD risk. Thiazide and potassium-sparing diuretics were associated with decreased risk of AD. The inverse association of potassium-sparing diuretics confirms an earlier finding in this cohort, now with longer follow-up, and merits further investigation. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Diverse Genome-wide Association Studies Associate the IL12/IL23 Pathway with Crohn Disease

    Science.gov (United States)

    Wang, Kai; Zhang, Haitao; Kugathasan, Subra; Annese, Vito; Bradfield, Jonathan P.; Russell, Richard K.; Sleiman, Patrick M.A.; Imielinski, Marcin; Glessner, Joseph; Hou, Cuiping; Wilson, David C.; Walters, Thomas; Kim, Cecilia; Frackelton, Edward C.; Lionetti, Paolo; Barabino, Arrigo; Van Limbergen, Johan; Guthery, Stephen; Denson, Lee; Piccoli, David; Li, Mingyao; Dubinsky, Marla; Silverberg, Mark; Griffiths, Anne; Grant, Struan F.A.; Satsangi, Jack; Baldassano, Robert; Hakonarson, Hakon

    2009-01-01

    Previous genome-wide association (GWA) studies typically focus on single-locus analysis, which may not have the power to detect the majority of genuinely associated loci. Here, we applied pathway analysis using Affymetrix SNP genotype data from the Wellcome Trust Case Control Consortium (WTCCC) and uncovered significant association between Crohn Disease (CD) and the IL12/IL23 pathway, harboring 20 genes (p = 8 × 10−5). Interestingly, the pathway contains multiple genes (IL12B and JAK2) or homologs of genes (STAT3 and CCR6) that were recently identified as genuine susceptibility genes only through meta-analysis of several GWA studies. In addition, the pathway contains other susceptibility genes for CD, including IL18R1, JUN, IL12RB1, and TYK2, which do not reach genome-wide significance by single-marker association tests. The observed pathway-specific association signal was subsequently replicated in three additional GWA studies of European and African American ancestry generated on the Illumina HumanHap550 platform. Our study suggests that examination beyond individual SNP hits, by focusing on genetic networks and pathways, is important to unleashing the true power of GWA studies. PMID:19249008

  4. Association Between Circulating Oxidized LDL and Atherosclerotic Cardiovascular Disease: A Meta-analysis of Observational Studies.

    Science.gov (United States)

    Gao, Shen; Zhao, Dong; Wang, Miao; Zhao, Fan; Han, Xueyu; Qi, Yue; Liu, Jing

    2017-12-01

    Although basic research has suggested that oxidized low-density lipoprotein (ox-LDL) is involved in the pathogenesis of atherosclerosis, population observational studies have yielded conflicting results about the association between circulating ox-LDL and atherosclerotic cardiovascular disease (ASCVD). Therefore, we performed a systematic review and meta-analysis of currently available observational studies to verify the association between circulating ox-LDL and ASCVD. We systematically searched PubMed and the Cochrane Library from their inception to March 27, 2017, for nested case-control studies, case-cohort studies, and prospective cohort studies on the relationship between ox-LDL and ASCVD. Studies that did not assess the hazard ratio, relative risk, or odds ratio of ox-LDL or did not adjust for other risk factors, or those without examination of ox-LDL before collection of ASCVD occurrences were excluded. The summarized effect size was combined using fixed effect models. Subgroup analyses were performed on the basis of study quality, study design, definition of ASCVD events, effect size types, types of ox-LDL assay, ox-LDL contrast level, and whether low-density lipoprotein cholesterol was adjusted in a multivariate model. A total of 12 included studies consisted of 3 nested case-control studies, 1 case-cohort study, 5 hospital-based cohort studies, and 3 community-based cohort studies. The summary effect size of increased circulating ox-LDL was 1.79 (95% confidence interval, 1.56-2.05) for ASCVD. Similar associations were shown in all subgroups. Our findings indicate that increased levels of circulating ox-LDL are associated with clinical ASCVD events. Further well designed community-based cohort studies or intervention studies are needed to confirm our findings. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  5. CT and MR Studies of Giant Dermoid Cyst Associated to Fat Dissemination at the Cortical and Cisternal Cerebral Spaces

    Directory of Open Access Journals (Sweden)

    Alessandro D'Amore

    2013-01-01

    Full Text Available This study focuses on CT and MR studies of adult patient with giant lesion of the posterior cranial fossa associated with micro- and macroaccumulations with density and signal like “fat” at the level of the cortical and cisternal cerebral spaces. This condition is compatible with previous asymptomatic ruptured dermoid cyst. Histological findings confirm the hypothesis formulated using the imaging. We also integrate elements of differential diagnosis by another giant lesion of the posterior cranial fossa.

  6. Power analysis for genome-wide association studies

    Directory of Open Access Journals (Sweden)

    Klein Robert J

    2007-08-01

    Full Text Available Abstract Background Genome-wide association studies are a promising new tool for deciphering the genetics of complex diseases. To choose the proper sample size and genotyping platform for such studies, power calculations that take into account genetic model, tag SNP selection, and the population of interest are required. Results The power of genome-wide association studies can be computed using a set of tag SNPs and a large number of genotyped SNPs in a representative population, such as available through the HapMap project. As expected, power increases with increasing sample size and effect size. Power also depends on the tag SNPs selected. In some cases, more power is obtained by genotyping more individuals at fewer SNPs than fewer individuals at more SNPs. Conclusion Genome-wide association studies should be designed thoughtfully, with the choice of genotyping platform and sample size being determined from careful power calculations.

  7. Prediction of disease and phenotype associations from genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Stephanie N Lewis

    Full Text Available BACKGROUND: Genome wide association studies (GWAS have proven useful as a method for identifying genetic variations associated with diseases. In this study, we analyzed GWAS data for 61 diseases and phenotypes to elucidate common associations based on single nucleotide polymorphisms (SNP. The study was an expansion on a previous study on identifying disease associations via data from a single GWAS on seven diseases. METHODOLOGY/PRINCIPAL FINDINGS: Adjustments to the originally reported study included expansion of the SNP dataset using Linkage Disequilibrium (LD and refinement of the four levels of analysis to encompass SNP, SNP block, gene, and pathway level comparisons. A pair-wise comparison between diseases and phenotypes was performed at each level and the Jaccard similarity index was used to measure the degree of association between two diseases/phenotypes. Disease relatedness networks (DRNs were used to visualize our results. We saw predominant relatedness between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis for the first three levels of analysis. Expected relatedness was also seen between lipid- and blood-related traits. CONCLUSIONS/SIGNIFICANCE: The predominant associations between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis can be validated by clinical studies. The diseases have been proposed to share a systemic inflammation phenotype that can result in progression of additional diseases in patients with one of these three diseases. We also noticed unexpected relationships between metabolic and neurological diseases at the pathway comparison level. The less significant relationships found between diseases require a more detailed literature review to determine validity of the predictions. The results from this study serve as a first step towards a better understanding of seemingly unrelated diseases and phenotypes with similar symptoms or modes of treatment.

  8. Population structure and association mapping studies for important ...

    Indian Academy of Sciences (India)

    Large phenotypic variability was observed for the agronomic traits under study indicating suitability of the genotypes for association studies. The maximum values for plant height, pods per plant, seeds per pod, 100-seed weight and seed yield per plant were approximately two and half to three times more than the minimum ...

  9. A genome-wide association study of aging

    NARCIS (Netherlands)

    S. Walter (Stefan); G. Atzmon (Gil); E.W. Demerath (Ellen); M. Garcia (Melissa); R.C. Kaplan (Robert); M. Kumari (Meena); K.L. Lunetta (Kathryn); Y. Milaneschi (Yuri); T. Tanaka (Toshiko); G.J. Tranah (Gregory); U. Völker (Uwe); L. Yu (Lei); A.M. Arnold (Alice); E.J. Benjamin (Emelia); R. Biffar (Reiner); A.S. Buchman (Aron); E.A. Boerwinkle (Eric); D. Couper (David); P.L. de Jager (Philip); D.A. Evans (Denis); T.B. Harris (Tamara); W. Hoffmann (Wolfgang); A. Hofman (Albert); D. Karasik (David); D.P. Kiel (Douglas); T. Kocher (Thomas); M. Kuningas (Maris); L.J. Launer (Lenore); K. Lohman (Kurt); P.L. Lutsey (Pamela); J.P. Mackenbach (Johan); K. Marciante (Kristin); B.M. Psaty (Bruce); E.M. Reiman (Eric); J.I. Rotter (Jerome); S. Seshadri (Sudha); M.D. Shardell (Michelle); A.V. Smith (Albert Vernon); P. Tikka-Kleemola (Päivi); J. Walston (Jeremy); M.C. Zillikens (Carola); S. Bandinelli (Stefania); S.E. Baumeister (Sebastian); D.A. Bennett (David); L. Ferrucci (Luigi); V. Gudnason (Vilmundur); M. Kivimaki (Mika); Y. Liu (Yongmei); J. Murabito (Joanne); A.B. Newman (Anne); H.W. Tiemeier (Henning); N. Franceschini (Nora)

    2011-01-01

    textabstractHuman longevity and healthy aging show moderate heritability (20%-50%). We conducted a meta-analysis of genome-wide association studies from 9 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium for 2 outcomes: (1) all-cause mortality, and (2)

  10. Update on bacterial meningitis: epidemiology, trials and genetic association studies

    NARCIS (Netherlands)

    Kasanmoentalib, E. Soemirien; Brouwer, Matthijs C.; van de Beek, Diederik

    2013-01-01

    Bacterial meningitis is a life-threatening disease that continues to inflict a heavy toll. We reviewed recent advances in vaccination, randomized studies on treatment, and genetic association studies in bacterial meningitis. The incidence of bacterial meningitis has decreased after implementation of

  11. A genome-wide association study of anorexia nervosa

    NARCIS (Netherlands)

    Boraska, V; Franklin, C S; Floyd, J A B; Thornton, L M; Huckins, L M; Southam, L; Rayner, N W; Tachmazidou, I; Klump, K L; Treasure, J; Lewis, C M; Schmidt, U; Tozzi, F; Kiezebrink, K; Hebebrand, J; Gorwood, P; Adan, R A H; Kas, M J H; Favaro, A; Santonastaso, P; Fernández-Aranda, F; Gratacos, M; Rybakowski, F; Dmitrzak-Weglarz, M; Kaprio, J; Keski-Rahkonen, A; Raevuori, A; Van Furth, E F; Slof-Op 't Landt, M C T; Hudson, J I; Reichborn-Kjennerud, T; Knudsen, G P S; Monteleone, P; Kaplan, A S; Karwautz, A; Hakonarson, H; Berrettini, W H; Guo, Y|info:eu-repo/dai/nl/369207084; Li, D; Schork, N J; Komaki, G; Ando, T; Inoko, H; Esko, T; Fischer, K; Männik, K; Metspalu, A; Baker, J H; Cone, R D; Dackor, J; DeSocio, J E; Hilliard, C E; O'Toole, J K; Pantel, J; Szatkiewicz, J P; Taico, C; Zerwas, S; Trace, S E; Davis, O S P; Helder, S; Bühren, K; Burghardt, R; de Zwaan, M; Egberts, K; Ehrlich, S; Herpertz-Dahlmann, B; Herzog, W; Imgart, H; Scherag, A; Scherag, S; Zipfel, S; Boni, C; Ramoz, N; Versini, A; Brandys, M K; Danner, U N; de Kovel, C; Hendriks, J; Koeleman, B P C; Ophoff, R A; Strengman, E; van Elburg, Annemarie|info:eu-repo/dai/nl/191430129; Bruson, A; Clementi, M; Degortes, D; Forzan, M; Tenconi, E; Docampo, E; Escaramís, G; Jiménez-Murcia, S; Lissowska, J; Rajewski, A; Szeszenia-Dabrowska, N; Slopien, A; Hauser, J; Karhunen, L; Meulenbelt, I; Slagboom, P E; Tortorella, A; Maj, M; Dedoussis, G; Dikeos, D; Gonidakis, F; Tziouvas, K; Tsitsika, A; Papezova, H; Slachtova, L; Martaskova, D; Kennedy, J L; Levitan, R D; Yilmaz, Z; Huemer, J; Koubek, D; Merl, E; Wagner, G; Lichtenstein, P; Breen, G; Cohen-Woods, S; Farmer, A; McGuffin, P; Cichon, S; Giegling, I; Herms, S; Rujescu, D; Schreiber, S; Wichmann, H-E; Dina, C; Sladek, R; Gambaro, G; Soranzo, N; Julia, A; Marsal, S; Rabionet, R; Gaborieau, V; Dick, D M; Palotie, A; Ripatti, S; Widén, E; Andreassen, O A; Espeseth, T; Lundervold, A; Reinvang, I; Steen, V M; Le Hellard, S; Mattingsdal, M; Ntalla, I; Bencko, V; Foretova, L; Janout, V; Navratilova, M; Gallinger, S; Pinto, D; Scherer, S W; Aschauer, H; Carlberg, L; Schosser, A; Alfredsson, L; Ding, B; Klareskog, L; Padyukov, L; Courtet, P; Guillaume, S; Jaussent, I; Finan, C; Kalsi, G; Roberts, M; Logan, D W; Peltonen, L; Ritchie, G R S; Barrett, J C; Estivill, X; Hinney, A; Sullivan, P F; Collier, D A; Zeggini, E; Bulik, C M

    2014-01-01

    Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14

  12. Association study of the oestrogen signalling pathway genes in ...

    Indian Academy of Sciences (India)

    Yamamoto T. 2004 Association study using single nucleotide polymorphisms in the estrogen receptor beta (ESR2) gene for preeclampsia. Hypertens Res. 27, 903–909. Murabito J. M., Yang Q., Fox C., Wilson P. W. and Cupples L. A.. 2005a Heritability of age at natural menopause in the Framing- ham Heart Study. J. Clin.

  13. Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study.

    Science.gov (United States)

    Hou, Liping; Heilbronner, Urs; Degenhardt, Franziska; Adli, Mazda; Akiyama, Kazufumi; Akula, Nirmala; Ardau, Raffaella; Arias, Bárbara; Backlund, Lena; Banzato, Claudio E M; Benabarre, Antoni; Bengesser, Susanne; Bhattacharjee, Abesh Kumar; Biernacka, Joanna M; Birner, Armin; Brichant-Petitjean, Clara; Bui, Elise T; Cervantes, Pablo; Chen, Guo-Bo; Chen, Hsi-Chung; Chillotti, Caterina; Cichon, Sven; Clark, Scott R; Colom, Francesc; Cousins, David A; Cruceanu, Cristiana; Czerski, Piotr M; Dantas, Clarissa R; Dayer, Alexandre; Étain, Bruno; Falkai, Peter; Forstner, Andreas J; Frisén, Louise; Fullerton, Janice M; Gard, Sébastien; Garnham, Julie S; Goes, Fernando S; Grof, Paul; Gruber, Oliver; Hashimoto, Ryota; Hauser, Joanna; Herms, Stefan; Hoffmann, Per; Hofmann, Andrea; Jamain, Stephane; Jiménez, Esther; Kahn, Jean-Pierre; Kassem, Layla; Kittel-Schneider, Sarah; Kliwicki, Sebastian; König, Barbara; Kusumi, Ichiro; Lackner, Nina; Laje, Gonzalo; Landén, Mikael; Lavebratt, Catharina; Leboyer, Marion; Leckband, Susan G; Jaramillo, Carlos A López; MacQueen, Glenda; Manchia, Mirko; Martinsson, Lina; Mattheisen, Manuel; McCarthy, Michael J; McElroy, Susan L; Mitjans, Marina; Mondimore, Francis M; Monteleone, Palmiero; Nievergelt, Caroline M; Nöthen, Markus M; Ösby, Urban; Ozaki, Norio; Perlis, Roy H; Pfennig, Andrea; Reich-Erkelenz, Daniela; Rouleau, Guy A; Schofield, Peter R; Schubert, K Oliver; Schweizer, Barbara W; Seemüller, Florian; Severino, Giovanni; Shekhtman, Tatyana; Shilling, Paul D; Shimoda, Kazutaka; Simhandl, Christian; Slaney, Claire M; Smoller, Jordan W; Squassina, Alessio; Stamm, Thomas; Stopkova, Pavla; Tighe, Sarah K; Tortorella, Alfonso; Turecki, Gustavo; Volkert, Julia; Witt, Stephanie; Wright, Adam; Young, L Trevor; Zandi, Peter P; Potash, James B; DePaulo, J Raymond; Bauer, Michael; Reininghaus, Eva Z; Novák, Tomas; Aubry, Jean-Michel; Maj, Mario; Baune, Bernhard T; Mitchell, Philip B; Vieta, Eduard; Frye, Mark A; Rybakowski, Janusz K; Kuo, Po-Hsiu; Kato, Tadafumi; Grigoroiu-Serbanescu, Maria; Reif, Andreas; Del Zompo, Maria; Bellivier, Frank; Schalling, Martin; Wray, Naomi R; Kelsoe, John R; Alda, Martin; Rietschel, Marcella; McMahon, Francis J; Schulze, Thomas G

    2016-03-12

    Lithium is a first-line treatment in bipolar disorder, but individual response is variable. Previous studies have suggested that lithium response is a heritable trait. However, no genetic markers of treatment response have been reproducibly identified. Here, we report the results of a genome-wide association study of lithium response in 2563 patients collected by 22 participating sites from the International Consortium on Lithium Genetics (ConLiGen). Data from common single nucleotide polymorphisms (SNPs) were tested for association with categorical and continuous ratings of lithium response. Lithium response was measured using a well established scale (Alda scale). Genotyped SNPs were used to generate data at more than 6 million sites, using standard genomic imputation methods. Traits were regressed against genotype dosage. Results were combined across two batches by meta-analysis. A single locus of four linked SNPs on chromosome 21 met genome-wide significance criteria for association with lithium response (rs79663003, p=1·37 × 10(-8); rs78015114, p=1·31 × 10(-8); rs74795342, p=3·31 × 10(-9); and rs75222709, p=3·50 × 10(-9)). In an independent, prospective study of 73 patients treated with lithium monotherapy for a period of up to 2 years, carriers of the response-associated alleles had a significantly lower rate of relapse than carriers of the alternate alleles (p=0·03268, hazard ratio 3·8, 95% CI 1·1-13·0). The response-associated region contains two genes for long, non-coding RNAs (lncRNAs), AL157359.3 and AL157359.4. LncRNAs are increasingly appreciated as important regulators of gene expression, particularly in the CNS. Confirmed biomarkers of lithium response would constitute an important step forward in the clinical management of bipolar disorder. Further studies are needed to establish the biological context and potential clinical utility of these findings. Deutsche Forschungsgemeinschaft, National Institute of Mental Health

  14. Genetic association studies of obesity in Africa: a systematic review.

    Science.gov (United States)

    Yako, Y Y; Echouffo-Tcheugui, J B; Balti, E V; Matsha, T E; Sobngwi, E; Erasmus, R T; Kengne, A P

    2015-03-01

    Obesity is increasing in Africa, but the underlying genetic background largely remains unknown. We assessed existing evidence on genetic determinants of obesity among populations within Africa. MEDLINE and EMBASE were searched and the bibliographies of retrieved articles were examined. Included studies had to report on the association of a genetic marker with obesity indices and the presence/occurrence of obesity/obesity trait. Data were extracted on study design and characteristics, genetic determinants and effect estimates of associations with obesity indices. According to this data, over 300 polymorphisms in 42 genes have been studied in various population groups within Africa mostly through the candidate gene approach. Polymorphisms in genes such as ACE, ADIPOQ, ADRB2, AGRP, AR, CAPN10, CD36, C7orf31, DRD4, FTO, MC3R, MC4R, SGIP1 and LEP were found to be associated with various measures of obesity. Of the 36 polymorphisms previously validated by genome-wide association studies (GWAS) elsewhere, only FTO and MC4R polymorphisms showed significant associations with obesity in black South Africans, Nigerians and Ghanaians. However, these data are insufficient to establish the true nature of genetic susceptibility to obesity in populations within Africa. There has been recent progress in describing the genetic architecture of obesity among populations within Africa. This effort needs to be sustained via GWAS studies. © 2015 World Obesity.

  15. Genome-Wide Association Studies of the Human Gut Microbiota.

    Directory of Open Access Journals (Sweden)

    Emily R Davenport

    Full Text Available The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both. These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%. For example, we identified an association between a taxon known to affect obesity (genus Akkermansia and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10-7. Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut.

  16. Genome-Wide Association Studies of the Human Gut Microbiota

    Science.gov (United States)

    Davenport, Emily R.; Cusanovich, Darren A.; Michelini, Katelyn; Barreiro, Luis B.; Ober, Carole; Gilad, Yoav

    2015-01-01

    The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both). These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%). For example, we identified an association between a taxon known to affect obesity (genus Akkermansia) and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL) mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10−7). Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut. PMID:26528553

  17. Studies of metabolic phenotypic correlates of 15 obesity associated gene variants.

    Directory of Open Access Journals (Sweden)

    Camilla Helene Sandholt

    Full Text Available Genome-wide association studies have identified novel BMI/obesity associated susceptibility loci. The purpose of this study is to determine associations with overweight, obesity, morbid obesity and/or general adiposity in a Danish population. Moreover, we want to investigate if these loci associate with type 2 diabetes and to elucidate potential underlying metabolic mechanisms.15 gene variants in 14 loci including TMEM18 (rs7561317, SH2B1 (rs7498665, KCTD15 (rs29941, NEGR1 (rs2568958, ETV5 (rs7647305, BDNF (rs4923461, rs925946, SEC16B (rs10913469, FAIM2 (rs7138803, GNPDA2 (rs10938397, MTCH2 (rs10838738, BAT2 (rs2260000, NPC1 (rs1805081, MAF (rs1424233, and PTER (rs10508503 were genotyped in 18,014 middle-aged Danes.Five of the 15 gene variants associated with overweight, obesity and/or morbid obesity. Per allele ORs ranged from 1.15-1.20 for overweight, 1.10-1.25 for obesity, and 1.41-1.46 for morbid obesity. Five of the 15 variants moreover associated with increased measures of adiposity. BDNF rs4923461 displayed a borderline BMI-dependent protective effect on type 2 diabetes (0.87 (0.78-0.96, p = 0.008, whereas SH2B1 rs7498665 associated with nominally BMI-independent increased risk of type 2 diabetes (1.16 (1.07-1.27, p = 7.8×10(-4.Associations with overweight and/or obesity and measures of obesity were confirmed for seven out of the 15 gene variants. The obesity risk allele of BDNF rs4923461 protected against type 2 diabetes, which could suggest neuronal and peripheral distinctive ways of actions for the protein. SH2B1 rs7498665 associated with type 2 diabetes independently of BMI.

