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Sample records for low-risk variants fgfr2

  1. A variant of fibroblast growth factor receptor 2 (Fgfr2 regulates left-right asymmetry in zebrafish.

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    Da-Wei Liu

    Full Text Available Many organs in vertebrates are left-right asymmetrical located. For example, liver is at the right side and stomach is at the left side in human. Fibroblast growth factor (Fgf signaling is important for left-right asymmetry. To investigate the roles of Fgfr2 signaling in zebrafish left-right asymmetry, we used splicing blocking morpholinos to specifically block the splicing of fgfr2b and fgfr2c variants, respectively. We found that the relative position of the liver and the pancreas were disrupted in fgfr2c morphants. Furthermore, the left-right asymmetry of the heart became random. Expression pattern of the laterality controlling genes, spaw and pitx2c, also became random in the morphants. Furthermore, lefty1 was not expressed in the posterior notochord, indicating that the molecular midline barrier had been disrupted. It was also not expressed in the brain diencephalon. Kupffer's vesicle (KV size became smaller in fgfr2c morphants. Furthermore, KV cilia were shorter in fgfr2c morphants. We conclude that the fgfr2c isoform plays an important role in the left-right asymmetry during zebrafish development.

  2. Variants of FGFR2 and their associations with breast cancer risk: a HUGE systematic review and meta-analysis.

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    Cui, Fei; Wu, Duoguang; Wang, Wenjian; He, Xiaotian; Wang, Minghui

    2016-01-01

    Extensive epidemiological studies have demonstrated that there are associations between variants in intron 2 of FGFR2 and the breast cancer risk in various populations; however, the relationships are not yet conclusively established. To comprehensively review the epidemiological studies showing associations between the variants of FGFR2 and the breast cancer risk, and to establish correlations via a meta-analysis. The PubMed and MEDLINE databases were searched for eligible studies. The associations between the variants and breast cancer risk were evaluated using a random-effects model. The heterogeneity among the studies and the potential publication bias were also evaluated. Fifty-three studies with a total of 121,740 cases and 198,549 controls have examined the associations between 23 variants in intron 2 of FGFR2 and the breast cancer risk. The relationships for the 10 most frequently evaluated variants-rs1078806, rs11200014, rs1219648, rs2420946, rs2981578, rs2981579, rs2981582, rs3135718, rs10736303, and rs3750817-were synthesized based on a meta-analysis. Interestingly, we found that all 10 variants were significantly associated with the risk of breast cancer. In studies stratified by ethnicity, we found that the associations were more notable in Caucasians and Asians compared to Africans. Similar pooled results were found in population-based and hospital-based case-control studies and in studies with small and large sample sizes. FGFR2 is a breast cancer susceptibility gene, and various variants of FGFR2 are significantly associated with the breast cancer risk. However, the biological mechanisms underlying the associations need to be elucidated in future studies.

  3. Genetic variants in FGFR2 and FGFR4 genes and skin cancer risk in the Nurses' Health Study

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    Qureshi Abrar A

    2009-06-01

    Full Text Available Abstract Background The human fibroblast growth factor (FGF and its receptor (FGFR play an important role in tumorigenesis. Deregulation of the FGFR2 gene has been identified in a number of cancer sites. Overexpression of the FGFR4 protein has been linked to cutaneous melanoma progression. Previous studies reported associations between genetic variants in the FGFR2 and FGFR4 genes and development of various cancers. Methods We evaluated the associations of four genetic variants in the FGFR2 gene highly related to breast cancer risk and the three common tag-SNPs in the FGFR4 gene with skin cancer risk in a nested case-control study of Caucasians within the Nurses' Health Study (NHS among 218 melanoma cases, 285 squamous cell carcinoma (SCC cases, 300 basal cell carcinoma (BCC cases, and 870 controls. Results We found no evidence for associations between these seven genetic variants and the risks of melanoma and nonmelanocytic skin cancer. Conclusion Given the power of this study, we did not detect any contribution of genetic variants in the FGFR2 or FGFR4 genes to inherited predisposition to skin cancer among Caucasian women.

  4. Fine-Scale Mapping of the FGFR2 Breast Cancer Risk Locus: Putative Functional Variants Differentially Bind FOXA1 and E2F1

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    Meyer, Kerstin B.; O’Reilly, Martin; Michailidou, Kyriaki; Carlebur, Saskia; Edwards, Stacey L.; French, Juliet D.; Prathalingham, Radhika; Dennis, Joe; Bolla, Manjeet K.; Wang, Qin; de Santiago, Ines; Hopper, John L.; Tsimiklis, Helen; Apicella, Carmel; Southey, Melissa C.; Schmidt, Marjanka K.; Broeks, Annegien; Van ’t Veer, Laura J.; Hogervorst, Frans B.; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A.; Lux, Michael P.; Ekici, Arif B.; Beckmann, Matthias W.; Peto, Julian; dos Santos Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Menegaux, Florence; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Milne, Roger L.; Zamora, M. Pilar; Arias, Jose I.; Benitez, Javier; Neuhausen, Susan; Anton-Culver, Hoda; Ziogas, Argyrios; Dur, Christina C.; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Schmutzler, Rita K.; Engel, Christoph; Ditsch, Nina; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Dörk, Thilo; Helbig, Sonja; Bogdanova, Natalia V.; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Chenevix-Trench, Georgia; Wu, Anna H.; Tseng, Chiu-chen; Van Den Berg, David; Stram, Daniel O.; Lambrechts, Diether; Thienpont, Bernard; Christiaens, Marie-Rose; Smeets, Ann; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Bonanni, Bernardo; Bernard, Loris; Couch, Fergus J.; Olson, Janet E.; Wang, Xianshu; Purrington, Kristen; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura; McLean, Catriona; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Teo, Soo-Hwang; Yip, Cheng-Har; Phuah, Sze-Yee; Kristensen, Vessela; Grenaker Alnæs, Grethe; Børresen-Dale, Anne-Lise; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert A.E.M.; Seynaeve, Caroline M.; García-Closas, Montserrat; Figueroa, Jonine; Chanock, Stephen J.; Lissowska, Jolanta; Czene, Kamila; Darabi, Hartef; Eriksson, Kimael; Hooning, Maartje J.; Martens, John W.M.; van den Ouweland, Ans M.W.; van Deurzen, Carolien H.M.; Hall, Per; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cox, Angela; Reed, Malcolm W.R.; Blot, William; Signorello, Lisa B.; Cai, Qiuyin; Pharoah, Paul D.P.; Ghoussaini, Maya; Harrington, Patricia; Tyrer, Jonathan; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K.; Noh, Dong-Young; Hartman, Mikael; Hui, Miao; Lim, Wei-Yen; Buhari, Shaik A.; Hamann, Ute; Försti, Asta; Rüdiger, Thomas; Ulmer, Hans-Ulrich; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Vachon, Celine; Slager, Susan; Fostira, Florentia; Pilarski, Robert; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Hou, Ming-Feng; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J.; Ponder, Bruce A.J.; Dunning, Alison M.; Easton, Douglas F.

    2013-01-01

    The 10q26 locus in the second intron of FGFR2 is the locus most strongly associated with estrogen-receptor-positive breast cancer in genome-wide association studies. We conducted fine-scale mapping in case-control studies genotyped with a custom chip (iCOGS), comprising 41 studies (n = 89,050) of European ancestry, 9 Asian ancestry studies (n = 13,983), and 2 African ancestry studies (n = 2,028) from the Breast Cancer Association Consortium. We identified three statistically independent risk signals within the locus. Within risk signals 1 and 3, genetic analysis identified five and two variants, respectively, highly correlated with the most strongly associated SNPs. By using a combination of genetic fine mapping, data on DNase hypersensitivity, and electrophoretic mobility shift assays to study protein-DNA binding, we identified rs35054928, rs2981578, and rs45631563 as putative functional SNPs. Chromatin immunoprecipitation showed that FOXA1 preferentially bound to the risk-associated allele (C) of rs2981578 and was able to recruit ERα to this site in an allele-specific manner, whereas E2F1 preferentially bound the risk variant of rs35054928. The risk alleles were preferentially found in open chromatin and bound by Ser5 phosphorylated RNA polymerase II, suggesting that the risk alleles are associated with changes in transcription. Chromatin conformation capture demonstrated that the risk region was able to interact with the promoter of FGFR2, the likely target gene of this risk region. A role for FOXA1 in mediating breast cancer susceptibility at this locus is consistent with the finding that the FGFR2 risk locus primarily predisposes to estrogen-receptor-positive disease. PMID:24290378

  5. Heterogeneity of Breast Cancer Associations with Common Genetic Variants in FGFR2 according to the Intrinsic Subtypes in Southern Han Chinese Women

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    Huiying Liang

    2015-01-01

    Full Text Available GWAS have identified variation in the FGFR2 locus as risk factors for breast cancer. Validation studies, however, have shown inconsistent results by ethnics and pathological characteristics. To further explore this inconsistency and investigate the associations of FGFR2 variants with breast cancer according to intrinsic subtype (Luminal-A, Luminal-B, ER−&PR−&HER2+, and triple negative among Southern Han Chinese women, we genotyped rs1078806, rs1219648, rs2420946, rs2981579, and rs2981582 polymorphisms in 609 patients and 882 controls. Significant associations with breast cancer risk were observed for rs2420946, rs2981579, and rs2981582 with OR (95% CI per risk allele of 1.19 (1.03–1.39, 1.24 (1.07–1.43, and 1.17 (1.01–1.36, respectively. In subtype specific analysis, above three SNPs were significantly associated with increased Luminal-A risk in a dose-dependent manner Ptrend<0.01; however, only rs2981579 was associated with Luminal-B, and none were linked to ER−&PR− subtypes (ER−&PR−&HER2+ and triple negative. Haplotype analyses also identified common haplotypes significantly associated with luminal-like subtypes (Luminal-A and Luminal-B, but not with ER−&PR− subtypes. Our results suggest that associations of FGFR2 SNPs with breast cancer were heterogeneous according to intrinsic subtype. Future studies stratifying patients by their intrinsic subtypes will provide new insights into the complex genetic mechanisms underlying breast cancer.

  6. A study on genetic variants of Fibroblast growth factor receptor 2 (FGFR2 and the risk of breast cancer from North India.

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    Sarah Siddiqui

    Full Text Available Genome-Wide Association Studies (GWAS have identified Fibroblast growth factor receptor 2 (FGFR2 as a candidate gene for breast cancer with single nucleotide polymorphisms (SNPs located in intron 2 region as the susceptibility loci strongly associated with the risk. However, replicate studies have often failed to extrapolate the association to diverse ethnic regions. This hints towards the existing heterogeneity among different populations, arising due to differential linkage disequilibrium (LD structures and frequencies of SNPs within the associated regions of the genome. It is therefore important to revisit the previously linked candidates in varied population groups to unravel the extent of heterogeneity. In an attempt to investigate the role of FGFR2 polymorphisms in susceptibility to the risk of breast cancer among North Indian women, we genotyped rs2981582, rs1219648, rs2981578 and rs7895676 polymorphisms in 368 breast cancer patients and 484 healthy controls by Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP assay. We observed a statistically significant association with breast cancer risk for all the four genetic variants (P<0.05. In per-allele model for rs2981582, rs1219648, rs7895676 and in dominant model for rs2981578, association remained significant after bonferroni correction (P<0.0125. On performing stratified analysis, significant correlations with various clinicopathological as well as environmental and lifestyle characteristics were observed. It was evident that rs1219648 and rs2981578 interacted with exogenous hormone use and advanced clinical stage III (after Bonferroni correction, P<0.000694, respectively. Furthermore, combined analysis on these four loci revealed that compared to women with 0-1 risk loci, those with 2-4 risk loci had increased risk (OR = 1.645, 95%CI = 1.152-2.347, P = 0.006. In haplotype analysis, for rs2981578, rs2981582 and rs1219648, risk haplotype (GTG was

  7. Genetic variants of fibroblast growth factor receptor 2 (FGFR2) are associated with breast cancer risk in Chinese women of the Han nationality.

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    Chen, Fan; Lu, Min; Lv, Min; Xue, Yun; Zhou, Jing; Hu, Feifei; Chen, Xin; Zhao, Zhanqin; Li, Yang; Wang, XingGuo

    2012-01-01

    Fibroblast growth factor receptor 2 (FGFR2), a recently described risk factor for breast cancer, plays important roles in cell growth, invasiveness, motility, and angiogenesis. In attempt to investigate whether FGFR2 polymorphisms are associated with a risk of breast cancer in Chinese women of the Han nationality, we genotyped single-nucleotide polymorphisms (SNPs) of seven FGFR2 sites (rs2981582, rs17102287, rs17542768, rs10510097, rs11200012, rs3750817, rs2981578) in 816 women including 388 breast cancer patients and 428 healthy controls via the polymerase chain reaction single-strand conformation polymorphism procedure as well as sequence detection. Our results suggest that the A allele and AA genotype of SNP rs2981578 appear to be protective factors associated with breast cancer, while the CT genotype of SNP rs3750817 is a putative risk factor.

  8. FGFR2 risk SNPs confer breast cancer risk by augmenting oestrogen responsiveness.

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    Campbell, Thomas M; Castro, Mauro A A; de Santiago, Ines; Fletcher, Michael N C; Halim, Silvia; Prathalingam, Radhika; Ponder, Bruce A J; Meyer, Kerstin B

    2016-08-01

    The fibroblast growth factor receptor 2 (FGFR2) locus is consistently the top hit in genome-wide association studies for oestrogen receptor-positive (ER(+)) breast cancer. Yet, its mode of action continues to be controversial. Here, we employ a systems biology approach to demonstrate that signalling via FGFR2 counteracts cell activation by oestrogen. In the presence of oestrogen, the oestrogen receptor (ESR1) regulon (set of ESR1 target genes) is in an active state. However, signalling by FGFR2 is able to reverse the activity of the ESR1 regulon. This effect is seen in multiple distinct FGFR2 signalling model systems, across multiple cells lines and is dependent on the presence of FGFR2. Increased oestrogen exposure has long been associated with an increased risk of breast cancer. We therefore hypothesized that risk variants should reduce FGFR2 expression and subsequent signalling. Indeed, transient transfection experiments assaying the three independent variants of the FGFR2 risk locus (rs2981578, rs35054928 and rs45631563) in their normal chromosomal context show that these single-nucleotide polymorphisms (SNPs) map to transcriptional silencer elements and that, compared with wild type, the risk alleles augment silencer activity. The presence of risk variants results in lower FGFR2 expression and increased oestrogen responsiveness. We thus propose a molecular mechanism by which FGFR2 can confer increased breast cancer risk that is consistent with oestrogen exposure as a major driver of breast cancer risk. Our findings may have implications for the clinical use of FGFR2 inhibitors.

  9. Identification of Functional Variants for Cleft Lip with or without Cleft Palate in or near PAX7, FGFR2, and NOG by Targeted Sequencing of GWAS Loci

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    Leslie, Elizabeth J; Taub, Margaret A; Liu, Huan

    2015-01-01

    Although genome-wide association studies (GWASs) for nonsyndromic orofacial clefts have identified multiple strongly associated regions, the causal variants are unknown. To address this, we selected 13 regions from GWASs and other studies, performed targeted sequencing in 1,409 Asian and European...... alleles for nonsyndromic clefting in humans....

  10. Associated expressions of FGFR-2 and FGFR-3: from mouse mammary gland physiology to human breast cancer.

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    Cerliani, Juan P; Vanzulli, Silvia I; Piñero, Cecilia Pérez; Bottino, María C; Sahores, Ana; Nuñez, Myriam; Varchetta, Romina; Martins, Rubén; Zeitlin, Eduardo; Hewitt, Stephen M; Molinolo, Alfredo A; Lanari, Claudia; Lamb, Caroline A

    2012-06-01

    Fibroblast growth factor receptors (FGFRs) are tyrosine kinase receptors which have been implicated in breast cancer. The aim of this study was to evaluate FGFR-1, -2, -3, and -4 protein expressions in normal murine mammary gland development, and in murine and human breast carcinomas. Using immunohistochemistry and Western blot, we report a hormonal regulation of FGFR during postnatal mammary gland development. Progestin treatment of adult virgin mammary glands resulted in changes in localization of FGFR-3 from the cytoplasm to the nucleus, while treatment with 17-β-estradiol induced changes in the expressions and/or localizations of FGFR-2 and -3. In murine mammary carcinomas showing different degrees of hormone dependence, we found progestin-induced increased expressions, mainly of FGFR-2 and -3. These receptors were constitutively activated in hormone-independent variants. We studied three luminal human breast cancer cell lines growing as xenografts, which particularly expressed FGFR-2 and -3, suggesting a correlation between hormonal status and FGFR expression. Most importantly, in breast cancer samples from 58 patients, we found a strong association (P FGFR-2 and -3 expressions and a weaker correlation of each receptor with estrogen receptor expression. FGFR-4 correlated with c-erbB2 over expression. We conclude that FGFR-2 and -3 may be mechanistically linked and can be potential targets for treatment of estrogen receptor-positive breast cancer patients.

  11. Polyclonal Secondary FGFR2 Mutations Drive Acquired Resistance to FGFR Inhibition in Patients with FGFR2 Fusion-Positive Cholangiocarcinoma.

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    Goyal, Lipika; Saha, Supriya K; Liu, Leah Y; Siravegna, Giulia; Leshchiner, Ignaty; Ahronian, Leanne G; Lennerz, Jochen K; Vu, Phuong; Deshpande, Vikram; Kambadakone, Avinash; Mussolin, Benedetta; Reyes, Stephanie; Henderson, Laura; Sun, Jiaoyuan Elisabeth; Van Seventer, Emily E; Gurski, Joseph M; Baltschukat, Sabrina; Schacher-Engstler, Barbara; Barys, Louise; Stamm, Christelle; Furet, Pascal; Ryan, David P; Stone, James R; Iafrate, A John; Getz, Gad; Porta, Diana Graus; Tiedt, Ralph; Bardelli, Alberto; Juric, Dejan; Corcoran, Ryan B; Bardeesy, Nabeel; Zhu, Andrew X

    2017-03-01

    Genetic alterations in the fibroblast growth factor receptor (FGFR) pathway are promising therapeutic targets in many cancers, including intrahepatic cholangiocarcinoma (ICC). The FGFR inhibitor BGJ398 displayed encouraging efficacy in patients with FGFR2 fusion-positive ICC in a phase II trial, but the durability of response was limited in some patients. Here, we report the molecular basis for acquired resistance to BGJ398 in three patients via integrative genomic characterization of cell-free circulating tumor DNA (cfDNA), primary tumors, and metastases. Serial analysis of cfDNA demonstrated multiple recurrent point mutations in the FGFR2 kinase domain at progression. Accordingly, biopsy of post-progression lesions and rapid autopsy revealed marked inter- and intralesional heterogeneity, with different FGFR2 mutations in individual resistant clones. Molecular modeling and in vitro studies indicated that each mutation led to BGJ398 resistance and was surmountable by structurally distinct FGFR inhibitors. Thus, polyclonal secondary FGFR2 mutations represent an important clinical resistance mechanism that may guide the development of future therapeutic strategies.Significance: We report the first genetic mechanisms of clinical acquired resistance to FGFR inhibition in patients with FGFR2 fusion-positive ICC. Our findings can inform future strategies for detecting resistance mechanisms and inducing more durable remissions in ICC and in the wide variety of cancers where the FGFR pathway is being explored as a therapeutic target. Cancer Discov; 7(3); 252-63. ©2016 AACR.See related commentary by Smyth et al., p. 248This article is highlighted in the In This Issue feature, p. 235.

  12. Association between rs2981582 polymorphism in the FGFR2 gene and the risk of breast cancer in Mexican women

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    Murillo-Zamora, Efrén; Moreno-Macías, Hortensia; Ziv, Elad; Romieu, Isabelle; Lazcano-Ponce, Eduardo; Ángeles-Llerenas, Angélica; Pérez-Rodríguez, Edelmiro; Vidal-Millán, Silvia; Fejerman, Laura; Torres-Mejía, Gabriela

    2014-01-01

    Background and Aims The rs2981582 single nucleotide polymorphism in the Fibroblast Growth Factor Receptor 2 gene has been consistently associated with an increased risk of breast cancer. We evaluated the effect of rs2981582 polymorphism in the FGFR2 gene on the risk of breast cancer and its interaction with non-genetic risk factors. Methods A population based case control study was conducted in Mexico. Data from 687 cases and 907 controls were analyzed. Results The T allele of the rs2981582 polymorphism was associated with an increased risk of breast cancer (OR per allele =1.24, 95% CI 1.06 – 1.46). There was also an interaction between this polymorphism and alcohol consumption (p = 0.043); the effect of alcohol consumption on the risk of breast cancer varied according to the allelic variants of the rs2981582 polymorphism in the FGFR2 gene: OR = 3.97 (95% CI 2.10 – 7.49), OR = 2.01 (95% CI 1.23 − 3.29) and OR = 1.21 (95% CI 0.48 − 3.05) for genotypes CC, CT and TT, respectively. Conclusions This is the first study exploring the association between rs2981582 polymorphism in the FGFR2 gene and breast cancer risk in Mexican women. The interaction found may be of great public health interest, since alcohol consumption is a modifiable breast cancer risk factor. Therefore, replication of this finding is of foremost importance. PMID:24054997

  13. FGFR2 protein expression in breast cancer: nuclear localisation and correlation with patient genotype

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    Thompson Alastair M

    2011-03-01

    Full Text Available Abstract Background Single Nucleotide Polymorphisms (SNPs in intron 2 of the Fibroblast Growth Factor Receptor Type 2 (FGFR2 gene, including rs2981582, contribute to multifactorial breast cancer susceptibility. The high risk polymorphism haplotype in the FGFR2 gene has been associated with increased mRNA transcription and altered transcription factor binding but the effect on FGFR2 protein expression is unknown. 40 breast tumours were identified from individuals with known rs2981582 genotype. Tumour sections were stained for FGFR2 protein expression, and scored for nuclear and cytoplasmic staining in tumour and surrounding normal tissue. Findings FGFR2 immunohistochemistry demonstrated variable nuclear staining in normal tissue and tumour tissue, as well as consistent cytoplasmic staining. We did not find an association between nuclear staining for FGFR2 and genotype, and there was no association between FGFR2 staining and estrogen or progestogen receptor status. There was an association between presence of nuclear staining for FGFR2 in normal tissue and presence of nuclear staining in the adjacent tumour (Fishers exact test, p = 0.002. Conclusions Variable nuclear staining for FGFR2 in breast cancer, but an absence of correlation with rs2981582 genotype suggests that the mechanism of action of polymorphisms at the FGFR2 locus may be more complex than a direct effect on mRNA expression levels in the final cancer. The effect may relate to FGFR2 function or localisation during breast development or tumourigenesis. Nuclear localisation of FGFR2 suggests an important additional role for this protein in breast development and breast cancer, in addition to its function as a classical cell surface receptor.

  14. Independent roles of Fgfr2 and Frs2α in ureteric epithelium

    OpenAIRE

    Sims-Lucas, Sunder; Cusack, Brian; Eswarakumar, Veraragavan P.; Zhang, Jue(Institute for Fundamental Theory, Department of Physics, University of Florida, Gainesville, FL, 32611, U.S.A.); Wang, Fen; Bates, Carlton M.

    2011-01-01

    Mice with conditional deletion of fibroblast growth factor receptor 2 (Fgfr2) in the ureteric bud using a Hoxb7cre line (Fgfr2UB−/−) develop severe ureteric branching defects; however, ureteric deletion of fibroblast growth factor receptor substrate 2α (Frs2α), a key docking protein that transmits fibroblast growth factor receptor intracellular signaling (Frs2αUB−/−) leads to mild ureteric defects. Mice with point mutations in the Frs2α binding site of Fgfr2 (Fgfr2LR/LR) have normal kidneys. ...

  15. FGFR2 abnormalities underlie a spectrum of bone, skin, and cancer pathologies.

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    Katoh, Masaru

    2009-08-01

    Fibroblast growth factor receptor (FGFR)2 is regulated on the basis of the balance of FGFs, heparan-sulfate proteoglycans, FGFR2 isoforms, endogenous inhibitors, and microRNAs. FGFR2 signals cross-talk with hedgehog, bone morphogenetic protein, and other regulatory networks. Some cases of congenital skeletal disorders with an FGFR2 mutation show skin phenotypes, including acne, cutis gyrata, and acanthosis nigricans. Gain-of-function mutations or variations of human FGFR2 occur in estrogen receptor-positive breast cancer, diffuse-type gastric cancer, and endometrial uterine cancer. Oral administration of AZD2171 or Ki23057 inhibits in vivo proliferation of cancer cells with aberrant FGFR2 activation in rodent therapeutic models. However, loss-of-function mutations of FGFR2 are reported in human melanoma. Conditional Fgfr2b knockout in the rodent epidermis leads to increased macrophage infiltration to the dermis and adipose tissue, epidermal thickening accompanied by basal-layer dysplasia and parakeratosis, and the promotion of chemically induced squamous-cell carcinoma. Dysregulation of FGFR2 results in a spectrum of bone and skin pathologies and several types of cancer.

  16. [From gene to disease; craniosynostosis syndromes due to FGFR2-mutation

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    Ravenswaaij-Arts, C.M.A. van; Ouweland, A.M.W. van den; Hoogeboom, A.J.M.; Herbergs, J.; Pals, G.

    2002-01-01

    One of the genes involved in craniosynostosis syndromes is the fibroblast growth factor receptor 2 (FGFR2) gene, a tyrosine kinase receptor gene. Upon ligand binding the FGFR2 receptors dimerise, and this is followed by activation of the intracellular tyrosine kinase domains. This initiates a cascad

  17. Structural Basis for Reduced FGFR2 Activity in LADD Syndrome: Implications for FGFR Autoinhibition and Activation

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    Lew,E.; Bae, J.; Rohmann, E.; Wollnik, B.; Schlessinger, J.

    2007-01-01

    Mutations in fibroblast growth factor receptor 2 (FGFR2) and its ligand, FGF10, are known to cause lacrimo-auriculo-dento-digital (LADD) syndrome. Multiple gain-of-function mutations in FGF receptors have been implicated in a variety of severe skeletal disorders and in many cancers. We aimed to elucidate the mechanism by which a missense mutation in the tyrosine kinase domain of FGFR2, described in the sporadic case of LADD syndrome, leads to reduced tyrosine kinase activity. In this report, we describe the crystal structure of a FGFR2 A628T LADD mutant in complex with a nucleotide analog. We demonstrate that the A628T LADD mutation alters the configuration of key residues in the catalytic pocket that are essential for substrate coordination, resulting in reduced tyrosine kinase activity. Further comparison of the structures of WT FGFR2 and WT FGFR1 kinases revealed that FGFR2 uses a less stringent mode of autoinhibition than FGFR1, which was also manifested in faster in vitro autophosphorylation kinetics. Moreover, the nearly identical conformation of WT FGFR2 kinase and the A628T LADD mutant to either the phosphorylated FGFR2 or FGFR2 harboring pathological activating mutations in the kinase hinge region suggests that FGFR autoinhibition and activation are better explained by changes in the conformational dynamics of the kinase rather than by static crystallographic snapshots of minor structural variations.

  18. Treatment with FGFR2-IIIc monoclonal antibody suppresses weight gain and adiposity in KKAy mice

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    Nonogaki, K; Kaji, T; Yamazaki, T; Murakami, Mari

    2016-01-01

    Expression of β-Kotho, fibroblast growth factor receptor (FGFR)-1c and 2c, which bind FGF21, is decreased in the white adipose tissue of obese mice. The aim of the present study was to determine the role of FGFR2c in the development of obesity and diabetes in KKAy mice. Treatment with mouse monoclonal FGFR2-IIIc antibody (0.5 mg kg−1) significantly suppressed body weight gain and epididymal white adipose tissue weight in individually housed KKAy mice while having no effect on daily food intake. In addition, treatment with FGFR2-IIIc antibody significantly increased plasma-free fatty acid levels while having no effect on blood glucose or plasma FGF21 levels. Moreover, treatment with FGFR2-IIIc antibody had no significant effect on the expression of uncoupling protein-1, uncoupling protein-2 or peroxisome proliferator-activated receptor-γ coactivator 1α in the epididymal white adipose tissue. The treatment with FGFR2-IIIc antibody had no significant effects on daily food intake and body weight gain in individually housed KK mice. These findings suggest that FGFR2-IIIc upregulates the adiposity induced by social isolation in KKAy mice, and that decreased expression and/or function of FGFR2c might be a compensatory response to enhanced adiposity. Inhibition of FGFR2-IIIc function might be a novel therapeutic approach for obesity. PMID:27892934

  19. FGFR2 promotes breast tumorigenicity through maintenance of breast tumor-initiating cells.

    Directory of Open Access Journals (Sweden)

    Sungeun Kim

    Full Text Available Emerging evidence suggests that some cancers contain a population of stem-like TICs (tumor-initiating cells and eliminating TICs may offer a new strategy to develop successful anti-cancer therapies. As molecular mechanisms underlying the maintenance of the TIC pool are poorly understood, the development of TIC-specific therapeutics remains a major challenge. We first identified and characterized TICs and non-TICs isolated from a mouse breast cancer model. TICs displayed increased tumorigenic potential, self-renewal, heterogeneous differentiation, and bipotency. Gene expression analysis and immunostaining of TICs and non-TICs revealed that FGFR2 was preferentially expressed in TICs. Loss of FGFR2 impaired self-renewal of TICs, thus resulting in marked decreases in the TIC population and tumorigenic potential. Restoration of FGFR2 rescued the defects in TIC pool maintenance, bipotency, and breast tumor growth driven by FGFR2 knockdown. In addition, pharmacological inhibition of FGFR2 kinase activity led to a decrease in the TIC population which resulted in suppression of breast tumor growth. Moreover, human breast TICs isolated from patient tumor samples were found enriched in a FGFR2+ population that was sufficient to initiate tumor growth. Our data suggest that FGFR2 is essential in sustaining the breast TIC pool through promotion of self-renewal and maintenance of bipotent TICs, and raise the possibility of FGFR2 inhibition as a strategy for anti-cancer therapy by eradicating breast TICs.

  20. Activating FGFR2-RAS-BRAF mutations in ameloblastoma.

    Science.gov (United States)

    Brown, Noah A; Rolland, Delphine; McHugh, Jonathan B; Weigelin, Helmut C; Zhao, Lili; Lim, Megan S; Elenitoba-Johnson, Kojo S J; Betz, Bryan L

    2014-11-01

    Ameloblastoma is an odontogenic neoplasm whose overall mutational landscape has not been well characterized. We sought to characterize pathogenic mutations in ameloblastoma and their clinical and functional significance with an emphasis on the mitogen-activated protein kinase (MAPK) pathway. A total of 84 ameloblastomas and 40 non-ameloblastoma odontogenic tumors were evaluated with a combination of BRAF V600E allele-specific PCR, VE1 immunohistochemistry, the Ion AmpliSeq Cancer Hotspot Panel, and Sanger sequencing. Efficacy of a BRAF inhibitor was evaluated in an ameloblastoma-derived cell line. Somatic, activating, and mutually exclusive RAS-BRAF and FGFR2 mutations were identified in 88% of cases. Somatic mutations in SMO, CTNNB1, PIK3CA, and SMARCB1 were also identified. BRAF V600E was the most common mutation, found in 62% of ameloblastomas and in ameloblastic fibromas/fibrodentinomas but not in other odontogenic tumors. This mutation was associated with a younger age of onset, whereas BRAF wild-type cases arose more frequently in the maxilla and showed earlier recurrences. One hundred percent concordance was observed between VE1 immunohistochemistry and molecular detection of BRAF V600E mutations. Ameloblastoma cells demonstrated constitutive MAPK pathway activation in vitro. Proliferation and MAPK activation were potently inhibited by the BRAF inhibitor vemurafenib. Our findings suggest that activating FGFR2-RAS-BRAF mutations play a critical role in the pathogenesis of most cases of ameloblastoma. Somatic mutations in SMO, CTNNB1, PIK3CA, and SMARCB1 may function as secondary mutations. BRAF V600E mutations have both diagnostic and prognostic implications. In vitro response of ameloblastoma to a BRAF inhibitor suggests a potential role for targeted therapy. ©2014 American Association for Cancer Research.

  1. Antitumor effects and molecular mechanisms of ponatinib on endometrial cancer cells harboring activating FGFR2 mutations.

    Science.gov (United States)

    Kim, Do-Hee; Kwak, Yeonui; Kim, Nam Doo; Sim, Taebo

    2016-01-01

    Aberrant mutational activation of FGFR2 is associated with endometrial cancers (ECs). AP24534 (ponatinib) currently undergoing clinical trials has been known to be an orally available multi-targeted tyrosine kinase inhibitor. Our biochemical kinase assay showed that AP24534 is potent against wild-type FGFR1-4 and 5 mutant FGFRs (V561M-FGFR1, N549H-FGFR2, K650E-FGFR3, G697C-FGFR3, N535K-FGFR4) and possesses the strongest kinase-inhibitory activity on N549H-FGFR2 (IC50 of 0.5 nM) among all FGFRs tested. We therefore investigated the effects of AP24534 on endometrial cancer cells harboring activating FGFR2 mutations and explored the underlying molecular mechanisms. AP24534 significantly inhibited the proliferation of endometrial cancer cells bearing activating FGFR2 mutations (N549K, K310R/N549K, S252W) and mainly induced G1/S cell cycle arrest leading to apoptosis. AP24534 also diminished the kinase activity of immunoprecipitated FGFR2 derived from MFE-296 and MFE-280 cells and reduced the phosphorylation of FGFR2 and FRS2 on MFE-296 and AN3CA cells. AP24534 caused substantial reductions in ERK phosphorylation, PLCγ signaling and STAT5 signal transduction on ECs bearing FGFR2 activating mutations. Akt signaling pathway was also deactivated by AP24534. AP24534 causes the chemotherapeutic effect through mainly the blockade of ERK, PLCγ and STAT5 signal transduction on ECs. Moreover, AP24534 inhibited migration and invasion of endometrial cancer cells with FGFR2 mutations. In addition, AP24534 significantly blocked anchorage-independent growth of endometrial cancer cells. We, for the first time, report the molecular mechanisms by which AP24534 exerts antitumor effects on ECs with FGFR2 activating mutations, which would provide mechanistic insight into ongoing clinical investigations of AP24534 for ECs.

  2. Switching addictions between HER2 and FGFR2 in HER2-positive breast tumor cells: FGFR2 as a potential target for salvage after lapatinib failure

    Energy Technology Data Exchange (ETDEWEB)

    Azuma, Koichi [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Tsurutani, Junji, E-mail: tsurutani_j@dotd.med.kindai.ac.jp [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Sakai, Kazuko; Kaneda, Hiroyasu [Department of Genome Biology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Fujisaka, Yasuhito; Takeda, Masayuki [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Watatani, Masahiro [Department of Surgery, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Arao, Tokuzo [Department of Genome Biology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Satoh, Taroh; Okamoto, Isamu; Kurata, Takayasu [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Nishio, Kazuto [Department of Genome Biology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Nakagawa, Kazuhiko [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan)

    2011-04-01

    Highlights: {yields} A lapatinib-resistant breast cancer cell line, UACC812 (UACC812/LR), was found to harbor amplification of the FGFR2 gene. {yields} Inhibition of the molecule by a specific inhibitor of FGFR dramatically induced growth inhibition accompanied by cell death. {yields} Immunohistochemical analysis of patients with HER2-positive breast cancer demonstrated an association between FGFR2 expression and poor outcome for lapatinib-containing chemotherapy. -- Abstract: Agents that target HER2 have improved the prognosis of patients with HER2-amplified breast cancers. However, patients who initially respond to such targeted therapy eventually develop resistance to the treatment. We have established a line of lapatinib-resistant breast cancer cells (UACC812/LR) by chronic exposure of HER2-amplified and lapatinib-sensitive UACC812 cells to the drug. The mechanism by which UACC812/LR acquired resistance to lapatinib was explored using comprehensive gene hybridization. The FGFR2 gene in UACC812/LR was highly amplified, accompanied by overexpression of FGFR2 and reduced expression of HER2, and a cell proliferation assay showed that the IC{sub 50} of PD173074, a small-molecule inhibitor of FGFR tyrosine kinase, was 10,000 times lower in UACC812/LR than in the parent cells. PD173074 decreased the phosphorylation of FGFR2 and substantially induced apoptosis in UACC812/LR, but not in the parent cells. FGFR2 appeared to be a pivotal molecule for the survival of UACC812/LR as they became independent of the HER2 pathway, suggesting that a switch of addiction from the HER2 to the FGFR2 pathway enabled cancer cells to become resistant to HER2-targeted therapy. The present study is the first to implicate FGFR in the development of resistance to lapatinib in cancer, and suggests that FGFR-targeted therapy might become a promising salvage strategy after lapatinib failure in patients with HER2-positive breast cancer.

  3. Novel molecular pathways elicited by mutant FGFR2 may account for brain abnormalities in Apert syndrome.

    Directory of Open Access Journals (Sweden)

    Erika Yeh

    Full Text Available Apert syndrome (AS, the most severe form craniosynostosis, is characterized by premature fusion of coronal sutures. Approximately 70% of AS patients carry S252W gain-of-function mutation in FGFR2. Besides the cranial phenotype, brain dysmorphologies are present and are not seen in other FGFR2-asociated craniosynostosis, such as Crouzon syndrome (CS. Here, we hypothesized that S252W mutation leads not only to overstimulation of FGFR2 downstream pathway, but likewise induces novel pathological signaling. First, we profiled global gene expression of wild-type and S252W periosteal fibroblasts stimulated with FGF2 to activate FGFR2. The great majority (92% of the differentially expressed genes (DEGs were divergent between each group of cell populations and they were regulated by different transcription factors. We than compared gene expression profiles between AS and CS cell populations and did not observe correlations. Therefore, we show for the first time that S252W mutation in FGFR2 causes a unique cell response to FGF2 stimulation. Since our gene expression results suggested that novel signaling elicited by mutant FGFR2 might be associated with central nervous system (CNS development and maintenance, we next investigated if DEGs found in AS cells were also altered in the CNS of an AS mouse model. Strikingly, we validated Strc (stereocilin in newborn Fgfr2(S252W/+ mouse brain. Moreover, immunostaining experiments suggest a role for endothelial cells and cerebral vasculature in the establishment of characteristic CNS dysmorphologies in AS that has not been proposed by previous literature. Our approach thus led to the identification of new target genes directly or indirectly associated with FGFR2 which are contributing to the pathophysiology of AS.

  4. Interaction between FGFR-2, STAT5, and progesterone receptors in breast cancer.

    Science.gov (United States)

    Cerliani, Juan P; Guillardoy, Tomás; Giulianelli, Sebastián; Vaque, José P; Gutkind, J Silvio; Vanzulli, Silvia I; Martins, Rubén; Zeitlin, Eduardo; Lamb, Caroline A; Lanari, Claudia

    2011-05-15

    Fibroblast growth factor (FGF) receptor 2 (FGFR-2) polymorphisms have been associated with an increase in estrogen receptor and progesterone receptor (PR)-positive breast cancer risk; however, a clear mechanistic association between FGFR-2 and steroid hormone receptors remains elusive. In previous works, we have shown a cross talk between FGF2 and progestins in mouse mammary carcinomas. To investigate the mechanisms underlying these interactions and to validate our findings in a human setting, we have used T47D human breast cancer cells and human cancer tissue samples. We showed that medroxyprogesterone acetate (MPA) and FGF2 induced cell proliferation and activation of ERK, AKT, and STAT5 in T47D and in murine C4-HI cells. Nuclear interaction between PR, FGFR-2, and STAT5 after MPA and FGF2 treatment was also showed by confocal microscopy and immunoprecipitation. This effect was associated with increased transcription of PRE and/or GAS reporter genes, and of PR/STAT5-regulated genes and proteins. Two antiprogestins and the FGFR inhibitor PD173074, specifically blocked the effects induced by FGF2 or MPA respectively. The presence of PR/FGFR-2/STAT5 complexes bound to the PRE probe was corroborated by using NoShift transcription and chromatin immunoprecipitation of the MYC promoter. Additionally, we showed that T47D cells stably transfected with constitutively active FGFR-2 gave rise to invasive carcinomas when transplanted into NOD/SCID mice. Nuclear colocalization between PR and FGFR-2/STAT5 was also observed in human breast cancer tissues. This study represents the first demonstration of a nuclear interaction between FGFR-2 and STAT5, as PR coactivators at the DNA progesterone responsive elements, suggesting that FGFRs are valid therapeutic targets for human breast cancer treatment.

  5. Novel mutation detection of fibroblast growth factor receptor 1 (FGFR1 gene, FGFR2IIIa, FGFR2IIIb, FGFR2IIIc, FGFR3, FGFR4 gene for craniosynostosis: A prospective study in Asian Indian patient

    Directory of Open Access Journals (Sweden)

    Mayadhar Barik

    2015-01-01

    Full Text Available Background: Craniosynostosis (CS syndrome is an autosomal dominant condition classically combining craniosynostosis and non-syndromic craniosynostosis with digital anomalies of the hands and feet. The majority of cases are caused by heterozygous mutations in the third immunoglobulin-like domain (IgIII of FGFR2, whilst a larger number of cases can be attributed to mutations outside this region of the protein. Aims: To find out the FGFR1, FGFR2, FGFR3 and FGFR4 gene in craniosynostosis syndrome. Settings and Design: A hospital based prospective study. Materials and Methods: Prospective analysis of clinical records of patients registered in CS clinic from December 2007 to January 2015 was done in patients between 4 months to 13 years of age. We have performed genetic findings in a three generation Indian family with Craniosynostosis syndrome. Results: We report for the first time the clinical and genetic findings in a three generation Indian family with Craniosynostosis syndrome caused by a heterozygous missense mutation, Thr 392 Thr and ser 311 try, located in the IgII domain of FGFR2. FGFR 3 and 4 gene basis syndrome was eponymously named. Genetic analysis demonstrated that 51/56 families to be unrelated. In FGFR3 gene 10/TM location of 1172 the nucleotide changes C>A, Ala 391 Glu 19/56 and Exon-19, 5q35.2 at conserved linker region the changes occurred pro 246 Arg in 25/56 families. Conclusions: Independent genetic origins, but phenotypic similarities in the 51 families add to the evidence supporting the theory of selfish spermatogonial selective advantage for this rare gain-of-function FGFR2 mutation.

  6. Reciprocal interactions of Fgf10/Fgfr2b modulate the mouse tongue epithelial differentiation.

    Science.gov (United States)

    Sohn, Wern-Joo; Jung, Hye-In; Choi, Min-A; Han, Jin-Hyun; Gwon, Gi-Jeong; Yamamoto, Hitoshi; Lee, Sanggyu; Ryoo, Zae Young; Park, Eui-Kyun; Shin, Hong-In; Jung, Han-Sung; Kim, Jae-Young

    2011-08-01

    The molecular mechanisms for epithelial differentiation have been studied by observing skin development in embryogenesis, but the early signaling modulations involved in tongue epithelial differentiation are not completely understood. Based on the gene expression patterns of the Fgf signaling molecules and previous results from Fgf10 and Fgfr2b knockout mice, it was hypothesized that there would be fundamental signaling interactions through the epithelial Fgfr2b and its mesenchymal ligand Fgf10 to regulate tongue epithelium differentiation. To elucidate these reciprocal interactions in tongue epithelial differentiation, this study employed an in vitro tongue organ culture system with antisense-oligodeoxynucleotides (AS-ODNs) and recombinant protein-soaked bead implantation for the loss-of-function and gain-of-function studies. Functional analysis of Fgf signaling revealed precise reciprocal interactions, which showed that mesenchymal Fgf10 rather than Fgf7 modulates tongue epithelial differentiation via Fgfr2b in a temporal- and spatial-specific manner.

  7. Fasciculation and guidance of spinal motor axons in the absence of FGFR2 signaling.

    Directory of Open Access Journals (Sweden)

    Rosa-Eva Huettl

    Full Text Available During development, fibroblast growth factors (FGF are essential for early patterning events along the anterior-posterior axis, conferring positional identity to spinal motor neurons by activation of different Hox codes. In the periphery, signaling through one of four fibroblast growth factor receptors supports the development of the skeleton, as well as induction and maintenance of extremities. In previous studies, FGF receptor 2 (FGFR2 was found to interact with axon bound molecules involved in axon fasciculation and extension, thus rendering this receptor an interesting candidate for the promotion of proper peripheral innervation. However, while the involvement of FGFR2 in limb bud induction has been extensively studied, its role during axon elongation and formation of distinct nervous projections has not been addressed so far. We show here that motor neurons in the spinal cord express FGFR2 and other family members during the establishment of motor connections to the forelimb and axial musculature. Employing a conditional genetic approach to selectively ablate FGFR2 from motor neurons we found that the patterning of motor columns and the expression patterns of other FGF receptors and Sema3A in the motor columns of mutant embryos are not altered. In the absence of FGFR2 signaling, pathfinding of motor axons is intact, and also fasciculation, distal advancement of motor nerves and gross morphology and positioning of axonal projections are not altered. Our findings therefore show that FGFR2 is not required cell-autonomously in motor neurons during the formation of initial motor projections towards limb and axial musculature.

  8. Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome.

    Science.gov (United States)

    Wilkie, A O; Slaney, S F; Oldridge, M; Poole, M D; Ashworth, G J; Hockley, A D; Hayward, R D; David, D J; Pulleyn, L J; Rutland, P

    1995-02-01

    Apert syndrome is a distinctive human malformation comprising craniosynostosis and severe syndactyly of the hands and feet. We have identified specific missense substitutions involving adjacent amino acids (Ser252Trp and Pro253Arg) in the linker between the second and third extracellular immunoglobulin (Ig) domains of fibroblast growth factor receptor 2 (FGFR2) in all 40 unrelated cases of Apert syndrome studied. Crouzon syndrome, characterized by craniosynostosis but normal limbs, was previously shown to result from allelic mutations of the third Ig domain of FGFR2. The contrasting effects of these mutations provide a genetic resource for dissecting the complex effects of signal transduction through FGFRs in cranial and limb morphogenesis.

  9. Fibroblast growth factor receptor 2 (FGFR2) is required for corneal epithelial cell proliferation and differentiation during embryonic development.

    Science.gov (United States)

    Zhang, Jinglin; Upadhya, Dinesh; Lu, Lin; Reneker, Lixing W

    2015-01-01

    Fibroblast growth factors (FGFs) play important roles in many aspects of embryonic development. During eye development, the lens and corneal epithelium are derived from the same surface ectodermal tissue. FGF receptor (FGFR)-signaling is essential for lens cell differentiation and survival, but its role in corneal development has not been fully investigated. In this study, we examined the corneal defects in Fgfr2 conditional knockout mice in which Cre expression is activated at lens induction stage by Pax6 P0 promoter. The cornea in LeCre, Fgfr2(loxP/loxP) mice (referred as Fgfr2(CKO)) was analyzed to assess changes in cell proliferation, differentiation and survival. We found that Fgfr2(CKO) cornea was much thinner in epithelial and stromal layer when compared to WT cornea. At embryonic day 12.5-13.5 (E12.5-13.5) shortly after the lens vesicle detaches from the overlying surface ectoderm, cell proliferation (judged by labeling indices of Ki-67, BrdU and phospho-histone H3) was significantly reduced in corneal epithelium in Fgfr2(CKO) mice. At later stage, cell differentiation markers for corneal epithelium and underlying stromal mesenchyme, keratin-12 and keratocan respectively, were not expressed in Fgfr2(CKO) cornea. Furthermore, Pax6, a transcription factor essential for eye development, was not present in the Fgfr2(CKO) mutant corneal epithelial at E16.5 but was expressed normally at E12.5, suggesting that FGFR2-signaling is required for maintaining Pax6 expression in this tissue. Interestingly, the role of FGFR2 in corneal epithelial development is independent of ERK1/2-signaling. In contrast to the lens, FGFR2 is not required for cell survival in cornea. This study demonstrates for the first time that FGFR2 plays an essential role in controlling cell proliferation and differentiation, and maintaining Pax6 levels in corneal epithelium via ERK-independent pathways during embryonic development.

  10. Nuclear staining of fgfr-2/stat-5 and runx-2 in mucinous breast cancer.

    Science.gov (United States)

    May, María; Mosto, Julián; Vazquez, Paula Martinez; Gonzalez, Pedro; Rojas, Paola; Gass, Hugo; Lanari, Claudia; Molinolo, Alfredo A

    2016-02-01

    Mucinous carcinoma (MBC) is a rare subtype of breast cancer characterized by the production of variable amounts of mucin, with a prognosis better than that of non-mucinous carcinomas (NMBC). The aim of this project was to evaluate the expression of STAT-5, RUNX-2, and FGFR-2 in a cohort of MBC and compare it with that of NMBC using standard immunohistochemistry. STAT-5 and RUNX-2 are two transcription factors with cytoplasmic and/or nuclear localization that have been related to FGFR-2, a tyrosine kinase growth factor receptor that can interact with STAT-5 and with PR in the nuclei of breast cancer cells. Membranous, cytoplasmic, and nuclear staining were evaluated and expressed as the percentage of stained cells (0-100%) multiplied by the staining intensity (0-3), thus obtaining an index ranging from 0 to 300. Nuclear and/or cytoplasmic immunoreactivity of the three proteins were detected in a high number of NMBC. Nuclear FGFR-2 staining correlated with nuclear STAT-5 (pFGFR-2 (p<0.01) and RUNX-2 (p<0.05) than that of NMBC, and displayed positive immunoreactivity of the 3 proteins in 70.8% of the cases. These results suggest that these proteins may have a role in the progression of the mucinous phenotype, in which nuclear STAT-5 may inhibit RUNX-2 prometastatic effect.

  11. Fine-Scale Mapping of the FGFR2 Breast Cancer Risk Locus

    DEFF Research Database (Denmark)

    Meyer, Kerstin B; O'Reilly, Martin; Michailidou, Kyriaki

    2013-01-01

    The 10q26 locus in the second intron of FGFR2 is the locus most strongly associated with estrogen-receptor-positive breast cancer in genome-wide association studies. We conducted fine-scale mapping in case-control studies genotyped with a custom chip (iCOGS), comprising 41 studies (n = 89,050) of...

  12. Investigation of FGFR2-IIIC signaling via FGF-2 ligand for advancing GCT stromal cell differentiation.

    Directory of Open Access Journals (Sweden)

    Shalini Singh

    Full Text Available Giant cell tumor of bone (GCT is an aggressive bone tumor consisting of multinucleated osteoclast-like giant cells and proliferating osteoblast-like stromal cells. The signaling mechanism involved in GCT stromal cell osteoblastic differentiation is not fully understood. Previous work in our lab reported that GCT stromal cells express high levels of TWIST1, a master transcription factor in skeletal development, which in turn down-regulates Runx2 expression and prevents terminal osteoblastic differentiation in these cells. The purpose of this study was to determine the upstream regulation of TWIST1 in GCT cells. Using GCT stromal cells obtained from patient specimens, we demonstrated that fibroblast growth factor receptor (FGFR-2 signaling plays an essential role in bone development and promotes differentiation of immature osteoblastic cells. Fibroblast growth factor (FGF-2 stimulates FGFR-2 expression, resulting in decreased TWIST1 expression and increased Runx2, alkaline phosphastase (ALP and osteopontin (OPN expression. Inhibition of FGFR-2 through siRNA decreased the expression of ALP, Runx2 and OPN in GCT stromal cells. Our study also confirmed that FGF-2 ligand activates downstream ERK1/2 signaling and pharmacological inhibition of the ERK1/2 signaling pathway suppresses FGF-2 stimulated osteogenic differentiation in these cells. Our results indicate a significant role of FGFR-2 signaling in osteoblastic differentiation in GCT stromal cells.

  13. Allele-specific up-regulation of FGFR2 increases susceptibility to breast cancer.

    Directory of Open Access Journals (Sweden)

    Kerstin B Meyer

    2008-05-01

    Full Text Available The recent whole-genome scan for breast cancer has revealed the FGFR2 (fibroblast growth factor receptor 2 gene as a locus associated with a small, but highly significant, increase in the risk of developing breast cancer. Using fine-scale genetic mapping of the region, it has been possible to narrow the causative locus to a haplotype of eight strongly linked single nucleotide polymorphisms (SNPs spanning a region of 7.5 kilobases (kb in the second intron of the FGFR2 gene. Here we describe a functional analysis to define the causative SNP, and we propose a model for a disease mechanism. Using gene expression microarray data, we observed a trend of increased FGFR2 expression in the rare homozygotes. This trend was confirmed using real-time (RT PCR, with the difference between the rare and the common homozygotes yielding a Wilcox p-value of 0.028. To elucidate which SNPs might be responsible for this difference, we examined protein-DNA interactions for the eight most strongly disease-associated SNPs in different breast cell lines. We identify two cis-regulatory SNPs that alter binding affinity for transcription factors Oct-1/Runx2 and C/EBPbeta, and we demonstrate that both sites are occupied in vivo. In transient transfection experiments, the two SNPs can synergize giving rise to increased FGFR2 expression. We propose a model in which the Oct-1/Runx2 and C/EBPbeta binding sites in the disease-associated allele are able to lead to an increase in FGFR2 gene expression, thereby increasing the propensity for tumour formation.

  14. Investigation of G-quadruplex formation in the FGFR2 promoter region and its transcriptional regulation by liensinine.

    Science.gov (United States)

    Zhang, Lulu; Tan, Wei; Zhou, Jiang; Xu, Ming; Yuan, Gu

    2017-04-01

    Fibroblast growth factor receptor 2 (FGFR2) is overexpressed in breast cancer tissues and cells, and has been shown to be a susceptibility factor for breast cancer. In this study, we found that the G-rich sequences in the FGFR2 promoter region can form G-quadruplexes, which could be the target and inhibitor of the FGFR2 gene. Initially, the formation of G-quadruplexes was confirmed by ESI-MS and CD, and DMS footprinting experiments gave the folding pattern of the G-quadruplexes. After luciferase reporter assays revealed that the G-quadruplex could inhibit the activity of the FGFR2 promoter, MS and SPR showed binding affinity and selectivity of the ligand. Then cell culture experiments and ChIP assay showed the bioactivity of the ligand. We found that three G-rich sequences (S1-S3) in the FGFR2 promoter region can form G-quadruplex structures. And a natural alkaloid, liensinine, was found to bind to the S1 G-quadruplex with relative high affinity and selectivity. Cell culture experiments showed that liensinine inhibits FGFR2 activity at both the transcriptional and translational levels. Moreover, chromatin immunoprecipitation assay (ChIP) results showed that liensinine blocks the binding of E2F1 at the transcription factor binding site (TFBS) in the S1 sequence, which is the mechanism through which liensinine inhibits the FGFR2 gene. A natural alkaloid was discovered to selectively bind to the S1 G-quadruplex with relative high affinity, and therefore inhibited FGFR2 transcription and translation. Our discovery offers a useful strategy to inhibit FGFR2 transcription, i.e., targeting the G-quadruplex with a natural alkaloid. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Fgfr1 and the IIIc isoform of Fgfr2 play critical roles in the metanephric mesenchyme mediating early inductive events in kidney development

    OpenAIRE

    Sims-Lucas, Sunder; Cusack, Brian; Baust, Jeffrey; Eswarakumar, Veraragavan P.; Masatoshi, Hagiwara; Takeuchi, Akihide; Bates, Carlton M.

    2011-01-01

    Fibroblast growth factor receptors (Fgfrs) have critical roles in kidney development. FgfrIIIb is thought to act in epithelium, while FgfrIIIc functions in mesenchyme. We aimed to determine roles of Fgfr2IIIc in kidney development. Mice with deletion of Fgfr2IIIc (Fgfr2IIIc−/−) had normal kidneys. Combination of Fgfr2IIIc−/− with conditional deletion of Fgfr1 in metanephric mesenchyme (MM) (Fgfr1Mes−/−Fgfr2IIIc−/−) had small but identifiable MM at E10.5, expressing mesenchymal markers includi...

  16. Bent bone dysplasia (BBD)-FGFR2 type: the radiologic manifestations in early gestation

    Energy Technology Data Exchange (ETDEWEB)

    Handa, Atsuhiko; Okajima, Yuka; Kurihara, Yasuyuki [St. Luke' s International Hospital, Department of Radiology, Tokyo (Japan); Izumi, Noriko; Yamanaka, Michiko [St. Luke' s International Hospital, Department of Integrated Women' s Health, Tokyo (Japan)

    2016-02-15

    Bent bone dysplasia-fibroblast growth factor receptor 2 type (BBD-FGFR2) is a recently identified skeletal dysplasia caused by specific FGFR2 mutations, characterized by craniosynostosis and prenatal bowing of the long bones. Only a few cases have been published. We report an affected fetus terminated at 21 weeks of gestation. The clinical and radiologic manifestations mostly recapitulate previous descriptions; however we suggest additional hallmarks of this disorder in early gestation. These hallmarks include distinctive short, thick clavicles and wavy ribs, as well as vertebral bodies that showed striking anteroposterior shortening. Femoral fractures were also present in our case. Although craniosynostosis is a hallmark of the disease, clinicians should be aware that craniosynostosis might not be readily apparent on plain films early in gestation. (orig.)

  17. Recombinant expression in E. coli of human FGFR2 with its transmembrane and extracellular domains

    Directory of Open Access Journals (Sweden)

    Adam Bajinting

    2017-06-01

    Full Text Available Fibroblast growth factor receptors (FGFRs are a family of receptor tyrosine kinases containing three domains: an extracellular receptor domain, a single transmembrane helix, and an intracellular tyrosine kinase domain. FGFRs are activated by fibroblast growth factors (FGFs as part of complex signal transduction cascades regulating angiogenesis, skeletal formation, cell differentiation, proliferation, cell survival, and cancer. We have developed the first recombinant expression system in E. coli to produce a construct of human FGFR2 containing its transmembrane and extracellular receptor domains. We demonstrate that the expressed construct is functional in binding heparin and dimerizing. Size exclusion chromatography demonstrates that the purified FGFR2 does not form a complex with FGF1 or adopts an inactive dimer conformation. Progress towards the successful recombinant production of intact FGFRs will facilitate further biochemical experiments and structure determination that will provide insight into how extracellular FGF binding activates intracellular kinase activity.

  18. FGFR2 is amplified in the NCI-H716 colorectal cancer cell line and is required for growth and survival.

    Science.gov (United States)

    Mathur, Anjili; Ware, Christopher; Davis, Lenora; Gazdar, Adi; Pan, Bo-Sheng; Lutterbach, Bart

    2014-01-01

    Aberrant kinase activation resulting from mutation, amplification, or translocation can drive growth and survival in a subset of human cancer. FGFR2 is amplified in breast and gastric cancer, and we report here the first characterization of FGFR2 gene amplification in colorectal cancer in the NCI-H716 colorectal cancer cell line. FGFR2 is highly expressed and activated in NCI-H716 cells, and FGFR selective small molecule inhibitors or FGFR2 shRNA strongly inhibited cell viability in vitro, indicating "addiction" of NCI-H716 cells to FGFR2. NCI-H716 growth in a xenograft model was also inhibited by an FGFR small molecule inhibitor. FGFR2 was required for activation of multiple downstream signaling proteins including AKT, ERK, S6RP and NFKB. Inhibition of downstream kinases such as AKT or ERK alone had modest effects on proliferation, whereas combined inhibition of AKT and ERK signaling resulted in a loss of viability similar to FGFR2 inhibition. We identified elevated FGFR2 expression in a small subset of primary colorectal cancer, however FGFR2 amplification was not observed. Although FGFR2 amplification is not common in primary colon cancer or lymph node and liver metastases, other subsets of colorectal cancer such as ascites, from which the NCI-H716 cell line was derived, have yet to be tested. These results suggest that emerging FGFR inhibitor therapeutics may have efficacy in a subset of colon cancer driven by FGFR2 amplification.

  19. FGFR2 is amplified in the NCI-H716 colorectal cancer cell line and is required for growth and survival.

    Directory of Open Access Journals (Sweden)

    Anjili Mathur

    Full Text Available Aberrant kinase activation resulting from mutation, amplification, or translocation can drive growth and survival in a subset of human cancer. FGFR2 is amplified in breast and gastric cancer, and we report here the first characterization of FGFR2 gene amplification in colorectal cancer in the NCI-H716 colorectal cancer cell line. FGFR2 is highly expressed and activated in NCI-H716 cells, and FGFR selective small molecule inhibitors or FGFR2 shRNA strongly inhibited cell viability in vitro, indicating "addiction" of NCI-H716 cells to FGFR2. NCI-H716 growth in a xenograft model was also inhibited by an FGFR small molecule inhibitor. FGFR2 was required for activation of multiple downstream signaling proteins including AKT, ERK, S6RP and NFKB. Inhibition of downstream kinases such as AKT or ERK alone had modest effects on proliferation, whereas combined inhibition of AKT and ERK signaling resulted in a loss of viability similar to FGFR2 inhibition. We identified elevated FGFR2 expression in a small subset of primary colorectal cancer, however FGFR2 amplification was not observed. Although FGFR2 amplification is not common in primary colon cancer or lymph node and liver metastases, other subsets of colorectal cancer such as ascites, from which the NCI-H716 cell line was derived, have yet to be tested. These results suggest that emerging FGFR inhibitor therapeutics may have efficacy in a subset of colon cancer driven by FGFR2 amplification.

  20. Enhanced Fitness of Adult Spermatogonial Stem Cells Bearing a Paternal Age-Associated FGFR2 Mutation

    Directory of Open Access Journals (Sweden)

    Laura A. Martin

    2014-08-01

    Full Text Available Pathogenic de novo mutations increase with fathers’ age and could be amplified through competition between genetically distinct subpopulations of spermatogonial stem cells (SSCs. Here, we tested the fitness of SSCs bearing wild-type human FGFR2 or an Apert syndrome mutant, FGFR2 (S252W, to provide experimental evidence for SSC competition. The S252W allele conferred enhanced FGFR2-mediated signaling, particularly at very low concentrations of ligand, and also subtle changes in gene expression. Mutant SSCs exhibited improved competitiveness in vitro and increased stem cell activity in vivo upon transplantation. The fitness advantage in vitro only occurred in low concentrations of fibroblast growth factor (FGF, was independent of FGF-driven proliferation, and was accompanied by increased response to glial cell line-derived neurotrophic factor (GDNF. Our studies provide experimental evidence of enhanced stem cell fitness in SSCs bearing a paternal age-associated mutation. Our model will be useful for interrogating other candidate mutations in the future to reveal mechanisms of disease risk.

  1. Suramin blocks interaction between human FGF1 and FGFR2 D2 domain and reduces downstream signaling activity

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Zong-Sian, E-mail: gary810426@hotmail.com [Department of Chemistry, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan (China); Liu, Che Fu, E-mail: s9823002@m98.nthu.edu.tw [Department of Chemistry, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan (China); Fu, Brian, E-mail: brianfu9@gmail.com [Northwood High School, Irvine, CA (United States); Chou, Ruey-Hwang, E-mail: rhchou@mail.cmu.edu.tw [Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, No.91, Hsueh-Shih Road, Taichung 40402, Taiwan (China); Department of Biotechnology, Asia University, Taiwan (China); Yu, Chin, E-mail: cyu.nthu@gmail.com [Department of Chemistry, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan (China)

    2016-09-02

    The extracellular portion of the human fibroblast growth factor receptor2 D2 domain (FGFR2 D2) interacts with human fibroblast growth factor 1 (hFGF1) to activate a downstream signaling cascade that ultimately affects mitosis and differentiation. Suramin is an antiparasiticdrug and a potent inhibitor of FGF-induced angiogenesis. Suramin has been shown to bind to hFGF1, and might block the interaction between hFGF1 and FGFR2 D2. Here, we titrated hFGF1 with FGFR2 D2 and suramin to elucidate their interactions using the detection of NMR. The docking results of both hFGF1-FGFR2 D2 domain and hFGF1-suramin complex were superimposed. The results indicate that suramin blocks the interaction between hFGF1 and FGFR2 D2. We used the PyMOL software to show the hydrophobic interaction of hFGF1-suramin. In addition, we used a Water-soluble Tetrazolium salts assay (WST1) to assess hFGF1 bioactivity. The results will be useful for the development of new antimitogenic activity drugs. - Highlights: • The interfacial residues on hFGF1-FGFR2 D2 and hFGF1-Suramin contact surface were mapped by {sup 1}H-{sup 15}N HSQC experiments. • hFGF1-FGFR2 D2 and hFGF1-Suramin complex models were generated from NMR restraints by using HADDOCK program. • We analyzed hFGF1-Suramin complex models and found the interaction between hFGF1-Suramin is hydrophobic. • The bioactivity of the hFGF1-FGFR2 D2 and hFGF1-Suramin complex was studied by using WST1 assay.

  2. FGF/FGFR2 signaling regulates the generation and correct positioning of Bergmann glia cells in the developing mouse cerebellum.

    Directory of Open Access Journals (Sweden)

    Florian Meier

    Full Text Available The normal cellular organization and layering of the vertebrate cerebellum is established during embryonic and early postnatal development by the interplay of a complex array of genetic and signaling pathways. Disruption of these processes and of the proper layering of the cerebellum usually leads to ataxic behaviors. Here, we analyzed the relative contribution of Fibroblast growth factor receptor 2 (FGFR2-mediated signaling to cerebellar development in conditional Fgfr2 single mutant mice. We show that during embryonic mouse development, Fgfr2 expression is higher in the anterior cerebellar primordium and excluded from the proliferative ventricular neuroepithelium. Consistent with this finding, conditional Fgfr2 single mutant mice display the most prominent defects in the anterior lobules of the adult cerebellum. In this context, FGFR2-mediated signaling is required for the proper generation of Bergmann glia cells and the correct positioning of these cells within the Purkinje cell layer, and for cell survival in the developing cerebellar primordium. Using cerebellar microexplant cultures treated with an FGFR agonist (FGF9 or antagonist (SU5402, we also show that FGF9/FGFR-mediated signaling inhibits the outward migration of radial glia and Bergmann glia precursors and cells, and might thus act as a positioning cue for these cells. Altogether, our findings reveal the specific functions of the FGFR2-mediated signaling pathway in the generation and positioning of Bergmann glia cells during cerebellar development in the mouse.

  3. The N550K/H Mutations in FGFR2 Confer Differential Resistance to PD173074, Dovitinib, and Ponatinib ATP-Competitive Inhibitors

    Directory of Open Access Journals (Sweden)

    Sara A Byron

    2013-08-01

    Full Text Available We sought to identify fibroblast growth factor receptor 2 (FGFR2 kinase domain mutations that confer resistance to the pan-FGFR inhibitor, dovitinib, and explore the mechanism of action of the drug-resistant mutations. We cultured BaF3 cells overexpressing FGFR2 in high concentrations of dovitinib and identified 14 dovitinib-resistant mutations, including the N550K mutation observed in 25% of FGFR2mutant endometrial cancers (ECs. Structural and biochemical in vitro kinase analyses, together with BaF3 proliferation assays, showed that the resistance mutations elevate the intrinsic kinase activity of FGFR2. BaF3 lines were used to assess the ability of each mutation to confer cross-resistance to PD173074 and ponatinib. Unlike PD173074, ponatinib effectively inhibited all the dovitinib-resistant FGFR2 mutants except the V565I gatekeeper mutation, suggesting ponatinib but not dovitinib targets the active conformation of FGFR2 kinase. EC cell lines expressing wild-type FGFR2 were relatively resistant to all inhibitors, whereas EC cell lines expressing mutated FGFR2 showed differential sensitivity. Within the FGFR2mutant cell lines, three of seven showed marked resistance to PD173074 and relative resistance to dovitinib and ponatinib. This suggests that alternative mechanisms distinct from kinase domain mutations are responsible for intrinsic resistance in these three EC lines. Finally, overexpression of FGFR2N550K in JHUEM-2 cells (FGFR2C383R conferred resistance (about five-fold to PD173074, providing independent data that FGFR2N550K can be associated with drug resistance. Biochemical in vitro kinase analyses also show that ponatinib is more effective than dovitinib at inhibiting FGFR2N550K. We propose that tumors harboring mutationally activated FGFRs should be treated with FGFR inhibitors that specifically bind the active kinase.

  4. Study on expression levels of Hpa, bFGF and FGFR - 2 in gastric cancer tissue%胃癌组织中Hpa、bFGF及FGFR-2表达水平的研究

    Institute of Scientific and Technical Information of China (English)

    黄志强; 刘胜; 陈森林; 陆健

    2008-01-01

    目的 探讨胃癌组织中Hpa、bFGF及FGFR-2表达水平与胃癌发生、发展的关系.方法 对55例胃癌、癌旁组织及正常胃组织应用免疫组化方法 检测Hpa、bFGF及FGFR-2的表达水平并进行分析.结果 对照组的bFGF、FGFR-2表达低于其余2组(P均<0.05);Hpa在胃癌组表达显著高于其他2组(P<0.01);bFGF、FGFR-2及Hpa的表达与胃癌浸润深度、淋巴结转移、远处转移及TNM分期有关(P均<0.01).结论 bFGF、FGFR-2及Hpa可能在胃癌的漫润和转移中起重要作用,可作为胃癌生物学行为的重要指标.

  5. 成纤维细胞生长因子受体2多态性与乳腺癌相关性研究%Relative research of FGFR2 Gene SNPs and breast neoplasm

    Institute of Scientific and Technical Information of China (English)

    徐维华; 王守彪

    2012-01-01

    Objective To investigate whether single nucleotide polymorphisms (SNP) of fibroblast growth receptor 2 (FGFR2) are associated with breast cancer risk. Methods In the present study of 280 breast cancer patients and 280 cancer-free controls, we tested three FGFR2 polymorphisms (rs2981582, rs2981578A/G and rs2912778) the method of ASA-PCR. Results Differences were found in the genotypes between the breast neoplasm group and the control group of all loci (P 0.05). Conclusion The findings indicate that genetic variants in FGFR2 may contribute to breast cancer occurrence.%目的 研究成纤维细胞生长因子受体2(FGFR2)基因单核苷酸多态性(SNP)与乳腺癌相关性.方法对280例乳腺癌患者及280例健康女性进行ASA-PCR检测,分析其三个位点(rs2912778、rs2981582、rs2981578)SNP与乳腺癌风险关系.结果三个位点(rs2912778、rs2981582、rs2981578)基因型分布在乳腺癌组和对照组中差异具有统计学意义(P < 0.05);与病理资料进一步联系分析,除rs2912778在淋巴结转移方面野生型与变异型差异具有高度统计学意义(P < 0.01)之外,其余三个位点野生型与变异型相比差异均无统计学意义(均P > 0.05).结论 FGFR2基因三个位点单核苷酸多态性可能与乳腺癌的发生有关.

  6. Q289p Mutation In Fgfr2 Gene Causes Saethre-chotzen Syndrome: Some Considerations About Familial Heterogeneity.

    OpenAIRE

    2015-01-01

    Objective: To describe the first report on a three-generation family presenting typical features of Saethre-Chotzen syndrome, in which the Q289P mutation in the FGFR2 gene was detected. Design: Dysmorphological evaluation was performed by a clinical geneticist. Direct sequencing of the polymerase chain reaction-amplified coding region of TWIST and screening for the P250R mutation in the FGFR3 gene were performed. Exons IIIa and IIIc of FGFR2 were sequenced also. The mutation was confirmed by ...

  7. Biochemical Analysis of Pathogenic Ligand-Dependent FGFR2 Mutations Suggests Distinct Pathophysiological Mechanisms for Craniofacial and Limb Abnormalities in Human Skeletal Disorders

    Energy Technology Data Exchange (ETDEWEB)

    Ibrahimi,O.; Zhang, F.; Eliseenkova, A.; Itoh, N.; Linhardt, R.; Mohammadi, M.

    2004-01-01

    Gain-of-function missense mutations in FGF receptor 2 (FGFR2) are responsible for a variety of craniosynostosis syndromes including Apert syndrome (AS), Pfeiffer syndrome (PS) and Crouzon syndrome (CS). Unlike the majority of FGFR2 mutations, S252W and P253R AS mutations and a D321A PS mutation retain ligand-dependency and are also associated with severe limb pathology. In addition, a recently identified ligand-dependent S252L/A315S double mutation in FGFR2 was shown to cause syndactyly in the absence of craniosynostosis. Here, we analyze the effect of the canonical AS mutations, the D321A PS mutation and the S252L/A315S double mutation on FGFR2 ligand binding affinity and specificity using surface plasmon resonance. Both AS mutations and the D321A PS mutation, but not the S252L/A315S double mutation, increase the binding affinity of FGFR2c to multiple FGFs expressed in the cranial suture. Additionally, all four pathogenic mutations also violate FGFR2c ligand binding specificity and enable this receptor to bind FGF10. Based on our data, we propose that an increase in mutant FGFR2c binding to multiple FGFs results in craniosynostosis, whereas binding of mutant FGFR2c to FGF10 results in severe limb pathology. Structural and biophysical analysis shows that AS mutations in FGFR2b also enhance and violate FGFR2b ligand binding affinity and specificity, respectively. We suggest that elevated AS mutant FGFR2b signaling may account for the dermatological manifestations of AS.

  8. Significance of bFGF, FGFR-2 and Hpa expression in gastric precancerous lesions and gastric carcinoma tissues%胃癌及癌前病变中bFGF FGFR-2及Hpa的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    覃山羽; 姜海行; 李信; 唐国都; 陈罡; 雷琳

    2007-01-01

    目的 探讨胃癌及癌前病变中碱性成纤维细胞生长因子(bFGF)、成纤维细胞生长因子受体-2(FGFR-2)及乙酰肝素酶(Hpa)的表达及其与胃癌发生发展的关系.方法 选择广西医科大学第一附属医院2001-2005年手术切除和内镜活检的胃黏膜标本145例,其中慢性浅表性胃炎(CSG)组30例、胃黏膜肠上皮化生(IM)组29例、不典型增生(Dys)组31例、胃癌(GC)组55例,采用免疫组化SP法检测各组bFGF、FGFR-2及Hpa的表达.结果 bFGF、FGFR-2的表达CSG组低于其余3组(P<0.05),IM组低于Dys组和GC组(P<0.05);Hpa在GC组表达显著高于其他3组(P<0.01);bFGF、FGFR-2及Hpa的表达与胃癌浸润深度、淋巴结转移、远处转移及TNM分期有关(P<0.01).结论 bFGF、FGFR-2及Hpa可能参与胃癌的发生发展过程,并可能加速胃癌的浸润和转移.

  9. Low Risk Anomalies?

    DEFF Research Database (Denmark)

    Schneider, Paul; Wagner, Christian; Zechner, Josef

    This paper shows theoretically and empirically that beta- and volatility-based low risk anomalies are driven by return skewness. The empirical patterns concisely match the predictions of our model that endogenizes the role of skewness for stock returns through default risk. With increasing downside...... of betting against beta/volatility among low skew firms compared to high skew firms is economically large. Our results suggest that the returns to betting against beta or volatility do not necessarily pose asset pricing puzzles but rather that such strategies collect premia that compensate for skew risk...

  10. Computational mouse atlases and their application to automatic assessment of craniofacial dysmorphology caused by the Crouzon mutation Fgfr2

    DEFF Research Database (Denmark)

    Ólafsdóttir, Hildur; Darvann, Tron Andre; Hermann, Nuno V.;

    2007-01-01

    Crouzon syndrome is characterised by premature fusion of sutures and synchondroses. Recently the first mouse model of the syndrome was generated, having the mutation Cys342Tyr in Fgfr2c, equivalent to the most common human Crouzon/Pfeiffer syndrome mutation. In this study, a set of Micro CT...

  11. Computational mouse atlases and their application to automatic assessment of craniofacial dysmorphology caused by the Crouzon mutation Fgfr2

    DEFF Research Database (Denmark)

    Ólafsdóttir, Hildur; Darvann, Tron Andre; Hermann, Nuno V.

    2007-01-01

    Crouzon syndrome is characterised by premature fusion of sutures and synchondroses. Recently the first mouse model of the syndrome was generated, having the mutation Cys342Tyr in Fgfr2c, equivalent to the most common human Crouzon/Pfeiffer syndrome mutation. In this study, a set of Micro CT...

  12. Rapidly acquired resistance to EGFR tyrosine kinase inhibitors in NSCLC cell lines through de-repression of FGFR2 and FGFR3 expression.

    Directory of Open Access Journals (Sweden)

    Kathryn E Ware

    Full Text Available Despite initial and sometimes dramatic responses of specific NSCLC tumors to EGFR TKIs, nearly all will develop resistance and relapse. Gene expression analysis of NSCLC cell lines treated with the EGFR TKI, gefitinib, revealed increased levels of FGFR2 and FGFR3 mRNA. Analysis of gefitinib action on a larger panel of NSCLC cell lines verified that FGFR2 and FGFR3 expression is increased at the mRNA and protein level in NSCLC cell lines in which the EGFR is dominant for growth signaling, but not in cell lines where EGFR signaling is absent. A luciferase reporter containing 2.5 kilobases of fgfr2 5' flanking sequence was activated after gefitinib treatment, indicating transcriptional regulation as a contributing mechanism controlling increased FGFR2 expression. Induction of FGFR2 and FGFR3 protein as well as fgfr2-luc activity was also observed with Erbitux, an EGFR-specific monoclonal antibody. Moreover, inhibitors of c-Src and MEK stimulated fgfr2-luc activity to a similar degree as gefitinib, suggesting that these pathways may mediate EGFR-dependent repression of FGFR2 and FGFR3. Importantly, our studies demonstrate that EGFR TKI-induced FGFR2 and FGFR3 are capable of mediating FGF2 and FGF7 stimulated ERK activation as well as FGF-stimulated transformed growth in the setting of EGFR TKIs. In conclusion, this study highlights EGFR TKI-induced FGFR2 and FGFR3 signaling as a novel and rapid mechanism of acquired resistance to EGFR TKIs and suggests that treatment of NSCLC patients with combinations of EGFR and FGFR specific TKIs may be a strategy to enhance efficacy of single EGFR inhibitors.

  13. CGH, cDNA and Tissue Microarray Analyses Implicate FGFR2 Amplification in a Small Subset of Breast Tumors

    Directory of Open Access Journals (Sweden)

    Mervi Heiskanen

    2001-01-01

    Full Text Available Multiple regions of the genome are often amplified during breast cancer development and progression, as evidenced in a number of published studies by comparative genomic hybridization (CGH. However, only relatively few target genes for such amplifications have been identified. Here, we indicate how small‐scale commercially available cDNA and CGH microarray formats combined with the tissue microarray technology enable rapid identification of putative amplification target genes as well as analysis of their clinical significance. According to CGH, the SUM‐52 breast cancer cell line harbors several high‐level DNA amplification sites, including the 10q26 chromosomal region where the fibroblast growth factor receptor 2 (FGFR2 gene has been localized. High level amplification of FGFR2 in SUM‐52 was identified using CGH analysis on a microarray of BAC clones. A cDNA microarray survey of 588 genes showed >40‐fold overexpression of FGFR2. Finally, a tissue microarray based FISH analysis of 750 uncultured primary breast cancers demonstrated in vivo amplification of the FGFR2 gene in about 1% of the tumors. In conclusion, three consecutive microarray (CGH, cDNA and tissue experiments revealed high‐level amplification and overexpression of the FGFR2 in a breast cancer cell line, but only a low frequency of involvement in primary breast tumors. Applied to a genomic scale with larger arrays, this strategy should facilitate identification of the most important target genes for cytogenetic rearrangements, such as DNA amplification sites detected by conventional CGH. Figures on http://www.esacp.org/acp/2001/22‐4/heiskanen.htm

  14. Low Risk Anomalies?

    DEFF Research Database (Denmark)

    Schneider, Paul; Wagner, Christian; Zechner, Josef

    risk, the standard capital asset pricing model (CAPM) increasingly overestimates expected equity returns relative to firms' true (skew-adjusted) market risk. Empirically, the profitability of betting against beta/volatility increases with firms' downside risk, and the risk-adjusted return differential...... of betting against beta/volatility among low skew firms compared to high skew firms is economically large. Our results suggest that the returns to betting against beta or volatility do not necessarily pose asset pricing puzzles but rather that such strategies collect premia that compensate for skew risk......This paper shows theoretically and empirically that beta- and volatility-based low risk anomalies are driven by return skewness. The empirical patterns concisely match the predictions of our model that endogenizes the role of skewness for stock returns through default risk. With increasing downside...

  15. Effects of FGFR2 kinase activation loop dynamics on catalytic activity

    Science.gov (United States)

    2017-01-01

    The structural mechanisms by which receptor tyrosine kinases (RTKs) regulate catalytic activity are diverse and often based on subtle changes in conformational dynamics. The regulatory mechanism of one such RTK, fibroblast growth factor receptor 2 (FGFR2) kinase, is still unknown, as the numerous crystal structures of the unphosphorylated and phosphorylated forms of the kinase domains show no apparent structural change that could explain how phosphorylation could enable catalytic activity. In this study, we use several enhanced sampling molecular dynamics (MD) methods to elucidate the structural changes to the kinase’s activation loop that occur upon phosphorylation. We show that phosphorylation favors inward motion of Arg664, while simultaneously favoring outward motion of Leu665 and Pro666. The latter structural change enables the substrate to bind leading to its resultant phosphorylation. Inward motion of Arg664 allows it to interact with the γ-phosphate of ATP as well as the substrate tyrosine. We show that this stabilizes the tyrosine and primes it for the catalytic phosphotransfer, and it may lower the activation barrier of the phosphotransfer reaction. Our work demonstrates the value of including dynamic information gleaned from computer simulation in deciphering RTK regulatory function. PMID:28151998

  16. Effects of FGFR2 kinase activation loop dynamics on catalytic activity.

    Science.gov (United States)

    Karp, Jerome M; Sparks, Samuel; Cowburn, David

    2017-02-01

    The structural mechanisms by which receptor tyrosine kinases (RTKs) regulate catalytic activity are diverse and often based on subtle changes in conformational dynamics. The regulatory mechanism of one such RTK, fibroblast growth factor receptor 2 (FGFR2) kinase, is still unknown, as the numerous crystal structures of the unphosphorylated and phosphorylated forms of the kinase domains show no apparent structural change that could explain how phosphorylation could enable catalytic activity. In this study, we use several enhanced sampling molecular dynamics (MD) methods to elucidate the structural changes to the kinase's activation loop that occur upon phosphorylation. We show that phosphorylation favors inward motion of Arg664, while simultaneously favoring outward motion of Leu665 and Pro666. The latter structural change enables the substrate to bind leading to its resultant phosphorylation. Inward motion of Arg664 allows it to interact with the γ-phosphate of ATP as well as the substrate tyrosine. We show that this stabilizes the tyrosine and primes it for the catalytic phosphotransfer, and it may lower the activation barrier of the phosphotransfer reaction. Our work demonstrates the value of including dynamic information gleaned from computer simulation in deciphering RTK regulatory function.

  17. Effects of FGFR2 kinase activation loop dynamics on catalytic activity.

    Directory of Open Access Journals (Sweden)

    Jerome M Karp

    2017-02-01

    Full Text Available The structural mechanisms by which receptor tyrosine kinases (RTKs regulate catalytic activity are diverse and often based on subtle changes in conformational dynamics. The regulatory mechanism of one such RTK, fibroblast growth factor receptor 2 (FGFR2 kinase, is still unknown, as the numerous crystal structures of the unphosphorylated and phosphorylated forms of the kinase domains show no apparent structural change that could explain how phosphorylation could enable catalytic activity. In this study, we use several enhanced sampling molecular dynamics (MD methods to elucidate the structural changes to the kinase's activation loop that occur upon phosphorylation. We show that phosphorylation favors inward motion of Arg664, while simultaneously favoring outward motion of Leu665 and Pro666. The latter structural change enables the substrate to bind leading to its resultant phosphorylation. Inward motion of Arg664 allows it to interact with the γ-phosphate of ATP as well as the substrate tyrosine. We show that this stabilizes the tyrosine and primes it for the catalytic phosphotransfer, and it may lower the activation barrier of the phosphotransfer reaction. Our work demonstrates the value of including dynamic information gleaned from computer simulation in deciphering RTK regulatory function.

  18. Variation in the FGFR2 gene and the effect of a low-fat dietary pattern on invasive breast cancer.

    Science.gov (United States)

    Prentice, Ross L; Huang, Ying; Hinds, David A; Peters, Ulrike; Cox, David R; Beilharz, Erica; Chlebowski, Rowan T; Rossouw, Jacques E; Caan, Bette; Ballinger, Dennis G

    2010-01-01

    The Women's Health Initiative dietary modification (DM) trial provided suggestive evidence of a benefit of a low-fat dietary pattern on breast cancer risk, with stronger evidence among women whose baseline diet was high in fat. Single nucleotide polymorphisms (SNP) in the FGFR2 gene relate strongly to breast cancer risk and could influence intervention effects. All 48,835 trial participants were postmenopausal and ages 50 to 79 years at enrollment (1993-1998). We interrogated eight SNPs in intron 2 of the FGFR2 gene for 1,676 women who developed breast cancer during trial follow-up (1993-2005). Case-only analyses were used to estimate odds ratios for the DM intervention in relation to SNP genotype. Odds ratios for the DM intervention did not vary significantly with the genotype for any of the eight FGFR2 SNPs (P > or = 0.18). However, odds ratios varied (P or =36.8%). This variation is most evident for SNP rs3750817, with odds ratios for the DM intervention at 0, 1, and 2 minor SNP alleles of 1.06 [95% confidence intervals (95% CI), 0.80-1.41], 0.53 (95% CI, 0.38-0.74), and 0.62 (95% CI, 0.33-1.15). The nominal significance level for this interaction is P = 0.005, and P = 0.03 following multiple testing adjustment, with most evidence deriving from hormone receptor-positive tumors. Invasive breast cancer odds ratios for a low-fat dietary pattern, among women whose usual diets are high in fat, seem to vary with SNP rs3750817 in the FGFR2 gene.

  19. FGFR2 is overexpressed in myxoid liposarcoma and inhibition of FGFR signaling impairs tumor growth in vitro.

    Science.gov (United States)

    Künstlinger, Helen; Fassunke, Jana; Schildhaus, Hans-Ulrich; Brors, Benedikt; Heydt, Carina; Ihle, Michaela Angelika; Mechtersheimer, Gunhild; Wardelmann, Eva; Büttner, Reinhard; Merkelbach-Bruse, Sabine

    2015-08-21

    Myxoid liposarcomas account for more than one third of liposarcomas and about 10% of all adult soft tissue sarcomas. The tumors are characterized by specific chromosomal translocations leading to the chimeric oncogenes FUS-DDIT3 or EWS1R-DDIT3. The encoded fusion proteins act as aberrant transcription factors. Therefore, we implemented comparative expression analyses using whole-genome microarrays in tumor and fat tissue samples. We aimed at identifying differentially expressed genes which may serve as diagnostic or prognostic biomarkers or as therapeutic targets. Microarray analyses revealed overexpression of FGFR2 and other members of the FGF/FGFR family. Overexpression of FGFR2 was validated by qPCR, immunohistochemistry and western blot analysis in primary tumor samples. Treatment of the myxoid liposarcoma cell lines MLS 402 and MLS 1765 with the FGFR inhibitors PD173074, TKI258 (dovitinib) and BGJ398 as well as specific siRNAs reduced cell proliferation, induced apoptosis and delayed cell migration. Combination of FGFR inhibitors with trabectedin further increased the effect. Our study demonstrates overexpression of FGFR2 and a functional role of FGFR signaling in myxoid liposarcoma. As FGFR inhibition showed effects on proliferation and cell migration and induced apoptosis in vitro, our data indicate the potential use of FGFR inhibitors as a targeted therapy for these tumors.

  20. Variation in the FGFR2 gene and the effects of postmenopausal hormone therapy on invasive breast cancer.

    Science.gov (United States)

    Prentice, Ross L; Huang, Ying; Hinds, David A; Peters, Ulrike; Pettinger, Mary; Cox, David R; Beilharz, Erica; Chlebowski, Rowan T; Rossouw, Jacques E; Caan, Bette; Ballinger, Dennis G

    2009-11-01

    Breast cancer concern is a major reason for the recent marked reduction in use of postmenopausal hormone therapy, although equally effective means of controlling menopausal symptoms are lacking. Single nucleotide polymorphisms (SNP) in the fibroblast growth factor receptor 2 (FGFR2) gene are substantially associated with postmenopausal breast cancer risk and could influence hormone therapy effects. We interrogated eight SNPs in intron 2 of the FGFR2 gene for 2,166 invasive breast cancer cases from the Women's Health Initiative clinical trial and one-to-one matched controls to confirm an association with breast cancer risk. We used case-only analyses to examine the dependence of estrogen plus progestin and estrogen-alone odds ratios on SNP genotype. Seven FGFR2 SNPs, including six in a single linkage disequilibrium region, were found to associate strongly (P rs3750817 (minor allele T with frequency 0.39) had an estimated per-minor-allele odds ratio of 0.78, and was not in such strong linkage disequilibrium with the other SNPs. The genotype of this SNP related significantly (P rs3750817 have a reduced breast cancer risk and seem to experience comparatively favorable effects of postmenopausal hormone therapy.

  1. Low-risk susceptibility alleles in 40 human breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Klijn Jan GM

    2009-07-01

    Full Text Available Abstract Background Low-risk breast cancer susceptibility alleles or SNPs confer only modest breast cancer risks ranging from just over 1.0 to1.3 fold. Yet, they are common among most populations and therefore are involved in the development of essentially all breast cancers. The mechanism by which the low-risk SNPs confer breast cancer risks is currently unclear. The breast cancer association consortium BCAC has hypothesized that the low-risk SNPs modulate expression levels of nearby located genes. Methods Genotypes of five low-risk SNPs were determined for 40 human breast cancer cell lines, by direct sequencing of PCR-amplified genomic templates. We have analyzed expression of the four genes that are located nearby the low-risk SNPs, by using real-time RT-PCR and Human Exon microarrays. Results The SNP genotypes and additional phenotypic data on the breast cancer cell lines are presented. We did not detect any effect of the SNP genotypes on expression levels of the nearby-located genes MAP3K1, FGFR2, TNRC9 and LSP1. Conclusion The SNP genotypes provide a base line for functional studies in a well-characterized cohort of 40 human breast cancer cell lines. Our expression analyses suggest that a putative disease mechanism through gene expression modulation is not operative in breast cancer cell lines.

  2. Analysis of the Fgfr2C342Y mouse model shows condensation defects due to misregulation of Sox9 expression in prechondrocytic mesenchyme

    Science.gov (United States)

    Peskett, Emma; Kumar, Samin; Baird, William; Jaiswal, Janhvi; Li, Ming; Patel, Priyanca; Britto, Jonathan A.

    2017-01-01

    ABSTRACT Syndromic craniosynostosis caused by mutations in FGFR2 is characterised by developmental pathology in both endochondral and membranous skeletogenesis. Detailed phenotypic characterisation of features in the membranous calvarium, the endochondral cranial base and other structures in the axial and appendicular skeleton has not been performed at embryonic stages. We investigated bone development in the Crouzon mouse model (Fgfr2C342Y) at pre- and post-ossification stages to improve understanding of the underlying pathogenesis. Phenotypic analysis was performed by whole-mount skeletal staining (Alcian Blue/Alizarin Red) and histological staining of sections of CD1 wild-type (WT), Fgfr2C342Y/+ heterozygous (HET) and Fgfr2C342Y/C342Y homozygous (HOM) mouse embryos from embryonic day (E)12.5-E17.5 stages. Gene expression (Sox9, Shh, Fgf10 and Runx2) was studied by in situ hybridisation and protein expression (COL2A1) by immunohistochemistry. Our analysis has identified severely decreased osteogenesis in parts of the craniofacial skeleton together with increased chondrogenesis in parts of the endochondral and cartilaginous skeleton in HOM embryos. The Sox9 expression domain in tracheal and basi-cranial chondrocytic precursors at E13.5 in HOM embryos is increased and expanded, correlating with the phenotypic observations which suggest FGFR2 signalling regulates Sox9 expression. Combined with abnormal staining of type II collagen in pre-chondrocytic mesenchyme, this is indicative of a mesenchymal condensation defect. An expanded spectrum of phenotypic features observed in the Fgfr2C342Y/C342Y mouse embryo paves the way towards better understanding the clinical attributes of human Crouzon–Pfeiffer syndrome. FGFR2 mutation results in impaired skeletogenesis; however, our findings suggest that many phenotypic aberrations stem from a primary failure of pre-chondrogenic/osteogenic mesenchymal condensation and link FGFR2 to SOX9, a principal regulator of skeletogenesis

  3. FGFR2 point mutations in 466 endometrioid endometrial tumors: relationship with MSI, KRAS, PIK3CA, CTNNB1 mutations and clinicopathological features.

    Directory of Open Access Journals (Sweden)

    Sara A Byron

    Full Text Available Mutations in multiple oncogenes including KRAS, CTNNB1, PIK3CA and FGFR2 have been identified in endometrial cancer. The aim of this study was to provide insight into the clinicopathological features associated with patterns of mutation in these genes, a necessary step in planning targeted therapies for endometrial cancer. 466 endometrioid endometrial tumors were tested for mutations in FGFR2, KRAS, CTNNB1, and PIK3CA. The relationships between mutation status, tumor microsatellite instability (MSI and clinicopathological features including overall survival (OS and disease-free survival (DFS were evaluated using Kaplan-Meier survival analysis and Cox proportional hazard models. Mutations were identified in FGFR2 (48/466; KRAS (87/464; CTNNB1 (88/454 and PIK3CA (104/464. KRAS and FGFR2 mutations were significantly more common, and CTNNB1 mutations less common, in MSI positive tumors. KRAS and FGFR2 occurred in a near mutually exclusive pattern (p = 0.05 and, surprisingly, mutations in KRAS and CTNNB1 also occurred in a near mutually exclusive pattern (p = 0.0002. Multivariate analysis revealed that mutation in KRAS and FGFR2 showed a trend (p = 0.06 towards longer and shorter DFS, respectively. In the 386 patients with early stage disease (stage I and II, FGFR2 mutation was significantly associated with shorter DFS (HR = 3.24; 95% confidence interval, CI, 1.35-7.77; p = 0.008 and OS (HR = 2.00; 95% CI 1.09-3.65; p = 0.025 and KRAS was associated with longer DFS (HR = 0.23; 95% CI 0.05-0.97; p = 0.045. In conclusion, although KRAS and FGFR2 mutations share similar activation of the MAPK pathway, our data suggest very different roles in tumor biology. This has implications for the implementation of anti-FGFR or anti-MEK biologic therapies.

  4. 胎儿、成人正常皮肤EGFR与FGFR-2表达的研究%A comparative study of EGFR and FGFR-2 expression in fetal and adult skin

    Institute of Scientific and Technical Information of China (English)

    程飚; 付小兵; 盛志勇; 孙同柱; 孙晓庆

    2003-01-01

    目的观察胎儿与成人正常皮肤中的表皮细胞生长因子受体(EGFR)与成纤维细胞生长因子受体(FGFR)在细胞膜上表达的差异,探讨胎儿无瘢痕形成的分子机制.方法对妇产科意外流产的不同妊娠期胎儿和整形外科手术过程中作为供皮区的成人正常皮肤标本,应用免疫组织化学技术观察EGFR与FGFR-2的变化.结果妊娠胎儿的皮肤内EGFR和FGFR-2染色阳性的表皮细胞较多,贯穿于全层上皮,而真皮中成纤维细胞呈阳性标记的极少.随胎龄的增加,两受体的表达增加;成年人正常皮肤中EGFR多集中在表皮细胞的基底层,两种生长因子受体抗体阳性染色的细胞明显多于胎儿皮肤.结论胎儿和成年人的皮肤中,EGFR染色与FGFR-2表达的差异,可能是造成胎儿无瘢痕愈合的重要因素之一.

  5. Molecular analysis of FGFR 2 and associated clinical observations in two Chinese families with Crouzon syndrome.

    Science.gov (United States)

    Lin, Ying; Gao, Hongbin; Ai, Siming; Eswarakumar, Jacob V P; Li, Tao; Liu, Bingqian; Jiang, Hongye; Liu, Yuhua; Liu, Xialin; Li, Yonghao; Ni, Yao; Chen, Jiangna; Lin, Zhuoling; Liang, Xiaoling; Jin, Chenjin; Huang, Xinhua; Lu, Lin; Liu, Yizhi

    2016-09-01

    Crouzon syndrome, a dominantly inherited disorder and the most common type of craniosynostosis syndrome, is caused by mutations in the fibroblast growth factor receptor 2 (FGFR 2) gene, and characterized by craniosynostosis, shallow orbits, ocular proptosis, midface hypoplasia and a curved, beak‑like nose. The purpose of the present study was to investigate the fibroblast growth factor receptor 2 (FGFR 2) gene in two Chinese families with Crouzon syndrome and to characterize the associated clinical features. Two families underwent complete ophthalmic examination, and three patients in two families were diagnosed with Crouzon syndrome. Genomic DNA was extracted from leukocytes of peripheral blood samples, which were collected from the family members and 200 unrelated control subjects from the same population. Exons 8 and 10 of the FGFR 2 gene were amplified using polymerase chain reaction analysis and were directly sequenced. Ophthalmic examinations, including best‑corrected visual acuity, slit‑lamp examination, fundus examination and Computerized Tomography scans, and physical examinations were performed to exclude systemic diseases. These patients were affected with shallow orbits and ocular proptosis, accompanied by midface hypoplasia, craniosynostosis, strabismus or papilloedema, with clinically normal hands and feet. A heterozygous FGFR 2 missense mutation, c.811‑812insGAG (p.273insGlu) in exon 8 was identified in the affected individual, but not in the unaffected family members or the normal control individuals in family 1. In family 2, another heterozygous FGFR 2 missense mutation, c.842A>G (P.Tyr281Cys or Y281C), in exon 8 was identified in the affected boy and his mother, but not in the unaffected family members or the normal control individuals. Although FGFR 2 gene mutations and polymorphisms have been reported in various ethnic groups, particularly in the area of osteology, the present study reported for the first time, to the best of

  6. Transient Inhibition of FGFR2b-ligands signaling leads to irreversible loss of cellular β-catenin organization and signaling in AER during mouse limb development.

    Science.gov (United States)

    Danopoulos, Soula; Parsa, Sara; Al Alam, Denise; Tabatabai, Reza; Baptista, Sheryl; Tiozzo, Caterina; Carraro, Gianni; Wheeler, Matthew; Barreto, Guillermo; Braun, Thomas; Li, Xiaokun; Hajihosseini, Mohammad K; Bellusci, Saverio

    2013-01-01

    The vertebrate limbs develop through coordinated series of inductive, growth and patterning events. Fibroblast Growth Factor receptor 2b (FGFR2b) signaling controls the induction of the Apical Ectodermal Ridge (AER) but its putative roles in limb outgrowth and patterning, as well as in AER morphology and cell behavior have remained unclear. We have investigated these roles through graded and reversible expression of soluble dominant-negative FGFR2b molecules at various times during mouse limb development, using a doxycycline/transactivator/tet(O)-responsive system. Transient attenuation (≤ 24 hours) of FGFR2b-ligands signaling at E8.5, prior to limb bud induction, leads mostly to the loss or truncation of proximal skeletal elements with less severe impact on distal elements. Attenuation from E9.5 onwards, however, has an irreversible effect on the stability of the AER, resulting in a progressive loss of distal limb skeletal elements. The primary consequences of FGFR2b-ligands attenuation is a transient loss of cell adhesion and down-regulation of P63, β1-integrin and E-cadherin, and a permanent loss of cellular β-catenin organization and WNT signaling within the AER. Combined, these effects lead to the progressive transformation of the AER cells from pluristratified to squamous epithelial-like cells within 24 hours of doxycycline administration. These findings show that FGFR2b-ligands signaling has critical stage-specific roles in maintaining the AER during limb development.

  7. BRAF kinase inhibitor exerts anti-tumor activity against breast cancer cells via inhibition of FGFR2.

    Science.gov (United States)

    Zhang, Zong Xin; Jin, Wen Jun; Yang, Sheng; Ji, Cun Li

    2016-01-01

    Most anti-angiogenic therapies currently being evaluated in clinical trials targetvascular endothelial growth factor (VEGF) pathway; however, the tumor vasculature can acquire resistance to VEGF-targeted therapy by shifting to other angiogenesis mechanisms. Therefore, other potential therapeutic agents that block non-VEGF angiogenic pathways need to be evaluated. Here we identified BRAF kinase inhibitor, vemurafenibas an agent with potential anti-angiogenic and anti-breast cancer activities. Vemurafenib demonstrated inhibition of endothelial cell proliferation, migration, and tube formation in response to basic fibroblast growth factor (bFGF). In ex vivo and in vivo angiogenesis assays, vemurafenib suppressed bFGF-induced microvessel sprouting of rat aortic rings and angiogenesis in vivo. To understand the underlying molecular basis, we examined the effects of vemurafenib on different molecular components in treated endothelial cell, and found that vemurafenib suppressed bFGF-triggered activation of FGFR2 and protein kinase B (AKT). Moreover, vemurafenib directly inhibited proliferation and blocked the oncogenic signaling pathways in breast cancer cell. In vivo, using xenograft models of breast cancer cells MDA-MB-231, vemurafenib showed growth-inhibitory activity associated with inhibition of tumor angiogenesis. Taken together, our results indicate that vemurafenib targets the FGFR2-mediated AKT signaling pathway in endothelial cells, leading to the suppression of tumor growth and angiogenesis.

  8. Apert Syndrome: Molecularly Confirmed C.758C>G (P.Pro253Arg) in FGFR2

    Energy Technology Data Exchange (ETDEWEB)

    Cha Gon, Lee, E-mail: leechagon@eulji.ac.kr [Department of Pediatrics, Eulji General Hospital, College of Medicine, Eulji University, 68 Hangeulbiseok-ro, Nowon-gu, Seoul 139-711 (Korea, Republic of)

    2016-03-21

    A 5-day-old girl was referred to our clinic for evaluation of congenital malformations. She was identified with a pathogenic mutation c.758C>G (p.Pro253Arg) in FGFR2 gene using targeted exome sequencing. The de novo mutation was confirmed with Sanger sequencing in the patient and her parents. She showed occipital plagiocephaly with frontal bossing (Figure A and B). Skull frontal and lateral radiography revealed fusion of most of the sutures except coronal suture, with convolutional markings (Figure D and E). She had complete cleft palate (Figure C). Her fused bilateral hands showed type II syndactyly with complete syndactyly between the ring and the little fingers (Figure F1-F3). Both toes were simple syndactyly with side-to-side fusion of skin (Figure G1-)

  9. Antitumor effect of FGFR inhibitors on a novel cholangiocarcinoma patient derived xenograft mouse model endogenously expressing an FGFR2-CCDC6 fusion protein.

    Science.gov (United States)

    Wang, Yu; Ding, Xiwei; Wang, Shaoqing; Moser, Catherine D; Shaleh, Hassan M; Mohamed, Essa A; Chaiteerakij, Roongruedee; Allotey, Loretta K; Chen, Gang; Miyabe, Katsuyuki; McNulty, Melissa S; Ndzengue, Albert; Barr Fritcher, Emily G; Knudson, Ryan A; Greipp, Patricia T; Clark, Karl J; Torbenson, Michael S; Kipp, Benjamin R; Zhou, Jie; Barrett, Michael T; Gustafson, Michael P; Alberts, Steven R; Borad, Mitesh J; Roberts, Lewis R

    2016-09-28

    Cholangiocarcinoma is a highly lethal cancer with limited therapeutic options. Recent genomic analysis of cholangiocarcinoma has revealed the presence of fibroblast growth factor receptor 2 (FGFR2) fusion proteins in up to 13% of intrahepatic cholangiocarcinoma (iCCA). FGFR fusions have been identified as a novel oncogenic and druggable target in a number of cancers. In this study, we established a novel cholangiocarcinoma patient derived xenograft (PDX) mouse model bearing an FGFR2-CCDC6 fusion protein from a metastatic lung nodule of an iCCA patient. Using this PDX model, we confirmed the ability of the FGFR inhibitors, ponatinib, dovitinib and BGJ398, to modulate FGFR signaling, inhibit cell proliferation and induce cell apoptosis in cholangiocarcinoma tumors harboring FGFR2 fusions. In addition, BGJ398 appeared to be superior in potency to ponatinib and dovitinib in this model. Our findings provide a strong rationale for the investigation of FGFR inhibitors, particularly BGJ398, as a therapeutic option for cholangiocarcinoma patients harboring FGFR2 fusions.

  10. Clinical and radiographic delineation of Bent Bone Dysplasia-FGFR2 type or Bent Bone Dysplasia with Distinctive Clavicles and Angel-shaped Phalanges.

    Science.gov (United States)

    Krakow, Deborah; Cohn, Daniel H; Wilcox, William R; Noh, Grace J; Raffel, Leslie J; Sarukhanov, Anna; Ivanova, Margarita H; Danielpour, Moise; Grange, Dorothy K; Elliott, Alison M; Bernstein, Jonathan A; Rimoin, David L; Merrill, Amy E; Lachman, Ralph S

    2016-10-01

    Bent Bone Dysplasia-FGFR2 type is a relatively recently described bent bone phenotype with diagnostic clinical, radiographic, and molecular characteristics. Here we report on 11 individuals, including the original four patients plus seven new individuals with three longer-term survivors. The prenatal phenotype included stillbirth, bending of the femora, and a high incidence of polyhydramnios, prematurity, and perinatal death in three of 11 patients in the series. The survivors presented with characteristic radiographic findings that were observed among those with lethality, including bent bones, distinctive (moustache-shaped) small clavicles, angel-shaped metacarpals and phalanges, poor mineralization of the calvarium, and craniosynostosis. Craniofacial abnormalities, hirsutism, hepatic abnormalities, and genitourinary abnormalities were noted as well. Longer-term survivors all needed ventilator support. Heterozygosity for mutations in the gene that encodes Fibroblast Growth Factor Receptor 2 (FGFR2) was identified in the nine individuals with available DNA. Description of these patients expands the prenatal and postnatal findings of Bent Bone Dysplasia-FGFR2 type and adds to the phenotypic spectrum among all FGFR2 disorders. © 2016 Wiley Periodicals, Inc.

  11. Kinase domain activation of FGFR2 yields high-grade lung adenocarcinoma sensitive to a Pan-FGFR inhibitor in a mouse model of NSCLC.

    Science.gov (United States)

    Tchaicha, Jeremy H; Akbay, Esra A; Altabef, Abigail; Mikse, Oliver R; Kikuchi, Eiki; Rhee, Kevin; Liao, Rachel G; Bronson, Roderick T; Sholl, Lynette M; Meyerson, Matthew; Hammerman, Peter S; Wong, Kwok-Kin

    2014-09-01

    Somatic mutations in FGFR2 are present in 4% to 5% of patients diagnosed with non-small cell lung cancer (NSCLC). Amplification and mutations in FGFR genes have been identified in patients with NSCLCs, and clinical trials are testing the efficacy of anti-FGFR therapies. FGFR2 and other FGFR kinase family gene alterations have been found in both lung squamous cell carcinoma and lung adenocarcinoma, although mouse models of FGFR-driven lung cancers have not been reported. Here, we generated a genetically engineered mouse model (GEMM) of NSCLC driven by a kinase domain mutation in FGFR2. Combined with p53 ablation, primary grade 3/4 adenocarcinoma was induced in the lung epithelial compartment exhibiting locally invasive and pleiotropic tendencies largely made up of multinucleated cells. Tumors were acutely sensitive to pan-FGFR inhibition. This is the first FGFR2-driven lung cancer GEMM, which can be applied across different cancer indications in a preclinical setting. ©2014 American Association for Cancer Research.

  12. Rare mutations of FGFR2 causing Apert syndrome : identification of the first partial gene deletion, and an Alu element insertion from a new subfamily

    NARCIS (Netherlands)

    Bochukova, E.G.; Roscioli, T.; Hedges, D.J.; Taylor, I.B.; Johnson, D.; David, D.J.; Deininger, P.L.; Wilkie, A.O.

    2009-01-01

    Apert syndrome (AS) is a severe disorder, characterized by craniosynostosis and complex syndactyly of the hands and feet. Two heterozygous gain-of-function substitutions (Ser252Trp and Pro253Arg) in exon IIIa of fibroblast growth factor receptor 2 (FGFR2) are responsible for >98% of cases. Here we d

  13. 青海地区藏族 FGFR2基因多态性与乳腺癌的相关性研究%The correlation study between FGFR2 gene polymorphisms and breast cancer in Qinghai Tibetan areas

    Institute of Scientific and Technical Information of China (English)

    沈国双; 郑方超; 曹成珠; 姬发祥; 李进章; 王树燕; 赵久达

    2016-01-01

    目的:探讨成纤维细胞生长因子受体2(FG FR2)基因rs2981582、rs1219648和 rs2420946位点基因多态性与青海地区藏族乳腺癌的相关性。方法采用病例对照研究的方法,收集青海地区210例藏族乳腺癌患者及230例藏族体检健康女性的外周血标本,提取基因组DNA ,以Taqman‐MGB探针PCR法及测序方法对两组标本的FGFR2基因 rs2981582、rs1219648和rs2420946位点进行统计分型,分析其与青海地区藏族乳腺癌发病风险的关系。结果藏族乳腺癌患者rs 2981582位点CC、CT、T T频率分别为40.48%、39.05%、20.47%,健康对照组为36.09%、48.69%、15.22%,藏族乳腺癌患者rs1219648位点GG、AG、AA频率分别为24.76%、26.19%、49.05%,健康对照组为23.91%、47.39%、28.70%,藏族乳腺癌患者rs2420946位点CC、CT、T T频率分别为29.05%、45.24%、25.71%,健康对照组为30.87%、51.74%、17.39%。两组rs2981582和 rs2420946各基因型位点基因型频率差异均无统计学意义(P>0.05),但存在于 rs1219648位点的AA基因型其频率差异有统计学意义(P<0.05),与GG基因型比较,AA基因型携带的女性发生乳腺癌的危险性增加[OR=1.65,95% CI=(1.01,2.69)]。结论 FGFR2 rs1219648 AA基因型与青海地区藏族女性乳腺癌发病风险有关。%Objective To explore the relationship between the fibroblast growth factor 2 (FGFR2) gene polymorphism (rs 2981582 ,rs 1219648 ,rs 2420946) and the breast cancer risk in Tibetan population ,Qinghai province .Methods This is a case con‐trol study .Peripheral blood samples from 210 breast cancer patients and 230 healthy women in Qinghai area were collected .DNA samples were extracted from peripheral blood cells .FGFR2 gene polymorphism (rs 2981582 ,rs 1219648 ,rs 2420946) were typed by Taqman‐MGB probe based on PCR and DNA sequencing ,then analyzed its

  14. FGFR2 mutation in a patient without typical features of Pfeiffer syndrome--The emerging role of combined NGS and phenotype based strategies.

    Science.gov (United States)

    Flöttmann, Ricarda; Knaus, Alexej; Zemojtel, Tomasz; Robinson, Peter N; Mundlos, Stefan; Horn, Denise; Spielmann, Malte

    2015-08-01

    Pfeiffer syndrome (MIM: #101600) is a rare autosomal dominant disorder classically characterized by limb and craniofacial anomalies. It is caused by heterozygous mutations in the fibroblast growth factor receptors types 1 and 2 (FGFR1 and FGFR2). We applied a next generation sequencing (NGS) panel approach comprising all 2877 genes currently known to be causative for one or more Mendelian diseases combined with the phenotype based computational tool PhenIX (Phenotypic Interpretation of eXomes). We report on a patient presenting with multiple anomalies of hands and feet including brachydactyly and symphalangism. No clinical diagnosis could be established based on the clinical findings and testing of several genes associated with brachydactyly and symphalangism failed to identify mutations. Via next generation sequencing (NGS) panel approach we then identified a novel de novo missense FGFR2 mutation affecting an amino acid reported to be mutated in Pfeiffer syndrome. Since our patient shows typical radiological findings of Pfeiffer syndrome in hands and feet but at the same time lacks several characteristic features such as clinical signs of craniosynostosis and prominent eyes we suggest introducing the term "FGFR2 associated phenotypes" for similar cases. Our results highlight the emerging role of combined NGS and phenotype based bioinformatics strategies to establish clinical diagnoses.

  15. Binding of FGF2 to FGFR2 in an autocrine mode in trophectoderm cells is indispensable for mouse blastocyst formation through PKC-p38 pathway.

    Science.gov (United States)

    Yang, Jing; Zhang, Dan; Yu, Ying; Zhang, Run-Ju; Hu, Xiao-Ling; Huang, He-Feng; Lu, Yong-Chao

    2015-01-01

    Fibroblast growth factors (FGF1, FGF2 and FGF4) and fibroblast growth factor receptors (FGFR1, FGFR2, FGFR3 and FGFR4) have been reported to be expressed in preimplantation embryos and be required for their development. However, the functions of these molecules in trophectoderm cells (TEs) that lead to the formation of the blastocyst as well as the underlying mechanism have not been elucidated. The present study has demonstrated for the first time that endogenous FGF2 secreted by TEs can regulate protein expression and distribution in TEs via the FGFR2-mediated activation of PKC and p38, which are important for the development of expanded blastocysts. This finding provides the first explanation for the long-observed phenomenon that only high concentrations of exogenous FGFs have effects on embryonic development, but in vivo the amount of endogenous FGFs are trace. Besides, the present results suggest that FGF2/FGFR2 may act in an autocrine fashion and activate the downstream PKC/p38 pathway in TEs during expanded blastocyst formation.

  16. Influenza Virus Infects Epithelial Stem/Progenitor Cells of the Distal Lung: Impact on Fgfr2b-Driven Epithelial Repair.

    Directory of Open Access Journals (Sweden)

    Jennifer Quantius

    2016-06-01

    Full Text Available Influenza Virus (IV pneumonia is associated with severe damage of the lung epithelium and respiratory failure. Apart from efficient host defense, structural repair of the injured epithelium is crucial for survival of severe pneumonia. The molecular mechanisms underlying stem/progenitor cell mediated regenerative responses are not well characterized. In particular, the impact of IV infection on lung stem cells and their regenerative responses remains elusive. Our study demonstrates that a highly pathogenic IV infects various cell populations in the murine lung, but displays a strong tropism to an epithelial cell subset with high proliferative capacity, defined by the signature EpCamhighCD24lowintegrin(α6high. This cell fraction expressed the stem cell antigen-1, highly enriched lung stem/progenitor cells previously characterized by the signature integrin(β4+CD200+, and upregulated the p63/krt5 regeneration program after IV-induced injury. Using 3-dimensional organoid cultures derived from these epithelial stem/progenitor cells (EpiSPC, and in vivo infection models including transgenic mice, we reveal that their expansion, barrier renewal and outcome after IV-induced injury critically depended on Fgfr2b signaling. Importantly, IV infected EpiSPC exhibited severely impaired renewal capacity due to IV-induced blockade of β-catenin-dependent Fgfr2b signaling, evidenced by loss of alveolar tissue repair capacity after intrapulmonary EpiSPC transplantation in vivo. Intratracheal application of exogenous Fgf10, however, resulted in increased engagement of non-infected EpiSPC for tissue regeneration, demonstrated by improved proliferative potential, restoration of alveolar barrier function and increased survival following IV pneumonia. Together, these data suggest that tropism of IV to distal lung stem cell niches represents an important factor of pathogenicity and highlight impaired Fgfr2b signaling as underlying mechanism. Furthermore, increase of

  17. Fibroblast Growth Factor (FGF-2 and Its Receptors FGFR-2 and FGFR-3 May Be Putative Biomarkers of Malignant Transformation of Potentially Malignant Oral Lesions into Oral Squamous Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Seema Nayak

    Full Text Available There are several factors like angiogenesis, lymphangiogenesis, genetic alterations, mutational factors that are involved in malignant transformation of potentially malignant oral lesions (PMOLs to oral squamous cell carcinoma (OSCC. Fibroblast growth factor-2 (FGF-2 is one of the prototypes of the large family of growth factors that bind heparin. FGF-2 induces angiogenesis and its receptors may play a role in synthesis of collagen. FGFs are involved in transmission of signals between the epithelium and connective tissue, and influence growth and differentiation of a wide variety of tissue including epithelia. The present study was undertaken to analyze expression of FGF-2 and its receptors FGFR-2 and FGFR-3 in 72 PMOLs, 108 OSCC and 52 healthy controls, and their role in risk assessment for malignant transformation of Leukoplakia (LKP and Oral submucous fibrosis (OSMF to OSCC. Immunohistochemistry was performed using antibodies against FGF-2, FGFR-2 and FGFR-3. IHC results were validated by Real Time PCR. Expression of FGF-2, FGFR-2 and FGFR-3 was upregulated from PMOLs to OSCC. While 90% (9/10 of PMOLs which showed malignant transformation (transformed expressed FGF-2, only 24.19% cases (15/62 of PMOLs which were not transformed (untransformed to OSCC expressed FGF-2. Similarly, FGFR-2 expression was seen in 16/62 (25.81% of untransformed PMOLs and 8/10 (80% cases of transformed PMOLs. FGFR-3 expression was observed in 23/62 (37.10% cases of untransformed PMOLs and 6/10 (60% cases of transformed PMOLs. A significant association of FGF-2 and FGFR-2 expression with malignant transformation from PMOLs to OSCC was observed both at phenotypic and molecular level. The results suggest that FGF-2 and FGFR-2 may be useful as biomarkers of malignant transformation in patients with OSMF and LKP.

  18. Fibroblast Growth Factor (FGF-2) and Its Receptors FGFR-2 and FGFR-3 May Be Putative Biomarkers of Malignant Transformation of Potentially Malignant Oral Lesions into Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Nayak, Seema; Goel, Madhu Mati; Makker, Annu; Bhatia, Vikram; Chandra, Saumya; Kumar, Sandeep; Agarwal, S P

    2015-01-01

    There are several factors like angiogenesis, lymphangiogenesis, genetic alterations, mutational factors that are involved in malignant transformation of potentially malignant oral lesions (PMOLs) to oral squamous cell carcinoma (OSCC). Fibroblast growth factor-2 (FGF-2) is one of the prototypes of the large family of growth factors that bind heparin. FGF-2 induces angiogenesis and its receptors may play a role in synthesis of collagen. FGFs are involved in transmission of signals between the epithelium and connective tissue, and influence growth and differentiation of a wide variety of tissue including epithelia. The present study was undertaken to analyze expression of FGF-2 and its receptors FGFR-2 and FGFR-3 in 72 PMOLs, 108 OSCC and 52 healthy controls, and their role in risk assessment for malignant transformation of Leukoplakia (LKP) and Oral submucous fibrosis (OSMF) to OSCC. Immunohistochemistry was performed using antibodies against FGF-2, FGFR-2 and FGFR-3. IHC results were validated by Real Time PCR. Expression of FGF-2, FGFR-2 and FGFR-3 was upregulated from PMOLs to OSCC. While 90% (9/10) of PMOLs which showed malignant transformation (transformed) expressed FGF-2, only 24.19% cases (15/62) of PMOLs which were not transformed (untransformed) to OSCC expressed FGF-2. Similarly, FGFR-2 expression was seen in 16/62 (25.81%) of untransformed PMOLs and 8/10 (80%) cases of transformed PMOLs. FGFR-3 expression was observed in 23/62 (37.10%) cases of untransformed PMOLs and 6/10 (60%) cases of transformed PMOLs. A significant association of FGF-2 and FGFR-2 expression with malignant transformation from PMOLs to OSCC was observed both at phenotypic and molecular level. The results suggest that FGF-2 and FGFR-2 may be useful as biomarkers of malignant transformation in patients with OSMF and LKP.

  19. 新致病基因在颅缝早闭Crouzon综合征中的初步机制研究%Fgfr2cC342Y/+ Mouse Model of Crouzon Syndrome in Craniosynostosis

    Institute of Scientific and Technical Information of China (English)

    杨娴娴; Jodie T Hatfield; Susan J Hinze; 穆雄铮; Peter J Anderson; Barry C Powell

    2012-01-01

    目的 研究Rbp4(Retinol binding protein 4)、Gpc3 (Glypican family of growth factor binding protein 3)、Clqtnf3 (Collagenous repeat-containing sequence of 26 KDa protein)等新致病基因在颅缝早闭症中的发病机制,为疾病非手术治疗奠定理论基础.方法 以Crouzon综合征Fgfr2cC342Y/+小鼠为实验模型,应用MicroCT和组织学染色,研究小鼠颅缝闭合模式;以Fgfr2cC342Y/+模型,RT-qPCR研究Rbp4、Gpc3、C1qtnf3等新致病基因的表达差异,初步探讨其在颅缝闭合过程中的调控作用;以体外培养的Fgfr2cC342Y/+小鼠颅缝细胞为模型,研究基因突变动物细胞增殖与代谢改变.结果 获得Fgfr2cC342Y/+小鼠后额缝、冠状缝、人字缝、矢状缝等颅缝闭合模式,随颅骨发育、颅缝闭合,OC (Osteocalcin)、ALP(Alkaline phosphatase)表达增加,目的基因Rbp4、Gpc3、Clqtnf3表达下降,Msx2(Muscle segment homeobox gene 2)表达增加,杂合子与野生型小鼠之间均存在显著统计学差异,与前期人颅缝组织Microarray研究结果一致.Gpc1 (Glypican family of growth factor binding protein 1)、FliⅠ(Flightless Ⅰ)在颅缝闭合中的表达较恒定,野生型与杂合子之间未见明显统计学差异.体外培养Fgfr2cC342Y/+小鼠颅缝细胞,CellTiter96 MTS和Quant-iT Picogreen dsDNA细胞增殖与代谢分析结果显示,Fgfr2功能获得性突变可促进冠状缝细胞的增殖,从而导致成骨增加,颅缝早闭.结论 Fgfr2cC342Y/+模型新致病基因表达趋势与前期人颅缝组织Microarray研究结果一致,Rbp4、Gpc3、C1qtnf3可能在颅缝早闭中具重要调控作用.%Objective To investigate a number of novel genes and their molecular mechanisms at play during the premature suture fusion using Fgfr2cC342Y/+ mouse model. Methods The pattern of cranial suture fusion in Fgfr2cC342Y/+ mice (a Cys342Tyr replacement into Fgfr2c to create a gain -of -function mutation equivalent to a mutation in human Crouzon syndromes) were analyzed using

  20. 沉默ESRP1基因表达对卵巢癌OVCAR5细胞中FGFR2亚型转化的影响%Silencing ESRP1 gene expression can induce FGFR2 isoform switch in ovarian cancer OVCAR5 cells

    Institute of Scientific and Technical Information of China (English)

    郭欣; 易祎; 杨宇; 胡锦辉; 李娜; 张米妮; 朱琳; 黄石榴; 孙贤青

    2016-01-01

    目的:研究沉默上皮剪接调节蛋白1(epithelial splicing regulatory protein 1,ESRP1)基因表达对卵巢癌OVCAR5细胞中成纤维细胞生长因子受体2(fibroblast growth factor receptor 2,FGFR2)亚型转换的影响.方法:构建靶向ESRP1基因的ESRP1-shRNA慢病毒表达载体(pLVTHM/ESRP1-shRNA1和pLVTHM/ESRP1-shRNA2), 同时设置阴性对照(negative control,NC)质粒(pLVTHM/NC-shRNA);将3种质粒分别转染到293T细胞中制备慢病毒.慢病毒感染卵巢癌OVCAR5细胞后,分别采用实时荧光定量PCR及蛋白质印迹法检测ESRP1 mRNA及蛋白的表达水平;采用限制性内切酶AvaⅠ和HinC Ⅱ检测沉默ESRP1基因后对FGFR2亚型转换的影响;MTT法检测沉默ESRP1基因后对OVCAR5细胞增殖的影响;蛋白质印迹法检测上皮标志物E-钙黏蛋白(E-cadherin)、间质标志物N-钙黏蛋白(N-cadherin)及β-链蛋白(β-catenin)表达的变化.结果:成功构建靶向ESRP1基因的shRNA慢病毒表达载体并包装获得慢病毒;与阴性对照组比较,靶向ESRP1基因的shRNA能明显抑制OVCAR5细胞中ESRP1 mRNA及蛋白的表达(P值均<0.05);沉默ESRP1基因的表达能诱导OVCAR5细胞中FGFR2由上皮亚型(FGFR2b)向间质亚型(FGFR2c)的转换,并促进OVCAR5细胞的增殖(P<0.05);同时,下调E-cadherin的表达水平而上调N-cadherin的表达水平,并激活β-catenin (P值均<0.05).结论:沉默ESRP1基因表达能诱导OVCAR5细胞中FGFR2亚型的转换,促进OVCAR5细胞增殖,并诱导OVCAR5细胞发生上皮-间质转化(epithelial-mesenchymal transition,EMT),该过程可能涉及Wnt/β-catenin信号通路.

  1. Low-Risk Investing without Industry Bets

    DEFF Research Database (Denmark)

    Asness, Clifford S.; Frazzini, Andrea; Heje Pedersen, Lasse

    2014-01-01

    The strategy of buying safe low-beta stocks while shorting (or underweighting) riskier high-beta stocks (“betting against beta”) has been shown to deliver significant risk-adjusted returns. Some have suggested, however, that such “low-risk investing” delivers high returns primarily because...

  2. Deformed Skull Morphology Is Caused by the Combined Effects of the Maldevelopment of Calvarias, Cranial Base and Brain in FGFR2-P253R Mice Mimicking Human Apert Syndrome

    Science.gov (United States)

    Luo, Fengtao; Xie, Yangli; Xu, Wei; Huang, Junlan; Zhou, Siru; Wang, Zuqiang; Luo, Xiaoqing; Liu, Mi; Chen, Lin; Du, Xiaolan

    2017-01-01

    Apert syndrome (AS) is a common genetic syndrome in humans characterized with craniosynostosis. Apert patients and mouse models showed abnormalities in sutures, cranial base and brain, that may all be involved in the pathogenesis of skull malformation of Apert syndrome. To distinguish the differential roles of these components of head in the pathogenesis of the abnormal skull morphology of AS, we generated mouse strains specifically expressing mutant FGFR2 in chondrocytes, osteoblasts, and progenitor cells of central nervous system (CNS) by crossing Fgfr2+/P253R-Neo mice with Col2a1-Cre, Osteocalcin-Cre (OC-Cre), and Nestin-Cre mice, respectively. We then quantitatively analyzed the skull and brain morphology of these mutant mice by micro-CT and micro-MRI using Euclidean distance matrix analysis (EDMA). Skulls of Col2a1-Fgfr2+/P253R mice showed Apert syndrome-like dysmorphology, such as shortened skull dimensions along the rostrocaudal axis, shortened nasal bone, and evidently advanced ossification of cranial base synchondroses. The OC-Fgfr2+/P253R mice showed malformation in face at 8-week stage. Nestin-Fgfr2+/P253R mice exhibited increased dorsoventral height and rostrocaudal length on the caudal skull and brain at 8 weeks. Our study indicates that the abnormal skull morphology of AS is caused by the combined effects of the maldevelopment in calvarias, cranial base, and brain tissue. These findings further deepen our knowledge about the pathogenesis of the abnormal skull morphology of AS, and provide new clues for the further analyses of skull phenotypes and clinical management of AS. PMID:28123344

  3. Fronto-facial advancement and bipartition in Crouzon-Pfeiffer and Apert syndromes: Impact of fronto-facial surgery upon orbital and airway parameters in FGFR2 syndromes.

    Science.gov (United States)

    Khonsari, Roman H; Way, Benjamin; Nysjö, Johan; Odri, Guillaume A; Olszewski, Raphaël; Evans, Robert D; Dunaway, David J; Nyström, Ingela; Britto, Jonathan A

    2016-10-01

    A major concern in FGFR2 craniofaciosynostosis is oculo-orbital disproportion, such that orbital malformation provides poor accommodation and support for the orbital contents and peri-orbita, leading to insufficient eyelid closure, corneal exposure and eventually to functional visual impairment. Fronto-facial monobloc osteotomy followed by distraction osteogenesis aims to correct midfacial growth deficiencies in Crouzon-Pfeiffer syndrome patients. Fronto-facial bipartition osteotomy followed by distraction is a procedure of choice in Apert syndrome patients. These procedures modify the shape and volume of the orbit and tend to correct oculo-orbital disproportion. Little is known about the detailed 3D shape of the orbital phenotype in CPS and AS, and about how this is modified by fronto-facial surgery. Twenty-eight patients with CMS, 13 patients with AS and 40 control patients were included. CT scans were performed before and after fronto-facial surgery. Late post-operative scans were available for the Crouzon-Pfeiffer syndrome group. Orbital morphology was investigated using conventional three-dimensional cephalometry and shape analysis after mesh-based segmentation of the orbital contents. We characterized the 3D morphology of CPS and AS orbits and showed how orbital shape is modified by surgery. We showed that monobloc-distraction in CPS and bipartition-distraction in AS specifically address the morphological characteristics of the two syndromes. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  4. 40 CFR 266.109 - Low risk waste exemption.

    Science.gov (United States)

    2010-07-01

    ... (CONTINUED) STANDARDS FOR THE MANAGEMENT OF SPECIFIC HAZARDOUS WASTES AND SPECIFIC TYPES OF HAZARDOUS WASTE MANAGEMENT FACILITIES Hazardous Waste Burned in Boilers and Industrial Furnaces § 266.109 Low risk waste... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Low risk waste exemption. 266.109...

  5. Panel Endorses Active Monitoring for Low-Risk Prostate Cancer

    Science.gov (United States)

    An independent panel convened this week by NIH has concluded that many men with localized, low-risk prostate cancer should be closely monitored, permitting treatment to be delayed until warranted by disease progression. However, monitoring strategies—such

  6. 'Observation' Best Option for Most Low-Risk Prostate Cancer

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_167181.html 'Observation' Best Option for Most Low-Risk Prostate Cancer ... majority of men with localized prostate cancer, selecting observation for their treatment choice can help them live ...

  7. Breast cancer susceptibility variants alter risk in familial ovarian cancer.

    Science.gov (United States)

    Latif, A; McBurney, H J; Roberts, S A; Lalloo, F; Howell, A; Evans, D G; Newman, W G

    2010-12-01

    Recent candidate gene and genome wide association studies have revealed novel loci associated with an increased risk of breast cancer. We evaluated the effect of these breast cancer associated variants on ovarian cancer risk in individuals with familial ovarian cancer both with and without BRCA1 or BRCA2 mutations. A total of 158 unrelated white British women (54 BRCA1/2 mutation positive and 104 BRCA1/2 mutation negative) with familial ovarian cancer were genotyped for FGFR2, TNRC9/TOX3 and CASP8 variants. The p.Asp302His CASP8 variant was associated with reduced ovarian cancer risk in the familial BRCA1/2 mutation negative ovarian cancer cases (P = 0.016). The synonymous TNRC9/TOX3 (Ser51) variant was present at a significantly lower frequency than in patients with familial BRCA1/2 positive breast cancer (P = 0.0002). Our results indicate that variants in CASP8 and TNRC9/TOX3 alter the risk of disease in individuals affected with familial ovarian cancer.

  8. MS ANTWERPEN: Emergency Management Training for Low-Risk Environments

    Science.gov (United States)

    Strohschneider, Stefan; Gerdes, Jurgen

    2004-01-01

    Emergency management training programs have been developed mostly for trainees from high-risk environments such as aviation or the chemical industry. This article describes a training program for staff members from low-risk environments such as hospitals or hotels, where the awareness of potential dangers is usually low and emergency plans are…

  9. Contemporary management of low-risk bladder cancer

    NARCIS (Netherlands)

    Falke, J.; Witjes, J.A.

    2011-01-01

    Bladder cancer comprises a heterogeneous group of tumors, the majority of which are non-muscle-invasive bladder cancer (NMIBC) at initial presentation. Low-risk bladder cancer--defined as pTa low-grade papillary tumors--is the type of NMIBC with the most favorable oncologic outcome. Although the

  10. Cellulase variants

    Energy Technology Data Exchange (ETDEWEB)

    Blazej, Robert; Toriello, Nicholas; Emrich, Charles; Cohen, Richard N.; Koppel, Nitzan

    2015-07-14

    This invention provides novel variant cellulolytic enzymes having improved activity and/or stability. In certain embodiments the variant cellulotyic enzymes comprise a glycoside hydrolase with or comprising a substitution at one or more positions corresponding to one or more of residues F64, A226, and/or E246 in Thermobifida fusca Cel9A enzyme. In certain embodiments the glycoside hydrolase is a variant of a family 9 glycoside hydrolase. In certain embodiments the glycoside hydrolase is a variant of a theme B family 9 glycoside hydrolase.

  11. Determinants for hospitalization in " low-risk" community acquired pneumonia

    Directory of Open Access Journals (Sweden)

    Aliyu Muktar H

    2003-06-01

    Full Text Available Abstract Background A variable decision in managing community acquired pneumonia (CAP is the initial site of care; in-patient versus outpatient. These variations persist despite comprehensive practice guidelines. Patients with a Pneumonia Severity Index (PSI score lower than seventy have low risk for complications and outpatient antibiotic management is recommended in this group. These patients are generally below the age of fifty years, non-nursing home residents, HIV negative and have no major cardiac, hepatic, renal or malignant diseases. Methods A retrospective analysis of 296 low-risk CAP patients evaluated within a year one period at St. Agnes Hospital, Baltimore, Maryland was undertaken. All patients were assigned a PSI score. 208 (70% were evaluated and discharged from the emergency department (E.D. to complete outpatient antibiotic therapy, while 88 (30% were hospitalized. Patients were sub-stratified into classes I-V according to PSI. A comparison of demographic, clinical, social and financial parameters was made between the E.D. discharged and hospitalized groups. Results Statistically significant differences in favor of the hospitalized group were noted for female gender (CI: 1.46-5.89, p= 0.0018, African Americans (CI: 0.31-0.73, p= 0.004, insurance coverage (CI: 0.19-0.63, p= 0.0034, temperature (CI: 0.04-0.09, p= 0.0001 and pulse rate (CI: 0.03-0.14, p= 0.0001. No statistically significant differences were observed between the two groups for altered mental status, hypotension, tachypnea, laboratory/radiological parameters and social indicators (p>0.05. The average length of stay for in-patients was 3.5 days at about eight time's higher cost than outpatient management. There was no difference in mortality or treatment failures between the two groups. The documentation rate and justifications for hospitalizing low risk CAP patients by admitting physicians was less than optimal. Conclusions High fever, tachycardia, female gender

  12. 幽门螺杆菌与胃黏膜bFGF,FGFR-2表达的关系及意义%Correlations of Helicobacter pylori infection with the expression of basic fibroblast growth factor and fibroblast growth factor receptor-2 in gastric mucosa and their significances

    Institute of Scientific and Technical Information of China (English)

    李信; 姜海行; 陈罡; 雷琳; 覃山羽

    2007-01-01

    目的:探讨幽门螺杆菌(H pylori)感染的胃黏膜上皮细胞碱性成纤维细胞生长因子(bFGF)、成纤维细胞生长因子受体-2(FGFR-2)的表达及其在胃黏膜癌变过程中的意义.方法:选择慢性浅表性胃炎(CSG)30例、胃黏膜肠上皮化生(IM)29例、不典型增生(Dys)31例及胃癌(GC)55例.采用免疫组化SP法检测胃黏膜上皮细胞bFGF,FGFR-2表达状况,用快速尿素酶试验和组织学Warthin-Starry嗜银染色法联合检测胃黏膜Hpylori感染情况.结果:CSG组bFGF,FGFR-2的表达显著低于其余三组(IM组:χ2=4.002,P<0.05;χ2=4.163,P<0.05;Dys组:χ2=15.779,P=0.000;χ2=15.949,P=0.000;GC组:χ2=24.110,P=0.000;χ2=18.736,P=0.000),IM组的表达低于Dys组及GC组(Dys组:χ2=4.258,P<0.05;χ2=4.212,P<0.05;GC组:χ2=7.786,P<0.01;χ2=4.687,P<0.05),而Dys组与GC组间无显著性差异.Hpylori阳性IM及Dys组bFGF, FGFR-2的表达均显著高于阴性组(IM组:χ2=10.076,P<0.01;χ2=7.535,P<0.01;Dys组:χ2=11.501,P<0.01;χ2=8.330,P<0.01).Hpylori阳性Dys组bFGF, FGFR-2表达显著高于GC组(χ2=4.201,P<0.05;χ2=3.982,P<0.05),H pylori阳性IM组则与G C组的表达无显著性差异;Hpylori阴性Dys组及IM组bFGF的表达均显著低于GG组(χ2=5.736,P<0.05;χ2=17.113,P=0.000),H pylori阴性Dys组FGFR-2表达与GC组无显著性差异而IM组的FGFR-2的表达显著低于GC组(χ2=11.091,P<0.05).结论:H pylori感染引起胃黏膜上皮细胞bFGF及FGFR-2的过度表达可能与H pylori感染致胃黏膜上皮细胞的癌变有关.

  13. Study of the susceptibility between the FGFR2 gene polymorphism and the breast cancer risk in Chinese Han nationality female population%中国汉族女性人群成纤维细胞生长因子受体2基因多态性与乳腺癌易感性的研究

    Institute of Scientific and Technical Information of China (English)

    单连峰; 高岩峰; 马建忠

    2011-01-01

    目的 探讨中国汉族女性成纤维细胞生长因子受体2(FGFR2)基因多态性与乳腺癌易感性的关系.方法 通过检索PubMed,EMBASE和CNKI数据库中有关FGFR2基因与乳腺癌易感性相关的文献,收集、整理中国汉族女性乳腺癌病例和正常对照的基因型数据,进行Meta分析和关联研究.结果 FGFR2的4个多态位点(rs2981582、rs1219648、rs2420946和rs2981579)的Meta分析结果显示优势比(OR)(95% CI区间)分别为1.25(1.15~1.36)、1.13(0.96~1.34)、1.12(1.02~1.23)和0.99(0.82~1.20);基因型的关联研究相应的概率P值分别是0.000002、0.0002、0.006和0.998.结论 FGFR2基因的rs2981582、rs2420946多态性增加了中国汉族女性人群患乳腺癌的危险,rs2981579位点与乳腺癌易感性无关联,需要迸一步证明rs1219648位点与乳腺癌易感性的关相程度.

  14. LOW RISK PROSTATE CANCER: ACTIVE TREATMENT OR ACTIVE SURVEILLANCE?

    Science.gov (United States)

    Tomašković, Igor

    2015-09-01

    The widely used screening for prostate cancer with prostate specific antigen has resulted in identification of potentially lethal prostate cancers at a much more curable stage and has been associated with significant falls in prostate cancer mortality. In spite of the fact that prostate cancer is one of the deadliest malignancies in men, the advent of sensitive diagnostic testing has also resulted in detection of low risk cancers due to the high incidence of latent prostate cancer in aging men and prolonged natural history of the disease. This, in turn, has entailed the problem of cancer overdiagnosis and subsequent overtreatment. Approximately 6 times as many men will be diagnosed with the disease as will die from it. Active surveillance appeared as a response to the clearly documented risks of overdiagnosis and overtreatment of low risk prostate cancer for localized prostate cancer. It entails initial expectant management rather than immediate therapy, with 'curative-intent' treatment deferred until there is evidence that the patient is at an increased risk of disease progression. This approach attempts to balance the risks and side effects of overtreatment against the possibility of disease progression and lost opportunity for cure. A systematic literature review brings current knowledge on the subject.