  18. Incidental Risk of Type 2 Diabetes Mellitus among Patients with Confirmed and Unconfirmed Prediabetes.

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    Kimberly D Brunisholz

    Full Text Available To determine the risk of type 2 diabetes (T2DM diagnosis among patients with confirmed and unconfirmed prediabetes (preDM relative to an at-risk group receiving care from primary care physicians over a 5-year period.Utilizing data from the Intermountain Healthcare (IH Enterprise Data Warehouse (EDW from 2006-2013, we performed a prospective analysis using discrete survival analysis to estimate the time to diagnosis of T2DM among groups.Adult patients who had at least one outpatient visit with a primary care physician during 2006-2008 at an IH clinic and subsequent visits through 2013. Patients were included for the study if they were (a at-risk for diabetes (BMI ≥ 25 kg/m2 and one additional risk factor: high risk ethnicity, first degree relative with diabetes, elevated triglycerides or blood pressure, low HDL, diagnosis of gestational diabetes or polycystic ovarian syndrome, or birth of a baby weighing >9 lbs; or (b confirmed preDM (HbA1c ≥ 5.7-6.49% or fasting blood glucose 100-125 mg/dL; or (c unconfirmed preDM (documented fasting lipid panel and glucose 100-125 mg/dL on the same day.Of the 33,838 patients who were eligible for study, 57.0% were considered at-risk, 38.4% had unconfirmed preDM, and 4.6% had confirmed preDM. Those with unconfirmed and confirmed preDM tended to be Caucasian and a greater proportion were obese compared to those at-risk for disease. Patients with unconfirmed and confirmed preDM tended to have more prevalent high blood pressure and depression as compared to the at-risk group. Based on the discrete survival analyses, patients with unconfirmed preDM and confirmed preDM were more likely to develop T2DM when compared to at-risk patients.Unconfirmed and confirmed preDM are strongly associated with the development of T2DM as compared to patients with only risk factors for disease.

  19. The first confirmed case of Diphyllobothrium latum in Brazil

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    FLN Santos

    2005-10-01

    Full Text Available Diphyllobothriasis is an infection of the small intestine by the broad tapeworm Diphyllobothrium sp. The associated symptomatology is nonspecific, but megaloblastic anemia is a well-described complication. Although the infection is common in temperate regions, descriptions in South America have so far been limited to Chile, Peru, and a few cases in Argentina. This paper presents the first confirmed Brazilian case of diphyllobothriasis. A 29-years-old woman living in Salvador (state of Bahia apparently acquired the infection from eating sushi. The diagnosis was based on fecal examination that revealed a large quantity of operculated eggs. A single dose of praziquantel (600 mg was sufficient to cure the infection.

  20. Genome-wide association study of serum minerals levels in children of different ethnic background.

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    Xiao Chang

    Full Text Available Calcium, magnesium, potassium, sodium, chloride and phosphorus are the major dietary minerals involved in various biological functions and are commonly measured in the blood serum. Sufficient mineral intake is especially important for children due to their rapid growth. Currently, the genetic mechanisms influencing serum mineral levels are poorly understood, especially for children. We carried out a genome-wide association (GWA study on 5,602 European-American children and 4,706 African-American children who had mineral measures available in their electronic medical records (EMR. While no locus met the criteria for genome-wide significant association, our results demonstrated a nominal association of total serum calcium levels with a missense variant in the calcium -sensing receptor (CASR gene on 3q13 (rs1801725, P = 1.96 × 10(-3 in the African-American pediatric cohort, a locus previously reported in Caucasians. We also confirmed the association result in our pediatric European-American cohort (P = 1.38 × 10(-4. We further replicated two other loci associated with serum calcium levels in the European-American cohort (rs780094, GCKR, P = 4.26 × 10(-3; rs10491003, GATA3, P = 0.02. In addition, we replicated a previously reported locus on 1q21, demonstrating association of serum magnesium levels with MUC1 (rs4072037, P = 2.04 × 10(-6. Moreover, in an extended gene-based association analysis we uncovered evidence for association of calcium levels with the previously reported gene locus DGKD in both European-American children and African-American children. Taken together, our results support a role for CASR and DGKD mediated calcium regulation in both African-American and European-American children, and corroborate the association of calcium levels with GCKR and GATA3, and the association of magnesium levels with MUC1 in the European-American children.

  1. A genome wide association study of Plasmodium falciparum susceptibility to 22 antimalarial drugs in Kenya.

    Science.gov (United States)

    Wendler, Jason P; Okombo, John; Amato, Roberto; Miotto, Olivo; Kiara, Steven M; Mwai, Leah; Pole, Lewa; O'Brien, John; Manske, Magnus; Alcock, Dan; Drury, Eleanor; Sanders, Mandy; Oyola, Samuel O; Malangone, Cinzia; Jyothi, Dushyanth; Miles, Alistair; Rockett, Kirk A; MacInnis, Bronwyn L; Marsh, Kevin; Bejon, Philip; Nzila, Alexis; Kwiatkowski, Dominic P

    2014-01-01

    Drug resistance remains a chief concern for malaria control. In order to determine the genetic markers of drug resistant parasites, we tested the genome-wide associations (GWA) of sequence-based genotypes from 35 Kenyan P. falciparum parasites with the activities of 22 antimalarial drugs. Parasites isolated from children with acute febrile malaria were adapted to culture, and sensitivity was determined by in vitro growth in the presence of anti-malarial drugs. Parasites were genotyped using whole genome sequencing techniques. Associations between 6250 single nucleotide polymorphisms (SNPs) and resistance to individual anti-malarial agents were determined, with false discovery rate adjustment for multiple hypothesis testing. We identified expected associations in the pfcrt region with chloroquine (CQ) activity, and other novel loci associated with amodiaquine, quinazoline, and quinine activities. Signals for CQ and primaquine (PQ) overlap in and around pfcrt, and interestingly the phenotypes are inversely related for these two drugs. We catalog the variation in dhfr, dhps, mdr1, nhe, and crt, including novel SNPs, and confirm the presence of a dhfr-164L quadruple mutant in coastal Kenya. Mutations implicated in sulfadoxine-pyrimethamine resistance are at or near fixation in this sample set. Sequence-based GWA studies are powerful tools for phenotypic association tests. Using this approach on falciparum parasites from coastal Kenya we identified known and previously unreported genes associated with phenotypic resistance to anti-malarial drugs, and observe in high-resolution haplotype visualizations a possible signature of an inverse selective relationship between CQ and PQ.

  2. Prospective examination of anxiety and depression before and during confirmed and pseudo-exacerbations in patients with Multiple Sclerosis

    Science.gov (United States)

    Burns, Michelle Nicole; Nawacki, Ewa; Siddique, Juned; Pelletier, Daniel; Mohr, David C.

    2012-01-01

    Objective Although some studies have suggested a relationship between MS exacerbations and psychological distress, methodological weaknesses limit their conclusions. This study was aimed to determine whether pseudo- and confirmed MS exacerbations are preceded by or concurrent with increased anxiety or depressive symptoms. Methods This was a secondary analysis of 121 patients with MS who were followed for 48 weeks during a randomized controlled trial. Participants completed monthly self-reports on depressive and anxiety symptoms. Patient-reported exacerbations were assessed through a phone-administered symptom checklist and neurological exam. Results Both pseudo-exacerbations and confirmed exacerbations were associated with concurrent somatic depressive, β = .16 and β = .33, respectively, ps anxiety symptoms, β = .24 and β = .20, ps anxiety symptoms relative to baseline predicted subsequent onset of pseudo-exacerbations, odds ratio [OR] = 1.54, p = .02, while increased somatic depressive symptoms predicted confirmed exacerbations, OR = 1.59, p = .01. Conclusion Patients with MS experiencing pseudo- or confirmed exacerbations should be assessed and monitored for depressive and anxiety symptoms, and confirmed exacerbations are particularly concerning in patients with a history of depression. The psychological or psychiatric antecedents of MS exacerbations generate new hypotheses on etiologies of confirmed and pseudo-exacerbations. Trial Registration ClinicalTrials.gov (NCT00147446). PMID:23197840

  3. Meta-analysis of two genome-wide association studies of bovine paratuberculosis.

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    Giulietta Minozzi

    Full Text Available BACKGROUND: Bovine paratuberculosis (ParaTB also known as Johne's disease, is a contagious fatal disease resulting from infection by Mycobacterium avium subspecies paratuberculosis (MAP. Previous studies have identified loci associated with ParaTB using different measurements to define cases and controls. The objective of this study was to combine the data from two recent studies to identify genetic loci associated with MAP tissue infection and humoral immune response, defined by MAP ELISA-positive cattle, by comparing cases and control animals for one or both measures of infection. METHODOLOGY/PRINCIPAL FINDINGS: The two populations used for the association analyses were a cohort of MAP tissue infected animals and control Holstein cows from the USA and the second cohort composed of ELISA-positive and ELISA-negative Holstein cows from Italy. Altogether 1190 cattle were genotyped with the Illumina BovineSNP50 BeadChip. SNP markers were removed if the minor allele frequency 5%. Animals were removed with >5% genotyping failure. Whole genome association analyses were conducted with the GRAMMAR-CG method using two different definitions of control populations. CONCLUSION/SIGNIFICANCE: The analyses identified several loci (P<5 e-05 associated with ParaTB, defined by positive ELISA and presence of bacteria in tissue compared to ELISA and tissue negative animals, on chromosomes 1, 12 and 15 and one unassigned SNP. These results confirmed associations on chromosome 12 and the unassigned SNP with ParaTB which had been found in the Italian population alone. Furthermore, several additional genomic regions were found associated with ParaTB when ELISA and tissue positive animals were compared with tissue negative samples. These loci were on chromosomes 1, 6, 7, 13, 16, 21,23 and 25 (P<5 e-05. The results clearly indicate the importance of the phenotype definition when seeking to identify markers associated with different disease responses.

  4. Subthalamic nucleus stimulation affects limbic and associative circuits: a PET study

    Energy Technology Data Exchange (ETDEWEB)

    Le Jeune, Florence [Centre Eugene Marquis, Service de Medecine Nucleaire, Rennes (France); Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); Centre Eugene Marquis, Service Medecine Nucleaire, Rennes (France); Peron, Julie [Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); Hopital Pontchaillou, CHU de Rennes, Clinique Neurologique, Rennes (France); University of Geneva, Neuroscience of Emotion and Affective Dynamics, Department of Psychology and Swiss Center for Affective Sciences, Geneva (Switzerland); Grandjean, Didier [University of Geneva, Neuroscience of Emotion and Affective Dynamics, Department of Psychology and Swiss Center for Affective Sciences, Geneva (Switzerland); Drapier, Sophie; Verin, Marc [Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); Hopital Pontchaillou, CHU de Rennes, Clinique Neurologique, Rennes (France); Haegelen, Claire [Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); Hopital Pontchaillou, CHU de Rennes, Service de Neurochirurgie, Rennes (France); Garin, Etienne [Centre Eugene Marquis, Service de Medecine Nucleaire, Rennes (France); Millet, Bruno [Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); S.H.U. Psychiatrie Adulte, CH Guillaume Regnier, Rennes (France)

    2010-08-15

    Although high-frequency deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in advanced Parkinson's disease (PD), clinical studies have reported cognitive, motivational and emotional changes. These results suggest that the STN forms part of a broadly distributed neural network encompassing the associative and limbic circuits. We sought to pinpoint the cortical and subcortical brain areas modulated by STN DBS, in order to assess the STN's functional role and explain neuropsychological modifications following STN DBS in PD. We studied resting state glucose metabolism in 20 PD patients before and after STN DBS and 13 age-matched healthy controls using {sup 18}F-FDG PET. We used statistical analysis (SPM2) first to compare pre-stimulation metabolism in PD patients with metabolism in healthy controls, then to study metabolic modifications in PD patients following STN DBS. The first analysis revealed no pre-stimulation metabolic abnormalities in associative or limbic circuitry. After STN DBS, metabolic modifications were found in several regions known for their involvement in the limbic and associative circuits. These metabolic results confirm the STN's central role in associative and limbic basal ganglia circuits. They will provide information for working hypotheses for future studies investigating neuropsychological changes and metabolic modifications related to STN DBS, with a view to improving our knowledge of this structure's functional role. (orig.)

  5. Genome-Wide Population-Based Association Study of Extremely Overweight Young Adults - The GOYA Study

    DEFF Research Database (Denmark)

    Paternoster, L.; Evans, D. M.; Nohr, E. A.

    2011-01-01

    Background: Thirty-two common variants associated with body mass index (BMI) have been identified in genome-wide association studies, explaining,similar to 1.45% of BMI variation in general population cohorts. We performed a genome-wide association study in a sample of young adults enriched...

  6. Evolutionary triangulation: informing genetic association studies with evolutionary evidence.

    Science.gov (United States)

    Huang, Minjun; Graham, Britney E; Zhang, Ge; Harder, Reed; Kodaman, Nuri; Moore, Jason H; Muglia, Louis; Williams, Scott M

    2016-01-01

    Genetic studies of human diseases have identified many variants associated with pathogenesis and severity. However, most studies have used only statistical association to assess putative relationships to disease, and ignored other factors for evaluation. For example, evolution is a factor that has shaped disease risk, changing allele frequencies as human populations migrated into and inhabited new environments. Since many common variants differ among populations in frequency, as does disease prevalence, we hypothesized that patterns of disease and population structure, taken together, will inform association studies. Thus, the population distributions of allelic risk variants should reflect the distributions of their associated diseases. Evolutionary Triangulation (ET) exploits this evolutionary differentiation by comparing population structure among three populations with variable patterns of disease prevalence. By selecting populations based on patterns where two have similar rates of disease that differ substantially from a third, we performed a proof of principle analysis for this method. We examined three disease phenotypes, lactase persistence, melanoma, and Type 2 diabetes mellitus. We show that for lactase persistence, a phenotype with a simple genetic architecture, ET identifies the key gene, lactase. For melanoma, ET identifies several genes associated with this disease and/or phenotypes related to it, such as skin color genes. ET was less obviously successful for Type 2 diabetes mellitus, perhaps because of the small effect sizes in known risk loci and recent environmental changes that have altered disease risk. Alternatively, ET may have revealed new genes involved in conferring disease risk for diabetes that did not meet nominal GWAS significance thresholds. We also compared ET to another method used to filter for phenotype associated genes, population branch statistic (PBS), and show that ET performs better in identifying genes known to associate with

  7. Prevalence of peripheral artery disease and its associated risk factors in Spain: The ESTIME Study.

    Science.gov (United States)

    Blanes, J I; Cairols, M A; Marrugat, J

    2009-02-01

    Several studies have demonstrated that patients with peripheral arterial disease (PAD), are at an increased risk of morbidity and mortality compared with those without PAD. However, few population-based studies have addressed the prevalence of PAD and intermittent claudication (IC). We assessed the prevalence of and the factors associated with PAD and IC in the Spanish population. A cross sectional study with 1324 participants aged 55 to 84 years randomly selected from the census was conducted in 12 Spanish regions. The presence of PAD and IC was determined by an ankle-brachial index (ABI) ESTIME study confirms the high prevalence of asymptomatic PAD, and its relation with typical cardiovascular risk factors. ABI provides early diagnosis before claudication symptoms in a high proportion of patients. ABI could contribute to developing early prevention programmes.

  8. Recommendations for using standardised phenotypes in genetic association studies

    Directory of Open Access Journals (Sweden)

    Naylor Melissa G

    2009-07-01

    Full Text Available Abstract Genetic association studies of complex traits often rely on standardised quantitative phenotypes, such as percentage of predicted forced expiratory volume and body mass index to measure an underlying trait of interest (eg lung function, obesity. These phenotypes are appealing because they provide an easy mechanism for comparing subjects, although such standardisations may not be the best way to control for confounders and other covariates. We recommend adjusting raw or standardised phenotypes within the study population via regression. We illustrate through simulation that optimal power in both population- and family-based association tests is attained by using the residuals from within-study adjustment as the complex trait phenotype. An application of family-based association analysis of forced expiratory volume in one second, and obesity in the Childhood Asthma Management Program data, illustrates that power is maintained or increased when adjusted phenotype residuals are used instead of typical standardised quantitative phenotypes.

  9. A genome-wide association study identifies novel single nucleotide polymorphisms associated with dermal shank pigmentation in chickens.

    Science.gov (United States)

    Li, Guangqi; Li, Dongfeng; Yang, Ning; Qu, Lujiang; Hou, Zhuocheng; Zheng, Jiangxia; Xu, Guiyun; Chen, Sirui

    2014-12-01

    Shank color of domestic chickens varies from black to blue, green, yellow, or white, which is controlled by the combination of melanin and xanthophylls in dermis and epidermis. Dermal shank pigmentation of chickens is determined by sex-linked inhibitor of dermal melanin (Id), which is located on the distal end of the long arm of Z chromosome, through controlling dermal melanin pigmentation. Although previous studies have focused on the identification of Id and the linear relationship with barring and recessive white skin, no causal mutations have yet been identified in relation to the mutant dermal pigment inhibiting allele at the Id locus. In this study, we first used the 600K Affymetrix Axiom HD genotyping array, which includes ~580,961 SNP of which 26,642 SNP were on the Z chromosome to perform a genome-wide association study on pure lines of 19 Tibetan hens with dermal pigmentation shank and 21 Tibetan hens with yellow shank to refine the Id location. Association analysis was conducted by the PLINK software using the standard chi-squared test, and then Bonferroni correction was used to adjust multiple testing. The genome-wide study revealed that 3 SNP located at 78.5 to 79.2 Mb on the Z chromosome in the current assembly of chicken genome (galGal4) were significantly associated with dermal shank pigmentation of chickens, but none of them were located in known genes. The interval we refined was partly converged with previous results, suggesting that the Id gene is in or near our refined genome region. However, the genomic context of this region was complex. There were only 15 SNP markers developed by the genotyping array within the interval region, in which only 1 SNP marker passed quality control. Additionally, there were about 5.8-Mb gaps on both sides of the refined interval. The follow-up replication studies may be needed to further confirm the functional significance for these newly identified SNP. ©2014 Poultry Science Association Inc.

  10. A Genome-Wide Association Study Identifies Genetic Variants Associated with Mathematics Ability.

    Science.gov (United States)

    Chen, Huan; Gu, Xiao-Hong; Zhou, Yuxi; Ge, Zeng; Wang, Bin; Siok, Wai Ting; Wang, Guoqing; Huen, Michael; Jiang, Yuyang; Tan, Li-Hai; Sun, Yimin

    2017-02-03

    Mathematics ability is a complex cognitive trait with polygenic heritability. Genome-wide association study (GWAS) has been an effective approach to investigate genetic components underlying mathematic ability. Although previous studies reported several candidate genetic variants, none of them exceeded genome-wide significant threshold in general populations. Herein, we performed GWAS in Chinese elementary school students to identify potential genetic variants associated with mathematics ability. The discovery stage included 494 and 504 individuals from two independent cohorts respectively. The replication stage included another cohort of 599 individuals. In total, 28 of 81 candidate SNPs that met validation criteria were further replicated. Combined meta-analysis of three cohorts identified four SNPs (rs1012694, rs11743006, rs17778739 and rs17777541) of SPOCK1 gene showing association with mathematics ability (minimum p value 5.67 × 10(-10), maximum β -2.43). The SPOCK1 gene is located on chromosome 5q31.2 and encodes a highly conserved glycoprotein testican-1 which was associated with tumor progression and prognosis as well as neurogenesis. This is the first study to report genome-wide significant association of individual SNPs with mathematics ability in general populations. Our preliminary results further supported the role of SPOCK1 during neurodevelopment. The genetic complexities underlying mathematics ability might contribute to explain the basis of human cognition and intelligence at genetic level.

  11. Power Analysis for Genetic Association Test (PAGEANT) provides insights to challenges for rare variant association studies.

    Science.gov (United States)

    Derkach, Andriy; Zhang, Haoyu; Chatterjee, Nilanjan

    2017-11-28

    Genome-wide association studies are now shifting focus from analysis of common to rare variants. As power for association testing for individual rare variants may often be low, various aggregate level association tests have been proposed to detect genetic loci. Typically, power calculations for such tests require specification of large number of parameters, including effect sizes and allele frequencies of individual variants, making them difficult to use in practice. We propose to approximate power to varying degree of accuracy using a smaller number of key parameters, including the total genetic variance explained by multiple variants within a locus. We perform extensive simulation studies to assess the accuracy of the proposed approximations in realistic settings. Using these simplified power calculations, we develop an analytic framework to obtain bounds on genetic architecture of an underlying trait given results from a genome-wide association studies with rare variants. Finally, we provide insights into the required quality of annotation/functional information for identification of likely causal variants to make meaningful improvement in power. A shiny application that allows a variety of Power Analysis of GEnetic AssociatioN Tests (PAGEANT), in R is made publicly available at https://andrewhaoyu.shinyapps.io/PAGEANT/. nilanjan@jhu.edu. Supplementary data are available at Bioinformatics online.