  15. Emergency caesarean section in low risk nulliparous women

    DEFF Research Database (Denmark)

    Haerskjold, Ann; Hegaard, H K; Kjaergaard, H

    2012-01-01

    the association between risk factors and indications for ECS. Smoking during pregnancy (OR 2.33; CI 1.18-4.61) and BMI ≥ 30 (OR 2.87, CI 1.34-6.16) were associated with increased risk of ECS due to SFD. Birth weight (BW) ≥ 4,000 (OR 2.95; CI 1.92-4.53) and smoking cessation during pregnancy (OR 2.02; CI 1......The rising incidence of caesarean section (CS), including emergency caesarean section (ECS) in nulliparas is of concern. Previous CS may have implications for future pregnancies and deliveries. This article describes the prevalence and indications for ECS in a cohort of low risk nulliparas...... and identifies maternal and fetal risk factors associated with ECS. We included 2,748 low-risk women and 8.7% had ECS. Failure-to-progress (FTP) accounted for 68.3% of the ECS and 30.4% were performed due to suspected fetal distress (SFD). Multivariate logistic regression analyses were done to estimate...

  16. Optimal Constrained Resource Allocation Strategies under Low Risk Circumstances

    CERN Document Server

    Andreica, Mugurel Ionut; Visan, Costel

    2009-01-01

    In this paper we consider multiple constrained resource allocation problems, where the constraints can be specified by formulating activity dependency restrictions or by using game-theoretic models. All the problems are focused on generic resources, with a few exceptions which consider financial resources in particular. The problems consider low-risk circumstances and the values of the uncertain variables which are used by the algorithms are the expected values of the variables. For each of the considered problems we propose novel algorithmic solutions for computing optimal resource allocation strategies. The presented solutions are optimal or near-optimal from the perspective of their time complexity. The considered problems have applications in a broad range of domains, like workflow scheduling in industry (e.g. in the mining and metallurgical industry) or the financial sector, motion planning, facility location and data transfer or job scheduling and resource management in Grids, clouds or other distribute...

  17. Active surveillance for low-risk prostate cancer.

    Science.gov (United States)

    Bangma, Chris H; Bul, Meelan; van der Kwast, Theo H; Pickles, Tom; Korfage, Ida J; Hoeks, Caroline M; Steyerberg, Ewout W; Jenster, Guido; Kattan, Michael W; Bellardita, Lara; Carroll, Peter R; Denis, Louis J; Parker, Chris; Roobol, Monique J; Emberton, Mark; Klotz, Laurence H; Rannikko, Antti; Kakehi, Yoshiyuki; Lane, Janet A; Schröder, Fritz H; Semjonow, Axel; Trock, Bruce J; Valdagni, Riccardo

    2013-03-01

    Active surveillance (AS) is an important management strategy for men diagnosed with low-risk prostate cancer (PCa). The need for AS is increasing due to the awareness that many PCa are identified that show a low growth potential and therefore are likely to remain clinically asymptomatic during the lifetime of an individual. Currently there is no good method to prevent the overdiagnosis of indolent cancers upfront. During the last decade, several studies on AS around the world have made observations that feed the discussion on how to select and monitor these patients, how to proceed with the research to develop a better and more precise clinical definition of indolent cancers and how to manage men under AS clinically. Furthermore, patients' perspectives have become clearer, and quality of life studies give direction to the practical approach and care for patients and partners. This paper reflects the consensus on the state of the art and the future direction of AS, based on the Inside Track Conference "Active Surveillance for low risk prostate cancer" (Chairmen: C.H. Bangma, NL, and L. Klotz, CA; Co-Chairmen: L.J. Denis, BE, and C. Parker, UK; Scientific Coordinators: M. J. Roobol, NL, and E.W. Steyerberg, NL), organized by the European School of Oncology in collaboration with Europa Uomo in Rotterdam, the Netherlands in January 2012. Topics for discussion were the optimisation of patient selection based on indolent disease definition, the incorporation of therapeutic agents into AS programs, the optimisation of patient care, and the application of emerging technologies and biomarkers.

  18. Expression of acidic fibroblast growth factor in rat gut ischemia/reperfusion injury%大鼠肠缺血-再灌注损伤中FGFR2表达的规律

    Institute of Scientific and Technical Information of China (English)

    翁立新; 付小兵

    2007-01-01

    目的 观察酸性成纤维细胞生长因子受体2(acid fibroblast growth factor receptor, FGFR2 )在肠缺血-再灌注损伤中表达规律.方法 以大鼠肠系膜上动脉(SMA)夹闭造成肠缺血-再灌注损伤模型,并将动物随机分为假手术组(C组)、生理盐水对照组(R组)、改构体aFGF治疗组(F组).除假手术组外,其余各组动物均于缺血45 min后于2、6、12、24 h活杀,取小肠组织标本,免疫组化和RT-PCR检测FGFR的表达规律.结果 在正常大鼠,FGFR分布在小肠绒毛上皮细胞的肠腔侧、侧壁和小肠隐窝朝向隐窝腔的一侧的细胞膜上.缺血和再灌注的初期,FGFR的表达未发生明显变化,随着再灌注时间的延长逐渐增强.FGF使FGFR的表达有明显的增强和提前表达.缺血和再灌注使FGFR mRNA的表达迅速增加,在再灌注后6 h达到高峰.F组FGFR mRNA的表达较R组相应时间点显著增加(P<0.05).结论 FGFR在肠缺血-再灌注损伤的修复中起积极作用.

  19. 7 CFR 3052.530 - Criteria for a low-risk auditee.

    Science.gov (United States)

    2010-01-01

    ... periods) shall qualify as a low-risk auditee and be eligible for reduced audit coverage in accordance with... part. A non-Federal entity that has biennial audits does not qualify as a low-risk auditee, unless... 7 Agriculture 15 2010-01-01 2010-01-01 false Criteria for a low-risk auditee. 3052.530...

  20. Current Management of Low Risk Differentiated Thyroid Cancer and Papillary Microcarcinoma.

    Science.gov (United States)

    Tarasova, V D; Tuttle, R M

    2017-01-10

    Each year, the proportion of thyroid cancer patients presenting with low risk disease is increasing. Moreover, the definition of low risk thyroid cancer is expanding and several histological subtypes beyond papillary microcarcinomas are now classified as low risk disease. This shift in the landscape of thyroid cancer presentation is forcing clinicians to critically re-evaluate whether or not traditional management paradigms that were effective in treating intermediate and high risk disease are applicable to these low risk patients. Here we review the definition of low risk disease, examine the various histological subtypes that are considered low risk in the 2015 American Thyroid Association guidelines for the management of thyroid nodules and thyroid cancer, and review our current approach to the management of these low risk tumours.

  1. Low risk of infection from IUD use shown.

    Science.gov (United States)

    1998-08-01

    The findings of a large, multicenter US study indicate that women who are screened for infection risks before IUD insertion are at low risk of such complications, regardless of whether prophylactic antibiotics are administered. More than 300 clinicians at 11 clinics in Los Angeles County, California, provided 1867 women with either 500 mcg of azithromycin or placebo capsules before insertion of a Copper T 380A IUD. The risk of sexually transmitted infection was assessed before IUD insertion through both self-reported medical history and screening for chlamydia and gonorrhea. At least 90 days of postinsertion follow-up was accumulated for about 98% of women in both groups. At 90 days, 92.7% of women who received the antibiotic and 93.2% of those who received a placebo still had their IUD in place. Only 1 woman in each group developed salpingitis. The rate of IUD removal for any reason other than spontaneous partial expulsion was 3.8% in the antibiotic group and 3.4% in the placebo group. At 12 months, approximately 80% of women still had their IUDs in place, indicating a high level of satisfaction with the device. Researchers have expressed hope that these findings will help counteract concerns about IUD safety.

  2. Is China a low risk area for dementia?

    Institute of Scientific and Technical Information of China (English)

    Zhen-xin Zhang; Jie-Hao Zhao; Jue-Bing Huang; Xia Hong; Jiahong Yao; Jian-Ming Wang; En-Li Yang; Jing Wei

    2000-01-01

    Objoctlve: To investigate whether China is a low riak area for dementia, we conducted a prevalence survey in Beijing, China. Participants: A total of 3244 residents aged 55 years and ovcr- from two Distncts and onc county covcring 7 urban and 8 rural communitics was drawn through a stratified multiple stage cluster sampling. Of these, 3094 (95.2%) were interviewed. Design: Using a two-phase procedure, a Chinese version of Mini-Mental State Examination with 3 cut-off scores depending on respondertt's level of education was administered to all participates in 1997 Those who scored below the cutoff points and a subsample of those with scores in the normal range were interviewed in phase 2 to identify those with dementia through a set of diagnostic examination and the DSM-V criteria. A follow-up study conducted in 1998 for all persons who entered in phase 2 to identify those with Alzheimer's dementia ando vascular dcmcntia by thc utilization of N1NCDS-ADRDA, and NINCDS-AIREN critcria and to classify the severity of dementia by GDS criteria. Results: The ovarall prevalence of dementia was 4. 7% in individuals aged 55 years and over, 7.8% in those aged 65 years and over. Tie prevalerce of AD was higher than VD, especially in older age group, 2.6 vs. 1.8%, 1.8 vs. 2.7%, and 11.5 w. 2.9% for individuals aged 55 years and over, 65 years and over and 75 years and over, respectively There was little difference in cruud prevalence in individuals aged 65 years and over between urban and rurai communities (4.2 vs. 5.8% for AD and 1.8 w. 4. 1% for VD). Concluslon: Our overall prevalence is c onsiderably higher than previously reported estimates fiom Chuna and similar to thosc rcpoitcd in whitcs, suggcating that China is not a low risk arca for AD

  3. [Doppler flowmetric fetal indices in low-risk pregnancies].

    Science.gov (United States)

    Romero Gutiérrez, G; Ponce de León, A L; Ramos Palma, S

    1999-10-01

    In order to measure the umbilical resistance and pulsatility Doppler indexes 60 pregnant women with low risk pregnancies were studied in a descriptive, observational and prospective study carried out at the Hospital de Gineco-Pediatria numero 48 del Instituto Mexicano del Seguro Social. Umbilical Doppler measurements were done of the fetal umbilical cord from the week 30 at the 40 of gestation. We carried out a total of 337 measurements and 178 (52.8%) corresponded to the resistance index and 159 (47.2%) to the pulsatility index. The average of the resistance index was 0.64 with a range average (average plus two standard deviations was 0.48-0.79) and the pulsatility index had an average value of 0.94 with an average range of 0.58-1.30. The percentil values of the resistance index were 0.52, 0.66 and 0.79 respectively in the percentil 5, 50 and 95 whereas the percentil values of the pulsatility index were 0.64, 0.94 and 1.28 respectively in the percentil 5, 50 and 95. The analysis of variance with the Bonferroni test for multiple comparisons showed that our found indexes can be applied from the week 31 to the 40 of gestation. Our findings are in according to reported by other authors and it should be kept in mind that the concept of normality of the Doppler velocimetry indexes is strictly statistical and that only its judicious use will offer the benefit to our pregnant patients to obtain products under good conditions of health.

  4. Nonsynonymous variants in MYH9 and ABCA4 are the most frequent risk loci associated with nonsyndromic orofacial cleft in Taiwanese population.

    Science.gov (United States)

    Peng, Hsiu-Huei; Chang, Nai-Chung; Chen, Kuo-Ting; Lu, Jang-Jih; Chang, Pi-Yueh; Chang, Shih-Cheng; Wu-Chou, Yah-Huei; Chou, Yi-Ting; Phang, Wanni; Cheng, Po-Jen

    2016-08-15

    Nonsyndromic orofacial cleft is a common birth defect with a complex etiology, including multiple genetic and environmental risk factors. Recent whole genome analyses suggested associations between nonsyndromic orofacial cleft and up to 18 genetic risk loci (ABCA4, BMP4, CRISPLD2, GSTT1, FGF8, FGFR2, FOXE1, IRF6, MAFB, MSX1, MTHFR, MYH9, PDGFC, PVRL1, SUMO1, TGFA, TGFB3, and VAX1), each of which confers a different relative risk in different populations. We evaluate the nonsynonymous variants in these 18 genetic risk loci in nonsyndromic orofacial clefts and normal controls to clarify the specific variants in Taiwanese population. We evaluated these 18 genetic risk loci in 103 cases of nonsyndromic orofacial clefts and 100 normal controls using a next-generation sequencing (NGS) customized panel and manipulated a whole-exon targeted-sequencing study based on the NGS system of an Ion Torrent Personal Genome Machine (IT-PGM). IT-PGM data processing, including alignment with the human genome build 19 reference genome (hg19), base calling, trimming of barcoded adapter sequences, and filtering of poor signal reads, was performed using the IT platform-specific pipeline software Torrent Suite, version 4.2, with the plug-in "variant caller" program. Further advanced annotation was facilitated by uploading the exported VCF file from Variant Caller to the commercial software package Ion Reporter; the free online annotation software Vanno and Mutation Taster. Benign or tolerated amino acid changes were excluded after analysis using sorting intolerant from tolerant and polymorphism phenotyping. Sanger sequencing was used to validate the significant variants identified by NGS. Furthermore, each variant was confirmed in asymptomatic controls using the Sequenom MassARRAY (San Diego, CA, USA). We identified totally 22 types of nonsynonymous variants specific in nonsyndromic orofacial clefts, including 19 single nucleotide variants, 2 deletions, and 1 duplication in 10 studied

  5. Research on the relationship between bFGF, FGFR2 and the fibroblast proliferation promoted by high density iodine%高碘促成纤维细胞增殖作用与成纤维细胞生长因子及其受体的关系

    Institute of Scientific and Technical Information of China (English)

    华浅近; 祖茂衡; 滕飞; 王磊; 胡琳

    2013-01-01

    目的 研究高碘促进成纤维细胞增殖作用与碱性成纤维细胞生长因子(bFGF)、成纤维细胞生长因子2型受体(FGFR2)的关系,探索.高碘因素在布-加综合征(BCS)隔膜组织形成过程中的作用机制.方法 ①将体外培养的成纤维细胞分成对照组、溶媒组、KI组、FGFR抑制剂组和KI与FGFR抑制剂共同作用组,采用CCK-8法检测各组成纤维细胞增殖率.②采用免疫印迹法检测不同碘浓度(0、250、500、1 000、2 000、3 000 μg/L)培养环境中bFGF、FGFR2蛋白表达量.多组间比较采用单因素方差分析(ANOVA),多个实验组与1个对照组比较采用最小显著差法(LSD).结果 ①在1 000 μg/L碘浓度组,KI与FGFR抑制剂共同作用组成纤维细胞增殖率(1.06±0.13)高于FGFR抑制剂组(0.40±0.12),而低于KI组(1.73±0.09),组问差异有统计学意义(P<0.05).②在500、1 000 μg/L碘浓度组,FGFR2蛋白相对表达量高于其他碘浓度组,而1 000 μg/L组高于500tμg/L组,组间差异有统计学意义(P<0.05).各碘浓度组间bFGF蛋白相对表达量差异无统计学意义(P>0.05).结论 ①高碘冈素可能通过上调FGFR2蛋白表达量而引起成纤维细胞增殖;②高碘导致的成纤维细胞增殖可能与隔膜形成相关.

  6. 29 CFR 99.530 - Criteria for a low-risk auditee.

    Science.gov (United States)

    2010-07-01

    ...) shall qualify as a low-risk auditee and be eligible for reduced audit coverage in accordance with § 99... part. A non-Federal entity that has biennial audits does not qualify as a low-risk auditee, unless... 29 Labor 1 2010-07-01 2010-07-01 true Criteria for a low-risk auditee. 99.530 Section 99.530...

  7. What is low-risk prostate cancer and what is its natural history?

    Science.gov (United States)

    O'Donnell, Helen; Parker, Chris

    2008-10-01

    This article reviews the definition, incidence, pathological characteristics and natural history of low risk localised prostate cancer. Low risk disease is typically defined as clinical stage T1/T2a, biopsy Gleason score reporting of outcomes and for the production of clinical guidelines. However, the low-risk disease is a broad category with a range of pathological characteristics and clinical behaviour. Many, but not all, low-risk prostate cancers are clinically insignificant, destined never to cause any harm. The challenge of managing low risk localized prostate cancer is to distinguish patients with clinically relevant cancers, who may benefit from radical treatment, from the remainder who do not need any intervention. The natural history of untreated low-risk localised prostate cancer has not been well studied, partly because it is a relatively recent entity, and partly because it has been standard practice for men with low risk disease to receive treatment. Data from watchful waiting in the pre-PSA era, modelling studies to take account of the lead time and overdiagnosis associated with PSA testing, and the early results of active surveillance can all provide insights into the likely natural history of low risk disease. There remains a major unmet need for markers of individual prostate cancer behaviour within the low-risk category. Such markers could be used to distinguish those men with truly indolent disease, suitable for observation, from those with significant prostate cancer that stand to benefit from treatment.

  8. Milk intake is not associated with low risk of diabetes or overweight-obesity

    DEFF Research Database (Denmark)

    Bergholdt, Helle K M; Nordestgaard, Børge G; Ellervik, Christina

    2015-01-01

    BACKGROUND: High dairy/milk intake has been associated with a low risk of type 2 diabetes observationally, but whether this represents a causal association is unknown. OBJECTIVE: We tested the hypothesis that high milk intake is associated with a low risk of type 2 diabetes and of overweight-obes...

  9. Home birth or short-stay hospital birth in a low risk population in The Netherlands.

    NARCIS (Netherlands)

    Wiegers, T.A.; Zee, J. van der; Kerssens, J.J.; Keirse, M.J.N.C.

    1998-01-01

    In the Netherlands women with low risk pregnancies can choose whether they want to give birth at home or in hospital, under the care of their own primary caregiver. The majority of these women prefer to give birth at home, but over the last few decades an increasing number of low risk women have

  10. 38 CFR 41.530 - Criteria for a low-risk auditee.

    Science.gov (United States)

    2010-07-01

    ... low-risk auditee and be eligible for reduced audit coverage in accordance with § 41.520: (a) Single... entity that has biennial audits does not qualify as a low-risk auditee, unless agreed to in advance by... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Criteria for a...

  11. Home birth or short-stay hospital birth in a low risk population in The Netherlands.

    NARCIS (Netherlands)

    Wiegers, T.A.; Zee, J. van der; Kerssens, J.J.; Keirse, M.J.N.C.

    1998-01-01

    In the Netherlands women with low risk pregnancies can choose whether they want to give birth at home or in hospital, under the care of their own primary caregiver. The majority of these women prefer to give birth at home, but over the last few decades an increasing number of low risk women have cho

  12. 中国人群FGFR2基因多态性与乳腺癌易感相关性研究的Meta分析%Fibroblast growth factor receptor 2 polymorphism and susceptibility to breast cancer in Chinese population:a Meta-analysis

    Institute of Scientific and Technical Information of China (English)

    邱秀娟; 成芳; 高俊

    2015-01-01

    OBJECTIVE To evaluate the association between the fibroblast growth factor receptor 2 (FGFR2) gene polymorphism (rs2981582,rs1219648,rs2420946) and the breast cancer risk in the Chinese populations.METHODS All studies published up to June 2014 on the association between three functional polymorphisms (rs2981582,rs1219648,rs2420946) in the promoter of FGFR2 gene and susceptibility to breast cancer in Chinese population were collected by searching PubMed,Embase,Cochrane library,CNKI,VIP,Wanfang and CBD database.The data were screened according to the inclusion and exclusion criteria,and extracted,and the quality of included studies was evaluated.The pooled odds ratios (OR) with 95 % confidence intervals (95 % CI) were calculated using Stata 12.0 software.Publication bias and sensitivity analysis were also assessed.RESULTS A total of 18 case-control studies involving 14568 cases and 12864 controls were included in the Meta-analysis.The FGFR2 rs2981582,rs1219648,rs2420946 polymorphisms were significantly associated with breast cancer risk susceptibility among Chinese populations.The subgroup analysis by region revealed that significant risks were found in southern and northern China populations for rs2981582 T allele(southern:OR=1.13,95 %CI:1.06-1.22,P =0.001 ; northern:OR =1.26,95% CI..1.06-1.49,P =0.008).Significant risks were found in southern China populations for rs2420946 T allele (OR=1.15,95 % CI:1.08-1.23,P<0.05),but not in northern China populations (OR=1.03,95 % CI:0.87-1.22,P =0.695).Significant risks were found in southern and northern China populations for rs1219648 G allele(southern:OR=1.19,95%CI:1.10-1.28,P<0.05; northern:OR=1.17,95%CI:1.00-1.37,P=0.05).CONCLUSION The FGFR2 rs2981582,rs1219648,rs2420946 polymorphisms are significantly associated with breast cancer risk susceptibility among Chinese populations.%目的 系统评估成纤维细胞生长因子受体2(fibroblast growth factor receptor 2,FGFR2)基因内含子的3

  13. Chromosome 8q23.3 and 11q23.1 Variants Modify Colorectal Cancer Risk in Lynch Syndrome

    NARCIS (Netherlands)

    Wijnen, Juul T.; Brohet, Richard M.; Van Eijk, Ronald; Jagmohan-Changur, Shanty; Middeldorp, Anneke; Tops, Carli M.; Van Puijenbroek, Mario; Ausems, Margreet G. E. M.; Garcia, Encarna Gomez; Hes, Frederik J.; Hoogerbrugge, Nicoline; Menko, Fred H.; Van Os, Theo A. M.; Sijmons, Rolf H.; Verhoef, Senno; Wagner, Anja; Nagengast, Fokko M.; Kleibeuker, Jan H.; Devilee, Peter; Morreau, Hans; Goldgar, David; Tomlinson, Ian P.; Houlston, Richard S.; Van Wezel, Tom; Vasen, Hans F. A.

    2009-01-01

    Background & Aims: Recent genome-wide association studies have identified common low-risk variants for colorectal cancer (CRC). To assess whether these influence CRC risk in the Lynch syndrome, we genotyped these variants in a large series of proven mutation carriers. Methods: We studied 675 individ

  14. Can MRI biomarkers at 3 T identify low-risk ductal carcinoma in situ?

    Science.gov (United States)

    Rahbar, Habib; Parsian, Sana; Lam, Diana L; Dontchos, Brian N; Andeen, Nicole K; Rendi, Mara H; Lehman, Constance D; Partridge, Savannah C

    2016-01-01

    The objective was to explore whether 3-T magnetic resonance imaging (MRI) can identify low-risk ductal carcinoma in situ (DCIS). Dynamic contrast-enhanced and diffusion-weighted (DWI) MRI features of 36 DCIS lesions [8 low risk, Van Nuys Pathologic Classification (VNPC) 1; 28 high risk, VNPC 2/3] were reviewed. An MRI model that best identified low-risk DCIS was determined using multivariate logistic regression. Low-risk DCIS exhibited different DWI properties [i.e., higher contrast-to-noise ratio (P=.02) and lower normalized apparent diffusion coefficients (P=.04)] than high-risk DCIS. A model combining these DWI features provided best performance (area under receiver operating characteristic curve =0.86). DWI may help identify DCIS lesions requiring less therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Parametrial involvement in women with low-risk, early-stage cervical cancer.

    Science.gov (United States)

    Vanichtantikul, A; Tantbirojn, P; Manchana, T

    2017-09-01

    This study identified the incidence of parametrial involvement in low risk, early-stage cervical cancer patients and evaluated the factors associated with parametrial involvement. All stage IA2-IB1 cervical cancer patients who underwent radical hysterectomy with pelvic lymphadenectomy were retrospectively reviewed. Patients with squamous cell carcinoma or adenocarcinoma grade 1-2, tumour size less than 2 cm, no lymphovascular space invasion (LVSI), negative pelvic nodes and depth of stromal invasion (DSI) less than 10 mm were identified as the low-risk group. A total of 243 patients were eligible. Squamous cell carcinomas were the most frequent histological cell type (65%). Most patients (81.5%) had tumour size less than 2 cm. Thirteen patients (5.3%) had parametrial involvement, 77 (31.7%) had DSI more than 10 mm, 121 (49.8%) had more than 50% invasion, 119 (49%) had LVSI and 19 (7.5%) had node metastasis. Ninety-five patients (39.1%) were defined as low risk. None of low-risk group had parametrial involvement. DSI more than 10 mm or more than 50% stromal invasion, presence of LVSI and pelvic node metastasis were significant factors associated with parametrial involvement. Parametrial involvement in low-risk, early-stage cervical cancer is extremely low. Less radical surgery may be an alternative treatment option. © 2016 John Wiley & Sons Ltd.

  16. How to identify twins at low risk of spontaneous preterm delivery

    DEFF Research Database (Denmark)

    Sperling, Lene; Kiil, C; Larsen, L U

    2005-01-01

    OBJECTIVE: The aim of this study was to evaluate transvaginal sonographic assessment of cervical length at 23 weeks as a screening test for spontaneous preterm delivery in order to define a cut-off value that could be used to select twin pregnancies at low risk of spontaneous preterm delivery...... at 23 weeks of gestation is a good screening test for predicting twins at low risk of preterm and very preterm delivery, especially in DC twins. The present results suggest that a cut-off of 25 mm should be recommended....

  17. Gender Differences in Empathy in Parents at High- and Low-Risk of Child Physical Abuse

    Science.gov (United States)

    Perez-Albeniz, A.; de Paul, Joaquin

    2004-01-01

    Objectives: The present research was designed to study empathy in high-risk parents for child physical abuse. The main objective was to study if high-risk mothers and fathers, compared to low-risk mothers and fathers, presented more Personal distress, less Perspective-taking, less Empathic concern and a deficit in dispositional empathy toward…

  18. 75 FR 66298 - Prompt Corrective Action; Amended Definition of Low-Risk Assets

    Science.gov (United States)

    2010-10-28

    ... of credit risk. The amendment will expand the definition of ``low-risk assets'' to include debt... ratio'' is based upon a risk-weighting applied to each of eight different portfolios of credit union... person credit union would fall within the ``investments'' risk portfolio, consisting of investments `` s...

  19. Low-risk susceptibility alleles in 40 human breast cancer cell lines

    NARCIS (Netherlands)

    M. Riaz (Muhammad); F. Elstrodt (Fons); A. Hollestelle (Antoinette); A. Dehghan (Abbas); J.G.M. Klijn (Jan); M. Schutte (Mieke)

    2009-01-01

    textabstractBackground: Low-risk breast cancer susceptibility alleles or SNPs confer only modest breast cancer risks ranging from just over 1.0 to 1.3 fold. Yet, they are common among most populations and therefore are involved in the development of essentially all breast cancers. The mechanism by w

  20. Determinants of prenatal health care utilisation by low-risk women : A prospective cohort study

    NARCIS (Netherlands)

    Feijen-de Jong, Esther I.; Jansen, Danielle E. M. C.; Baarveld, Frank; Boerleider, Agatha W.; Spelten, Evelien; Schellevis, Francois; Reijneveld, Sijmen A.

    Background: Prenatal health care is pivotal in providing adequate prevention and care to pregnant women. Aim: We examined the determinants of inadequate prenatal health care utilisation by low-risk women in primary midwifery-led care in the Netherlands. Methods: We used longitudinal data from the

  1. Determinants of prenatal health care utilisation by low-risk women: a prospective cohort study.

    NARCIS (Netherlands)

    Feijen-de Jong, E.I.; Jansen, D.E.M.C.; Baarveld, F.; Boerleider, A.W.; Spelten, E.; Schellevis, F.; Reijneveld, S.A.

    2015-01-01

    Background: Prenatal health care is pivotal in providing adequate prevention and care to pregnant women. Aim: We examined the determinants of inadequate prenatal health care utilisation by low-risk women in primary midwifery-led care in the Netherlands. Methods: We used longitudinal data from the

  2. Low-risk susceptibility alleles in 40 human breast cancer cell lines

    NARCIS (Netherlands)

    M. Riaz (Muhammad); F. Elstrodt (Fons); A. Hollestelle (Antoinette); A. Dehghan (Abbas); J.G.M. Klijn (Jan); M. Schutte (Mieke)

    2009-01-01

    textabstractBackground: Low-risk breast cancer susceptibility alleles or SNPs confer only modest breast cancer risks ranging from just over 1.0 to 1.3 fold. Yet, they are common among most populations and therefore are involved in the development of essentially all breast cancers. The mechanism by w

  3. Increasing Threat of Brucellosis to Low-Risk Persons in Urban Settings, China

    OpenAIRE

    Chen, Shouyi; Zhang, Hao; Liu, Xiaoning; Wang, Wenjing; Hou, Shuiping; Li, Tingting; Zhao, Shuoxian; Yang,Zhicong; Li, Chengyao

    2014-01-01

    Cases of brucellosis were diagnosed in 3-month-old twins and their mother. An epidemiologic survey suggested that raw sheep or goat meat might be the source of Brucella melitensis infection. This finding implies that the increasing threat of brucellosis might affect low-risk persons in urban settings in China.

  4. Breast SeIf-Examination Behavior Among High and Low Risk Women

    Science.gov (United States)

    1986-04-10

    melatonin levels monitored for a 24-hour period. Transportation was provided by the Institute. The response rate was 100 per cent. Low risk...20 - for potential health problems in the areas or vision, blood Pressure, diabetes and others). They were informed that this study was one

  5. Biomarkers and low risk in heart failure. Data from COACH and TRIUMPH

    NARCIS (Netherlands)

    Meijers, Wouter C.; de Boer, Rudolf A.; van Veldhuisen, Dirk J.; Jaarsma, Tiny; Hillege, Hans L.; Maisel, Alan S.; Di Somma, Salvatore; Voors, Adriaan A.; Peacock, W. Frank

    2015-01-01

    AimTraditionally, risk stratification in heart failure (HF) emphasizes assessment of high risk. We aimed to determine if biomarkers could identify patients with HF at low risk for death or HF rehospitalization. Methods and resultsThis analysis was a substudy of The Coordinating Study Evaluating Outc

  6. Spontaneous preterm delivery among primiparous women at low risk in Denmark: a population based study

    DEFF Research Database (Denmark)

    Langhoff-Roos, Jens; Kesmodel, Ulrik; Jacobsson, Bo

    2006-01-01

    can be compared internationally. DESIGN: Population based study. PARTICIPANTS: 99.8% of all deliveries in Denmark, 1995-2004. MAIN OUTCOME MEASURES: Proportion of babies born at less than 37 weeks' completed gestation for each year in the overall population and in a standard population at low risk...

  7. Spontaneous preterm delivery among primiparous women at low risk in Denmark: a population based study

    DEFF Research Database (Denmark)

    Langhoff-Roos, Jens; Kesmodel, Ulrik; Jacobsson, Bo

    2006-01-01

    can be compared internationally. DESIGN: Population based study. PARTICIPANTS: 99.8% of all deliveries in Denmark, 1995-2004. MAIN OUTCOME MEASURES: Proportion of babies born at less than 37 weeks' completed gestation for each year in the overall population and in a standard population at low risk...

  8. New prognostic parameters for very-low-risk gastrointestinal stromal tumors

    Institute of Scientific and Technical Information of China (English)

    WU Xian-hua; HOU Ying-yong; XU Chen; LIU Ya-lan; SHI Yuan; TAN Yun-shan; ZHU Xiong-zeng

    2011-01-01

    Background According to the National Institutes of Health consensus criteria, gastrointestinal stromal tumors (GISTs) smaller than 2 cm in diameter with less than 5 mitotic figures per 50 high-power fields are considered very-low-risk GISTs, but these two indices alone cannot reliably predict a benign outcome during long-term follow-ups. Therefore, identification of additional parameters for predicting the clinical behavior of GISTs is necessary.Methods Eighty-eight patients with tumors that meet the very-low-risk GIST criteria were retrospectively investigated and morphological parameters of tumors associated with the biological behavior of very-low-risk GISTs were evaluated in the present study. The Kaplan-Meier method was used to calculate disease-free survival rates.Results Eighty-one patients were followed up for one to 16.3 years. Five cases of relapses were identified in the patients. Distinctive infiltrative growth patterns such as muscularis propria, muscularis mucosa, or nerve infiltration were identified by microscopy in 4 patients with the relapse, including three patients who experienced multiple recurrences. The infiltrative growth features became more obvious in multiple recurrent tumors compared to the single recurrent tumor, while only one developed relapse in 76 patients without infiltration (P <0.0001).Conclusion Microscopic infiltrative growth patterns of the tumor may have clinical significance in predicting the prognosis of very-low-risk GISTs.

  9. The Clinical Significance of Unknown Sequence Variants in BRCA Genes

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    Calò, Valentina; Bruno, Loredana; Paglia, Laura La; Perez, Marco; Margarese, Naomi [Department of Surgery and Oncology, Regional Reference Center for the Biomolecular Characterization and Genetic Screening of Hereditary Tumors, University of Palermo, Via del Vespro 127, 90127 Palermo (Italy); Gaudio, Francesca Di [Department of Medical Biotechnologies and Legal Medicine, University of Palermo, Palermo (Italy); Russo, Antonio, E-mail: lab-oncobiologia@usa.net [Department of Surgery and Oncology, Regional Reference Center for the Biomolecular Characterization and Genetic Screening of Hereditary Tumors, University of Palermo, Via del Vespro 127, 90127 Palermo (Italy)

    2010-09-10

    Germline mutations in BRCA1/2 genes are responsible for a large proportion of hereditary breast and/or ovarian cancers. Many highly penetrant predisposition alleles have been identified and include frameshift or nonsense mutations that lead to the translation of a truncated protein. Other alleles contain missense mutations, which result in amino acid substitution and intronic variants with splicing effect. The discovery of variants of uncertain/unclassified significance (VUS) is a result that can complicate rather than improve the risk assessment process. VUSs are mainly missense mutations, but also include a number of intronic variants and in-frame deletions and insertions. Over 2,000 unique BRCA1 and BRCA2 missense variants have been identified, located throughout the whole gene (Breast Cancer Information Core Database (BIC database)). Up to 10–20% of the BRCA tests report the identification of a variant of uncertain significance. There are many methods to discriminate deleterious/high-risk from neutral/low-risk unclassified variants (i.e., analysis of the cosegregation in families of the VUS, measure of the influence of the VUSs on the wild-type protein activity, comparison of sequence conservation across multiple species), but only an integrated analysis of these methods can contribute to a real interpretation of the functional and clinical role of the discussed variants. The aim of our manuscript is to review the studies on BRCA VUS in order to clarify their clinical relevance.

  10. A COMPARATIVE STUDY OF PERINATAL OUTCOME IN LOW RISK PREGNANCIES WITH CTG MONITORING AND INTERMITTENT AUSCULTATION

    Directory of Open Access Journals (Sweden)

    Velimala Ratna

    2015-12-01

    Full Text Available EFM was introduced into widespread clinical practice in the 1970s to 1980s on the premise that it would facilitate early detection of abnormal FHR patterns thought to be associated with hypoxia thus allowing earlier intervention to prevent foetal neurological damage and/or death. There is a lack of evidence of benefit supporting the use of the admission CTG in low-risk pregnancy. In this study we the aim to evaluate the effects of Cardiotocograph Foetal Monitoring on perinatal outcome in low risk Obstetric population and determine the cost effective and reliable method of fetal monitoring that is applicable to low-risk population. METHODOLOGY A prospective randomized study conducted on 200 low risk pregnant women in labour divided into 2 groups of 100 each. Group A includes those monitored with admission CTG and Group B includes those monitored with intermittent auscultation (IA. OBSERVATION AND RESULTS The demographic features, parity and gestational age in both the groups were comparable; 10 out of the 100 in CTG group had meconium stained liquor whereas 15 of them had meconium in IA group; 71% of the patients in CTG group had normal delivery, whereas it was 84% in IA group. Incidence of LSCS was 23% in CTG group as against 9% in IA group. A ‘P’ value of 0.02, RR of 2 5 for operative deliveries in CTG group was observed which was significant. Incidence of AVD was 6% in CTG group and 7% in IA group with a p value of <0.05, which is statistically significant. The incidence of MSL, APGAR scores at 1, 5 and 10 minutes and NICU admissions were comparable in both the groups. There was no significant difference in babies with low APGAR <7 at 5 min and NICU admissions in both the groups. In our study the sensitivity of CTG was 63.63%, specificity 80.35%, positive predictive value 33.3%, negative predictive value 94.93%. The low sensitivity and high false positives led to the intervention in delivery and increase in operative delivery with no

  11. Comprehensive analysis of human papillomavirus prevalence and the potential role of low-risk types in verrucous carcinoma.

    Science.gov (United States)

    del Pino, Marta; Bleeker, Maaike C G; Quint, Wim G; Snijders, Peter J F; Meijer, Chris J L M; Steenbergen, Renske D M

    2012-10-01

    The role of human papillomavirus (HPV) infections in the development of verrucous carcinoma, a well-differentiated variant of squamous cell carcinoma with difficult differential diagnosis, is controversial in the literature. In this study, we analysed verrucous carcinoma from different origins for the presence and activity of a broad spectrum of HPV types, and carefully reviewed the histopathological features. A random series of 27 formalin-fixed, paraffin-embedded specimens of verrucous carcinoma was taken, representing the head and neck region (n=6), anogenital area (n=16) and extragenital skin region (n=5). After review of the histological slides, all samples were subjected to different polymerase chain reaction-based HPV detection techniques, together detecting a total of 83 HPV types, including both mucosal and cutaneous types. Histological revision was carefully performed. Lesions with keratinised papillae, blunt stromal invaginations and minimal cytological atypia were considered verrucous carcinoma. Condylomatous lesions with viral changes were defined as giant condyloma. Verrucous lesions that did not meet those criteria were classified as verrucous hyperplasia. Tumours with stromal infiltration were considered as invasive squamous cell carcinoma. Histological revision revealed that 13 out of 27 cases were verrucous carcinoma (one showing a double infection with HPV 35 and 45), 5 invasive squamous cell carcinomas, 5 verrucous hyperplasia (one with a double infection with HPV 4 and 8), 1 pseudoepitheliomatous hyperplasia and 3 giant condylomas. All three giant condylomas were low-risk HPV positive (HPV 6 and 11) and showed active mRNA transcription. None of the HPV-positive samples tested positive for diffuse p16(INK4A) staining. In conclusion, our results do not support a causal role of HPV in the development of verrucous carcinoma. Testing for LR-HPV, particularly HPV 6 and 11, may help in the differential diagnosis of lesions suspicious of verrucous

  12. CT coronary angiography: new risks for low-risk chest pain.

    Science.gov (United States)

    Radecki, Ryan Patrick

    2013-10-01

    Widespread conservative management of low-risk chest pain has motivated the development of a rapid triage strategy based on CT coronary angiography (CTCA) in the Emergency Department (ED). Recently, three prominent trials using this technology in the ED setting have presented results in support of its routine use. However, these studies fail to show the incremental prognostic value of CTCA over clinical and biomarker-based risk-stratification strategies, demonstrate additional downstream costs and interventions, and result in multiple harms associated with radio-contrast and radiation exposure. Observing the widespread overdiagnosis of pulmonary embolism following availability of CT pulmonary angiogram as a practice pattern parallel, CTCA use for low-risk chest pain in the ED should be advanced only with caution.

  13. Targeted deep sequencing improves outcome stratification in chronic myelomonocytic leukemia with low risk cytogenetic features

    Science.gov (United States)

    Palomo, Laura; Garcia, Olga; Arnan, Montse; Xicoy, Blanca; Fuster, Francisco; Cabezón, Marta; Coll, Rosa; Ademà, Vera; Grau, Javier; Jiménez, Maria-José; Pomares, Helena; Marcé, Sílvia; Mallo, Mar; Millá, Fuensanta; Alonso, Esther; Sureda, Anna; Gallardo, David; Feliu, Evarist; Ribera, Josep-Maria; Solé, Francesc; Zamora, Lurdes

    2016-01-01

    Clonal cytogenetic abnormalities are found in 20-30% of patients with chronic myelomonocytic leukemia (CMML), while gene mutations are present in >90% of cases. Patients with low risk cytogenetic features account for 80% of CMML cases and often fall into the low risk categories of CMML prognostic scoring systems, but the outcome differs considerably among them. We performed targeted deep sequencing of 83 myeloid-related genes in 56 CMML patients with low risk cytogenetic features or uninformative conventional cytogenetics (CC) at diagnosis, with the aim to identify the genetic characteristics of patients with a more aggressive disease. Targeted sequencing was also performed in a subset of these patients at time of acute myeloid leukemia (AML) transformation. Overall, 98% of patients harbored at least one mutation. Mutations in cell signaling genes were acquired at time of AML progression. Mutations in ASXL1, EZH2 and NRAS correlated with higher risk features and shorter overall survival (OS) and progression free survival (PFS). Patients with SRSF2 mutations associated with poorer OS, while absence of TET2 mutations (TET2wt) was predictive of shorter PFS. A decrease in OS and PFS was observed as the number of adverse risk gene mutations (ASXL1, EZH2, NRAS and SRSF2) increased. On multivariate analyses, CMML-specific scoring system (CPSS) and presence of adverse risk gene mutations remained significant for OS, while CPSS and TET2wt were predictive of PFS. These results confirm that mutation analysis can add prognostic value to patients with CMML and low risk cytogenetic features or uninformative CC. PMID:27486981

  14. First-line chemotherapy in low-risk gestational trophoblastic neoplasia.

    LENUS (Irish Health Repository)

    Alazzam, Mo'iad

    2012-01-01

    This is an update of a Cochrane review that was first published in Issue 1, 2009. Gestational trophoblastic neoplasia (GTN) is a rare but curable disease arising in the fetal chorion during pregnancy. Most women with low-risk GTN will be cured by evacuation of the uterus with or without single-agent chemotherapy. However, chemotherapy regimens vary between treatment centres worldwide and the comparable benefits and risks of these different regimens are unclear.

  15. Determinants of prenatal health care utilisation by low-risk women: a prospective cohort study.

    OpenAIRE

    Feijen-de Jong, E.I.; Jansen, D. E. M. C.; Baarveld, F.; Boerleider, A.W.; Spelten, E.; Schellevis, F.; Reijneveld, S.A.

    2015-01-01

    Background: Prenatal health care is pivotal in providing adequate prevention and care to pregnant women. Aim: We examined the determinants of inadequate prenatal health care utilisation by low-risk women in primary midwifery-led care in the Netherlands. Methods: We used longitudinal data from the population-based DELIVER study with 20 midwifery practices across the Netherlands in 2009 and 2010 as the experimental setting. The participants were 3070 pregnant women starting pregnancy care in pr...

  16. Overweight and Severe Acute Maternal Morbidity in a Low-Risk Pregnant Population in The Netherlands

    OpenAIRE

    Tom Witteveen; Zwart, Joost J.; Gast, Karin B.; Bloemenkamp, Kitty W M; Jos van Roosmalen

    2013-01-01

    OBJECTIVE: To investigate the association between overweight and severe acute maternal morbidity (SAMM) in a low-risk pregnant population. DESIGN: Nationwide case-control study. SETTING: The Netherlands, august 2004 to august 2006. POPULATION: 1567 cases from initially primary care and 2994 women from primary care practices as controls, out of 371 012 women delivering in the Netherlands during the study period. METHODS: Cases were women with SAMM obtained from a nationwide prospective study. ...

  17. Towards Providing Low-Risk and Economically Feasible Network Data Transfer Services

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    Andreica, Mugurel Ionut; Tipa, Stelian

    2010-01-01

    In the first part of this paper we present the first steps towards providing low-risk and economically feasible network data transfer services. We introduce three types of data transfer services and present general guidelines and algorithms for managing service prices, risks and schedules. In the second part of the paper we solve two packet scheduling cost optimization problems and present efficient algorithms for identifying maximum weight (k-level-) caterpillar subtrees in tree networks.

  18. Induction of labor and risk of postpartum hemorrhage in low risk parturients.

    Directory of Open Access Journals (Sweden)

    Imane Khireddine

    Full Text Available OBJECTIVE: Labor induction is an increasingly common procedure, even among women at low risk, although evidence to assess its risks remains sparse. Our objective was to assess the association between induction of labor and postpartum hemorrhage (PPH in low-risk parturients, globally and according to its indications and methods. METHOD: Population-based case-control study of low-risk women who gave birth in 106 French maternity units between December 2004 and November 2006, including 4450 women with PPH, 1125 of them severe, and 1744 controls. Indications for labor induction were standard or non-standard, according to national guidelines. Induction methods were oxytocin or prostaglandins. Multilevel multivariable logistic regression modelling was used to test the independent association between induction and PPH, quantified as odds ratios. RESULTS: After adjustment for all potential confounders, labor induction was associated with a significantly higher risk of PPH (adjusted odds ratio, AOR1.22, 95%CI 1.04-1.42. This excess risk was found for induction with both oxytocin (AOR 1.52, 95%CI 1.19-1.93 for all and 1.57, 95%CI 1.11-2.20 for severe PPH and prostaglandins (AOR 1.21, 95%CI 0.97-1.51 for all and 1.42, 95%CI 1.04-1.94 for severe PPH. Standard indicated induction was significantly associated with PPH (AOR1.28, 95%CI 1.06-1.55 while no significant association was found for non-standard indicated inductions. CONCLUSION: Even in low risk women, induction of labor, regardless of the method used, is associated with a higher risk of PPH than spontaneous labor. However, there was no excess risk of PPH in women who underwent induction of labor for non-standard indications. This raises the hypothesis that the higher risk of PPH associated with labor induction may be limited to unfavorable obstetrical situations.

  19. Posture Development in Infants at Heightened vs. Low Risk for Autism Spectrum Disorders

    OpenAIRE

    Nickel, Lindsay R.; Thatcher, Alyssa R.; Keller, Flavio; Wozniak, Robert H.; Iverson, Jana M.

    2013-01-01

    Evidence suggests that children and adults diagnosed with autism spectrum disorders (ASD) exhibit difficulties with postural control. Retrospective video studies of infants later diagnosed with ASD indicate that infants who eventually receive an ASD diagnosis exhibit delays in postural development. This study investigates early posture development prospectively and longitudinally in 22 infants at heightened biological risk for ASD (HR) and 18 infants with no such risk (Low Risk; LR). Four HR ...

  20. [Clinical guideline for management of patients with low risk differentiated thyroid carcinoma].

    Science.gov (United States)

    Díez, Juan José; Oleaga, Amelia; Álvarez-Escolá, Cristina; Martín, Tomás; Galofré, Juan Carlos

    2015-01-01

    Incidence of thyroid cancer is increasing in Spain and worldwide. Overall thyroid cancer survival is very high, and stratification systems to reliably identify patients with worse prognosis have been developed. However, marked differences exist between the different specialists in clinical management of low-risk patients with thyroid carcinoma. Almost half of all papillary thyroid carcinomas are microcarcinomas, and 90% are tumors < 2 cm that have a particularly good prognosis. However, they are usually treated more aggressively than needed, despite the lack of adequate scientific support. Surgery remains the gold standard treatment for these tumors. However, lobectomy may be adequate in most patients, without the need for total thyroidectomy. Similarly, prophylactic lymph node dissection of the central compartment is not required in most cases. This more conservative approach prevents postoperative complications such as hypoparathyroidism or recurrent laryngeal nerve injury. Postoperative radioiodine remnant ablation and strict suppression of serum thyrotropin, although effective for the more aggressive forms of thyroid cancer, have not been shown to be beneficial for the treatment of low risk patients, and may impair their quality of life. This guideline provides recommendations from the task force on thyroid cancer of the Spanish Society of Endocrinology and Nutrition for adequate management of patients with low-risk thyroid cancer.

  1. Tumor suppressor p53 protein expression: prognostic significance in patients with low-risk myelodysplastic syndrome

    Directory of Open Access Journals (Sweden)

    Fernando Barroso Duarte

    2014-06-01

    Full Text Available BACKGROUND: At the time of diagnosis, more than 50% of patients with myelodysplastic syndrome have a normal karyotype and are classified as having a favorable prognosis. However, these patients often show very variable clinical outcomes. Furthermore, current diagnostic tools lack the ability to look at genetic factors beyond karyotyping in order to determine the cause of this variability.OBJECTIVE: To evaluate the impact of p53 protein expression at diagnosis in patients with low-risk myelodysplastic syndrome.METHODS: This study enrolled 38 patients diagnosed with low-risk myelodysplastic syndrome. Clinical data were collected by reviewing medical records, and immunohistochemical p53 staining was performed on bone marrow biopsies.RESULTS: Of the 38 participants, 13 (34.21% showed p53 expression in their bone marrow. At diagnosis, this group of patients also presented clinical features characteristic of a poor prognosis more often than patients who did not express p53. Furthermore, patients expressing p53 had a shorter median survival time compared to those without p53 expression.CONCLUSION: This study shows that the expression of p53 at diagnosis is a useful indicator of distinct clinical characteristics and laboratory profiles found in low-risk myelodysplastic syndrome patients. These data indicate that the immunohistochemical analysis of p53 may be a prognostic tool for myelodysplastic syndrome and should be used as an auxiliary test to help determine the best therapeutic choice.

  2. Treatment of low-risk ductal carcinoma in situ: is nothing better than something?

    Science.gov (United States)

    Benson, John R; Jatoi, Ismail; Toi, Masakazu

    2016-10-01

    The heterogeneous nature of ductal carcinoma in situ has been emphasised by data for breast-cancer screening that show substantial increases in the detection of early-stage non-invasive breast cancer but no noteworthy change in the incidence of invasive and distant metastatic disease. Indolent non-progressive forms of ductal carcinoma in situ are managed according to similar surgical strategies as high-risk disease, with extent of resection dictated by radiological and pathological estimates of tumour dimensions. Although adjuvant treatments might be withheld for low-risk lesions, surgical treatments incur potential morbidity, especially when mastectomy and breast reconstruction are done for widespread low-grade or intermediate-grade ductal carcinoma in situ. Low rates of deaths from breast cancer coupled with overdiagnosis within screening programmes have prompted a fundamental rethink of approaches to the management of both low-risk and high-risk ductal carcinoma in situ. Changes include active surveillance for low-risk lesions and a watchful waiting policy with intervention when invasive local recurrence after breast-conserving surgery is detected. Prediction of ipsilateral invasive recurrence is likely to be improved by integration of molecular biomarkers with conventional histopathological parameters. Moreover, further genetic interrogation of ductal carcinoma in situ might lead to a reclassification of some low-grade lesions as non-cancerous entities.

  3. Histone Variants and Epigenetics

    Science.gov (United States)

    Henikoff, Steven; Smith, M. Mitchell

    2015-01-01

    Histones package and compact DNA by assembling into nucleosome core particles. Most histones are synthesized at S phase for rapid deposition behind replication forks. In addition, the replacement of histones deposited during S phase by variants that can be deposited independently of replication provide the most fundamental level of chromatin differentiation. Alternative mechanisms for depositing different variants can potentially establish and maintain epigenetic states. Variants have also evolved crucial roles in chromosome segregation, transcriptional regulation, DNA repair, and other processes. Investigations into the evolution, structure, and metabolism of histone variants provide a foundation for understanding the participation of chromatin in important cellular processes and in epigenetic memory. PMID:25561719

  4. Identifying Emergency Department Patients at Low Risk for a Variceal Source of Upper Gastrointestinal Hemorrhage.

    Science.gov (United States)

    Klein, Lauren R; Money, Joel; Maharaj, Kaveesh; Robinson, Aaron; Lai, Tarissa; Driver, Brian E

    2017-08-22

    Assessing the likelihood of a variceal versus nonvariceal source of upper gastrointestinal bleeding (UGIB) guides therapy, but can be difficult to determine on clinical grounds. The objective of this study was to determine if there are easily ascertainable clinical and laboratory findings that can identify a patient as low risk for a variceal source of hemorrhage. This was a retrospective cohort study of adult ED patients with UGIB between January 2008 and December 2014 who had upper endoscopy performed during hospitalization. Clinical and laboratory data were abstracted from the medical record. The source of the UGIB was defined as variceal or nonvariceal based on endoscopic reports. Binary recursive partitioning was utilized to create a clinical decision rule. The rule was internally validated and test characteristics were calculated with 1,000 bootstrap replications. 719 patients were identified; mean age was 55 years old and 61% were male. There were 71 (10%) patients with a variceal UGIB identified on endoscopy. Binary recursive partitioning yielded a two-step decision rule (platelet count greater than 200,000/uL, and an INR less than 1.3), which identified patients who were low risk for a variceal source of hemorrhage. For the bootstrapped samples, the rule performed with 97% sensitivity (95% confidence interval [CI] 91-100%) and 49% specificity (95% CI 44- 53%). Although this derivation study must be externally validated before widespread use, patients presenting to the ED with an acute UGIB with platelets of greater than 200,000/uL and an INR less than 1.3 may be at very low risk for a variceal source of their upper gastrointestinal hemorrhage. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Prognostic value of adenosine stress cardiovascular magnetic resonance in patients with low-risk chest pain

    Directory of Open Access Journals (Sweden)

    Oshinski John N

    2009-09-01

    Full Text Available Abstract Background Approximately 5% of patients with an acute coronary syndrome are discharged from the emergency room with an erroneous diagnosis of non-cardiac chest pain. Highly accurate non-invasive stress imaging is valuable for assessment of low-risk chest pain patients to prevent these errors. Adenosine stress cardiovascular magnetic resonance (AS-CMR is an imaging modality with increasing application. The goal of this study was to evaluate the negative prognostic value of AS-CMR among low-risk acute chest pain patients. Methods We studied 103 patients, mean 56.7 ± 12.3 years of age, with chest pain and no electrocardiographic evidence of ischemia and negative cardiac biomarkers of necrosis, who were admitted to the Cardiac Decision Unit of our institution. All patients underwent AS-CMR. A negative AS-CMR was defined as absence of all the following: regional wall motion abnormalities at rest; perfusion defects during stress (adenosine and rest; and myocardial scar on late gadolinium enhancement images. The patients were followed for a mean of 277 (range 161-462 days. The primary end point was defined as the combination of cardiac death, nonfatal acute myocardial infarction, re-hospitalization for chest pain, obstructive coronary artery disease (>50% coronary stenosis on invasive angiography and coronary revascularization. Results In 14 patients (13.6%, AS-CMR was positive. The remaining 89 patients (86.4%, who had negative AS-CMR, were discharged. No patient with negative AS-CMR reached the primary end-point during follow-up. The negative predictive value of AS-CMR was 100%. Conclusion AS-CMR holds promise as a useful tool to rule out significant coronary artery disease in patients with low-risk chest pain. Patients with negative AS-CMR have an excellent short and mid-term prognosis.

  6. Antiplatelet therapy versus observation in low-risk essential thrombocythemia with a CALR mutation

    Science.gov (United States)

    Alvarez-Larrán, Alberto; Pereira, Arturo; Guglielmelli, Paola; Hernández-Boluda, Juan Carlos; Arellano-Rodrigo, Eduardo; Ferrer-Marín, Francisca; Samah, Alimam; Griesshammer, Martin; Kerguelen, Ana; Andreasson, Bjorn; Burgaleta, Carmen; Schwarz, Jiri; García-Gutiérrez, Valentín; Ayala, Rosa; Barba, Pere; Gómez-Casares, María Teresa; Paoli, Chiara; Drexler, Beatrice; Zweegman, Sonja; McMullin, Mary F.; Samuelsson, Jan; Harrison, Claire; Cervantes, Francisco; Vannucchi, Alessandro M.; Besses, Carlos

    2016-01-01

    The role of antiplatelet therapy as primary prophylaxis of thrombosis in low-risk essential thrombocythemia has not been studied in randomized clinical trials. We assessed the benefit/risk of low-dose aspirin in 433 patients with low-risk essential thrombocythemia (271 with a CALR mutation, 162 with a JAK2V617F mutation) who were on antiplatelet therapy or observation only. After a follow up of 2215 person-years free from cytoreduction, 25 thrombotic and 17 bleeding episodes were recorded. In CALR-mutated patients, antiplatelet therapy did not affect the risk of thrombosis but was associated with a higher incidence of bleeding (12.9 versus 1.8 episodes per 1000 patient-years, P=0.03). In JAK2V617F-mutated patients, low-dose aspirin was associated with a reduced incidence of venous thrombosis with no effect on the risk of bleeding. Coexistence of JAK2V617F-mutation and cardiovascular risk factors increased the risk of thrombosis, even after adjusting for treatment with low-dose aspirin (incidence rate ratio: 9.8; 95% confidence interval: 2.3–42.3; P=0.02). Time free from cytoreduction was significantly shorter in CALR-mutated patients with essential thrombocythemia than in JAK2V617F-mutated ones (median time 5 years and 9.8 years, respectively; P=0.0002) and cytoreduction was usually necessary to control extreme thrombocytosis. In conclusion, in patients with low-risk, CALR-mutated essential thrombocythemia, low-dose aspirin does not reduce the risk of thrombosis and may increase the risk of bleeding. PMID:27175028

  7. A pharmacoeconomic analysis of the use of single MMC instillation in low risk NMIBC in Italy

    Directory of Open Access Journals (Sweden)

    Renzo Colombo

    2013-03-01

    Full Text Available BACKGROUND: Bladder cancer accounts for 5-10% of all cancers in Europe and up to 85% patients presents a noninvasive tumor, whose treatment of choice is the transurethral bladder resection (TURB paired with adjuvant intravesical chemotherapy or immunotherapy. Despite several clinical trials showed that this treatment is safe and decreases recurrences by 17% to 44% this practice is limited for many reasons. The study objective is to analyze the economical advantages of the single immediate post operative Mitomycin C instillation in Non Muscle-invasive Bladder Cancer (NMIBC low-risk patients.METHODS: A cost-benefit analysis was performed evaluating the economical gain that would raised from a scenario with a single immediate post operative mitomycin C instillation in each low-risk NMIBC patient who underwent to TURB. Net present value and cost-benefit ratio were calculated and sensitivity analyses were performed. Base case analysis was performed considering tumor recurrence rate reduction of 11.7% and a TURB costs of 2,167.0 €, while sensitivity analyses were performed using a recurrence rate reduction of 19.2% and 15.0% and a TURB cost of 2,472.93 €. The discount rate was 2%.RESULTS: The single immediate post operative instillation of mitomycin C resulted to be cost-beneficial with a cost-benefit ratio that goes from 0.48 to 0.79 when compared to TURB alone raising a Net Present Value that goes from 660,284.39 € to 2,650,530.79 €.CONCLUSION: This study demonstrates that even assuming conservative parameters for recurrence rates reduction, a single immediate post operative mitomycin C instillation in low risk NMIBC patients would lower not only the recurrence rate but also the caring cost for bladder cancer.

  8. Caesarean Section, Epidural, and Forceps Intervention Rates for Low-Risk Obstetric Deliveries

    OpenAIRE

    Rourke, James T.B.

    1989-01-01

    A retrospective chart audit of 237 consecutive deliveries at a community hospital identified 71.3% as “low risk” at admission for labour and delivery. For this low-risk group, 94.7% were delivered vaginally. The epidural rate was 25.6% and the forceps rate was 20.0% for these vaginal deliveries. This study shows it is possible to identify patients as “low risk” at admission for labour and delivery who can be managed expectantly with a relatively low intervention outcome. The author recommends...

  9. Spirituality and low-risk consumption of alcohol in young adults

    Directory of Open Access Journals (Sweden)

    Luz Patricia Díaz Heredia

    2013-07-01

    Full Text Available The relationship between spirituality and health, as well as it effect on adopting healthy behaviors, is a topic of interest for nursing and, in general, for social and life sciences. Spirituality, as a human realm, is a relevant research theme that is often related to the promotion of health in individuals. Studies indicate that spirituality is related to mental and physical health, being a protective and promoting factor of healthy behaviors, among them low-risk consumption of alcohol in young adults.

  10. Clinically low-risk prostate cancer: evaluation with transrectal doppler ultrasound and functional magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Maria Inês Novis

    2011-01-01

    Full Text Available OBJECTIVES: To evaluate transrectal ultrasound, amplitude Doppler ultrasound, conventional T2-weighted magnetic resonance imaging, spectroscopy and dynamic contrast-enhanced magnetic resonance imaging in localizing and locally staging low-risk prostate cancer. INTRODUCTION: Prostate cancer has been diagnosed at earlier stages and the most accepted classification for low-risk prostate cancer is based on clinical stage T1c or T2a, Gleason score <6, and prostate-specific antigen (PSA <10 ng/ml. METHODS: From 2005 to 2006, magnetic resonance imaging was performed in 42 patients, and transrectal ultrasound in 26 of these patients. Seven patients were excluded from the study. Mean patient age was 64.94 years and mean serum PSA was 6.05 ng/ml. The examinations were analyzed for tumor identification and location in prostate sextants, detection of extracapsular extension, and seminal vesicle invasion, using surgical pathology findings as the gold standard. RESULTS: Sixteen patients (45.7% had pathologically proven organ-confined disease, 11 (31.4% had positive surgical margin, 8 (28.9% had extracapsular extension, and 3 (8.6% presented with extracapsular extension and seminal vesicle invasion. Sensitivity, specificity, positive predictive value (PPV, negative predictive value (NPV and accuracy values for localizing low-risk prostate cancer were 53.1%, 48.3%, 63.4%, 37.8% and 51.3% for transrectal ultrasound; 70.4%, 36.2%, 65.1%, 42.0% and 57.7% for amplitude Doppler ultrasound; 71.5%, 58.9%, 76.6%, 52.4% and 67.1% for magnetic resonance imaging; 70.4%, 58.7%, 78.4%, 48.2% and 66.7% for magnetic resonance spectroscopy; 67.2%, 65.7%, 79.3%, 50.6% and 66.7% for dynamic contrast-enhanced magnetic resonance imaging, respectively. Sensitivity, specificity, PPV, NPV and accuracy values for detecting extracapsular extension were 33.3%, 92%, 14.3%, 97.2% and 89.7% for transrectal ultrasound and 50.0%, 77.6%, 13.7%, 95.6% and 75.7% for magnetic resonance imaging

  11. A case series of Nasopharyngeal Carcinoma among Indians, a low risk population, in Perak State, Malaysia.

    Science.gov (United States)

    Anusha, B; Philip, R; Norain, K; Harvinder, S; Gurdeep, S M

    2012-12-01

    Nasopharyngeal carcinoma (NPC) is rare among people of Indian ethnicity. A short retrospective case review of clinical records of Indian patients diagnosed with nasopharyngeal carcinoma in a period of 5 years was conducted. Their slides were further subjected to EBV encoded RNA (EBER) - In- situ Hybridization (ISH). The histologic subtype was nonkeratinizing carcinoma in all 4 patients. All were Epstein Barr Virus (EBV) positive. We believe that the crucial factor responsible for nasopharyngeal carcinoma is genetics; either a genetic susceptibility among high risk groups or genetic resistance/immunity in low risk groups. Further genetic studies are required to look for somatic or inherited chromosomal mutations among the various risk populations.

  12. Obesity is associated with risk of progression for low-risk prostate cancers managed expectantly.

    Science.gov (United States)

    Bhindi, Bimal; Kulkarni, Girish S; Finelli, Antonio; Alibhai, Shabbir M H; Hamilton, Robert J; Toi, Ants; van der Kwast, Theodorus H; Evans, Andrew; Hersey, Karen; Jewett, Michael A S; Zlotta, Alexandre R; Trachtenberg, John; Fleshner, Neil E

    2014-11-01

    Active surveillance (AS) is an expectant management strategy for prostate cancer (PCa). The impact of obesity on progression is not well characterized in this population. To determine if obesity is associated with progression in men on AS for low-risk PCa. Men undergoing AS for low-risk PCa (no Gleason pattern ≥4, three or fewer cores involved or one-third or less of the total number of cores involved, and no core with >50% cancer involvement) were identified at our institution. The outcomes were pathologic progression (defined as no longer meeting low-risk criteria on follow-up biopsy) and therapeutic progression (defined as intent to initiate active treatment). Kaplan-Meier curves and multivariable logistic regression and Cox proportional hazards models were used, with separate models for reclassification at confirmatory biopsy (first biopsy after diagnostic biopsy) and progression beyond confirmatory biopsy. In this cohort of 565 men (median follow-up: 48 mo), 124 (22%) were obese (body mass index [BMI] ≥30kg/m(2)). Pathologic and therapeutic progression occurred in 168 men (30%) and 172 men (30%), respectively. No association was noted between obesity and risk of progression at the confirmatory biopsy. However, beyond confirmatory biopsy, obesity was associated with a greater probability of pathologic progression (p=0.007) and therapeutic progression (p=0.007) in Kaplan-Meier analyses. In adjusted Cox models, each 5-unit increase in BMI was associated with an increased risk of pathologic progression (hazard ratio [HR]: 1.5; 95% confidence interval [CI], 1.1-2.1; p=0.02) and therapeutic progression (HR: 1.4; 95% CI, 1.0-1.9; p=0.05). The main limitation is the retrospective design, limiting the ability to assess BMI changes over time. Obesity was associated with a significantly increased risk of progression beyond the confirmatory biopsy. This suggests an increased risk of long-term biologic progression rather than solely misclassification. As opposed to

  13. Common genetic variants and modification of penetrance of BRCA2-associated breast cancer.

    Directory of Open Access Journals (Sweden)

    Mia M Gaudet

    2010-10-01

    Full Text Available The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (<40 years affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (λ was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values<10(-5 and 39 SNPs had p-values<10(-4. These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499 and chromosome 10 (rs16917302. The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR and 95% confidence intervals (CI for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, and for rs311499 was 0.72 (95% CI 0.61-0.85, . FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, . These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.

  14. Common genetic variants and modification of penetrance of BRCA2-associated breast cancer.

    Science.gov (United States)

    Gaudet, Mia M; Kirchhoff, Tomas; Green, Todd; Vijai, Joseph; Korn, Joshua M; Guiducci, Candace; Segrè, Ayellet V; McGee, Kate; McGuffog, Lesley; Kartsonaki, Christiana; Morrison, Jonathan; Healey, Sue; Sinilnikova, Olga M; Stoppa-Lyonnet, Dominique; Mazoyer, Sylvie; Gauthier-Villars, Marion; Sobol, Hagay; Longy, Michel; Frenay, Marc; GEMO Study Collaborators; Hogervorst, Frans B L; Rookus, Matti A; Collée, J Margriet; Hoogerbrugge, Nicoline; van Roozendaal, Kees E P; Piedmonte, Marion; Rubinstein, Wendy; Nerenstone, Stacy; Van Le, Linda; Blank, Stephanie V; Caldés, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomäki, Kristiina; Lazaro, Conxi; Blanco, Ignacio; Arason, Adalgeir; Johannsson, Oskar T; Barkardottir, Rosa B; Devilee, Peter; Olopade, Olofunmilayo I; Neuhausen, Susan L; Wang, Xianshu; Fredericksen, Zachary S; Peterlongo, Paolo; Manoukian, Siranoush; Barile, Monica; Viel, Alessandra; Radice, Paolo; Phelan, Catherine M; Narod, Steven; Rennert, Gad; Lejbkowicz, Flavio; Flugelman, Anath; Andrulis, Irene L; Glendon, Gord; Ozcelik, Hilmi; Toland, Amanda E; Montagna, Marco; D'Andrea, Emma; Friedman, Eitan; Laitman, Yael; Borg, Ake; Beattie, Mary; Ramus, Susan J; Domchek, Susan M; Nathanson, Katherine L; Rebbeck, Tim; Spurdle, Amanda B; Chen, Xiaoqing; Holland, Helene; John, Esther M; Hopper, John L; Buys, Saundra S; Daly, Mary B; Southey, Melissa C; Terry, Mary Beth; Tung, Nadine; Overeem Hansen, Thomas V; Nielsen, Finn C; Greene, Mark H; Greene, Mark I; Mai, Phuong L; Osorio, Ana; Durán, Mercedes; Andres, Raquel; Benítez, Javier; Weitzel, Jeffrey N; Garber, Judy; Hamann, Ute; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Platte, Radka; Evans, D Gareth; Lalloo, Fiona; Eeles, Ros; Izatt, Louise; Walker, Lisa; Eason, Jacqueline; Barwell, Julian; Godwin, Andrew K; Schmutzler, Rita K; Wappenschmidt, Barbara; Engert, Stefanie; Arnold, Norbert; Gadzicki, Dorothea; Dean, Michael; Gold, Bert; Klein, Robert J; Couch, Fergus J; Chenevix-Trench, Georgia; Easton, Douglas F; Daly, Mark J; Antoniou, Antonis C; Altshuler, David M; Offit, Kenneth

    2010-10-28

    The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (<40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (λ) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values<10(-5) and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, ) and for rs311499 was 0.72 (95% CI 0.61-0.85, ). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, ). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.

  15. Common genetic variants and modification of penetrance of BRCA2-associated breast cancer.

    Directory of Open Access Journals (Sweden)

    Mia M Gaudet

    2010-10-01

    Full Text Available The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (<40 years affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (λ was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values<10(-5 and 39 SNPs had p-values<10(-4. These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499 and chromosome 10 (rs16917302. The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR and 95% confidence intervals (CI for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, and for rs311499 was 0.72 (95% CI 0.61-0.85, . FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, . These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.

  16. Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer

    Science.gov (United States)

    Guiducci, Candace; Segrè, Ayellet V.; McGee, Kate; McGuffog, Lesley; Kartsonaki, Christiana; Morrison, Jonathan; Healey, Sue; Sinilnikova, Olga M.; Stoppa-Lyonnet, Dominique; Mazoyer, Sylvie; Gauthier-Villars, Marion; Sobol, Hagay; Longy, Michel; Frenay, Marc; GEMO Study Collaborators; Hogervorst, Frans B. L.; Rookus, Matti A.; Collée, J. Margriet; Hoogerbrugge, Nicoline; van Roozendaal, Kees E. P.; Piedmonte, Marion; Rubinstein, Wendy; Nerenstone, Stacy; Van Le, Linda; Blank, Stephanie V.; Caldés, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomäki, Kristiina; Lazaro, Conxi; Blanco, Ignacio; Arason, Adalgeir; Johannsson, Oskar T.; Barkardottir, Rosa B.; Devilee, Peter; Olopade, Olofunmilayo I.; Neuhausen, Susan L.; Wang, Xianshu; Fredericksen, Zachary S.; Peterlongo, Paolo; Manoukian, Siranoush; Barile, Monica; Viel, Alessandra; Radice, Paolo; Phelan, Catherine M.; Narod, Steven; Rennert, Gad; Lejbkowicz, Flavio; Flugelman, Anath; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Toland, Amanda E.; Montagna, Marco; D'Andrea, Emma; Friedman, Eitan; Laitman, Yael; Borg, Ake; Beattie, Mary; Ramus, Susan J.; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Tim; Spurdle, Amanda B.; Chen, Xiaoqing; Holland, Helene; John, Esther M.; Hopper, John L.; Buys, Saundra S.; Daly, Mary B.; Southey, Melissa C.; Terry, Mary Beth; Tung, Nadine; Overeem Hansen, Thomas V.; Nielsen, Finn C.; Greene, Mark I.; Mai, Phuong L.; Osorio, Ana; Durán, Mercedes; Andres, Raquel; Benítez, Javier; Weitzel, Jeffrey N.; Garber, Judy; Hamann, Ute; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Platte, Radka; Evans, D. Gareth; Lalloo, Fiona; Eeles, Ros; Izatt, Louise; Walker, Lisa; Eason, Jacqueline; Barwell, Julian; Godwin, Andrew K.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engert, Stefanie; Arnold, Norbert; Gadzicki, Dorothea; Dean, Michael; Gold, Bert; Klein, Robert J.; Couch, Fergus J.; Chenevix-Trench, Georgia; Easton, Douglas F.; Daly, Mark J.; Antoniou, Antonis C.; Altshuler, David M.; Offit, Kenneth

    2010-01-01

    The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (<40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (λ) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values<10−5 and 39 SNPs had p-values<10−4. These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66–0.86, ) and for rs311499 was 0.72 (95% CI 0.61–0.85, ). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18–1.39, ). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer. PMID:21060860

  17. Should Endovascular Repair Be Reimbursed for Low Risk Abdominal Aortic Aneurysm Patients? Evidence from Ontario, Canada

    Directory of Open Access Journals (Sweden)

    Jean-Eric Tarride

    2011-01-01

    Full Text Available Background. This paper presents unpublished clinical and economic data associated with open surgical repair (OSR in low risk (LR patients and how it compares with EVAR and OSR in high risk (HR patients with an AAA > 5.5 cm. Design. Data from a 1-year prospective observational study was used to compare EVAR in HR patients versus OSR in HR and LR patients. Results. Between 2003 and 2005, 140 patients were treated with EVAR and 195 with OSR (HR: 52; LR: 143. The 1-year mortality rate with EVAR was statistically lower than HR OSR patients and comparable to LR OSR patients. One-year health-related quality of life was lower in the EVAR patients compared to OSR patients. EVAR was cost-effective compared to OSR HR but not when compared to OSR LR patients. Conclusions. Despite a similar clinical effectiveness, these results suggest that, at the current price, EVAR is more expensive than open repair for low risk patients.

  18. Elective induction of labour increases caesarean section rate in low risk multiparous women.

    Science.gov (United States)

    Jacquemyn, Y; Michiels, I; Martens, G

    2012-04-01

    The aim of this study was to compare the risk of secondary caesarean section in induced versus spontaneous labour in the second delivery of low risk women who had a vaginal delivery in their first pregnancy. The data were retrospective cohort from an existing regional database, comparing term (between 37 and 42 gestational weeks) second deliveries in cephalic position in women who had previously given vaginal birth. Diabetes, hypertension and multiple pregnancy were excluded as were those with a birth weight less than 2500 g or more than 4500 g. The difference was not significant when induction was performed after 41 weeks. The results showed a total number of 29693 deliveries were included, 21243 in spontaneous labour and 8450 after induction of labour. In the spontaneous group 312 (1.5%) underwent secondary caesarean section, as compared to 237 (2.8%) in the induced group, p elective induction of labour in low risk women who have previously given vaginal birth is associated with an almost doubled rate of secondary caesarean section if performed before 41 weeks.

  19. Foot length measurements of newborns of high and low risk pregnancies

    Directory of Open Access Journals (Sweden)

    Ana Karina Marques Salge

    Full Text Available Abstract OBJECTIVE Comparing foot length measurements of newborns in high and low risk pregnancies at a public hospital in Goiânia, GO, Brazil. METHOD A cross-sectional study carried out between April, 2013 and May, 2015, with a sample consisting of 180 newborns; 106 infants of women from high-risk pregnancies and 74 of women from low-risk pregnancies. Data were descriptively analyzed. Foot length measurement was performed using a stiff transparent plastic ruler, graduated in millimeters. The length of both feet was measured from the tip of the hallux (big toe to the end of the heel. RESULTS A statistically significant relationship was found between the foot length and newborn’s weight, between the cephalic and thoracic perimeters in the high-risk group and between the cephalic perimeter in the control group. CONCLUSION There is a need for creating cut-off points to identify newborns with intrauterine growth disorders using foot length.

  20. Patient selection for TAVI 2015 - TAVI in low-risk patients: fact or fiction?

    Science.gov (United States)

    Haussig, Stephan; Linke, Axel

    2015-09-01

    For decades, surgical aortic valve replacement (SAVR) has been the standard treatment for severe aortic stenosis (AS). With the clinical introduction of the concept of transcatheter aortic valve implantation (TAVI), a rapid development took place and, based on the results of landmark randomised controlled trials, within a few years TAVI became first-line therapy for inoperable patients with severe AS and an alternative to SAVR in operable high-risk patients. Indeed, data from a recent randomised controlled trial suggest that TAVI is superior to SAVR in higher-risk patients with AS. New TAVI devices have been developed to address current limitations, to optimise results further and to minimise complications. First results using these second-generation valves are promising. However, no data from randomised controlled trials assessing TAVI in younger, low-risk patients are yet available. While we await the results of trials addressing these issues (e.g., SURTAVI [NCT01586910] and PARTNER II [NCT01314313]), recent data from TAVI registries suggest that treatment of low-risk patients is already fact and no longer fiction.

  1. TLMA Expression in Condyloma Acuminata from Patients with High and Low Risk HPV

    Institute of Scientific and Technical Information of China (English)

    涂亚庭; 陈善娟; 范超; 林能兴; 刘厚君; 刘志香

    2002-01-01

    Objective: To detect the activated expression oftelomerase in condyloma acuminata lesions in low-risk (6/11)and high-risk (16/18) human papilloma virus (HPV)infection and examine the role played by telomerase in theoccurrence, development and carcinomatous change ofcondyloma acuminata. Methods: Assaying the expression of telomerase and thetype of HPV in damaged skin of 42 CA patients and normalskin of 30 healthy control individuals through telomeraserepeat amplification protocol (TRAP) and polymerase chainreaction (PCR). Results: In all the normal skin controls, PCR for HPV wasnegative and only 16.7% of samples were positive for TLMAexpression; in CA lesions, HPV testing was positive in all (32cases were low-risk, 3 were high-risk, and 7 were of mixedtype) and all were positive for TLMA expression. Conclusion: TLMA may be activated by HPV infection,and in turn cause the hyperplasia of epidermal cells. It wasalso indicated that HPV, especially high risk types, canactivate TLMA. The activation of TLMA may play animportant role in abnormal hyperplasia and carcinomatouschanges in CA lesions.

  2. Fetal Hemodynamic Parameters in Low Risk Pregnancies: Doppler Velocimetry of Uterine, Umbilical, and Middle Cerebral Artery

    Directory of Open Access Journals (Sweden)

    C. O. Figueira

    2016-01-01

    Full Text Available Objective. To elaborate curves of longitudinal reference intervals of pulsatility index (PI and systolic velocity (SV for uterine (UtA, umbilical (UA, and middle cerebral arteries (MCA, in low risk pregnancies. Methods. Doppler velocimetric measurements of PI and SV from 63 low risk pregnant women between 16 and 41 weeks of gestational age. Means (±SD for intervals of gestational age and percentiles 5, 50, and 95 were calculated for each parameter. The Intraclass Correlation Coefficients (ICC were also estimated for assessing intra- and intervariability of measurements. Results. Mean PI of UtA showed decreasing values during pregnancy, but no regular pattern was identified for mean SV. For UA, PI decreased and SV increased along gestation. MCA presented PI increasing values until 32–35 weeks. SV showed higher levels with increasing gestation. High ICC values indicated good reproducibility. Conclusions. Reference intervals for the assessment of SV and PI of UtA, UA, and MCA were established. These reference intervals showed how a normal pregnancy is expected to progress regarding these Doppler velocimetric parameters and are useful to follow high risk pregnancies. The comparison between results using different curves may provide insights about the best patterns to be used.

  3. Ureteral diameter in low-risk vesicoureteral reflux in infancy and childhood

    Energy Technology Data Exchange (ETDEWEB)

    Hellstroem, M.; Hjaelmaas, K.; Jacobsson, B.; Jodal, U.

    In order to improve the accuracy of the grading of vesicoureteral reflux (VUR), reference values for ureteral diameter at micturition cystourethrography (MCUG) were established in infants and children with low-risk VUR. Low-risk VUR was defined as VUR not associated with infection, obstruction, calculi, duplication, malformations (except for hypospadia) or neurogenic bladder disturbances. Forty-six children (age 1 day - 14 years) were selected by examining the records of 12000 MCUG:s performed 1960-1983. Ureteral diameter was measured at the widest point of the ureter on the films from MCUG:s and urographies. Ureteral diameter was slightly larger at MCUG than at urography in the same individuals but the difference was not significant. The ureteral diameter at MCUG also correlated closely to normal values at urography in a previous study. It is proposed that the reference values obtained at MCUG in the present investigation can be used for the differentiation between dilatation and no dilatation in the grading of VUR.

  4. Stereotactic body radiotherapy for low-risk prostate cancer: five-year outcomes

    Directory of Open Access Journals (Sweden)

    King Christopher R

    2011-01-01

    Full Text Available Abstract Purpose Hypofractionated, stereotactic body radiotherapy (SBRT is an emerging treatment approach for prostate cancer. We present the outcomes for low-risk prostate cancer patients with a median follow-up of 5 years after SBRT. Method and Materials Between Dec. 2003 and Dec. 2005, a pooled cohort of 41 consecutive patients from Stanford, CA and Naples, FL received SBRT with CyberKnife for clinically localized, low-risk prostate cancer. Prescribed dose was 35-36.25 Gy in five fractions. No patient received hormone therapy. Kaplan-Meier biochemical progression-free survival (defined using the Phoenix method and RTOG toxicity outcomes were assessed. Results At a median follow-up of 5 years, the biochemical progression-free survival was 93% (95% CI = 84.7% to 100%. Acute side effects resolved within 1-3 months of treatment completion. There were no grade 4 toxicities. No late grade 3 rectal toxicity occurred, and only one late grade 3 genitourinary toxicity occurred following repeated urologic instrumentation. Conclusion Five-year results of SBRT for localized prostate cancer demonstrate the efficacy and safety of shorter courses of high dose per fraction radiation delivered with SBRT technique. Ongoing clinical trials are underway to further explore this treatment approach.

  5. Desmoplastic variant of ameloblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Jeong Ick; Kim, Dong Youn; Choi, Karp Shik [Dept. of Dental Radiology, College of Dentistry, Kyungpook National University, Daegu (Korea, Republic of)

    1995-02-15

    Desmoplastic variant of ameloblastoma is new and unusual variant of ameloblastoma with extensive stromal desmoplastic proliferation. The authors experienced a case of desmoplastic variant of amleloblastoma with moderate-defined radiolucency on the right maxillary anterior area in 62-year-old female. As a result of careful analysis of clinical, radiological examinations, we diagnosed it as desmoplastic variant of ameloblastoma. The following results were obtained; 1. Main clinical symptoms were nontender bony swelling with normal intact overlying mucosa on the right maxillary anterior area. 2. Radiographically, moderate-defined, multilocular radioluceney on the right maxillary anterior area were shown, and severe cortical bony thinning and expansion to labial and palatal sides were also observed. And this lesion was shown to be extended to the right nasal cavity. 3. Histopathologically, follicle-like epithelial islands with densely abundant collagenous stroma were morphologically compressed.

  6. High-Risk and Low-Risk Human Papillomavirus and the Absolute Risk of Cervical Intraepithelial Neoplasia or Cancer

    DEFF Research Database (Denmark)

    Thomsen, Louise T; Frederiksen, Kirsten; Munk, Christian

    2014-01-01

    OBJECTIVE: To determine the absolute risk of cervical intraepithelial neoplasia (CIN) grade 3 or cervical cancer (CIN 3 or worse) after detection of low-risk human papillomavirus (HPV) and after a negative high-risk HPV test. METHODS: In this prospective cohort study, consecutive liquid......-based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark, during 2002-2005. Samples were tested with a clinical test for 13 high-risk and five low-risk HPV types. The cohort (N=35,539; aged 14-90 years) was monitored in a nationwide pathology register for up...... cytology. Detection of low-risk HPV does not predict CIN 3 or worse. Cervical cancer screening should not include testing for low-risk HPV types. LEVEL OF EVIDENCE: II....

  7. Trichomonas vaginalis infection in a low-risk women attended in Obstetrics and Gynaecology Clinic, Universiti Kebangsaan Malaysia Medical Centre

    Directory of Open Access Journals (Sweden)

    Norhayati Moktar

    2016-08-01

    Conclusions: The present study reported zero incidence rate of trichomoniasis. The low incidence rate was postulated due to all women who participated in this study were categorized into a low-risk group.

  8. A comparison of genetic variants between proficient low- and high-risk sport participants.

    Science.gov (United States)

    Thomson, Cynthia J; Power, Rebecca J; Carlson, Scott R; Rupert, Jim L; Michel, Grégory

    2015-01-01

    Athletes participating in high-risk sports consistently report higher scores on sensation-seeking measures than do low-risk athletes or non-athletic controls. To determine whether genetic variants commonly associated with sensation seeking were over-represented in such athletes, proficient practitioners of high-risk (n = 141) and low-risk sports (n = 132) were compared for scores on sensation seeking and then genotyped at 33 polymorphic loci in 14 candidate genes. As expected, athletes participating in high-risk sports score higher on sensation seeking than did low-risk sport athletes (P sport participation for two genes (stathmin, (P = .004) and brain-derived neurotrophic factor (P = .03)) as well as when demographically matched subsets of the sport cohorts were compared (P < .05); however, in all cases, associations did not survive correction for multiple testing.

  9. Fear of childbirth and emergency caesarean section in low-risk nulliparous women

    DEFF Research Database (Denmark)

    Jespersen, Cecilie; Hegaard, Hanne Kristine; Schroll, Anne-Mette

    2014-01-01

    OBJECTIVE: To assess the association between fear of childbirth (FOC) and emergency caesarean section. DESIGN: A prospective cohort study of low-risk nulliparous women at term. SETTING: Nine obstetric departments in Denmark, May 2004-July 2005. POPULATION: A total of 2598 nulliparous women...... in spontaneous labor with a single fetus in cephalic presentation at term. METHODS: Self-reported FOC was assessed at 37 weeks of gestation by the Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ) version A and at admission to the labor ward by the Delivery Fear Scale (DFS). Mode of delivery...... was recorded by the attending staff. Logistic regression analyses were used to estimate unadjusted and adjusted odds ratios (OR). MAIN OUTCOME MEASURES: Risk of emergency caesarean section in women who feared childbirth. RESULTS: FOC (W-DEQ sum score ≥ 85 and DFS sum score ≥ 70) was not associated...

  10. Cellular transformation by human papillomaviruses: Lessons learned by comparing high- and low-risk viruses

    Science.gov (United States)

    Klingelhutz, Aloysius J.; Roman, Ann

    2013-01-01

    The oncogenic potential of papillomaviruses (PVs) has been appreciated since the 1930s yet the mechanisms of virally-mediated cellular transformation are still being revealed. Reasons for this include: a) the oncoproteins are multifunctional, b) there is an ever-growing list of cellular interacting proteins, c) more than one cellular protein may bind to a given region of the oncoprotein, and d) there is only limited information on the proteins encoded by the corresponding non-oncogenic PVs. The perspective of this review will be to contrast the activities of the viral E6 and E7 proteins encoded by the oncogenic human PVs (termed high-risk HPVs) to those encoded by their non-oncogenic counterparts (termed low-risk HPVs) in an attempt to sort out viral life cycle-related functions from oncogenic functions. The review will emphasize lessons learned from the cell culture studies of the HPVs causing mucosal/genital tract cancers. PMID:22284986

  11. Radioiodine remnant ablation in low-risk differentiated thyroid cancer: the "con" point of view.

    Science.gov (United States)

    Lamartina, Livia; Cooper, David S

    2015-09-01

    A growing body of evidence is challenging the indiscriminate use of postoperative radioiodine for remnant ablation (RRA) in low-risk (LR) differentiated thyroid cancer patients. We critically reviewed the current evidence on which the rationale for RRA is based for LR patients and analyzed the new evidence-based recommendations for LR patients from the draft of the 2015 American Thyroid Association (ATA) guidelines. Cost-effective tools for staging and follow-up, such as neck ultrasonography and serial thyroglobulin testing, are useful for monitoring non-RRA-treated patients. Recurrence rates are very low in non-RRA-treated LR patient cohorts. Most RRA side effects are mild and transient, but can impair a patient's quality of life. RRA is appropriately not routinely recommended in LR patients according to the draft 2015 ATA guidelines and should be reserved for higher-risk patients.

  12. Comparison of three prenatal risk scores in a series of low-risk pregnancies.

    Science.gov (United States)

    Kelly, R B; Acheson, L S; Zyzanski, S J

    1988-01-01

    Three prepartum obstetrical risk-scoring methods (Goodwin, Halliday, Hobel) were retrospectively applied to a consecutive series of 795 singleton pregnancies. The study population was low risk overall, with a perinatal mortality rate of 11 per 1000 and a primary cesarean section rate of 9.7%. The predictive ability of the scores was tested for individual outcomes as well as for a "combined measure" designed to group outcomes of clinical interest. Outcome variables examined included labor arrests, need for augmentation of labor, fetal heartrate abnormalities during labor, selection of or transfer to a more intensive level of care, indicated forceps delivery, cesarean section, resuscitation, Apgar scores, permanent injury, and perinatal deaths. Along with expected differences in sensitivity and specificity, there were differences among the three scores in performance as measured by positive and negative predictive value. Goodwin's system performed somewhat better overall. All three systems performed better in multiparous than in primiparous patients, but primiparas experienced more adverse outcomes.

  13. Factors predicting long-term survival in low-risk diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Møller, Michael B; Pedersen, Niels T; Christensen, Bjarne E

    2003-01-01

    population-based data from the Danish Lymphoma Group, we analyzed if prognostic clinical pretreatment factors could be identified in patients with low-risk DLBCL. One hundred seventy-seven patients, all with a prognostic profile as favorable as possible according to the IPI and treated with anthracycline-based...... combination chemotherapy (92%) or loco-regional radiotherapy/surgery (8%) with curative intent were included. The median age was 50 years and 170 achieved complete remission. The median follow-up time was 11 years. Twenty-six patients relapsed, with a median time to relapse of 12.1 months. Overall survival...... at 5 years and 10 years was 85% and 75%, respectively. Stage II was associated with poor response to treatment (P=0.044). In a multivariate analysis, Stage II (P=0.001) and age >50 years (P=0.043) were independently associated with poor outcome. Patients without these adverse factors had an excellent...

  14. Elective amniocentesis in low-risk pregnancies: decision making in the era of information and uncertainty.

    Science.gov (United States)

    Lesser, Y; Rabinowitz, J

    2001-04-01

    Rational choice theory was applied to explain women's use of amniocentesis. Variables included knowledge about prenatal diagnostics, attitudes, and emotional preferences. Using structured instruments at 9 to 14 and at 29 to 34 weeks' gestation, we interviewed 232 Israeli women who had low-risk pregnancies. Women who had elective amniocentesis (n = 39) were more knowledgeable about prenatal diagnostics, risks of invasive procedures, and probability of fetal abnormality in high maternal age; had fewer children; and had less favorable attitudes toward parenthood than those who had medically indicated amniocentesis (n = 57) and those who did not have amniocentesis (n = 136). The use and possible overuse of amniocentesis were associated with having more information about prenatal diagnostics and definite emotional preferences.

  15. Prospective Validation of Modified NEXUS Cervical Spine Injury Criteria in Low-risk Elderly Fall Patients

    Directory of Open Access Journals (Sweden)

    John Tran

    2016-05-01

    Full Text Available Introduction: The National Emergency X-radiography Utilization Study (NEXUS criteria are used extensively in emergency departments to rule out C-spine injuries (CSI in the general population. Although the NEXUS validation set included 2,943 elderly patients, multiple case reports and the Canadian C-Spine Rules question the validity of applying NEXUS to geriatric populations. The objective of this study was to validate a modified NEXUS criteria in a low-risk elderly fall population with two changes: a modified definition for distracting injury and the definition of normal mentation. Methods: This is a prospective, observational cohort study of geriatric fall patients who presented to a Level I trauma center and were not triaged to the trauma bay. Providers enrolled non-intoxicated patients at baseline mental status with no lateralizing neurologic deficits. They recorded midline neck tenderness, signs of trauma, and presence of other distracting injury. Results: We enrolled 800 patients. One patient fall event was excluded due to duplicate enrollment, and four were lost to follow up, leaving 795 for analysis. Average age was 83.6 (range 65-101. The numbers in parenthesis after the negative predictive value represent confidence interval. There were 11 (1.4% cervical spine injuries. One hundred seventeen patients had midline tenderness and seven of these had CSI; 366 patients had signs of trauma to the face/neck, and 10 of these patients had CSI. Using signs of trauma to the head/neck as the only distracting injury and baseline mental status as normal alertness, the modified NEXUS criteria was 100% sensitive (CI [67.9-100] with a negative predictive value of 100 (98.7-100. Conclusion: Our study suggests that a modified NEXUS criteria can be safely applied to low-risk elderly falls.

  16. Determinants of prenatal health care utilisation by low-risk women: a prospective cohort study.

    Science.gov (United States)

    Feijen-de Jong, Esther I; Jansen, Danielle E M C; Baarveld, Frank; Boerleider, Agatha W; Spelten, Evelien; Schellevis, François; Reijneveld, Sijmen A

    2015-06-01

    Prenatal health care is pivotal in providing adequate prevention and care to pregnant women. We examined the determinants of inadequate prenatal health care utilisation by low-risk women in primary midwifery-led care in the Netherlands. We used longitudinal data from the population-based DELIVER study with 20 midwifery practices across the Netherlands in 2009 and 2010 as the experimental setting. The participants were 3070 pregnant women starting pregnancy care in primary midwifery care. We collected patient-reported data on potential determinants of prenatal care utilisation derived from the Andersen model. Prenatal health care utilisation was measured by a revised version of the Kotelchuck Index, which measures a combination of care entry and number of visits. Low-risk pregnant women (not referred during pregnancy) were more likely to use prenatal care inadequately if they intended to deliver at a hospital, if they did not use folic acid adequately periconceptionally, or if they were exposed to cigarette smoke during pregnancy. Among those who were referred to secondary care, women reporting a chronic illnesses or disabilities, and women who did not use folic acid periconceptionally were more likely to make inadequate use of prenatal care. Inadequate prenatal health care use in primary midwifery care is more likely in specific groups, and the risk groups differ when women are referred to secondary care. The findings suggest routes that can target interventions to women who are at risk of not adequately using prenatal prevention and care services. Copyright © 2015 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  17. Unwarranted Variation in Utilization of Cesarean Birth Among Low-Risk Childbearing Women.

    Science.gov (United States)

    Jolles, Diana R

    2017-01-01

    Unwarranted variations in care are defined as differences in utilization of health care resources that cannot be explained by patient risk factors, standards of evidence-based medicine, or patient preferences. Also known as nonmedical determinants of variation, differences in health care utilization across the United States have been well documented in the literature during the past 40 years. The purpose of the literature review is to summarize the state of the science related to the nonmedical determinants of variation in cesarean birth among low-risk childbearing women, defined within national quality standards as nulliparous women with term, singleton pregnancies in the vertex presentation. A literature search was performed using the electronic databases PubMed, CINAHL, Ovid MEDLINE, Google Scholar, Cochrane Database of Systematic Reviews, and ProQuest Dissertation Database. Articles published in English, with full text available, including birth in the United States after 1995, are included in the analysis. Nine studies met criteria for inclusion. Forty-four states are represented within the data, with Arizona, California, Massachusetts, New Jersey, and New York being the subject of more than one of the publications analyzed. This literature review includes more than one million births, in at least 44 states between 1996 through 2009, revealing significant unwarranted variation in cesarean birth. Nonmedical determinants of variation, such as access to resources, hospital characteristics, payer source, and provider practice styles, are identified as independent predictors of increased cesarean utilization in more than half of the studies reviewed. In all studies reviewed, women of low medical risk demonstrate susceptibility to unwarranted variation in the use of cesarean birth. Continued emphasis on the specific needs of low-risk childbearing women is necessary to decrease unwarranted variation in the use of cesarean birth in the United States. Specific

  18. Addition of a biomarker panel to a clinical score to identify patients at low risk for appendicitis.

    Science.gov (United States)

    Depinet, Holly; Copeland, Karen; Gogain, Joseph; Hennes, Halim; Paradis, Norman A; Andrews-Dickert, Rebecca; Vance, Cheryl W; Huckins, David S

    2016-12-01

    The diagnosis of pediatric acute appendicitis can be difficult. Although scoring systems such as the Pediatric Appendicitis Score (PAS) are helpful, they lack adequate sensitivity and specificity as standalone diagnostics. When used for risk stratification, they often result in large percentages of moderate-risk patients requiring further diagnostic evaluation. We applied a biomarker panel (the APPY1 Test) that has high sensitivity and negative predictive value (NPV) to patients with PAS in the moderate-risk range (3-7) and reclassified those patients with a negative result to the low-risk group. We compared the specificity, sensitivity, and NPV of the original and reclassified low-risk groups at several different PAS low-risk cutoffs. The application of a negative biomarker panel to a group of patients with a moderate risk for appendicitis (PAS, 3-7) resulted in 4 times more patients (586 vs 145) being safely classified as low risk. Reclassification increased the overall specificity or the proportion of patients without appendicitis who were correctly identified as low risk, from 10.3% to 42.0%. The high NPV (97.2%) in the original group was preserved (97.6%) in the reclassified low-risk group, as was the sensitivity (original 99.1% vs reclassified 96.9%). The addition of negative biomarker test results to patients with a moderate risk of appendicitis based on the PAS can safely reclassify many to a low-risk group. This may allow clinicians to provide more conservative management in children with suspected appendicitis and decrease unnecessary resource utilization. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Hemoglobin Variants in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Popp, Raymond A.

    1965-04-22

    Variability among mammalian hemoglobins was observed many years ago (35). The chemical basis for differences among hemoglobins from different species of mammals has been studied by several investigators (5, 11, 18, 48). As well as interspecies differences, hemoglobin variants are frequently found within a species of mammals (2, 3, 7, 16) The inheritance of these intraspecies variants can be studied, and pedigrees indicate that the type of hemoglobin synthesized in an individual is genetically controlled (20). Several of the variant human hemoglobins are f'unctionally deficient (7, 16). Such hemoglobin anomalies are of basic interest to man because of the vital role of hemoglobin for transporting oxygen to all tissues of the body.

  20. Absence of survival benefit of radioactive iodine (RAI) after thyroidectomy in low risk differentiated thyroid cancer (DTC) patients

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, C.; Fieffe, S.; Pochart, J.M. [Endocrinology Nuclear Medicine, Institut Jean Godinot, Reims (France); Bonnetain, F.; Gauthier, M.; Cueff, A. [Statistics and Epidemiology, Centre Georges Francois Leclerc, Dijon (France); Crevisy, E.; Dygai-Cochet, I.; Toubeau, M. [Nuclear Medicine, Centre Georges Francois Leclerc, Dijon (France)

    2012-07-01

    After thyroidectomy, the goal of the first dose of radioactive iodine (RAI) is remnant ablation to facilitate the initial staging with the post-therapy scan and to facilitate the early detection of recurrences. The purpose of this study is to the survival benefit of RAI in low-risk thyroid cancer patients. Using Cancer thyroid registry of Marne Ardennes (1041 patients) and hospital data base of centre Leclerc (257 patients), we included all differentiated thyroid cancer (DTC) patients at low risk from 1975 to 2005. Median follow-up was 10.3 years, during which 19 recurrences, 61 other malignant diseases and 105 deaths were registered. 387 patients (30%) received no RAI and 911 had RAI (70%). If we confirmed that some clinical characteristics were associated with RAI intake, the study failed to demonstrate any survival benefit of RAI in low risk DTC patients

  1. Impact of educational strategies in low-risk prenatal care: systematic review of randomized clinical trials.

    Science.gov (United States)

    Silva, Esther Pereira da; Lima, Roberto Teixeira de; Osório, Mônica Maria

    2016-09-01

    This study aimed to analyze the impact of educational strategies developed in low-risk prenatal care on obstetric outcomes from a systematic literature review. This review consulted databases PubMed, Medline, SciELO and Lilacs, analyzing randomized clinical trials with the following birth outcomes: birth weight, prematurity and breastfeeding, using the following combination of keywords: pre-natal, antenatal visits, education, health education, pregnancy outcomes, birth weight, prematurity, breastfeeding and randomized clinical trial. Nine studies were included following quality evaluation. Actions prove to be more effective when extended to the postpartum period. Most of them occurred during home visits and had a positive impact on breastfeeding and birth weight. The establishment of groups of pregnant women contributed to lower prevalence of prematurity. Breastfeeding was found to be the outcome most sensitive to educational strategies. Educational practices during the prenatal period contributed to favorable obstetric outcomes as they minimized pregnant women concerns and anxiety during the pregnancy process, preparing them for childbirth and postpartum, and should be incorporated into health services' work process.

  2. Malaria morbidity and temperature variation in a low risk Kenyan district: a case of overdiagnosis?

    Science.gov (United States)

    Njuguna, John; Muita, James; Mundia, George

    2009-05-01

    Diagnosis of malaria using only clinical means leads to overdiagnosis. This has implications due to safety concerns and the recent introduction of more expensive drugs. Temperature is a major climatic factor influencing the transmission dynamics of malaria. This study looked at trends in malaria morbidity in the low risk Kenyan district of Nyandarua, coupled with data on temperature and precipitation for the years 2003-2006. July had the highest number of cases (12.2% of all cases) followed by August (10.2% of all cases). July and August also had the lowest mean maximum temperatures, 20.1 and 20.2 °C respectively. April, July and August had the highest rainfall, with daily means of 4.0, 4.3 and 4.9 mm, respectively. Observation showed that the coldest months experienced the highest number of cases of malaria. Despite the high rainfall, transmission of malaria tends to be limited by low temperatures due to the long duration required for sporogony, with fewer vectors surviving. These cold months also tend to have the highest number of cases of respiratory infections. There is a possibility that some of these were misdiagnosed as malaria based on the fact that only a small proportion of malaria cases were diagnosed using microscopy or rapid diagnostic tests. We conclude that overdiagnosis may be prevalent in this district and there may be a need to design an intervention to minimise it.

  3. Long-term oral sensitivity and feeding skills of low-risk pre-term infants.

    Science.gov (United States)

    Dodrill, Pamela; McMahon, Sandra; Ward, Elizabeth; Weir, Kelly; Donovan, Tim; Riddle, Bena

    2004-01-01

    This study examined the oral sensitivity and feeding skills of low-risk pre-term infants at 11-17 months corrected age. Twenty pre-term infants (PT) born between 32 and 37 weeks at birth without any medical comorbidities were assessed. All of this PT group received supplemental nasogastric (NG) tube feeds during their birth-stay in hospital. A matched control group of 10 healthy full-term infants (FT) was also assessed. Oral sensitivity and feeding skills were assessed during a typical mealtime using the Royal Children's Hospital Oral Sensitivity Checklist (OSC) and the Pre-Speech Assessment Scale (PSAS). Results demonstrated that, at 11-17 months corrected age, the PT group displayed significantly more behaviours suggestive of altered oral sensitivity and facial defensiveness, and a trend of more delayed feeding development than the FT group. Further, results demonstrated that, relative to the FT group, pre-term infants who received greater than 3 weeks of NG feeding (PT>3NG) displayed significantly more facial defensive behaviour, and displayed significant delays across more aspects of their feeding development than pre-term infants who received less than 2 weeks of NG feeding (PToral sensitivity and facial defensiveness, as well as feeding delays. These observations warrant further investigation on this topic.

  4. Families at high and low risk for depression: a three-generation startle study.

    Science.gov (United States)

    Grillon, Christian; Warner, Virginia; Hille, Jeffrey; Merikangas, Kathleen R; Bruder, Gerard E; Tenke, Craig E; Nomura, Yoko; Leite, Paul; Weissman, Myrna M

    2005-05-01

    Anxiety symptoms might be a vulnerability factor for the development of major depressive disorder (MDD). Because elevated startle magnitude in threatening contexts is a marker for anxiety disorder, the present study investigated the hypothesis that enhanced startle reactivity would also be found in children and grandchildren of individuals with MDD. The magnitude of startle was investigated in two tests (anticipation of an unpleasant blast of air and during darkness) in children (second generation) and grandchildren (third generation) of probands with (high risk) or without (low risk) MDD (first generation). Startle discriminated between the low- and high-risk groups. In the probands' children, the high-risk group showed increased startle magnitude throughout the fear-potentiated startle test. In the probands' grandchildren, a gender-specific abnormality was found in the high-risk group with high-risk girls, but not boys, exhibiting elevated startle magnitude throughout the procedure. Increased startle reactivity in threatening contexts, previously found in patients with anxiety disorder and in children of parents with an anxiety disorder, might also constitute a vulnerability marker for MDD. These findings suggest that there might be common biologic diatheses underlying depression and anxiety.

  5. HTLV-I/II and blood donors: determinants associated with seropositivity in a low risk population

    Directory of Open Access Journals (Sweden)

    Bernadette Catalan Soares

    2003-08-01

    Full Text Available OBJECTIVE: Blood donors in Brazil have been routinely screened for HTLV-I/II since 1993. A study was performed to estimate the prevalence of HTLV-I/II infection in a low risk population and to better understand determinants associated with seropositivity. METHODS: HTLV-I/II seropositive (n=135, indeterminate (n=167 and seronegative blood donors (n=116 were enrolled in an open prevalence prospective cohort study. A cross-sectional epidemiological study of positive, indeterminate and seronegative HTLV-I/II subjects was conducted to assess behavioral and environmental risk factors for seropositivity. HTLV-I/II serological status was confirmed using enzyme-linked immunosorbent assay (EIA and Western blot (WB. RESULTS: The three groups were not homogeneous. HTLV-I/II seropositivity was associated to past blood transfusion and years of schooling, a marker of socioeconomic status, and use of non-intravenous illegal drugs. CONCLUSIONS: The study results reinforce the importance of continuous monitoring and improvement of blood donor selection process.

  6. A comparison of labor outcome with oxytocin and spontaneous delivery in low risk pregnant women

    Directory of Open Access Journals (Sweden)

    parvin Asti

    2015-02-01

    Full Text Available Background: Medical interventions in labor have been common in recent years. Oxytocin is amongst them which is used to speed delivery. Unfortunately the indiscriminate administration of it could lead to maternal and infant complications. The aim of this study was to compare labor outcome with oxytocin and spontaneous delivery in low risk pregnant women. Materials and Methods: In this descriptive – comparative study, 395 women with single fetus, cephalic presentation, normal delivery, in the active phase of labor were selected. 197 of the cases, as Oxytocin group, received oxytocin by physician,s order during their labor and 198 of the samples, as the second group, had spontaneous vaginal delivery. In both groups, some of the maternal and neonatal outcomes including: maternal morbidity , Apgar score at minutes one and five, admitted in neonatal intensive care unit and were studied.Data were analyzed using SPSS 16, t-test, Chi-square and Mann Whitney tests. Results: The findings showed that oxytocin significantly increased rates of episiotomy, laceration, post partum hemorrhage, hospitalization of neonate in intensive care unit and reduction of Apgar score at minutes one and five that were statistically significant (p <0.05. Conclusion: The results showed that the acceleration of delivery is not a safe method and increases the rate of maternal and infant complications. Therefore, it should be used in the case of medical necessities.

  7. Obstetric interventions during labor and childbirth in Brazilian low-risk women.

    Science.gov (United States)

    Carmo Leal, Maria do; Pereira, Ana Paula Esteves; Domingues, Rosa Maria Soares Madeira; Theme Filha, Mariza Miranda; Dias, Marcos Augusto Bastos; Nakamura-Pereira, Marcos; Bastos, Maria Helena; Gama, Silvana Granado Nogueira da

    2014-08-01

    This study evaluated the use of best practices (eating, movement, use of nonpharmacological methods for pain relief and partograph) and obstetric interventions in labor and delivery among low-risk women. Data from the hospital-based survey Birth in Brazil conducted between 2011 and 2012 was used. Best practices during labor occurred in less than 50% of women and prevalence of the use of these practices was lower in the North, Northeast and Central West Regions. The rate of use of oxytocin drips and amniotomy was 40%, and was higher among women admitted to public hospitals and in women with a low level of education. The uterine fundal pressure, episiotomy and lithotomy were used in 37%, 56% and 92% of women, respectively. Caesarean section rates were lower in women using the public health system, nonwhites, women with a low level of education and multiparous women. To improve the health of mothers and newborns and promote quality of life, a change of approach to labor and childbirth that focuses on evidence-based care is required in both the public and private health sectors.

  8. Posture Development in Infants at Heightened vs. Low Risk for Autism Spectrum Disorders.

    Science.gov (United States)

    Nickel, Lindsay R; Thatcher, Alyssa R; Keller, Flavio; Wozniak, Robert H; Iverson, Jana M

    2013-09-01

    Evidence suggests that children and adults diagnosed with autism spectrum disorders (ASD) exhibit difficulties with postural control. Retrospective video studies of infants later diagnosed with ASD indicate that infants who eventually receive an ASD diagnosis exhibit delays in postural development. This study investigates early posture development prospectively and longitudinally in 22 infants at heightened biological risk for ASD (HR) and 18 infants with no such risk (Low Risk; LR). Four HR infants received an autism diagnosis (AD infants) at 36 months. Infants were videotaped at home at 6, 9, 12, and 14 months during everyday activities and play. All infant postures were coded and classified as to whether or not they were infant-initiated. Relative to LR infants, HR infants were slower to develop skill in sitting and standing postures. AD infants exhibited substantial delays in the emergence of more advanced postures and initiated fewer posture changes. Because posture advances create opportunities for infants to interact with objects and people in new and progressively more sophisticated ways, postural delays may have cascading effects on opportunities for infant exploration and learning. These effects may be greater for infants with ASD, for whom posture delays are more significant.

  9. Neonatal hearing screening in a low-risk maternity hospital in São Paulo state

    Directory of Open Access Journals (Sweden)

    Adriana Aparecida Tahara Kemp

    2015-10-01

    Full Text Available ABSTRACT INTRODUCTION: The literature indicates that neonatal hearing screening should be universal, so a description of programs that adopt this recommendation is relevant. OBJECTIVE: To describe the results of newborn hearing screening and the profile of mothers and newborns attended to in a low-risk maternity setting, and to correlate the characteristics of this population with the results of transient evoked otoacoustic emissions. METHODS: A contemporary cross-sectional cohort study. The sample consisted of 670 infants and the procedures performed were audiological history, transient-evoked otoacoustic emissions (TEOAE, distortion product-evoked otoacoustic emissions (DPEOAE, and automated-brainstem auditory evoked potential (ABSAEP. RESULTS: The rate of success in this program was 98.5%, the failure rate was 0.62%, and that of non-attendance to finalize the diagnostic process, 0.93%. When correlating the variables studied with the results of transient evoked otoacoustic emissions, there was a significant negative correlation only for age of infant. CONCLUSION: The program of this maternity hospital was effective and complies with national and international recommendations. The population consisted of young mothers with few pregnancy complications and healthy infants. The only variable that influenced transient evoked otoacoustic emission results, after hospital discharge, was the age at which infants were evaluated.

  10. Strategies for obstacle crossing in older adults with high and low risk of falling

    Science.gov (United States)

    Pan, Hui-Fen; Hsu, Horng-Chaung; Chang, Wei-Ning; Renn, Jenn-Huei; Wu, Hong-Wen

    2016-01-01

    [Purpose] Tripping is a frequent cause of falls among aging adults. Appropriate limb movements while negotiating obstacles are critical to trip avoidance. The aim of our study was to investigate the mechanics of obstacle crossing in older adults at low or high risk of falling. [Subjects and Methods] Twenty community-dwelling adults aged ≥55 years, were evaluated with the Tinetti Balance and Gait scale and classified as being at high or low risk of falling. Between-group comparisons of kinematics were evaluated for obstacle heights of 10%, 20%, and 30% of leg length. [Results] The high-risk group demonstrated greater toe-obstacle clearance of the leading leg. Increasing obstacle height led to increased maximal toe-obstacle clearance, toe-obstacle distance, and shortened swing phase of the leading limb. Adaptation of clearance height was greater for the trailing leg. Individuals at high risk of falling demonstrated less symmetry between the leading and trailing legs and a narrower step width, features that increase the likelihood of tripping. [Conclusion] Kinematic parameters of obstacle clearance, including the symmetry index described in our study, could provide clinicians with a quick screening tool to identify patients at risk of falling and to evaluate outcomes of training programs. PMID:27313384

  11. Intermittent hypoxia: a low-risk research tool with therapeutic value in humans.

    Science.gov (United States)

    Mateika, Jason H; El-Chami, Mohamad; Shaheen, David; Ivers, Blake

    2015-03-01

    Intermittent hypoxia has generally been perceived as a high-risk stimulus, particularly in the field of sleep medicine, because it is thought to initiate detrimental cardiovascular, respiratory, cognitive, and metabolic outcomes. In contrast, the link between intermittent hypoxia and beneficial outcomes has received less attention, perhaps because it is not universally understood that outcome measures following exposure to intermittent hypoxia may be linked to the administered dose. The present review is designed to emphasize the less recognized beneficial outcomes associated with intermittent hypoxia. The review will consider the role intermittent hypoxia has in cardiovascular and autonomic adaptations, respiratory motor plasticity, and cognitive function. Each section will highlight the literature that contributed to the belief that intermittent hypoxia leads primarily to detrimental outcomes. The second segment of each section will consider the possible risks associated with experimentally rather than naturally induced intermittent hypoxia. Finally, the body of literature indicating that intermittent hypoxia initiates primarily beneficial outcomes will be considered. The overarching theme of the review is that the use of intermittent hypoxia in research investigations, coupled with reasonable safeguards, should be encouraged because of the potential benefits linked to the administration of a variety of low-risk intermittent hypoxia protocols.

  12. [Open clinical trial with oral acyclovir for the prophylaxis of disease by Cytomegalovirus in low risk liver transplant recipients].

    Science.gov (United States)

    Moreno, J; Montero, J L; Gavilán, F; Costán, G; Herrero, C; Cárdenas, M; Sánchez-Guijo, P; Torre-Cisneros, J

    1999-10-01

    Checking the first 70 low risk liver transplantation performed in our hospital, who did not receive prophylaxis for Cytomegalovirus, we found that the incidence of Cytomegalovirus-infection and Cytomegalovirus-disease were 47% and 16% respectively. For this reason we started a prospective, open clinical study, to address the safety of acyclovir prophylaxis in low-risk liver transplant patients. Seventy patients did not receive acyclovir. Fifty patients received oral acyclovir during 3 months (800-3,200 mg/day). The occurrence of Cytomegalovirus infection was not modified (40%) but Cytomegalovirus disease decreased dramatically (4%, p Varicela-zoster symptomatic disease in this group of patients.

  13. Histone variants and lipid metabolism

    NARCIS (Netherlands)

    Borghesan, Michela; Mazzoccoli, Gianluigi; Sheedfar, Fareeba; Oben, Jude; Pazienza, Valerio; Vinciguerra, Manlio

    2014-01-01

    Within nucleosomes, canonical histones package the genome, but they can be opportunely replaced with histone variants. The incorporation of histone variants into the nucleosome is a chief cellular strategy to regulate transcription and cellular metabolism. In pathological terms, cellular steatosis

  14. Migraine Variants And Beyond

    Directory of Open Access Journals (Sweden)

    Chakravarty A

    2002-01-01

    Full Text Available The Classic presenting features of both migraine with and without aura have been clearly defined. Occasionally however migrainous headaches are accompanied by abrupt appearance of focal and ominous neurological signs. Such attacks can be labelled as migraine variants and the diagnosis in reality is one made by exclusion of other CNS diseases. Some but not all such conditions are mentioned in the International Headache Society (IHS classification under the general heading of migraine with aura. Rarely, the focal neurological deficit may outlast the migraine attack by days and occasionally with appearance of structural brain lesions on neuroimaging. Such attacks have been labelled as complicated Migraine by the IHS. The present review deal with the clinical, radiologic and pathophysiologic aspects of both these conditions - migraine variants and complicated migraine.

  15. Variants of Uncertainty

    Science.gov (United States)

    1981-05-15

    Variants of Uncertainty Daniel Kahneman University of British Columbia Amos Tversky Stanford University DTI-C &%E-IECTE ~JUNO 1i 19 8 1j May 15, 1981... Dennett , 1979) in which different parts have ac- cess to different data, assign then different weights and hold different views of the situation...2robable and t..h1 provable. Oxford- Claredor Press, 1977. Dennett , D.C. Brainstorms. Hassocks: Harvester, 1979. Donchin, E., Ritter, W. & McCallum, W.C

  16. A Comparative Study of Two Groups of Sex Offenders Identified as High and Low Risk on the Static-99

    Science.gov (United States)

    Coxe, Ray; Holmes, William

    2009-01-01

    The purpose of this study was to identify possible differences between high- and low-risk sex offenders. The subjects included 285 sex offenders on probation. They were evaluated with the Static-99, Abel Assessment, Raven's, and MMPI-2. A criminal history review identified the number of prior offenses and the age/sex category in the index offense.…

  17. Adverse outcomes in maternity care for women with a low risk profile in The Netherlands: a case series analysis

    NARCIS (Netherlands)

    Martijn, L.; Jacobs, A.; Amelink-Verburg, M.; Wentzel, R.; Buitendijk, S.; Wensing, M.

    2013-01-01

    BACKGROUND: This study aimed to perform a structural analysis of determinants of risk of critical incidents in care for women with a low risk profile at the start of pregnancy with a view on improving patient safety. METHODS: We included 71 critical incidents in primary midwifery care and subsequent

  18. [Adverse outcomes in maternity care for women with a low risk profile in The Netherlands: a case series analysis

    NARCIS (Netherlands)

    Martijn, L.M.; Jacobs, A.; Amelink-Verburg, M.P.; Wentzel, R.; Buitendijk, S.E.; Wensing, M.

    2014-01-01

    BACKGROUND: This study aimed to perform a structural analysis of determinants of risk of critical incidents in care for women with a low risk profile at the start of pregnancy with a view on improving patient safety. METHODS: We included 71 critical incidents in primary midwifery care and subsequent

  19. Relapse rates after two versus three consolidation courses of methotrexate in the treatment of low-risk gestational trophoblastic neoplasia.

    NARCIS (Netherlands)

    Lybol, C.; Sweep, F.C.; Harvey, R.; Mitchell, H.; Short, D.; Thomas, C.M.G.; Ottevanger, P.B.; Savage, P.M.; Massuger, L.F.A.G.; Seckl, M.J.

    2012-01-01

    OBJECTIVE: Methotrexate (MTX) alternating with folinic acid is a commonly used treatment regimen for low-risk gestational trophoblastic neoplasia (GTN). In The Netherlands, two courses of MTX are administered after normalization of serum human chorionic gonadotrophin (hCG) levels (consolidation cour

  20. LUGH, the Proposed Mercury Express Mission, as an Ideal, Current, Low-Cost, Low-Risk Option for Mercury Exploration

    Science.gov (United States)

    Clark, P. E.; Lawlor, S. McKenna; Curtis, S.; Marr, G.; Giles, B.

    2000-01-01

    We propose an ESA Flexi Mission, LUGH, Mercury Express Mission, an extremely fast, low cost, low risk, high return, three-platform, multiple flyby mission which would provide data which are unique and complimentary to recently selected long lead time Mercury missions.

  1. High incidence of pseudotumours after hip resurfacing even in low risk patients; results from an intensified MRI screening protocol.

    NARCIS (Netherlands)

    Weegen, W. van der; Smolders, J.M.; Sijbesma, T.; Hoekstra, H.J.; Brakel, K.; Susante, J.L.C. van

    2013-01-01

    We intensified our screening protocol for the presence of pseudotumours in a consecutive series of patients with a hip resurfacing arthroplasty (HRA), to establish whether we should be alert to the presence of 'silent' pseudotumours. Patients categorised with high risk (11 hips) and low risk (10 hip

  2. LUGH, the Proposed Mercury Express Mission, as an Ideal, Current, Low-Cost, Low-Risk Option for Mercury Exploration

    Science.gov (United States)

    Clark, P. E.; Lawlor, S. McKenna; Curtis, S.; Marr, G.; Giles, B.

    2000-01-01

    We propose an ESA Flexi Mission, LUGH, Mercury Express Mission, an extremely fast, low cost, low risk, high return, three-platform, multiple flyby mission which would provide data which are unique and complimentary to recently selected long lead time Mercury missions.

  3. Identification of patients with low-risk pulmonary embolism suitable for outpatient treatment using the pulmonary embolism severity index (PESI).

    LENUS (Irish Health Repository)

    McCabe, A

    2013-06-01

    There is increasing evidence that outpatient treatment of patients with low-risk stable pulmonary embolism (PE) is safe, effective and potentially reduces costs. It is not clear how many patients presenting to an Irish Emergency Department (ED) are potentially suitable for outpatient management.

  4. Quantification of CT images for the classification of high- and low-risk pancreatic cysts

    Science.gov (United States)

    Gazit, Lior; Chakraborty, Jayasree; Attiyeh, Marc; Langdon-Embry, Liana; Allen, Peter J.; Do, Richard K. G.; Simpson, Amber L.

    2017-03-01

    Pancreatic cancer is the most lethal cancer with an overall 5-year survival rate of 7%1 due to the late stage at diagnosis and the ineffectiveness of current therapeutic strategies. Given the poor prognosis, early detection at a pre-cancerous stage is the best tool for preventing this disease. Intraductal papillary mucinous neoplasms (IPMN), cystic tumors of the pancreas, represent the only radiographically identifiable precursor lesion of pancreatic cancer and are known to evolve stepwise from low-to-high-grade dysplasia before progressing into an invasive carcinoma. Observation is usually recommended for low-risk (low- and intermediate-grade dysplasia) patients, while high-risk (high-grade dysplasia and invasive carcinoma) patients undergo resection; hence, patient selection is critically important in the management of pancreatic cysts.2 Radiologists use standard criteria such as main pancreatic duct size, cyst size, or presence of a solid enhancing component in the cyst to optimally select patients for surgery.3 However, these findings are subject to a radiologist's interpretation and have been shown to be inconsistent with regards to the presence of a mural nodule or solid component.4 We propose objective classification of risk groups based on quantitative imaging features extracted from CT scans. We apply new features that represent the solid component (i.e. areas of high intensity) within the cyst and extract standard texture features. An adaptive boost classifier5 achieves the best performance with area under receiver operating characteristic curve (AUC) of 0.73 and accuracy of 77.3% for texture features. The random forest classifier achieves the best performance with AUC of 0.71 and accuracy of 70.8% with the solid component features.

  5. Does Preendoscopy Rockall Score Safely Identify Low Risk Patients following Upper Gastrointestinal Haemorrhage?

    Directory of Open Access Journals (Sweden)

    Matthew R. Johnston

    2015-01-01

    Full Text Available Objective. To determine if preendoscopy Rockall score (PERS enables safe outpatient management of New Zealanders with upper gastrointestinal haemorrhage (UGIH. Methods. Retrospective analysis of adults with UGIH over 59 consecutive months. PERS, diagnosis, demographics, need for endoscopic therapy, transfusion or surgery and 30-day mortality and 14-day rebleeding rate, and sensitivity and specificity of PERS for enabling safe discharge preendoscopy were calculated. Results. 424 admissions with UGIH. Median age was 74.3 years (range 19–93 years, with 55.1% being males. 30-day mortality was 4.6% and 14-day rebleeding rate was 6.0%. Intervention was required in 181 (46.6%: blood transfusion (147 : 37.9%, endoscopic intervention (75 : 19.3%, and surgery (8 : 2.1%. 42 (10.8% had PERS = 0 with intervention required in 15 (35.7%. Females more frequently required intervention, OR 1.73 (CI: 1.12–2.69. PERS did not predict intervention but did predict 30-day mortality: each point increase equated to an increase in mortality of OR 1.46 (CI: 1.11–1.92. Taking NSAIDs/aspirin reduced 30-day mortality, OR 0.22 (CI: 0.08–0.60. Conclusion. PERS identifies 10.8% of those with UGIH as low risk but 35.7% required intervention or died. It has a limited role in assessing these patients and should not be used to identify those suitable for outpatient endoscopy.

  6. Association of Trichomonas vaginalis and cytological abnormalities of the cervix in low risk women.

    Directory of Open Access Journals (Sweden)

    Gilbert G G Donders

    Full Text Available OBJECTIVE: Is Trichomonas vaginalis (TV an inducing factor for the development of (pre-cancerous lesions of the cervix? DESIGN: Cross sectional study. SETTING: Screening healthy Belgian women with low infection risk. SAMPLE: 63,251 consecutive liquid based cervical samples. METHODS: Real time quantitative PCR for presence of TV, 18 HPV types and Pap smear analysis of cytologic abnormalities. MAIN OUTCOME MEASURES: Association of TV and HPV with cervix dysplasia. RESULTS: The overall prevalence of TV DNA was 0.37%, of low risk HPV 2%, of high risk HPV 13.2%, and 8.8 % had cytological abnormalities. Both LR-HPV and HR-HPV were significantly associated with all cytological abnormalities. Presence of TV was associated with LR- and HR-HPV, ASC-US and HSIL, but not with other abnormalities. All women with TV and HSIL also had HR-HPV, while the latter was present in only 59% of women with TV and ASC-US. Amongst HPV negative women, TV was found in 1.3% of women with ASC-US, but only in 0.03% of women with normal cytology (OR 4.2, CL95% 2.1-8.6. In HR-HPV positive women, presence of TV increased the likelihood of cytological abnormalities somewhat (P=0.05, mainly due to an increase in ASC-US and LSIL, but not HSIL. CONCLUSIONS: We conclude that TV infection is associated with both LR and HR-HPV infection of the cervix, as well as with ASC-US and HSIL. TV is a concomitant STI, but is not thought to be a co-factor in the causation of HSIL and cervical cancer. However, TV may cause false positive diagnoses of ASC-US.

  7. Evaluation of weekly intramuscular methotrexate in the treatment of low risk gestational trophoblastic neoplasia

    Directory of Open Access Journals (Sweden)

    Malihe Hasanzadeh

    2014-01-01

    Aims: The aim of this study was to determine the rate of response to weekly intramuscular (IM methotrexate (MTX in patients with low-risk GTN (LR-GTN. Settings and Design: The study was designed cross-sectional and prospectively. Patients followed for 1 year. Materials and Methods: From 2006 to 2011, a total of 117 women with LR-GTN were studied. A weekly MTX regimen (50 mg/m 2 with dose escalation to 75 mg/m 2 was administered to 87 of patients. A biweekly pulsed intravenous bolus of 1.25 mg/m 2 of actinomycin D was administered in patients resistant to MTX (n = 30 and combination therapy was performed in those who did not respond to aforesaid treatments (n = 8. Statistical Analysis: The data were analyzed using Statistical Package for Social Sciences (SPSS 11.5 and Chi-square model was applied. Descriptive statistics and compare means (t-test was used as well. P < 0.05 was statistically significant. Results: All 117 patients with LR-GTN were cured. The primary remission rate was 74.3%, with primary dose of 50 mg/m 2 of MTX and escalation to 75 mg/m 2 . Another patient achieved complete remission with actinomycin and combination chemotherapy. There were significant statistical correlation between remission and World Health Organization (WHO scoring, International Federation of Gynecology and Obstetrics (FIGO staging, pretreatment beta-human chorionic gonadotropin (β-hCG level, and antecedent pregnancy (P < 0.05. Conclusion: We suggest that cases with score ≥6 should be considered high risk. First-line combination chemotherapy is advised in GTN with score ≥6.

  8. Ultrasonographic study and Doppler flow velocimetry of maternal kidneys and liver in low-risk pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Daher, Cibele Helena; Gomes, Andrea Cavalanti; Kobayashi, Sergio; Chammas, Maria Cristina, E-mail: cibeledaher@hotmail.com [Universidade de Sao Paulo (In-Rad/HC-FMUSP), Sao Paulo, SP (Brazil). Hospital das Clinicas. Inst. de Radiologia; Cerri, Giovanni Guido [Universidade de Sao Paulo (FMUSP), Sao Paulo, SP (Brazil). Fac. de Medicina

    2015-05-15

    Objective: longitudinal study with B-mode ultrasonography and Doppler ultrasonography of maternal kidneys and liver in low-risk pregnancy, to establish and quantify normality parameters, correlating them with physiological changes. Materials and methods: twenty-five pregnant women were assessed and selected to participate in the study, each of them undergoing four examinations at the first, second, third trimesters and postpartum. Results: findings during pregnancy were the following: increased renal volume, pyelocaliceal dilatation with incidence of 45.4% in the right kidney, and 9% in the left kidney; nephrolithiasis, 18.1% in the right kidney, 13.6% in the left kidney. With pyelocaliceal dilatation, mean values for resistivity index were: 0.68 for renal arteries; 0.66 for segmental arteries; 0.64 for interlobar arteries; 0.64 for arcuate arteries. Without pyelocaliceal dilatation, 0.67 for renal arteries; 0.64 for segmental arteries; 0.63 for interlobar arteries; and 0.61 for arcuate arteries. Portal vein flow velocities presented higher values in pregnancy, with mean value for maximum velocity of 28.9 cm/s, and 22.6 cm/s postpartum. The waveform pattern of the right hepatic vein presented changes persisting in the postpartum period in 31.8% of the patients. Cholelithiasis was observed in 18.1% of the patients. Conclusion: alterations in renal volume, pyelocaliceal dilatation, nephrolithiasis, cholelithiasis, changes in portal vein flow velocity, alterations in waveform pattern of the right hepatic vein, proved to be significant. (author)

  9. Ultrasonographic study and Doppler flow velocimetry of maternal kidneys and liver in low-risk pregnancy*

    Science.gov (United States)

    Daher, Cibele Helena; Gomes, Andrea Cavalanti; Kobayashi, Sergio; Cerri, Giovanni Guido; Chammas, Maria Cristina

    2015-01-01

    Objective Longitudinal study with B-mode ultrasonography and Doppler ultrasonography of maternal kidneys and liver in low-risk pregnancy, to establish and quantify normality parameters, correlating them with physiological changes. Materials and Methods Twenty-five pregnant women were assessed and selected to participate in the study, each of them undergoing four examinations at the first, second, third trimesters and postpartum. Results Findings during pregnancy were the following: increased renal volume, pyelocaliceal dilatation with incidence of 45.4% in the right kidney, and 9% in the left kidney; nephrolithiasis, 18.1% in the right kidney, 13.6% in the left kidney. With pyelocaliceal dilatation, mean values for resistivity index were: 0.68 for renal arteries; 0.66 for segmental arteries; 0.64 for interlobar arteries; 0.64 for arcuate arteries. Without pyelocaliceal dilatation, 0.67 for renal arteries; 0.64 for segmental arteries; 0.63 for interlobar arteries; and 0.61 for arcuate arteries. Portal vein flow velocities presented higher values in pregnancy, with mean value for maximum velocity of 28.9 cm/s, and 22.6 cm/s postpartum. The waveform pattern of the right hepatic vein presented changes persisting in the postpartum period in 31.8% of the patients. Cholelithiasis was observed in 18.1% of the patients. Conclusion Alterations in renal volume, pyelocaliceal dilatation, nephrolithiasis, cholelithiasis, changes in portal vein flow velocity, alterations in waveform pattern of the right hepatic vein, proved to be significant. PMID:26185338

  10. Ultrasonographic study and Doppler flow velocimetry of maternal kidneys and liver in low-risk pregnancy

    Directory of Open Access Journals (Sweden)

    Cibele Helena Daher

    2015-06-01

    Full Text Available Abstract Objective: Longitudinal study with B-mode ultrasonography and Doppler ultrasonography of maternal kidneys and liver in low-risk pregnancy, to establish and quantify normality parameters, correlating them with physiological changes. Materials and Methods: Twenty-five pregnant women were assessed and selected to participate in the study, each of them undergoing four examinations at the first, second, third trimesters and postpartum. Results: Findings during pregnancy were the following: increased renal volume, pyelocaliceal dilatation with incidence of 45.4% in the right kidney, and 9% in the left kidney; nephrolithiasis, 18.1% in the right kidney, 13.6% in the left kidney. With pyelocaliceal dilatation, mean values for resistivity index were: 0.68 for renal arteries; 0.66 for segmental arteries; 0.64 for interlobar arteries; 0.64 for arcuate arteries. Without pyelocaliceal dilatation, 0.67 for renal arteries; 0.64 for segmental arteries; 0.63 for interlobar arteries; and 0.61 for arcuate arteries. Portal vein flow velocities presented higher values in pregnancy, with mean value for maximum velocity of 28.9 cm/s, and 22.6 cm/s postpartum. The waveform pattern of the right hepatic vein presented changes persisting in the postpartum period in 31.8% of the patients. Cholelithiasis was observed in 18.1% of the patients. Conclusion: Alterations in renal volume, pyelocaliceal dilatation, nephrolithiasis, cholelithiasis, changes in portal vein flow velocity, alterations in waveform pattern of the right hepatic vein, proved to be significant.

  11. Clinical trial registration was not an indicator for low risk of bias.

    Science.gov (United States)

    Farquhar, Cynthia M; Showell, Marian G; Showell, Emily A E; Beetham, Penny; Baak, Nora; Mourad, Selma; Jordan, Vanessa M B

    2017-04-01

    To determine the prevalence of registered trials and to evaluate the risk of bias between registered and unregistered clinical trials. The Cochrane Gynecology and Fertility Group's specialized register was searched on November 5, 2015, for randomized controlled trials published from 2010 to 2014. Studies were selected if they had randomized women or men for fertility treatments, were published in full text and written in English. Two reviewers then independently assessed trial registration status for each trial, by searching the publication, trial registries, and by contacting the original authors. Of 693 eligible randomized controlled trials, only 44% were found to be registered. Unregistered clinical trials had smaller sample sizes than registered trials (P risk of bias using five of the Cochrane Risk of Bias "domains." Registered and unregistered trials differed in their risk of bias for random sequence generation (P = 0.001), allocation concealment (P = 0.003), and selective reporting (P  0.05) domains. Only 54 (43.2%) of the 125 registered trials were registered prospectively. This study has the following limitations. Only English language trials were included in this review. We were unable to obtain protocols for the unregistered trials and therefore were unable to assess the risk of bias in the selective reporting domain. All available trials should be included in systematic reviews and assessed for risk of bias as there are both registered trials with high risk of bias and unregistered trials with low risk of bias and by excluding unregistered trials more than half of the available evidence will be lost. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Thyroid nodules with minimal cystic changes have a low risk of malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Na, Dong Gyu; Kim, Dae Sik; Kim, Soo Jin [Dept. of Radiology, Human Medical Imaging and Intervention Center, Seoul (Korea, Republic of); Kim, Ji Hoon [Dept. of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2016-03-15

    The goal of this study was to determine the risk of malignancy of thyroid nodules with minimal cystic changes. A total of consecutive 1,000 thyroid nodules (≥1 cm) with final diagnoses from two institutions were included in this study. The risk of malignancy of thyroid nodules was analyzed according to the internal content, which was categorized as purely solid, minimally cystic (cystic changes ≤10%), and partially cystic (cystic changes >10%). We also assessed the risk of malignancy of nodules with minimal cystic changes depending on echogenicity and presence of any suspicious ultrasonografic (US) features. The overall frequency of purely solid, minimally cystic, and partially cystic nodules was 730/1,000 (73%), 61/1,000 (6.1%), and 209/1,000 (20.9%), respectively, with risks of malignancy of 14.8% (108/730), 3.3% (2/61), and 3.3% (7/209), respectively. The risk of malignancy of nodules with minimal cystic changes was significantly lower than that of purely solid nodules (P=0.013). The risk of malignancy of nodules with minimal cystic changes was also lower than that of purely solid nodules in the group of hypoechoic nodules (P=0.063) and in the group of nodules with suspicious US features (P=0.028), but was not significantly different from that of partially cystic nodules regardless of echogenicity or the presence of suspicious US features (P≥0.652). Thyroid nodules with minimal cystic changes have a low risk of malignancy, similar to that of partially cystic nodules regardless of echogenicity or the presence of suspicious US features. The US lexicon could define solid nodules as nodules with purely solid internal content in order to enhance the accuracy of estimated risks of malignancy.

  13. Costing Alternative Birth Settings for Women at Low Risk of Complications: A Systematic Review.

    Directory of Open Access Journals (Sweden)

    Vanessa Scarf

    Full Text Available There is demand from women for alternatives to giving birth in a standard hospital setting however access to these services is limited. This systematic review examines the literature relating to the economic evaluations of birth setting for women at low risk of complications.Searches of the literature to identify economic evaluations of different birth settings of the following electronic databases: MEDLINE, CINAHL, EconLit, Business Source Complete and Maternity and Infant care. Relevant English language publications were chosen using keywords and MeSH terms between 1995 and 2015. Inclusion criteria included studies focussing on the comparison of birth setting. Data were extracted with respect to study design, perspective, PICO principles, and resource use and cost data.Eleven studies were included from Australia, Canada, the Netherlands, Norway, the USA, and the UK. Four studies compared costs between homebirth and the hospital setting and the remaining seven focussed on the cost of birth centre care and the hospital setting. Six studies used a cost-effectiveness analysis and the remaining five studies used cost analysis and cost comparison methods. Eight of the 11 studies found a cost saving in the alternative settings. Two found no difference in the cost of the alternative settings and one found an increase in birth centre care.There are few studies that compare the cost of birth setting. The variation in the results may be attributable to the cost data collection processes, difference in health systems and differences in which costs were included. A better understanding of the cost of birth setting is needed to inform policy makers and service providers.

  14. Applicator-guided volumetric-modulated arc therapy for low-risk endometrial cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cilla, Savino, E-mail: savinocilla@gmail.com [Medical Physics Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Macchia, Gabriella [Radiation Oncology Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Sabatino, Domenico [Medical Physics Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Digesù, Cinzia; Deodato, Francesco [Radiation Oncology Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Piermattei, Angelo [Physics Institute, Università Cattolica del Sacro Cuore, Rome (Italy); De Spirito, Marco [Medical Physics Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Morganti, Alessio G. [Radiation Oncology Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Radiation Oncology Unit, Università Cattolica del Sacro Cuore, Rome (Italy)

    2013-04-01

    The aim of this study was to report the feasibility of volumetric-modulated arc therapy (VMAT) in the postoperative irradiation of the vaginal vault. Moreover, the VMAT technique was compared with 3D conformal radiotherapy (3D-CRT) and fixed-field intensity-modulated radiotherapy (IMRT), in terms of target coverage and organs at risk sparing. The number of monitor units and the delivery time were analyzed to score the treatment efficiency. All plans were verified in a dedicated solid water phantom using a 2D array of ionization chambers. Twelve patients with endometrial carcinoma who underwent radical hystero-adenexectomy and fixed-field IMRT treatments were retrospectively included in this analysis; for each patient, plans were compared in terms of dose-volume histograms, homogeneity index, and conformity indexes. All techniques met the prescription goal for planning target volume coverage, with VMAT showing the highest level of conformity at all dose levels. VMAT resulted in significant reduction of rectal and bladder volumes irradiated at all dose levels compared with 3D-CRT. No significant differences were found with respect to IMRT. Moreover, a significant improvement of the dose conformity was reached by VMAT technique not only at the 95% dose level (0.74 vs. 0.67 and 0.62) but also at 50% and 75% levels of dose prescription. In addition, VMAT plans showed a significant reduction of monitor units by nearly 28% with respect to IMRT, and reduced treatment time from 11 to <3 minutes for a single 6-Gy fraction. In conclusion, VMAT plans can be planned and carried out with high quality and efficiency for the irradiation of vaginal vault alone, providing similar or better sparing of organs at risk to fixed-field IMRT and resulting in the most efficient treatment option. VMAT is currently our standard approach for radiotherapy of low-risk endometrial cancer.