  12. Psychiatric disorders and obesity: A review of association studies

    Directory of Open Access Journals (Sweden)

    T M Rajan

    2017-01-01

    Full Text Available Background: Inconsistent evidence exists regarding the strength, direction, and moderators in the relationship between obesity and psychiatric disorders. Aim: This study aims to summarize the evidence on the association between psychiatric illness and obesity with particular attention to the strength and direction of association and also the possible moderators in each postulated link. Materials and Methods: Systematic electronic searches of MEDLINE through PubMed, ScienceDirect, PsycINFO, and Google Scholar were carried out from inception till October 2016. Generated abstracts were screened for eligibility to be included in the review. Study designs that evaluated the strength of relationship between obesity and psychiatric disorders were included in the study. Quality assessment of included studies was done using the Newcastle–Ottawa checklist tool. Results: From a total of 2424 search results, 21 eligible articles were identified and reviewed. These included studies on obesity and depression (n = 15, obesity and anxiety (four and one each on obesity and personality disorders, eating disorder (ED, attention deficit hyperactivity disorder, and alcohol use. Maximal evidence existed for the association between depression and obesity with longitudinal studies demonstrating a bidirectional link between the two conditions. The odds ratios (ORs were similar for developing depression in obesity (OR: 1.21–5.8 and vice versa (OR: 1.18–3.76 with a stronger association observed in women. For anxiety disorders, evidence was mostly cross-sectional, and associations were of modest magnitude (OR: 1.27–1.40. Among other disorders, obesity, and EDs appear to have a close link (OR: 4.5. Alcohol use appears to be a risk factor for obesity and not vice versa but only among women (OR: 3.84. Conclusion: Obesity and depression have a significant and bidirectional association. Evidence is modest for anxiety disorders and inadequate for other psychiatric

  13. Psychiatric disorders and obesity: A review of association studies

    Science.gov (United States)

    Rajan, TM; Menon, V

    2017-01-01

    Background: Inconsistent evidence exists regarding the strength, direction, and moderators in the relationship between obesity and psychiatric disorders. Aim: This study aims to summarize the evidence on the association between psychiatric illness and obesity with particular attention to the strength and direction of association and also the possible moderators in each postulated link. Materials and Methods: Systematic electronic searches of MEDLINE through PubMed, ScienceDirect, PsycINFO, and Google Scholar were carried out from inception till October 2016. Generated abstracts were screened for eligibility to be included in the review. Study designs that evaluated the strength of relationship between obesity and psychiatric disorders were included in the study. Quality assessment of included studies was done using the Newcastle–Ottawa checklist tool. Results: From a total of 2424 search results, 21 eligible articles were identified and reviewed. These included studies on obesity and depression (n = 15), obesity and anxiety (four) and one each on obesity and personality disorders, eating disorder (ED), attention deficit hyperactivity disorder, and alcohol use. Maximal evidence existed for the association between depression and obesity with longitudinal studies demonstrating a bidirectional link between the two conditions. The odds ratios (ORs) were similar for developing depression in obesity (OR: 1.21–5.8) and vice versa (OR: 1.18–3.76) with a stronger association observed in women. For anxiety disorders, evidence was mostly cross-sectional, and associations were of modest magnitude (OR: 1.27–1.40). Among other disorders, obesity, and EDs appear to have a close link (OR: 4.5). Alcohol use appears to be a risk factor for obesity and not vice versa but only among women (OR: 3.84). Conclusion: Obesity and depression have a significant and bidirectional association. Evidence is modest for anxiety disorders and inadequate for other psychiatric conditions

  14. Genetic association studies in osteoarthritis: is it fairytale?

    Science.gov (United States)

    Warner, Sophie C; Valdes, Ana M

    2017-01-01

    Osteoarthritis is a common complex disorder with a strong genetic component. Other identified risk factors such as increasing age and overweight do not fully explain the risk of osteoarthritis. Here, we highlight the main findings from genetic association studies on osteoarthritis to date. Currently, genetic association studies have identified 21 independent susceptibility loci for osteoarthritis. Studies have focused on hip, knee and hand osteoarthritis, as well as posttotal joint replacement and minimum joint space width, a proxy for cartilage thickness. Four distinct loci have recently been identified in a genome-wide association scan on minimum joint space width. The role of mitochondrial DNA variants has been the focus of a recent meta-analysis. Findings have previously been mixed, however, this study suggests a plausible involvement of mitochondrial DNA in the progression of radiographic knee osteoarthritis. Identifying genetic locations of interest provides a framework upon which to base future studies, for example replication analysis and functional work. Genetic association studies have shaped and will continue to shape research in this field. Improving the understanding of osteoarthritis could improve the diagnosis and treatment of the disease and improve quality of life for many individuals.

  15. Small, hard macular drusen and peripheral drusen: associations with AMD genotypes in the Inter99 Eye Study

    DEFF Research Database (Denmark)

    Munch, Inger Christine; Ek, Jakob; Kessel, Line

    2010-01-01

    PURPOSE: To study associations of small, hard macular drusen and peripheral drusen with genotypes associated with age-related macular degeneration (AMD). METHODS: Digital grayscale fundus photographs recorded in red-free illumination were graded for the presence of drusen in 1107 subjects aged 30...... to 66 years. Participants were genotyped for AMD-related polymorphisms in complement factor H (CFH), in LOC387715, and in complement factor B (CFB). RESULTS: The prevalence of 20 or more small, hard macular drusen per eye was 14%, with no association to the investigated polymorphisms. Peripheral drusen...... macular drusen (OR, 1.7; 95% CI, 1.1-2.6) and with peripheral drusen (OR, 2.5; 95% CI,1.2-5.4) CONCLUSIONS: In this study, the presence of 20 or more small, hard macular drusen per eye was not associated with known AMD-related polymorphisms, whereas the study confirmed an association of peripheral drusen...

  16. Epigenome-wide association study of chronic obstructive pulmonary disease and lung function in Koreans.

    Science.gov (United States)

    Lee, Mi Kyeong; Hong, Yoonki; Kim, Sun-Young; Kim, Woo Jin; London, Stephanie J

    2017-07-01

    To identify differentially methylated probes (DMPs) and regions (DMRs) in relation to chronic obstructive pulmonary disease (COPD) and lung function traits. We performed an epigenome-wide association study of COPD and spirometric parameters, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC, in blood DNA using the Infinium HumanMethylation450 (n = 100, a Korean COPD cohort). We found one significant DMP (cg03559389, DIP2C) and 104 significant DMRs after multiple-testing correction. Of these, 34 DMRs mapped to genes differential expressed with respect to the same trait. Five of the genes were associated with more than two traits: CTU2, USP36, ZNF516, KLK10 and CPT1B. We identified novel differential methylation loci related to COPD and lung function in blood DNA in Koreans and confirmed previous findings in non-Asians. Epigenetic modification could contribute to the etiology of these phenotypes.

  17. Genome-wide association study identifies new prostate cancer susceptibility loci

    DEFF Research Database (Denmark)

    Schumacher, Fredrick R.; Berndt, Sonja I.; Siddiq, Afshan

    2011-01-01

    published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P= 4.3 x 10–8). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P= 8.6 x 10–9). The estimated per-allele odds ratios......Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have...

  18. Association between stimulus-evoked somatosensory inhibition and movement-related sensorimotor oscillation: A magnetoencephalographic study.

    Science.gov (United States)

    Hsiao, Fu-Jung; Chen, Wei-Ta; Lin, Yung-Yang

    2017-11-08

    The interaction between the somatosensory and motor cortices is understood; however, their functional relationship remains elusive. To elucidate the association between somatosensory and sensorimotor functions, this study investigated the correlation between somatosensory activities in response to paired-pulse stimulation and sensorimotor oscillations during self-paced finger movement in 18 healthy male subjects by using a magnetoencephalographic recording. The main finding was that stimulus-evoked somatosensory gating activities were significantly correlated with movement-related sensorimotor oscillatory responses. Specifically, the gating ratios of somatosensory N20m were related to the power changes of sensorimotor beta event-related desynchronization (ERD) (p=0.003) and event-related synchronization (ERS) (p=0.05). In conclusion, we confirmed that the inhibition of stimulus-evoked somatosensory responses is associated with the oscillatory characteristics of movement-related sensorimotor activities. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Association study of ankylosing spondylitis and polymorphisms in ERAP1 gene in Zhejiang Han Chinese population.

    Science.gov (United States)

    Liu, Yangbo; Li, Liangda; Shi, Shanfen; Chen, Xin; Gao, Jianqing; Zhu, Minyu; Yuan, Jiandong

    2016-02-01

    The susceptibility loci of ERAP1 polymorphisms have been found to be strongly associated with ankylosing spondylitis (AS). The researches in multiple ethnic cohorts suggested that the population attributable risk in ERAP1 polymorphisms is at a high significance level. This study was undertaken to estimate the prevalence and incidence of subsets of AS and investigate the specific variants of ERAP1 polymorphisms in AS susceptibility, in the Han ethnic Chinese population in Zhejiang Province. AS patients were selected, diagnosed, and confirmed by a qualified rheumatologist. The basal clinical and demographic characteristics were compared with all subjects. Genotypes for eight selected single nucleotide polymorphisms (SNPs) in ERAP1 gene (rs27038, rs27037, rs27434, rs27980, rs7711564, rs30187, rs10050860, and rs17482078) were determined by using the Sequenom MassARRAY iPLEX platform in Zhejiang Han Chinese population. Association analyses were performed on the whole genotyped data set in 707 unrelated ankylosing spondylitis cases and 837 ethnically matched controls. We observed the strongest association between AS and HLA-B27, which confers over 90 % of ankylosing spondylitis cases. Moreover, we found three loci of ERAP1 polymorphisms were at a high significance level (rs27037 P = 0.00451; rs27434 P = 0.00012; rs27980 P = 0.00682) with AS in Zhejiang population. We also confirmed polymorphism locus of ERAP1 previously reported association with AS (rs27434; P = 5.3 × 10(-12)). Our results indicated a difference in the mechanism of susceptibility loci in subsets of Zhejiang Han Chinese population and provided further evidence that rs27434 is the key polymorphism associated with AS in ERAP1 gene.

  20. A comprehensive genetic association study of Alzheimer disease in African Americans.

    Science.gov (United States)

    Logue, Mark W; Schu, Matthew; Vardarajan, Badri N; Buros, Jacki; Green, Robert C; Go, Rodney C P; Griffith, Patrick; Obisesan, Thomas O; Shatz, Rhonna; Borenstein, Amy; Cupples, L Adrienne; Lunetta, Kathryn L; Fallin, M Daniele; Baldwin, Clinton T; Farrer, Lindsay A

    2011-12-01

    To evaluate the association of genetic variation with late-onset Alzheimer disease (AD) in African Americans, including genes implicated in recent genome-wide association studies of whites. We analyzed a genome-wide set of 2.5 million imputed markers to evaluate the genetic basis of AD in an African American population. Five hundred thirteen well-characterized African American AD cases and 496 cognitively normal African American control subjects. Data were collected from multiple sites as part of the Multi-Institutional Research on Alzheimer Genetic Epidemiology (MIRAGE) Study and the Henry Ford Health System as part of the Genetic and Environmental Risk Factors for Alzheimer Disease Among African Americans (GenerAAtions) Study. Several significant single-nucleotide polymorphisms (SNPs) were observed in the region of the apolipoprotein E gene (APOE). After adjusting for the confounding effects of APOE genotype, one of these SNPs, rs6859 in PVRL2, remained significantly associated with AD (P = .0087). Association was also observed with SNPs in CLU, PICALM, BIN1, EPHA1, MS4A, ABCA7, and CD33, although the effect direction for some SNPs and the most significant SNPs differed from findings in data sets consisting of whites. Finally, using the African American genome-wide association study data set as a discovery sample, we obtained suggestive evidence of association with SNPs for several novel candidate genes. Some genes contribute to AD pathogenesis in both white and African American cohorts, although it is unclear whether the causal variants are the same. A larger African American sample will be needed to confirm novel gene associations, which may be population specific.

  1. Associations Between Autoimmune Diseases and Attention-Deficit/Hyperactivity Disorder: A Nationwide Study.

    Science.gov (United States)

    Nielsen, Philip Rising; Benros, Michael Eriksen; Dalsgaard, Søren

    2017-03-01

    Recent studies have suggested that autoimmune diseases and immune activation play a part in the pathogenesis of different neurodevelopmental disorders. This study investigated the association between a personal history and a family history of autoimmune disease and the risk of developing attention-deficit/hyperactivity disorder (ADHD). A cohort was formed of all singletons born in Denmark from 1990 to 2007, resulting in a study population of 983,680 individuals followed from 1995 to 2012. Information on autoimmune diseases was obtained from the Danish National Hospital Register. Individuals with ADHD were identified through the Danish National Hospital Register and the Danish Psychiatric Central Register. In total, 23,645 children were diagnosed with ADHD during the study period. Autoimmune disease in the individual was associated with an increased risk of ADHD by an incidence rate ratio of 1.24 (95% CI 1.10-1.40). The primary analyses associated maternal autoimmune disease with ADHD in the offspring (incidence rate ratio 1.12, 95% CI 1.06-1.19), whereas a paternal history of autoimmune diseases was not significantly associated with ADHD in the offspring. In exploratory analyses, an increased risk of ADHD was observed for children with a family history of thyrotoxicosis, type 1 diabetes, autoimmune hepatitis, psoriasis, and ankylosing spondylitis. A personal history and a maternal history of autoimmune disease were associated with an increased risk of ADHD. The previously reported association between type 1 diabetes and ADHD was confirmed. In addition, specific parental autoimmune diseases were associated with ADHD in offspring. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  2. Optimal Trend Tests for Genetic Association Studies of Heterogeneous Diseases.

    Science.gov (United States)

    Lee, Wen-Chung

    2016-06-09

    The Cochran-Armitage trend test is a standard procedure in genetic association studies. It is a directed test with high power to detect genetic effects that follow the gene-dosage model. In this paper, the author proposes optimal trend tests for genetic association studies of heterogeneous diseases. Monte-Carlo simulations show that the power gain of the optimal trend tests over the conventional Cochran-Armitage trend test is striking when the genetic effects are heterogeneous. The easy-to-use R 3.1.2 software (R Foundation for Statistical Computing, Vienna, Austria) code is provided. The optimal trend tests are recommended for routine use.

  3. Susceptibility to Chronic Mucus Hypersecretion, a Genome Wide Association Study

    DEFF Research Database (Denmark)

    Dijkstra, A. E.; Smolonska, J.; van den Berge, M.

    2014-01-01

    of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations. Methods: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed...... of SATB1 (4.3610 29) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture. Conclusions: Our findings, that SNP rs6577641...

  4. Genome-Wide Association Study of Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Naomi Ogawa

    2010-01-01

    Full Text Available Coronary artery disease (CAD is a multifactorial disease with environmental and genetic determinants. The genetic determinants of CAD have previously been explored by the candidate gene approach. Recently, the data from the International HapMap Project and the development of dense genotyping chips have enabled us to perform genome-wide association studies (GWAS on a large number of subjects without bias towards any particular candidate genes. In 2007, three chip-based GWAS simultaneously revealed the significant association between common variants on chromosome 9p21 and CAD. This association was replicated among other ethnic groups and also in a meta-analysis. Further investigations have detected several other candidate loci associated with CAD. The chip-based GWAS approach has identified novel and unbiased genetic determinants of CAD and these insights provide the important direction to better understand the pathogenesis of CAD and to develop new and improved preventive measures and treatments for CAD.

  5. Association between urbanisation and type 2 diabetes: an ecological study.

    Science.gov (United States)

    Gassasse, Zakariah; Smith, Dianna; Finer, Sarah; Gallo, Valentina

    2017-01-01

    Previous studies have explored the effect of urbanisation on the prevalence of type 2 diabetes (T2D) at regional/national level. The aim of this study is to investigate the association between urbanisation and T2D at country level, worldwide, and to explore the role of intermediate variables (physical inactivity, sugar consumption and obesity). The potential effect modification of gross domestic product (GDP) was also assessed. Data for 207 countries were collected from accessible datasets. Direct acyclic graphs were used to describe the association between urbanisation, T2D and their intermediate variables (physical inactivity, sugar consumption and obesity). Urbanisation was measured as urban percentage (UP) and as agglomeration index (AI). Crude and multivariate linear regression analyses were conducted to explore selected associations. The interaction between urbanisation and T2D across levels of GDP per capita was investigated. The association between urbanisation and T2D diverged by exposure: AI was positively associated, while UP negatively associated with T2D prevalence. Physical inactivity and obesity were statistically significantly associated with increased prevalence of T2D. In middle-income countries (MIC) UP, AI and GDP were significantly associated with T2D prevalence, while in high-income countries (HIC), physical inactivity and obesity were the main determinant of T2D prevalence. The type of urban growth, not urbanisation per se, predicted T2D prevalence at country level. In MIC, population density and GDP were the main determinant of diabetes, while in HIC. these were physical inactivity and obesity. Globalisation is playing an important role in the rise of T2D worldwide.

  6. Gene-Centric Genomewide Association Study via Entropy

    Science.gov (United States)

    Cui, Yuehua; Kang, Guolian; Sun, Kelian; Qian, Minping; Romero, Roberto; Fu, Wenjiang

    2008-01-01

    Genes are the functional units in most organisms. Compared to genetic variants located outside genes, genic variants are more likely to affect disease risk. The development of the human HapMap project provides an unprecedented opportunity for genetic association studies at the genomewide level for elucidating disease etiology. Currently, most association studies at the single-nucleotide polymorphism (SNP) or the haplotype level rely on the linkage information between SNP markers and disease variants, with which association findings are difficult to replicate. Moreover, variants in genes might not be sufficiently covered by currently available methods. In this article, we present a gene-centric approach via entropy statistics for a genomewide association study to identify disease genes. The new entropy-based approach considers genic variants within one gene simultaneously and is developed on the basis of a joint genotype distribution among genetic variants for an association test. A grouping algorithm based on a penalized entropy measure is proposed to reduce the dimension of the test statistic. Type I error rates and power of the entropy test are evaluated through extensive simulation studies. The results indicate that the entropy test has stable power under different disease models with a reasonable sample size. Compared to single SNP-based analysis, the gene-centric approach has greater power, especially when there is more than one disease variant in a gene. As the genomewide genic SNPs become available, our entropy-based gene-centric approach would provide a robust and computationally efficient way for gene-based genomewide association study. PMID:18458106

  7. Genome-wide Association Study of Susceptibility to Particulate Matter-Associated QT Prolongation.

    Science.gov (United States)

    Gondalia, Rahul; Avery, Christy L; Napier, Melanie D; Méndez-Giráldez, Raúl; Stewart, James D; Sitlani, Colleen M; Li, Yun; Wilhelmsen, Kirk C; Duan, Qing; Roach, Jeffrey; North, Kari E; Reiner, Alexander P; Zhang, Zhu-Ming; Tinker, Lesley F; Yanosky, Jeff D; Liao, Duanping; Whitsel, Eric A

    2017-06-08

    Ambient particulate matter (PM) air pollution exposure has been associated with increases in QT interval duration (QT). However, innate susceptibility to PM-associated QT prolongation has not been characterized. To characterize genetic susceptibility to PM-associated QT prolongation in a multi-racial/ethnic, genome-wide association study (GWAS). Using repeated electrocardiograms (1986–2004), longitudinal data on PMQT-PM10 association (p=2.11×10−8). At PM10 concentrations >90th percentile, QT increased 7 ms across the CC and TT genotypes: 397 (95% confidence interval: 396, 399) to 404 (403, 404) ms. However, QT changed minimally across rs1619661 genotypes at lower PM10 concentrations. The rs1619661 variant is on chromosome 10, 132 kilobase (kb) downstream from CXCL12, which encodes a chemokine, stromal cell-derived factor 1, that is expressed in cardiomyocytes and decreases calcium influx across the L-type Ca2+ channel. The findings suggest that biologically plausible genetic factors may alter susceptibility to PM10-associated QT prolongation in populations protected by the U.S. Environmental Protection Agency’s National Ambient Air Quality Standards. Independent replication and functional characterization are necessary to validate our findings. https://doi.org/10.1289/EHP347

  8. Computational Characterization of Osteoporosis Associated SNPs and Genes Identified by Genome-Wide Association Studies.

    Directory of Open Access Journals (Sweden)

    Longjuan Qin

    Full Text Available Genome-wide association studies (GWASs have revealed many SNPs and genes associated with osteoporosis. However, influence of these SNPs and genes on the predisposition to osteoporosis is not fully understood. We aimed to identify osteoporosis GWASs-associated SNPs potentially influencing the binding affinity of transcription factors and miRNAs, and reveal enrichment signaling pathway and "hub" genes of osteoporosis GWAS-associated genes.We conducted multiple computational analyses to explore function and mechanisms of osteoporosis GWAS-associated SNPs and genes, including SNP conservation analysis and functional annotation (influence of SNPs on transcription factors and miRNA binding, gene ontology analysis, pathway analysis and protein-protein interaction analysis.Our results suggested that a number of SNPs potentially influence the binding affinity of transcription factors (NFATC2, MEF2C, SOX9, RUNX2, ESR2, FOXA1 and STAT3 and miRNAs. Osteoporosis GWASs-associated genes showed enrichment of Wnt signaling pathway, basal cell carcinoma and Hedgehog signaling pathway. Highly interconnected "hub" genes revealed by interaction network analysis are RUNX2, SP7, TNFRSF11B, LRP5, DKK1, ESR1 and SOST.Our results provided the targets for further experimental assessment and further insight on osteoporosis pathophysiology.

  9. Susceptibility to chronic mucus hypersecretion, a genome wide association study.

    Directory of Open Access Journals (Sweden)

    Akkelies E Dijkstra

    Full Text Available Chronic mucus hypersecretion (CMH is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA study of CMH in Caucasian populations.GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years. Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP.A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25×10(-6, OR = 1.17, located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1 on chromosome 3. The risk allele (G was associated with higher mRNA expression of SATB1 (4.3×10(-9 in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture.Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH.

  10. A questionnaire study of associations between potential risk factors and salmonella status in Swedish dairy herds.

    Science.gov (United States)

    Ågren, Estelle C C; Frössling, Jenny; Wahlström, Helene; Emanuelson, Ulf; Sternberg Lewerin, Susanna

    2017-08-01

    In this study associations between potential risk factors and salmonella status in Swedish dairy herds were investigated. A case-control study design was used, including existing as well as new cases. Herds were assigned a salmonella status on the basis of antibody analysis of bulk milk samples. Information on potential risk factors was collected from registry data and from farmers via a questionnaire. Univariable and multivariable logistic regression analyses were used to investigate associations between salmonella status and potential risk factors. In addition, multivariate analysis with Additive Bayesian Network (ABN) modelling was performed to improve understanding of the complex relationship between all the variables. Because of the difficulty in identifying associations between potential risk factors and infections with low prevalence and a large regional variation, exposure of potential risk factors in the high-prevalence region (Öland) were compared to exposure in other regions in Sweden. In total 483 of 996 (48%) farmers responded to the questionnaire, 69 herds had test-positive bulk milk samples. The strongest association with salmonella status was 'presence of salmonella test-positive herds salmonella status were also seen between 'feeding calves residue milk only' (OR 2.4, 95% CI 1.2-4.6), 'certified organic herds' (OR 2.5, 95% CI 1.2-4.9) and 'frequently seeing signs of rodents' (OR 0.4, 95% CI 0.13-0.97). The ABN model showed associations between Öland and four of the variables: salmonella status, presence of test-positive herds salmonella by other studies. The study confirms the importance of local transmission routes for salmonella, but does not identify specific components in this local spread. Therefore, it supports the use of a broad biosecurity approach in the prevention of salmonella. In Öland, some potential risk factors are more common than in other parts of Sweden. Theoretically these could contribute to the spread of salmonella, but this

  11. HIV is associated with airway obstruction: a matched controlled study.

    Science.gov (United States)

    Makinson, Alain; Hayot, Maurice; Eymard-Duvernay, Sabrina; Ribet, Céline; Raffi, François; Pialoux, Gilles; Zucman, David; Poizot-Martin, Isabelle; Bonnet, Fabrice; Abgrall, Sophie; Tattevin, Pierre; Cheret, Antoine; Ferry, Tristan; Mauboussin, Jean-Marc; Marchand, Lucie; Rouzaud, Claire; Reynes, Jacques; Zins, Marie; Le Moing, Vincent

    2018-01-14

    To explore whether airway obstruction is associated with HIV in a cohort of HIV-infected and uninfected smokers. People living with HIV (PLWHIV) participated in the ANRS EP48 HIV CHEST study, an early lung cancer diagnosis study with low-dose chest tomography. HIV-uninfected study participants were from the CONSTANCES cohort. Inclusion criteria were an age greater than 40 years, a smoking history of at least 20 pack-years, and for PLWHIV, a CD4 T-lymphocyte nadir less than 350/μl and last CD4 cell count more than 100 cells/μl. Two randomly selected HIV-uninfected study participants were matched by age and sex with one PLWHIV. Prebronchodilatator forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio was the primary outcome, and association of FEV1/FVC ratio less than 0.70 and FEV1 less than 80% of the theoretical value, as a proxy of chronic obstructive pulmonary disease, the secondary outcome. In total, 351 PLWHIV and 702 HIV-uninfected study participants were included. Median age was 50 years, and 17% of study participants were women. Plasma HIV RNA was less than 50 copies/ml in 89% of PLWHIV, with a median CD4 cell count of 573 cells/μl. HIV (β -2.19), age (per 10 years increase; β -2.81), tobacco use (per 5 pack-years increase; β -0.34), and hepatitis C virus serology (β-2.50) were negatively associated with FEV1/FVC. HIV [odds ratio (OR: 1.72)], age (per 10 years increase; OR 1.77), and tobacco use (per 5 pack-years increase; OR 1.11) were significantly associated with the secondary outcome. Our study found a significant association of airway obstruction with HIV status in smokers aged more than 40 years with previous immunodeficiency.