  15. Pilot Study of Physiologic Partograph Use Among Low-Risk, Nulliparous Women With Spontaneous Labor Onset.

    Science.gov (United States)

    Neal, Jeremy L; Lowe, Nancy K; Nacht, Amy S; Koschoreck, Kate; Anderson, Jessica

    2016-01-01

    Neal and Lowe developed a physiologic partograph to give clinicians an evidence-based, uniform approach to assessing active labor progress and diagnosing dystocia in high-resource settings. The aim of this pilot study was to examine the feasibility of implementing the Neal and Lowe partograph for in-hospital labor assessment. A descriptive study of low-risk, nulliparous women with spontaneous labor onset was performed at an academic medical center. Eight certified nurse-midwives from a single practice used the Neal and Lowe partograph for the assessment of labor progress. Descriptive statistics were used to summarize characteristics, interventions, and outcomes for women with partograph-assessed labors. Labors assessed by nurse-midwives (n = 83) or obstetricians (n = 75) using their usual assessment strategies were also described for the year prior to partograph introduction to contextualize partograph-assessed labor findings. Inferential statistical tests were not performed. Thirty-one of 34 (91.2%) partographs were used correctly. Seventy-one percent (n = 22) of these women progressed to complete dilatation within expected physiologic time frames while the remaining women (n = 9) experienced labor dystocia. Similar proportions of women in the partograph and usual labor assessment groups received oxytocin during labor. The cesarean rate was lower in the partograph group than in the usual care groups. No cesareans were performed for dystocia in active labor for women whose labors were assessed via partograph. Implementation of the Neal and Lowe partograph for in-hospital labor assessment is feasible. Incorrect plotting and/or interpretation of the partograph may be further minimized by providing clinicians opportunities for ongoing partograph training after implementation or through partograph software development. The Neal and Lowe partograph may assist clinicians in safely and significantly decreasing primary cesarean births performed for active labor dystocia in

  16. Variants of glycoside hydrolases

    Energy Technology Data Exchange (ETDEWEB)

    Teter, Sarah; Ward, Connie; Cherry, Joel; Jones, Aubrey; Harris, Paul; Yi, Jung

    2017-07-11

    The present invention relates to variants of a parent glycoside hydrolase, comprising a substitution at one or more positions corresponding to positions 21, 94, 157, 205, 206, 247, 337, 350, 373, 383, 438, 455, 467, and 486 of amino acids 1 to 513 of SEQ ID NO: 2, and optionally further comprising a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2 a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2, wherein the variants have glycoside hydrolase activity. The present invention also relates to nucleotide sequences encoding the variant glycoside hydrolases and to nucleic acid constructs, vectors, and host cells comprising the nucleotide sequences.

  17. Variants of glycoside hydrolases

    Energy Technology Data Exchange (ETDEWEB)

    Teter, Sarah (Davis, CA); Ward, Connie (Hamilton, MT); Cherry, Joel (Davis, CA); Jones, Aubrey (Davis, CA); Harris, Paul (Carnation, WA); Yi, Jung (Sacramento, CA)

    2011-04-26

    The present invention relates to variants of a parent glycoside hydrolase, comprising a substitution at one or more positions corresponding to positions 21, 94, 157, 205, 206, 247, 337, 350, 373, 383, 438, 455, 467, and 486 of amino acids 1 to 513 of SEQ ID NO: 2, and optionally further comprising a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2 a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2, wherein the variants have glycoside hydrolase activity. The present invention also relates to nucleotide sequences encoding the variant glycoside hydrolases and to nucleic acid constructs, vectors, and host cells comprising the nucleotide sequences.

  18. Shared decision making in patients with low risk chest pain: prospective randomized pragmatic trial

    Science.gov (United States)

    Hollander, Judd E; Schaffer, Jason T; Kline, Jeffrey A; Torres, Carlos A; Diercks, Deborah B; Jones, Russell; Owen, Kelly P; Meisel, Zachary F; Demers, Michel; Leblanc, Annie; Shah, Nilay D; Inselman, Jonathan; Herrin, Jeph; Castaneda-Guarderas, Ana; Montori, Victor M

    2016-01-01

    Objective To compare the effectiveness of shared decision making with usual care in choice of admission for observation and further cardiac testing or for referral for outpatient evaluation in patients with possible acute coronary syndrome. Design Multicenter pragmatic parallel randomized controlled trial. Setting Six emergency departments in the United States. Participants 898 adults (aged >17 years) with a primary complaint of chest pain who were being considered for admission to an observation unit for cardiac testing (451 were allocated to the decision aid and 447 to usual care), and 361 emergency clinicians (emergency physicians, nurse practitioners, and physician assistants) caring for patients with chest pain. Interventions Patients were randomly assigned (1:1) by an electronic, web based system to shared decision making facilitated by a decision aid or to usual care. The primary outcome, selected by patient and caregiver advisers, was patient knowledge of their risk for acute coronary syndrome and options for care; secondary outcomes were involvement in the decision to be admitted, proportion of patients admitted for cardiac testing, and the 30 day rate of major adverse cardiac events. Results Compared with the usual care arm, patients in the decision aid arm had greater knowledge of their risk for acute coronary syndrome and options for care (questions correct: decision aid, 4.2 v usual care, 3.6; mean difference 0.66, 95% confidence interval 0.46 to 0.86), were more involved in the decision (observing patient involvement scores: decision aid, 18.3 v usual care, 7.9; 10.3, 9.1 to 11.5), and less frequently decided with their clinician to be admitted for cardiac testing (decision aid, 37% v usual care, 52%; absolute difference 15%; P<0.001). There were no major adverse cardiac events due to the intervention. Conclusions Use of a decision aid in patients at low risk for acute coronary syndrome increased patient knowledge about their risk, increased

  19. Blunt Abdominal Trauma Patients Are at Very Low Risk for Intra-Abdominal Injury after Emergency Department Observation

    Directory of Open Access Journals (Sweden)

    Jason S Haukoos

    2011-05-01

    Full Text Available Introduction: Patients are commonly admitted to the hospital for observation following blunt abdominal trauma (BAT, despite initially negative emergency department (ED evaluations. With the current use of screening technology, such as computed tomography (CT of the abdomen and pelvis, ultrasound, and laboratory evaluations, it is unclear which patients require observation. The objective of this study was to determine the prevalence of intra-abdominal injury (IAI and death in hemodynamically normal and stable BAT patients with initially negative ED evaluations admitted to an ED observation unit and to define a low-risk subgroup of patients and assess whether they may be discharged without abdominal/pelvic CT or observation. Methods: This was a retrospective cohort study performed at an urban level 1 trauma center and included all BAT patients admitted to an ED observation unit as part of a BAT key clinical pathway. All were observed for at least 8 hours as part of the key clinical pathway, and only minors and pregnant women were excluded. Outcomes included the presence of IAI or death during a 40-month follow-up period. Prior to data collection, low-risk criteria were defined as no intoxication, no hypotension or tachycardia, no abdominal pain or tenderness, no hematuria, and no distracting injury. To be considered low risk, patients needed to meet all low-risk criteria. Results: Of the 1,169 patients included over the 2-year study period, 29% received a CT of the abdomen and pelvis, 6% were admitted to the hospital from the observation unit for further management, 0.4% (95% confidence interval [CI], 0.1%–1% were diagnosed with IAI, and 0% (95% CI, 0%–0.3% died. Patients had a median combined ED and observation length of stay of 9.5 hours. Of the 237 (20% patients who met low-risk criteria, 7% had a CT of the abdomen and pelvis and 0% (95% CI, 0%–1.5% were diagnosed with IAI or died. Conclusion: Most BAT patients who have initially negative

  20. Valproic acid for the treatment of low-risk myelodysplastic syndromes: A case report and a review of the literature

    OpenAIRE

    2013-01-01

    Myelodysplastic syndromes are heterogeneous myeloid neoplasms ranging from indolent conditions with a near-normal life expectancy to forms approaching acute myeloid leukemia. Here we report a 51-year-old woman with depression and severe obesity who was diagnosed with an International Prognostic Scoring System low-risk myelodysplastic syndrome, presenting mainly with thrombocytopenia, treated with escalating dose of valproic acid as a single agent. After two years of treatment her platelet cou...

  1. Derivation and Validation of a Novel Prediction Model to Identify Low-Risk Patients With Acute Pulmonary Embolism.

    Science.gov (United States)

    Subramanian, Muthiah; Gopalan, Sowmya; Ramadurai, Srinivasan; Arthur, Preetam; Prabhu, Mukund A; Thachathodiyl, Rajesh; Natarajan, Kumaraswamy

    2017-08-15

    Accurate identification of low-risk patients with acute pulmonary embolism (PE) who may be eligible for outpatient treatment or early discharge can have substantial cost-saving benefit. The purpose of this study was to derive and validate a prediction model to effectively identify patients with PE at low risk of short-term mortality, right ventricular dysfunction, and other nonfatal outcomes. This study analyzed data from 400 consecutive patients with acute PE. We derived and internally validated our prediction rule based on clinically significant variables that are routinely available at initial examination and that were categorized and weighted using coefficients in the multivariate logistic regression. The model was externally validated in an independent cohort of 82 patients. The final model (HOPPE score) consisted of 5 categorized patient variables (1, 2, or 3 points, respectively): systolic blood pressure (>120, 100 to 119, 80, 65 to 79, 101 beats/min), arterial partial pressure of oxygen (>80, 60 to 79, 4). The 30-day mortality rates were 0% in low risk (0 to 6 points), 7.5% to 8.5% in intermediate risk (7 to 10), and 18.2% to 18.8% in high-risk patients (≥11) across the derivation and validation cohorts. In comparison with the previously validated PESI score, the HOPPE score had a higher discriminatory power (area under the curve 0.74 vs 0.85, p = 0.033) and significantly improved both the discrimination (integrated discrimination improvement, p = 0.002) and reclassification (net reclassification improvement, p = 0.003) of the model for short-term mortality. In conclusion, the HOPPE score accurately identifies acute patients with PE at low risk of short-term mortality, right ventricular dysfunction, and other nonfatal outcomes. Prospective validation of the prediction model is necessary before implementation in clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Cognitive and Affective Representations of Active Surveillance as a Treatment Option for Low-Risk Prostate Cancer.

    Science.gov (United States)

    Lyons, Kathleen D; Li, Hsin H; Mader, Emily M; Stewart, Telisa M; Morley, Christopher P; Formica, Margaret K; Perrapato, Scott D; Seigne, John D; Hyams, Elias S; Irwin, Brian H; Mosher, Terry; Hegel, Mark T

    2016-06-29

    Benefits of early diagnosis and treatment remain debatable for men with low-risk prostate cancer. Active surveillance (AS) is an alternative to treatment. The goal of AS is to identify patients whose cancer is progressing rapidly while avoiding treatment in the majority of patients. The purpose of this study was to explore cognitive and affective representations of AS within a clinical environment that promotes AS a viable option for men with low-risk prostate cancer. Participants included patients for whom AS and active treatment were equally viable options, as well as practitioners who were involved in consultations for prostate cancer. Data were generated from semistructured interviews and audits of consultation notes and were analyzed using thematic analysis. Nineteen patients and 16 practitioners completed a semistructured interview. Patients generally viewed AS as a temporary strategy that was largely equated with inaction. There was variation in the degree to which inaction was viewed as warranted or favorable. Patient perceptions of AS were generally malleable and able to be influenced by information from trusted sources. Encouraging slow deliberation and multiple consultations may facilitate greater understanding and acceptance of AS as a viable treatment option for low-risk prostate cancer.

  3. Qualitative insights into how men with low-risk prostate cancer choosing active surveillance negotiate stress and uncertainty.

    Science.gov (United States)

    Mader, Emily M; Li, Hsin H; Lyons, Kathleen D; Morley, Christopher P; Formica, Margaret K; Perrapato, Scott D; Irwin, Brian H; Seigne, John D; Hyams, Elias S; Mosher, Terry; Hegel, Mark T; Stewart, Telisa M

    2017-05-08

    Active surveillance is a management strategy for men diagnosed with early-stage, low-risk prostate cancer in which their cancer is monitored and treatment is delayed. This study investigated the primary coping mechanisms for men following the active surveillance treatment plan, with a specific focus on how these men interact with their social network as they negotiate the stress and uncertainty of their diagnosis and treatment approach. Thematic analysis of semi-structured interviews at two academic institutions located in the northeastern US. Participants include 15 men diagnosed with low-risk prostate cancer following active surveillance. The decision to follow active surveillance reflects the desire to avoid potentially life-altering side effects associated with active treatment options. Men on active surveillance cope with their prostate cancer diagnosis by both maintaining a sense of control over their daily lives, as well as relying on the support provided them by their social networks and the medical community. Social networks support men on active surveillance by encouraging lifestyle changes and serving as a resource to discuss and ease cancer-related stress. Support systems for men with low-risk prostate cancer do not always interface directly with the medical community. Spousal and social support play important roles in helping men understand and accept their prostate cancer diagnosis and chosen care plan. It may be beneficial to highlight the role of social support in interventions targeting the psychosocial health of men on active surveillance.

  4. Does performing fetal ultrasound assessment once versus twice in the third trimester in low risk women alter the stillbirth rate?

    Science.gov (United States)

    Mone, F; Meti, S; Ong, S

    2014-06-01

    The aim of this retrospective observational study was to evaluate if performing fetal growth scans once or twice in the third trimester impacts on stillbirth rates in low risk pregnancies. The study was performed in a tertiary centre with 6,000 deliveries per annum. Data on all deliveries was collected via the National Maternity System Database and high risk pregnancies were excluded to calculate the stillbirth rate before and after 2011 when ultrasound assessment was performed twice and once in the third trimester. Between 2009-2012 there were 18,856 low risk-pregnancy deliveries with 45 stillbirths, (average stillbirth rate 0.26%). The stillbirth rate in 2009/2010 was 54/9423 (0.25%). The stillbirth rate in 2012 was 13/5615 (0.27%). [p = 0.897; chi square = 0.017; df = 1]. There was no statistical difference in the stillbirth rate when low risk women were scanned once or twice in the third trimester.

  5. Identification of patients at low risk of dying after acute myocardial infarction, by simple clinical and submaximal exercise test criteria.

    Science.gov (United States)

    Campbell, S; A'Hern, R; Quigley, P; Vincent, R; Jewitt, D; Chamberlain, D

    1988-09-01

    A consecutive series of 559 hospital survivors of acute myocardial infarction aged less than 66 years were studied; 93 were designated prospectively as low-risk because they were suitable for early submaximal exercise testing and had none of the following clinical or exercise test 'risk factors': (1) angina for at least one month prior to infarction; (2) symptomatic ventricular arrhythmias, or (3) recurrent ischaemic pain, both after the first 24 h of infarction; (4) cardiac failure; (5) cardiomegaly; and (6) an abnormal exercise test (angina, ST-depression or poor blood pressure response). Altogether 301 patients were exercised; their mortality over a median follow-up of 2.4 years was 10.2%, versus 24.6% in the 258 patients not exercised (P = 0.0005). Absence of clinical 'risk factors' alone, in the exercised patients, identified 156 with a mortality of 5.4% versus 15.6% in the 145 with at least one clinical 'risk factor' (P = 0.004). The fully defined low-risk group comprised 93 of the former patients who had neither clinical nor exercise test 'risk factors'. None of these patients died compared with 19 of those with at least one 'risk factor' (mortality = 14.7%; P = 0.002). Their respective rates of non-fatal reinfarction were similar and never exceeded 5% per annum. Therefore, simple clinical and exercise test criteria can positively identify low-risk patients after infarction in whom secondary prevention may be inappropriate.

  6. Product Variant Master as a Means to Handle Variant Design

    DEFF Research Database (Denmark)

    Hildre, Hans Petter; Mortensen, Niels Henrik; Andreasen, Mogens Myrup

    1996-01-01

    The overall time requiered to design a new product variant relies on two factor: how good the methods to design the new variant are and how good these method are supported by computers.It has been estimated that 80% of all design tasks are variational in that the goal of the design is to adapt an...

  7. Variants of windmill nystagmus.

    Science.gov (United States)

    Choi, Kwang-Dong; Shin, Hae Kyung; Kim, Ji-Soo; Kim, Sung-Hee; Choi, Jae-Hwan; Kim, Hyo-Jung; Zee, David S

    2016-07-01

    Windmill nystagmus is characterized by a clock-like rotation of the beating direction of a jerk nystagmus suggesting separate horizontal and vertical oscillators, usually 90° out of phase. We report oculographic characteristics in three patients with variants of windmill nystagmus in whom the common denominator was profound visual loss due to retinal diseases. Two patients showed a clock-like pattern, while in the third, the nystagmus was largely diagonal (in phase or 180° out of phase) but also periodically changed direction by 180°. We hypothesize that windmill nystagmus is a unique manifestation of "eye movements of the blind." It emerges when the central structures, including the cerebellum, that normally keep eye movements calibrated and gaze steady can no longer perform their task, because they are deprived of the retinal image motion that signals a need for adaptive recalibration.

  8. Exploitation of resources and cardiovascular outcomes in low-risk patients with chest pain hospitalized in coronary care units

    Directory of Open Access Journals (Sweden)

    Saadat H

    2011-10-01

    Full Text Available Habibollah Saadat¹, Hossein Shiri², Zahra Salarpour², Tahereh Ashktorab² , Hamid Alavi Majd², Zahra Saadat¹, Hosein Vakili¹ 1Cardiovascular Research Center, Modarres Hospital, Shaheed Beheshti University of Medical Sciences, Tehran; 2Nursing School, Shaheed Beheshti University of Medical Sciences, Tehran, Iran Background: Most patients who present to medical centers due to chest pain do not suffer from acute coronary syndromes and do not need to be hospitalized in coronary care units (CCUs. This study was done to determine exploitation of resources and cardiovascular outcomes in low-risk patients with chest pain hospitalized in CCUs of educational hospitals affiliated with a major medical university. Methods: Over a 4-month period, 550 patients with chest pain who were hospitalized in the CCUs belonging to six hospitals affiliated to the authors' medical university were recruited by census method. Using Thrombolysis in Myocardial Infarction risk score, 95 patients (17.27% were categorized as low-risk patients. This group was evaluated with respect to demographics, bed occupancy rate, mean hospitalization period, expenses during admission, and cardiovascular outcomes in the 30-day period postdischarge. Results: Mean (± standard deviation hospitalization duration was 3.04 (±0.71 days. No significant difference was seen between the six surveyed hospitals regarding hospitalization duration (P = 0.602. The highest bed occupancy rate was seen in Taleghani and Shohada Tajrish hospitals and the lowest was in Modarres Hospital. The mean paid treatment expenses by low-risk patients was IRR 2,050,000 (US$205. Mean total hospitalization expenses was US$205. No significant difference was seen between the six surveyed hospitals (P = 0.699. Of the patients studied, 89.5% did not show any cardiovascular complications in 1 month and no deaths occurred. Conclusion: Given the high bed-occupancy rate by low-risk patients, associated high hospitalization

  9. The role of genetic breast cancer susceptibility variants as prognostic factors

    DEFF Research Database (Denmark)

    Fasching, Peter A; Pharoah, Paul D P; Cox, Angela

    2012-01-01

    Recent genome-wide association studies identified 11 single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. We investigated these and 62 other SNPs for their prognostic relevance. Confirmed BC risk SNPs rs17468277 (CASP8), rs1982073 (TGFB1), rs2981582 (FGFR2), rs13281615 ...

  10. Histone variants and lipid metabolism

    NARCIS (Netherlands)

    Borghesan, Michela; Mazzoccoli, Gianluigi; Sheedfar, Fareeba; Oben, Jude; Pazienza, Valerio; Vinciguerra, Manlio

    2014-01-01

    Within nucleosomes, canonical histones package the genome, but they can be opportunely replaced with histone variants. The incorporation of histone variants into the nucleosome is a chief cellular strategy to regulate transcription and cellular metabolism. In pathological terms, cellular steatosis i

  11. Cellobiohydrolase variants and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Wogulis, Mark

    2017-04-04

    The present invention relates to variants of a parent cellobiohydrolase II. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants.

  12. Risk assessment of lymph node metastasis before surgery in endometrial cancer: do we need a clinical trial for low-risk patients?

    Science.gov (United States)

    Kang, Sokbom; Todo, Yukiharu; Watari, Hidemichi

    2014-02-01

    Due to advances of radiological imaging and tumor biomarkers, the extent of information provided by preoperative assessment is rapidly growing. The Korean Gynecologic Oncology Group (KGOG) recently proposed new preoperative criteria to identify patients at low risk for lymph node metastasis in endometrial cancer. In the multicenter study, serum carbohydrate antigen 125 levels and three magnetic resonance imaging parameters were found to be independent risk factors for nodal metastasis, and classified 53% of patients as part of a low-risk group. The false-negative predictive value (NPV) was 1.7%, and was 1.4% in the validation set. Furthermore, the KGOG low-risk criteria were validated in 319 Japanese patients with endometrial cancer. The criteria identified 181 of 319 patients as a low-risk group (51%), and three false-negative cases were found (1.9%). These results indicate that we are able to identify low-risk patients with a negligible NPV before surgery. In addition, the low false NPV implies that there is great difficulty in performing a randomized trial to determine the efficacy of routine lymphadenectomy in patients at low risk of lymph node metastasis. Based on these data, the challenges and possible solutions for developing a consensus on the optimized management of low-risk endometrial cancer will be discussed in this review. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  13. Physiologic partograph to improve birth safety and outcomes among low-risk, nulliparous women with spontaneous labor onset.

    Science.gov (United States)

    Neal, Jeremy L; Lowe, Nancy K

    2012-02-01

    Oxytocin augmentation and cesarean rates among low-risk, term, nulliparous women with a spontaneous onset of labor in the United States approximate 50% and 26.5%, respectively. This indicates that the quality of obstetrical care is less than optimal in this nation. Exorbitant oxytocin use, the intervention most commonly associated with preventable adverse perinatal outcomes, jeopardizes birth safety while the high cesarean rate in this high-volume group compromises population health and increases health care costs. Dystocia, characterized by the slow, abnormal progression of labor, is the most commonly reported indication for primary cesareans, accounting directly for approximately 50% of all nulliparous cesareans and indirectly for most repeat cesareans. Diagnoses of dystocia are most often based on ambiguously defined delays in cervical dilation beyond which labor augmentation is deemed justified. Dystocia is known to be over-diagnosed which undoubtedly contributes to contemporary oxytocin augmentation and primary cesarean rates. Labor attendants would benefit from an evidence-based framework for homogenous labor assessment. To this end, we present a physiologically-based partograph for 'in-hospital' use in assessing the labors of low-risk, term, nulliparous women with spontaneous labor onset. This tool incorporates several evidence-based labor principles that combine to give needed clinical meaning to 'dystocia' as a diagnosis. It is hypothesized that our partograph will safely limit diagnoses of dystocia to only the slowest 10% of low-risk, nulliparous women. This should, in turn, safe-guard against unnecessary, injudicious, and potentially harmful use of oxytocin when labor is already adequately progressing while also indicating when its use may be justified. We further hypothesize that cesareans performed for dystocia in this population will decrease by ≥ 50%. No significant influence on other labor process or labor outcome variables is expected with

  14. [FRAX® thresholds to identify people with high or low risk of osteoporotic fracture in Spanish female population].

    Science.gov (United States)

    Azagra, Rafael; Roca, Genís; Martín-Sánchez, Juan Carlos; Casado, Enrique; Encabo, Gloria; Zwart, Marta; Aguyé, Amada; Díez-Pérez, Adolf

    2015-01-06

    To detect FRAX(®) threshold levels that identify groups of the population that are at high/low risk of osteoporotic fracture in the Spanish female population using a cost-effective assessment. This is a cohort study. Eight hundred and sixteen women 40-90 years old selected from the FRIDEX cohort with densitometry and risk factors for fracture at baseline who received no treatment for osteoporosis during the 10 year follow-up period and were stratified into 3 groups/levels of fracture risk (low20%) according to the real fracture incidence. The thresholds of FRAX(®) baseline for major osteoporotic fracture were: low riskrisk (3.6%; 95% CI 2.2-5.9), intermediate risk (13.7%; 95% CI 7.1-24.2) and high risk (21.4%; 95% CI12.9-33.2). The most cost-effective option was to refer to dual energy X-ray absorptiometry (DXA-scan) for FRAX(®)≥ 5 (Intermediate and high risk) to reclassify by FRAX(®) with DXA-scan at high/low risk. These thresholds select 17.5% of women for DXA-scan and 10% for treatment. With these thresholds of FRAX(®), compared with the strategy of opportunistic case finding isolated risk factors, would improve the predictive parameters and reduce 82.5% the DXA-scan, 35.4% osteoporosis prescriptions and 28.7% cost to detect the same number of women who suffer fractures. The use of FRAX ® thresholds identified as high/low risk of osteoporotic fracture in this calibration (FRIDEX model) improve predictive parameters in Spanish women and in a more cost-effective than the traditional model based on the T-score ≤ -2.5 of DXA scan. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  15. Trajectory of platelets in pregnancy - do low-risk women need an intrapartum full blood count prior to epidural?

    Science.gov (United States)

    Duong, Christine; Kidson-Gerber, Giselle; Peters, Nancy; Listijono, Dave R; Henry, Amanda

    2015-10-01

    This study aimed to investigate whether pregnant women with a normal 28-week gestation platelet count and no high-risk conditions for thrombocytopenia require a pre-epidural platelet count. All 1844 included women (platelet count > 150 × 10(9) /L at 28 weeks' gestation, term singleton birth, no thrombocytopenia risk conditions) had a platelet count > 100 × 10(9) /L prebirth, suggesting low-risk pregnant women do not require pre-epidural full blood count solely to check platelet count.

  16. Clinical governance and research ethics as barriers to UK low-risk population-based health research?

    Directory of Open Access Journals (Sweden)

    Douglas Flora

    2008-11-01

    Full Text Available Abstract Background Since the Helsinki Declaration was introduced in 1964 as a code of practice for clinical research, it has generally been agreed that research governance is also needed in the field of public health and health promotion research. Recently, a range of factors led to the development of more stringent bureaucratic procedures, governing the conduct of low-risk population-based health research in the United Kingdom. Methods Our paper highlights a case study of the application process to medical research ethics committees in the United Kingdom for a study of the promotion of physical activity by health care providers. The case study presented here is an illustration of the challenges in conducting low-risk population-based health research. Results Our mixed-methods approach involved a questionnaire survey of and semi-structured interviews with health professionals (who were all healthy volunteers. Since our study does not involve the participation of either patients or the general population, one would expect the application to the relevant research ethics committees to be a formality. This proved not to be the case! Conclusion Research ethics committees could be counter-productive, rather than protecting the vulnerable in the research process, they can stifle low-risk population-based health research. Research ethics in health services research is first and foremost the responsibility of the researcher(s, and we need to learn to trust health service researchers again. The burden of current research governance regulation to address the perceived ethical problems is neither appropriate nor adequate. Senior researchers/academics need to educate and train students and junior researchers in the area of research ethics, whilst at the same time reducing pressures on them that lead to unethical research, such as commercial funding, inappropriate government interference and the pressure to publish. We propose that non-invasive low-risk

  17. Accuracy of a sequential approach to identify young febrile infants at low risk for invasive bacterial infection.

    Science.gov (United States)

    Mintegi, Santiago; Bressan, Silvia; Gomez, Borja; Da Dalt, Liviana; Blázquez, Daniel; Olaciregui, Izaskun; de la Torre, Mercedes; Palacios, Miriam; Berlese, Paola; Benito, Javier

    2014-10-01

    Much effort has been put in the past years to create and assess accurate tools for the management of febrile infants. However, no optimal strategy has been so far identified. A sequential approach evaluating, first, the appearance of the infant, second, the age and result of the urinanalysis and, finally, the results of the blood biomarkers, including procalcitonin, may better identify low risk febrile infants suitable for outpatient management. To assess the value of a sequential approach ('step by step') to febrile young infants in order to identify patients at a low risk for invasive bacterial infections (IBI) who are suitable for outpatient management and compare it with other previously described strategies such as the Rochester criteria and the Lab-score. A retrospective comparison of three different approaches (step by step, Lab-score and Rochester criteria) was carried out in 1123 febrile infants less than 3 months of age attended in seven European paediatric emergency departments. IBI was defined as isolation of a bacterial pathogen from the blood or cerebrospinal fluid. Of the 1123 infants (IBI 48; 4.2%), 488 (43.4%) were classified as low-risk criteria according to the step by step approach (vs 693 (61.7%) with the Lab-score and 458 (40.7%) with the Rochester criteria). The prevalence of IBI in the low-risk criteria patients was 0.2% (95% CI 0% to 0.6%) using the step by step approach; 0.7% (95% CI 0.1% to 1.3%) using the Lab-score; and 1.1% (95% CI 0.1% to 2%) using the Rochester criteria. Using the step by step approach, one patient with IBI was not correctly classified (2.0%, 95% CI 0% to 6.12%) versus five using the Lab-score or Rochester criteria (10.4%, 95% CI 1.76% to 19.04%). A sequential approach to young febrile infants based on clinical and laboratory parameters, including procalcitonin, identifies better patients more suitable for outpatient management. Published by the BMJ Publishing Group Limited. For permission to use (where not already

  18. Certain variants of multipermutohedron ideals

    Indian Academy of Sciences (India)

    AJAY KUMAR; CHANCHAL KUMAR

    2016-10-01

    Multipermutohedron ideals have rich combinatorial properties. An explicit combinatorial formula for the multigraded Betti numbers of a multipermutohedron ideal and their Alexander duals are known. Also, the dimension of the Artinian quotient of an Alexander dual of a multipermutohedron ideal is the number of generalized parking functions. In this paper, monomial ideals which are certain variants of multipermutohedron ideals are studied. Multigraded Betti numbers of these variant monomial ideals and their Alexander duals are obtained. Further, many interesting combinatorial properties of multipermutohedron ideals are extended to these variant monomial ideals.

  19. ANALYSIS OF EFFICACY IN TREATMENT OF LOW-RISK WELL-DIFFERENTIATED THYROID CANCER WITHOUT CERVICAL LYMPH NODE INVOLVEMENT: 42 CASES REPORT

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To assess the more appropriate surgical treatment for low-risk group differentiated thyroid cancer. Methods A total of 42 low-risk patients with DTC, according to the AMES system ( male, n = 6; female, n = 36), were chosen for total thyroidectomy or subtotal thyroidectomy with center compartment lymphadectomy. Results Nineteen patients had cervical lymph node involvement. Two patients had recurrent nerve injured. One patient had hypoparathyroidism. There were no mortality or local lymph recurrent up to present.Conclusion Total thyroidectomy or subtotal thyroidectomy with prophylactic center compartment lymphadectomy is an appropriate approach for the treatment of low-risk group differentiated thyroed cancer, to prevent recurrent and improve life quality.

  20. Gene Variants Reduce Opioid Risks

    Science.gov (United States)

    ... Opioids Prescription Drugs & Cold Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/Nicotine ... variant of the gene for the μ-opioid receptor (OPRM1) with a decreased risk for addiction to ...

  1. The impact of ultrasonographic placental architecture on antenatal course, labor and delivery in a low-risk primigravid population.

    LENUS (Irish Health Repository)

    Cooley, Sharon M

    2012-02-01

    OBJECTIVE: To ascertain the impact of placental architecture on antenatal course and labor delivery in a low-risk primigravid population. METHODS: This study involves prospective recruitment of 1011 low-risk primigravids with placental ultrasound at 22?24 weeks and 36 weeks. Detailed postnatal review of all mothers and infants was undertaken. Retrospective analysis of ultrasound and clinical outcome data was performed. RESULTS: Eight hundred ten women with complete outcome data were available. Anterior placentation was statistically associated with intrauterine growth restriction (IUGR) and preterm birth and fundal placentation was significantly associated with a higher incidence of pregnancy-induced hypertension and infants with a birthweight less than the 9th centile. Placental infarcts in the third trimester was significantly increased in cases complicated by pre-eclampsia (PET) and in cases with fetal acidosis. Placental calcification was associated a 40-fold increase in the incidence of IUGR. Placental lakes in the second trimester were more prevalent in patients with threatened miscarriage. Increased placental thickness was associated with a higher rate of fetal acidosis. The Grannum grade of the placenta was higher with threatened first or second trimester loss, PET and in infants born less than 9th centile for gestation. CONCLUSION: Placental site and architecture impact on the incidence of maternal and fetal disease.

  2. LH/hCG-Receptor Expression May Have a Negative Prognostic Value in Low-Risk Endometrial Cancer.

    Science.gov (United States)

    Noci, Ivo; Sorbi, Flavia; Mannini, Luca; Projetto, Elisabetta; Pillozzi, Serena; Ghizzoni, Viola; Lottini, Tiziano; Moncini, Daniela; Baroni, Gianna; Mungai, Francesco; Arcangeli, Annarosa; Fambrini, Massimiliano

    2016-01-01

    A 51 year-old woman was diagnosed with endometrial cancer (EC) and underwent surgical staging. Pathological evaluation showed a 2 cm × 1 cm G2 endometrioid EC with a 30% myometrial deep invasion (FIGO Stage 1A). The patient was classified as low risk of recurrence, and no adjuvant treatment was offered. Six months after surgery, the patient developed an early vescico-vaginal recurrence, and chemotherapy treatment was started. Few months later, a subsequent involvement of vaginal wall, ileum, and omentum was detected, and the patient underwent second surgery. LH/hCG-receptor (LH/hCG-R) expression has been previously reported to be associated with an invasive phenotype in EC cells. Moreover, in a preclinical mouse model of EC behaves as a prometastatic molecular device. We analyzed the expression level of LH/hCG-R in cancer specimens collected during surgeries. Molecular and immunohistochemical analyses showed a strong expression of both mRNA and protein for LH/hCG-R in all specimens. LH/hCG-R expression may be assessed together with other clinicopathological parameters in order to better predict the risk of recurrence in low-risk EC patients. Further clinical trials are warranted in order to validate LH/hCG-R as biomarker in EC.

  3. Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the breast cancer association consortium: a combined case-control study.

    Science.gov (United States)

    Milne, Roger L; Gaudet, Mia M; Spurdle, Amanda B; Fasching, Peter A; Couch, Fergus J; Benítez, Javier; Arias Pérez, José Ignacio; Zamora, M Pilar; Malats, Núria; Dos Santos Silva, Isabel; Gibson, Lorna J; Fletcher, Olivia; Johnson, Nichola; Anton-Culver, Hoda; Ziogas, Argyrios; Figueroa, Jonine; Brinton, Louise; Sherman, Mark E; Lissowska, Jolanta; Hopper, John L; Dite, Gillian S; Apicella, Carmel; Southey, Melissa C; Sigurdson, Alice J; Linet, Martha S; Schonfeld, Sara J; Freedman, D Michal; Mannermaa, Arto; Kosma, Veli-Matti; Kataja, Vesa; Auvinen, Päivi; Andrulis, Irene L; Glendon, Gord; Knight, Julia A; Weerasooriya, Nayana; Cox, Angela; Reed, Malcolm Wr; Cross, Simon S; Dunning, Alison M; Ahmed, Shahana; Shah, Mitul; Brauch, Hiltrud; Ko, Yon-Dschun; Brüning, Thomas; Lambrechts, Diether; Reumers, Joke; Smeets, Ann; Wang-Gohrke, Shan; Hall, Per; Czene, Kamila; Liu, Jianjun; Irwanto, Astrid K; Chenevix-Trench, Georgia; Holland, Helene; Giles, Graham G; Baglietto, Laura; Severi, Gianluca; Bojensen, Stig E; Nordestgaard, Børge G; Flyger, Henrik; John, Esther M; West, Dee W; Whittemore, Alice S; Vachon, Celine; Olson, Janet E; Fredericksen, Zachary; Kosel, Matthew; Hein, Rebecca; Vrieling, Alina; Flesch-Janys, Dieter; Heinz, Judith; Beckmann, Matthias W; Heusinger, Katharina; Ekici, Arif B; Haeberle, Lothar; Humphreys, Manjeet K; Morrison, Jonathan; Easton, Doug F; Pharoah, Paul D; García-Closas, Montserrat; Goode, Ellen L; Chang-Claude, Jenny

    2010-01-01

    Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in the Breast Cancer Association Consortium. We evaluated two-way interactions between each of age at menarche, ever having had a live birth, number of live births, age at first birth and body mass index (BMI) and each of 12 single nucleotide polymorphisms (SNPs) (10q26-rs2981582 (FGFR2), 8q24-rs13281615, 11p15-rs3817198 (LSP1), 5q11-rs889312 (MAP3K1), 16q12-rs3803662 (TOX3), 2q35-rs13387042, 5p12-rs10941679 (MRPS30), 17q23-rs6504950 (COX11), 3p24-rs4973768 (SLC4A7), CASP8-rs17468277, TGFB1-rs1982073 and ESR1-rs3020314). Interactions were tested for by fitting logistic regression models including per-allele and linear trend main effects for SNPs and risk factors, respectively, and single-parameter interaction terms for linear departure from independent multiplicative effects. These analyses were applied to data for up to 26,349 invasive breast cancer cases and up to 32,208 controls from 21 case-control studies. No statistical evidence of interaction was observed beyond that expected by chance. Analyses were repeated using data from 11 population-based studies, and results were very similar. The relative risks for breast cancer associated with the common susceptibility variants identified to date do not appear to vary across women with different reproductive histories or body mass index (BMI). The assumption of multiplicative combined effects for these established genetic and other risk factors in risk prediction models appears justified.

  4. A Low-Cost, Low-Risk Mission Concept for the Return of Martian Atmospheric Dust: Relevance to Human Exploration of Mars

    Science.gov (United States)

    Wadhwa, M.; Leshin, L.; Clark, B.; Jones, S.; Jurewicz, A.; McLennan, S.; Mischna, M.; Ruff, S.; Squyres, S.; Westphal, A.

    2017-06-01

    We present a low-cost, low-risk mission concept for return of martian atmospheric dust. Such a mission would serve as a scientific, technological and operational pathfinder for future surface sample return and human exploration to Mars.

  5. Prostate Cancer in Patients With High Prostate-Specific Antigen Levels but Otherwise Very-Low-Risk Disease Behaves Like Prostate Cancer in High-Risk Patients.

    Science.gov (United States)

    Gestaut, Matthew M; Pruszynski, Jessica E; Swanson, Gregory P

    2017-08-01

    Rarely, patients with prostate cancer present with prostate-specific antigen (PSA) scores > 20 ng/mL but with otherwise very-low-risk disease. Oncologists have debated whether the malignancies in these patients behave more comparably to low-risk or high-risk disease. Our objective was to elucidate the behavior of these malignancies. A retrospective review was conducted of prostate cancer patients treated with radiation from 2000 to 2013. The inclusion criteria for very-low-risk disease included stage T1a-T1c, Gleason score ≤ 6, ≤ 3 positive cores, ≤ 50% involvement of any core, and PSA level high-grade, low-volume group consisted of patients with stage T1c-T2a, PSA level low-risk, and high-grade groups, respectively. Biochemical progression-free survival at 5 years was 71.3% for the divergent group, 68.8% for the high-grade group, and 98.3% for the low-risk group. The biochemical failure rate for the divergent group differed significantly from the low-risk group (P = .021), and that for the low-risk group was significantly different from that of the high-grade group (P = .025). However, the divergent group did not appear different from the high-grade group (P = .53). The results of our study have shown that the disease prognosis for the divergent-risk group is worse than that for the very-low-risk disease group and does not appear to be different from that for the low-volume, high-grade disease group. Oncologists should be aware that the outcomes for divergent patients are similarly poor to their low-volume, classically high-risk counterparts. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Validation of Gene Expression Signatures to Identify Low-risk Clear-cell Renal Cell Carcinoma Patients at Higher Risk for Disease-related Death.

    Science.gov (United States)

    Parasramka, Mansi; Serie, Daniel J; Asmann, Yan W; Eckel-Passow, Jeanette E; Castle, Erik P; Stanton, Melissa L; Leibovich, Brad C; Thompson, Robert Houston; Thompson, E Aubrey; Parker, Alexander S; Ho, Thai H; Joseph, Richard W

    2016-12-15

    Approximately 5-10% of patients with "low-risk" clear cell renal cell carcinoma (ccRCC), as stratified by externally validated clinicopathologic prognostic algorithms, eventually have disease relapse and die. Improving prognostic algorithms for these low-risk patients could help to provide improved individualized surveillance recommendations. To identify genes that are differentially expressed in patients with low-risk ccRCC who did and did not die of their disease. Using the Mayo Clinic Renal Registry, we identified formalin-fixed paraffin-embedded samples from patients with low-risk ccRCC, as defined by Mayo Clinic stage, size, grade, and necrosis score of 0-3. We conducted a nested case-control study between patients who did (cases) and did not (controls) have ccRCC relapse and death, using two independent sets (discovery and validation). We performed RNA sequencing of all samples in the discovery set to identify differentially expressed genes. In the independent validation set, we assessed the top 50 expressed genes using the nCounter Analysis System (NanoString Technologies, Seattle, WA, USA). In the discovery set of 24 cases and 24 controls, 92 genes were differentially expressed with pidentify patients with low-risk ccRCC who die of their disease. This finding provides an opportunity to help guide improved surveillance in patients with low-risk ccRCC. In the current study we identified RNA signatures from low-risk clear cell renal cell carcinoma patients who died from this disease. Improving prognostic algorithms for these low-risk patients could help to provide improved individualized surveillance recommendations. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  7. Post-term pregnancy is an independent risk factor for neonatal morbidity even in low-risk singleton pregnancies.

    Science.gov (United States)

    Linder, Nehama; Hiersch, Liran; Fridman, Elana; Klinger, Gil; Lubin, Daniel; Kouadio, Franck; Melamed, Nir

    2017-07-01

    To determine the independent association of post-term pregnancy with neonatal outcome in low-risk newborns. Retrospective cohort. Tertiary university-affiliated medical centre. All newborns of low-risk singleton pregnancies born at 39+0 to 44+0 weeks' gestation over a 5-year period. multiple gestation, maternal hypertensive disorder, diabetes or cholestasis, placental abruption or intrapartum fever (>38°C), small for gestational age (post-term (≥42+0 weeks), late term (41+0 to 41+6 weeks) and full term (39+0 to 40+6 weeks). Of the 23 524 eligible neonates, 747 (3.2%) were born post-term, 4632 (19.7%) late term and 18 145 (77.1%) full term. Women in the post-term group versus the late-term group had a significantly higher rate of caesarean section (8.9% vs 5.6%, poperative vaginal delivery (9.6% vs 7.4%, p=0.024). Post-term pregnancy versus full-term pregnancy was associated with an increased risk of NICU admission (OR 2.0, 95% CI 1.4 to 2.8), respiratory morbidity (OR 2.2, 95% CI 1.3 to 3.8) and infectious morbidity (OR 1.88, 95% CI 1.32 to 2.69). Post-term pregnancy versus late-term pregnancy was similarly associated with an increased risk of NICU admission (OR 2.0, 95% CI 1.4 to 2.9), respiratory morbidity (OR 2.7, 95% CI 1.5 to 5.0) and infectious morbidity (OR 1.8, 95% CI 1.2 to 2.7) and with hypoglycaemia (OR 2.6, 95% CI 1.2 to 5.4). Post-term delivery was not associated with neonatal mortality. Post-term pregnancy is an independent risk factor for neonatal morbidity even in low-risk singleton pregnancies. 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/.

  8. Management of low-risk well-differentiated thyroid cancer based only on thyroglobulin measurement after recombinant human thyrotropin.

    Science.gov (United States)

    Wartofsky, Leonard

    2002-07-01

    A multicenter study was undertaken to ascertain prevalence and significance of recombinant human thyrotropin (rhTSH)-stimulated increases in thyroglobulin (Tg) levels in thyroid cancer patients classified to be at low risk for recurrence. Patients were eligible for enrollment if they had undergone near-total or total thyroidectomy and remnant ablation between 1-10 years prior to enrollment and had received thyroxine suppression therapy (THST) with a TSH level of < 0.5 mU/L and Tg level less than or equal to 5 ng/mL within the prior year. Patients with anti-Tg antibodies, distant metastases, or other evidence of residual disease were excluded. Four hundred eighty-six patients were entered into the study, and 300 were considered eligible and comprise the study population. TSH, Tg, and anti-Tg antibody levels were obtained at baseline, followed by intramuscular injection of 0.9 mg of rhTSH on days 1 and 2 and measurement of Tg on day 5. After rhTSH, 53 patients (18%) had elevations in Tg of at least 2 ng/mL, including 33 patients (11%) with increases from baseline of equal to or greater than 5 ng/mL. Patients with an initial advanced stage of disease were more likely to display elevations in Tg after rhTSH. One third of those with stage III disease displayed elevations in Tg of 2 ng/mL or more. Patients within 5 years of thyroidectomy were as likely to display elevations in rhTSH-stimulated Tg as those 5-10 years from surgery. In conclusion, these data suggest rhTSH-stimulated Tg testing without scan may be a useful tool in the follow-up of patients with low-risk thyroid cancer, and may serve to identify patients previously thought free of disease on the basis of undetectable Tg levels while undergoing THST. A strategy is presented for incorporation of this approach into the management of patients with low-risk well-differentiated thyroid cancer.

  9. Intelligence, classroom behavior, and academic achievement in children at high and low risk for psychopathology: a structural equation analysis.

    Science.gov (United States)

    Worland, J; Weeks, D G; Janes, C L; Strock, B D

    1984-09-01

    The intelligence, academic achievement, and classroom behavior of 158 children were assessed in a sample that is being followed longitudinally. The sample included children at high risk for mental disorder by virtue of having a parent with a psychiatric diagnosis of schizophrenia or affective disorder, children at moderate risk, and children at low risk. A series of path analyses indicated that in this sample (1) classroom behavior was more likely an affect that a cause of academic achievement, and (2) the influence of parental psychopathology on classroom behavior was mediated by a child's intelligence and academic achievement. We were unable to substantiate an unmediated causal link between parental psychopathology and children's academic achievement or classroom behavior.

  10. Urokinase plasminogen activator receptor is expressed in invasive cells in gastric carcinomas from high- and low-risk countries

    DEFF Research Database (Denmark)

    Alpizar Alpizar, Warner Enrique; Nielsen, Boye Schnack; Sierra, Rafaela

    2010-01-01

    Gastric cancer is the second cancer causing death worldwide. Both incidence and mortality rates vary according to geographical regions. The receptor for urokinase plasminogen activator (uPAR) is involved in extracellular matrix degradation by mediating cell surface associated plasminogen activation......, and its presence on gastric cancer cells is linked to micro-metastasis and poor prognosis. Immunohistochemical analyses of a set of 44 gastric cancer lesions from Costa Rica showed expression of uPAR in cancer cells in both intestinal subtype (14 of 27) and diffuse subtype (10 of 17). We compared...... the expression pattern of uPAR in gastric cancers from a high-risk country (Costa Rica) with a low-risk country (Norway). We found uPAR on gastric cancer cells in 24 of 44 cases (54%) from Costa Rica and in 13 of 23 cases (56%) from Norway. uPAR was seen in macrophages and neutrophils in all cases. We also...

  11. Validity Assessment of Low-risk SCORE Function and SCORE Function Calibrated to the Spanish Population in the FRESCO Cohorts.

    Science.gov (United States)

    Baena-Díez, José Miguel; Subirana, Isaac; Ramos, Rafael; Gómez de la Cámara, Agustín; Elosua, Roberto; Vila, Joan; Marín-Ibáñez, Alejandro; Guembe, María Jesús; Rigo, Fernando; Tormo-Díaz, María José; Moreno-Iribas, Conchi; Cabré, Joan Josep; Segura, Antonio; Lapetra, José; Quesada, Miquel; Medrano, María José; González-Diego, Paulino; Frontera, Guillem; Gavrila, Diana; Ardanaz, Eva; Basora, Josep; García, José María; García-Lareo, Manel; Gutiérrez-Fuentes, José Antonio; Mayoral, Eduardo; Sala, Joan; R Degano, Irene; Francès, Albert; Castell, Conxa; Grau, María; Marrugat, Jaume

    2017-05-26

    To assess the validity of the original low-risk SCORE function without and with high-density lipoprotein cholesterol and SCORE calibrated to the Spanish population. Pooled analysis with individual data from 12 Spanish population-based cohort studies. We included 30 919 individuals aged 40 to 64 years with no history of cardiovascular disease at baseline, who were followed up for 10 years for the causes of death included in the SCORE project. The validity of the risk functions was analyzed with the area under the ROC curve (discrimination) and the Hosmer-Lemeshow test (calibration), respectively. Follow-up comprised 286 105 persons/y. Ten-year cardiovascular mortality was 0.6%. The ratio between estimated/observed cases ranged from 9.1, 6.5, and 9.1 in men and 3.3, 1.3, and 1.9 in women with original low-risk SCORE risk function without and with high-density lipoprotein cholesterol and calibrated SCORE, respectively; differences were statistically significant with the Hosmer-Lemeshow test between predicted and observed mortality with SCORE (P < .001 in both sexes and with all functions). The area under the ROC curve with the original SCORE was 0.68 in men and 0.69 in women. All versions of the SCORE functions available in Spain significantly overestimate the cardiovascular mortality observed in the Spanish population. Despite the acceptable discrimination capacity, prediction of the number of fatal cardiovascular events (calibration) was significantly inaccurate. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  12. A Cost-Effectiveness Analysis of Low-Risk Deliveries: A Comparison of Midwives, Family Physicians and Obstetricians.

    Science.gov (United States)

    Walters, Dylan; Gupta, Archna; Nam, Austin E; Lake, Jennifer; Martino, Frank; Coyte, Peter C

    2015-08-01

    To investigate the cost-effectiveness of in-hospital obstetrical care by obstetricians (OBs), family physicians (FPs) and midwives (MWs) for delivery of low-risk obstetrical patients. Cost-effectiveness analysis from the Ministry of Health perspective using a retrospective cohort study. The time horizon was from hospital admission of a low-risk pregnant patient to the discharge of the mother and infant. Costing data included human resource, intervention and hospital case-mix costs. Interventions measured were induction or augmentation of labour with oxytocin, epidural use, forceps or vacuum delivery and caesarean section. The outcome measured was avoidance of transfer to a neonatal intensive care unit (NICU). Model results were tested using various types of sensitivity analyses. The mean maternal age by provider groups was 29.7 for OBs, 29.8 for FPs and 31.2 for MWs - a statistically higher mean for the MW group. The MW deliveries had lower costs and better outcomes than FPs and OBs. FPs also dominated OB.s The differences in cost per delivery were small, but slightly lower in MW ($5,102) and FP ($5,116) than in OB ($5,188). Avoidance of transfer to an NICU was highest for MW at 94.0% (95% CI: 91.0-97.0), compared with 90.2% for FP (95% CI: 88.2-92.2) and 89.6% for OB (95% CI: 88.6-90.6). The cost-effectiveness of the MW group is diminished by increases in compensation, and the cost-effectiveness of the FP group is sensitive to changes in intervention rates and costs. The MW strategy was the most cost-effective in this hospital setting. Given data limitations to further examine patient characteristics between groups, the overall conservative findings of this study support investments and better integration for MWs in the current system. Copyright © 2015 Longwoods Publishing.

  13. The value of routine mid-trimester ultrasound in low-risk pregnancies at primary care level

    Directory of Open Access Journals (Sweden)

    EJ Buchmann

    2008-12-01

    Full Text Available This study investigated the effect of routine second-trimester ultrasound scanning on obstetric management and pregnancy outcomes. This was an open cluster, randomised, controlled trial. Clusters of women with low-risk pregnancies presenting in the second trimester were randomised to receive an ultrasound scan followed by usual antenatal care, or to an unscanned control group undergoing conventional antenatal care only. Out of the 962 women randomised, follow-up was successful for 804 (83.6%, with 416 allocated to the ultrasound scan group and 388 controls. There were no significant differences between the ultrasound scan group and the control group in terms of prenatal hospitalisation, mode of delivery, miscarriage, perinatal mortality rate and low birthweight rate. Ultrasound dating was associated with a lower rate of induction of labour for post-term pregnancy (1.4% vs. 3.6%; P=0.049. However, ultrasound scanning in low-risk pregnancies was not associated with improvements in pregnancy outcome. Opsomming Hierdie studie het die effek van roetine mid-trimester ultraklankskandering op swangerskapsorg en –uitkomste ondersoek. Dit was ’n oop tros, lukrake, beheerde proef. Groepe vroue met laerisikoswanger- skap in die midtrimester is lukraak toegewys vir ’n ultraklank-skandering, gevolg deur voorgeskrewe voorgeboor-tesorg, of vir ’n kontrolegroep wat voorgeboortesorg volgens nasionaal voorgeskrewe protokol sonder skandering ontvang het. Van die 962 vroue wat aan die steekproef deelgeneem het kon data vir 804 (83.6% suksesvol opgevolg word, met 416 in die ultraklankgroep en 388 in die kontrolegroep. Geen beduidende verskille is tussen die twee groepe gevind ten opsigte van voorgeboorte-hospitalisasie, geboortemetode, miskraamstatistiek, perinatale komplikasies of laegeboortegewig nie. Ultraklankdatering van swangerskappe is met minder kraaminduksie (1.4% teen 3.6%; P=0.049 vir natrimesterswangerskap geassosieer. Roetine

  14. Outcomes of Low-Risk Ductal Carcinoma In Situ in Southeast Asian Women Treated With Breast Conservation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Fuh Yong, E-mail: fuhyong@yahoo.com [Department of Radiation Oncology, National Cancer Centre Singapore (Singapore); Wang, Fuqiang [Department of Radiation Oncology, National Cancer Centre Singapore (Singapore); Chen, John Ju [Department of Cancer Informatics, National Cancer Centre Singapore (Singapore); Tan, Chiew Har [Department of Radiation Oncology, National Cancer Centre Singapore (Singapore); Tan, Puay Hoon [Department of Pathology, Singapore General Hospital (Singapore)

    2014-04-01

    Purpose: To examine the outcomes of Southeast Asian (SEA) women with low-risk ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS) and adjuvant radiation therapy. Methods and Materials: Retrospective chart reviews of patients treated with BCS for DCIS from 1995 to 2011 were performed. Patients meeting the selection criteria from Eastern Cooperative Oncology Group 5194 were included. Most patients received adjuvant radiation therapy (RT) consisting of whole-breast RT delivered to 50 Gy followed by a 10-Gy boost to the tumor bed. Results: Of 744 patients with pathologic diagnosis of pure DCIS identified, 273 met the selection criteria: low-intermediate grade (LIG), n=219; high grade (HG), n=54. Median follow-up for these patients was 60 months. There were 8 ipsilateral breast tumor recurrences (IBTRs) in total, 7 of which were DCIS. The estimated actuarial IBTR rates at 5 and 10 years for the entire cohort are 1.8% and 4.3%, respectively. Of the 219 patients with LIG DCIS, 210 received RT and 9 did not. There were 7 IBTRs in LIG DCIS, 2 among the 9 patients who did not receive RT. The IBTR rates in LIG DCIS at 5 and 10 years are 2.3% and 4.2%, respectively. All patients with HG DCIS received RT. There was only 1 IBTR occurring beyond 5 years, giving an estimated IBTR rate of 4.5% at 10 years. Conclusions: SEA women with screen-detected DCIS have exceedingly low rates of IBTR after BCS, comparable to that observed in reports of similar patients with low-risk DCIS treated with adjuvant radiation.

  15. Prevalence and Overlap of Noncardiac Conditions in the Evaluation of Low-risk Acute Chest Pain Patients

    Science.gov (United States)

    Al-Ani, Mohammad; Winchester, David E.

    2017-01-01

    Background When patients present to the emergency department with a complaint concerning for heart disease, this often becomes the primary focus of their evaluation. While patients with noncardiac causes of chest pain outnumber those with cardiac causes, noncardiac etiologies are frequently overlooked. We investigated symptoms and noncardiac conditions in a cohort of patients with chest pain at low risk of cardiac disease. Methods We analyzed data from a prospective registry of patients who were evaluated in our chest pain evaluation center. Registry participants completed standardized and validated instruments for depression (by Patient Health Questionnaire PHQ-9), anxiety (by Generalized Anxiety Disorder GAD-7), and Gastroesophageal Reflux Disorder (GERD; by GERD Symptom Frequency Questionnaire). Chest pain characteristics were recorded; severity was reported on a 10-point scale. Results A total of 195 patients were included in the investigation. Using the instruments noted above, the prevalence of depression was 34%, anxiety was 30%, and GERD was 44%, each of at least moderate severity. 32.5% of patients had 2 or more conditions. The median for the severity of angina was 7/10 and the number of episodes over the preceding week was 2, respectively. Severity of angina was associated with PHQ-9 (r = 0.238; P tobacco, diabetes mellitus, hypertension, or hyperlipidemia. Conclusion In our cohort of low-risk acute chest pain patients, depression, anxiety, and GERD were common, substantial overlap was observed. The severity of these noncardiac causes of chest pain causes correlated with the self-reported severity and frequency of angina, but weakly. These conditions should be part of a comprehensive plan of care for chest pain management. PMID:26214812

  16. An identification and brief advice programme for low-risk alcohol consumption in an acute medical setting: an implementation study

    Science.gov (United States)

    Green, Stuart A; Phekoo, Karen J; Grover, Vijay PB; Lovendoski, James; Anderson, Mike; Bowden-Jones, Owen; Foxton, Matthew R

    2013-01-01

    Objectives To implement an identification and brief advice (IBA) intervention to detect low-risk/hazardous alcohol consumption. Design Implementation was guided through the use of quality improvement tools and training. Setting This study was conducted over an 18-month period from April 2010 to September 2011 on a 42-bed acute medical unit at a central London acute hospital. Participants All medical patients over the age of 18 admitted to the acute assessment unit were eligible; any patient unable to provide a medical history either through language barriers or due to illness was excluded. Main outcome measures Percentage of medical patients admitted each week to the acute assessment unit who were screened for low-risk/hazardous alcohol consumption. Results Weekly data were analysed in time series run charts and cross-referenced to the date of educational sessions and their effect on the uptake of screening monitored. A demonstrable change in the mean percentage number of patients screened was observed in different time periods, 67.3–80.1%, following targeted teaching on the AAU. Conclusions Our study demonstrates the successful use of quality improvement methodology to guide the implementation of Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), an IBA intervention, in the acute medical setting. The incorporation of the AUDIT-C into an admission document has been well accepted by the junior doctors, attaining an average (mean) of 80% of patients being screened using the tool. Targeted teaching of clinical staff involved in admitting patients appears to be the most effective method in improving uptake of IBA by junior doctors. PMID:23772314

  17. Less-Restrictive Food Intake During Labor in Low-Risk Singleton Pregnancies: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Ciardulli, Andrea; Saccone, Gabriele; Anastasio, Hannah; Berghella, Vincenzo

    2017-03-01

    To evaluate benefits and harms of food intake during labor. Electronic databases such as MEDLINE and ClinicalTrials.gov were searched from their inception until October 2016. We included randomized trials comparing a policy of less-restrictive food intake with a policy of more restrictive food intake during labor. The primary outcome was the mean duration of labor. Meta-analysis was performed using the random-effects model of DerSimonian and Laird to produce summary treatment effects in terms of either a relative risk or a mean difference with 95% confidence interval (CI). Ten trials, including 3,982 laboring women, were included. All the studies involved laboring singletons considered at low risk because they had no obstetric or medical complications that would increase the likelihood of cesarean delivery. In three studies, women were allowed to select from a low-residue diet throughout the course of labor. One study had honey date syrup as the allowed food intake. Five studies had carbohydrate drinks as food intake in labor. The last one was the only trial that allowed unrestrictive food intake. In the included studies, all women in the intervention group were allowed the assigned food intake until delivery, whereas women in a control group were allowed only ice chips, water, or sips of water until delivery. A policy of less-restrictive food intake was associated with a significantly shorter duration of labor (mean difference -16 minutes, 95% CI -25 to -7). No other benefits or harms in obstetric or neonatal outcome were noticed. Regurgitation during general anesthesia and Mendelson syndrome did not occur in either group. Women with low-risk singleton pregnancies who were allowed to eat more freely during labor had a shorter duration of labor. A policy of less-restrictive food intake during labor did not influence other obstetric or neonatal outcomes nor did it increase the incidence of vomiting. Operative delivery rates were similar.

  18. Omission of Breast Radiotherapy in Low-risk Luminal A Breast Cancer: Impact on Health Care Costs.

    Science.gov (United States)

    Han, K; Yap, M L; Yong, J H E; Mittmann, N; Hoch, J S; Fyles, A W; Warde, P; Gutierrez, E; Lymberiou, T; Foxcroft, S; Liu, F F

    2016-09-01

    The economic burden of cancer care is substantial, including steep increases in costs for breast cancer management. There is mounting evidence that women age ≥ 60 years with grade I/II T1N0 luminal A (ER/PR+, HER2- and Ki67 ≤ 13%) breast cancer have such low local recurrence rates that adjuvant breast radiotherapy might offer limited value. We aimed to determine the total savings to a publicly funded health care system should omission of radiotherapy become standard of care for these patients. The number of women aged ≥ 60 years who received adjuvant radiotherapy for T1N0 ER+ HER2- breast cancer in Ontario was obtained from the provincial cancer agency. The cost of adjuvant breast radiotherapy was estimated through activity-based costing from a public payer perspective. The total saving was calculated by multiplying the estimated number of luminal A cases that received radiotherapy by the cost of radiotherapy minus Ki-67 testing. In 2010, 748 women age ≥ 60 years underwent surgery for pT1N0 ER+ HER2- breast cancer; 539 (72%) underwent adjuvant radiotherapy, of whom 329 were estimated to be grade I/II luminal A subtype. The cost of adjuvant breast radiotherapy per case was estimated at $6135.85; the cost of Ki-67 at $114.71. This translated into an annual saving of about $2.0million if radiotherapy was omitted for all low-risk luminal A breast cancer patients in Ontario and $5.1million across Canada. There will be significant savings to the health care system should omission of radiotherapy become standard practice for women with low-risk luminal A breast cancer. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  19. The WHO score predicts treatment outcome in low risk gestational trophoblastic neoplasia patients treated with weekly intramuscular methotrexate

    Directory of Open Access Journals (Sweden)

    Mitra M Gilani

    2013-01-01

    Full Text Available Background: Gestational trophoblastic neoplasia (GTN includes a spectrum of disease ranging from hydatidifrom mole to choriocarcinoma. Low risk GTN is defined as persistent molar pregnancy with a WHO score lower than seven. The optimal chemotherapeutic regimen still remains controversial. Aim: The objectives of this study was to determine efficacy and safety of weekly intramuscular methotrexte in the treatment of low risk gestational trophoblastic neoplasia.(LRGTN and also identify prognostic factors associated with treatment failure, necessitating second line chemotherapy. Materials and Methods: Sixty-six women with LRGTN from 2001 to 2009 were treated with weekly intramuscular methotrexate at 40mg/m 2 as first line therapy.Monitoring of treatment was done with weekly checking of βhCG level. Three consecutive negative βhCG measurements showed complete response. After first negative βhCG measurement, one additional dose was administered for consolidation. Results: Of 66 patients, who started the treatment five continued their treatment in other medical centres and were excluded from final analysis for treatment evaluation, and seven discontinued first line therapy because of hepatotoxicity. Of the remaining 54, complete remission occurred in 43 (79.6% and eleven were resistant to first line therapy. Mean WHO score prior to starting chemotherapy was significantly different between two groups of response and resistance according to our data. Change of treatment to second line Actinomycin-D was necessary in eigtheen cases because of resistance to first line in eleven and liver enzyme elevation in seven patients. Sixteen of these 18 responded to Actinomycin-D as second line and one needed hysterectomy for complete response. One patient received multiagent chemotherapy for complete remission. Conclusion: We recommend this effective and safe method of chemotherapy for women with LRGTN. According to our data, lower mean WHO score predicts a better

  20. Clinical problems in neurodevelopmental diagnosis: a 7-year neurological and psychological follow-up study of low risk preterm infants.

    Science.gov (United States)

    Fedrizzi, E; Zuccarino, M L; Vizziello, P

    1986-04-01

    24 selected urban middle class low risk preterm infants and 10 full term infants have been followed up to the age of 7 years in a prospective neurodevelopmental study. The aim was to find out whether the neurological and behavioral peculiarities of the preterm infant fall within the range of variability of sign and function development or whether they are the clinical features of minor neurological dysfunction. The infants were assessed neurologically according to Amiel-Tison at 3, 6, 9 and 12 months of corrected age and by Touwen's examination for minor neurological dysfunction at 3, 5 and 7 years. They were assessed psychologically at 6, 9, 12 and 36 months on Griffiths' Developmental Scale and at 7 years on the Wechsler Bellevue Scale. 33% of the sample was lost to follow-up. The outcome of neurological assessment was as follows: no major sequelae such as cerebral palsy or mental deficiency; 50% had transient neurological anomalies (TNA) during the first year of life, lasting more than 6 months in 16.7%; no minor neurological dysfunctions were detected at 5 and 7 years but the non optimal signs scores were higher in infants of low gestational age. The scores on the Griffiths scale were poorer in the preterm infants between 6 months and 5 years of corrected age, especially in the performance and hearing-speech areas. Performance failures seemed to be related to the duration and type of TNA in the first year of life. General, verbal and performance quotients on the WISC at 7 years were normal and there were no learning or behavior problems. The mild TNA found in low risk preterm infants in the first year of life appear to be of no predictive value for school age problems.

  1. Clinical performance of transperineal template guided mapping biopsy for therapeutic decision making in low risk prostate cancer.

    Science.gov (United States)

    Ahallal, Y; Sanchez-Salas, R; Sivaraman, A; Barret, E; Secin, F P; Validire, P; Rozet, F; Galiano, M; Cathelineau, X

    2016-12-01

    To evaluate the role of Transperineal Template guided Mapping Biopsy (TTMB) in determining the management strategy in patients with low risk prostate cancer (PCa). We retroscpectively evaluated 169 patients who underwent TTMB at our institution from February 2008 to June 2011. Ninety eight of them harbored indolent PCa defined as: Prostate Specific Antigen<10ng/ml, Gleason score 6 or less, clinical stage T2a or less, unilateral disease and a maximum of one third positive cores at first biopsy and<50% of the core involved. TTMB results were analyzed for Gleason score upgrading and upstaging as compared to initial TransRectal UltraSound (TRUS) biopsies and its influence on the change in the treatment decisions. TTMB detected cancer in 64 (65%) patients. The upgrade, upstage and both were noted in 33% (n=21), 12% (n=8) and 7% (n=5) respectively of the detected cancers. The disease characteristics was similar to initial TRUS in 30 (48%) patients and TTMB was negative in 34 (35%) patients. Prostate volume was significantly smaller in patients with upgrade and/or upstage noted at TTMB (45.4 vs 37.9; P=.03). TTMB results influenced 73.5% of upgraded and/or upstaged patients to receive radical treatment while 81% of the patients with unmodified stage and/or grade continued active surveillance or focal therapy. In patients with low risk PCa diagnosed by TRUS, subsequent TTMB demonstrated cancer upgrade and/or upstage in about one-third of the patients and resulted in eventual change in treatment decision. Copyright © 2016. Publicado por Elsevier España, S.L.U.

  2. Identifying patients with mild traumatic intracranial hemorrhage at low risk of decompensation who are safe for ED observation.

    Science.gov (United States)

    Pruitt, Peter; Penn, Joshua; Peak, David; Borczuk, Pierre

    2017-02-01

    Patients with traumatic intracranial hemorrhage and mild traumatic brain injury (mTIH) receive broadly variable care which often includes transfer to a trauma center, neurosurgery consultation and ICU admission. However, there may be a low risk cohort of patients who can be managed without utilizing such significant resources. Describe mTIH patients who are at low risk of clinical or radiographic decompensation and can be safely managed in an ED observation unit (EDOU). Retrospective evaluation of patients age≥16, GCS≥13 with ICH on CT. Primary outcomes included clinical/neurologic deterioration, CT worsening or need for neurosurgery. 1185 consecutive patients were studied. 814 were admitted and 371 observed patients (OP) were monitored in the EDOU or discharged from the ED after a period of observation. None of the OP deteriorated clinically. 299 OP (81%) had a single lesion on CT; 72 had mixed lesions. 120 patients had isolated subarachnoid hemorrhage (iSAH) and they did uniformly well. Of the 119 OP who had subdural hematoma (SDH), 6 had worsening CT scans and 3 underwent burr hole drainage procedures as inpatients due to persistent SDH without new deficit. Of the 39 OP who had cerebral contusions, 3 had worsening CT scans and one required NSG admission. No patient returned to the ED with a complication. Follow-up was obtained on 81% of OP. 2 patients with SDH required burr hole procedure >2weeks after discharge. Patients with mTIH, particularly those with iSAH, have very low rates of clinical or radiographic deterioration and may be safe for monitoring in an emergency department observation unit. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Rhinovirus wheezing illness in infancy is associated with medically attended third year wheezing in low risk infants: results of a healthy birth cohort study.

    Science.gov (United States)

    de Winter, Janneke J H; Bont, Louis; Wilbrink, Berry; van der Ent, Cornelis K; Smit, Henriette A; Houben, Michiel L

    2015-12-01

    Rhinoviruses may be pathogens contributing to the development of childhood wheezing. However, their role in low risk infants without an asthmatic predisposition is unknown. Knowing which healthy, low risk children are at increased risk for childhood wheezing after rhinovirus wheezing illness (RV-WI) in infancy, might help in developing prevention and treatment strategies for childhood wheezing. The aim of this study was to determine the association of medically attended wheezing at the age of three with RV-WI in the first year of life in low risk children without parental asthma. In a low risk, prospective birth cohort study, we followed 181 healthy born children from birth through the third year of life. We considered children 'low risk' if neither parent had a doctor's diagnosis of asthma. We determined infant RV-WI by parent-reported wheezing (based on daily logs) and simultaneous molecular rhinovirus detection in the first year of life. Respiratory function and blood eosinophil count were both measured in the first month of life. The primary outcome, third year wheezing, was defined as the use of prescribed inhaled asthma medications together with a doctor's visit for respiratory symptoms in the third year of life. We calculated the association of RV-WI with medically attended third year wheezing and other known possible risk factors for wheezing at the age of three. Among low risk children, third year wheezing was observed in 7 out of 18 (39%) children with versus 10 out of 163 (6%) children without infant RV-WI (OR 9.7, 95% CI 3.1-33.5, P third year wheezing was unchanged after adjustment for potential confounders such as eosinophilia and atopic eczema. RV-WI is a robust and independent risk factor for third year wheezing in low risk children without parental asthma. Future research will identify and protect those children at increased risk for RV-WI.

  4. Elevated Oestrogen Receptor Splice Variant ERαΔ5 Expression in Tumour-adjacent Hormone-responsive Tissue

    Directory of Open Access Journals (Sweden)

    Pierre L. Martin-Hirsch

    2010-11-01

    Full Text Available Susceptibility to prostate or endometrial cancer is linked with obesity, a state of oestrogen excess. Oestrogen receptor (ER splice variants may be responsible for the tissue-level of ER activity. Such micro-environmental regulation may modulate cancer initiation and/or progression mechanisms. Real-time reverse transcriptase (RT polymerase chain reaction (PCR was used to quantitatively assess the levels of four ER splice variants (ERαΔ3, ERαΔ5, ERβ2 and ERβ5, plus the full-length parent isoforms ERα and ERβ1, in high-risk [tumour-adjacent prostate (n = 10 or endometrial cancer (n = 9] vs. low-risk [benign prostate (n = 12 or endometrium (n = 9], as well as a comparison of UK (n = 12 vs. Indian (n = 15 benign prostate. All three tissue groups expressed the ER splice variants at similar levels, apart from ERαΔ5. This splice variant was markedly raised in all of the tumour-adjacent prostate samples compared to benign tissues. Immunofluorescence analysis for ERβ2 in prostate tissue demonstrated that such splice variants are present in comparable, if not greater, amounts as the parent full-length isoform. This small pilot study demonstrates the ubiquitous nature of ER splice variants in these tissue sites and suggests that ERαΔ5 may be involved in progression of prostate adenocarcinoma.

  5. Data-variant kernel analysis

    CERN Document Server

    Motai, Yuichi

    2015-01-01

    Describes and discusses the variants of kernel analysis methods for data types that have been intensely studied in recent years This book covers kernel analysis topics ranging from the fundamental theory of kernel functions to its applications. The book surveys the current status, popular trends, and developments in kernel analysis studies. The author discusses multiple kernel learning algorithms and how to choose the appropriate kernels during the learning phase. Data-Variant Kernel Analysis is a new pattern analysis framework for different types of data configurations. The chapters include

  6. Genome-wide profiling of methylation identifies novel targets with aberrant hypermethylation and reduced expression in low-risk myelodysplastic syndromes.

    Science.gov (United States)

    del Rey, M; O'Hagan, K; Dellett, M; Aibar, S; Colyer, H A A; Alonso, M E; Díez-Campelo, M; Armstrong, R N; Sharpe, D J; Gutiérrez, N C; García, J L; De Las Rivas, J; Mills, K I; Hernández-Rivas, J M

    2013-03-01

    Gene expression profiling signatures may be used to classify the subtypes of Myelodysplastic syndrome (MDS) patients. However, there are few reports on the global methylation status in MDS. The integration of genome-wide epigenetic regulatory marks with gene expression levels would provide additional information regarding the biological differences between MDS and healthy controls. Gene expression and methylation status were measured using high-density microarrays. A total of 552 differentially methylated CpG loci were identified as being present in low-risk MDS; hypermethylated genes were more frequent than hypomethylated genes. In addition, mRNA expression profiling identified 1005 genes that significantly differed between low-risk MDS and the control group. Integrative analysis of the epigenetic and expression profiles revealed that 66.7% of the hypermethylated genes were underexpressed in low-risk MDS cases. Gene network analysis revealed molecular mechanisms associated with the low-risk MDS group, including altered apoptosis pathways. The two key apoptotic genes BCL2 and ETS1 were identified as silenced genes. In addition, the immune response and micro RNA biogenesis were affected by the hypermethylation and underexpression of IL27RA and DICER1. Our integrative analysis revealed that aberrant epigenetic regulation is a hallmark of low-risk MDS patients and could have a central role in these diseases.

  7. Ductal Carcinoma In Situ of the Breast: Evaluating the Role of Radiation Therapy in the Management and Attempts to Identify Low-risk Patients.

    Science.gov (United States)

    Shah, Chirag; Vicini, Frank A; Berry, Sameer; Julian, Thomas B; Wilkinson, John Ben; Shaitelman, Simona F; Khan, Atif; Finkelstein, Steven E; Goldstein, Neal

    2015-10-01

    Ductal carcinoma in situ of the breast has rapidly increased in incidence over the past several decades secondary to an increased use of screening mammography. Local treatment options for women diagnosed with ductal carcinoma in situ include mastectomy or breast-conserving therapy. Although several randomized trials have confirmed a >50% reduction in the risk of local recurrence with the administration of radiation therapy (RT) compared with breast-conserving surgery alone, controversy persists regarding whether or not RT is needed in selected "low-risk" patients. Over the past two decades, two prospective single-arm studies and one randomized trial have been performed and confirm that the omission of RT after surgery is associated with higher rates of local recurrence even after selecting patients with optimal clinical and pathologic features. Importantly, these trials have failed to consistently and reproducibly identify a low-risk cohort of patients (based on clinical and pathologic features) that does not benefit from RT. As a result, adjuvant RT is still advocated in the majority of patients, even in low-risk cases. Future research is moving beyond traditional clinical and pathologic risk factors and instead focusing on approaches such as multigene assays and biomarkers with the hopes of identifying truly low-risk patients who may not require RT. However, recent studies confirm that even low-risk patients identified from multigene assays have higher rates of local recurrence with local excision alone than would be expected with the addition of RT.

  8. Variant Creutzfeldt-Jakob disease

    NARCIS (Netherlands)

    E.A. Croes (Esther); C.M. van Duijn (Cock)

    2003-01-01

    textabstractA variant form of Creutzfeldt-Jakob disease (vCJD) has had major impact in Europe during the last decade. In this article, we review the aetiology of vCJD and its relation with bovine spongiform encephalopathy. Further, treatment of the disease, the strategies focusing on prevention of t

  9. Effects of caesarean section on maternal health in low risk nulliparous women: a prospective matched cohort study in Shanghai, China

    Directory of Open Access Journals (Sweden)

    Gao Xiao-ling

    2010-12-01

    Full Text Available Abstract Background Rates of caesarean section are progressively increasing in many parts of the world. As a result of psychosocial factors there has been an increasing tendency for pregnant women without justifiable medical indications for caesarean section to ask for this procedure in China. A critical examination of this issue in relation to maternal outcomes is important. At present there are no clinical trials to help assess the risks and benefits of caesarean section in low risk women. To fill the gap left by trials, this indication-matched cohort study was carried out to examine prospectively the outcomes of caesarean section on women with no absolute obstetric indication compared with similar women who had vaginal delivery. Methods An indication-matched cohort study was undertaken to compare maternal outcomes following caesarean section with those undergoing vaginal delivery, in which the two groups were matched for non-absolute indications. 301 nulliparous women with caesarean section were matched successfully with 301 women who delivered vaginally in the Maternal and Children's Hospitals (MCHs in Shanghai, China. Logistic regression model or binomial regression model was used to estimate the relative risk (RR directly. Adjusted RRs were calculated adjusting for propensity score and medical indications. Results The incidence of total complications was 2.2 times higher in the caesarean section group during hospitalization post-partum, compared with the vaginal delivery group (RR = 2.2; 95% CI: 1.1-4.4. The risk of haemorrhage from the start of labour until 2 hours post-partum was significantly higher in the caesarean group (RR = 5.6; 95% CI: 1.2-26.9. The risk of chronic abdominal pain was significantly higher for the caesarean section group (RR = 3.6; 95% CI: 1.2-10.9 than for the vaginal delivery group within 12 months post-partum. The two groups had similar incidences of anaemia and complicating infections such as wound complications

  10. Functional variants of human papillomavirus type 16 demonstrate host genome integration and transcriptional alterations corresponding to their unique cancer epidemiology.

    Science.gov (United States)

    Jackson, Robert; Rosa, Bruce A; Lameiras, Sonia; Cuninghame, Sean; Bernard, Josee; Floriano, Wely B; Lambert, Paul F; Nicolas, Alain; Zehbe, Ingeborg

    2016-11-02

    Human papillomaviruses (HPVs) are a worldwide burden as they are a widespread group of tumour viruses in humans. Having a tropism for mucosal tissues, high-risk HPVs are detected in nearly all cervical cancers. HPV16 is the most common high-risk type but not all women infected with high-risk HPV develop a malignant tumour. Likely relevant, HPV genomes are polymorphic and some HPV16 single nucleotide polymorphisms (SNPs) are under evolutionary constraint instigating variable oncogenicity and immunogenicity in the infected host. To investigate the tumourigenicity of two common HPV16 variants, we used our recently developed, three-dimensional organotypic model reminiscent of the natural HPV infectious cycle and conducted various "omics" and bioinformatics approaches. Based on epidemiological studies we chose to examine the HPV16 Asian-American (AA) and HPV16 European Prototype (EP) variants. They differ by three non-synonymous SNPs in the transforming and virus-encoded E6 oncogene where AAE6 is classified as a high- and EPE6 as a low-risk variant. Remarkably, the high-risk AAE6 variant genome integrated into the host DNA, while the low-risk EPE6 variant genome remained episomal as evidenced by highly sensitive Capt-HPV sequencing. RNA-seq experiments showed that the truncated form of AAE6, integrated in chromosome 5q32, produced a local gene over-expression and a large variety of viral-human fusion transcripts, including long distance spliced transcripts. In addition, differential enrichment of host cell pathways was observed between both HPV16 E6 variant-containing epithelia. Finally, in the high-risk variant, we detected a molecular signature of host chromosomal instability, a common property of cancer cells. We show how naturally occurring SNPs in the HPV16 E6 oncogene cause significant changes in the outcome of HPV infections and subsequent viral and host transcriptome alterations prone to drive carcinogenesis. Host genome instability is closely linked to viral

  11. Swine Influenza/Variant Influenza Viruses

    Science.gov (United States)

    ... Address What's this? Submit What's this? Submit Button Influenza Types Seasonal Avian Swine Variant Other Information on Swine Influenza/Variant Influenza Virus Language: English (US) Español ...

  12. Water aerobics II: maternal body composition and perinatal outcomes after a program for low risk pregnant women

    Directory of Open Access Journals (Sweden)

    Bernardo Ana L

    2009-01-01

    Full Text Available Abstract Background To evaluate the effectiveness and safety of water aerobics during pregnancy. Methods A randomized controlled trial carried out in 71 low-risk sedentary pregnant women, randomly allocated to water aerobics or no physical exercise. Maternal body composition and perinatal outcomes were evaluated. For statistical analysis Chi-square, Fisher's or Student's t-tests were applied. Risk ratios and their 95% CI were estimated for main outcomes. Body composition was evaluated across time using MANOVA or Friedman multiple analysis. Results There were no significant differences between the groups regarding maternal weight gain, BMI or percentage of body fat during pregnancy. Incidence of preterm births (RR = 0.84; 95%CI:0.28–2.53, vaginal births (RR = 1.24; 95%CI:0.73–2.09, low birthweight (RR = 1.30; 95%CI:0.61–2.79 and adequate weight for gestational age (RR = 1.50; 95%CI:0.65–3.48 were also not significantly different between groups. There were no significant differences in systolic and diastolic blood pressure and heart rate between before and immediately after the water aerobics session. Conclusion Water aerobics for sedentary pregnant women proved to be safe and was not associated with any alteration in maternal body composition, type of delivery, preterm birth rate, neonatal well-being or weight.

  13. Psychological Distress in Healthy Low-Risk First-Time Mothers during the Postpartum Period: An Exploratory Study

    Science.gov (United States)

    Carter, Patricia; Price, Larry R.; Champion, Jane Dimmitt; Nichols, Francine

    2017-01-01

    Psychological distress, defined as depression, anxiety, and insomnia in this study, can occur following the birth of a baby as new mothers, in addition to marked physiological changes, are faced with adapting to new roles and responsibilities. We investigated the cooccurrence of stress, depression, anxiety, and insomnia in mothers during the postpartum period; tested the feasibility of study methods and procedures for use in this population; and identified new mothers interest in using cranial electrotherapy stimulation (CES) as an intervention for reducing psychological distress. We recruited healthy, low-risk, English speaking first-time mothers, ages 18–32 years, with healthy babies (N = 33), within 12 months of an uncomplicated birth. Participants completed the PSS, HAM-D14, HAM-A17, and PSQI19. No problems were encountered with study procedures. Mothers reported a high interest (4.9) in the potential use of CES to treat or prevent the occurrence of psychological distress. All participants (N = 33) reported moderate levels of depression and anxiety, while 75.8% (n = 25) reported insomnia. PSS scores were within the norms for healthy women. Further research is recommended to investigate if our findings can be replicated or if different patterns of associations emerge. Implications for clinical practice are addressed. PMID:28191350

  14. Differential Short-Term Repeated Forearm Hyperaemic Reactivity in Coronary Artery Disease Patients Compared to Healthy Low Risk Participants

    Directory of Open Access Journals (Sweden)

    Simon L. Bacon

    2012-01-01

    Full Text Available The hyperaemic response of the forearm is a widely used technique to assess the vascular reactivity. Little is known about the short-term reproducibility and the possible exhaustion of this response in normal or diseased states. As such, the current study was conducted to assess this phenomenon using a unique nuclear medicine- (NM- based technique. 19 patients with coronary artery disease (CAD undergoing NM exercise stress tests and 15 low risk (LR participants completed 2 reactive hyperaemia tests, using a SPECT-based technique, separated by 15  min. Analyses revealed that CAD patients had lower hyperaemic responses than LR participants (P<.001, and that there was a significant group × time interaction (P<.005, such that LR participants showed a larger decrease in the reactivity (5.2±0.4 to 3.6±0.4 than the CAD patients (2.9±0.3 to 2.6±0.3. These results suggest that there is a variability, due to disease states, in the reproducibility of the hypaeremic reactivity. This needs to be taken into account in short-term repeated measure studies.

  15. Psychological Distress in Healthy Low-Risk First-Time Mothers during the Postpartum Period: An Exploratory Study

    Directory of Open Access Journals (Sweden)

    Christina Murphey

    2017-01-01

    Full Text Available Psychological distress, defined as depression, anxiety, and insomnia in this study, can occur following the birth of a baby as new mothers, in addition to marked physiological changes, are faced with adapting to new roles and responsibilities. We investigated the cooccurrence of stress, depression, anxiety, and insomnia in mothers during the postpartum period; tested the feasibility of study methods and procedures for use in this population; and identified new mothers interest in using cranial electrotherapy stimulation (CES as an intervention for reducing psychological distress. We recruited healthy, low-risk, English speaking first-time mothers, ages 18–32 years, with healthy babies (N=33, within 12 months of an uncomplicated birth. Participants completed the PSS, HAM-D14, HAM-A17, and PSQI19. No problems were encountered with study procedures. Mothers reported a high interest (4.9 in the potential use of CES to treat or prevent the occurrence of psychological distress. All participants (N=33 reported moderate levels of depression and anxiety, while 75.8% (n=25 reported insomnia. PSS scores were within the norms for healthy women. Further research is recommended to investigate if our findings can be replicated or if different patterns of associations emerge. Implications for clinical practice are addressed.

  16. Offshore Evidence for an Undocumented Tsunami Event in the 'Low Risk' Gulf of Aqaba-Eilat, Northern Red Sea.

    Directory of Open Access Journals (Sweden)

    Beverly Goodman Tchernov

    Full Text Available Although the Gulf of Aqaba-Eilat is located in the tectonically active northern Red Sea, it has been described as low-risk with regard to tsunami activity because there are no modern records of damaging tsunami events and only one tsunami (1068 AD referred to in historical records. However, this assessment may be poorly informed given that the area was formed by and is located along the seismically active Dead Sea Fault, its population is known to fluctuate in size and literacy in part due to its harsh hyper-arid climate, and there is a dearth of field studies addressing the presence or absence of tsunamigenic deposits. Here we show evidence from two offshore cores for a major paleotsunami that occurred ~2300 years ago with a sedimentological footprint that far exceeds the scarce markers of the historically mentioned 1068 AD event. The interpretation is based on the presence of a laterally continuous and synchronous, anomalous sedimentological deposit that includes allochtonous inclusions and unique structural characteristics. Based on sedimentological parameters, these deposits could not be accounted for by other transport events, or other known background sedimentological processes.

  17. "Active labor" duration and dilation rates among low-risk, nulliparous women with spontaneous labor onset: a systematic review.

    Science.gov (United States)

    Neal, Jeremy L; Lowe, Nancy K; Ahijevych, Karen L; Patrick, Thelma E; Cabbage, Lori A; Corwin, Elizabeth J

    2010-01-01

    Laboring women are often admitted to labor units under criteria that are commonly associated with the onset of active-phase labor (i.e., cervical dilatation of 3-5 cm in the presence of regular contractions). Beginning with these criteria through complete dilatation, this systematic review describes labor duration and cervical dilation rates among low-risk, nulliparous women with spontaneous labor onset. Studies published in English (between 1990 and 2008) were identified via MEDLINE and CINAHL searches. Data were abstracted and weighted "active labor" durations (i.e., from 3-5 cm through complete dilatation) and linear dilation rates were calculated. Eighteen studies (n = 7009) reported mean "active labor" duration. The weighted mean duration was 6.0 hours, and the calculated dilation rate was 1.2 cm per hour. These findings closely parallel those found at the median. At the statistical limits, the weighted "active labor" duration was 13.4 hours (mean + 2 standard deviations) and the dilation rate was 0.6 cm per hour (mean - 2 standard deviations). These findings indicate that nulliparous women with spontaneous labor onset have longer "active" labors and therefore slower dilation rates than are traditionally associated with active labor when commonly used criteria are applied as the starting point. Revision of existing active labor expectations and/or criteria used to prospectively identify active phase onset is warranted. Copyright 2010 American College of Nurse-Midwives. Published by Elsevier Inc. All rights reserved.

  18. Comparison of hepatitis B, core, HBc, and hepatitis B antibody, anti HBs, in a presumed low risk donor population.

    Science.gov (United States)

    Heck, Ellen; Cavanagh, H Dwight

    2014-09-01

    Donors screened by medical social history interview negative for high risk behavior or communicable disease history, but subsequently exhibiting reactive serological markers, emphasize importance of duel safe guarding factors for determining donor suitability. This report examines a relationship between two immunoabsorption assay tests, hepatitis B core (HBc) antibody, a required food and drug administration (FDA) test, and hepatitis B antibody (anti HBs), non-required test. Reactive serology results, 129 cases, 3,581 donors (2008-2012) for HBc as the only initially positive serological marker were subjected to anti HBs testing in this history pre-screened donor population. Enzyme linked immunoabsorption assay kits hepatitis B, core and antibody, were used in this study. All samples were initially tested for human immunodeficiency virus, hepatitis B, and hepatitis C, utilizing nucleic acid testing and antigen antibody immunoabsorption assay. Testing was performed by a FDA-registered CLEA-certified reference laboratory. Samples were deceased donor blood samples and a limited number of pre-mortem samples, separated, stored and analyzed according to manufacturer recommendation and FDA regulations. 129 reactive HBc only samples, were subsequently tested for anti HBs. Of these 129, 94 were found to be reactive for anti HBs. This represented 72 % of samples tested for antibody, a higher percentage than anticipated for a medical history negative, low risk population.

  19. Costs and effects of screening and treating low risk women with a singleton pregnancy for asymptomatic bacteriuria, the ASB study.

    Science.gov (United States)

    Kazemier, Brenda M; Schneeberger, Caroline; De Miranda, Esteriek; Van Wassenaer, Aleid; Bossuyt, Patrick M; Vogelvang, Tatjana E; Reijnders, Frans J L; Delemarre, Friso M C; Verhoeven, Corine J M; Oudijk, Martijn A; Van Der Ven, Jeanine A; Kuiper, Petra N; Feiertag, Nicolette; Ott, Alewijn; De Groot, Christianne J M; Mol, Ben Willem J; Geerlings, Suzanne E

    2012-06-21

    The prevalence of asymptomatic bacteriuria (ASB) in pregnancy is 2-10% and is associated with both maternal and neonatal adverse outcomes as pyelonephritis and preterm delivery. Antibiotic treatment is reported to decrease these adverse outcomes although the existing evidence is of poor quality. We plan a combined screen and treat study in women with a singleton pregnancy. We will screen women between 16 and 22 weeks of gestation for ASB using the urine dipslide technique. The dipslide is considered positive when colony concentration ≥105 colony forming units (CFU)/mL of a single microorganism or two different colonies but one ≥105 CFU/mL is found, or when Group B Streptococcus bacteriuria is found in any colony concentration. Women with a positive dipslide will be randomly allocated to receive nitrofurantoin or placebo 100 mg twice a day for 5 consecutive days (double blind). Primary outcomes of this trial are maternal pyelonephritis and/or preterm delivery before 34 weeks. Secondary outcomes are neonatal and maternal morbidity, neonatal weight, time to delivery, preterm delivery rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal admission days and costs. This trial will provide evidence for the benefit and cost-effectiveness of dipslide screening for ASB among low risk women at 16-22 weeks of pregnancy and subsequent nitrofurantoin treatment. Dutch trial registry: NTR-3068.

  20. Trichomonas vaginalis infection in a low-risk women attended in Obstetrics and Gynaecology Clinic, Universiti Kebangsaan Malaysia Medical Centre

    Institute of Scientific and Technical Information of China (English)

    Norhayati Moktar; Nor Liyana Ismail; Phoy Cheng Chun; Mohamad Asyrab Sapie; Nor Farahin Abdul Kahar; Yusof Suboh; Noraina Abdul Rahim; Nor Azlin Mohamed Ismail; Tengku Shahrul Anuar

    2016-01-01

    Objective: To investigate the presence of trichomoniasis among women attending the Obstetrics and Gynaecology Clinic, Universiti Kebangsaan Malaysia Medical Centre.Methods: A total of 139 high vaginal swabs were taken from the subjects and sent to the laboratory in Amies gel transport media. The specimens were examined for the presence of Trichomonas vaginalis using wet mount, Giemsa staining and cultured in Diamond’s medium. Sociodemographic characteristics and gynaecological complaints were obtained in private using structured questionnaire applied by one investigator.Results: The median age was 32 years, with an interquartile interval of 9.96. Most of the subjects were Malays(76.9%) and the remaining were Chinese(15.1%), Indians(2.2%)and other ethnic groups(5.8%). One hundred and thirty eight(99.3%) of the women were married and 98.6% had less than 6 children. More than half(75.5%) of the women’s last child birth was less than 6 years ago. Forty seven percent of them were involved in supporting administrative work and 64.7% of the women gave a history of previous or current vaginal discharge.Conclusions: The present study reported zero incidence rate of trichomoniasis. The low incidence rate was postulated due to all women who participated in this study were categorized into a low-risk group.

  1. Trichomonas vaginalis infection in a low-risk women attended in Obstetrics and Gynaecology Clinic, Universiti Kebangsaan Malaysia Medical Centre

    Institute of Scientific and Technical Information of China (English)

    Norhayati Moktar; Nor Liyana Ismail; Phoy Cheng Chun; Mohamad Asyrab Sapie; Nor Farahin Abdul Kahar; Yusof Suboh; Noraina Abdul Rahim; Nor Azlin Mohamed Ismail; Tengku Shahrul Anuar

    2016-01-01

    Objective: To investigate the presence of trichomoniasis among women attending the Obstetrics and Gynaecology Clinic, Universiti Kebangsaan Malaysia Medical Centre. Methods: A total of 139 high vaginal swabs were taken from the subjects and sent to the laboratory in Amies gel transport media. The specimens were examined for the presence of Trichomonas vaginalis using wet mount, Giemsa staining and cultured in Diamond's medium. Sociodemographic characteristics and gynaecological complaints were obtained in private using structured questionnaire applied by one investigator. Results: The median age was 32 years, with an interquartile interval of 9.96. Most of the subjects were Malays (76.9%) and the remaining were Chinese (15.1%), Indians (2.2%) and other ethnic groups (5.8%). One hundred and thirty eight (99.3%) of the women were married and 98.6%had less than 6 children. More than half (75.5%) of the women's last child birth was less than 6 years ago. Forty seven percent of them were involved in supporting administrative work and 64.7% of the women gave a history of previous or current vaginal discharge. Conclusions: The present study reported zero incidence rate of trichomoniasis. The low incidence rate was postulated due to all women who participated in this study were categorized into a low-risk group.

  2. Mycophenolate mofetil in low-risk renal transplantation in patients receiving no cyclosporine: a single-centre experience.

    LENUS (Irish Health Repository)

    Raheem, Omer A

    2011-05-28

    BACKGROUND: We assess our long-term experience with regards the safety and efficacy of Mycophenolate Mofetil (MMF) in our low risk renal transplant population and compared it retrospectively to Azathioprine (AZA) immunosuppressive regimen. Patients and methods. Between January 1999 and December 2005, 240 renal transplants received MMF as part of their immunosuppressive protocol (MMF group). AZA group of 135 renal transplants was included for comparative analysis (AZA group). Patients received Cyclosporine was excluded from this study. RESULTS: The incidence of biopsy proven 3-month acute rejections was 30 (12.5%) in MMF group and 22 (16%) in AZA group respectively (P = 0.307). Patient survival rates at 1 and 5 years for the MMF group were 97 and 94%, respectively, compared to 100% and 91% at 1 and 5 years respectively for the AZA group (P = 0.61). Graft survival rates at 1 and 5 years for the MMF group were 95 and 83%, respectively, compared to 97 and 84% at 1 and 5 years, respectively for the AZA group (P = 0.62). CONCLUSION: There was no difference in acute rejection episodes between MMF and AZA based immunotherapy. Additionally, we observed no significant difference concerning graft survival in the MMF group when compared to AZA group.

  3. Mycophenolate mofetil in low-risk renal transplantation in patients receiving no cyclosporine: a single-centre experience.

    LENUS (Irish Health Repository)

    2012-02-01

    BACKGROUND: We assess our long-term experience with regards the safety and efficacy of Mycophenolate Mofetil (MMF) in our low risk renal transplant population and compared it retrospectively to Azathioprine (AZA) immunosuppressive regimen. Patients and methods. Between January 1999 and December 2005, 240 renal transplants received MMF as part of their immunosuppressive protocol (MMF group). AZA group of 135 renal transplants was included for comparative analysis (AZA group). Patients received Cyclosporine was excluded from this study. RESULTS: The incidence of biopsy proven 3-month acute rejections was 30 (12.5%) in MMF group and 22 (16%) in AZA group respectively (P = 0.307). Patient survival rates at 1 and 5 years for the MMF group were 97 and 94%, respectively, compared to 100% and 91% at 1 and 5 years respectively for the AZA group (P = 0.61). Graft survival rates at 1 and 5 years for the MMF group were 95 and 83%, respectively, compared to 97 and 84% at 1 and 5 years, respectively for the AZA group (P = 0.62). CONCLUSION: There was no difference in acute rejection episodes between MMF and AZA based immunotherapy. Additionally, we observed no significant difference concerning graft survival in the MMF group when compared to AZA group.

  4. Mycophenolate mofetil in low-risk renal transplantation in patients receiving no cyclosporine: a single-centre experience.

    Science.gov (United States)

    Raheem, Omer A; Daly, Padraig J; O'Kelly, Patrick; Shields, William P; Zimmerman, Antonio J; Mohan, Ponnusamy; Power, Richard; Little, Dilly M; Conlon, Peter J; Hickey, David P

    2012-02-01

    We assess our long-term experience with regards the safety and efficacy of Mycophenolate Mofetil (MMF) in our low risk renal transplant population and compared it retrospectively to Azathioprine (AZA) immunosuppressive regimen. Patients and methods. Between January 1999 and December 2005, 240 renal transplants received MMF as part of their immunosuppressive protocol (MMF group). AZA group of 135 renal transplants was included for comparative analysis (AZA group). Patients received Cyclosporine was excluded from this study. The incidence of biopsy proven 3-month acute rejections was 30 (12.5%) in MMF group and 22 (16%) in AZA group respectively (P = 0.307). Patient survival rates at 1 and 5 years for the MMF group were 97 and 94%, respectively, compared to 100% and 91% at 1 and 5 years respectively for the AZA group (P = 0.61). Graft survival rates at 1 and 5 years for the MMF group were 95 and 83%, respectively, compared to 97 and 84% at 1 and 5 years, respectively for the AZA group (P = 0.62). There was no difference in acute rejection episodes between MMF and AZA based immunotherapy. Additionally, we observed no significant difference concerning graft survival in the MMF group when compared to AZA group.

  5. Costs and effects of screening and treating low risk women with a singleton pregnancy for asymptomatic bacteriuria, the ASB study

    Directory of Open Access Journals (Sweden)

    Kazemier Brenda M

    2012-06-01

    Full Text Available Abstract Background The prevalence of asymptomatic bacteriuria (ASB in pregnancy is 2-10% and is associated with both maternal and neonatal adverse outcomes as pyelonephritis and preterm delivery. Antibiotic treatment is reported to decrease these adverse outcomes although the existing evidence is of poor quality. Methods/Design We plan a combined screen and treat study in women with a singleton pregnancy. We will screen women between 16 and 22 weeks of gestation for ASB using the urine dipslide technique. The dipslide is considered positive when colony concentration ≥105 colony forming units (CFU/mL of a single microorganism or two different colonies but one ≥105 CFU/mL is found, or when Group B Streptococcus bacteriuria is found in any colony concentration. Women with a positive dipslide will be randomly allocated to receive nitrofurantoin or placebo 100 mg twice a day for 5 consecutive days (double blind. Primary outcomes of this trial are maternal pyelonephritis and/or preterm delivery before 34 weeks. Secondary outcomes are neonatal and maternal morbidity, neonatal weight, time to delivery, preterm delivery rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal admission days and costs. Discussion This trial will provide evidence for the benefit and cost-effectiveness of dipslide screening for ASB among low risk women at 16–22 weeks of pregnancy and subsequent nitrofurantoin treatment. Trial registration Dutch trial registry: NTR-3068

  6. Resistance of Abaca Somaclonal Variant Against Fusarium

    OpenAIRE

    RULLY DYAH PURWATI; SUDARSONO

    2007-01-01

    The objectives of this study were (i) to evaluate responses against F. oxysporum f.sp. cubense (Foc) infection of abaca variants regenerated using four different methods, (ii) to determine initial root length and plant height effects on survival of inoculated abaca variants, and (iii) to identify Foc resistance abaca variants. In the previous experiment, four abaca variant lines were regenerated from (i) embryogenic calli (TC line), (ii) ethyl methyl sulphonate (EMS) treated embryogenic calli...

  7. Variant Humicola grisea CBH1.1

    Energy Technology Data Exchange (ETDEWEB)

    Goedegebuur, Frits; Gualfetti, Peter; Mitchinson, Colin; Larenas, Edmund

    2017-05-09

    Disclosed are variants of Humicola grisea CeI7A (CBH1.1), H. jecorina CBH1 variant or S. thermophilium CBH1, nucleic acids encoding the same and methods for producing the same. The variant cellulases have the amino acid sequence of a glycosyl hydrolase of family 7A wherein one or more amino acid residues are substituted.

  8. DHAD variants and methods of screening

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, Kristen J.; Ye, Rick W.

    2017-02-28

    Methods of screening for dihydroxy-acid dehydratase (DHAD) variants that display increased DHAD activity are disclosed, along with DHAD variants identified by these methods. Such enzymes can result in increased production of compounds from DHAD requiring biosynthetic pathways. Also disclosed are isolated nucleic acids encoding the DHAD variants, recombinant host cells comprising the isolated nucleic acid molecules, and methods of producing butanol.

  9. Clinical variants of lichen planus.

    Science.gov (United States)

    Wagner, Gunnar; Rose, Christian; Sachse, Michael Max

    2013-04-01

    Lichen planus is characterized by lichenoid, polygonal papules with fine white lines, called Wickham striae. Lesions most commonly occur on the limbs and on the dorsal aspect of the trunk. At the same time often leukoplakia of mucous membranes as well as nail disorders are seen. There are numerous variants of lichen planus which can be distinguished from the classical form on the basis of morphology and distribution of the lesions. The typical primary lesion of lichen planus may be replaced by other forms, such as patches, hyperkeratoses, ulcerations, or bullous lesions. Moreover, distribution patterns of these lesions may vary and include erythrodermic, inverse or linear arrangements. In contrast to these numerous clinical features, histologic findings remain characteristic in the variants, so that the diagnosis can be made securely. Differential diagnoses of lichen planus include diverse dermatoses such as bullous pemphigoid or paronychia.

  10. Coronary artery anatomy and variants

    Energy Technology Data Exchange (ETDEWEB)

    Malago, Roberto; Pezzato, Andrea; Barbiani, Camilla; Alfonsi, Ugolino; Nicoli, Lisa; Caliari, Giuliana; Pozzi Mucelli, Roberto [Policlinico G.B. Rossi, University of Verona, Department of Radiology, Verona (Italy)

    2011-12-15

    Variants and congenital anomalies of the coronary arteries are usually asymptomatic, but may present with severe chest pain or cardiac arrest. The introduction of multidetector CT coronary angiography (MDCT-CA) allows the detection of significant coronary artery stenosis. Improved performance with isotropic spatial resolution and higher temporal resolution provides a valid alternative to conventional coronary angiography (CCA) in many patients. MDCT-CA is now considered the ideal tool for three-dimensional visualization of the complex and tortuous anatomy of the coronary arteries. With multiplanar and volume-rendered reconstructions, MDCT-CA may even outperform CCA in determining the relative position of vessels, thus providing a better view of the coronary vascular anatomy. The purpose of this review is to describe the normal anatomy of the coronary arteries and their main variants based on MDCT-CA with appropriate reconstructions. (orig.)

  11. [Mirizzi syndrome and its variants].

    Science.gov (United States)

    Meyer, G J; Runge, D; Gebhardt, J

    1990-04-01

    Between 1981 and 1987 5434 patients were studied by ERCP in Allgemeines Krankenhaus Hamburg-Barmbeck. 26 (i.e. 0.43%) suffered from Mirizze syndrome with the triad of cholelithiasis, cholecystitis and obstructive biliary disease. They were classified in four different types according to the variable localisation and origin of the biliary obstruction. 16 patients corresponded to the classical type (I and II) with compression, penetration, and obturation by the concrement, five patients matched borderline with infiltration (III) and five patients were classified as variants of this syndrome. A mild elevation of serum bilirubine and alkaline phosphatase indicated more likely the benign etiology of type I to III, however, a marked elevation of alkaline phosphatase in the variants suggested more likely a malignant underlying disease. The diagnosis was ascertained in all cases by ERC and sonography preoperatively and was verified by laparotomy (n = 18) and follow-up (n = 6).

  12. Variants of lumbosacral elastic band.

    Directory of Open Access Journals (Sweden)

    Carlos Cesar Santín Alfaro

    2011-06-01

    Full Text Available It is made an intervention research, qualitative and quantitative of two variants of lumbosacral elastic bands used in Provincial Laboratory of Technical Orthopedics in Sancti Spiritus Province, taking into account the high demand for this device and that the laboratory do not often count with the raw material needed for the original lumbosacral belt made by denim cloth which is the conventional belt. The main goal of this research is to explain the technological process and to compare the cost of production of both elastic variants with lumbosacral belt made by cloth which are offer to patients who look for this service , giving them a rapid solution so that they can feel comfortable.

  13. Unusual variant of Cantrell's pentalogy?

    OpenAIRE

    Kumar, Basant; Sharma, S.B.; Kandpal, Deepak K.; Agrawal, L. D.

    2008-01-01

    A 12-hour-old male infant presented with prolapsed abdominal content through a defect on left side of chest wall with respiratory distress. A thorough clinical examination suggested absence of ectopia cordis, abdominal wall defect, and any bony anomaly. The child expired after 6 hours of admission because of respiratory distress and electrolyte imbalance. Is congenital defect of chest wall associated with diaphragmatic hernia without ectopia cordis and omphalocele, an unusual variant of Cantr...

  14. Dorsal variant blister aneurysm repair.

    Science.gov (United States)

    Couldwell, William T; Chamoun, Roukoz

    2012-01-01

    Dorsal variant proximal carotid blister aneurysms are treacherous lesions to manage. It is important to recognize this variant on preoperative angiographic imaging, in anticipation of surgical strategies for their treatment. Strategies include trapping the involved segment and revascularization if necessary. Other options include repair of the aneurysm rupture site directly. Given that these are not true berry aneurysms, repair of the rupture site involves wrapping or clip-grafting techniques. The case presented here was a young woman with a subarachnoid hemorrhage from a ruptured dorsal variant blister aneurysm. The technique used is demonstrated in the video and is a modified clip-wrap technique using woven polyester graft material. The patient was given aspirin preoperatively as preparation for the clip-wrap technique. It is the authors' current protocol to attempt a direct repair with clip-wrapping and leaving artery sacrifice with or without bypass as a salvage therapy if direct repair is not possible. Assessment of vessel patency after repair is performed by intraoperative Doppler and indocyanine green angiography. Intraoperative somatosensory and motor evoked potential monitoring is performed in all cases. The video can be found here: http://youtu.be/crUreWGQdGo.

  15. Microcystic Variant of Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Anthony Kodzo-Grey Venyo

    2013-01-01

    Full Text Available Background. Microcystic variant of urothelial carcinoma is one of the new variants of urothelial carcinoma that was added to the WHO classification in 2004. Aims. To review the literature on microcystic variant of urothelial carcinoma. Methods. Various internet search engines were used to identify reported cases of the tumour. Results. Microscopic features of the tumour include: (i Conspicuous intracellular and intercellular lumina/microcysts encompassed by malignant urothelial or squamous cells. (ii The lumina are usually empty; may contain granular eosinophilic debris, mucin, or necrotic cells. (iii The cysts may be variable in size; round, or oval, up to 2 mm; lined by urothelium which are either flattened cells or low columnar cells however, they do not contain colonic epithelium or goblet cells; are infiltrative; invade the muscularis propria; mimic cystitis cystica and cystitis glandularis; occasionally exhibit neuroendocrine differentiation. (iv Elongated and irregular branching spaces are usually seen. About 17 cases of the tumour have been reported with only 2 patients who have survived. The tumour tends to be of high-grade and high-stage. There is no consensus opinion on the best option of treatment of the tumour. Conclusions. It would prove difficult at the moment to be dogmatic regarding its prognosis but it is a highly aggressive tumour. New cases of the tumour should be reported in order to document its biological behaviour.

  16. Plasma IL-8 and IL-6 levels can be used to define a group with low risk of septicaemia among cancer patients with fever and neutropenia

    NARCIS (Netherlands)

    de Bont, ESJM; Vellenga, E; Swaanenburg, JCJM; Fidler, [No Value; Visser-van Brummen, PJ; Kamps, WA

    1999-01-01

    The standard therapy for patients with fever and chemotherapy-related neutropenia is hospitalization and infusion of broad-spectrum antibiotics. Early discharge of a defined group of patients at low risk for septicaemia would be of great advantage for these patients. Ih this study plasma

  17. Predictive value of general movements' quality in low-risk infants for minor neurological dysfunction and behavioural problems at preschool age

    NARCIS (Netherlands)

    Bennema, Anne N; Schendelaar, Pamela; Seggers, Jorien; Haadsma, Maaike L; Heineman, Maas Jan; Hadders-Algra, Mijna

    2016-01-01

    BACKGROUND: General movement (GM) assessment is a well-established tool to predict cerebral palsy in high-risk infants. Little is known on the predictive value of GM assessment in low-risk populations. AIMS: To assess the predictive value of GM quality in early infancy for the development of the cli

  18. Ultrasound assessment of placental function: the effectiveness of placental biometry in a low-risk population as a predictor of a small for gestational age neonate.

    LENUS (Irish Health Repository)

    McGinty, Patricia

    2012-07-01

    The aims of the study were to establish reference ranges for placental length and thickness in a low-risk obstetric population and to assess the likelihood of a small for gestational age (SGA) neonate on the basis of placental length at 18-24 weeks\\' gestation.

  19. Four-group classification of left ventricular hypertrophy based on ventricular concentricity and dilatation identifies a low-risk subset of eccentric hypertrophy in hypertensive patients

    DEFF Research Database (Denmark)

    Bang, Casper N; Gerdts, Eva; Aurigemma, Gerard P

    2014-01-01

    with relatively mild LVH without either increased LV volume or concentricity have similar risk of all-cause mortality or cardiovascular events because hypertensive patients with normal LVM seem to be a low-risk group. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00338260....

  20. Plasma IL-8 and IL-6 levels can be used to define a group with low risk of septicaemia among cancer patients with fever and neutropenia

    NARCIS (Netherlands)

    de Bont, ESJM; Vellenga, E; Swaanenburg, JCJM; Fidler, [No Value; Visser-van Brummen, PJ; Kamps, WA

    1999-01-01

    The standard therapy for patients with fever and chemotherapy-related neutropenia is hospitalization and infusion of broad-spectrum antibiotics. Early discharge of a defined group of patients at low risk for septicaemia would be of great advantage for these patients. Ih this study plasma interleukin

  1. Cost-effectiveness of adjuvant systemic therapy in low-risk breast cancer patients with nodal isolated tumor cells or micrometastases

    NARCIS (Netherlands)

    Boer, M. de; Adang, E.M.M.; Dycke, K.C.G. van; Dijck, J.A.A.M. van; Borm, G.F.; Seferina, S.C.; Deurzen, C.H. van; Diest, P.J. van; Bult, P.; Donders, A.R.T.; Tjan-Heijnen, V.C.

    2012-01-01

    BACKGROUND: The cost-effectiveness of adjuvant systemic therapy in patients with low-risk breast cancer and nodal isolated tumor cells or micrometastases is unknown. PATIENTS AND METHODS: A cost-effectiveness analysis of adjuvant systemic therapy was carried out using the costs per 1% event

  2. The Mother-Infant Feeding Relationship across the First Year and the Development of Feeding Difficulties in Low-Risk Premature Infants

    Science.gov (United States)

    Silberstein, Dalia; Feldman, Ruth; Gardner, Judith M.; Karmel, Bernard Z.; Kuint, Jacob; Geva, Ronny

    2009-01-01

    Although feeding problems are common during infancy and are typically accompanied by relational difficulties, little research observed the mother-infant feeding relationship across the first year as an antecedent to the development of feeding difficulties. We followed 76 low-risk premature infants and their mothers from the transition to oral…

  3. Predictive value of general movements' quality in low-risk infants for minor neurological dysfunction and behavioural problems at preschool age

    NARCIS (Netherlands)

    Bennema, Anne N; Schendelaar, Pamela; Seggers, Jorien; Haadsma, Maaike L; Heineman, Maas Jan; Hadders-Algra, Mijna

    2016-01-01

    Background: General movement (GM) assessment is a well-established tool to predict cerebral palsy in high-risk infants. Little is known on the predictive value of GM assessment in low-risk populations. Aims: To assess the predictive value of GM quality in early infancy for the development of the cli

  4. Perinatal and maternal outcomes by planned place of birth for healthy women with low risk pregnancies: the Birthplace in England national prospective cohort study.

    NARCIS (Netherlands)

    Brocklehurst, P.; Kwee, A.; Birthplace in England Collaborative Group

    2011-01-01

    Objective: To compare perinatal outcomes, maternal outcomes, and interventions in labour by planned place of birth at the start of care in labour for women with low risk pregnancies. Design: Prospective cohort study. Setting: England: all NHS trusts providing intrapartum care at home, all freestandi

  5. Left Visual Field Biases when Infants Process Faces: A Comparison of Infants at High- and Low-Risk for Autism Spectrum Disorder

    Science.gov (United States)

    Dundas, Eva; Gastgeb, Holly; Strauss, Mark S.

    2012-01-01

    While it is well-known that individuals with autism spectrum disorder (ASD) have difficulties processing faces, very little is known about the origins of these deficits. The current study focused on 6- and 11-month-old infants who were at either high-risk (n = 43) or low-risk (n = 31) for developing ASD based on having a sibling already diagnosed…

  6. An observational study of the success and complications of 2546 external cephalic versions in low-risk pregnant women performed by trained midwives

    NARCIS (Netherlands)

    Beuckens, A.; Rijnders, M.; Verburgt-Doeleman, G.H.M.; Rijninks-van Driel, G.C.; Thorpe, J.; Huttom, E.K.

    2016-01-01

    Objective To evaluate the success of an external cephalic version (ECV) training programme, and to determine the rates of successful ECV, complications, and caesarean birth in a low-risk population. Design Prospective observational study. Setting Primary health care and hospital settings throughout

  7. Application of the MASCC and CISNE Risk-Stratification Scores to Identify Low-Risk Febrile Neutropenic Patients in the Emergency Department.

    Science.gov (United States)

    Coyne, Christopher J; Le, Vivian; Brennan, Jesse J; Castillo, Edward M; Shatsky, Rebecca A; Ferran, Karen; Brodine, Stephanie; Vilke, Gary M

    2017-06-01

    Although validated risk-stratification tools have been used to send low-risk febrile neutropenic patients home from clinic and inpatient settings, there is a dearth of research evaluating these scores in the emergency department (ED). We compare the predictive accuracy of the Multinational Association for Supportive Care in Cancer (MASCC) and Clinical Index of Stable Febrile Neutropenia (CISNE) scores for patients with chemotherapy-induced febrile neutropenia and presenting to the ED. We conducted a retrospective cohort study to evaluate all patients with febrile neutropenia (temperature ≥38°C [100.4°F], absolute neutrophil count identified 53 (23%) of these patients as low risk and was highly specific in the identification of a low-risk cohort for all outcome variables (98.3% specific, 95% confidence interval [CI] 89.7% to 99.9%; positive predictive value 98.1%, 95% CI 88.6% to 99.9%). Median length of stay was shorter for low-risk versus high-risk CISNE patients (3-day difference; Prisk cohort. Our results suggest that the CISNE score may be the most appropriate febrile neutropenia risk-stratification tool for use in the ED. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  8. Effect of rosuvastatin on the echolucency of the common carotid intima-media in low-risk individuals: the METEOR trial

    NARCIS (Netherlands)

    Lind, L.; Peters, S.A.; Ruijter, H.M. Den; Palmer, M.K.; Grobbee, D.E.; Crouse, J.R.; O'Leary, D.H.; Evans, G.W.; Raichlen, J.S.; Bots, M.L.; Goldstein, M.; Staessen, J.A.; Marchal, G.; Linhart, A.; Salonen, J.T.; Simon, A.

    2012-01-01

    BACKGROUND: The echolucency of the carotid intima-media is related to increased cardiovascular risk factor levels, morbidity, and mortality. The aim of this study was to assess the effect of statins on the echolucency of the common carotid intima-media in a low-risk population. METHODS: Data from th

  9. Long-Term Outcomes From a Prospective Trial of Stereotactic Body Radiotherapy for Low-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    King, Christopher R., E-mail: crking@mednet.ucla.edu [Departments of Radiation Oncology and Urology, University of California Los Angeles School of Medicine, Los Angeles, CA (United States); Brooks, James D.; Gill, Harcharan; Presti, Joseph C. [Department of Urology, Stanford University School of Medicine, Stanford, CA (United States)

    2012-02-01

    Purpose: Hypofractionated radiotherapy has an intrinsically different normal tissue and tumor radiobiology. The results of a prospective trial of stereotactic body radiotherapy (SBRT) for prostate cancer with long-term patient-reported toxicity and tumor control rates are presented. Methods and Materials: From 2003 through 2009, 67 patients with clinically localized low-risk prostate cancer were enrolled. Treatment consisted of 36.25 Gy in 5 fractions using SBRT with the CyberKnife as the delivery technology. No patient received hormone therapy. Patient self-reported bladder and rectal toxicities were graded on the Radiation Therapy Oncology Group scale (RTOG). Results: Median follow-up was 2.7 years. There were no grade 4 toxicities. Radiation Therapy Oncology Group Grade 3, 2, and 1 bladder toxicities were seen in 3% (2 patients), 5% (3 patients), and 23% (13 patients) respectively. Dysuria exacerbated by urologic instrumentation accounted for both patients with Grade 3 toxicity. Urinary incontinence, complete obstruction, or persistent hematuria was not observed. Rectal Grade 3, 2, and 1 toxicities were seen in 0, 2% (1 patient), and 12.5% (7 patients), respectively. Persistent rectal bleeding was not observed. Low-grade toxicities were substantially less frequent with QOD vs. QD dose regimen (p = 0.001 for gastrointestinal and p = 0.007 for genitourinary). There were two prostate-specific antigen (PSA), biopsy-proven failures with negative metastatic workup. Median PSA at follow-up was 0.5 {+-} 0.72 ng/mL. The 4-year Kaplan-Meier PSA relapse-free survival was 94% (95% confidence interval, 85%-102%). Conclusion: Significant late bladder and rectal toxicities from SBRT for prostate cancer are infrequent. PSA relapse-free survival compares favorably with other definitive treatments. The current evidence supports consideration of stereotactic body radiotherapy among the therapeutic options for localized prostate cancer.

  10. Distribution of high and low risk HPV types by cytological status: a population based study from Italy

    Directory of Open Access Journals (Sweden)

    Pini Maria T

    2011-01-01

    Full Text Available Abstract Background HPV type distribution by cytological status represents useful information to predict the impact of mass vaccination on screening programs. Methods women aged from 25 to 64 who attended cervical cancer screening in five different Italian regions were tested for HPV infection with Hybrid Capture II (HCII low and high risk probes. Women repeating Pap-test upon unsatisfactory or positive results, or as a post-treatment and post-colposcopy follow-up analysis, were excluded from our study. High risk (HR HPV positive samples were typed using GP5+/GP6+ primed PCR, followed by Reverse Line Blot for 18 high/intermediate risk HPV types, while low risk (LR HPV positive samples were tested with type specific primers for HPV6 and HPV11. Results 3410 women had a valid HCII and Pap-test. The prevalence of HR and LR infections was 7.0% and 3.6%, 29.1% and 13.7%, 68.1% and 31.9%, 60.0% and 0.0%, 65.0% and 12.0%, for negative, ASC-US, L-SIL, ASC-H and H-SIL cytology, respectively. The fraction of ASC-US+ cytology due to HPV 16 and 18 ranged from 11.2 (HPV 16/18 alone to 15.4% (including HPV 16/18 in co-infection with other virus strains, and that due to HPV 6 and 11 ranged from 0.2% (HPV 6/11 alone to 0.7% (including HPV 6/11 in co-infection with other LR virus strains. Conclusions mass vaccination with bivalent or quadrivalent HPV vaccine would modestly impact on prevalence of abnormal Pap-test in screening.

  11. Can perineural invasion detected in prostate needle biopsy specimens predict surgical margin positivity in D’Amico low risk patients?

    Directory of Open Access Journals (Sweden)

    Ozgur Haki Yuksel

    2016-07-01

    Full Text Available Objectives: In this study, our aim was to estimate the value of perineural invasion (PNI in prostate needle biopsy (PNB specimens in the prediction of surgical margin positivity (SMP and its prognostic significance (upgrade Gleason Score in patients who had undergone radical retropubic prostatectomy (RRP with low risk prostate cancer according to D’Amico risk assessment. Materials and Methods: We retrospectively analyzed the data of 65 patients who were diagnosed as clinical stage T1c prostate cancer (PC and underwent RRP between January 2010 and June 2013. Pathological specimens of PNB and RRP were separately examined for the parameters of PNI, vascular invasion (VI, Gleason Score (GS and SMP. Results: The patients’ mean age was 63.65 ± 4.93 (range 47- 75 years. PNI in PNB specimens were identified in 12 of 65 patients and 11 of 12 patients showed SMP on RRP specimens. While 53 of 65 patients had not PNI on PNB, only 11 of them demonstrated SMP on RRP specimens. SMP was 30.64-fold more frequently encountered in PNB specimens obtained from PNI-positive patients relative to PNI-negative patients. In our study, PNI detected in PNB specimens was statistically significantly associated with SMP on RRP specimens (P = 0.0001. Conclusion: It is well known that higher PSA values and GS were independent predictors of SMP in clinically localized prostate cancer (CLPC. We think that PNI in PNB specimens may be a useful prognostic factor for predicting SMP in cases with CLPC.

  12. Can Single Positive Core Prostate Cancer at biopsy be Considered a Low-Risk Disease after Radical Prostatectomy?

    Directory of Open Access Journals (Sweden)

    Ricardo Kupka da Silva

    2013-12-01

    Full Text Available Purpose Single positive core in a prostate biopsy is usually associated with indolent prostate cancer (PCa and is one of the active surveillance (AS inclusion criteria. We investigated whether single positive core PCa at biopsy could define an archetype of low-risk disease. Materials and Methods A total of 1320 consecutive patients were enrolled. Among them, 249 patients with single positive core PCa were followed up, and the clinical and pathological parameters influencing prognosis were analyzed. Results Out of the 249 patients, 172 (69.0% had pathological findings ≥ pT2c and 87 (34.9% had an undergraded Gleason Score (GS based on the biopsy. Positive surgical margins (PSMs, extraprostatic extension (EPE and seminal vesicle invasion (SVI were found in 20.8%, 10.0% and 6.0% of patients, respectively. In a comparative analysis, we found that the PSA level, prostate weight and number of cores at biopsy are essential to correctly predict an indolent PCa. A total of 125 patients (67.3% with nonpalpable tumors became high-risk tumors (pT2c-T3. Analyzing only nonpalpable tumors with a GS of 6 at biopsy (156 patients, we noted that 106 (67.9% of cT1 progressed from cT1c to pT2c-pT3. Conclusions Single core PCa have clinically significant disease in the Radical Prostatectomy specimens, with considerable rates of overgrading for the GS, pT2c-pT3, PSMs, EPE and SVI. The treatment plan must be evaluated individually for patients with single core PCa and must take into account other prognostic factors when determining whether a patient should be managed with AS.

  13. SERIAL NECK ULTRASOUND IS MORE LIKELY TO IDENTIFY FALSE-POSITIVE ABNORMALITIES THAN CLINICALLY SIGNIFICANT DISEASE IN LOW-RISK PAPILLARY THYROID CANCER PATIENTS.

    Science.gov (United States)

    Yang, Samantha Peiling; Bach, Ariadne M; Tuttle, R Michael; Fish, Stephanie A

    2015-12-01

    American Thyroid Association (ATA) low-risk papillary thyroid cancer (PTC) patients without structural evidence of disease on initial posttreatment evaluation have a low risk of recurrence. Despite this, most patients undergo frequent surveillance neck ultrasound (US). The objective of the study was to evaluate the clinical utility of routine neck US in ATA low-risk PTC patients with no structural evidence of disease after their initial thyroid surgery. We performed a retrospective review of 171 ATA low-risk PTC patients after total thyroidectomy, with or without radioactive iodine (RAI) ablation, who had a neck US without suspicious findings after therapy. The main outcome measure was a comparison of the frequency of finding false-positive US abnormalities and the frequency of identifying structural disease recurrence. Over a median follow-up of 8 years, 171 patients underwent a median of 5 neck US (range 2-17). Structural recurrence with low-volume disease (≤1 cm) was identified in 1.2% (2/171) of patients at a median of 2.8 years (range 1.6-4.1 years) after their initial diagnosis. Recurrence was associated with rising serum thyroglobulin (Tg) level in 1 of the 2 patients and was detected without signs of biochemical recurrence in the other patient. Conversely, false-positive US abnormalities were identified in 67% (114/171) of patients after therapy, leading to additional testing without identifying clinically significant disease. In ATA low-risk patients without structural evidence of disease on initial surveillance evaluation, routine screening US is substantially more likely to identify false-positive results than clinically significant structural disease recurrence.

  14. Outpatient treatment of low-risk venous thromboembolism with monotherapy oral anticoagulation: patient quality of life outcomes and clinician acceptance

    Directory of Open Access Journals (Sweden)

    Kline JA

    2016-04-01

    Full Text Available Jeffrey A Kline,1,2 Zachary P Kahler,1,3 Daren M Beam1,2 1Department of Emergency Medicine, 2Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, 3Department of Emergency Medicine, University of South Carolina Greenville School of Medicine, Greenville, SC, USA Background: Oral monotherapy anticoagulation has facilitated home treatment of venous thromboembolism (VTE in outpatients. Objectives: The aim of this study was to measure efficacy, safety, as well as patient and physician perceptions produced by a protocol that selected VTE patients as low-risk patients by the Hestia criteria, and initiated home anticoagulation with an oral factor Xa antagonist. Methods: Patients were administered the Venous Insufficiency Epidemiological and Economic Study Quality of life/Symptoms ques­tionnaire [VEINEs QoL/Sym] and the physical component summary [PCS] from the Rand 36-Item Short Form Health Survey [SF36]. The primary outcomes were VTE recurrence and hemorrhage at 30 days. Secondary outcomes compared psychometric test scores between patients with deep vein thrombosis (DVT to those with pulmonary embolism (PE. Patient perceptions were abstracted from written comments and physician perceptions specific to PE outpatient treatment obtained from structured survey. Results: From April 2013 to September 2015, 253 patients were treated, including 67 with PE. Within 30 days, 2/ 253 patients had recurrent DVT and 2/253 had major hemor­rhage; all four had DVT at enrollment. The initial PCS scores did not differ between DVT and PE patients (37.2±13.9 and 38.0±12.1, respectively and both DVT and PE patients had similar improvement over the treatment period (42.2±12.9 and 43.4±12.7, respectively, consistent with prior literature. The most common adverse event was menorrhagia, present in 15% of women. Themes from patient-written responses reflected satisfaction with increased autonomy. Physicians’ (N=116

  15. Potential impact of combined high- and low-risk human papillomavirus infection on the progression of cervical intraepithelial neoplasia 2.

    Science.gov (United States)

    Okadome, Masao; Saito, Toshiaki; Tanaka, Hideyuki; Nogawa, Takayoshi; Furuta, Reiko; Watanabe, Kayoko; Kita, Tsunekazu; Yamamoto, Kaichiro; Mikami, Mikio; Takizawa, Ken

    2014-02-01

    Few studies have examined the effect of combined low-risk human papillomavirus (LR-HPV) and high-risk human papillomavirus (HR-HPV) infection on the progression of cervical intraepithelial neoplasia (CIN)2 to CIN3. This multi-institutional prospective cohort study investigated the risk of progression of CIN2 with various combinations of HR-HPV and LR-HPV infection. Between January 2007 and May 2008, 122 women with CIN2 (aged 20-50 years) from 24 hospitals throughout Japan were enrolled in the study. Ninety-three women were analyzed after a 2-year follow-up with cytology, colposcopy, HR-HPV testing and HPV genotyping. Colposcopy-directed biopsy was performed at entry and the end of this study, or when disease progression was suspected. Among 93 women with CIN2, 87 (93.5%) had HR-HPV infection. Among these 87 cases, 24 (27.6%) progressed to CIN3 and 49 (56.3%) regressed. None of the six women with CIN2 without HR-HPV infection progressed. The progression rate was significantly lower in women with combined HR-HPV and LR-HPV infection (3/28, 10.7%) than in those with HR-HPV infection only (21/59, 35.6%; P = 0.016). Multivariate analyses showed that CIN2 progression in women with HR-HPV infection was negatively associated with LR-HPV co-infection (hazard ratio = 0.152; 95% confidence interval [CI] = 0.042-0.553). CIN2 regression was positively associated with LR-HPV co-infection (odds ratio = 4.553; 95% CI = 1.378-15.039). The risk of CIN2 progression is low in women with combined infection of HR-HPV and LR-HPV. The finding may be useful for management of women diagnosed with CIN2. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

  16. Progressive transfusion and growth factor independence with adjuvant sertraline in low risk myelodysplastic syndrome treated with an erythropoiesis stimulating agent and granulocyte-colony stimulating factor

    Directory of Open Access Journals (Sweden)

    Kirtan Nautiyal

    2015-01-01

    Full Text Available Refractoriness to growth factor therapy is commonly associated with inferior outcome in patients with low-risk myelodysplastic syndrome (LR-MDS who require treatment for cytopenias. However, the mechanisms leading to refractoriness are unknown. Here we describe a clinically depressed 74-year-old male with refractory cytopenia with multilineage dysplasia (RCMD and documented growth factor refractory anemia after erythropoeisis stimulating agent (ESA therapy, who attained transfusion and growth factor independence after the addition of sertraline to his medication regimen. Our case demonstrates hematological improvement-erythroid (HI-E in growth factor refractory, low risk MDS and highlights a potential mechanistic link between common inflammatory diseases and LR-MDS.

  17. Increasing observation rates in low-risk pediatric immune thrombocytopenia using a standardized clinical assessment and management plan (SCAMP(®) ).

    Science.gov (United States)

    Schoettler, Michelle L; Graham, Dionne; Tao, Wen; Stack, Margaret; Shu, Elaine; Kerr, Lauren; Neufeld, Ellis J; Grace, Rachael F

    2017-05-01

    An observational approach is recommended in newly diagnosed children with immune thrombocytopenia (ITP) at low risk of bleeding; however, there is no standard definition of risk. A standardized clinical assessment and management plan (SCAMP(®) ), a modifiable practice guideline, was implemented and revised (SCAMP-1 and SCAMP-2) and applied to 71 newly diagnosed patients with ITP. The Buchanan and Adix bleeding score guided treatment and was modified by stratifying by low- and high-risk grade 3 bleeding in SCAMP-2. Observation rates increased from 40% to 74% from SCAMP-1 to SCAMP-2 (P < 0.05) with no bleeding complications. We propose a modified bleeding score that increased observation rates in low-risk patients with ITP. © 2016 Wiley Periodicals, Inc.

  18. Debunking the claim that abstinence is usually healthier for smokers than switching to a low-risk alternative, and other observations about anti-tobacco-harm-reduction arguments

    Directory of Open Access Journals (Sweden)

    Phillips Carl V

    2009-11-01

    Full Text Available Abstract Nicotine is so desirable to many people that when they are given only the options of consuming nicotine by smoking, with its high health costs, and not consuming nicotine at all, many opt for the former. Few smokers realize that there is a third choice: non-combustion nicotine sources, such as smokeless tobacco, electronic cigarettes, or pharmaceutical nicotine, which eliminate almost all the risk while still allowing consumption of nicotine. Widespread dissemination of misleading health claims is used to prevent smokers from learning about this lifesaving option, and to discourage opinion leaders from telling smokers the truth. One common misleading claim is a risk-risk comparison that has not before been quantified: A smoker who would have eventually quit nicotine entirely, but learns the truth about low-risk alternatives, might switch to an alternative instead of quitting entirely, and thus might suffer a net increase in health risk. While this has mathematical face validity, a simple calculation of the tradeoff -- switching to lifelong low-risk nicotine use versus continuing to smoke until quitting -- shows that such net health costs are extremely unlikely and of trivial maximum magnitude. In particular, for the average smoker, smoking for just one more month before quitting causes greater health risk than switching to a low-risk nicotine source and never quitting it. Thus, discouraging a smoker, even one who would have quit entirely, from switching to a low-risk alternative is almost certainly more likely to kill him than it is to save him. Similarly, a strategy of waiting for better anti-smoking tools to be developed, rather than encouraging immediate tobacco harm reduction using current options, kills more smokers every month than it could possibly ever save.

  19. Admission rates for emergency department patients with venous thromboembolism and estimation of the proportion of low risk pulmonary embolism patients: a US perspective

    Science.gov (United States)

    Singer, Adam J.; Thode, Henry C.; Peacock, W. Frank

    2016-01-01

    Objective Introduction of target specific anticoagulants and recent guidelines encourage outpatient management of low risk patients with venous thromboembolism. We describe hospital admission rates over time for patients presenting to US emergency departments (EDs) with deep vein thrombosis (DVT) and pulmonary embolism (PE) and estimate the proportion of low-risk PE patients who could potentially be managed as outpatients. Methods We performed a structured analysis of the National Hospital Ambulatory Medical Care Survey (a nationally representative weighted sampling of US ED visits) database for the years 2006–2010 including all adult patients with a primary diagnosis of DVT or PE. Simplified pulmonary embolus scoring index (sPESI) scores were determined in patients with PE to identify low risk patients. Results There were an estimated 652,000 and 394,000 ED visits for DVT and PE over the 5-year period (0.17%). Mean (SE) age was 59 (1.3), 50% were female, and 40% were > 65 years. Admission rates for DVT and PE were 52% and 90% respectively with no significant changes over time. In patients with DVT, predictors for admission were age (odds ratio, 1.03 per year of age [95% confidence interval, 1.01 to 1.05]) and race (odds ratio, 4.1 [95% confidence interval, 0.9 to 19.8] for Hispanics and 2.9 [1.2 to 7.4] for Blacks). Of all ED patients with PE, 51% were low risk based on sPESI scores. Conclusion Admission rates for DVT and PE have remained high and unchanged, especially with PE, minorities, and in older patients. Based on sPESI scores, up to half of PE patients might be eligible for early discharge or outpatient therapy.

  20. The use of exome genotyping to predict pathological Gleason score upgrade after radical prostatectomy in low-risk prostate cancer patients.

    Directory of Open Access Journals (Sweden)

    Jong Jin Oh

    Full Text Available Active surveillance (AS is a promising option for patients with low-risk prostate cancer (PCa, however current criteria could not select the patients correctly, many patients who fulfilled recent AS criteria experienced pathological Gleason score upgrade (PGU after radical prostatectomy (RP. In this study, we aimed to develop an accurate model for predicting PGU among low-risk PCa patients by using exome genotyping.We genotyped 242,221 single nucleotide polymorphisms (SNPs on a custom HumanExome BeadChip v1.0 (Illuminam Inc. in blood DNA from 257 low risk PCa patients (PSA <10 ng/ml, biopsy Gleason score (GS ≤6 and clinical stage ≤T2a who underwent radical prostatectomy. Genetic data were analyzed using an unconditional logistic regression to calculate an odds ratio as an estimate of relative risk of PGU, which defined pathologic GS above 7. Among them, we selected persistent SNPs after multiple testing using FDR method, and we compared accuracies from the multivariate logistic model incorporating clinical factors between included and excluded selected SNP information.After analysis of exome genotyping, 15 SNPs were significant to predict PGU in low risk PCa patients. Among them, one SNP--rs33999879 remained significant after multiple testing. When a multivariate model incorporating factors in Epstein definition--PSA density, biopsy GS, positive core number, tumor per core ratio and age was devised for the prediction of PGU, the predictive accuracy of the multivariate model was 78.4% (95%CI: 0.726-0.834. By addition the factor of rs33999879 in aforementioned multivariate model, the predictive accuracy was 82.9%, which was significantly increased (p = 0.0196.The rs33999879 SNP is a predictor for PGU. The addition of genetic information from the exome sequencing effectively enhanced the predictive accuracy of the multivariate model to establish suitable active surveillance criteria.

  1. ROLE OF DOPPLER IN PRED ICTION OF PERINATAL OUTCOME: A COMPARATIVE STUDY OF DOPPLER INDICES IN LOW RISK AND HIGH RISK PREGNANCIES

    Directory of Open Access Journals (Sweden)

    Uma

    2015-09-01

    Full Text Available AIMS AND OBJECTIVES: to evaluate Doppler abnormalities in low risk and high risk pregnancies and to determine their relation to the outcome of pregnancy . METHODS: A total of 60 no. of pregnant women without any known risk factors are included in the low risk group and 60 no. of pregnant women with pre - eclampsia or gestational hypertension or intra uterine growth restriction, are included in the high risk group. Doppler evaluation done at term and the outcome is noted in terms of mode of delivery and perinatal complications in both the groups. RESULTS: Forty percent of high risk pregnant women and 1.6 percent of low risk pregnant women are found to be associated with abnormal Doppler results. Abnormal UA - PI , in association with high risk pregnancy is significantly associated wit h abnormal mode of delivery (P - 0.0005 and perinatal complications (P - 0.0009. Abnormal MCA - PI and abnormal MCA - PI/UA - PI ratio of <1.1 are associated with perinatal complications with highest significance (P - <0.0001. High risk pregnancy with normal Doppl er results, also had perinatal complications with slightly lower significance (0.0011. CONCLUSION: There is definite association of Doppler abnormalities with high risk pregnancy. Low risk pregnancy is almost never associated with Doppler abnormalities an d it is not necessary to perform Doppler to all women. Of all the Doppler indices, the ratio of MCA - PI/ UA - PI appears to be the best predictor of poor outcome. Normal Doppler results in association with high risk pregnancy cannot ensure uncomplicated outco me.

  2. Acute kidney injury patterns and outcomes in low-risk versus high-risk critically ill patients admitted to the medical intensive care unit

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    Cyriacus Anaele

    2017-01-01

    Full Text Available Background: Acute kidney injury (AKI is often one component of multiple organ failure (MOF in the intensive care unit (ICU. However, not all patients with MOF develop AKI, and AKI may develop in the absence of MOF. We compared the impact of AKI alone and in combination with MOF on the survival of patients admitted to a large tertiary care medical intensive care unit (MICU.  Methods: We abstracted data from the electronic medical records of patients admitted to the MICU from April 2012 through June 2013 and categorized patients as either high-risk or low- risk status based on use of vasopressor support or mechanical ventilation during the ICU stay. The outcomes we considered were in-hospital, 30-day, 90-day, 180-day, and 1-year mortality. Results: Of the 834 critically ill patients, 743 (89% developed some degree of AKI. Ninety-one percent of the high-risk cohort developed AKI and 87% of the low-risk cohort developed AKI. Patients with AKI had higher mortality at 1-year than patients without AKI (adjusted odds ratio [OR], 2.5; 95% confidence interval [CI], 1.38 to 4.53; P interaction 0.0026.  Hospital mortality was greater for high-risk patients without AKI than for low-risk patients with AKI. Conclusion: Acute kidney injury occurs at similar frequency in high and low-risk ICU patients and has significant impact on survival in both groups.  Cardiovascular collapse or respiratory failure has greater impact on short term mortality than AKI, but this effect diminishes over time. Conversely, the impact of AKI on mortality increased over time and remained an independent risk factor for mortality.

  3. Comparison of pathological data between prostate biopsy and radical prostatectomy specimen in patients with low to very low risk prostate cancer.