  12. Novel loci associated with usual sleep duration: The CHARGE Consortium Genome-Wide Association Study

    NARCIS (Netherlands)

    Gottlieb, D.J.; Hek, K.; Chen, T.H.; Watson, N.F.; Eiriksdottir, G.; Byrne, E.M.; Cornelis, M.; Warby, S.C.; Bandinelli, S.; Cherkas, L.; Evans, D.S.; Grabe, H.J.; Lahti, J.; Li, M.; Lehtimaki, T.; Lumley, T.; Marciante, K.D.; Pérusse, L.; Psaty, B.M.; Robbins, J.; Tranah, G.J.; Vink, J.M.; Wilk, J.B.; Stafford, J.M.; Bellis, C.; Biffar, R.; Bouchard, C.; Cade, B.; Curhan, G.C.; Eriksson, J.G.; Ewert, R.; Ferrucci, L.; Fulop, T.; Gehrman, P.R.; Goodloe, R.; Harris, T.B.; Heath, A.C.; Hernandez, D.G.; Hofman, A.; Hottenga, J.J.; Hunter, D.J.; Jensen, M.K.; Johnson, A.D.; Kahonen, M.; Kao, L.; Kraft, P.; Larkin, E.K.; Lauderdale, D.S.; Luik, A.I.; Medici, M.; Montgomery, G.W.; Palotie, A.; Patel, S.R.; Pistis, G.; Porcu, E.; Quaye, L.; Raitakari, O.; Redline, S.; Rimm, E.B.; Rotter, J.I.; Smith, A.V.; Spector, T.D.; Teumer, A.; Uitterlinden, A.G.; Vohl, M.C.; Widen, E.; Willemsen, G.; Young, T.; Zhang, X.; Liu, Y.; Blangero, J.; Boomsma, D.I.; Gudnason, V.; Hu, F.; Mangino, M.; Martin, N.G.; O'Connor, G.T.; Stone, K.L.; Tanaka, T.; Viikari, J.; Gharib, S.A.; Punjabi, N.M.; Raikkonen, K.; Völzke, H.; Mignot, E.; Tiemeier, H.

    2015-01-01

    Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based

  13. Genome-wide association study identifies four loci associated with eruption of permanent teeth

    DEFF Research Database (Denmark)

    Geller, Frank; Feenstra, Bjarke; Zhang, Hao

    2011-01-01

    The sequence and timing of permanent tooth eruption is thought to be highly heritable and can have important implications for the risk of malocclusion, crowding, and periodontal disease. We conducted a genome-wide association study of number of permanent teeth erupted between age 6 and 14 years, ...

  14. Genome-wide association study identifies 74 loci associated with educational attainment

    NARCIS (Netherlands)

    Okbay, Aysu; Beauchamp, Jonathan P.; Fontana, Mark Alan; Lee, James J.; Pers, Tune H.; Rietveld, Cornelius A.; Turley, Patrick; Chen, Guo-Bo; Emilsson, Valur; Meddens, S. Fleur W.; Oskarsson, Sven; Pickrell, Joseph K.; Thom, Kevin; Timshel, Pascal; de Vlaming, Ronald; Abdellaoui, Abdel; Ahluwalia, Tarunveer S.; Bacelis, Jonas; Baumbach, Clemens; Bjornsdottir, Gyda; Brandsma, Johannes H.; Concas, Maria Pina; Derringer, Jaime; Furlotte, Nicholas A.; Galesloot, Tessel E.; Girotto, Giorgia; Gupta, Richa; Hall, Leanne M.; Harris, Sarah E.; Hofer, Edith; Horikoshi, Momoko; Huffman, Jennifer E.; Kaasik, Kadri; Kalafati, Ioanna P.; Karlsson, Robert; Kong, Augustine; Lahti, Jari; van der Lee, Sven J.; de Leeuw, Christiaan; Lind, Penelope A.; Lindgren, Karl-Oskar; Liu, Tian; Mangino, Massimo; Marten, Jonathan; Mihailov, Evelin; Miller, Michael B.; van der Most, Peter J.; Oldmeadow, Christopher; Payton, Antony; Pervjakova, Natalia; Peyrot, Wouter J.; Qian, Yong; Raitakari, Olli; Rueedi, Rico; Salvi, Erika; Schmidt, Brge; Schraut, Katharina E.; Shi, Jianxin; Smith, Albert V.; Poot, Raymond A.; St Pourcain, Beate; Teumer, Alexander; Thorleifsson, Gudmar; Verweij, Niek; Vuckovic, Dragana; Wellmann, Juergen; Westra, Harm-Jan; Yang, Jingyun; Zhao, Wei; Zhu, Zhihong; Alizadeh, Behrooz Z.; Amin, Najaf; Bakshi, Andrew; Baumeister, Sebastian E.; Biino, Ginevra; Bonnelykke, Klaus; Boyle, Patricia A.; Campbell, Harry; Cappuccio, Francesco P.; Davies, Gail; De Neve, Jan-Emmanuel; Deloukas, Panos; Demuth, Ilja; Ding, Jun; Eibich, Peter; Eisele, Lewin; Eklund, Niina; Evans, David M.; Faul, Jessica D.; Feitosa, Mary F.; Forstner, Andreas J.; Gandin, Ilaria; Gunnarsson, Bjarni; Halldorsson, Bjarni V.; Harris, Tamara B.; Heath, Andrew C.; Hocking, Lynne J.; Holliday, Elizabeth G.; Homuth, Georg; Horan, Michael A.; Hottenga, Jouke-Jan; de Jager, Philip L.; Joshi, Peter K.; Jugessur, Astanand; Kaakinen, Marika A.; Kahonen, Mika; Kanoni, Stavroula; Keltigangas-Jarvinen, Liisa; Kiemeney, Lambertus A. L. M.; Kolcic, Ivana; Koskinen, Seppo; Kraja, Aldi T.; Kroh, Martin; Kutalik, Zoltan; Latvala, Antti; Launer, Lenore J.; Lebreton, Mael P.; Levinson, Douglas F.; Lichtenstein, Paul; Lichtner, Peter; Liewald, David C. M.; Loukola, Anu; Madden, Pamela A.; Magi, Reedik; Maki-Opas, Tomi; Marioni, Riccardo E.; Marques-Vidal, Pedro; Meddens, Gerardus A.; McMahon, George; Meisinger, Christa; Meitinger, Thomas; Milaneschi, Yusplitri; Milani, Lili; Montgomery, Grant W.; Myhre, Ronny; Nelson, Christopher P.; Nyholt, Dale R.; Ollier, William E. R.; Palotie, Aarno; Paternoster, Lavinia; Pedersen, Nancy L.; Petrovic, Katja E.; Porteous, David J.; Raikkonen, Katri; Ring, Susan M.; Robino, Antonietta; Rostapshova, Olga; Rudan, Igor; Rustichini, Aldo; Salomaa, Veikko; Sanders, Alan R.; Sarin, Antti-Pekka; Schmidt, Helena; Scott, Rodney J.; Smith, Blair H.; Smith, Jennifer A.; Staessen, Jan A.; Steinhagen-Thiessen, Elisabeth; Strauch, Konstantin; Terracciano, Antonio; Tobin, Martin D.; Ulivi, Sheila; Vaccargiu, Simona; Quaye, Lydia; van Rooij, Frank J. A.; Venturini, Cristina; Vinkhuyzen, Anna A. E.; Volker, Uwe; Volzke, Henry; Vonk, Judith M.; Waage, Johannes; Ware, Erin B.; Willemsen, Gonneke; Attia, John R.; Bennett, David A.; Berger, Klaus; Bertram, Lars; Bisgaard, Hans; Boomsma, Dorret I.; Borecki, Ingrid B.; Bultmann, Ute; Chabris, Christopher F.; Cucca, Francesco; Cusi, Daniele; Deary, Ian J.; Dedoussis, George V.; van Duijn, Cornelia M.; Eriksson, Johan G.; Franke, Barbara; Franke, Lude; Gasparini, Paolo; Gejman, Pablo V.; Gieger, Christian; Grabe, Hans-Jorgen; Gratten, Jacob; Groenen, Patrick J. F.; Gudnason, Vilmundur; van der Harst, Pim; Hayward, Caroline; Hinds, David A.; Hoffmann, Wolfgang; Hyppnen, Elina; Iacono, William G.; Jacobsson, Bo; Jarvelin, Marjo-Riitta; Jockel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L. R.; Lehtimaki, Terho; Lehrer, Steven F.; Magnusson, Patrik K. E.; Martin, Nicholas G.; McGue, Matt; Metspalu, Andres; Pendleton, Neil; Penninx, Brenda W. J. H.; Perola, Markus; Pirastu, Nicola; Pirastu, Mario; Polasek, Ozren; Posthuma, Danielle; Power, Christine; Province, Michael A.; Samani, Nilesh J.; Schlessinger, David; Schmidt, Reinhold; Sorensen, Thorkild I. A.; Spector, Tim D.; Stefansson, Kari; Thorsteinsdottir, Unnur; Thurik, A. Roy; Timpson, Nicholas J.; Tiemeier, Henning; Tung, Joyce Y.; Uitterlinden, Andre G.; Vitart, Veronique; Vollenweider, Peter; Weir, David R.; Wilson, James F.; Wright, Alan F.; Conley, Dalton C.; Krueger, Robert F.; Smith, George Davey; Hofman, Albert; Laibson, David I.; Medland, Sarah E.; Meyer, Michelle N.; Yang, Jian; Johannesson, Magnus; Visscher, Peter M.; Esko, Tonu; Koellinger, Philipp D.; Cesarini, David; Benjamin, Daniel J.

    2016-01-01

    Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals(1). Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends

  15. Perivascular spaces are associated with atherosclerosis: an insight from the Northern Manhattan Study.

    Science.gov (United States)

    Gutierrez, J; Rundek, T; Ekind, M S V; Sacco, R L; Wright, C B

    2013-09-01

    Perivascular spaces are potential spaces found between brain blood vessels and surrounding leptomeninges that have been associated with cardiovascular risk factors and dementia, but less is known about their relationship to atherosclerosis. We tested the hypothesis that perivascular spaces are associated with atherosclerosis. Participants from the Northern Manhattan Study who remained stroke-free were invited to participate in an MR imaging substudy. Parenchymal hypointensities of spaces. A semiquantitative score was created to express the degree of brain involvement. Generalized linear models were used to assess statistical associations with carotid plaque as a surrogate marker of atherosclerosis. The studied sample included 706 participants (mean age, 72.6 ± 8.0 years; 60% women, 61% Hispanic, 68% with hypertension, 19% with diabetes, and 57% with high cholesterol). The perivascular spaces score ranged from 0 to 19 with 52% of the sample having a perivascular spaces score of ≤4. In unadjusted analysis, perivascular spaces were associated with age (β = 0.01 per year, P = spaces. Perivascular spaces were more frequently found in older participants, in those with hypertension, and in the presence of carotid plaque. These results suggest that mechanisms leading to atherosclerosis might also lead to an increased number of perivascular spaces. These results need confirmation in prospective studies.

  16. Association between bullous pemphigoid and neurologic diseases: a case-control study.

    Science.gov (United States)

    Casas-de-la-Asunción, E; Ruano-Ruiz, J; Rodríguez-Martín, A M; Vélez García-Nieto, A; Moreno-Giménez, J C

    2014-11-01

    In the past 10 years, bullous pemphigoid has been associated with other comorbidities and neurologic and psychiatric conditions in particular. Case series, small case-control studies, and large population-based studies in different Asian populations, mainland Europe, and the United Kingdom have confirmed this association. However, no data are available for the Spanish population. This was an observational, retrospective, case-control study with 1:2 matching. Fifty-four patients with bullous pemphigoid were selected. We compared the percentage of patients in each group with concurrent neurologic conditions, ischemic heart disease, diabetes, chronic obstructive pulmonary disease, and solid tumors using univariate logistic regression. An association model was constructed with conditional multiple logistic regression. The case group had a significantly higher percentage of patients with cerebrovascular accident and/or transient ischemic attack (odds ratio [OR], 3.06; 95% CI, 1.19-7.87], dementia (OR, 5.52; 95% CI, 2.19-13.93), and Parkinson disease (OR, 5; 95% CI, 1.57-15.94). A significantly higher percentage of cases had neurologic conditions (OR, 6.34; 95% CI, 2.89-13.91). Dementia and Parkinson disease were independently associated with bullous pemphigoid in the multivariate analysis. Patients with bullous pemphigoid have a higher frequency of neurologic conditions. Copyright © 2013 Elsevier España, S.L.U. and AEDV. All rights reserved.

  17. A population-based study of preschoolers' food neophobia and its associations with food preferences.

    Science.gov (United States)

    Russell, Catherine Georgina; Worsley, Anthony

    2008-01-01

    This cross-sectional study was designed to investigate the relationships between food preferences, food neophobia, and children's characteristics among a population-based sample of preschoolers. A parent-report questionnaire. Child-care centers, kindergartens, playgroups, day nurseries, and swimming centers. 371 two- to five-year-old Australian children. Associations between food neophobia and the food preferences and characteristics. Analysis of variance, analysis of covariance, Pearson product-moment correlations, and Fisher z test were used to estimate and compare the associations between these variables. Food neophobia was associated with reduced preferences for all food groups, but especially for vegetables (r = -0.60; P food types (r = -0.55; P food types (r = 0.42; P food types (r = 0.25; P food preferences (r = -0.59; P food preferences overall (r = -0.55; P food neophobia and a child's age, sex, or history of breast-feeding. The study confirms and extends results obtained in experimental research and population-based intake studies of food neophobia to children's everyday food preferences. The findings suggest that preschool children's everyday food preferences are strongly associated with food neophobia but not with children's age, sex, or history of breast-feeding. When aiming to influence children's food preferences, the effects of food neophobia and strategies to reduce it should be considered.

  18. Genome-wide association study of maternal and inherited loci for conotruncal heart defects.

    Directory of Open Access Journals (Sweden)

    A J Agopian

    Full Text Available Conotruncal and related heart defects (CTDs are a group of serious and relatively common birth defects. Although both maternal and inherited genotypes are thought to play a role in the etiology of CTDs, few specific genetic risk factors have been identified. To determine whether common variants acting through the genotype of the mother (e.g. via an in utero effect or the case are associated with CTDs, we conducted a genome-wide association study of 750 CTD case-parent triads, with follow-up analyses in 358 independent triads. Log-linear analyses were used to assess the association of CTDs with the genotypes of both the mother and case. No association achieved genomewide significance in either the discovery or combined (discovery+follow-up samples. However, three loci with p-values suggestive of association (p<10-5 in the discovery sample had p-values <0.05 in the follow-up sample and p-values in the combined data that were lower than in the discovery sample. These included suggestive association with an inherited intergenic variant at 20p12.3 (rs6140038, combined p = 1.0 × 10(-5 and an inherited intronic variant in KCNJ4 at 22q13.1 (rs2267386, combined p = 9.8 × 10(-6, as well as with a maternal variant in SLC22A24 at 11q12.3 (rs11231379, combined p = 4.2 × 10(-6. These observations suggest novel candidate loci for CTDs, including loci that appear to be associated with the risk of CTDs via the maternal genotype, but further studies are needed to confirm these associations.

  19. Genome-wide Association Study Identifies Genes for Biomarkers of Cardiovascular Disease: Serum Urate and Dyslipidemia

    Science.gov (United States)

    Wallace, Chris; Newhouse, Stephen J.; Braund, Peter; Zhang, Feng; Tobin, Martin; Falchi, Mario; Ahmadi, Kourosh; Dobson, Richard J.; Marçano, Ana Carolina B.; Hajat, Cother; Burton, Paul; Deloukas, Panagiotis; Brown, Morris; Connell, John M.; Dominiczak, Anna; Lathrop, G. Mark; Webster, John; Farrall, Martin; Spector, Tim; Samani, Nilesh J.; Caulfield, Mark J.; Munroe, Patricia B.

    2008-01-01

    Summary Many common diseases are accompanied by disturbances in biochemical traits. Identifying the genetic determinants could provide novel insights into disease mechanisms and reveal avenues for developing new therapies. Here, we report a genome-wide association analysis for commonly measured serum and urine biochemical traits. As part of the WTCCC, 500,000 SNPs genome wide were genotyped in 1955 hypertensive individuals characterized for 25 serum and urine biochemical traits. For each trait, we assessed association with individual SNPs, adjusting for age, sex, and BMI. Lipid measurements were further examined in a meta-analysis of genome-wide data from a type 2 diabetes scan. The most promising associations were examined in two epidemiological cohorts. We discovered association between serum urate and SLC2A9, a glucose transporter (p = 2 × 10−15) and confirmed this in two independent cohorts, GRAPHIC study (p = 9 × 10−15) and TwinsUK (p = 8 × 10−19). The odds ratio for hyperuricaemia (defined as urate >0.4 mMol/l) is 1.89 (95% CI = 1.36–2.61) per copy of common allele. We also replicated many genes previously associated with serum lipids and found previously recognized association between LDL levels and SNPs close to genes encoding PSRC1 and CELSR2 (p = 1 × 10−7). The common allele was associated with a 6% increase in nonfasting serum LDL. This region showed increased association in the meta-analysis (p = 4 × 10−14). This finding provides a potential biological mechanism for the recent association of this same allele of the same SNP with increased risk of coronary disease. PMID:18179892

  20. Toppar: An interactive browser for viewing association study results.

    Science.gov (United States)

    Juliusdottir, Thorhildur; Banasik, Karina; Robertson, Neil R; Mott, Richard; McCarthy, Mark I

    2018-01-08

    Data integration and visualization help geneticists make sense of large amounts of data. To help facilitate interpretation of genetic association data we developed Toppar, a customizable visualization tool that stores results from association studies and enables browsing over multiple results, by combining features from existing tools and linking to appropriate external databases. Detailed information on Toppar's features and functionality are on our website http://mccarthy.well.ox.ac.uk/toppar/docs along with instructions on how to download, install and run Toppar. Our online version of Toppar is accessible from the website and can be test-driven using Firefox, Safari or Chrome on sub-sets of publicly available genome-wide association study (GWAS) anthropometric waist and body mass index (BMI) data (Locke, et al., 2015; Shungin, et al., 2015) from the Genetic Investigation of ANthropometric Traits (GIANT) consortium. totajuliusd@gmail.com.

  1. Genome-wide association studies and resting heart rate

    DEFF Research Database (Denmark)

    Oskari Kilpeläinen, Tuomas

    2016-01-01

    Genome-wide association studies (GWASs) have revolutionized the search for genetic variants regulating resting heart rate. In the last 10 years, GWASs have led to the identification of at least 21 novel heart rate loci. These discoveries have provided valuable insights into the mechanisms...... and pathways that regulate heart rate and link heart rate to cardiovascular morbidity and mortality. GWASs capture majority of genetic variation in a population sample by utilizing high-throughput genotyping chips measuring genotypes for up to several millions of SNPs across the genome in thousands...... of individuals. This allows the identification of the strongest heart rate associated signals at genome-wide level. While GWASs provide robust statistical evidence of the association of a given genetic locus with heart rate, they are only the starting point for detailed follow-up studies to locate the causal...

  2. Multi-generational genome wide association studies identify chromosomal regions associated with ascites phenotype.

    Science.gov (United States)

    Tarrant, K J; Dey, S; Kinney, R; Anthony, N B; Rhoads, D D

    2017-06-01

    Ascites is a multi-faceted disease commonly observed in fast growing broilers, which is initiated when the body is insufficiently oxygenated. A series of events follow, including an increase in pulmonary artery pressure, right ventricle hypertrophy, and accumulation of fluid in the abdominal cavity and pericardium. Advances in management practices along with improved selection programs have decreased ascites incidence in modern broilers. However, ascites syndrome remains an economically important disease throughout the world, causing estimated losses of $100 million per year. In this study, a 60 K Illumina SNP BeadChip was used to perform a series of genome wide association studies (GWAS) on the 16th and 18th generation of our relaxed (REL) line descended from a commercial elite broiler line beginning in 1995. Regions significantly associated with ascites incidence were identified on chromosome 2 around 70 megabase pairs (Mbp) and on chromosome Z around 60 Mbp. Five candidate single nucleotide polymorphisms (SNP) were evaluated as indicators for these 2 regions in order to identify association with ascites and right ventricle to total ventricle weight (RVTV) ratios. Chromosome 2 SNP showed an association with RVTV ratios in males phenotyped as ascites resistant and ascites susceptible (P = 0.02 and P = 0.03, respectively). The chromosome Z region also indicates an association with resistant female RVTV values (P = 0.02). Regions of significance identified on chromosomes 2 and Z described in this study will be used as proposed candidate regions for further investigation into the genetics of ascites. This information will lead to a better understanding of the underlying genetics and gene networks contributing to ascites, and thus advances in ascites reduction through commercial breeding schemes. © 2017 Poultry Science Association Inc.

  3. Factors associated with the duration of disability benefits claims among Canadian workers: a retrospective cohort study.

    Science.gov (United States)

    Mulla, Sohail M; Makosso-Kallyth, Sun; St-Hilaire, Nathalie; Munsch, Katrena; Gove, Peter B; Heels-Ansdell, Diane; Guyatt, Gordon H; Busse, Jason W

    2017-01-01

    Disability insurance protects workers from total loss of income in case of a disabling injury or illness by providing wage-replacement benefits. To better inform early identification of claims at risk of prolonged recovery, we explored predictors of the duration of disability benefits claims. We conducted a retrospective cohort study using claims data provided by SSQ Life Insurance Company Inc., a private Canadian disability insurer. We examined all claims SSQ approved for short- and long-term disability benefits from Jan. 1, 2007, to Mar. 31, 2014, and evaluated the association between 9 variables and duration of short- and long-term disability benefits using Cox proportional hazards regression analyses. For both short- (n = 70 776) and long-term disability (n = 22 205) claims, and across all disorders, older age, female sex, heavy job demands, presence of comorbidity, attending an independent medical evaluation, receipt of rehabilitation therapy and longer time to claim approval were associated with longer claim duration. Higher predisability salary was associated with longer short-term disability claim duration. Quebec residency was associated with longer short-term disability claim duration among workers with psychological disorders, but shorter short-term disability claim duration among those with musculoskeletal complaints and other illnesses. For long-term disability claims, however, residing in Quebec was associated with shorter claim duration, although the size of the association differed across clinical conditions. The factors we found to be associated with the duration of short- and long-term disability claims may be helpful to identify claims at risk of prolonged recovery. Our study has limitations, however, and well-designed prospective studies are needed to confirm our findings and identify other promising predictors.

  4. Genome-wide association studies in asthma: progress and pitfalls

    Directory of Open Access Journals (Sweden)

    March ME

    2015-01-01

    Full Text Available Michael E March,1 Patrick MA Sleiman,1,2 Hakon Hakonarson1,2 1Center for Applied Genomics, Children's Hospital of Philadelphia Research Institute, 2Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Abstract: Genetic studies of asthma have revealed that there is considerable heritability to the phenotype. An extensive history of candidate-gene studies has identified a long list of genes associated with immune function that are potentially involved in asthma pathogenesis. However, many of the results of candidate-gene studies have failed to be replicated, leaving in question the true impact of the implicated biological pathways on asthma. With the advent of genome-wide association studies, geneticists are able to examine the association of hundreds of thousands of genetic markers with a phenotype, allowing the hypothesis-free identification of variants associated with disease. Many such studies examining asthma or related phenotypes have been published, and several themes have begun to emerge regarding the biological pathways underpinning asthma. The results of many genome-wide association studies have currently not been replicated, and the large sample sizes required for this experimental strategy invoke difficulties with sample stratification and phenotypic heterogeneity. Recently, large collaborative groups of researchers have formed consortia focused on asthma, with the goals of sharing material and data and standardizing diagnosis and experimental methods. Additionally, research has begun to focus on genetic variants that affect the response to asthma medications and on the biology that generates the heterogeneity in the asthma phenotype. As this work progresses, it will move asthma patients closer to more specific, personalized medicine. Keywords: asthma, genetics, GWAS, pharmacogenetics, biomarkers

  5. Clinical and Laboratory Factors Associated with Severe Dengue: A Case-Control Study of Hospitalized Children.

    Science.gov (United States)

    Wakimoto, Mayumi Duarte; Camacho, Luiz Antonio Bastos; Gonin, Michelle Luiza; Brasil, Patrícia

    2017-10-20

    More than half of the hospitalizations because of dengue in Brazil occurred in children <15 years of age in 2007 and 2008, an unexpected change in the epidemiological pattern. We sought to determine clinical and laboratory parameters associated with severity. A case-control study was conducted in three pediatric hospitals in Rio de Janeiro, Brazil; 233 laboratory-confirmed dengue patients were included: 69 cases and 164 controls. Specific clinical and laboratory factors were assessed using univariate and multivariate logistic regression models. Lethargy [adjusted odds ratio (ORa): 9.15, 95% confidence interval (CI): 3.08-27.12], dyspnea (ORa: 8.24, 95% CI: 3.27-20.72) and abdominal pain (ORa: 6.78, 95% CI: 1.44-31.84) were independently associated with severe dengue in children. Lethargy and dyspnea presented as early as 72 and 48 h, respectively, before shock. Abdominal pain and lethargy confirmed their role as warning signs, which along with dyspnea might be helpful in identifying cases progressing to severe dengue.

  6. A genome-wide association study identifies four novel susceptibility loci underlying inguinal hernia

    Science.gov (United States)

    Jorgenson, Eric; Makki, Nadja; Shen, Ling; Chen, David C.; Tian, Chao; Eckalbar, Walter L.; Hinds, David; Ahituv, Nadav; Avins, Andrew

    2015-01-01

    Inguinal hernia repair is one of the most commonly performed operations in the world, yet little is known about the genetic mechanisms that predispose individuals to develop inguinal hernias. We perform a genome-wide association analysis of surgically confirmed inguinal hernias in 72,805 subjects (5,295 cases and 67,510 controls) and confirm top associations in an independent cohort of 92,444 subjects with self-reported hernia repair surgeries (9,701 cases and 82,743 controls). We identify four novel inguinal hernia susceptibility loci in the regions of EFEMP1, WT1, EBF2 and ADAMTS6. Moreover, we observe expression of all four genes in mouse connective tissue and network analyses show an important role for two of these genes (EFEMP1 and WT1) in connective tissue maintenance/homoeostasis. Our findings provide insight into the aetiology of hernia development and highlight genetic pathways for studies of hernia development and its treatment. PMID:26686553

  7. A proteomic study of potential VEGF-C-associated proteins in bladder cancer T24 cells.

    Science.gov (United States)

    Zhang, Hui-hui; Qi, Fan; Zu, Xiong-bing; Cao, You-han; Miao, Jian-guang; Xu, Liang; Qi, Lin

    2012-11-01

    Overexpression of vascular endothelial growth factor-C (VEGF-C) has been found to play an important role in malignant progression of various cancer cells, in addition to lymphangiogenesis. However, the mechanisms involved are still largely unknown. Our early research has confirmed that the expression of VEGF-C in bladder cancer was markedly higher than that in normal bladder tissues. VEGF-C can also obviously promote proliferation and invasion of bladder cancer T24 cells. In the present work, we attempted to use proteomic analysis to screen out potential VEGF-C-associated proteins involved in malignant progression of the bladder cancer T24 cells. Lentivirus vector-based RNA interference (RNAi) was employed to diminish VEGF-C expression of bladder cancer T24 cells. Then we performed comparative proteome analysis to explore differentially expressed proteins in T24 cells with and without VEGF-C siRNA, by two-dimensional difference gel electrophoresis (2D-DIGE). Twenty-three proteins were identified. Some proteins (matrix metalloproteinase-9, Keratin 8, Serpin B5, Annexin A8) with significant differences were further confirmed by Western blotting. The 23 potential VEGF-C-associated proteins identified in our study provide us with further insights into the mechanism of VEGF-C promoting malignant progression of bladder cancer cells.

  8. Association of diabetes mellitus and dementia : The Rotterdam study

    NARCIS (Netherlands)

    Ott, A; Stolk, RP; Hofman, A; vanHarskamp, F; Grobbee, DE; Breteler, MMB

    1996-01-01

    Dementia and non-insulin-dependent diabetes mellitus (NIDDM) are highly prevalent disorders in the elderly. Diabetes has repeatedly been reported to affect cognition, but its relation with dementia is uncertain. We therefore studied the association between diabetes and dementia in the Rotterdam

  9. Genome-wide association study identifies five new schizophrenia loci

    NARCIS (Netherlands)

    Ripke, Stephan; Sanders, Alan R.; Kendler, Kenneth S.; Levinson, Douglas F.; Sklar, Pamela; Holmans, Peter A.; Lin, Dan-Yu; Duan, Jubao; Ophoff, Roel A.; Andreassen, Ole A.; Scolnick, Edward; Cichon, Sven; Clair, David St.; Corvin, Aiden; Gurling, Hugh; Werge, Thomas; Rujescu, Dan; Blackwood, Douglas H. R.; Pato, Carlos N.; Malhotra, Anil K.; Purcell, Shaun; Dudbridge, Frank; Neale, Benjamin M.; Rossin, Lizzy; Visscher, Peter M.; Posthuma, Danielle; Ruderfer, Douglas M.; Fanous, Ayman; Stefansson, Hreinn; Steinberg, Stacy; Mowry, Bryan J.; Golimbet, Vera; De Hert, Marc; Jonsson, Erik G.; Bitter, Istvan; Pietilainen, Olli P. H.; Collier, David A.; Tosato, Sarah; Agartz, Ingrid; Albus, Margot; Alexander, Madeline; Amdur, Richard L.; Amin, Farooq; Bass, Nicholas; Bergen, Sarah E.; Black, Donald W.; Borglum, Anders D.; Brown, Matthew A.; Bruggeman, Richard; Buccola, Nancy G.; Byerley, William F.; Cahn, Wiepke; Cantor, Rita M.; Carr, Vaughan J.; Catts, Stanley V.; Choudhury, Khalid; Cloninger, C. Robert; Cormican, Paul; Craddock, Nicholas; Danoy, Patrick A.; Datta, Susmita; De Haan, Lieuwe; Demontis, Ditte; Dikeos, Dimitris; Djurovic, Srdjan; Donnelly, Peter; Donohoe, Gary; Duong, Linh; Dwyer, Sarah; Fink-Jensen, Anders; Freedman, Robert; Freimer, Nelson B.; Friedl, Marion; Georgieva, Lyudmila; Giegling, Ina; Gill, Michael; Glenthoj, Birte; Godard, Stephanie; Hamshere, Marian; Hansen, Mark; Hansen, Thomas; Hartmann, Annette M.; Henskens, Frans A.; Hougaard, David M.; Hultman, Christina M.; Ingason, Andres; Jablensky, Assen V.; Jakobsen, Klaus D.; Jay, Maurice; Juergens, Gesche; Kahn, Renes; Keller, Matthew C.; Kenis, Gunter; Kenny, Elaine; Kim, Yunjung; Kirov, George K.; Konnerth, Heike; Konte, Bettina; Krabbendam, Lydia; Krasucki, Robert; Lasseter, Virginia K.; Laurent, Claudine; Lawrence, Jacob; Lencz, Todd; Lerer, F. Bernard; Liang, Kung-Yee; Lichtenstein, Paul; Lieberman, Jeffrey A.; Linszen, Don H.; Lonnqvist, Jouko; Loughland, Carmel M.; Maclean, Alan W.; Maher, Brion S.; Maier, Wolfgang; Mallet, Jacques; Malloy, Pat; Mattheisen, Manuel; Mattingsdal, Morten; McGhee, Kevin A.; McGrath, John J.; McIntosh, Andrew; McLean, Duncan E.; McQuillin, Andrew; Melle, Ingrid; Michie, Patricia T.; Milanova, Vihra; Morris, Derek W.; Mors, Ole; Mortensen, Preben B.; Moskvina, Valentina; Muglia, Pierandrea; Myin-Germeys, Inez; Nertney, Deborah A.; Nestadt, Gerald; Nielsen, Jimmi; Nikolov, Ivan; Nordentoft, Merete; Norton, Nadine; Noethen, Markus M.; O'Dushlaine, Colm T.; Olincy, Ann; Olsen, Line; O'Neill, F. Anthony; Orntoft, Torben F.; Owen, Michael J.; Pantelis, Christos; Papadimitriou, George; Pato, Michele T.; Peltonen, Leena; Petursson, Hannes; Pickard, Ben; Pimm, Jonathan; Pulver, Ann E.; Puri, Vinay; Quested, Digby; Quinn, Emma M.; Rasmussen, Henrik B.; Rethelyi, Janos M.; Ribble, Robert; Rietschel, Marcella; Riley, Brien P.; Ruggeri, Mirella; Schall, Ulrich; Schulze, Thomas G.; Schwab, Sibylle G.; Scott, Rodney J.; Shi, Jianxin; Sigurdsson, Engilbert; Silverman, Jeremy M.; Spencer, Chris C. A.; Stefansson, Kari; Strange, Amy; Strengman, Eric; Stroup, T. Scott; Suvisaari, Jaana; Terenius, Lars; Thirumalai, Srinivasa; Thygesen, Johan H.; Timm, Sally; Toncheva, Draga; van den Oord, Edwin; van Os, Jim; van Winkel, Ruud; Veldink, Jan; Walsh, Dermot; Wang, August G.; Wiersma, Durk; Wildenauer, Dieter B.; Williams, Hywel J.; Williams, Nigel M.; Wormley, Brandon; Zammit, Stan; Sullivan, Patrick F.; O'Donovan, Michael C.; Daly, Mark J.; Gejman, Pablo V.

    2011-01-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded

  10. Genomewide association study of body weight traits in Baluchi sheep

    Indian Academy of Sciences (India)

    2Faculty of Agronomy Sciences, Department of Animal Sciences, College of Agriculture and Natural Resources,. University of Tehran, Karaj 31587111674111, Iran. [Gholizadeh M., Rahimi-Mianji G. and Nejati-Javaremi A. 2015 Genomewide association study of body weight traits in Baluchi sheep. J. Genet. 94, 143–146].

  11. Factors associated with early adiposity rebound. ALSPAC Study Team.

    Science.gov (United States)

    Dorosty, A R; Emmett, P M; Cowin, S d; Reilly, J J

    2000-05-01

    The age at which body mass index (BMI) increases after its nadir in childhood, adiposity rebound (AR), is a critical period for the development of obesity. Children with early AR are at substantially increased risk of adult obesity. Few studies have examined the factors that influence the timing of the AR. The aims of this study were to test for influences on the timing of the AR, and to test the hypothesis that early AR is promoted by high-protein intake. Longitudinal cohort study of 889 children representative of the United Kingdom, followed from birth to 5 years. We tested for differences in dietary intake, parental BMI, socioeconomic status, and childhood BMI between 3 groups of children characterized by the following: very early AR (at or before 43 months), early AR (from 49 but before 61 months), and later AR (after 61 months). There was no evidence of associations between dietary protein intake, or any other dietary variable, and timing of the AR. Children with very early AR and early AR had parents with significantly higher BMI, and were significantly more likely to have at least 1 obese parent. This study does not support the hypothesis that early AR is promoted by high-protein intake. None of the dietary variables tested were significantly associated with timing of the AR, and timing of AR was not associated with socioeconomic status. Parental obesity was associated with an earlier AR.

  12. Genomewide association studies: history, rationale, and prospects for psychiatric disorders.

    NARCIS (Netherlands)

    Franke, B.; Buitelaar, J.K.; Cichon, S.; Craddock, N.; Daly, M.; Faraone, S.V.; Gejman, P.V.; Kelsoe, J.; Lehner, T.; Levinson, D.F.; Moran, A.; Sklar, P.; Sullivan, P.F.

    2009-01-01

    OBJECTIVE: The authors conducted a review of the history and empirical basis of genomewide association studies (GWAS), the rationale for GWAS of psychiatric disorders, results to date, limitations, and plans for GWAS meta-analyses. METHOD: A literature review was carried out, power and other issues

  13. A Retrospective Study on Magnitude and Factors Associated with ...

    African Journals Online (AJOL)

    Background: Anemia in the postnatal period is a common problem, which has been subject of research recently. Though, it is a common problem, it is a less researched topic in India. Hence, this study was undertaken. Aim: The aim was to know the clinic.social factors associated with anemia in the postpartum period.

  14. Histological and morphometric studies on the age-associated ...

    African Journals Online (AJOL)

    Histological and morphometric studies on the age-associated changes in the colon of the mouse. MA Motabagani. Abstract. No Abstract. Journal of Experimental and Clinical Anatomy Vol. 5(1) 2006: 48-58. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT.

  15. Study of Ventilator Associated Pneumonia in Neonatal Intensive ...

    African Journals Online (AJOL)

    Study of Ventilator Associated Pneumonia in Neonatal Intensive Care Unit: characteristics, risk factors and outcome. ... Most common bacterial isolated from endotracheal aspirate of VAP patients was Klebsiella spp (32.8%), E.coli (23.2%) and Acinetobacter (17.8%) being the other two common organisms. Very low birth ...

  16. Dental trauma in association with maxillofacial fractures: an epidemiological study

    NARCIS (Netherlands)

    Ruslin, M.; Wolff, J.; Boffano, P.; Brand, H.S.; Forouzanfar, T.

    2015-01-01

    Aim The aim of this study was to retrospectively investigate the incidence and associated factors of dental trauma in patients with maxillofacial fractures at the VU Medical Center in Amsterdam. Material and methods Data from 707 patients who were treated surgically for maxillofacial fractures were

  17. Dental trauma in association with maxillofacial fractures: an epidemiological study

    NARCIS (Netherlands)

    Ruslin, M.; Wolff, J.; Boffano, P.; Brand, H.S.; Forouzanfar, T.

    2015-01-01

    Aim: The aim of this study was to retrospectively investigate the incidence and associated factors of dental trauma in patients with maxillofacial fractures at the VU Medical Center in Amsterdam. Material and methods: Data from 707 patients who were treated surgically for maxillofacial fractures

  18. Molecular evaluation of genetic diversity and association studies in ...

    Indian Academy of Sciences (India)

    Molecular evaluation of genetic diversity and association studies in rice. (Oryza sativa L.) C. Vanniarajan, K. K. Vinod and Andy Pereira. J. Genet. 91, 9–19. Table 1. Chromosome-wise distribution of SSR alleles and their number (k), polymorphic information content (PIC) and allele discrimination index (Dm). Chromosome.

  19. Genome-Wide Association Study of Serum Selenium Concentrations

    Directory of Open Access Journals (Sweden)

    Ulrike Peters

    2013-05-01

    Full Text Available Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated this hypothesis. Therefore, we conducted a two-stage genome-wide association study to identify genetic variants associated with serum selenium concentrations in 1203 European descents from two cohorts: the Prostate, Lung, Colorectal, and Ovarian (PLCO Cancer Screening and the Women’s Health Initiative (WHI. We tested association between 2,474,333 single nucleotide polymorphisms (SNPs and serum selenium concentrations using linear regression models. In the first stage (PLCO 41 SNPs clustered in 15 regions had p < 1 × 10−5. None of these 41 SNPs reached the significant threshold (p = 0.05/15 regions = 0.003 in the second stage (WHI. Three SNPs had p < 0.05 in the second stage (rs1395479 and rs1506807 in 4q34.3/AGA-NEIL3; and rs891684 in 17q24.3/SLC39A11 and had p between 2.62 × 10−7 and 4.04 × 10−7 in the combined analysis (PLCO + WHI. Additional studies are needed to replicate these findings. Identification of genetic variation that impacts selenium concentrations may contribute to a better understanding of which genes regulate circulating selenium concentrations.

  20. Genome association study of human chromosome 13 and ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 92; Issue 1. Genome association study of human chromosome 13 and susceptibility to coronary artery disease in a Chinese population. Peng Jie Chen Xing Li Tingting Xie Yi Zhang Jianning Jiang Tingting Liu Tianjiao Chen Gang Guo Yuan. Research Note Volume 92 Issue 1 ...

  1. A Genome-Wide Association Study for Agronomic Traits in Soybean Using SNP Markers and SNP-Based Haplotype Analysis.

    Science.gov (United States)

    Contreras-Soto, Rodrigo Iván; Mora, Freddy; de Oliveira, Marco Antônio Rott; Higashi, Wilson; Scapim, Carlos Alberto; Schuster, Ivan

    2017-01-01

    Mapping quantitative trait loci through the use of linkage disequilibrium (LD) in populations of unrelated individuals provides a valuable approach for dissecting the genetic basis of complex traits in soybean (Glycine max). The haplotype-based genome-wide association study (GWAS) has now been proposed as a complementary approach to intensify benefits from LD, which enable to assess the genetic determinants of agronomic traits. In this study a GWAS was undertaken to identify genomic regions that control 100-seed weight (SW), plant height (PH) and seed yield (SY) in a soybean association mapping panel using single nucleotide polymorphism (SNP) markers and haplotype information. The soybean cultivars (N = 169) were field-evaluated across four locations of southern Brazil. The genome-wide haplotype association analysis (941 haplotypes) identified eleven, seventeen and fifty-nine SNP-based haplotypes significantly associated with SY, SW and PH, respectively. Although most marker-trait associations were environment and trait specific, stable haplotype associations were identified for SY and SW across environments (i.e., haplotypes Gm12_Hap12). The haplotype block 42 on Chr19 (Gm19_Hap42) was confirmed to be associated with PH in two environments. These findings enable us to refine the breeding strategy for tropical soybean, which confirm that haplotype-based GWAS can provide new insights on the genetic determinants that are not captured by the single-marker approach.

  2. Robust Association Tests for the Replication of Genome-Wide Association Studies.

    Science.gov (United States)

    Joo, Jungnam; Park, Ju-Hyun; Lee, Bora; Park, Boram; Kim, Sohee; Yoon, Kyong-Ah; Lee, Jin Soo; Geller, Nancy L

    2015-01-01

    In genome-wide association study (GWAS), robust genetic association tests such as maximum of three CATTs (MAX3), each corresponding to recessive, additive, and dominant genetic models, the minimum p value of Pearson's Chi-square test with 2 degrees of freedom, and CATT based on additive genetic model (MIN2), genetic model selection (GMS), and genetic model exclusion (GME) methods have been shown to provide better power performance under wide range of underlying genetic models. In this paper, we demonstrate how these robust tests can be applied to the replication study of GWAS and how the overall statistical significance can be evaluated using the combined test formed by p values of the discovery and replication studies.

  3. Robust Association Tests for the Replication of Genome-Wide Association Studies

    Directory of Open Access Journals (Sweden)

    Jungnam Joo

    2015-01-01

    Full Text Available In genome-wide association study (GWAS, robust genetic association tests such as maximum of three CATTs (MAX3, each corresponding to recessive, additive, and dominant genetic models, the minimum p value of Pearson’s Chi-square test with 2 degrees of freedom, and CATT based on additive genetic model (MIN2, genetic model selection (GMS, and genetic model exclusion (GME methods have been shown to provide better power performance under wide range of underlying genetic models. In this paper, we demonstrate how these robust tests can be applied to the replication study of GWAS and how the overall statistical significance can be evaluated using the combined test formed by p values of the discovery and replication studies.