    Science.gov (United States)

    Lendínez-Cano, G; Alonso-Flores, J; Beltrán-Aguilar, V; Cayuela, A; Salazar-Otero, S; Bachiller-Burgos, J

    2015-10-01

    To analyze the correlation between pathological data found in radical prostatectomy and previously performed biopsy in patients at low risk prostate cancer. A descriptive, cross-sectional study was conducted to assess the characteristics of radical prostatectomies performed in our center from January 2012 to November 2014. The inclusion criteria were patients with low-risk disease (cT1c-T2a, PSA≤10ng/mL and Gleason score≤6). We excluded patients who had fewer than 8 cores in the biopsy, an unspecified number of affected cores, rectal examinations not reported in the medical history or biopsies performed in another center. Of the 184 patients who underwent prostatectomy during this period, 87 met the inclusion criteria, and 26 of these had<3 affected cores and PSA density≤.15 (very low risk). In the entire sample, the percentage of undergrading (Gleason score≥7) and extracapsular invasion (pT3) was 18.4% (95% CI 10.3-27.6) and 10.35% (95% CI 4.6-17.2), respectively. The percentage of positive margins was 21.8% (95% CI 12.6-29.9). In the very low-risk group, we found no cases of extracapsular invasion and only 1 case of undergrading (Gleason 7 [3+4]), representing 3.8% of the total (95% CI 0-12.5). Predictors of no correlation (stage≥pT3a or undergrading) were the initial risk group, volume, PSA density and affected cores. Prostate volume, PSA density, the number of affected cores and the patient's initial risk group influence the poor pathological prognosis in the radical prostatectomy specimen (extracapsular invasion and Gleason score≥7). Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Management of low-risk early-stage cervical cancer: Should conization, simple trachelectomy, or simple hysterectomy replace radical surgery as the new standard of care?

    Science.gov (United States)

    Ramirez, Pedro T.; Pareja, Rene; Rendón, Gabriel J.; Millan, Carlos; Frumovitz, Michael; Schmeler, Kathleen M.

    2014-01-01

    The standard treatment for women with early-stage cervical cancer (IA2-IB1) remains radical hysterectomy with pelvic lymphadenectomy. In select patients interested in future fertility, the option of radical trachelectomy with pelvic lymphadenectomy is also considered a viable option. The possibility of less radical surgery may be appropriate not only for patients desiring to preserve fertility but also for all patients with low-risk early-stage cervical cancer. Recently, a number of studies have explored less radical surgical options for early-stage cervical cancer, including simple hysterectomy, simple trachelectomy, and cervical conization with or without sentinel lymph node biopsy and pelvic lymph node dissection. Such options may be available for patients with low-risk early-stage cervical cancer. Criteria that define this low-risk group include: squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma, tumor size <2 cm, stromal invasion <10mm, and no lymph-vascular space invasion. In this report, we provide a review of the existing literature on the conservative management of cervical cancer and describe ongoing multi-institutional trials evaluating the role of conservative surgery in selected patients with early-stage cervical cancer. PMID:24041877

  5. Is {sup 131}I ablation necessary for patients with low-risk papillary thyroid carcinoma and slightly elevated stimulated thyroglobulin after thyroidectomy?

    Energy Technology Data Exchange (ETDEWEB)

    Rosario, Pedro Weslley; Mourao, Gabriela Franco, E-mail: pedrowsrosario@gmail.com [Santa Casa de Belo Horizonte, MG (Brazil). Instituto de Ensino e Pesquisa

    2016-02-15

    Objective: This prospective study evaluated the recurrence rate in low-risk patients with papillary thyroid cancer (PTC) who presented slightly elevated thyroglobulin (Tg) after thyroidectomy and who did not undergo ablation with {sup 131}I. Subjects and methods: The study included 53 low-risk patients (non aggressive histology; pT1b-3, cN0pNx, M0) with slightly elevated Tg after thyroidectomy (> 1 ng/mL, but ≤ 5 ng/mL after levothyroxine withdrawal or ≤ 2 ng/mL after recombinant human TSH). Results: The time of follow-up ranged from 36 to 96 months. Lymph node metastases were detected in only one patient (1.9%). Fifty-two patients continued to present negative neck ultrasound. None of these patients without apparent disease presented an increase in Tg. Conclusions: Low-risk patients with PTC who present slightly elevated Tg after thyroidectomy do not require ablation with {sup 131}I. (author)

  6. Obese sedentary patients with dyspnoea on exertion who are at low risk for coronary artery disease by clinical criteria have a very low prevalence of coronary artery disease.

    Science.gov (United States)

    Bruckel, J T; Larsen, G; Benson, M R

    2014-06-01

    Dyspnoea, a much less specific symptom of ischaemia than chest discomfort, is common among obese patients. Patients with dyspnoea often undergo stress testing as part of their evaluation. We sought to examine the yield of stress testing in non-elderly, obese, sedentary patients with dyspnoea on exertion (DOE) as a chief complaint.We reviewed stress echocardiograms carried out on 203 patients in a stress testing laboratory at a major tertiary care centre. Of these, 81 (40%) fell into a group that was at low risk for coronary artery disease (CAD) by clinical criteria. Ischaemia was detected in two patients in the low-risk group (2.5%), and these results were likely false positives. In the higher risk group, 9.0% of functional tests showed ischaemia; after further testing, 2.5% of the higher risk patients were found to have obstructive coronary lesions. Clinical follow-up was performed for a mean of 815 days. New obstructive coronary disease was detected in 1.6% of all patients, and these patients were from the higher risk group. In obese sedentary patients with DOE but otherwise at low risk of coronary disease stress testing is of very low yield. DOE is generally not an anginal equivalent in this patient population.

  7. Resistance of Abaca Somaclonal Variant Against Fusarium

    Directory of Open Access Journals (Sweden)

    RULLY DYAH PURWATI

    2007-12-01

    Full Text Available The objectives of this study were (i to evaluate responses against F. oxysporum f.sp. cubense (Foc infection of abaca variants regenerated using four different methods, (ii to determine initial root length and plant height effects on survival of inoculated abaca variants, and (iii to identify Foc resistance abaca variants. In the previous experiment, four abaca variant lines were regenerated from (i embryogenic calli (TC line, (ii ethyl methyl sulphonate (EMS treated embryogenic calli (EMS line, (iii EMS treated embryogenic calli, followed by in vitro selection on Foc culture filtrate (EMS+CF line, and (iv EMS treated embryogenic calli, followed by in vitro selection on fusaric acid (EMS+FA line. All abaca variants were grown in a glasshouse and inoculated with Banyuwangi isolate of Foc (Foc Bw. Initial root length (RL and plant height (PH of the abaca variants were recorded before inoculation, while scores of plant damage (SPD, and their survival were recorded at 60 days after inoculation (DAI. The results showed that the initial RL and PH did not affect survival of the tested abaca variants. Regardless of their initial RL and PH, susceptible abaca variants died before 60 DAI while resistance ones still survived. Abaca variants regenerated from single clump of embryogenic callus showed an array of responses against Foc Bw infection, indicating the existence of a mix cells population. The Foc Bw resistance abaca variants were successfully identified from four tested abaca variant lines, although with different frequencies. However, more Foc Bw resistance abaca plants were identified from EMS+CF line than the others. Using the developed procedures, 8 resistance abaca plants were identified from abaca cv. Tangongon and 12 from abaca cv. Sangihe-1.

  8. Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers

    NARCIS (Netherlands)

    Antoniou, Antonis C.; Sinilnikova, Olga M.; McGuffog, Lesley; Healey, Sue; Nevanlinna, Heli; Heikkinen, Tuomas; Simard, Jacques; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Neuhausen, Susan L.; Ding, Yuan C.; Couch, Fergus J.; Wang, Xianshu; Fredericksen, Zachary; Peterlongo, Paolo; Peissel, Bernard; Bonanni, Bernardo; Viel, Alessandra; Bernard, Loris; Radice, Paolo; Szabo, Csilla I.; Foretova, Lenka; Zikan, Michal; Claes, Kathleen; Greene, Mark H.; Mai, Phuong L.; Rennert, Gad; Lejbkowicz, Flavio; Andrulis, Irene L.; Ozcelik, Hilmi; Glendon, Gord; Gerdes, Anne-Marie; Thomassen, Mads; Sunde, Lone; Caligo, Maria A.; Laitman, Yael; Kontorovich, Tair; Cohen, Shimrit; Kaufman, Bella; Dagan, Efrat; Baruch, Ruth Gershoni; Friedman, Eitan; Harbst, Katja; Barbany-Bustinza, Gisela; Rantala, Johanna; Ehrencrona, Hans; Karlsson, Per; Domchek, Susan M.; Nathanson, Katherine L.; Osorio, Ana; Blanco, Ignacio; Lasa, Adriana; Benitez, Javier; Hamann, Ute; Hogervorst, Frans B. L.; Rookus, Matti A.; Collee, J. Margriet; Devilee, Peter; Ligtenberg, Marjolijn J.; van der Luijt, Rob B.; Aalfs, Cora M.; Waisfisz, Quinten; Wijnen, Juul; van Roozendaal, Cornelis E. P.; Peock, Susan; Cook, Margaret; Frost, Debra; Oliver, Clare; Platte, Radka; Evans, D. Gareth; Lalloo, Fiona; Eeles, Rosalind; Izatt, Louise; Davidson, Rosemarie; Chu, Carol; Eccles, Diana; Cole, Trevor; Hodgson, Shirley; Godwin, Andrew K.; Stoppa-Lyonnet, Dominique; Buecher, Bruno; Leone, Melanie; Bressac-de Paillerets, Brigitte; Remenieras, Audrey; Caron, Olivier; Lenoir, Gilbert M.; Sevenet, Nicolas; Longy, Michel; Ferrer, Sandra Fert; Prieur, Fabienne; Goldgar, David; Miron, Alexander; John, Esther M.; Buys, Saundra S.; Daly, Mary B.; Hopper, John L.; Terry, Mary Beth; Yassin, Yosuf; Singer, Christian; Gschwantler-Kaulich, Daphne; Staudigl, Christine; Hansen, Thomas V. O.; Barkardottir, Rosa Bjork; Kirchhoff, Tomas; Pal, Prodipto; Kosarin, Kristi; Offit, Kenneth; Piedmonte, Marion; Rodriguez, Gustavo C.; Wakeley, Katie; Boggess, John F.; Basil, Jack; Schwartz, Peter E.; Blank, Stephanie V.; Toland, Amanda E.; Montagna, Marco; Casella, Cinzia; Imyanitov, Evgeny N.; Allavena, Anna; Schmutzler, Rita K.; Versmold, Beatrix; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Niederacher, Dieter; Deissler, Helmut; Fiebig, Britta; Suttner, Christian; Schoenbuchner, Ines; Gadzicki, Dorothea; Caldes, Trinidad; de la Hoya, Miguel; Pooley, Karen A.; Easton, Douglas F.; Chenevix-Trench, Georgia

    2009-01-01

    Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and

  9. Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers

    NARCIS (Netherlands)

    Antoniou, Antonis C.; Sinilnikova, Olga M.; McGuffog, Lesley; Healey, Sue; Nevanlinna, Heli; Heikkinen, Tuomas; Simard, Jacques; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Neuhausen, Susan L.; Ding, Yuan C.; Couch, Fergus J.; Wang, Xianshu; Fredericksen, Zachary; Peterlongo, Paolo; Peissel, Bernard; Bonanni, Bernardo; Viel, Alessandra; Bernard, Loris; Radice, Paolo; Szabo, Csilla I.; Foretova, Lenka; Zikan, Michal; Claes, Kathleen; Greene, Mark H.; Mai, Phuong L.; Rennert, Gad; Lejbkowicz, Flavio; Andrulis, Irene L.; Ozcelik, Hilmi; Glendon, Gord; Gerdes, Anne-Marie; Thomassen, Mads; Sunde, Lone; Caligo, Maria A.; Laitman, Yael; Kontorovich, Tair; Cohen, Shimrit; Kaufman, Bella; Dagan, Efrat; Baruch, Ruth Gershoni; Friedman, Eitan; Harbst, Katja; Barbany-Bustinza, Gisela; Rantala, Johanna; Ehrencrona, Hans; Karlsson, Per; Domchek, Susan M.; Nathanson, Katherine L.; Osorio, Ana; Blanco, Ignacio; Lasa, Adriana; Benitez, Javier; Hamann, Ute; Hogervorst, Frans B. L.; Rookus, Matti A.; Collee, J. Margriet; Devilee, Peter; Ligtenberg, Marjolijn J.; van der Luijt, Rob B.; Aalfs, Cora M.; Waisfisz, Quinten; Wijnen, Juul; van Roozendaal, Cornelis E. P.; Peock, Susan; Cook, Margaret; Frost, Debra; Oliver, Clare; Platte, Radka; Evans, D. Gareth; Lalloo, Fiona; Eeles, Rosalind; Izatt, Louise; Davidson, Rosemarie; Chu, Carol; Eccles, Diana; Cole, Trevor; Hodgson, Shirley; Godwin, Andrew K.; Stoppa-Lyonnet, Dominique; Buecher, Bruno; Leone, Melanie; Bressac-de Paillerets, Brigitte; Remenieras, Audrey; Caron, Olivier; Lenoir, Gilbert M.; Sevenet, Nicolas; Longy, Michel; Ferrer, Sandra Fert; Prieur, Fabienne; Goldgar, David; Miron, Alexander; John, Esther M.; Buys, Saundra S.; Daly, Mary B.; Hopper, John L.; Terry, Mary Beth; Yassin, Yosuf; Singer, Christian; Gschwantler-Kaulich, Daphne; Staudigl, Christine; Hansen, Thomas V. O.; Barkardottir, Rosa Bjork; Kirchhoff, Tomas; Pal, Prodipto; Kosarin, Kristi; Offit, Kenneth; Piedmonte, Marion; Rodriguez, Gustavo C.; Wakeley, Katie; Boggess, John F.; Basil, Jack; Schwartz, Peter E.; Blank, Stephanie V.; Toland, Amanda E.; Montagna, Marco; Casella, Cinzia; Imyanitov, Evgeny N.; Allavena, Anna; Schmutzler, Rita K.; Versmold, Beatrix; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Niederacher, Dieter; Deissler, Helmut; Fiebig, Britta; Suttner, Christian; Schoenbuchner, Ines; Gadzicki, Dorothea; Caldes, Trinidad; de la Hoya, Miguel; Pooley, Karen A.; Easton, Douglas F.; Chenevix-Trench, Georgia

    2009-01-01

    Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and M

  10. Comparison of Four Bleeding Risk Scores to Identify Rivaroxaban-treated Patients With Venous Thromboembolism at Low Risk for Major Bleeding.

    Science.gov (United States)

    Kline, Jeffrey A; Jimenez, David; Courtney, D Mark; Ianus, Juliana; Cao, Lynn; Lensing, Anthonie W A; Prins, Martin H; Wells, Philip S

    2016-02-01

    Outpatient treatment of acute venous thromboembolism (VTE) requires the selection of patients with a low risk of bleeding during the first few weeks of anticoagulation. The accuracy of four systems, originally derived for predicting bleeding in VTE treated with vitamin K antagonists (VKAs), was assessed in VTE patients treated with rivaroxaban. All patients treated with rivaroxaban in the multinational EINSTEIN deep vein thrombosis (DVT) and pulmonary embolism (PE) trials were included. Major bleeding was defined as ≥2 g/dL drop in hemoglobin or ≥2-unit blood transfusion, bleeding in critical area, or bleeding contributing to death. The authors examined the incidence of major bleeding in patients with low-risk assignment by the systems of Ruiz-Gimenez et al. (score = 0 to 1), Beyth et al. (score = 0), Kuijer et al. (score = 0), and Landefeld and Goldman. (score = 0). For clinical relevance, the definition of low risk for all scores except Kuijer includes all patients risk patients during the entire treatment period were similar: Ruiz-Gimenez et al., 12 of 2,622 (0.5%; 95% CI = 0.2% to 0.8%); Beyth et al., nine of 2,249 (0.4%; 95% CI = 0.2% to 0.8%); Kuijer et al., four of 1,186 (0.3%; 95% CI = 0.1% to 0.9%); and Landefeld and Goldman, 11 of 2,407 (0.5%; 95% CI = 0.2% to 0.8%). At 30 days, major bleed rates for low-risk patients were as follows: Ruiz-Gimenez et al., five of 2,622 (0.2%; 95% CI = 0.1% to 0.4%); Beyth et al., five of 2,249 (0.2%; 95% CI = 0.1% to 0.5%); Kuijer et al., three of 1,186 (0.3%; 95% CI = 0.1% to 0.7%); and Landefeld and Goldman, seven of 2,407 (0.3%; 95% CI = 0.1% to 0.6%). No low-risk patient had a fatal bleed. Four scoring systems that use criteria obtained in routine clinical practice, derived to predict low bleeding risk with VKA treatment for VTE, identified patients with less than a 1% risk of major bleeding during full-course treatment with rivaroxaban. © 2016 by the Society for Academic Emergency Medicine.

  11. Semantic prioritization of novel causative genomic variants

    KAUST Repository

    Boudellioua, Imane

    2017-04-17

    Discriminating the causative disease variant(s) for individuals with inherited or de novo mutations presents one of the main challenges faced by the clinical genetics community today. Computational approaches for variant prioritization include machine learning methods utilizing a large number of features, including molecular information, interaction networks, or phenotypes. Here, we demonstrate the PhenomeNET Variant Predictor (PVP) system that exploits semantic technologies and automated reasoning over genotype-phenotype relations to filter and prioritize variants in whole exome and whole genome sequencing datasets. We demonstrate the performance of PVP in identifying causative variants on a large number of synthetic whole exome and whole genome sequences, covering a wide range of diseases and syndromes. In a retrospective study, we further illustrate the application of PVP for the interpretation of whole exome sequencing data in patients suffering from congenital hypothyroidism. We find that PVP accurately identifies causative variants in whole exome and whole genome sequencing datasets and provides a powerful resource for the discovery of causal variants.

  12. Fundamental Characteristics of Industrial Variant Specification Systems

    DEFF Research Database (Denmark)

    Hansen, Benjamin Loer; Hvam, Lars

    2004-01-01

    fundamental concepts related to this task, which are relevant to understand for academia and practitioners working with the subject. This is done through a description of variant specification tasks and typical aspects of system solutions. To support the description of variant specification tasks and systems...

  13. Beta-glucosidase I variants with improved properties

    Energy Technology Data Exchange (ETDEWEB)

    Bott, Richard R.; Kaper, Thijs; Kelemen, Bradley; Goedegebuur, Frits; Hommes, Ronaldus Wilhelmus; Kralj, Slavko; Kruithof, Paulien; Nikolaev, Igor; Van Der Kley, Wilhelmus Antonious Hendricus; Van Lieshout, Johannes Franciscus Thomas; Van Stigt Thans, Sander

    2016-09-20

    The present disclosure is generally directed to enzymes and in particular beta-glucosidase variants. Also described are nucleic acids encoding beta-glucosidase variants, compositions comprising beta-glucosidase variants, methods of using beta-glucosidase variants, and methods of identifying additional useful beta-glucosidase variants.

  14. Plasma Levels of Risk-Variant APOL1 Do Not Associate with Renal Disease in a Population-Based Cohort.

    Science.gov (United States)

    Kozlitina, Julia; Zhou, Haihong; Brown, Patricia N; Rohm, Rory J; Pan, Yi; Ayanoglu, Gulesi; Du, Xiaoyan; Rimmer, Eric; Reilly, Dermot F; Roddy, Thomas P; Cully, Doris F; Vogt, Thomas F; Blom, Daniel; Hoek, Maarten

    2016-10-01

    Two common missense variants in APOL1 (G1 and G2) have been definitively linked to CKD in black Americans. However, not all individuals with the renal-risk genotype develop CKD, and little is known about how APOL1 variants drive disease. Given the association of APOL1 with HDL particles, which are cleared by the kidney, differences in the level or quality of mutant APOL1‑HDL particles could be causal for disease and might serve as a useful risk stratification marker. We measured plasma levels of G0 (low risk), G1, and G2 APOL1 in 3450 individuals in the Dallas Heart Study using a liquid chromatography-MS method that enabled quantitation of the different variants. Additionally, we characterized native APOL1‑HDL from donors with no or two APOL1 risk alleles by size-exclusion chromatography and analysis of immunopurified APOL1‑HDL particles. Finally, we identified genetic loci associated with plasma APOL1 levels and tested for APOL1-dependent association with renal function. Although we replicated the previous association between APOL1 variant status and renal function in nondiabetic individuals, levels of circulating APOL1 did not associate with microalbuminuria or GFR. Furthermore, the size or known components of APOL1‑HDL did not consistently differ in subjects with the renal-risk genotype. Genetic association studies implicated variants in loci harboring haptoglobin-related protein (HPR), APOL1, and ubiquitin D (UBD) in the regulation of plasma APOL1 levels, but these variants did not associate with renal function. Collectively, these data demonstrate that the risk of renal disease associated with APOL1 is probably not related to circulating levels of the mutant protein.

  15. Local binary patterns new variants and applications

    CERN Document Server

    Jain, Lakhmi; Nanni, Loris; Lumini, Alessandra

    2014-01-01

    This book introduces Local Binary Patterns (LBP), arguably one of the most powerful texture descriptors, and LBP variants. This volume provides the latest reviews of the literature and a presentation of some of the best LBP variants by researchers at the forefront of textual analysis research and research on LBP descriptors and variants. The value of LBP variants is illustrated with reported experiments using many databases representing a diversity of computer vision applications in medicine, biometrics, and other areas. There is also a chapter that provides an excellent theoretical foundation for texture analysis and LBP in particular. A special section focuses on LBP and LBP variants in the area of face recognition, including thermal face recognition. This book will be of value to anyone already in the field as well as to those interested in learning more about this powerful family of texture descriptors.

  16. Histones in functional diversification. Core histone variants.

    Science.gov (United States)

    Pusarla, Rama-Haritha; Bhargava, Purnima

    2005-10-01

    Recent research suggests that minor changes in the primary sequence of the conserved histones may become major determinants for the chromatin structure regulating gene expression and other DNA-related processes. An analysis of the involvement of different core histone variants in different nuclear processes and the structure of different variant nucleosome cores shows that this may indeed be so. Histone variants may also be involved in demarcating functional regions of the chromatin. We discuss in this review why two of the four core histones show higher variation. A comparison of the status of variants in yeast with those from higher eukaryotes suggests that histone variants have evolved in synchrony with functional requirement of the cell.

  17. Fundamental Characteristics of Industrial Variant Specification Systems

    DEFF Research Database (Denmark)

    Hansen, Benjamin Loer; Hvam, Lars

    2004-01-01

    This paper focuses on the operational task of creating customised variants of industrial specifications (e.g. drawings, routings and bill-of-materials). Rooted in a lack of existing literature on the subject the paper describes the nature of variant specification systems. It introduces some funda...... examples. In general the paper discusses an important focus area within mass customization and build-to-order production: the nature of industrial variant specification systems.......This paper focuses on the operational task of creating customised variants of industrial specifications (e.g. drawings, routings and bill-of-materials). Rooted in a lack of existing literature on the subject the paper describes the nature of variant specification systems. It introduces some...

  18. Different Variants of Fundamental Portfolio

    Directory of Open Access Journals (Sweden)

    Tarczyński Waldemar

    2014-06-01

    Full Text Available The paper proposes the fundamental portfolio of securities. This portfolio is an alternative for the classic Markowitz model, which combines fundamental analysis with portfolio analysis. The method’s main idea is based on the use of the TMAI1 synthetic measure and, in limiting conditions, the use of risk and the portfolio’s rate of return in the objective function. Different variants of fundamental portfolio have been considered under an empirical study. The effectiveness of the proposed solutions has been related to the classic portfolio constructed with the help of the Markowitz model and the WIG20 market index’s rate of return. All portfolios were constructed with data on rates of return for 2005. Their effectiveness in 2006- 2013 was then evaluated. The studied period comprises the end of the bull market, the 2007-2009 crisis, the 2010 bull market and the 2011 crisis. This allows for the evaluation of the solutions’ flexibility in various extreme situations. For the construction of the fundamental portfolio’s objective function and the TMAI, the study made use of financial and economic data on selected indicators retrieved from Notoria Serwis for 2005.

  19. Chemokine gene variants in schizophrenia.

    Science.gov (United States)

    Dasdemir, Selcuk; Kucukali, Cem Ismail; Bireller, Elif Sinem; Tuzun, Erdem; Cakmakoglu, Bedia

    2016-08-01

    Background Chemokines are known to play a major role in driving inflammation and immune responses in several neuroinflammatory diseases, including multiple sclerosis, Alzheimer's disease and Parkinson's disease. Inflammation has also been implicated in the pathogenesis of schizophrenia. Aim We aimed to investigate a potential link between chemokines and schizophrenia and analyze the role of MCP-1-A2518G, SDF-1-3'A, CCR5-delta32, CCR5-A55029G, CXCR4-C138T and CCR2-V64I gene polymorphisms in the Turkish population. Methods Genotyping was conducted by PCR-RFLP based on 140 patients and 123 unrelated healthy controls to show the relation between chemokine gene variants and schizophrenia risk. Results Frequencies of CCR5-A55029G A genotypes and CCR5-A55029G AG genotypes were found higher in patients than the controls and even also CCR2-V64I WT: CCR5-A55029G A and CCR2-V64I 64I: CCR5-A55029G A haplotypes significantly associated according to Bonferroni correction. However, no significant association was found for any of the other polymorphisms with the risk of schizophrenia. Conclusions Our findings suggest that CCR5-A55029G polymorphisms and CCR2-V64I WT: CCR5-A55029G A and CCR2-V64I 64I: CCR5-A55029G A haplotypes might have association with schizophrenia pathogenesis.

  20. Genetic variants in the MRPS30 region and postmenopausal breast cancer risk.

    Science.gov (United States)

    Huang, Ying; Ballinger, Dennis G; Dai, James Y; Peters, Ulrike; Hinds, David A; Cox, David R; Beilharz, Erica; Chlebowski, Rowan T; Rossouw, Jacques E; McTiernan, Anne; Rohan, Thomas; Prentice, Ross L

    2011-06-24

    Genome-wide association studies have identified several genomic regions that are associated with breast cancer risk, but these provide an explanation for only a small fraction of familial breast cancer aggregation. Genotype by environment interactions may contribute further to such explanation, and may help to refine the genomic regions of interest. We examined genotypes for 4,988 SNPs, selected from recent genome-wide studies, and four randomized hormonal and dietary interventions among 2,166 women who developed invasive breast cancer during the intervention phase of the Women's Health Initiative (WHI) clinical trial (1993 to 2005), and one-to-one matched controls. These SNPs derive from 3,224 genomic regions having pairwise squared correlation (r2) between adjacent regions less than 0.2. Breast cancer and SNP associations were identified using a test statistic that combined evidence of overall association with evidence for SNPs by intervention interaction. The combined 'main effect' and interaction test led to a focus on two genomic regions, the fibroblast growth factor receptor two (FGFR2) and the mitochondrial ribosomal protein S30 (MRPS30) regions. The ranking of SNPs by significance level, based on this combined test, was rather different from that based on the main effect alone, and drew attention to the vicinities of rs3750817 in FGFR2 and rs7705343 in MRPS30. Specifically, rs7705343 was included with several FGFR2 SNPs in a group of SNPs having an estimated false discovery rate < 0.05. In further analyses, there were suggestions (nominal P < 0.05) that hormonal and dietary intervention hazard ratios varied with the number of minor alleles of rs7705343. Genotype by environment interaction information may help to define genomic regions relevant to disease risk. Combined main effect and intervention interaction analyses raise novel hypotheses concerning the MRPS30 genomic region and the effects of hormonal and dietary exposures on postmenopausal breast cancer

  1. A prospective study of health-related quality-of-life outcomes for patients with low-risk prostate cancer managed by active surveillance or radiation therapy.

    Science.gov (United States)

    Banerji, John S; Hurwitz, Lauren M; Cullen, Jennifer; Wolff, Erika M; Levie, Katherine E; Rosner, Inger L; Brand, Timothy C; LʼEsperance, James O; Sterbis, Joseph R; Porter, Christopher R

    2017-05-01

    Patients with low-risk prostate cancer (PCa) often have excellent oncologic outcomes. However, treatment with curative intent can lead to decrements in health-related quality of life (HRQoL). Patients treated with radical prostatectomy have been shown to suffer declines in urinary and sexual HRQoL as compared to those managed with active surveillance (AS). Similarly, patients treated with external-beam radiation therapy (EBRT) are hypothesized to experience greater declines in bowel HRQoL. As health-related quality-of-life (HRQoL) concerns are paramount when selecting among treatment options for low-risk PCa, this study examined HRQoL outcomes in men undergoing EBRT as compared to AS in a prospective, racially diverse cohort. A prospective study of HRQoL in patients with PCa enrolled in the Center for Prostate Disease Research (CPDR) Multicenter National Database was initiated in 2007. The current study included patients diagnosed through April 2014. HRQoL was assessed with the Expanded Prostate Cancer Index Composite (EPIC) and the Medical Outcomes Study Short Form (SF-36). Temporal changes in HRQoL were compared for patients with low-risk PCa managed on AS vs. EBRT at baseline, 1-, 2-, and 3 years post-PCa diagnosis. Longitudinal patterns were modeled using linear regression models fitted with generalized estimating equations (GEE), adjusting for baseline HRQoL, demographic, and clinical patient characteristics. Of the 499 eligible patients with low-risk PCa, 103 (21%) selected AS and 60 (12%) were treated with EBRT. Demographic characteristics of the treatment groups were similar, though a greater proportion of patients in the EBRT group were African American (P = 0.0003). At baseline, both treatment groups reported comparable HRQoL. EBRT patients experienced significantly worse bowel function and bother at 1 year (adjusted mean score: 87 vs. 95, P = 0.001 and 89 vs. 95, P = 0.008, respectively) and 2 years (87 vs. 93, P = 0.007 and 87 vs. 96, P = 0

  2. No survival difference after successful {sup 131}I ablation between patients with initially low-risk and high-risk differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Verburg, Frederik Anton [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); University Medical Center Utrecht, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands); Stokkel, Marcel P.M.; Verkooijen, Robbert B.T. [Leiden University Medical Center, Department of Radiology, Division of Nuclear Medicine, Leiden (Netherlands); Dueren, Christian; Reiners, Christoph [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Maeder, Uwe [University of Wuerzburg, Comprehensive Cancer Center, Wuerzburg (Germany); Isselt, Johannes W. van [University Medical Center Utrecht, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands); Marlowe, Robert J. [Spencer-Fontayne Corporation, Jersey City, NJ (United States); Smit, Johannes W. [Leiden University Medical Center, Department of Endocrinology, Leiden (Netherlands); Luster, Markus [University of Ulm, Department of Nuclear Medicine, Ulm (Germany)

    2010-02-15

    To compare disease-specific survival and recurrence-free survival (RFS) after successful {sup 131}I ablation in patients with differentiated thyroid carcinoma (DTC) between those defined before ablation as low-risk and those defined as high-risk according to the European Thyroid Association 2006 consensus statement. Retrospective data from three university hospitals were pooled. Of 2009 consecutive patients receiving ablation, 509 were identified as successfully ablated based on both undetectable stimulated serum thyroglobulin in the absence of antithyroglobulin antibodies and a negative diagnostic whole-body scan in a follow-up examination conducted 8.1{+-}4.6 months after ablation. Of these 509 patients, 169 were defined as high-risk. After a mean follow-up of 81{+-}64 months (range 4-306 months), only three patients had died of DTC, rendering assessment of disease-specific survival differences impossible. Of the 509 patients, 12 (2.4%) developed a recurrence a mean 35 months (range 12-59 months) after ablation. RFS for the duration of follow-up was 96.6% according to the Kaplan-Meier method. RFS did not differ between high-risk and low-risk patients (p=0.68). RFS differed slightly but significantly between those with papillary and those with follicular thyroid carcinoma (p=0.03) and between those aged {<=}45 years those aged >45 years at diagnosis (p=0.018). After (near) total thyroidectomy and successful {sup 131}I ablation, RFS does not differ between patients classified as high-risk and those classified as low-risk based on TNM stage at diagnosis. Consequently, the follow-up protocol should be determined on the basis of the result of initial treatment rather than on the initial tumour classification. (orig.)

  3. Outpatient rapid 4-step desensitization for gynecologic oncology patients with mild to low-risk, moderate hypersensitivity reactions to carboplatin/cisplatin.

    Science.gov (United States)

    Li, Quan; Cohn, David; Waller, Allyson; Backes, Floor; Copeland, Larry; Fowler, Jeffrey; Salani, Ritu; O'Malley, David

    2014-10-01

    The primary objective of this study is to assess the efficacy and safety of an outpatient, 4-step, one-solution desensitization protocol in gynecologic oncology patients with history of mild to low-risk, moderate hypersensitivity reactions (HSRs) to platinums (carboplatin and cisplatin). This was a single institutional retrospective review. Gynecologic oncology patients with a documented history of mild or low-risk, moderate immediate HSRs to carboplatin/cisplatin and continued treatment with 4-step, one-solution desensitization protocols in the outpatient infusion center were included. Patients with delayed HSRs or immediate high-risk, moderate or severe HSRs were excluded. The primary end point was the rate of successful administrations of each course of platinums. From January 2011 to June 2013, eighteen eligible patients were evaluated for outpatient 4-step, one-solution desensitization. Thirteen patients had a history of HSRs to carboplatin and 5 with HSRs to cisplatin. All of 18 patients successfully completed 94 (98.9%) of 95 desensitization courses in the outpatient infusion center. Eight of 8 (100%) patients with initial mild HSRs completed 29/29 (100%) desensitization courses, and 9 of 10 (90%) of patients with initial moderate HSRs completed 65/66 (94%) desensitization courses. In total, 65/95 (68%) desensitizations resulted in no breakthrough reactions, and mild, moderate and severe breakthrough reactions were seen in 19%, 12% and 1% desensitizations, respectively. No patients were hospitalized during desensitization. The outpatient rapid, 4-step, one-solution desensitization protocol was effective and appeared safe among gynecologic oncology patients who experienced mild to low-risk, moderate HSRs to carboplatin/cisplatin. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Obesity as a Risk Factor for Unfavorable Disease in Men with Low Risk Prostate Cancer and its Relationship with Anatomical Location of Tumor.

    Science.gov (United States)

    Jeong, In Gab; Yoo, Sangjun; Lee, Chunwoo; Kim, Myong; You, Dalsan; Song, Cheryn; Park, Sungchan; Hong, Jun Hyuk; Ahn, Hanjong; Kim, Choung-Soo

    2017-07-01

    We investigated the influence of obesity on unfavorable disease in men with low risk prostate cancer eligible for active surveillance and verified the underlying relationship with tumor location. We analyzed the records of 890 patients with biopsy Gleason score 6 who underwent radical prostatectomy for prostate cancer via multicore (12 or more) biopsy at our institution. Unfavorable disease was defined as primary Gleason pattern 4 or greater, or pathological stage T3 or greater. Multivariate logistic regression analysis was performed to identify factors associated with unfavorable disease. The association of unfavorable disease with anatomical location of the index tumor was assessed. Overall 216 (24.3%), 544 (61.1%) and 130 men (14.6%) had a body mass index of less than 23 (normal), 23 to 27.5 (overweight) and 27.5 kg/m(2) or greater (obese), respectively, according to established cutoff points for Asian men. Multivariate analysis showed that age, prostate volume and body mass index were independent factors for predicting unfavorable disease regardless of the various active surveillance criteria used. For Johns Hopkins Hospital criteria the risk of unfavorable disease was higher in obese patients than in normal weight patients (OR 3.30, p = 0.022). Unfavorable disease was more frequent in cases of transition zone cancer than nontransition zone cancer across all criteria for active surveillance (all p cancer was 4.2% for normal weight, 11.6% for overweight and 16.7% for obesity, respectively (p = 0.022). Obese men with low risk prostate cancer who are eligible for active surveillance are at higher risk for unfavorable pathological features. Obese men more frequently had transition zone cancer, which was associated with unfavorable pathology findings in those with very low risk prostate cancer. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  5. Validation of the North American Chest Pain Rule in Prediction of Very Low-Risk Chest Pain; a Diagnostic Accuracy Study

    Directory of Open Access Journals (Sweden)

    Somayeh Valadkhani

    2017-01-01

    Full Text Available Introduction: Acute coronary syndrome accounts for more than 15% of the chest pains. Recently, Hess et al. developed North American Chest Pain Rule (NACPR to identify very low-risk patients who can be safely discharged from emergency department (ED. The present study aimed to validate this rule in EDs of two academic hospitals.Methods: A prospective diagnostic accuracy study was conducted on consecutive patients 24 years of age and older presenting to the ED with the chief complaint of acute chest pain, during March 2013 to June 2013. Chest pain characteristics, cardiac history, electrocardiogram findings, and cardiac biomarker measurement of patients were collected and screening performance characteristics of NACPR with 95% confidence interval were calculated using SPSS 21.Results: From 400 eligible patients with completed follow up, 69 (17.25 % developed myocardial infarction, 121 (30.25% underwent coronary revascularization, and 4 (2% died because of cardiac or unidentifiable causes. By using NACPR, 34 (8.50% of all the patients could be considered very low- risk and discharged after a brief ED assessment. Among these patients, none developed above-mentioned adverse outcomes within 30 days. Sensitivity, specificity, positive prediction value, and negative prediction value of the rule were 100% (95% CI: 87.35 - 100.00, 45.35 (95% CI: 40.19 - 50.61, 14.52 (95% CI: 10.40 – 19.85, and 100 (95% CI: 97.18 - 100.00, respectively.Conclusions: The present multicenter study showed that NACPR is a good screening tool for early discharge of patients with very low-risk chest pain from ED.

  6. Molecular beacon-based real-time PCR method for detection of 15 high-risk and 5 low-risk HPV types.

    Science.gov (United States)

    Takács, Tibor; Jeney, Csaba; Kovács, Laura; Mózes, Johanna; Benczik, Márta; Sebe, Attila

    2008-04-01

    Detection of HPV infections requires a robust time-effective single-step method for efficient screening. A molecular beacon-based one-step multiplex real-time PCR system was developed to detect 15 high-risk (HPV types 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68) and 5 low-risk HPV types (HPV types 6, 11, 42, 43, 44). Molecular beacons detecting high-risk types are 5'-FAM-3'-DABCYL-labelled, molecular beacons for low-risk detection are 5'-TET-3'-DABCYL-labelled, while the internal control added before sample DNA extraction is detected by a 5'-FAM-TexasRed-3'-DABCYL wavelength-shifting molecular beacon. Accordingly, fluorescent data for HPV detection are collected at 530 nm for high-risk types, 560 nm in case of low-risk types and the reaction internal control is detected at 610 nm on a Roche LightCycler 2.0 instrument. The sensitivity for detected types varies between 22 and 700 copies/reaction. The clinical performance was tested on 161 clinical sample DNAs. The MB-RT PCR results were compared to the typing results obtained by the L1F/L1R PCR and hybridization-based system described previously, and the concordance rate between the two systems was 89.44%. The favorable characteristics shown by this multiplex single-step real-time HPV detection system make this promising approach worthy for further development and application for clinical screening.

  7. Histological variants of cutaneous Kaposi sarcoma

    Directory of Open Access Journals (Sweden)

    Pantanowitz Liron

    2008-07-01

    Full Text Available Abstract This review provides a comprehensive overview of the broad clinicopathologic spectrum of cutaneous Kaposi sarcoma (KS lesions. Variants discussed include: usual KS lesions associated with disease progression (i.e. patch, plaque and nodular stage; morphologic subtypes alluded to in the older literature such as anaplastic and telangiectatic KS, as well as several lymphedematous variants; and numerous recently described variants including hyperkeratotic, keloidal, micronodular, pyogenic granuloma-like, ecchymotic, and intravascular KS. Involuting lesions as a result of treatment related regression are also presented.

  8. Ultrasonographic imaging of papillary thyroid carcinoma variants

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Jung Hee [Dept. of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2017-04-15

    Ultrasonography (US) is routinely used to evaluate thyroid nodules. The US features of papillary thyroid carcinoma (PTC), the most common thyroid malignancy, include hypoechogenicity, spiculated/microlobulated margins, microcalcifications, and a nonparallel orientation. However, many PTC variants have been identified, some of which differ from the classic type of PTC in terms of biological behavior and clinical outcomes. This review describes the US features and clinical implications of the variants of PTC. With the introduction of active surveillance replacing immediate biopsy or surgical treatment of indolent, small PTCs, an understanding of the US characteristics of PTC variants will facilitate the individualized management of patients with PTC.

  9. Are freestanding midwifery units a safe alternative to obstetric units for low-risk, primiparous childbirth? An analysis of effect differences by parity in a matched cohort study.

    Science.gov (United States)

    Christensen, Louise Fischer; Overgaard, Charlotte

    2017-01-09

    Intrapartum complications and the use of obstetric interventions are more common in primiparous childbirth than in multiparous childbirth, leading to concern about out of hospital birth for primiparous women. The purpose of this study was to determine whether the effect of birthplace on perinatal and maternal morbidity and the use of obstetric interventions differed by parity among low-risk women intending to give birth in a freestanding midwifery unit or in an obstetric unit in the North Denmark Region. The study is a secondary analysis of data from a matched cohort study including 839 low-risk women intending birth in a freestanding midwifery unit (primary participants) and 839 low-risk women intending birth in an obstetric unit (individually matched control group). Analysis was by intention-to-treat. Conditional logistic regression analysis was applied to compute odds ratios and effect ratios with 95% confidence intervals for matched pairs stratified by parity. On no outcome did the effect of birthplace differ significantly between primiparous and multiparous women. Compared with their counterparts intending birth in an obstetric unit, both primiparous and multiparous women intending birth in a freestanding midwifery unit were significantly more likely to have an uncomplicated, spontaneous birth with good outcomes for mother and infant and less likely to require caesarean section, instrumental delivery, augmented labour or epidural analgesia (although for caesarean section this trend did not attain statistical significance for multiparous women). Perinatal outcomes were comparable between the two birth settings irrespective of parity. Compared to multiparas, transfer rates were substantially higher for primiparas, but fell over time while rates for multiparas remained stable. Freestanding midwifery units appear to confer significant advantages over obstetric units to both primiparous and multiparous mothers, while their infants are equally safe in both settings

  10. Randomized phase II trial of urethral sparing intensity modulated radiation therapy in low-risk prostate cancer: implications for focal therapy

    Directory of Open Access Journals (Sweden)

    Vainshtein Jeffrey

    2012-06-01

    Full Text Available Abstract Background Low-risk prostate cancer (PCa patients have excellent outcomes, with treatment modality often selected by perceived effects on quality of life. Acute urinary symptoms are common during external beam radiotherapy (EBRT, while chronic symptoms have been linked to urethral dose. Since most low-risk PCa occurs in the peripheral zone (PZ, we hypothesized that EBRT using urethral sparing intensity modulated radiation therapy (US-IMRT could improve urinary health-related quality of life (HRQOL while maintaining high rates of PCa control. Methods Patients with National Comprehensive Cancer Network (NCCN defined low-risk PCa with no visible lesion within 5 mm of the prostatic urethra on MRI were randomized to US-IMRT or standard (S- IMRT. Prescription dose was 75.6 Gy in 41 fractions to the PZ + 3–5 mm for US-IMRT and to the prostate + 3 mm for S-IMRT. For US-IMRT, mean proximal and distal urethral doses were limited to 65 Gy and 74 Gy, respectively. HRQOL was assessed using the Expanded Prostate Cancer Index (EPIC Quality of Life questionnaire. The primary endpoint was change in urinary HRQOL at 3 months. Results From June 2004 to November 2006, 16 patients were randomized, after which a futility analysis concluded that continued accrual was unlikely to demonstrate a difference in the primary endpoint. Mean change in EPIC urinary HRQOL at 3 months was −0.5 ± 11.2 in the US-IMRT arm and +3.9 ± 15.3 in the S-IMRT arm (p = 0.52. Median PSA nadir was higher in the US-IMRT arm (1.46 vs. 0.78, p = 0.05. At 4.7 years median follow-up, three US-IMRT and no S-IMRT patients experienced PSA failure (p = 0.06; HR 8.8, 95% CI 0.9–86. Two out of 3 patients with PSA failure had biopsy-proven local failure, both located contralateral to the original site of disease. Conclusions Compared with S-IMRT, US-IMRT failed to improve urinary HRQOL and resulted in higher PSA nadir and inferior biochemical

  11. Genetic risk variants associated with in situ breast cancer.

    Science.gov (United States)

    Campa, Daniele; Barrdahl, Myrto; Gaudet, Mia M; Black, Amanda; Chanock, Stephen J; Diver, W Ryan; Gapstur, Susan M; Haiman, Christopher; Hankinson, Susan; Hazra, Aditi; Henderson, Brian; Hoover, Robert N; Hunter, David J; Joshi, Amit D; Kraft, Peter; Le Marchand, Loic; Lindström, Sara; Willett, Walter; Travis, Ruth C; Amiano, Pilar; Siddiq, Afshan; Trichopoulos, Dimitrios; Sund, Malin; Tjønneland, Anne; Weiderpass, Elisabete; Peeters, Petra H; Panico, Salvatore; Dossus, Laure; Ziegler, Regina G; Canzian, Federico; Kaaks, Rudolf

    2015-06-13

    Breast cancer in situ (BCIS) diagnoses, a precursor lesion for invasive breast cancer, comprise about 20 % of all breast cancers (BC) in countries with screening programs. Family history of BC is considered one of the strongest risk factors for BCIS. To evaluate the association of BC susceptibility loci with BCIS risk, we genotyped 39 single nucleotide polymorphisms (SNPs), associated with risk of invasive BC, in 1317 BCIS cases, 10,645 invasive BC cases, and 14,006 healthy controls in the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3). Using unconditional logistic regression models adjusted for age and study, we estimated the association of SNPs with BCIS using two different comparison groups: healthy controls and invasive BC subjects to investigate whether BCIS and BC share a common genetic profile. We found that five SNPs (CDKN2BAS-rs1011970, FGFR2-rs3750817, FGFR2-rs2981582, TNRC9-rs3803662, 5p12-rs10941679) were significantly associated with BCIS risk (P value adjusted for multiple comparisons <0.0016). Comparing invasive BC and BCIS, the largest difference was for CDKN2BAS-rs1011970, which showed a positive association with BCIS (OR = 1.24, 95 % CI: 1.11-1.38, P = 1.27 x 10(-4)) and no association with invasive BC (OR = 1.03, 95 % CI: 0.99-1.07, P = 0.06), with a P value for case-case comparison of 0.006. Subgroup analyses investigating associations with ductal carcinoma in situ (DCIS) found similar associations, albeit less significant (OR = 1.25, 95 % CI: 1.09-1.42, P = 1.07 x 10(-3)). Additional risk analyses showed significant associations with invasive disease at the 0.05 level for 28 of the alleles and the OR estimates were consistent with those reported by other studies. Our study adds to the knowledge that several of the known BC susceptibility loci are risk factors for both BCIS and invasive BC, with the possible exception of rs1011970, a putatively functional SNP situated in the CDKN2BAS gene that may be a specific

  12. Histone variants in plant transcriptional regulation.

    Science.gov (United States)

    Jiang, Danhua; Berger, Frédéric

    2017-01-01

    Chromatin based organization of eukaryotic genome plays a profound role in regulating gene transcription. Nucleosomes form the basic subunits of chromatin by packaging DNA with histone proteins, impeding the access of DNA to transcription factors and RNA polymerases. Exchange of histone variants in nucleosomes alters the properties of nucleosomes and thus modulates DNA exposure during transcriptional regulation. Growing evidence indicates the important function of histone variants in programming transcription during developmental transitions and stress response. Here we review how histone variants and their deposition machineries regulate the nucleosome stability and dynamics, and discuss the link between histone variants and transcriptional regulation in plants. This article is part of a Special Issue entitled: Plant Gene Regulatory Mechanisms and Networks, edited by Dr. Erich Grotewold and Dr. Nathan Springer.

  13. TCM Differential Treatment of Cough Variant Asthma

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhong-de; DENG Yi-qi; ZHANG Yu; HAN Yun; LIN Lin; CHAO En-xiang

    2010-01-01

    @@ Cough variant asthma (CVA), also called latent asthma or cough asthma, is a special type of asthma. With gradually deepened understanding of CVA in recent years, good curative effect has been achieved in TCM treatment of CVA.

  14. Variant profiling of evolving prokaryotic populations

    Science.gov (United States)

    Zojer, Markus; Schuster, Lisa N.; Schulz, Frederik; Pfundner, Alexander; Horn, Matthias

    2017-01-01

    Genomic heterogeneity of bacterial species is observed and studied in experimental evolution experiments and clinical diagnostics, and occurs as micro-diversity of natural habitats. The challenge for genome research is to accurately capture this heterogeneity with the currently used short sequencing reads. Recent advances in NGS technologies improved the speed and coverage and thus allowed for deep sequencing of bacterial populations. This facilitates the quantitative assessment of genomic heterogeneity, including low frequency alleles or haplotypes. However, false positive variant predictions due to sequencing errors and mapping artifacts of short reads need to be prevented. We therefore created VarCap, a workflow for the reliable prediction of different types of variants even at low frequencies. In order to predict SNPs, InDels and structural variations, we evaluated the sensitivity and accuracy of different software tools using synthetic read data. The results suggested that the best sensitivity could be reached by a union of different tools, however at the price of increased false positives. We identified possible reasons for false predictions and used this knowledge to improve the accuracy by post-filtering the predicted variants according to properties such as frequency, coverage, genomic environment/localization and co-localization with other variants. We observed that best precision was achieved by using an intersection of at least two tools per variant. This resulted in the reliable prediction of variants above a minimum relative abundance of 2%. VarCap is designed for being routinely used within experimental evolution experiments or for clinical diagnostics. The detected variants are reported as frequencies within a VCF file and as a graphical overview of the distribution of the different variant/allele/haplotype frequencies. The source code of VarCap is available at https://github.com/ma2o/VarCap. In order to provide this workflow to a broad community

  15. Bisalbuminemia. A new molecular variant, albumin Vancouver.

    Science.gov (United States)

    Frohlich, J; Kozier, J; Campbell, D J; Curnow, J V; Tárnoky, A L

    1978-11-01

    Of 18 members of a Fiji Indian family investigated, eight of the 12 males and two of the six females had an electrophoretically slow-type bisalbuminemia (alloalbuminemia). The albumin was characterized by the hiterto unique ratio of the two bands (Al A 35%: variant 65%), and by dye-binding studies and electrophoretic mobility in different media. The data suggest that this is a new variant, which we propose to call albumin Vancouver (Al Va).

  16. Another new variant of Bouveret's syndrome

    Institute of Scientific and Technical Information of China (English)

    Seong-Heum Park; Sang-Woo Lee; Tae-Jin Song

    2009-01-01

    Although Bouveret's syndrome, i.e. gastric outlet obstruction by a large gallstone impacted in the proximal duodenum secondary to a cholecystoduodenal fistula,is rare, its pathogenesis and clinical features are well characterized. However, existence of variant forms of the syndrome are not well known, and as far as we have been described in the English-language literature.We present a case of another new variant of Bouveret's syndrome in a 54-year-old Korean woman.

  17. Brief Analysis of Regional Variants in English%Brief Analysis of Regional Variants in Enghsh

    Institute of Scientific and Technical Information of China (English)

    张炳科

    2008-01-01

    It is universally acknowledged that regional variants exist in each language, for it is impossible that people always employ the same pronunciation or vocabulary or even grammar to express the same meaning no matter how large the scope in which a language is used may be. The author of this paper is just to exemplify some regional variants in English and to analyze the factors that account for the variants ,with the purpose of teaching English well in the most efficient way.

  18. Histone variants: key players of chromatin.

    Science.gov (United States)

    Biterge, Burcu; Schneider, Robert

    2014-06-01

    Histones are fundamental structural components of chromatin. Eukaryotic DNA is wound around an octamer of the core histones H2A, H2B, H3, and H4. Binding of linker histone H1 promotes higher order chromatin organization. In addition to their structural role, histones impact chromatin function and dynamics by, e.g., post-translational histone modifications or the presence of specific histone variants. Histone variants exhibit differential expression timings (DNA replication-independent) and mRNA characteristics compared to canonical histones. Replacement of canonical histones with histone variants can affect nucleosome stability and help to create functionally distinct chromatin domains. In line with this, several histone variants have been implicated in the regulation of cellular processes such as DNA repair and transcriptional activity. In this review, we focus on recent progress in the study of core histone variants H2A.X, H2A.Z, macroH2A, H3.3, and CENP-A, as well as linker histone H1 variants, their functions and their links to development and disease.

  19. Familial Thoracic Aortic Aneurysms and Dissections: Identification of a Novel Locus for Stable Aneurysms with a Low Risk for Progression to Aortic Dissection

    Science.gov (United States)

    Guo, Dong-Chuan; Regalado, Ellen S.; Minn, Charles; Tran-Fadulu, Van; Coney, Joshua; Cao, Jiumei; Wang, Min; Yu, Robert K.; Estrera, Anthony L.; Safi, Hazim J.; Shete, Sanjay S.; Milewicz, Dianna M.

    2013-01-01

    Background Thoracic aortic aneurysms leading to acute aortic dissections (TAAD) are the major diseases that affect the thoracic aorta. Approximately 20% of patients with TAAD have a family history of TAAD, and these patients present younger with more rapidly enlarging aneurysms than patients without a family history of aortic disease. Methods and Results A large family with multiple members with TAAD inherited in an autosomal dominant manner was identified. The ascending aortic aneurysms were associated with slow enlargement, a low risk of dissection, and decreased penetrance in women. Genome-wide linkage analysis was performed and a novel locus on chromosome 12 was identified for the mutant gene causing disease in this family. Of the 12 male members who carry the disease-linked microsatellite haplotype, nine had ascending aortic aneurysms with an average diameter of 4.7 cm and average age of 55 years (age range, 32-76) at the time of diagnosis; only one individual had progressed to acute aortic dissection and no other members with aortic dissections were identified. Women harboring the disease-linked haplotype did not have thoracic aortic disease, including an 84 year old woman. Sequencing of 9 genes within the critical interval at the chromosome 12 locus did not identify the mutant gene. Conclusion Mapping a locus for ascending thoracic aortic aneurysms associated with a low risk of aortic dissection supports our hypothesis that genes leading to familial disease can be associated with less aggressive thoracic aortic disease. PMID:21163914

  20. High expression of AKR1B10 predicts low risk of early tumor recurrence in patients with hepatitis B virus-related hepatocellular carcinoma

    Science.gov (United States)

    Wang, Yan-Yan; Qi, Lu-Nan; Zhong, Jian-Hong; Qin, Hong-Gui; Ye, Jia-Zhou; Lu, Shi-Dong; Ma, Liang; Xiang, Bang-De; Li, Le-Qun; You, Xue-Mei

    2017-01-01

    To clarify the relationship between aldo-keto reductase family 1 member B10 (AKR1B10) expression and early hepatocellular carcinoma (HCC) recurrence, this study detected AKR1B10 expression in tumor and adjacent non-tumor tissues from 110 patients with hepatitis B virus (HBV)-related HCC underwent liver resection and analyzed its correlations with clinicopathological characteristics and prognosis of these patients. Detected by quantitative reverse transcription polymerase chain reaction, AKR1B10 mRNA expression showed significantly higher in HCC tissues than in adjacent non-tumor tissues, with a low level in normal liver tissues. Similar results was confirmed at the protein level using immunohistochemistry and Western blotting. High AKR1B10 expression was negatively correlated with serum alpha-fetoprotein level and positively correlated with HBV-DNA level. Patients with high AKR1B10 expression had significantly higher disease-free survival than those with low expression within 2 years after liver resection. Multivariate analysis also confirmed high AKR1B10 expression to be a predictor of low risk of early HCC recurrence. In addition, high AKR1B10 expression was found to be a favorable factor of overall survival. These results suggest that AKR1B10 is involved in HBV-related hepatocarcinogenesis, but its high expression could predict low risk of early tumor recurrence in patients with HBV-related HCC after liver resection. PMID:28181486

  1. Limiting overdiagnosis of low-risk prostate cancer through an evaluation of the predictive value of transrectal and power Doppler ultrasonography.

    Science.gov (United States)

    Sauvain, Jean Luc; Sauvain, Elise; Papavero, Roger; Louis, Didier; Rohmer, Paul

    2016-12-01

    Overdiagnosis induced by prostate cancer screening makes necessary a better selection of candidate patients for prostate biopsy. The objective of our study is to assess the probability of having a high- or low-risk lesion that could require active surveillance (AS) after biopsies and a normal or abnormal examination, including transrectal and power Doppler ultrasonography (TRUS-PDS). Four hundred and twenty-nine consecutive patients with a PSA level risk of a biological recurrence and Dall'Era's criteria to assess possible AS. The TRUS-PDS was considered positive if one biopsy was positive in the same sextant as the suspect image. One hundred and seventy-seven out of 429 (41 %) T1c cancers were diagnosed; 131 out of 177 (74 %) could be qualified as low risk, and 119 out of 177 (67 %) could require AS. The TRUS-PDS was normal in 285 of 429 patients (66 %). With a normal TRUS-PDS, the probability of not having cancer with a high or intermediate risk was 96 % (negative predictive value). With an abnormal TRUS-PDS, the probability of having a positive biopsy was 59 %, and the probability of having a significant cancer was 30 %, according to the Dall'Era criteria. When TRUS-PDS was normal, these probabilities significantly decreased to 32 and 5 %, respectively (p risk of high- or intermediate-risk cancer.

  2. Low-risk and high-risk histologic features in conjunctival primary acquired melanosis with atypia: Clinicopathologic analysis of 29 cases.

    Science.gov (United States)

    Sugiura, Mitsuhiro; Colby, Kathryn A; Mihm, Martin C; Zembowicz, Artur

    2007-02-01

    The current World Health Organization classification of conjunctival melanocytic proliferations divides them into conjunctival nevi and invasive melanoma but, in contrast to other anatomic sites, does not recognize melanoma in situ. All atypical intraepithelial conjunctival proliferations are included in a heterogeneous category designated as primary acquired melanosis (PAM) with atypia. We performed clinicopathologic analysis of 29 cases of PAM with atypia. On the basis of histologic features and frequency of association with invasive melanoma and metastases, we were able to divide our cases into 2 histologic groups. The low-risk group (13 cases) included lesions composed of small to medium size melanocytes with high nuclear to cytoplasmic ratio and small to medium size hyperchromatic nuclei devoid of nucleoli showing predominantly single cell lentiginous growth pattern. Invasive melanoma occurred in only 2 cases from this group. None of these lesions metastasized. The second, high-risk group (16 cases), showed increased frequency of association with invasive melanoma (15/16 cases, 94%) and metastases (4/16 cases, 25%). These lesions were more heterogeneous architecturally but were all composed of melanocytes showing various degrees of epithelioid features such as abundant cytoplasm, vesicular nuclei, or prominent nucleoli. In 4 cases discrete areas showing high-risk and low-risk features were identified. All 4 lesions were associated with invasion. Our findings offer a practical approach for prognostically useful subclassification of PAM with atypia, which emphasizes cytologic features of intraepithelial conjunctival melanocytic proliferation.

  3. Maternal uterine artery Doppler in the first and second trimesters as screening method for hypertensive disorders and adverse perinatal outcomes in low-risk pregnancies

    Science.gov (United States)

    Scandiuzzi, Rosiane Maciel; Prado, Caio Antonio de Campos; Duarte, Geraldo; Quintana, Silvana Maria; da Silva Costa, Fabrício; Tonni, Gabriele; Cavalli, Ricardo de Carvalho; Marcolin, Alessandra Cristina

    2016-01-01

    Objective To assess the maternal demographic characteristics and uterine artery (UA) Doppler parameters at first and second trimesters of pregnancy as predictors for hypertensive disorders (HDs) and adverse perinatal outcomes. Methods This prospective cohort study comprised 162 singleton low-risk women undergoing routine antenatal care. The left and right UA were assessed by color and pulsed Doppler and the mean pulsatility and resistance indices as well as the presence of a bilateral protodiastolic notch were recorded at 11 to 14 and 20 to 24 weeks' gestation. Multilevel regression analysis was used to determine the effects of maternal characteristics and abnormal UA Doppler parameters on the incidence of HD, small for gestational age newborn, cesarean section rate, Apgar score 95th percentile only at the first trimester showed an increased risk for HD (odds ratio, 23.25; 95% confidence interval, 3.47 to 155.73; P95th percentile (odds ratio, 9.84; 95% confidence interval, 1.05 to 92.10; P=0.05). The model including maternal age, maternal and paternal ethnicity, occupation, parity and UA mean RI increased the relative risk for HD (area under receiver operating characteristics, 0.81). Conclusion A first-trimester screening combining maternal characteristics and UA Doppler parameters is useful to predict HD in a low-risk population. PMID:27668197

  4. Performance of Interleukin-6 and Interleukin-8 serum levels in pediatric oncology patients with neutropenia and fever for the assessment of low-risk

    Directory of Open Access Journals (Sweden)

    Kontny Udo

    2008-03-01

    Full Text Available Abstract Background Patients with chemotherapy-related neutropenia and fever are usually hospitalized and treated on empirical intravenous broad-spectrum antibiotic regimens. Early diagnosis of sepsis in children with febrile neutropenia remains difficult due to non-specific clinical and laboratory signs of infection. We aimed to analyze whether IL-6 and IL-8 could define a group of patients at low risk of septicemia. Methods A prospective study was performed to assess the potential value of IL-6, IL-8 and C-reactive protein serum levels to predict severe bacterial infection or bacteremia in febrile neutropenic children with cancer during chemotherapy. Statistical test used: Friedman test, Wilcoxon-Test, Kruskal-Wallis H test, Mann-Whitney U-Test and Receiver Operating Characteristics. Results The analysis of cytokine levels measured at the onset of fever indicated that IL-6 and IL-8 are useful to define a possible group of patients with low risk of sepsis. In predicting bacteremia or severe bacterial infection, IL-6 was the best predictor with the optimum IL-6 cut-off level of 42 pg/ml showing a high sensitivity (90% and specificity (85%. Conclusion These findings may have clinical implications for risk-based antimicrobial treatment strategies.

  5. The impact of umbilical and uterine artery Doppler indices on antenatal course, labor and delivery in a low-risk primigravid population.

    LENUS (Irish Health Repository)

    Cooley, Sharon M

    2012-02-01

    AIMS: To evaluate the impact of umbilical and uterine artery Doppler in the second and third trimester on antenatal course, labor and delivery in a low-risk primigravid population. METHODS: Prospective recruitment of 1011 low-risk primigravidas with uterine and umbilical artery Doppler assessment at 22-24 weeks and 36 weeks. All mothers and infants were reviewed postnatally with a retrospective analysis of ultrasound and clinical outcome data. RESULTS: Elevated uterine artery indices were associated with increased rates of threatened miscarriage, higher rates of pre-eclampsia (PET) and a higher incidence of fetal birth weight <2nd and 9th centile for gestation. Uterine artery pulsatility index (PI) >95th centile for gestation was associated with statistically higher rates of small-for-gestational age (SGA) infants. Elevated umbilical artery indices were associated with higher rates of induction of labor and a higher incidence of fetal birth weight infants <2nd and 9th centile for gestation. Umbilical artery PI >95th centile for gestation was associated with statistically higher rates of SGA infants. CONCLUSION: Elevated uterine and umbilical artery indices are associated with higher rates of maternal and fetal disease.

  6. Is the peripheral arterial disease in low risk type 2 diabetic patients influenced by body mass index, lipidemic control, and statins?

    Directory of Open Access Journals (Sweden)

    Jayesh Dalpatbhai Solanki

    2016-01-01

    Full Text Available Objective: To correlate BMI, lipidemic control, and statin therapy with PAD measured by ABI in low risk type 2 diabetics. Materials and Methods: A sample of 101 nonsmoking, asymptomatic type 2 diabetics (50 males, 51 females with known glycemic (fasting blood sugar, postprandial blood sugar, glycosylated hemoglobin and lipidemic (total cholesterol, lipoproteins, and triglycerides [TGAs] control was taken. Vascular Doppler was used to derive ABI and PAD was defined as ABI <0.9. ABI values were compared amongst groups and P < 0.05 was considered statistically significant. Results: We found fairly good lipid but poor glycemic control and prevalence of PAD 30%. There was insignificantly low ABI profile in patient having BMI ≥25, hyperlipidemia and absent statin therapy with odds ratio being highest for TGAs ≥150 (3.23 followed by BMI ≥25 (2.61, high-density lipoprotein ≤50 (1.61, low-density lipoprotein ≥100 (1.20, and disuse of statin (1.14 with significance only for BMI. Conclusion: We observed small, insignificant PAD risk by dyslipidemia or non-use of statins in low-risk ambulatory T2DM patients, not so by BMI. This suggests importance of good glycemic control, maintenance of optimum weight, and lifestyle modifications as primary prevention rather than opting for costly and inefficient secondary prevention.

  7. Quality of antenatal care provided by nurse midwives in an Urban health centre with regard to low-risk antenatal mothers

    Directory of Open Access Journals (Sweden)

    Ruby Angeline Pricilla

    2017-01-01

    Full Text Available Background:India contributes to 19% of the global maternal deaths. Good quality antenatal care can prevent maternal deaths by early detection of complications and maintaining maternal health. There are few studies documenting quality of antenatal care in India. This study aimed to document the antenatal services provided by nurse midwives to low-risk pregnant mothers from an urban population. Aims: The primary objective was to describe the quality of the antenatal care provided by nurse midwives of an urban health centre with regard to low-risk mothers. The secondary objective was to document the maternal and early neonatal outcomes of the enrolled mothers during the period of study. Methods: This prospective cohort study was done on 200 pregnant women who had antenatal care by nurse midwives between April 2014 and November 2014. The quality of care was assessed by a checklist adapted from World Health Organization (WHO. Results: We report that the quality of antenatal care for all domains was above 90% except for the health education domain, which was poor with regard to breastfeeding and family planning in the enrolled 200 pregnant women. Conclusion: Our study concluded that trained nurse midwives when regularly monitored, audited and linked with reliable referral facilities can deliver good quality antenatal care.

  8. Evidence that the 5p12 Variant rs10941679 Confers Susceptibility to Estrogen-Receptor-Positive Breast Cancer through FGF10 and MRPS30 Regulation.

    Science.gov (United States)

    Ghoussaini, Maya; French, Juliet D; Michailidou, Kyriaki; Nord, Silje; Beesley, Jonathan; Canisus, Sander; Hillman, Kristine M; Kaufmann, Susanne; Sivakumaran, Haran; Moradi Marjaneh, Mahdi; Lee, Jason S; Dennis, Joe; Bolla, Manjeet K; Wang, Qin; Dicks, Ed; Milne, Roger L; Hopper, John L; Southey, Melissa C; Schmidt, Marjanka K; Broeks, Annegien; Muir, Kenneth; Lophatananon, Artitaya; Fasching, Peter A; Beckmann, Matthias W; Fletcher, Olivia; Johnson, Nichola; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marme, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Flyger, Henrik; Benitez, Javier; González-Neira, Anna; Alonso, M Rosario; Pita, Guillermo; Neuhausen, Susan L; Anton-Culver, Hoda; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Hamann, Ute; Tessier, Daniel C; Vincent, Daniel; Nevanlinna, Heli; Khan, Sofia; Matsuo, Keitaro; Ito, Hidemi; Dörk, Thilo; Bogdanova, Natalia V; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Wu, Anna H; Van Den Berg, David; Lambrechts, Diether; Floris, Giuseppe; Chang-Claude, Jenny; Rudolph, Anja; Radice, Paolo; Barile, Monica; Couch, Fergus J; Hallberg, Emily; Giles, Graham G; Haiman, Christopher A; Le Marchand, Loic; Goldberg, Mark S; Teo, Soo H; Yip, Cheng Har; Borresen-Dale, Anne-Lise; Zheng, Wei; Cai, Qiuyin; Winqvist, Robert; Pylkäs, Katri; Andrulis, Irene L; Devilee, Peter; Tollenaar, Rob A E M; García-Closas, Montserrat; Figueroa, Jonine; Hall, Per; Czene, Kamila; Brand, Judith S; Darabi, Hatef; Eriksson, Mikael; Hooning, Maartje J; Koppert, Linetta B; Li, Jingmei; Shu, Xiao-Ou; Zheng, Ying; Cox, Angela; Cross, Simon S; Shah, Mitul; Rhenius, Valerie; Choi, Ji-Yeob; Kang, Daehee; Hartman, Mikael; Chia, Kee Seng; Kabisch, Maria; Torres, Diana; Luccarini, Craig; Conroy, Don M; Jakubowska, Anna; Lubinski, Jan; Sangrajrang, Suleeporn; Brennan, Paul; Olswold, Curtis; Slager, Susan; Shen, Chen-Yang; Hou, Ming-Feng; Swerdlow, Anthony; Schoemaker, Minouk J; Simard, Jacques; Pharoah, Paul D P; Kristensen, Vessela; Chenevix-Trench, Georgia; Easton, Douglas F; Dunning, Alison M; Edwards, Stacey L

    2016-10-06

    Genome-wide association studies (GWASs) have revealed increased breast cancer risk associated with multiple genetic variants at 5p12. Here, we report the fine mapping of this locus using data from 104,660 subjects from 50 case-control studies in the Breast Cancer Association Consortium (BCAC). With data for 3,365 genotyped and imputed SNPs across a 1 Mb region (positions 44,394,495-45,364,167; NCBI build 37), we found evidence for at least three independent signals: the strongest signal, consisting of a single SNP rs10941679, was associated with risk of estrogen-receptor-positive (ER(+)) breast cancer (per-g allele OR ER(+) = 1.15; 95% CI 1.13-1.18; p = 8.35 × 10(-30)). After adjustment for rs10941679, we detected signal 2, consisting of 38 SNPs more strongly associated with ER-negative (ER(-)) breast cancer (lead SNP rs6864776: per-a allele OR ER(-) = 1.10; 95% CI 1.05-1.14; p conditional = 1.44 × 10(-12)), and a single signal 3 SNP (rs200229088: per-t allele OR ER(+) = 1.12; 95% CI 1.09-1.15; p conditional = 1.12 × 10(-05)). Expression quantitative trait locus analysis in normal breast tissues and breast tumors showed that the g (risk) allele of rs10941679 was associated with increased expression of FGF10 and MRPS30. Functional assays demonstrated that SNP rs10941679 maps to an enhancer element that physically interacts with the FGF10 and MRPS30 promoter regions in breast cancer cell lines. FGF10 is an oncogene that binds to FGFR2 and is overexpressed in ∼10% of human breast cancers, whereas MRPS30 plays a key role in apoptosis. These data suggest that the strongest signal of association at 5p12 is mediated through coordinated activation of FGF10 and MRPS30, two candidate genes for breast cancer pathogenesis.