  4. Genome-wide association study of antisocial personality disorder.

    Science.gov (United States)

    Rautiainen, M-R; Paunio, T; Repo-Tiihonen, E; Virkkunen, M; Ollila, H M; Sulkava, S; Jolanki, O; Palotie, A; Tiihonen, J

    2016-09-06

    The pathophysiology of antisocial personality disorder (ASPD) remains unclear. Although the most consistent biological finding is reduced grey matter volume in the frontal cortex, about 50% of the total liability to developing ASPD has been attributed to genetic factors. The contributing genes remain largely unknown. Therefore, we sought to study the genetic background of ASPD. We conducted a genome-wide association study (GWAS) and a replication analysis of Finnish criminal offenders fulfilling DSM-IV criteria for ASPD (N=370, N=5850 for controls, GWAS; N=173, N=3766 for controls and replication sample). The GWAS resulted in suggestive associations of two clusters of single-nucleotide polymorphisms at 6p21.2 and at 6p21.32 at the human leukocyte antigen (HLA) region. Imputation of HLA alleles revealed an independent association with DRB1*01:01 (odds ratio (OR)=2.19 (1.53-3.14), P=1.9 × 10(-5)). Two polymorphisms at 6p21.2 LINC00951-LRFN2 gene region were replicated in a separate data set, and rs4714329 reached genome-wide significance (OR=1.59 (1.37-1.85), P=1.6 × 10(-9)) in the meta-analysis. The risk allele also associated with antisocial features in the general population conditioned for severe problems in childhood family (β=0.68, P=0.012). Functional analysis in brain tissue in open access GTEx and Braineac databases revealed eQTL associations of rs4714329 with LINC00951 and LRFN2 in cerebellum. In humans, LINC00951 and LRFN2 are both expressed in the brain, especially in the frontal cortex, which is intriguing considering the role of the frontal cortex in behavior and the neuroanatomical findings of reduced gray matter volume in ASPD. To our knowledge, this is the first study showing genome-wide significant and replicable findings on genetic variants associated with any personality disorder.

  5. Genome-Wide Association Study for Carcass Traits in an Experimental Nelore Cattle Population.

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    Rafael Medeiros de Oliveira Silva

    Full Text Available The purpose of this study was to identify genomic regions associated with carcass traits in an experimental Nelore cattle population. The studied data set contained 2,306 ultrasound records for longissimus muscle area (LMA, 1,832 for backfat thickness (BF, and 1,830 for rump fat thickness (RF. A high-density SNP panel (BovineHD BeadChip assay 700k, Illumina Inc., San Diego, CA was used for genotyping. After genomic data quality control, 437,197 SNPs from 761 animals were available, of which 721 had phenotypes for LMA, 669 for BF, and 718 for RF. The SNP solutions were estimated using a single-step genomic BLUP approach (ssGWAS, which calculated the variance for windows of 50 consecutive SNPs and the regions that accounted for more than 0.5% of the additive genetic variance were used to search for candidate genes. The results indicated that 12, 18, and 15 different windows were associated to LMA, BF, and RF, respectively. Confirming the polygenic nature of the studied traits, 43, 65, and 53 genes were found in those associated windows, respectively for LMA, BF, and RF. Among the candidate genes, some of them, which already had their functions associated with the expression of energy metabolism, were found associated with fat deposition in this study. In addition, ALKBH3 and HSD17B12 genes, which are related in fibroblast death and metabolism of steroids, were found associated with LMA. The results presented here should help to better understand the genetic and physiologic mechanism regulating the muscle tissue deposition and subcutaneous fat cover expression of Zebu animals. The identification of candidate genes should contribute for Zebu breeding programs in order to consider carcass traits as selection criteria in their genetic evaluation.

  6. Sample Size and Statistical Power Calculation in Genetic Association Studies

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    Eun Pyo Hong

    2012-06-01

    Full Text Available A sample size with sufficient statistical power is critical to the success of genetic association studies to detect causal genes of human complex diseases. Genome-wide association studies require much larger sample sizes to achieve an adequate statistical power. We estimated the statistical power with increasing numbers of markers analyzed and compared the sample sizes that were required in case-control studies and case-parent studies. We computed the effective sample size and statistical power using Genetic Power Calculator. An analysis using a larger number of markers requires a larger sample size. Testing a single-nucleotide polymorphism (SNP marker requires 248 cases, while testing 500,000 SNPs and 1 million markers requires 1,206 cases and 1,255 cases, respectively, under the assumption of an odds ratio of 2, 5% disease prevalence, 5% minor allele frequency, complete linkage disequilibrium (LD, 1:1 case/control ratio, and a 5% error rate in an allelic test. Under a dominant model, a smaller sample size is required to achieve 80% power than other genetic models. We found that a much lower sample size was required with a strong effect size, common SNP, and increased LD. In addition, studying a common disease in a case-control study of a 1:4 case-control ratio is one way to achieve higher statistical power. We also found that case-parent studies require more samples than case-control studies. Although we have not covered all plausible cases in study design, the estimates of sample size and statistical power computed under various assumptions in this study may be useful to determine the sample size in designing a population-based genetic association study.

  7. A genome-wide association study of thyroid stimulating hormone and free thyroxine in Danish children and adolescents

    DEFF Research Database (Denmark)

    Nielsen, Tenna Ruest Haarmark; Appel, Emil Vincent Rosenbaum; Svendstrup, Mathilde

    2017-01-01

    associated with TSH in adults were confirmed in this study population (PDE10A (rs2983511: beta = 0.112SD, p = 4.8.10(-16)), FOXE1 (rs7847663: beta = 0.223SD, p = 1.5 . 10(-20)), NR3C2 (rs9968300: beta = 0.194SD), p = 2.4 . 10(-11)), VEGFA (rs2396083: beta = 0.088SD, p = 2.2 . 10(-10))). Effect sizes...

  8. Genome-wide association studies in nephrology: using known associations for data checks.

    Science.gov (United States)

    Wuttke, Matthias; Schaefer, Franz; Wong, Craig S; Köttgen, Anna

    2015-02-01

    Prior to conducting genome-wide association studies (GWAS) of renal traits and diseases, systematic checks to ensure data integrity and analytical work flow should be conducted. Using positive controls (ie, known associations between a single-nucleotide polymorphism [SNP] and a corresponding trait) allows for identifying errors that are not apparent solely from global evaluation of summary statistics. Strong genetic control associations of chronic kidney disease (CKD), as derived from GWAS, are lacking in the non-African ancestry CKD population; thus, in this perspective, we provide examples of and considerations for using positive controls among patients with CKD. Using data from individuals with CKD who participated in the CRIC (Chronic Renal Insufficiency Cohort) Study or PediGFR (Pediatric Investigation for Genetic Factors Linked to Renal Progression) Consortium, we evaluated 2 kinds of positive control traits: traits unrelated to kidney function (bilirubin level and body height) and those related to kidney function (cystatin C and urate levels). For the former, the proportion of variance in the control trait that is explained by the control SNP is the main determinant of the strength of the observable association, irrespective of adjustment for kidney function. For the latter, adjustment for kidney function can be effective in uncovering known associations among patients with CKD. For instance, in 1,092 participants in the PediGFR Consortium, the P value for the association of cystatin C concentrations and rs911119 in the CST3 gene decreased from 2.7×10(-3) to 2.4×10(-8) upon adjustment for serum creatinine-based estimated glomerular filtration rate. In this perspective, we give recommendations for the appropriate selection of control traits and SNPs that can be used for data checks prior to conducting GWAS among patients with CKD. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  9. Genome-wide association study identifies three novel genetic markers associated with elite endurance performance

    Directory of Open Access Journals (Sweden)

    Ildus I Ahmetov

    2014-10-01

    Full Text Available To investigate the association between multiple single-nucleotide polymorphisms (SNPs, aerobic performance and elite endurance athlete status in Russians. By using GWAS approach, we examined the association between 1,140,419 SNPs and relative maximal oxygen consumption rate (VO 2 max in 80 international-level Russian endurance athletes (46 males and 34 females. To validate obtained results, we further performed case-control studies by comparing the frequencies of the most significant SNPs (with P <10 -5 -10 -8 between 218 endurance athletes and opposite cohorts (192 Russian controls, 1367 European controls, and 230 Russian power athletes. Initially, six ‘endurance alleles’ were identified showing discrete associations with VO 2 max both in males and females. Next, case-control studies resulted in remaining three SNPs ( NFIA-AS2 rs1572312, TSHR rs7144481, RBFOX1 rs7191721 associated with endurance athlete status. The C allele of the most significant SNP, rs1572312, was associated with high values of VO 2 max (males: P =0.0051; females: P =0.0005. Furthermore, the frequency of the rs1572312 C allele was significantly higher in elite endurance athletes (95.5% in comparison with non-elite endurance athletes (89.8%, P =0.0257, Russian (88.8%, P =0.007 and European (90.6%, P =0.0197 controls and power athletes (86.2%, P =0.0005. The rs1572312 SNP is located on the nuclear factor I A antisense RNA 2 ( NFIA-AS2 gene which is supposed to regulate the expression of the NFIA gene (encodes transcription factor involved in activation of erythropoiesis and repression of the granulopoiesis. Our data show that the NFIA-AS2 rs1572312, TSHR rs7144481 and RBFOX1 rs7191721 polymorphisms are associated with aerobic performance and elite endurance athlete status.

  10. Association between tobacco use in pregnancy and placenta-associated syndromes: a population-based study.

    Science.gov (United States)

    Aliyu, Muktar H; Lynch, O'Neil; Wilson, Ronee E; Alio, Amina P; Kristensen, Sibylle; Marty, Phillip J; Whiteman, Valerie E; Salihu, Hamisu M

    2011-04-01

    Cigarette smoking is an established risk factor for adverse perinatal outcomes. The purpose of this study is to examine the association between maternal smoking in pregnancy and the occurrence of placental-associated syndromes (PAS). We analyzed data from a population-based retrospective cohort of singleton deliveries that occurred in the state of Missouri from 1989 through 2005 (N = 1,224,133). The main outcome was PAS, a composite outcome defined as the occurrence of placental abruption, placenta previa, preeclampsia, small for gestational age, preterm or stillbirth. We used logistic regression models to generate adjusted odd ratios and their 95 percent confidence intervals. Non-smoking gravidas served as the referent category. The overall prevalence of prenatal smoking was 19.6%. Cigarette smoking in pregnancy was associated with the composite outcome of placental syndromes (odds ratio, 95% confidence interval = 1.59, 1.57-1.60). This association showed a dose-response relationship, with the risk of PAS increasing with increased quantity of cigarettes smoked. Similar results were observed between smoking in pregnancy and independent risks for abruption, previa, SGA, stillbirth, and preterm delivery. Maternal smoking in pregnancy is a risk factor for the development of placenta-associated syndrome. Smoking cessation interventions in pregnancy should continue to be encouraged in all maternity care settings.

  11. Physical Confirmation and Comparative Genomics of the Rat Mammary carcinoma susceptibility 3 Quantitative Trait Locus

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    Saasha Le

    2017-06-01

    Full Text Available Human breast and rat mammary cancer susceptibility are complex phenotypes where complete sets of risk associated loci remain to be identified for both species. We tested multiple congenic rat strains to physically confirm and positionally map rat Mammary carcinoma susceptibility 3 (Mcs3—a mammary cancer resistance allele previously predicted at Rattus norvegicus chromosome 1 (RNO1. The mammary cancer susceptible Wistar Furth (WF strain was the recipient, and the mammary cancer resistant Copenhagen (Cop strain was the RNO1-segment donor for congenics. Inbred WF females averaged 6.3 carcinogen-induced mammary carcinomas per rat. Two WF.Cop congenic strains averaged 2.8 and 3.4 mammary carcinomas per rat, which confirmed Mcs3 as an independently acting allele. Two other WF.Cop congenic strains averaged 6.6 and 8.1 mammary carcinomas per rat, and, thus, did not contain Mcs3. Rat Mcs3 was delimited to 27.8 Mb of RNO1 from rs8149408 to rs105131702 (RNO1:143700228-171517317 of RGSC 6.0/rn6. Human genetic variants with p values for association to breast cancer risk below 10−7 had not been reported for Mcs3 orthologous loci; however, human variants located in Mcs3-orthologous regions with potential association to risk (10−7 < p < 10−3 were listed in some population-based studies. Further, rat Mcs3 contains sequence orthologous to human 11q13/14—a region frequently amplified in female breast cancer. We conclude that Mcs3 is an independently acting mammary carcinoma resistance allele. Human population-based, genome-targeted association studies interrogating Mcs3 orthologous loci may yield novel breast cancer risk associated variants and genes.

  12. Napping is associated with increased risk of type 2 diabetes: the Guangzhou Biobank Cohort Study.

    Science.gov (United States)

    Lam, Kin-Bong Hubert; Jiang, Chao Qiang; Thomas, G Neil; Arora, Teresa; Zhang, Wei Sen; Taheri, Shahrad; Adab, Peymané; Lam, Tai Hing; Cheng, Kar Keung

    2010-03-01

    Intentional napping is very common, particularly in China. However, there are limited data regarding its potential health effects. We therefore examined the possible relationship between napping and type 2 diabetes. Cross-sectional analysis of baseline data from the Guangzhou Biobank Cohort Study. Community-based elderly association in Guangzhou, China. 19,567 Chinese men and women aged 50 years or older. Self-reported frequency of napping was obtained by questionnaire and type 2 diabetes was assessed by fasting blood glucose and/or self-reports of physician diagnosis or treatment. Participants reporting frequent naps (4-6 days/week and daily) were 42% to 52% more likely to have diabetes. The relationships remained essentially unchanged after adjustments were made for demographics, lifestyle and sleep habits, health status, adiposity, and metabolic markers (odds ratio for diabetes 1.36 [95% CI 1.17-1.57] in 4-6 days/week, 1.28 [1.15-1.44] in daily nappers). Similar associations were found between napping and impaired fasting glucose. Removal of those with potential ill health and daytime sleepiness did not alter the observed associations. Napping is associated with elevated prevalence of diabetes and impaired fasting glucose in this older Chinese sample. Our finding suggests that it is less likely that diabetes leads to daytime sleepiness. This raises the possibility that napping may increase the risk of diabetes. Confirmation by longitudinal studies is needed.

  13. Association between HIV status and Positive Prostate Biopsy in a Study of U.S. Veterans

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    Wayland Hsiao

    2009-01-01

    Full Text Available HIV infection is associated with increased incidence of malignancies, such as lymphomas and testicular cancers. We reviewed the relationship between HIV infection and prostate cancer in a contemporary series of prostate biopsy patients. The study is a retrospective analysis of consecutive prostate biopsies performed at a VA Medical Center. The indications for performing a prostate biopsy included an abnormal digital rectal examination and/or an elevated PSA. Patients were categorized according to their HIV status, biopsy results, and various demographic and clinical characteristics. Univariate and multivariate analyses compared distributions of HIV status, and various clinical and demographic characteristics. The adjusted measures of association between HIV status and positive biopsy were expressed as odds ratios (ORs and corresponding 95% confidence intervals (CI. The likelihood of positive biopsy was significantly higher among 18 HIV-positive patients compared to patients with negative HIV tests (adjusted OR = 3.9; 95% CI: 1.3–11.5. In analyses restricted to prostate cancer patients, HIV-positive patients were not different from the remaining group with respect to their prostate cancer stage, PSA level, PSA velocity, PSA density, or Gleason grade. There is an association between HIV infection and prostate biopsy positive for carcinoma in a population referred for urologic workup. Further confirmation of this association by prospective studies may impact the current screening practices in HIV patients.

  14. Unraveling the genetic etiology of adult antisocial behavior: a genome-wide association study.

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    Jorim J Tielbeek

    Full Text Available Crime poses a major burden for society. The heterogeneous nature of criminal behavior makes it difficult to unravel its causes. Relatively little research has been conducted on the genetic influences of criminal behavior. The few twin and adoption studies that have been undertaken suggest that about half of the variance in antisocial behavior can be explained by genetic factors. In order to identify the specific common genetic variants underlying this behavior, we conduct the first genome-wide association study (GWAS on adult antisocial behavior. Our sample comprised a community sample of 4816 individuals who had completed a self-report questionnaire. No genetic polymorphisms reached genome-wide significance for association with adult antisocial behavior. In addition, none of the traditional candidate genes can be confirmed in our study. While not genome-wide significant, the gene with the strongest association (p-value = 8.7×10(-5 was DYRK1A, a gene previously related to abnormal brain development and mental retardation. Future studies should use larger, more homogeneous samples to disentangle the etiology of antisocial behavior. Biosocial criminological research allows a more empirically grounded understanding of criminal behavior, which could ultimately inform and improve current treatment strategies.

  15. The association between gall bladder mucoceles and hyperlipidaemia in dogs: a retrospective case control study.

    Science.gov (United States)

    Kutsunai, M; Kanemoto, H; Fukushima, K; Fujino, Y; Ohno, K; Tsujimoto, H

    2014-01-01

    The diagnosis of gall bladder mucoceles (GM) in dogs has become increasingly frequent in veterinary medicine. Primary breed-specific hyperlipidaemia is reported in Shetland Sheepdogs and Miniature Schnauzers, breeds in which GM are known to occur more frequently than in other breeds. The objective of this study was to evaluate the association between GM and hyperlipidaemia in dogs. The study design was a retrospective case control study. Medical records of dogs diagnosed with GM at the Veterinary Medical Centre of The University of Tokyo between 1 April 2007 and 31 March 2012, were reviewed. Fifty-eight dogs with GM and a record of either serum cholesterol, triglyceride, or glucose concentrations were included in the study. Hypercholesterolaemia (15/37 cases; odds ratio [OR]: 2.92; 95% confidence interval [CI]: 1.02-8.36) and hypertriglyceridaemia (13/24 cases; OR: 3.55; 95% CI:1.12-15.91) showed significant association with GM. Pomeranians (OR: 10.69), American Cocker Spaniels (OR: 8.94), Shetland Sheepdogs (OR: 6.21), Miniature Schnauzers (OR: 5.23), and Chihuahuas (OR: 3.06) were significantly predisposed to GM. Thirty-nine out of 58 cases had at least one concurrent disease, including pancreatitis (five cases), hyperadrenocorticism (two cases), and hypothyroidism (two cases). A significant association between GM and hyperlipidaemia was confirmed, suggesting that hyperlipidaemia may play a role in the pathogenesis of GM. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. FDG-PET in pathologically confirmed spontaneous 4R-tauopathy variants.

    Science.gov (United States)

    Zalewski, Nicholas; Botha, Hugo; Whitwell, Jennifer L; Lowe, Val; Dickson, Dennis W; Josephs, Keith A

    2014-04-01

    The 4-repeat (4R)-tauopathies can be clinically heterogeneous and difficult to diagnose. An FDG-PET pattern of hypometabolism has been previously reported in clinically suspected 4R-tauopathies. Considering that pathological confirmation has not been used as inclusion criteria in these studies, however, the possibility exists that atypical cases were excluded. We studied pathologically confirmed cases of 4R-tauopathies to determine if FDG-PET patterns of hypometabolism different than those previously described exist. We identified all autopsy confirmed 4R-tauopathies with FDG-PET imaging performed between 2010 and 2013 within the Mayo Clinic database. Clinical features and FDG-PET imaging were compared to a group of normal controls. Ten patients, seven of which had autopsy-confirmed progressive supranuclear palsy (PSP), were identified. We also identified two cases with globular glial tauopathy (GGT) and one case of corticobasal degeneration (CBD). The overall predominant imaging findings included bilateral caudate hypometabolism in nine cases, mild asymmetric thalamic hypometabolism in eight, midbrain hypometabolism in seven, and bilateral hypometabolism in the supplementary motor area in seven. No differences were observed between PSP and GGT. The one CBD case had asymmetric parietal hypometabolism that was not seen in the PSP and GGT cases. As previously described, 4R-tauopathies are associated with frontal, caudate, midbrain and thalamic hypometabolism on FDG-PET. This is the first report of FDG-PET in GGT, and although our series was limited, no features distinguish GGT from PSP. There was some evidence that parietal hypometabolism may be suggestive of CBD.

  17. Risk Factors for Fatal Hyperglycaemia Confirmed by Forensic Postmortem Examination - A Nationwide Cohort in Sweden

    Science.gov (United States)

    Walz, Lotta; Jönsson, Anna K.; Zilg, Brita; Östgren, Carl Johan; Druid, Henrik

    2016-01-01

    Aims/Hypothesis The aim of this study was to identify risk factors associated with confirmed fatal hyperglycaemia, which could predispose potentially preventable deaths in individuals on glucose lowering drugs. Methods A retrospective register-based case-control study conducted on a nationwide cohort with individuals who died due to hyperglycaemia as determined by forensic postmortem examination, in Sweden August 2006 to December 2012. Vitreous glucose was used to diagnose hyperglycaemia postmortem. The forensic findings stored in the National Forensic Medicine Database were linked to nationwide registers. Cases that died due to confirmed hyperglycemia with dispensed glucose lowering drugs were identified and living controls with dispensed glucose lowering drugs were randomly selected in the Swedish prescribed drug register and matched on age and sex. Information on comorbidities, dispensed pharmaceuticals, clinical data and socioeconomic factors were obtained for cases and controls. Adjusted multiple logistic regression models were used to identify risk factors associated with fatal hyperglycaemia. Results During the study period 322 individuals, mostly males (79%) with the mean age of 53.9 years (SD.± 14) died due to confirmed hyperglycaemia. Risk factors for fatal hyperglycaemia included; insulin treatment (OR = 4.40; 95%CI,1.96, 9.85), poor glycaemic control (OR = 2.00 95%CI,1.23, 3.27), inadequate refill-adherence before death (OR = 3.87; 95%CI,1.99, 7.53), microvascular disease (OR = 3.26; 95% CI, 1.84, 5.79), psychiatric illness (OR = 2.30; 95% CI,1.32, 4.01), substance abuse (OR = 8.85; 95%CI,2.34, 35.0) and/or living alone (OR = 2.25; 95%CI,1.21, 4.18). Conclusions/Interpretation Our results demonstrate the importance of clinical attention to poor glycaemic control in subjects with psychosocial problems since it may indicate serious non-adherence, which consequently could lead to fatal hyperglycaemia. PMID:27768720

  18. EHR-based phenome wide association study in pancreatic cancer.

    Science.gov (United States)

    Adamusiak, Tomasz; Shimoyama, Mary

    2014-01-01

    Pancreatic cancer is one of the most common causes of cancer-related deaths in the United States, it is difficult to detect early and typically has a very poor prognosis. We present a novel method of large-scale clinical hypothesis generation based on phenome wide association study performed using Electronic Health Records (EHR) in a pancreatic cancer cohort. The study population consisted of 1,154 patients diagnosed with malignant neoplasm of pancreas seen at The Froedtert & The Medical College of Wisconsin academic medical center between the years 2004 and 2013. We evaluated death of a patient as the primary clinical outcome and tested its association with the phenome, which consisted of over 2.5 million structured clinical observations extracted out of the EHR including labs, medications, phenotypes, diseases and procedures. The individual observations were encoded in the EHR using 6,617 unique ICD-9, CPT-4, LOINC, and RxNorm codes. We remapped this initial code set into UMLS concepts and then hierarchically expanded to support generalization into the final set of 10,164 clinical concepts, which formed the final phenome. We then tested all possible pairwise associations between any of the original 10,164 concepts and death as the primary outcome. After correcting for multiple testing and folding back (generalizing) child concepts were appropriate, we found 231 concepts to be significantly associated with death in the study population. With the abundance of structured EHR data, phenome wide association studies combined with knowledge engineering can be a viable method of rapid hypothesis generation.

  19. A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease.

    Science.gov (United States)

    Amin Al Olama, Ali; Kote-Jarai, Zsofia; Schumacher, Fredrick R; Wiklund, Fredrik; Berndt, Sonja I; Benlloch, Sara; Giles, Graham G; Severi, Gianluca; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Hunter, David J; Henderson, Brian E; Thun, Michael J; Gaziano, Michael; Giovannucci, Edward L; Siddiq, Afshan; Travis, Ruth C; Cox, David G; Canzian, Federico; Riboli, Elio; Key, Timothy J; Andriole, Gerald; Albanes, Demetrius; Hayes, Richard B; Schleutker, Johanna; Auvinen, Anssi; Tammela, Teuvo L J; Weischer, Maren; Stanford, Janet L; Ostrander, Elaine A; Cybulski, Cezary; Lubinski, Jan; Thibodeau, Stephen N; Schaid, Daniel J; Sorensen, Karina D; Batra, Jyotsna; Clements, Judith A; Chambers, Suzanne; Aitken, Joanne; Gardiner, Robert A; Maier, Christiane; Vogel, Walther; Dörk, Thilo; Brenner, Hermann; Habuchi, Tomonori; Ingles, Sue; John, Esther M; Dickinson, Joanne L; Cannon-Albright, Lisa; Teixeira, Manuel R; Kaneva, Radka; Zhang, Hong-Wei; Lu, Yong-Jie; Park, Jong Y; Cooney, Kathleen A; Muir, Kenneth R; Leongamornlert, Daniel A; Saunders, Edward; Tymrakiewicz, Malgorzata; Mahmud, Nadiya; Guy, Michelle; Govindasami, Koveela; O'Brien, Lynne T; Wilkinson, Rosemary A; Hall, Amanda L; Sawyer, Emma J; Dadaev, Tokhir; Morrison, Jonathan; Dearnaley, David P; Horwich, Alan; Huddart, Robert A; Khoo, Vincent S; Parker, Christopher C; Van As, Nicholas; Woodhouse, Christopher J; Thompson, Alan; Dudderidge, Tim; Ogden, Chris; Cooper, Colin S; Lophatonanon, Artitaya; Southey, Melissa C; Hopper, John L; English, Dallas; Virtamo, Jarmo; Le Marchand, Loic; Campa, Daniele; Kaaks, Rudolf; Lindstrom, Sara; Diver, W Ryan; Gapstur, Susan; Yeager, Meredith; Cox, Angela; Stern, Mariana C; Corral, Roman; Aly, Markus; Isaacs, William; Adolfsson, Jan; Xu, Jianfeng; Zheng, S Lilly; Wahlfors, Tiina; Taari, Kimmo; Kujala, Paula; Klarskov, Peter; Nordestgaard, Børge G; Røder, M Andreas; Frikke-Schmidt, Ruth; Bojesen, Stig E; FitzGerald, Liesel M; Kolb, Suzanne; Kwon, Erika M; Karyadi, Danielle M; Orntoft, Torben Falck; Borre, Michael; Rinckleb, Antje; Luedeke, Manuel; Herkommer, Kathleen; Meyer, Andreas; Serth, Jürgen; Marthick, James R; Patterson, Briony; Wokolorczyk, Dominika; Spurdle, Amanda; Lose, Felicity; McDonnell, Shannon K; Joshi, Amit D; Shahabi, Ahva; Pinto, Pedro; Santos, Joana; Ray, Ana; Sellers, Thomas A; Lin, Hui-Yi; Stephenson, Robert A; Teerlink, Craig; Muller, Heiko; Rothenbacher, Dietrich; Tsuchiya, Norihiko; Narita, Shintaro; Cao, Guang-Wen; Slavov, Chavdar; Mitev, Vanio; Chanock, Stephen; Gronberg, Henrik; Haiman, Christopher A; Kraft, Peter; Easton, Douglas F; Eeles, Rosalind A

    2013-01-15

    Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one-third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four GWAS including 5953 cases of aggressive PrCa and 11 463 controls (men without PrCa). We computed association tests for approximately 2.6 million SNPs and followed up the most significant SNPs by genotyping 49 121 samples in 29 studies through the international PRACTICAL and BPC3 consortia. We not only confirmed the association of a PrCa susceptibility locus, rs11672691 on chromosome 19, but also showed an association with aggressive PrCa [odds ratio = 1.12 (95% confidence interval 1.03-1.21), P = 1.4 × 10(-8)]. This report describes a genetic variant which is associated with aggressive PrCa, which is a type of PrCa associated with a poorer prognosis.

  20. Methods for Analyzing Multivariate Phenotypes in Genetic Association Studies

    Directory of Open Access Journals (Sweden)

    Qiong Yang

    2012-01-01

    Full Text Available Multivariate phenotypes are frequently encountered in genetic association studies. The purpose of analyzing multivariate phenotypes usually includes discovery of novel genetic variants of pleiotropy effects, that is, affecting multiple phenotypes, and the ultimate goal of uncovering the underlying genetic mechanism. In recent years, there have been new method development and application of existing statistical methods to such phenotypes. In this paper, we provide a review of the available methods for analyzing association between a single marker and a multivariate phenotype consisting of the same type of components (e.g., all continuous or all categorical or different types of components (e.g., some are continuous and others are categorical. We also reviewed causal inference methods designed to test whether the detected association with the multivariate phenotype is truly pleiotropy or the genetic marker exerts its effects on some phenotypes through affecting the others.

  1. Genome-Wide Association Study of Down Syndrome-Associated Atrioventricular Septal Defects.

    Science.gov (United States)

    Ramachandran, Dhanya; Zeng, Zhen; Locke, Adam E; Mulle, Jennifer G; Bean, Lora J H; Rosser, Tracie C; Dooley, Kenneth J; Cua, Clifford L; Capone, George T; Reeves, Roger H; Maslen, Cheryl L; Cutler, David J; Feingold, Eleanor; Sherman, Stephanie L; Zwick, Michael E

    2015-07-20

    The goal of this study was to identify the contribution of common genetic variants to Down syndrome-associated atrioventricular septal defect, a severe heart abnormality. Compared with the euploid population, infants with Down syndrome, or trisomy 21, have a 2000-fold increased risk of presenting with atrioventricular septal defects. The cause of this increased risk remains elusive. Here we present data from the largest heart study conducted to date on a trisomic background by using a carefully characterized collection of individuals from extreme ends of the phenotypic spectrum. We performed a genome-wide association study using logistic regression analysis on 452 individuals with Down syndrome, consisting of 210 cases with complete atrioventricular septal defects and 242 controls with structurally normal hearts. No individual variant achieved genome-wide significance. We identified four disomic regions (1p36.3, 5p15.31, 8q22.3, and 17q22) and two trisomic regions on chromosome 21 (around PDXK and KCNJ6 genes) that merit further investigation in large replication studies. Our data show that a few common genetic variants of large effect size (odds ratio >2.0) do not account for the elevated risk of Down syndrome-associated atrioventricular septal defects. Instead, multiple variants of low-to-moderate effect sizes may contribute to this elevated risk, highlighting the complex genetic architecture of atrioventricular septal defects even in the highly susceptible Down syndrome population. Copyright © 2015 Ramachandran et al.

  2. Genetic association study of synphilin-1 in idiopathic Parkinson's disease

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    Farrer Matthew J

    2008-03-01

    Full Text Available Abstract Background Post-mortem Lewy body and Lewy neuritic inclusions are a defining feature of Parkinson's disease (PD and dementia with Lewy bodies (DLB. With the discovery of missense and multiplication mutations in the alpha-synuclein gene (SNCA in familial parkinsonism, Lewy inclusions were found to stain intensely with antibodies raised against the protein. Yeast-two-hybrid studies identified synphilin-1 as an interacting partner of alpha-synuclein, and both proteins show co-immunolocalization in a subset of Lewy body inclusions. In the present study, we have investigated whether common variability in synphilin-1, including coding substitutions are genetically associated with disease pathogenesis. Methods We screened the synphilin-1 gene for 11 single nucleotide polymorphisms (SNPs in 300 affected subjects with idiopathic Parkinson's disease and 412 healthy controls. Six of these were rare variants including five previously identified amino acid substitutions that were chosen in a direct approach for association of rare disease causing mutations. An additional five highly heterozygous SNPs were chosen for an indirect association approach including haplotype analysis, based on the assumption that any disease causing mutations might be in linkage disequilibrium with the SNPs selected. We also genotyped a microsatellite marker (D5S2950 within intron 6 of the gene and five additional microsatellites clustered downstream of the 5p23.1-23.3 synphilin-1 locus. Genome-wide linkage analysis, in a number of independent studies, has previously highlighted suggestive linkage to PD in this region of chromosome 5. Results Screening of previously known amino acid substitutions in the synphilin-1 gene, identified the C1861>T (R621C substitution in four patients (chromosomes n = 600 and 10 control subjects (chromosomes n = 824, whereas the G2125>C (E706Q substitution was detected in one patient and four control subject, suggesting both these substitutions

  3. Higher Caffeinated Coffee Intake Is Associated with Reduced Malignant Melanoma Risk: A Meta-Analysis Study

    Science.gov (United States)

    Liu, Jibin; Shen, Biao; Shi, Minxin; Cai, Jing

    2016-01-01

    Background Several epidemiological studies have determined the associations between coffee intake level and skin cancer risk; however, the results were not yet conclusive. Herein, we conducted a systematic review and meta-analysis of the cohort and case-control studies for the association between coffee intake level and malignant melanoma (MM) risk. Methods Studies were identified through searching the PubMed and MEDLINE databases (to November, 2015). Study-specific risk estimates were pooled under the random-effects model. Results Two case-control studies (846 MM patients and 843 controls) and five cohort studies (including 844,246 participants and 5,737 MM cases) were identified. For caffeinated coffee, the pooled relative risk (RR) of MM was 0.81 [95% confidential interval (95% CI) = 0.68–0.97; P-value for Q-test = 0.003; I2 = 63.5%] for those with highest versus lowest quantity of intake. In the dose-response analysis, the RR of MM was 0.955 (95% CI = 0.912–0.999) for per 1 cup/day increment of caffeinated coffee consumption and linearity dose-response association was found (P-value for nonlinearity = 0.326). Strikingly, no significant association was found between the decaffeinated coffee intake level and MM risk (pooled RR = 0.92, 95% CI = 0.81–1.05; P-value for Q-test = 0.967; I2 = 0%; highest versus lowest quantity of intake). Conclusions This meta-analysis suggested that caffeinated coffee might have chemo-preventive effects against MM but not decaffeinated coffee. However, larger prospective studies and the intervention studies are warranted to confirm these findings. PMID:26816289

  4. Higher Caffeinated Coffee Intake Is Associated with Reduced Malignant Melanoma Risk: A Meta-Analysis Study.

    Directory of Open Access Journals (Sweden)

    Jibin Liu

    Full Text Available Several epidemiological studies have determined the associations between coffee intake level and skin cancer risk; however, the results were not yet conclusive. Herein, we conducted a systematic review and meta-analysis of the cohort and case-control studies for the association between coffee intake level and malignant melanoma (MM risk.Studies were identified through searching the PubMed and MEDLINE databases (to November, 2015. Study-specific risk estimates were pooled under the random-effects model.Two case-control studies (846 MM patients and 843 controls and five cohort studies (including 844,246 participants and 5,737 MM cases were identified. For caffeinated coffee, the pooled relative risk (RR of MM was 0.81 [95% confidential interval (95% CI = 0.68-0.97; P-value for Q-test = 0.003; I2 = 63.5%] for those with highest versus lowest quantity of intake. In the dose-response analysis, the RR of MM was 0.955 (95% CI = 0.912-0.999 for per 1 cup/day increment of caffeinated coffee consumption and linearity dose-response association was found (P-value for nonlinearity = 0.326. Strikingly, no significant association was found between the decaffeinated coffee intake level and MM risk (pooled RR = 0.92, 95% CI = 0.81-1.05; P-value for Q-test = 0.967; I2 = 0%; highest versus lowest quantity of intake.This meta-analysis suggested that caffeinated coffee might have chemo-preventive effects against MM but not decaffeinated coffee. However, larger prospective studies and the intervention studies are warranted to confirm these findings.

  5. Structural confirmation of oligosaccharides newly isolated from sugar beet molasses

    Directory of Open Access Journals (Sweden)

    Abe Tatsuya

    2012-08-01

    Full Text Available Abstract Background Sugar beet molasses is a viscous by-product of the processing of sugar beets into sugar. The molasses is known to contain sucrose and raffinose, a typical trisaccharide, with a well-established structure. Although sugar beet molasses contains various other oligosaccharides as well, the structures of those oligosaccharides have not been examined in detail. The purpose of this study was isolation and structural confirmation of these other oligosaccharides found in sugar beet molasses. Results Four oligosaccharides were newly isolated from sugar beet molasses using high-performance liquid chromatography (HPLC and carbon-Celite column chromatography. Structural confirmation of the saccharides was provided by methylation analysis, matrix-assisted laser desorption/ionaization time of flight mass spectrometry (MALDI-TOF-MS, and nuclear magnetic resonance (NMR measurements. Conclusion The following oligosaccharides were identified in sugar beet molasses: β-D-galactopyranosyl-(1- > 6-β-D-fructofuranosyl-(2 1-α-D-glucopyranoside (named β-planteose, α-D-galactopyranosyl-(1- > 1-β-D-fructofuranosyl-(2 1-α-D-glucopyranoside (named1-planteose, α-D-glucopyranosyl-(1- > 6-α-D-glucopyranosyl-(1 2-β-D-fructofuranoside (theanderose, and β-D-glucopyranosyl-(1- > 3-α-D-glucopyranosyl-(1 2-β-D-fructofuranoside (laminaribiofructose. 1-planteose and laminaribiofructose were isolated from natural sources for the first time.

  6. Sex differences in step count-blood pressure association: a preliminary study in type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Priya Manjoo

    Full Text Available BACKGROUND: Walking and cardiovascular mortality are inversely associated in type 2 diabetes, but few studies have objectively measured associations of walking with individual cardiovascular risk factors. Such information would be useful for "dosing" daily steps in clinical practice. This study aimed to quantify decrements in blood pressure and glycated hemoglobin (A1C per 1,000 daily step increments. METHODOLOGY/PRINCIPAL FINDINGS: Two hundred and one subjects with type 2 diabetes underwent assessments of step counts (pedometer-measured, blood pressure, A1C and anthropometric parameters. Due to missing data, the final analysis was conducted on 83 women and 102 men, with a mean age of 60 years. Associations of daily steps with blood pressure and A1C were evaluated using sex-specific multivariate linear regression models (adjusted for age, ethnicity, and BMI. Potential sex differences were confirmed in a combined model (women and men with interaction terms. Mean values for daily steps, blood pressure, A1C and BMI were 5,357 steps/day; 137/80 mm Hg; 7.7% and 30.4 kg/m(2 respectively. A 1,000 daily step increment among women was associated with a -2.6 (95% CI: -4.1 to -1.1 mm Hg change in systolic and a -1.4 (95% CI: -2.2 to -0.6 mm Hg change in diastolic blood pressure. Among men, corresponding changes were -0.7 (95% CI: -2.1 to 0.7 and -0.6 (95% CI: -1.4 to 0.3 mm Hg, respectively. Sex differences were confirmed in combined models. Step counts and A1C did not demonstrate clinically important associations. CONCLUSIONS/SIGNIFICANCE: A 1,000 steps/day increment is associated with important blood pressure decrements among women with type 2 diabetes but the data were inconclusive among men. Targeted "dose increments" of 1,000 steps/day in women may lead to measurable blood pressure reductions. This information may be of potential use in the titration or "dosing" of daily steps. No associations were found between step count increments and A1C.

  7. Liposomes- and ethosomes-associated distamycins: a comparative study.

    Science.gov (United States)

    Cortesi, Rita; Romagnoli, Romeo; Drechsler, Markus; Menegatti, Enea; Zaid, Abdel N; Ravani, Laura; Esposito, Elisabetta

    2010-12-01

    The present article describes a comparative study of the performances of liposomes and ethosomes as specialized delivery systems for distamycin A (DA) and two of its derivatives. Liposomes and ethosomes were prepared by classical methods, extruded through polycarbonate filters, and characterized in terms of dimensions, morphology, and encapsulation efficiency. It was found that DA was associated with vesicles (either liposomes or ethosomes) by around 16.0%, while both derivatives of DA showed a percentage of association around 80% in the case of liposomes and around 50% in the case of ethosomes. In vitro antiproliferative activity experiments performed on cultured human and mouse leukemic cells demonstrated that vesicles were able to increase the activity of both derivatives of DA. In addition, it was demonstrated that the aging of both liposomes- and ethosomes-associated distamycin suspensions did not heavily influence the vesicle size, while all samples showed a relevant drug leakage with time. Moreover, according to the different physicochemical characteristics of DA and its derivatives (i.e., log P), vesicle-associated DA showed the highest loss of drug with respect to both its derivatives. In conclusion, the enhancement of drug activity expressed by these specialized delivery systems-associated DD could be interesting to obtain an efficient therapeutic effect aimed at reducing or minimizing toxic effects occurring with distamycins administration.

  8. Neuroimaging findings in children with retinopathy-confirmed cerebral malaria

    Energy Technology Data Exchange (ETDEWEB)

    Potchen, Michael J. [Michigan State University, Department of Radiology, 184 Radiology Building, East Lansing, MI 48824-1303 (United States)], E-mail: mjp@rad.msu.edu; Birbeck, Gretchen L. [Michigan State University, International Neurologic and Psychiatric Epidemiology Program, 324 West Fee Hall, East Lansing, MI 48824 (United States)], E-mail: Gretchen.Birbeck@ht.msu.edu; DeMarco, J. Kevin [Michigan State University, Department of Radiology, 184 Radiology Building, East Lansing, MI 48824-1303 (United States)], E-mail: jkd@rad.msu.edu; Kampondeni, Sam D. [University of Malawi, Department of Radiology, Queen Elizabeth Central Hospital, Blantyre (Malawi)], E-mail: kamponde@msu.edu; Beare, Nicholas [St. Paul' s Eye Unit, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP (United Kingdom)], E-mail: nbeare@btinternet.com; Molyneux, Malcolm E. [Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine (Malawi); School of Tropical Medicine, University of Liverpool, Liverpool (United Kingdom)], E-mail: mmolyneux999@google.com; Taylor, Terrie E. [Michigan State University, College of Osteopathic Medicine, B309-B West Fee Hall, East Lansing, MI 48824 (United States); University of Malawi, College of Medicine, Blantyre Malaria Project, Blantyre (Malawi)], E-mail: taylort@msu.edu

    2010-04-15

    Purpose: To describe brain CT findings in retinopathy-confirmed, paediatric cerebral malaria. Materials and methods: In this outcomes study of paediatric cerebral malaria, a subset of children with protracted coma during initial presentation was scanned acutely. Survivors experiencing adverse neurological outcomes also underwent a head CT. All children had ophthalmological examination to confirm the presence of the retinopathy specific for cerebral malaria. Independent interpretation of CT images was provided by two neuroradiologists. Results: Acute brain CT findings in three children included diffuse oedema with obstructive hydrocephalus (2), acute cerebral infarctions in multiple large vessel distributions with secondary oedema and herniation (1), and oedema of thalamic grey matter (1). One child who was reportedly normal prior to admission had parenchymal atrophy suggestive of pre-existing CNS injury. Among 56 survivors (9-84 months old), 15 had adverse neurologic outcomes-11/15 had a follow-up head CT, 3/15 died and 1/15 refused CT. Follow-up head CTs obtained 7-18 months after the acute infection revealed focal and multifocal lobar atrophy correlating to regions affected by focal seizures during the acute infection (5/11). Other findings were communicating hydrocephalus (2/11), vermian atrophy (1/11) and normal studies (3/11). Conclusions: The identification of pre-existing imaging abnormalities in acute cerebral malaria suggests that population-based studies are required to establish the rate and nature of incidental imaging abnormalities in Malawi. Children with focal seizures during acute cerebral malaria developed focal cortical atrophy in these regions at follow-up. Longitudinal studies are needed to further elucidate mechanisms of CNS injury and death in this common fatal disease.

  9. Association between fat mass, lean mass, and bone loss: the Dubbo Osteoporosis Epidemiology Study.

    Science.gov (United States)

    Yang, S; Center, J R; Eisman, J A; Nguyen, T V

    2015-04-01

    Lower body fat mass is a risk factor for bone loss at lumbar spine in postmenopausal women, but not in men. Body lean mass and fat mass were not associated with femoral neck bone loss in either gender. Bone density and body mass are closely associated. Whole body lean mass (LM) and fat mass (FM) together account for approximately 95 % of body mass. Bone loss is associated with loss of body mass but which of the components of body mass (FM or LM) is related to bone loss is not well understood. Therefore, in this study, we sought to assess whether baseline FM or LM has predictive value for future relative rate of bone mineral density (BMD) changes (%/year). The present population-based cohort study was part of the ongoing Dubbo Osteoporosis Epidemiology Study (DOES). BMD, FM, and LM were measured with dual energy X-ray absorptiometry (GE-LUNAR Corp, Madison, WI). BMD measurements were taken in approximately every 2 years between 2000 and 2010. We only included the participants with at least two BMD measurements at the femoral neck and lumbar spine. In total, 717 individuals (204 men and 513 women) aged 50 years or older were studied. Rate of bone loss at femoral neck and lumbar spine was faster in women than in men (all P loss at lumbar spine. This magnitude of association remained virtually unchanged after adjusting for LM and/or other covariates (P = 0.03). After adjusting for covariates, variation of FM accounted for ∼1.5 % total variation in lumbar spine bone loss. However, there was no significant association between FM and change in femoral neck BMD in either men or women. Lower FM was an independent but modest risk factor for greater bone loss at the lumbar spine in women but not in men. If further studies confirm our findings, FM can help predict lumbar spine bone loss in women.

  10. Genome wide association study (GWAS) of Chagas cardiomyopathy in Trypanosoma cruzi seropositive subjects.

    Science.gov (United States)

    Deng, Xutao; Sabino, Ester C; Cunha-Neto, Edecio; Ribeiro, Antonio L; Ianni, Barbara; Mady, Charles; Busch, Michael P; Seielstad, Mark

    2013-01-01

    Familial aggregation of Chagas cardiac disease in T. cruzi-infected persons suggests that human genetic variation may be an important determinant of disease progression. To perform a GWAS using a well-characterized cohort to detect single nucleotide polymorphisms (SNPs) and genes associated with cardiac outcomes. A retrospective cohort study was developed by the NHLBI REDS-II program in Brazil. Samples were collected from 499 T. cruzi seropositive blood donors who had donated between 1996 and 2002, and 101 patients with clinically diagnosed Chagas cardiomyopathy. In 2008-2010, all subjects underwent a complete medical examination. After genotype calling, quality control filtering with exclusion of 20 cases, and imputation of 1,000 genomes variants; association analysis was performed for 7 cardiac and parasite related traits, adjusting for population stratification. The cohort showed a wide range of African, European, and modest Native American admixture proportions, consistent with the recent history of Brazil. No SNPs were found to be highly (P<10(-8)) associated with cardiomyopathy. The two mostly highly associated SNPs for cardiomyopathy (rs4149018 and rs12582717; P-values <10(-6)) are located on Chromosome 12p12.2 in the SLCO1B1 gene, a solute carrier family member. We identified 44 additional genic SNPs associated with six traits at P-value <10(-6): Ejection Fraction, PR, QRS, QT intervals, antibody levels by EIA, and parasitemia by PCR. This GWAS identified suggestive SNPs that may impact the risk of progression to cardiomyopathy. Although this Chagas cohort is the largest examined by GWAS to date, (580 subjects), moderate sample size may explain in part the limited number of significant SNP variants. Enlarging the current sample through expanded cohorts and meta-analyses, and targeted studies of candidate genes, will be required to confirm and extend the results reported here. Future studies should also include exposed seronegative controls to investigate

  11. Nonallergic rhinitis and its association with smoking and lower airway disease: A general population study.

    Science.gov (United States)

    Håkansson, Kåre; von Buchwald, Christian; Thomsen, Simon F; Thyssen, Jacob P; Backer, Vibeke; Linneberg, Allan

    2011-01-01

    The cause of nonallergic rhinitis (NAR) and its relation to lower airway disease remains unclear. The purpose of this study was to perform a descriptive analysis of the occurrence of rhinitis in a Danish general population with focus on NAR and its association with smoking and lower airway disease. A population-based, cross-sectional study conducted in Copenhagen, Denmark was performed. A random sample from the general population (n = 7931; age, 18-69 years) was invited to a general health examination including measurements of serum-specific immunoglobulin E (IgE) to common aeroallergens; 3471 (44%) persons were accepted. For further analysis, we divided the population into the following groups: (I) negative specific IgE and no rhinitis (controls); (II) negative specific IgE and rhinitis (NAR); (III) positive specific IgE and rhinitis (allergic rhinitis [AR]); and (IV) positive specific IgE but no rhinitis (sensitized). We found that NAR was associated with asthma (odds ratio [OR] = 2.51 [1.87-3.37]); chronic bronchitis (OR = 2.27 [1.85-2.79]); current smoking (>15 g/day; OR = 1.57 [1.18-2.08]); lower forced expiratory volume in 1 second/forced vital capacity (FEV(1)/FVC) ratios and reduced FEV(1) values. The association with chronic bronchitis was stronger in NAR than in AR, whereas the opposite was true for asthma. FEV(1)/FVC of <70% was not significantly associated to any group. This epidemiological study indicates that both asthma and chronic bronchitis are important comorbidities in NAR confirming the "united airway" hypothesis, and that smoking might be a significant modulator of disease. Although NAR was significantly associated with poor lung function, no significant association with chronic obstructive pulmonary disease was shown.

  12. Genome-wide association study of sporadic brain arteriovenous malformations.

    Science.gov (United States)

    Weinsheimer, Shantel; Bendjilali, Nasrine; Nelson, Jeffrey; Guo, Diana E; Zaroff, Jonathan G; Sidney, Stephen; McCulloch, Charles E; Al-Shahi Salman, Rustam; Berg, Jonathan N; Koeleman, Bobby P C; Simon, Matthias; Bostroem, Azize; Fontanella, Marco; Sturiale, Carmelo L; Pola, Roberto; Puca, Alfredo; Lawton, Michael T; Young, William L; Pawlikowska, Ludmila; Klijn, Catharina J M; Kim, Helen

    2016-09-01

    The pathogenesis of sporadic brain arteriovenous malformations (BAVMs) remains unknown, but studies suggest a genetic component. We estimated the heritability of sporadic BAVM and performed a genome-wide association study (GWAS) to investigate association of common single nucleotide polymorphisms (SNPs) with risk of sporadic BAVM in the international, multicentre Genetics of Arteriovenous Malformation (GEN-AVM) consortium. The Caucasian discovery cohort included 515 BAVM cases and 1191 controls genotyped using Affymetrix genome-wide SNP arrays. Genotype data were imputed to 1000 Genomes Project data, and well-imputed SNPs (>0.01 minor allele frequency) were analysed for association with BAVM. 57 top BAVM-associated SNPs (51 SNPs with pJAG1 and BNC2. Of the 6 candidate SNPs, 2 in ACVRL1 and MMP3 had a nominal p<0.05 in the replication cohort. We performed the first GWAS of sporadic BAVM in the largest BAVM cohort assembled to date. No GWAS SNPs were replicated, suggesting that common SNPs do not contribute strongly to BAVM susceptibility. However, heritability estimates suggest a modest but significant genetic contribution. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  13. Association study of 182 candidate genes in anorexia nervosa.

    Science.gov (United States)

    Pinheiro, Andrea Poyastro; Bulik, Cynthia M; Thornton, Laura M; Sullivan, Patrick F; Root, Tammy L; Bloss, Cinnamon S; Berrettini, Wade H; Schork, Nicholas J; Kaye, Walter H; Bergen, Andrew W; Magistretti, Pierre; Brandt, Harry; Crawford, Steve; Crow, Scott; Fichter, Manfred M; Goldman, David; Halmi, Katherine A; Johnson, Craig; Kaplan, Allan S; Keel, Pamela K; Klump, Kelly L; La Via, Maria; Mitchell, James E; Strober, Michael; Rotondo, Alessandro; Treasure, Janet; Woodside, D Blake

    2010-07-01

    We performed association studies with 5,151 SNPs that were judged as likely candidate genetic variations conferring susceptibility to anorexia nervosa (AN) based on location under reported linkage peaks, previous results in the literature (182 candidate genes), brain expression, biological plausibility, and estrogen responsivity. We employed a case-control design that tested each SNP individually as well as haplotypes derived from these SNPs in 1,085 case individuals with AN diagnoses and 677 control individuals. We also performed separate association analyses using three increasingly restrictive case definitions for AN: all individuals with any subtype of AN (All AN: n = 1,085); individuals with AN with no binge eating behavior (AN with No Binge Eating: n = 687); and individuals with the restricting subtype of AN (Restricting AN: n = 421). After accounting for multiple comparisons, there were no statistically significant associations for any individual SNP or haplotype block with any definition of illness. These results underscore the importance of large samples to yield appropriate power to detect genotypic differences in individuals with AN and also motivate complementary approaches involving Genome-Wide Association (GWA) studies, Copy Number Variation (CNV) analyses, sequencing-based rare variant discovery assays, and pathway-based analysis in order to make up for deficiencies in traditional candidate gene approaches to AN. (c) 2010 Wiley-Liss, Inc.

  14. Genome-wide association study identifies 74 loci associated with educational attainment

    DEFF Research Database (Denmark)

    Okbay, Aysu; P. Beauchamp, Jonathan; Alan Fontana, Mark

    2016-01-01

    Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals1. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends......, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases....

  15. Aortic aneurysm association with SLE - a case-control study.

    Science.gov (United States)

    Guy, A; Tiosano, S; Comaneshter, D; Tekes-Manova, D; Shovman, O; Cohen, A D; Amital, H

    2016-08-01

    Aortic aneurysm is a life threatening cardiovascular complication in patients with systemic lupus erythematosus (SLE).The purpose of this study was to investigate the association between SLE and occurrence of aortic aneurysms. Patients with SLE were compared with age- and sex-matched controls regarding the proportion of aortic aneurysm in a case-control study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services. The study included 5018 patients with SLE and 25,090 age- and sex-matched controls. The proportion of aortic aneurysm in patients with SLE was increased compared with the proportion in controls (0.6% and 0.1%, respectively, p SLE was associated with the coexistence of aortic aneurysms (odds ratio 2.06, 95% confidence interval 1.21-3.51). Patients with SLE have a higher proportion of aortic aneurysms as compared with matched controls. Therefore, physicians treating patients with SLE should be aware of this life threatening association. © The Author(s) 2016.

  16. Association studies in common endocrine diseases (review article

    Directory of Open Access Journals (Sweden)

    Akrami SM

    2007-05-01

    Full Text Available Our understanding of the pathogenesis of endocrine disorders increase rapidly by genetic studies at the molecular level. Common endocrine disorders such as diabetes mellitus, obesity, osteoporosis, dyslipidemia and cancer follow the multifactorial model in the genetic aspect. This review tries to clarify the approach in molecular studies of such diseases for clinicians in different specialties. How to evaluate a possible association between a single nucleotide polymorphism and an endocrinopathy or its complication is the main concern of this review. Two approaches for gene mapping will be discussed as well as main challenges regarding each approach. All such genetic studies ideally include some test of the association between genome sequence variation and the phenotype of interest such as the trait itself, the presence of a given complication, or measures of some endocrinopathy-related intermediate trait. Despite different advances in this analysis, there are major concerns regarding the overall performance and robustness of genetic association studies. By using powerful new high-throughput methods, further insights to molecular basis of such endocrine disorders can be expected. Close correlation between geneticists and clinicians can effectively bridge between basic sciences and clinical investigations.

  17. Genome-wide association study of pathological gambling.

    Science.gov (United States)

    Lang, M; Leménager, T; Streit, F; Fauth-Bühler, M; Frank, J; Juraeva, D; Witt, S H; Degenhardt, F; Hofmann, A; Heilmann-Heimbach, S; Kiefer, F; Brors, B; Grabe, H-J; John, U; Bischof, A; Bischof, G; Völker, U; Homuth, G; Beutel, M; Lind, P A; Medland, S E; Slutske, W S; Martin, N G; Völzke, H; Nöthen, M M; Meyer, C; Rumpf, H-J; Wurst, F M; Rietschel, M; Mann, K F

    2016-08-01

    Pathological gambling is a behavioural addiction with negative economic, social, and psychological consequences. Identification of contributing genes and pathways may improve understanding of aetiology and facilitate therapy and prevention. Here, we report the first genome-wide association study of pathological gambling. Our aims were to identify pathways involved in pathological gambling, and examine whether there is a genetic overlap between pathological gambling and alcohol dependence. Four hundred and forty-five individuals with a diagnosis of pathological gambling according to the Diagnostic and Statistical Manual of Mental Disorders were recruited in Germany, and 986 controls were drawn from a German general population sample. A genome-wide association study of pathological gambling comprising single marker, gene-based, and pathway analyses, was performed. Polygenic risk scores were generated using data from a German genome-wide association study of alcohol dependence. No genome-wide significant association with pathological gambling was found for single markers or genes. Pathways for Huntington's disease (P-value=6.63×10(-3)); 5'-adenosine monophosphate-activated protein kinase signalling (P-value=9.57×10(-3)); and apoptosis (P-value=1.75×10(-2)) were significant. Polygenic risk score analysis of the alcohol dependence dataset yielded a one-sided nominal significant P-value in subjects with pathological gambling, irrespective of comorbid alcohol dependence status. The present results accord with previous quantitative formal genetic studies which showed genetic overlap between non-substance- and substance-related addictions. Furthermore, pathway analysis suggests shared pathology between Huntington's disease and pathological gambling. This finding is consistent with previous imaging studies. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Translating genome wide association study results to associations among common diseases: in silico study with an electronic medical record.

    Science.gov (United States)

    Anand, Vibha; Rosenman, Marc B; Downs, Stephen M

    2013-09-01

    To develop a map of disease associations exclusively using two publicly available genetic sources: the catalog of single nucleotide polymorphisms (SNPs) from the HapMap, and the catalog of Genome Wide Association Studies (GWAS) from the NHGRI, and to evaluate it with a large, long-standing electronic medical record (EMR). A computational model, In Silico Bayesian Integration of GWAS (IsBIG), was developed to learn associations among diseases using a Bayesian network (BN) framework, using only genetic data. The IsBIG model (I-Model) was re-trained using data from our EMR (M-Model). Separately, another clinical model (C-Model) was learned from this training dataset. The I-Model was compared with both the M-Model and the C-Model for power to discriminate a disease given other diseases using a test dataset from our EMR. Area under receiver operator characteristics curve was used as a performance measure. Direct associations between diseases in the I-Model were also searched in the PubMed database and in classes of the Human Disease Network (HDN). On the basis of genetic information alone, the I-Model linked a third of diseases from our EMR. When compared to the M-Model, the I-Model predicted diseases given other diseases with 94% specificity, 33% sensitivity, and 80% positive predictive value. The I-Model contained 117 direct associations between diseases. Of those associations, 20 (17%) were absent from the searches of the PubMed database; one of these was present in the C-Model. Of the direct associations in the I-Model, 7 (35%) were absent from disease classes of HDN. Using only publicly available genetic sources we have mapped associations in GWAS to a human disease map using an in silico approach. Furthermore, we have validated this disease map using phenotypic data from our EMR. Models predicting disease associations on the basis of known genetic associations alone are specific but not sensitive. Genetic data, as it currently exists, can only explain a fraction

  19. Association study between vitamin D receptor gene polymorphisms and asthma in the chinese han population: a case-control study

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    Gong Yaoqin

    2009-07-01

    Full Text Available Abstract Background Modulation of the immune system is one of the principal roles of Vitamin D, for which the effects are exerted via the vitamin D receptor (VDR. Importantly, variants in the VDR gene have been susceptible in the past to raise the risk of asthma in several populations. These effects of VDR allelic markers remain speculative in the Chinese Han population. Results A case-control study of 1090 individuals including 567 asthmatic patients was realized on five SNPs within the VDR gene. Only rs7975232 (ApaI marker showed a significant association with asthma (P = 0.009. Haplotype analysis of the five VDR polymorphisms showed a significant association with asthma (global-p value = 0.012. Conclusion Although the susceptibility of VDR gene variants with asthma could not be confirmed for all SNPs tested in this study, the significant association obtained for rs7975232 provides evidence for a previously unknown report about the Chinese Han population and may raise the susceptibility of VDR to be a candidate gene for asthma.

  20. Association of Torsion With Testicular Cancer: A Retrospective Study.

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    Uguz, Sami; Yilmaz, Sercan; Guragac, Ali; Topuz, Bahadır; Aydur, Emin

    2016-02-01

    Testicular torsion is a medical emergency that usually requires surgical exploration. However, testicular malignancy has been anecdotally reported with the association of torsion in surgical specimens, and the published data remain scant on the association of torsion with testicular tumors. By retrospective medical record review, we identified 32 patients who had been diagnosed with testicular torsion, 20 of whom had undergone orchiectomy. Of these 20 patients, 2 were diagnosed with a malignancy. Our study, the largest case series to date, has shown an association between testicular torsion and testicular cancer of 6.4%. Testicular torsion is a medical emergency that usually requires surgical exploration. However, testicular malignancy has been anecdotally reported in association with torsion in surgical specimens. However, the published data remain scant on the association between torsion and the presence of testicular tumors. The present retrospective study explored the association between torsion and testicular cancer in patients with testicular torsion undergoing orchiectomy during scrotal exploration. A medical record review was performed of patients who had had a diagnosis of testicular torsion from January 2003 to February 2015. The clinicopathologic characteristics of the patients were recorded. A total of 32 patients were identified. Their mean age was 21.1 years (range, 7-39 years). All the patients had unilateral testicular torsion, which affected the left side in 17 and the right side in 15. Manual detorsion was successful in 6 patients, and 26 patients underwent emergency surgery with testicular detorsion (6 fixation surgery and 20 orchiectomy). The type of incision was scrotal in 6, inguinal in 10, and unspecified in 4. Pathologic examination of the orchiectomy specimens showed malignancy in 2 cases (seminoma and malign mixed germ cell tumor). To the best of our knowledge, the present single-center case series is the largest case series to date of

  1. Association between diabetes and pesticides: a case-control study among Thai farmers.

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    Juntarawijit, Chudchawal; Juntarawijit, Yuwayong

    2018-01-27

    Pesticides are an agricultural chemical suspected to be a significant contributor to a global diabetes pandemic. The purpose of this study was to confirm previous findings of the link between diabetes and some agricultural pesticides and to identify the particular pesticides that are most likely to pose a risk of diabetes in the community. A population-based case-controlled study was conducted among residents in the Bang Rakam district of Phitsanulok Province in Thailand. Lifetime pesticide exposure and other relevant data were collected from 866 participating cases with diabetes mellitus and 1021 healthy controls. After adjusting for gender, age, BMI, cigarette smoking, alcohol consumption, family history of diabetes, and occupation, it was found that the prevalence of diabetes was positively associated with exposure to all types of pesticides, including insecticides, herbicides, fungicides, rodenticides, and molluscicides, with exposure to rodenticides being statistically significant (OR = 1.35; 95%CI 1.04-1.76). Among 35 individual brand-named pesticides investigated, we found statistically significant ORs with three insecticides, including one organochlorine [endosulfan (OR = 1.40; 95%CI 1.01-1.95)], one organophosphate [mevinphos (OR = 2.22; 95%CI 1.17-4.19)], and one carbamate [carbaryl/Sevin (OR = 1.50; 95%CI 1.02-2.19)]; and one fungicides [benlate (OR = 2.08; 95%CI 1.03-4.20)]. Our results suggest that the occurrence of diabetes among Thai farmer was associated with pesticide exposure. This finding is in line with previous epidemiological and animal studies. Further study using a larger sample size is needed to confirm the relationship and to identify the more toxic compounds.

  2. Confirming theoretical pay constructs of a variable pay scheme

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    Sibangilizwe Ncube

    2013-01-01

    Full Text Available Orientation: Return on the investment in variable pay programmes remains controversial because their cost versus contribution cannot be empirically justified. Research purpose: This study validates the findings of the model developed by De Swardt on the factors related to successful variable pay programmes.Motivation for the study: Many organisations blindly implement variable pay programmes without any means to assess the impact these programmes have on the company’s performance. This study was necessary to validate the findings of an existing instrument that validates the contribution of variable pay schemes.Research design, approach and method: The study was conducted using quantitative research. A total of 300 completed questionnaires from a non-purposive sample of 3000 participants in schemes across all South African industries were returned and analysed.Main findings: Using exploratory and confirmatory factor analysis, it was found that the validation instrument developed by De Swardt is still largely valid in evaluating variable pay schemes. The differences between the study and the model were reported.Practical/managerial implications: The study confirmed the robustness of an existing model that enables practitioners to empirically validate the use of variable pay plans. This model assists in the design and implementation of variable pay programmes that meet critical success factors.Contribution/value-add: The study contributed to the development of a measurement instrument that will assess whether a variable pay plan contributes to an organisation’s success.

  3. Study of the association between blood types and breast cancer among Isfahanian women with breast cancer.

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    Flavarjani, Amir Hossein Mirlohi; Hedayatpour, Behnood; Bashardoost, Nasrollah; Nourian, Sayed Mohammad

    2014-01-01

    Previous studies suggest a possible association between ABO blood group and the risk of breast cancer. The aim of this study is to investigate the presence of a possible association between breast cancer and blood groups ABO and Rh. 549 women including 173 cases and 376 controls were selected. The case group included patients with breast cancer and the cancer diagnosis was confirmed for all of them. The control group included women with no reports of breast cancer. Blood group sampling of all cases was performed. The obtained information regarding presence or absence of cancer, blood type, age group and type of cancer were analyzed. There is no significant association between blood types ABO (Rh) and the breast cancer. (P > 0.05) It has been found that the prevalence of invasive intraductal carcinoma was 85% among the cases. About 5% of the total diagnosed cancers in the case group were allocated to modularly carcinoma, invasive lobular carcinoma and Paget's disease. There was no relative frequency in specific blood group for these three types of cancer. The blood types ABO (Rh) and breast cancer type showed no significant relation (P = 0.2). According to the obtained results from this study, there was no relative frequency in specific blood group for these three types of cancer and the blood type could not be influenced as a risk factor in breast cancer.

  4. Association of dyslipidemia with renal cell carcinoma: a 1∶2 matched case-control study.

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    Chunfang Zhang

    Full Text Available Abnormal serum lipid profiles are associated with the risk of some cancers, but the direction and magnitude of the association with renal cell carcinoma is unclear. We explore the relationship between serum lipids and renal cell carcinoma via a matched case-control study. A 1∶2-matched case-control study design was applied, where one renal cell carcinoma patient was matched to two non-renal-cell-carcinoma residents with respect to age (±0 year and gender. Cases (n = 248 were inpatients with a primary diagnosis of renal cell carcinoma, confirmed by pathology after operations. Controls were sampled from a community survey database matched on age and gender with cases, 2 controls for each case. Stratified Cox proportional hazard regression analysis was used to obtain hazard ratios and corresponding 95% confidence intervals of lipids level and dyslipidemia for the risk of renal cell carcinoma. Elevated serum cholesterol (p<0.001, LDL cholesterol (p<0.001, and HDL cholesterol (p = 0.003 are associated with decreased hazard of renal cell carcinoma, adjusting for obesity, smoke, hypertension and diabetes. However, risk caused by hTG showed no statistical significance (p = 0.263. This study indicates that abnormal lipid profile influences the risk of renal cell carcinoma.

  5. Epidemiological and Genome-Wide Association Study of Gastritis or Gastric Ulcer in Korean Populations

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    Sumin Oh

    2014-09-01

    Full Text Available Gastritis is a major disease that has the potential to grow as gastric cancer. Gastric cancer is a very common cancer, and