  9. Beta-glucosidase variants and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Wogulis, Mark; Harris, Paul; Osborn, David

    2017-06-27

    The present invention relates to beta-glucosidase variants, e.g. beta-glucosidase variants of a parent Family GH3A beta-glucosidase from Aspergillus fumigatus. The present invention also relates to polynucleotides encoding the beta-glucosidase variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the beta-glucosidase variants.

  10. BRCA1 and BRCA2 missense variants of high and low clinical significance influence lymphoblastoid cell line post-irradiation gene expression.

    Directory of Open Access Journals (Sweden)

    Nic Waddell

    2008-05-01

    Full Text Available The functional consequences of missense variants in disease genes are difficult to predict. We assessed if gene expression profiles could distinguish between BRCA1 or BRCA2 pathogenic truncating and missense mutation carriers and familial breast cancer cases whose disease was not attributable to BRCA1 or BRCA2 mutations (BRCAX cases. 72 cell lines from affected women in high-risk breast ovarian families were assayed after exposure to ionising irradiation, including 23 BRCA1 carriers, 22 BRCA2 carriers, and 27 BRCAX individuals. A subset of 10 BRCAX individuals carried rare BRCA1/2 sequence variants considered to be of low clinical significance (LCS. BRCA1 and BRCA2 mutation carriers had similar expression profiles, with some subclustering of missense mutation carriers. The majority of BRCAX individuals formed a distinct cluster, but BRCAX individuals with LCS variants had expression profiles similar to BRCA1/2 mutation carriers. Gaussian Process Classifier predicted BRCA1, BRCA2 and BRCAX status, with a maximum of 62% accuracy, and prediction accuracy decreased with inclusion of BRCAX samples carrying an LCS variant, and inclusion of pathogenic missense carriers. Similarly, prediction of mutation status with gene lists derived using Support Vector Machines was good for BRCAX samples without an LCS variant (82-94%, poor for BRCAX with an LCS (40-50%, and improved for pathogenic BRCA1/2 mutation carriers when the gene list used for prediction was appropriate to mutation effect being tested (71-100%. This study indicates that mutation effect, and presence of rare variants possibly associated with a low risk of cancer, must be considered in the development of array-based assays of variant pathogenicity.

  11. Neural cell adhesion molecule differentially interacts with isoforms of the fibroblast growth factor receptor

    DEFF Research Database (Denmark)

    Christensen, Claus; Berezin, Vladimir; Bock, Elisabeth

    2011-01-01

    -binding immunoglobulin-like modules 2 and 3 of FGFR1b, FGFR1c, FGFR2b, FGFR2c, FGFR3b, FGFR3c, and FGFR4, and found that all FGFR isoforms, except for FGFR4, interacted with NCAM. The binding affinity of NCAM-FGFR interactions was considerably higher for splice variant 'b' than for splice variant 'c'. We suggest...

  12. Association of smoking, alcohol drinking and dietary factors with esophageal cancer in high- and low-risk areas of Jiangsu Province, China

    Institute of Scientific and Technical Information of China (English)

    Ming Wu; Zuo-Feng Zhang; Kok J Frans; Pieter van't Veer; Jin-Kou Zhao; Xiao-Shu Hu; Pei-Hua Wang; Yu Qin; Yin-Chang Lu; Jie Yang; Ai-Min Liu; De-Lin Wu

    2006-01-01

    AIM: To study the main environmental and lifestyle factors that account for the regional differences in esophageal cancer (EC) risk in low- and high-risk areas of Jiangsu Province, China.METHODS: Since 2003, a population-based casecontrol study has been conducted simultaneously in lowrisk (Ganyu County) and high-risk (Dafeng County) areas of Jiangsu Province, China. Using identical protocols and pre-tested standardized questionnaire, following written informed consent, eligible subjects were inquired about their detail information on potential determinants of EC, including demographic information, socio-economic status, living conditions, disease history, family cancer history, smoking, alcohol drinking, dietary habits, frequency, amount of food intake, etc. Conditional logistic regression with maximum likelihood estimation was used to obtain Odds ratio (OR) and 95 % confidence interval (95% CI), after adjustment for potential confounders.RESULTS: In the preliminary analysis of the ongoing study, we recruited 291 pairs of cases and controls in Dafeng and 240 pairs of cases and controls in Ganyu,respectively. In both low-risk and high-risk areas, EC was inversely associated with socio-economic status, such as level of education, past economic status and body mass index. However, this disease was more frequent among those who had a family history of cancer or encountered misfortune in the past 10 years. EC was also more frequent among smokers, alcohol drinkers and fast eaters.Furthermore, there was a geographic variation of the associations between smoking, alcohol drinking and EC risk despite the similar prevalence of these risk factors in both low-risk and high-risk areas. The dose-response relationship of smoking and smoking related variables,such as age of the first smoking, duration and amount were apparent only in high-risk areas. On the contrary, a dose-response relationship on the effect of alcohol drinking on EC was observed only in low-risk areas

  13. Blockade of CCR7 leads to decreased dendritic cell migration to draining lymph nodes and promotes graft survival in low-risk corneal transplantation.

    Science.gov (United States)

    Hos, D; Dörrie, J; Schaft, N; Bock, F; Notara, M; Kruse, F E; Krautwald, S; Cursiefen, C; Bachmann, B O

    2016-05-01

    The chemokine receptor CCR7 is essential for migration of mature dendritic cells (DCs) to the regional lymph nodes, and it has been shown that blocking of CCR7 improves graft survival after high-risk corneal transplantation in vascularized recipient corneas. However, it is so far unknown whether blocking of CCR7 reduces migration of DCs from the avascular cornea to the draining lymph nodes and whether this leads to improved graft survival also in the low-risk setting of corneal transplantation, which accounts for the majority of perforating transplantations performed. Therefore, in this study, pellets containing Freund's adjuvant and bovine serum albumin (BSA) conjugated to Alexa488 fluorescent dye were implanted into the corneal stroma of BALB/c mice to analyze antigen uptake by corneal DCs and their migration to the regional lymph nodes. After pellet implantation, mice were either treated by local administration of a CCR7 blocking fusion protein that consisted of CCL19 fused to the Fc part of human IgG1 or a control-IgG. In vivo fluorescence microscopy showed uptake of Alexa488-conjugated BSA by corneal DCs within 8 h. Furthermore, analysis of single cell suspensions of draining lymph nodes prepared after 48 h revealed that 2.1 ± 0.3% of CD11c(+) cells were also Alexa488(+). Importantly, DC migration was significantly reduced after topical administration of CCL19-IgG (1.2 ± 0.2%; p CCR7 blockade on graft rejection after allogeneic low-risk keratoplasty, corneal transplantations were performed using C57BL/6-mice as donors and BALB/c-mice as recipients. Treatment mice received two intraperitoneal loading doses of CCL19-IgG prior to transplantation, followed by local treatment with CCL19-IgG containing eye drops for the first two weeks after transplantation. Control mice received same amounts of control-IgG. Kaplan-Meier survival analysis showed that in the CCL19-IgG treated group, 76% of the grafts survived through the end of the 8 week observation period

  14. Milk intake is not associated with low risk of diabetes or overweight-obesity: a Mendelian randomization study in 97,811 Danish individuals.

    Science.gov (United States)

    Bergholdt, Helle K M; Nordestgaard, Børge G; Ellervik, Christina

    2015-08-01

    High dairy/milk intake has been associated with a low risk of type 2 diabetes observationally, but whether this represents a causal association is unknown. We tested the hypothesis that high milk intake is associated with a low risk of type 2 diabetes and of overweight-obesity, observationally and genetically. In 97,811 individuals from the Danish general population, we examined the risk of incident type 2 diabetes and of overweight-obesity by milk intake observationally and by LCT-13910 C/T genotype [polymorphism (rs4988235) upstream from the lactase (LCT) gene], where TT and TC genotypes are associated with lactase persistence and CC with nonpersistence. Observationally for any compared with no milk intake, the HR for type 2 diabetes was 1.10 (95% CI: 0.98, 1.24; P = 0.11), whereas the OR for overweight-obesity was 1.06 (1.02, 1.09; P = 0.002). Median milk intake was 5 glasses/wk (IQR: 0-10) for lactase TT/TC persistence and 3 (0-7) for CC nonpersistence. Genetically for lactase TT/TC persistence compared with CC nonpersistence, the OR was 0.96 (0.86, 1.08; P = 0.50) for type 2 diabetes and 1.06 (1.00, 1.12; P = 0.04) for overweight-obesity. In a stratified analysis for type 2 diabetes, corresponding values in those with and without milk intake were 0.88 (0.76, 1.03; P = 0.11) and 1.35 (1.07, 1.70; P = 0.01) (P-interaction: 0.002), whereas no gene-milk interaction on overweight-obesity was found. For a 1-glass/wk higher milk intake, the genetic risk ratio for type 2 diabetes was 0.99 (0.93, 1.06), and the corresponding observational risk was 1.01 (1.00, 1.01). For overweight-obesity, the corresponding values were 1.01 (1.00, 1.02) genetically and 1.00 (1.00, 1.01) observationally. High milk intake is not associated with a low risk of type 2 diabetes or overweight-obesity, observationally or genetically via lactase persistence. The higher risk of type 2 diabetes in lactase-persistent individuals without milk intake likely is explained by collider stratification

  15. Placental Growth Factor Levels in Populations with High Versus Low Risk for Cardiovascular Disease and Stressful Physiological Environments such as Microgravity: A Pilot Study

    Science.gov (United States)

    Sundaresan, Alamelu; Mehta, Satish K.; Schlegel, Todd. T.; Russomano, Thais; Pierson, Duane L.; Mann, Vivek; Mansoor, Elvedina; Olamigoke, Loretta; Okoro, Elvis

    2017-02-01

    This pilot study compared placental growth factor (PIGF) levels in populations with high versus low risk for cardiovascular disease. Previous experiments from our laboratory (Sundaresan et al. 2005, 2009) revealed that the angiogenic factor PIGF was up regulated in modeled microgravity conditions in human lymphocytes leading to possible atherogenesis and pathogenesis in microgravity. Since the findings came from microgravity analog experiments, there is a strong link to its usefulness in the microgravity field as a biomarker. It is important to understand, that these findings came from both studies on expression levels of this cardiovascular marker in human lymphocytes in microgravity ( in vitro microgravity analog), and a follow up gene expression study in hind limb suspended mice ( in vivo microgravity analog). The relevance is enhanced because in life on earth, PIGF is an inflammatory biomarker for cardiovascular disease. Studies on the levels of PIGF would help to reduce the risk and prevention of heart failures in astronauts. If we can use this marker to predict and reduce the risk of cardiac events in astronauts and pilots, it would significantly help aerospace medicine operations. The investigations here confirmed that in a cardiovascular stressed population such as coronary artery disease (CAD) and acute coronary syndrome (ACS) patients, PIGF could be overexpressed. We desired to re-evaluate this marker in patients with cardiovascular disease in our own study. PIGF is a marker of inflammation and a predictor of short-term and long-term adverse outcome in ACS. In addition, elevated PIGF levels may be associated with increased risk for CAD.PIGF levels were determined in thirty-one patients undergoing cardiovascular catheterization for reasons other than ACS and in thirty-three low-risk asymptomatic subjects. Additional data on traditional cardiovascular risk factors for both populations were also compiled and compared. We found that PIGF levels were

  16. Rising cesarean deliveries among apparently low-risk mothers at university teaching hospitals in Jordan: analysis of population survey data, 2002–2012

    Science.gov (United States)

    Rifai, Rami Al

    2014-01-01

    Background: Cesarean delivery conducted without medical indication places mothers and infants at risk for adverse outcomes. This study assessed changes in trends of, and factors associated with, cesarean deliveries in Jordan, from 2002 to 2012. Methods: Data for ever-married women ages 15–49 years from the 2002, 2007, and 2012 Jordan Population and Family Health Surveys were used. Analyses were restricted to mothers who responded to a question regarding the hospital-based mode of delivery for their last birth occurring within the 5 years preceding each survey (2002, N = 3,450; 2007, N = 6,307; 2012, N = 6,365). Normal birth weight infants and singleton births were used as markers for births that were potentially low risk for cesarean delivery, because low/high birth weight and multiple births are among the main obstetric variables that have been documented to increase risk of cesareans. Weighted descriptive and multivariate analyses were conducted using 4 logistic regression models: (1) among all mothers; and among mothers stratified (2) by place of delivery; (3) by birth weight of infants; and (4) by singleton vs. multiple births. Results: The cesarean delivery rate increased significantly over time, from 18.2% in 2002, to 20.1% in 2007, to 30.3% in 2012. Place of delivery, birth weight, and birth multiplicity were significantly associated with cesarean delivery after adjusting for confounding factors. Between 2002 and 2012, the rate increased by 99% in public hospitals vs. 70% in private hospitals; by 93% among normal birth weight infants vs. 73% among low/high birth weight infants; and by 92% among singleton births vs. 29% among multiple births. The changes were significant across all categories except among multiple births. Further stratification revealed that the cesarean delivery rate was 2.29 times higher in university teaching hospitals (UTHs) than in private hospitals (Pcesarean delivery rate among births that may have been at low risk for

  17. Distinguishing Low-Risk Luminal A Breast Cancer Subtypes with Ki-67 and p53 Is More Predictive of Long-Term Survival.

    Science.gov (United States)

    Lee, Se Kyung; Bae, Soo Youn; Lee, Jun Ho; Lee, Hyun-Chul; Yi, Hawoo; Kil, Won Ho; Lee, Jeong Eon; Kim, Seok Won; Nam, Seok Jin

    2015-01-01

    Overexpression of p53 is the most frequent genetic alteration in breast cancer. Recently, many studies have shown that the expression of mutant p53 differs for each subtype of breast cancer and is associated with different prognoses. In this study, we aimed to determine the suitable cut-off value to predict the clinical outcome of p53 overexpression and its usefulness as a prognostic factor in each subtype of breast cancer, especially in luminal A breast cancer. Approval was granted by the Institutional Review Board of Samsung Medical Center. We analyzed a total of 7,739 patients who were surgically treated for invasive breast cancer at Samsung Medical Center between Dec 1995 and Apr 2013. Luminal A subtype was defined as ER&PR + and HER2- and was further subclassified according to Ki-67 and p53 expression as follows: luminal A (Ki-67-,p53-), luminal A (Ki-67+, p53-), luminal A (Ki-67 -, p53+) and luminal A (Ki-67+, p53+). Low-risk luminal A subtype was defined as negative for both Ki-67 and p53 (luminal A [ki-67-, p53-]), and others subtypes were considered to be high-risk luminal A breast cancer. A cut-off value of 10% for p53 was a good predictor of clinical outcome in all patients and luminal A breast cancer patients. The prognostic role of p53 overexpression for OS and DFS was only significant in luminal A subtype. The combination of p53 and Ki-67 has been shown to have the best predictive power as calculated by the area under curve (AUC), especially for long-term overall survival. In this study, we have shown that overexpression of p53 and Ki-67 could be used to discriminate low-risk luminal A subtype in breast cancer. Therefore, using the combination of p53 and Ki-67 expression in discriminating low-risk luminal A breast cancer may improve the prognostic power and provide the greatest clinical utility.

  18. Maisonneuve-hyperplantarflexion variant ankle fracture.

    Science.gov (United States)

    Hinds, Richard M; Tran, Wesley H; Lorich, Dean G

    2014-11-01

    Maisonneuve fractures are rare ankle injuries, accounting for up to 7% of all ankle fractures. They consist of a proximal third fibula fracture, syndesmotic disruption, and medial ankle injury (either a deltoid ligament disruption or a medial malleolus fracture), and are often successfully managed with nonoperative treatment of the proximal fibula fracture and open reduction and internal fixation (ORIF) of the medial ankle injury and syndesmotic disruption. The hyperplantarflexion variant ankle fracture comprises approximately 7% of all ankle fractures and features dual posterior tibial lip fractures featuring a posterolateral fragment and a posteromedial fragment. Good functional results have been reported in the literature after ORIF of both the posterolateral and posteromedial fragments of this variant fracture that is not described by the Lauge-Hansen classification. In this report, the authors present the unique case of an isolated ankle fracture demonstrating characteristics of both a Maisonneuve fracture and a hyperplantarflexion variant ankle fracture. They also highlight the diagnostic imaging characteristics, including magnetic resonance imaging (MRI) and preoperative radiograph findings, surgical treatment, and postoperative clinical outcome for this patient with a Maisonneuve-hyperplantarflexion variant ankle fracture. To the authors' knowledge, this unique fracture pattern has not been reported previously in the literature. The authors conclude that although good results were seen postoperatively in this case, the importance of ORIF of both the posteromedial and posterolateral fragments of variant fractures cannot be overstated. They also found MRI to be a particularly helpful adjunct in formulating the correct diagnosis and treatment plan.

  19. Word Variant Identification in Old French

    Directory of Open Access Journals (Sweden)

    Peter Willett

    1997-01-01

    Full Text Available Increasing numbers of historical texts are available in machine-readable form, which retain the original spelling, which can be very different from the modern-day equivalents due to the natural evolution of a language, and because the concept of standardisation in spelling is comparatively modern. Among medieval vernacular writers, the same word could be spelled in different ways and the same author (or scribe might even use several alternative spellings in the same passage. Thus, we do not know,a priori, how many variant forms of a particular word there are in such texts, let alone what these variants might be. Searching on the modern equivalent, or even the commonest historical variant, of a particular word may thus fail to retrieve an appreciable number of occurrences unless the searcher already has an extensive knowledge of the language of the documents. Moreover, even specialist scholars may be unaware of some idiosyncratic variants. Here, we consider the use of computer methods to retrieve variant historical spellings.

  20. Local Control With Reduced-Dose Radiotherapy for Low-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group D9602 Study

    Energy Technology Data Exchange (ETDEWEB)

    Breneman, John, E-mail: john.breneman@uchealth.com [Department of Radiation Oncology, University of Cincinnati and Cincinnati Children' s Hospital Medical Center, Cincinnati, OH (United States); Meza, Jane [Department of Biostatistics, University of Nebraska Medical Center College of Public Health, Omaha, NE (United States); Donaldson, Sarah S. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); Raney, R. Beverly [Children' s Cancer Hospital and Division of Pediatrics, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Children' s Ambulatory Blood and Cancer Center, Dell Children' s Medical Center of Central Texas, Austin, TX (United States); Wolden, Suzanne [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY (United States); Michalski, Jeff [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO (United States); Laurie, Fran [Quality Assurance Review Center, Lincoln, RI (United States); Rodeberg, David A. [Department of Surgery, East Carolina University, Greenville, NC (United States); Meyer, William [Section of Pediatric Hematology/Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Walterhouse, David [Division of Hematology/Oncology, Children' s Memorial Medical Center, Chicago, IL (United States); Hawkins, Douglas S. [Department of Pediatrics, Seattle Children' s Hospital, University of Washington, Seattle, WA (United States)

    2012-06-01

    Purpose: To analyze the effect of reduced-dose radiotherapy on local control in children with low-risk rhabdomyosarcoma (RMS) treated in the Children's Oncology Group D9602 study. Methods and Materials: Patients with low-risk RMS were nonrandomly assigned to receive radiotherapy doses dependent on the completeness of surgical resection of the primary tumor (clinical group) and the presence of involved regional lymph nodes. After resection, most patients with microscopic residual and uninvolved nodes received 36 Gy, those with involved nodes received 41.4 to 50.4 Gy, and those with orbital primary tumors received 45 Gy. All patients received vincristine and dactinomycin, with cyclophosphamide added for patient subsets with a higher risk of relapse in Intergroup Rhabdomyosarcoma Study Group III and IV studies. Results: Three hundred forty-two patients were eligible for analysis; 172 received radiotherapy as part of their treatment. The cumulative incidence of local/regional failure was 15% in patients with microscopic involved margins when cyclophosphamide was not part of the treatment regimen and 0% when cyclophosphamide was included. The cumulative incidence of local/regional failure was 14% in patients with orbital tumors. Protocol-specified omission of radiotherapy in girls with Group IIA vaginal tumors (n = 5) resulted in three failures for this group. Conclusions: In comparison with Intergroup Rhabdomyosarcoma Study Group III and IV results, reduced-dose radiotherapy does not compromise local control for patients with microscopic tumor after surgical resection or with orbital primary tumors when cyclophosphamide is added to the treatment program. Girls with unresected nonbladder genitourinary tumors require radiotherapy for postsurgical residual tumor for optimal local control to be achieved.

  1. Frequency of CDH1 germline mutations in gastric carcinoma coming from high- and low-risk areas: metanalysis and systematic review of the literature

    Directory of Open Access Journals (Sweden)

    Corso Giovanni

    2012-01-01

    Full Text Available Abstract Background The frequency of E-cadherin germline mutations in countries with different incidence rates for gastric carcinoma has not been well established. The goal of this study was to assess the worldwide frequency of CDH1 germline mutations in gastric cancers coming from low- and high-risk areas. Methods English articles using MEDLINE access (from 1998 to 2011. Search terms included CDH1, E-cadherin, germline mutation, gastric cancer, hereditary, familial and diffuse histotype. The study included all E-cadherin germline mutations identified in gastric cancer patients; somatic mutations and germline mutations reported in other tumors were excluded. The method of this study was scheduled in accordance with the "PRISMA statement for reporting systematic reviews and meta-analyses". Countries were classified as low- or middle/high risk-areas for gastric carcinoma incidence. Statistical analysis was performed to correlate the CDH1 mutation frequency with gastric cancer incidence areas. Results A total of 122 E-cadherin germline mutations have been identified; the majority (87.5% occurred in gastric cancers coming from low-risk areas. In high-risk areas, we identified 16 mutations in which missense mutations were predominant. (68.8%. We verified a significant association between the mutation frequency and the gastric cancer risk area (p Conclusions E-cadherin genetic screenings performed in low-risk areas for gastric cancer identified a higher frequency of CDH1 germline mutations. This data could open new approaches in the gastric cancer prevention test; before proposing a proband candidate for the CDH1 genetic screening, geographic variability, alongside the family history should be considered.

  2. Adverse trends of cardiovascular risk factors among low risk populations (1983-1994 - a cohort study of workers and farmers in Guangzhou, China

    Directory of Open Access Journals (Sweden)

    Liu Xiaoqing

    2011-12-01

    Full Text Available Abstract Background The levels and trends of cardiovascular risk factors vary greatly throughout China. We examine 10-year trends of cardiovascular risk factors (1983-1994 and the factors related to these trends among low-risk cohorts of workers and farmers in Guangzhou, China. Methods This is a cohort study of 3,131 workers and 3,493 farmers aged 25-64 years at baseline with 10 years of follow-up. We performed a longitudinal analysis to account for the aging of the cohorts and the repeated measures of the same individual. Results At baseline the prevalence of overweight (including obese ranged from 1.0% to 11.8%, hypertension ranged from 3.8% to 10.5%, and mean serum total cholesterol (TC ranged from 155.4 mg/dl to 187.2 mg/dl. Although prevalence of smoking declined, blood pressure levels and body mass index (BMI increased significantly, and lipid profiles changed unfavorably during the 10-year follow-ups. The prevalence of hypertension increased from 5.0 percentage points (female farmers to 12.3 percentage points (male farmers. Mean TC increased significantly (e.g., +22.8 mg/dl and +17.0 mg/dl in male and female farmers, respectively. In the longitudinal data analyses, increase in BMI was associated with increase in blood pressure levels and TC. Significant adverse trends of risk factors persisted after adjustment for aging, education, BMI, smoking, and alcohol intake. Conclusion Urgent action is needed to prevent and reverse the unhealthy trends occurring among these low risk Chinese workers and farmers.

  3. A dosimetric study of volumetric modulated arc therapy planning techniques for treatment of low-risk prostate cancer in patients with bilateral hip prostheses

    Directory of Open Access Journals (Sweden)

    Suresh B Rana

    2014-01-01

    Full Text Available Background and Purpose: Recently, megavoltage (MV photon volumetric modulated arc therapy (VMAT has gained widespread acceptance as the technique of choice for prostate cancer patients undergoing external beam radiation therapy. However, radiation treatment planning for patients with metallic hip prostheses composed of high-Z materials can be challenging due to (1 presence of streak artifacts from prosthetic hips in computed tomography dataset, and (2 inhomogeneous dose distribution within the target volume. The purpose of this study was to compare the dosimetric quality of VMAT techniques in the form of Rapid Arc (RA for treating low-risk prostate cancer patient with bilateral prostheses. Materials and Methods: Three treatment plans were created using RA techniques utilizing 2 arcs (2-RA, 3 arcs (3-RA, and 4 arcs (4-RA for 6 MV photon beam in Eclipse treatment planning system. Each plan was optimized for total dose of 79.2 Gy prescribed to the planning target volume (PTV over 44 fractions. All three RA plans were calculated with anisotropic analytical algorithm. Results : The mean and maximum doses to the PTV as well as the homogeneity index among all three RA plans were comparable. The plan conformity index was highest in the 2-Arc plan (1.19 and lowest in the 4-Arc plan (1.10. In comparison to the 2-RA technique, the 4-RA technique reduced the doses to rectum by up to 18.8% and to bladder by up to 7.8%. In comparison to the 3-RA technique, the 4-RA technique reduced the doses to rectum by up to 14.6% and to bladder by up to 3.5%. Conclusion: Based on the RA techniques investigated for a low-risk prostate cancer patient with bilateral prostheses, the 4-RA plan produced lower rectal and bladder dose and better dose conformity across the PTV in comparison with the 2-RA and 3-RA plans.

  4. Home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban. Rationale and design of the HoT-PE Trial.

    Science.gov (United States)

    Barco, Stefano; Lankeit, Mareike; Binder, Harald; Schellong, Sebastian; Christ, Michael; Beyer-Westendorf, Jan; Duerschmied, Daniel; Bauersachs, Rupert; Empen, Klaus; Held, Matthias; Schwaiblmair, Martin; Fonseca, Cândida; Jiménez, David; Becattini, Cecilia; Quitzau, Kurt; Konstantinides, Stavros

    2016-07-01

    Pulmonary embolism (PE) is a potentially life-threatening acute cardiovascular syndrome. However, more than 95 % of patients are haemodynamically stable at presentation, and among them are patients at truly low risk who may qualify for immediate or early discharge. The Home Treatment of Pulmonary Embolism (HoT-PE) study is a prospective international multicentre single-arm phase 4 management (cohort) trial aiming to determine whether home treatment of acute low-risk PE with the oral factor Xa inhibitor rivaroxaban is feasible, effective, and safe. Patients with confirmed PE, who have no right ventricular dysfunction or free floating thrombi in the right atrium or ventricle, are eligible if they meet none of the exclusion criteria indicating haemodynamic instability, serious comorbidity or any condition mandating hospitalisation, or a familial/social environment unable to support home treatment. The first dose of rivaroxaban is given in hospital, and patients are discharged within 48 hours of presentation. Rivaroxaban is taken for at least three months. The primary outcome is symptomatic recurrent venous thromboembolism or PE-related death within three months of enrolment. Secondary outcomes include quality of life and patient satisfaction, and health care resource utilisation compared to existing data on standard-duration hospital treatment. HoT-PE is planned to analyse 1,050 enrolled patients, providing 80 % power to reject the null hypothesis that the recurrence rate of venous thromboembolism is >3 % with α≤0.05. If the hypothesis of HoT-PE is confirmed, early discharge and out-of-hospital treatment may become an attractive, potentially cost-saving option for a significant proportion of patients with acute PE.

  5. Knowledge of pathologically versus clinically negative lymph nodes is associated with reduced use of radioactive iodine post-thyroidectomy for low-risk papillary thyroid cancer.

    Science.gov (United States)

    Ruel, Ewa; Thomas, Samantha; Dinan, Michaela A; Perkins, Jennifer M; Roman, Sanziana A; Sosa, Julie Ann

    2016-06-01

    Cervical lymph node metastases are common in papillary thyroid cancer (PTC). Clinically negative lymph nodes confer uncertainty about true lymph node status, potentially prompting empiric postoperative radioactive iodine (RAI) administration even in low-risk patients. We examined the association of clinically (cN0) versus pathologically negative (pN0) lymph nodes with utilization of RAI for low-risk PTC. Using the National Cancer Database 1998-2011, adults with PTC who underwent total thyroidectomy for Stage I/II tumors 1-4 cm were evaluated for receipt of RAI based on cN0 versus pN0 status. Cut-point analysis was conducted to determine the number of pN0 nodes associated with the greatest decrease in the odds of receipt of RAI. Survival models and multivariate analyses predicting RAI use were conducted separately for all patients and patients negative surgical margins and multifocal disease (all p negative nodes reported in surgical pathology specimens was 4; ≥5 pathologically negative lymph nodes provided the best cut-point associated with reduced RAI administration (OR 0.91, CI 0.85-0.97). After multivariable adjustment, pN0 patients with ≥5 nodes examined were less likely to receive RAI compared to cN0 patients across all ages (OR 0.89, p negative lymph nodes in patients with PTC appears to influence the decision to administer postoperative RAI if ≥5 negative lymph nodes are removed. It is possible that fewer excised lymph nodes may be viewed by clinicians as incidentally resected and thus may suboptimally represent the true nodal status of the central neck. Further research is warranted to determine if there is an optimal number of lymph nodes that should be resected to standardize pathological diagnosis.

  6. Variants of Monteggia Type Injury: Case Reports

    Directory of Open Access Journals (Sweden)

    Kamudin NAF

    2015-03-01

    Full Text Available Background: Monteggia fracture-dislocation is rare in children. Various reports attest to its rarity, while recording the many variant of this injury. It is, therefore, easy to miss the diagnosis in the absence of proper clinical examination and radiographs. Case Report : This report highlights two rare variants of Monteggia fracture-dislocation seen in children. The first case was a 12-year old girl alleged to have fallen from a 15-feet tall tree and sustaining a combined type III Monteggia injury with ipsilateral Type II Salter-Harris injury of distal end radius with a metaphyseal fracture of the distal third of the ulna. The second case was a 13-year old who had sustained a closed fracture of atypical Type I Monteggia hybrid lesion, in a road traffic accident. Conclusion: This report highlights the rare variants of Monteggia fracture dislocation which could have been missed without proper clinical examinations and radiographs.

  7. Variants of Monteggia Type Injury: Case Reports

    Science.gov (United States)

    Firdouse, M; Han, CS; M Yusof, A

    2015-01-01

    Background Monteggia fracture-dislocation is rare in children. Various reports attest to its rarity, while recording the many variant of this injury. It is, therefore, easy to miss the diagnosis in the absence of proper clinical examination and radiographs. Case Report This report highlights two rare variants of Monteggia fracture-dislocation seen in children. The first case was a 12-year old girl alleged to have fallen from a 15- feet tall tree and sustaining a combined type III Monteggia injury with ipsilateral Type II Salter-Harris injury of distal end radius with a metaphyseal fracture of the distal third of the ulna. The second case was a 13-year old who had sustained a closed fracture of atypical Type I Monteggia hybrid lesion, in a road traffic accident. Conclusion This report highlights the rare variants of Monteggia fracture dislocation which could have been missed without proper clinical examinations and radiographs. PMID:28435591

  8. Genetics in psychiatry: common variant association studies

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    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.

  9. A case of reninoma with variant angina

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    Hyung Ah Jo

    2014-06-01

    Full Text Available Reninoma is a tumor of the renal juxtaglomerular cell apparatus that causes hypertension and hypokalemia because of hypersecretion of renin. We present a case of a 29-year-old female patient with reninoma and concomitant variant angina. The patient had uncontrolled hypertension and elevated plasma renin activity and aldosterone levels. Imaging studies revealed a mass in the left kidney, which was further confirmed as a renin-producing lesion via selective venous catheterization. During the evaluation, the patient had acute-onset chest pain that was diagnosed as variant angina after a provocation test. After partial nephrectomy, the plasma renin activity and plasma aldosterone levels decreased and blood pressure normalized. We report a case of reninoma with variant angina.

  10. Hemoglobin variants: biochemical properties and clinical correlates.

    Science.gov (United States)

    Thom, Christopher S; Dickson, Claire F; Gell, David A; Weiss, Mitchell J

    2013-03-01

    Diseases affecting hemoglobin synthesis and function are extremely common worldwide. More than 1000 naturally occurring human hemoglobin variants with single amino acid substitutions throughout the molecule have been discovered, mainly through their clinical and/or laboratory manifestations. These variants alter hemoglobin structure and biochemical properties with physiological effects ranging from insignificant to severe. Studies of these mutations in patients and in the laboratory have produced a wealth of information on hemoglobin biochemistry and biology with significant implications for hematology practice. More generally, landmark studies of hemoglobin performed over the past 60 years have established important paradigms for the disciplines of structural biology, genetics, biochemistry, and medicine. Here we review the major classes of hemoglobin variants, emphasizing general concepts and illustrative examples.

  11. Coding variants at hexa-allelic amino acid 13 of HLA-DRB1 explain independent SNP associations with follicular lymphoma risk.

    Science.gov (United States)

    Foo, Jia Nee; Smedby, Karin E; Akers, Nicholas K; Berglund, Mattias; Irwan, Ishak D; Jia, Xiaoming; Li, Yi; Conde, Lucia; Darabi, Hatef; Bracci, Paige M; Melbye, Mads; Adami, Hans-Olov; Glimelius, Bengt; Khor, Chiea Chuen; Hjalgrim, Henrik; Padyukov, Leonid; Humphreys, Keith; Enblad, Gunilla; Skibola, Christine F; de Bakker, Paul I W; Liu, Jianjun

    2013-07-11

    Non-Hodgkin lymphoma represents a diverse group of blood malignancies, of which follicular lymphoma (FL) is a common subtype. Previous genome-wide association studies (GWASs) have identified in the human leukocyte antigen (HLA) class II region multiple independent SNPs that are significantly associated with FL risk. To dissect these signals and determine whether coding variants in HLA genes are responsible for the associations, we conducted imputation, HLA typing, and sequencing in three independent populations for a total of 689 cases and 2,446 controls. We identified a hexa-allelic amino acid polymorphism at position 13 of the HLA-DR beta chain that showed the strongest association with FL within the major histocompatibility complex (MHC) region (multiallelic p = 2.3 × 10⁻¹⁵). Out of six possible amino acids that occurred at that position within the population, we classified two as high risk (Tyr and Phe), two as low risk (Ser and Arg), and two as moderate risk (His and Gly). There was a 4.2-fold difference in risk (95% confidence interval = 2.9-6.1) between subjects carrying two alleles encoding high-risk amino acids and those carrying two alleles encoding low-risk amino acids (p = 1.01 × 10⁻¹⁴). This coding variant might explain the complex SNP associations identified by GWASs and suggests a common HLA-DR antigen-driven mechanism for the pathogenesis of FL and rheumatoid arthritis.

  12. Cryptanalysis of SIMON Variants with Connections

    DEFF Research Database (Denmark)

    Alizadeh, Javad; Alkhzaimi, Hoda A.; Aref, Mohammad Reza

    2014-01-01

    SIMON is a family of 10 lightweight block ciphers published by Beaulieu et al. from the United States National Security Agency (NSA). A cipher in this family with K-bit key and N-bit block is called SIMONN/K. We present several linear characteristics for reduced-round SIMON32/64 that can be used...... the presented observations do not directly yield an attack, but provide a basis for further analysis for the specific SIMON variant. Finally, we exploit a connection between linear and differential characteristics for SIMON to construct linear characteristics for different variants of reduced-round SIMON. Our...

  13. Histone variants and melanoma: facts and hypotheses.

    Science.gov (United States)

    Konstantinov, Nikifor K; Ulff-Møller, Constance J; Dimitrov, Stefan

    2016-07-01

    Melanoma is the most aggressive form of skin cancer with rising incidence and morbidity. Despite advances in treatment, the 10-yr survival for patients with metastatic disease is less than 10%. During the past few years, ongoing research on different epigenomic aberrations in melanoma has catalyzed better understanding of its pathogenesis and identification of new therapeutics. In our review, we will focus on the role of histone variants, key epigenetic players in melanoma initiation and progression. Specifically, incorporation of histone variants enables additional layers of chromatin structure, and here, we will describe how alterations in this epigenetic behavior impact melanoma.

  14. Variant profiling of evolving prokaryotic populations

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    Markus Zojer

    2017-02-01

    Full Text Available Genomic heterogeneity of bacterial species is observed and studied in experimental evolution experiments and clinical diagnostics, and occurs as micro-diversity of natural habitats. The challenge for genome research is to accurately capture this heterogeneity with the currently used short sequencing reads. Recent advances in NGS technologies improved the speed and coverage and thus allowed for deep sequencing of bacterial populations. This facilitates the quantitative assessment of genomic heterogeneity, including low frequency alleles or haplotypes. However, false positive variant predictions due to sequencing errors and mapping artifacts of short reads need to be prevented. We therefore created VarCap, a workflow for the reliable prediction of different types of variants even at low frequencies. In order to predict SNPs, InDels and structural variations, we evaluated the sensitivity and accuracy of different software tools using synthetic read data. The results suggested that the best sensitivity could be reached by a union of different tools, however at the price of increased false positives. We identified possible reasons for false predictions and used this knowledge to improve the accuracy by post-filtering the predicted variants according to properties such as frequency, coverage, genomic environment/localization and co-localization with other variants. We observed that best precision was achieved by using an intersection of at least two tools per variant. This resulted in the reliable prediction of variants above a minimum relative abundance of 2%. VarCap is designed for being routinely used within experimental evolution experiments or for clinical diagnostics. The detected variants are reported as frequencies within a VCF file and as a graphical overview of the distribution of the different variant/allele/haplotype frequencies. The source code of VarCap is available at https://github.com/ma2o/VarCap. In order to provide this workflow to

  15. The current state of clinical interpretation of sequence variants.

    Science.gov (United States)

    Hoskinson, Derick C; Dubuc, Adrian M; Mason-Suares, Heather

    2017-01-31

    Accurate and consistent variant classification is required for Precision Medicine. But clinical variant classification remains in its infancy. While recent guidelines put forth jointly by the American College of Medical Genetics and Genomics (ACMG) and Association of Molecular Pathology (AMP) for the classification of Mendelian variants has advanced the field, the degree of subjectivity allowed by these guidelines can still lead to inconsistent classification across clinical molecular genetic laboratories. In addition, there are currently no such guidelines for somatic cancer variants, only published institutional practices. Additional variant classification guidelines, including disease- or gene-specific criteria, along with inter-laboratory data sharing is critical for accurate and consistent variant interpretation.

  16. Cellobiohydrolase I gene and improved variants

    Science.gov (United States)

    Adney, William S.; Decker, Stephen R.; Mc Carter, Suzanne; Baker, John O.; Nieves, Raphael; Himmel, Michael E.; Vinzant, Todd B.

    2008-05-20

    The disclosure provides a method for preparing an active exoglucanase in a heterologous host of eukaryotic origin. The method includes mutagenesis to reduce glycosylation of the exoglucanase when expressed in a heterologous host. It is further disclosed a method to produce variant cellobiohydrolase that is stable at high temperature through mutagenesis.

  17. Developing consistent pronunciation models for phonemic variants

    CSIR Research Space (South Africa)

    Davel, M

    2006-09-01

    Full Text Available from a lexicon containing variants. In this paper we (the authors) address both these issues by creating ‘pseudo-phonemes’ associated with sets of ‘generation restriction rules’ to model those pronunciations that are consistently realised as two or more...

  18. Mining Process Variants: Goals and Issues

    NARCIS (Netherlands)

    Li, C.; Reichert, M.U.; Wombacher, A.

    2008-01-01

    Recently, Process-Aware Information Systems (PAIS) were introduced, which allow for dynamic process and service changes. This, in turn, has led to a large number of process model variants, which are difficult to maintain and expensive to configure. This paper deals with goals and issues related to t

  19. Splicing variants of porcine synphilin-1

    DEFF Research Database (Denmark)

    Larsen, Knud Erik; Madsen, Lone Bruhn; Farajzadeh, Leila

    2015-01-01

    RNA was investigated by RNAseq. The presented work reports the molecular cloning and characterization of the porcine (Sus scrofa) synphilin-1 cDNA (SNCAIP) and three splice variants hereof. The porcine SNCAIP cDNA codes for a protein (synphilin-1) of 919 amino acids which shows a high similarity to human (90...

  20. Report of a rare anatomic variant

    DEFF Research Database (Denmark)

    De Brucker, Y; Ilsen, B; Muylaert, C;

    2015-01-01

    We report the CT findings in a case of partial anomalous pulmonary venous return (PAPVR) from the left upper lobe in an adult. PAPVR is an anatomic variant in which one to three pulmonary veins drain into the right atrium or its tributaries, rather than into the left atrium. This results in a lef...

  1. Splicing variants of porcine synphilin-1

    Directory of Open Access Journals (Sweden)

    Knud Larsen

    2015-09-01

    Full Text Available Parkinson's disease (PD, idiopathic and familial, is characterized by degradation of dopaminergic neurons and the presence of Lewy bodies (LB in the substantia nigra. LBs contain aggregated proteins of which α-synuclein is the major component. The protein synphilin-1 interacts and colocalizes with α-synuclein in LBs. The aim of this study was to isolate and characterize porcine synphilin-1 and isoforms hereof with the future perspective to use the pig as a model for Parkinson's disease. The porcine SNCAIP cDNA was cloned by reverse transcriptase PCR. The spatial expression of SNCAIP mRNA was investigated by RNAseq. The presented work reports the molecular cloning and characterization of the porcine (Sus scrofa synphilin-1 cDNA (SNCAIP and three splice variants hereof. The porcine SNCAIP cDNA codes for a protein (synphilin-1 of 919 amino acids which shows a high similarity to human (90% and to mouse (84% synphilin-1. Three shorter transcript variants of the synphilin-1 gene were identified, all lacking one or more exons. SNCAIP transcripts were detected in most examined organs and tissues and the highest expression was found in brain tissues and lung. Conserved splicing variants and a novel splice form of synhilin-1 were found in this study. All synphilin-1 isoforms encoded by the identified transcript variants lack functional domains important for protein degradation.

  2. HLogo: a parallel Haskell variant of Netlogo

    NARCIS (Netherlands)

    N. Bezirgiannis (Nikolaos); Prasetya, I.S.W.B.; Sakellariou, I.

    2016-01-01

    textabstractAgent-based Modeling (ABM) has become quite popular to the simulation community for its usability and wide area of applicability. However, speed is not usually a trait that ABM tools are characterized of attaining. This paper presents HLogo, a parallel variant of the NetLogo ABM framewor

  3. PIN1 gene variants in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Siedlecki Janusz

    2009-11-01

    Full Text Available Abstract Background Peptidyl-prolyl isomerase, NIMA-interacting 1 (PIN1 plays a significant role in the brain and is implicated in numerous cellular processes related to Alzheimer's disease (AD and other neurodegenerative conditions. There are confounding results concerning PIN1 activity in AD brains. Also PIN1 genetic variation was inconsistently associated with AD risk. Methods We performed analysis of coding and promoter regions of PIN1 in early- and late-onset AD and frontotemporal dementia (FTD patients in comparison with healthy controls. Results Analysis of eighteen PIN1 common polymorphisms and their haplotypes in EOAD, LOAD and FTD individuals in comparison with the control group did not reveal their contribution to disease risk. In six unrelated familial AD patients four novel PIN1 sequence variants were detected. c.58+64C>T substitution that was identified in three patients, was located in an alternative exon. In silico analysis suggested that this variant highly increases a potential affinity for a splicing factor and introduces two intronic splicing enhancers. In the peripheral leukocytes of one living patient carrying the variant, a 2.82 fold decrease in PIN1 expression was observed. Conclusion Our data does not support the role of PIN1 common polymorphisms as AD risk factor. However, we suggest that the identified rare sequence variants could be directly connected with AD pathology, influencing PIN1 splicing and/or expression.

  4. New genetic variants associated with prostate cancer

    Science.gov (United States)

    Researchers have newly identified 23 common genetic variants -- one-letter changes in DNA known as single-nucleotide polymorphisms or SNPs -- that are associated with risk of prostate cancer. These results come from an analysis of more than 10 million SNP

  5. Histone Variants in Development and Diseases

    Institute of Scientific and Technical Information of China (English)

    Ping Chen; Jicheng Zhao; Guohong Li

    2013-01-01

    Eukaryotic genomic DNA is highly packaged into chromatin by histones to fit inside the nucleus.Other than the bulk packaging role of canonical histones with an expression peak at S phase and replication-coupled deposition,different histone variants have evolved distinct regulatory mechanisms for their expression,deposition and functional implications.The diversity of histone variants results in structural plasticity of chromatin and highlights functionally distinct chromosomal domain,which plays critical roles in development from a fertilized egg into a complex organism,as well as in aging and diseases.However,the mechanisms of this fundamental process are poorly understood so far.It is of particular interest to investigate how the variants are incorporated into chromatin and mark specific chromatin states to regulate gene expression,and how they are involved in development and diseases.In this review,we focus on recent progress in studies of epigenetic regulation of three extensively investigated variants including H2A.Z,macroH2A and H3.3,and their functional implications in development and diseases.

  6. A compendium of genetic variant data

    DEFF Research Database (Denmark)

    Cardoso, Joao; Schöning, Lars Yannik; Herrgard, Markus

    2014-01-01

    Laboratory strains are genetically unstable if exposed to selective pressure as encountered, for example, during molecular cloning, fermentation, or adaptive laboratory evolution experiments. This genetic variation is the consequence of an adaptation process of the microorganism to stress...... obtained from distinct experiments. This compendium of genetic variant is a critical step to develop approaches to automatically and systematically characterize mutated strains in the future....

  7. Gene variants as risk factors for gastroschisis

    Science.gov (United States)

    Yang, Wei; Schultz, Kathleen; Tom, Lauren; Lin, Bin; Carmichael, Suzan L.; Lammer, Edward J.; Shaw, Gary M.

    2016-01-01

    In a population‐based case‐control study in California of 228 infants, we investigated 75 genetic variants in 20 genes and risk of gastroschisis with regard to maternal age, race/ethnicity, vitamin use, and smoking exposure. We hypothesized that genes related to vascular compromise may interact with environmental factors to affect the risk of gastroschisis. Haplotypes were constructed for 75 gene variants using the HaploView program. Risk for gastroschisis associated with each gene variant was calculated for both the homozygotes and the heterozygotes, with the homozygous wildtypes as the referent. Risks were estimated as odds ratios (ORs) with 95% confidence intervals (CIs) by logistic regression. We found 11 gene variants with increased risk and four variants with decreased risk of gastroschisis for heterozygous (ORh) or homozygous variants (ORv) genotypes. These included NOS3 (rs1036145) ORh = 0.4 (95% CI: 0.2–0.7); NOS3 (rs10277237) ORv = 2.7 (95% CI: 1.3–6.0); ADD1 (rs12503220) ORh = 2.9 (95% CI: 1.6–5.4), GNB3 (rs5443) ORh = 0.2 (95% CI: 0.1–0.5), ORv = 0.4 (95% CI: 0.2–0.9); ICAM1 (rs281428) ORv = 6.9 (95% CI: 2.1–22.9), ICAM1 (rs3093030) ORv = 2.6 (95% CI: 1.2–5.6); ICAM4 (rs281438) ORv = 4.9 (95% CI: 1.4–16.6), ICAM5 (rs281417) ORh = 2.1 (95% CI: 1.1–4.1), ORv = 4.8 (95% CI: 1.7–13.6); ICAM5 (rs281440) ORh = 23.7 (95% CI: 5.5–102.5), ORv = 20.6 (95% CI: 3.4–124.3); ICAM5 (rs2075741) ORv = 2.2 (95% CI: 1.1–4.4); NAT1 ORv = 0.3 (95% CI: 0.1–0.9). There were additional associations between several gene variants and gastroschisis among women aged 20–24 and among mothers with and without vitamin use. NOS3, ADD1, ICAM1, ICAM4, and ICAM5 warrant further investigation in additional populations and with the interaction of additional environmental exposures. © 2016 Wiley Periodicals, Inc. PMID:27616475

  8. HIV Type 1 Integrase Natural Polymorphisms in Viral Variants Circulating in FSU Countries.

    Science.gov (United States)

    Lapovok, Ilya; Laga, Vita; Kazennova, Elena; Bobkova, Marina

    2017-08-15

    Natural variability of integrase (IN) across HIV-1 variants may influence the emergence of resistant viruses. The most apparent explanation of these fact is the IN polymorphism and the associated differences in codon usage, which, in turn, influence the probability and the terms of DRMs acquisition. Possible mechanisms by which polymorphisms affect DRMs emergence remain disputed and should still be clarified because these substitutions may be associated with a reduced activity of some INSTIs and may impact on ART regimen choice depending of HIV-1 subtype. The aim of this work was to assess the prevalence of naturally occurring polymorphisms within the HIV-1 integrase gene, which might influence the susceptibility to INSTIs, among the patients from Russia and former USSR countries, according to HIV-1 subtypes. A study involved 506 HIV-1 IN sequences of INSTI-naive patients from Russia, Ukraine, Armenia, Kyrgyzstan, Kazakhstan, Uzbekistan, Belarus, and Georgia. Among them, 194 sequences were newly obtained in this study and 312 were downloaded from Los-Alamos database. The proviral DNA was sequenced using an in-house PCR protocol designed on the basis of a well-conserved integrase region in order to detect all HIV-1 variants. The phylogenetic analyses based on IN population sequencing found subtype A6 being the most prevalent (259) (51.2%) in the collection studied, followed by subtype G (36) (7.1%), AG-recombinants (148) (29.3%), subtype B (50) (9.9%), and CRF03_AB (5) (1,0%). The major INSTI resistance-associated mutations (DRMs) were found only in two A6 samples. The prevalence of minor/accessory substitutions depended on HIV-1 variants, while the most notable findings were L74I in subtype A6 (93.1%) and E157Q in subtype B (44.0%). Most of minor DRMs and polymorphic substitutions were concentrated in the central catalytic domain of the IN molecule. Both the DDE triad and HHCC zinc binding motifs were fully conserved. The results of the study suggest a very low

  9. Sentinel lymph node biopsy is unsuitable for routine practice in younger female patients with unilateral low-risk papillary thyroid carcinoma

    Directory of Open Access Journals (Sweden)

    Zhou ShuMei

    2011-09-01

    Full Text Available Abstract Background Sentinel lymph node (SLN biopsy has been used to assess patients with papillary thyroid carcinoma (PTC. To achieve its full potential the rate of SLN identification must be as close to 100 percent as possible. In the present study we compared the combination of preoperative lymphoscintigraphy scanning by sulfur colloid labeled with 99 m Technetium, gamma-probe guided surgery, and methylene blue with methylene blue, alone, for sentinel node identification in younger women with unilateral low-risk PTC. Methods From January 2004 to January 2007, 90 female patients, ages 23 to 44 (mean = 35, with unilateral low-risk PTC (T1-2N0M0 were prospectively studied. Mean tumor size was 1.3 cm (range, 0.8-3.7 cm. All patients underwent unilateral modified neck dissection. Prior to surgery, patients had, by random assignment, identification and biopsy of SLNs by methylene blue, alone (Group 1, or by sulfur colloid labeled with 99 m Technetium, gamma-probe guided surgery and methylene blue (Group 2. Results In the methylene blue group, SLNs were identified in 39 of 45 patients (86.7%. Of the 39 patients, 28 (71.8% had positive cervical lymph nodes (pN+, and 21 patients (53.8% had pSLN+. In 7 of the 28 pN+ patients (25%, metastases were also detected in non-SLN, thus giving a false-negative rate (FNR of 38.9% (7/18, a negative predictive value (NPV of 61.1% (11/18, and an accuracy of 82.1% (32/39. In the combined technique group, the identification rate (IR of SLN was 100% (45/45. Of the 45 patients, 27 (60.0% had pN+, 24 (53.3% had pSLN+. There was a FNR of 14.3% (3/21, a NPV of 85.7% (18/21, and an accuracy of 93.3% (42/45. The combined techniques group was significantly superior to the methylene blue group in IR (p = 0.035. There were no significant differences between two groups in sensitivity, specificity, NPV, or accuracy. Location of pN+ (55 patients in 84 patients was: level I and V, no patients; level II, 1 patient (1.2%; level III

  10. Increased arterial stiffness in systemic lupus erythematosus (SLE patients at low risk for cardiovascular disease: a cross-sectional controlled study.

    Directory of Open Access Journals (Sweden)

    Karim Sacre

    Full Text Available Cardiovascular disease (CVD is a major cause of death in systemic lupus erythematosus (SLE patients. Although the risk for cardiovascular events in patients with SLE is significant, the absolute number of events per year in any given cohort remains small. Thus, CVD risks stratification in patients with SLE focuses on surrogate markers for atherosclerosis at an early stage, such as reduced elasticity of arteries. Our study was designed to determine whether arterial stiffness is increased in SLE patients at low risk for CVD and analyze the role for traditional and non-traditional CVD risk factors on arterial stiffness in SLE. Carotid-femoral pulse wave velocity (PWV was prospectively assessed as a measure of arterial stiffness in 41 SLE patients and 35 controls (CTL. Adjustment on age or Framingham score was performed using a logistic regression model. Factors associated with PWV were identified separately in SLE patients and in controls using Pearson's correlation coefficient for univariate analysis and multiple linear regression for multivariate analysis. SLE patients and controls displayed a low 10-year risk for CVD according to Framingham score (1.8±3.6% in SLE vs 1.6±2.8% in CTL, p = 0.46. Pulse wave velocity was, however, higher in SLE patients (7.1±1.6 m/s as compared to controls (6.3±0.8 m/s; p = 0.01, after Framingham score adjustment and correlated with internal carotid wall thickness (p = 0.0017. In multivariable analysis, only systolic blood pressure (p = 0.0005 and cumulative dose of glucocorticoids (p = 0.01 were associated with PWV in SLE patients. Interestingly, the link between systolic blood pressure (SBP and arterial stiffness was also confirmed in SLE patients with normal systolic blood pressure. In conclusion, arterial stiffness is increased in SLE patients despite a low risk for CVD according to Framingham score and is associated with systolic blood pressure and glucocorticoid therapy.

  11. OBSTETRIC AND PERINATAL OUTCOME OF LOW-RISK PREGNANCIES WITH TERM LABOUR AND MECONIUM-STAINED AMNIOTIC FLUID AT ST. PHILOMENA’S HOSPITAL

    Directory of Open Access Journals (Sweden)

    Roopashree D

    2016-12-01

    Full Text Available BACKGROUND Meconium-stained amniotic fluid has been considered as sign of foetal distress in presentations other than breech and is associated with poor foetal outcome, but others consider meconium passage by foetus as physiological phenomenon and procedures of environmental hazards to foetus before birth. MATERIALS AND METHODS 200 women with meconium-stained amniotic fluid in labour, all low-risk pregnancies were included in our study from September 2010 to August 2012 admitted in our department. For uniformity of results, cases with obstetric and medical complications were excluded. The cases were divided into three groups depending upon grades of meconium staining as thin, moderate and thick. Foetal monitoring, uterine contractions and Apgar score, birth weight, resuscitation of baby noted. All babies were followed up to first week of neonatal life. RESULTS Of 200 cases, 147 had caesarean delivery 73.5% and 53 had vaginal delivery 26.5%. The incidence of LSCS was found to be maximum in the thick MSAF group 54.5%, 14% in moderate and 5% in this MSAF group. In moderate MSAF group, 2.17% had <7, 1 minute Apgar. In thick MSAF group, 3.33% had <7 Apgar; in thin MSAF group, 11.76% had <7 Apgar at 1 minute. The p value was 0.094 in all grades of MSAF, the 5 min. Apgar’s were more than 7. The occurrence of complications in the baby did not depend on the mode of delivery. The p value was 0.58, which was insignificant. The ‘p value of association of CTG abnormality and foetal morbidity was significant <0.001. The association of grades of meconium and foetal morbidity, the p value was 0.337, which was insignificant. There was no perinatal mortality in our study. CONCLUSION The incidence of low-risk pregnancies with MSAF in our study was 4.5%. There was increased tendency for LSCS in the MSAF. The foetal morbidity depends on the reactivity to CTG not on grades of MSAF. Therefore, close intrapartum monitoring has to be done in such cases and LSCS done

  12. Elective cesarean section or not? Maternal age and risk of adverse outcomes at term: a population-based registry study of low-risk primiparous women.

    Science.gov (United States)

    Herstad, Lina; Klungsøyr, Kari; Skjærven, Rolv; Tanbo, Tom; Forsén, Lisa; Åbyholm, Thomas; Vangen, Siri

    2016-08-17

    Maternal age at delivery and cesarean section rates are increasing. In older women, the decision on delivery mode may be influenced by a reported increased risk of surgical interventions during labor and complications with increasing maternal age. We examined the association between maternal age and adverse outcomes in low-risk primiparous women, and the risk of adverse outcomes by delivery modes, both planned and performed (elective and emergency cesarean section, operative vaginal delivery, and unassisted vaginal delivery) in women aged ≥ 35 years. A population-based registry study was conducted using data from the Medical Birth Registry of Norway and Statistics Norway including 169,583 low-risk primiparas with singleton, cephalic labors at ≥ 37 weeks during 1999 - 2009. Outcomes studied were obstetric blood loss, maternal transfer to intensive care units, 5-min Apgar score, and neonatal complications. We adjusted for potential confounders using relative risk models and multinomial logistic regression. Most adverse outcomes increased with increasing maternal age. However, the increase in absolute risks was low, except for moderate obstetric blood loss and transfer to the neonatal intensive care unit (NICU). Operative deliveries increased with increasing maternal age and in women aged ≥ 35 years, the risk of maternal complications in operative delivery increased. Neonatal adverse outcomes increased mainly in emergency operative deliveries. Moderate blood loss was three times more likely in elective and emergency cesarean section than in unassisted vaginal delivery, and twice as likely in operative vaginal delivery. Low Apgar score and neonatal complications occurred two to three times more often in emergency operative deliveries than in unassisted vaginal delivery. However, comparing outcomes after elective cesarean section and planned vaginal delivery, only moderate blood loss (higher in elective cesarean section), neonatal transfer to

  13. Perinatal and maternal outcomes by planned place of birth for healthy women with low risk pregnancies: the Birthplace in England national prospective cohort study.

    Science.gov (United States)

    Brocklehurst, Peter; Hardy, Pollyanna; Hollowell, Jennifer; Linsell, Louise; Macfarlane, Alison; McCourt, Christine; Marlow, Neil; Miller, Alison; Newburn, Mary; Petrou, Stavros; Puddicombe, David; Redshaw, Maggie; Rowe, Rachel; Sandall, Jane; Silverton, Louise; Stewart, Mary

    2011-11-23

    To compare perinatal outcomes, maternal outcomes, and interventions in labour by planned place of birth at the start of care in labour for women with low risk pregnancies. Prospective cohort study. England: all NHS trusts providing intrapartum care at home, all freestanding midwifery units, all alongside midwifery units (midwife led units on a hospital site with an obstetric unit), and a stratified random sample of obstetric units. 64,538 eligible women with a singleton, term (≥37 weeks gestation), and "booked" pregnancy who gave birth between April 2008 and April 2010. Planned caesarean sections and caesarean sections before the onset of labour and unplanned home births were excluded. A composite primary outcome of perinatal mortality and intrapartum related neonatal morbidities (stillbirth after start of care in labour, early neonatal death, neonatal encephalopathy, meconium aspiration syndrome, brachial plexus injury, fractured humerus, or fractured clavicle) was used to compare outcomes by planned place of birth at the start of care in labour (at home, freestanding midwifery units, alongside midwifery units, and obstetric units). There were 250 primary outcome events and an overall weighted incidence of 4.3 per 1000 births (95% CI 3.3 to 5.5). Overall, there were no significant differences in the adjusted odds of the primary outcome for any of the non-obstetric unit settings compared with obstetric units. For nulliparous women, the odds of the primary outcome were higher for planned home births (adjusted odds ratio 1.75, 95% CI 1.07 to 2.86) but not for either midwifery unit setting. For multiparous women, there were no significant differences in the incidence of the primary outcome by planned place of birth. Interventions during labour were substantially lower in all non-obstetric unit settings. Transfers from non-obstetric unit settings were more frequent for nulliparous women (36% to 45%) than for multiparous women (9% to 13%). The results support a policy

  14. Utilizing time-driven activity-based costing to understand the short- and long-term costs of treating localized, low-risk prostate cancer.

    Science.gov (United States)

    Laviana, Aaron A; Ilg, Annette M; Veruttipong, Darlene; Tan, Hung-Jui; Burke, Michael A; Niedzwiecki, Douglas R; Kupelian, Patrick A; King, Chris R; Steinberg, Michael L; Kundavaram, Chandan R; Kamrava, Mitchell; Kaplan, Alan L; Moriarity, Andrew K; Hsu, William; Margolis, Daniel J A; Hu, Jim C; Saigal, Christopher S

    2016-02-01

    Given the costs of delivering care for men with prostate cancer remain poorly described, this article reports the results of time-driven activity-based costing (TDABC) for competing treatments of low-risk prostate cancer. Process maps were developed for each phase of care from the initial urologic visit through 12 years of follow-up for robotic-assisted laparoscopic prostatectomy (RALP), cryotherapy, high-dose rate (HDR) and low-dose rate (LDR) brachytherapy, intensity-modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and active surveillance (AS). The last modality incorporated both traditional transrectal ultrasound (TRUS) biopsy and multiparametric-MRI/TRUS fusion biopsy. The costs of materials, equipment, personnel, and space were calculated per unit of time and based on the relative proportion of capacity used. TDABC for each treatment was defined as the sum of its resources. Substantial cost variation was observed at 5 years, with costs ranging from $7,298 for AS to $23,565 for IMRT, and they remained consistent through 12 years of follow-up. LDR brachytherapy ($8,978) was notably cheaper than HDR brachytherapy ($11,448), and SBRT ($11,665) was notably cheaper than IMRT, with the cost savings attributable to shorter procedure times and fewer visits required for treatment. Both equipment costs and an inpatient stay ($2,306) contributed to the high cost of RALP ($16,946). Cryotherapy ($11,215) was more costly than LDR brachytherapy, largely because of increased single-use equipment costs ($6,292 vs $1,921). AS reached cost equivalence with LDR brachytherapy after 7 years of follow-up. The use of TDABC is feasible for analyzing cancer services and provides insights into cost-reduction tactics in an era focused on emphasizing value. By detailing all steps from diagnosis and treatment through 12 years of follow-up for low-risk prostate cancer, this study has demonstrated significant cost variation between competing treatments. © 2015

  15. Gene Variant from Africa Linked to Black Obesity

    Science.gov (United States)

    ... html Gene Variant From Africa Linked to Black Obesity Study sees first biological pathway to weight gain ... identified an Africa-specific gene variant associated with obesity. The team found that about 1 percent of ...

  16. Rare variant density across the genome and across populations

    OpenAIRE

    Raska Paola; Zhu Xiaofeng

    2011-01-01

    Abstract Next-generation sequencing allows for a new focus on rare variant density for conducting analyses of association to disease and for narrowing down the genomic regions that show evidence of functionality. In this study we use the 1000 Genomes Project pilot data as distributed by Genetic Analysis Workshop 17 to compare rare variant densities across seven populations. We made the comparisons using regressions of rare variants on total variant counts per gene for each population and Taji...

  17. Combined analyses of 20 common obesity susceptibility variants

    DEFF Research Database (Denmark)

    Sandholt, Camilla Helene; Sparsø, Thomas; Grarup, Niels;

    2010-01-01

    Genome-wide association studies and linkage studies have identified 20 validated genetic variants associated with obesity and/or related phenotypes. The variants are common, and they individually exhibit small-to-modest effect sizes.......Genome-wide association studies and linkage studies have identified 20 validated genetic variants associated with obesity and/or related phenotypes. The variants are common, and they individually exhibit small-to-modest effect sizes....

  18. Novel potential ALL low-risk markers revealed by gene expression profiling with new high-throughput SSH-CCS-PCR.

    Science.gov (United States)

    Qiu, J; Gunaratne, P; Peterson, L E; Khurana, D; Walsham, N; Loulseged, H; Karni, R J; Roussel, E; Gibbs, R A; Margolin, J F; Gingras, M C

    2003-09-01

    The current systems of risk grouping in pediatric acute lymphoblastic leukemia (ALL) fail to predict therapeutic success in 10-35% of patients. To identify better predictive markers of clinical behavior in ALL, we have developed an integrated approach for gene expression profiling that couples suppression subtractive hybridization, concatenated cDNA sequencing, and reverse transcriptase real-time quantitative PCR. Using this approach, a total of 600 differentially expressed genes were identified between t(4;11) ALL and pre-B ALL with no determinant chromosomal translocation. The expression of 67 genes was analyzed in different cytogenetic ALL subgroups and B lymphocytes isolated from healthy donors. Three genes, BACH1, TP53BPL, and H2B/S, were consistently expressed as a significant cluster associated with the low-risk ALL subgroups. A total of 42 genes were differentially expressed in ALL vs normal B lymphocytes, with no specific association with any particular ALL subgroups. The remaining 22 genes were part of a specific expression profile associated with the hyperdiploid, t(12;21), or t(4;11) subgroups. Using an unsupervised hierarchical cluster analysis, the discriminating power of these specific expression profiles allowed the clustering of patients according to their subgroups. These genes could help to understand the difference in treatment response and become therapeutical targets to improve ALL clinical outcomes.

  19. Ponderal index (PI) vs birth weight centiles in the low-risk primigravid population: which is the better predictor of fetal wellbeing?

    LENUS (Irish Health Repository)

    Cooley, S M

    2012-07-01

    Our objective was to compare Ponderal index (PI) with birth weight centiles as predictors of perinatal morbidity and to determine which best reflects the presence of placental disease. We prospectively recruited 1,011 low-risk primigravidas and calculated PI and birth weight centiles following delivery. Perinatal morbidity was defined as: pre-term birth (PTB); fetal acidosis; an Apgar score <7 at 5 min or neonatal resuscitation. Placental disease was defined as chronic uteroplacental insufficiency (CUPI); villous dysmaturity; infection or vascular pathology. Ponderal index was statistically reduced (25.33 vs 27.79 p =0.001) and the incidence of infant birth weight <9th centile was statistically higher (11.1% vs 5.1%; p =0.004) in cases with PTB and in CUPI (26.23 vs 27.84; p =0.001 and 28.2.1% vs 10.4%; p =0.002). Both PI and infant birth weight centile <9th centile for gestational age correlate with PTB, however overall, both are poor predictors of neonatal and placental disease.

  20. Codetection of Trichomonas vaginalis and Candida albicans by PCR in Urine Samples in a Low-Risk Population Attended in a Clinic First Level in Central Veracruz, Mexico

    Directory of Open Access Journals (Sweden)

    A. López-Monteon

    2013-01-01

    Full Text Available The aim of this study is to estimate the prevalence of Trichomonas vaginalis and Candida albicans in low-risk patients treated at a first level clinic (primary health care represents the first level of contact of individuals, families, and the community with the system national health. Using a cross-sectional study in patients treated in clinical laboratory of the Sanitary District no. 7 of the city of Orizaba during the months June-July, 252 urine samples were collected for the identification of T. vaginalis and C. albicans by PCR. Furthermore, we analyzed the sociodemographic characteristics of the studied population. We observed an overall prevalence of 23.41% (95% CI 22.10–24.72 for T. vaginalis and 38.88% (95% CI 37.73–40.03 for C. albicans. There was also presence of coinfection in 14.28% (95% CI 13.10–15.46, which was associated with the presence of pain. Most of the positive cases were observed in women house-maker (80%, 95% CI 50.36–48.98. The results of this study provide evidence that the majority of positive cases observed in the studied population are presented in an asymptomatic form and usually are not associated with any risk factor.

  1. Association of Low-Risk Human Papillomavirus Infection with Male Circumcision in Young Men: Results from a Longitudinal Study Conducted in Orange Farm (South Africa

    Directory of Open Access Journals (Sweden)

    Chloé Tarnaud

    2011-01-01

    Full Text Available Background. Low-Risk Human Papillomavirus (LR-HPV genotypes 6 and 11 cause genital warts. This study investigated the association of LR-HPV infection with male circumcision (MC. Methods. We used data from the South African MC trial conducted among young men. Urethral swabs, collected among intervention (circumcised and control (uncircumcised groups, were analyzed using HPV linear array. Adjusted LR-HPV prevalence rate ratio (aPPR and Poisson mean ratio (aPMR of number of LR-HPV genotypes were estimated using log-Poisson regression, controlling for background characteristics, sexual behaviour, and HIV and HSV-2 statuses. Results. Compared to controls, LR-HPV prevalence and mean number of genotypes were significantly lower among the intervention group ((8.5% versus 15.8%; aPRR: 0.54, P<.001 and (0.33 versus 0.18; aPMR: 0.54, P<.001, resp.. Mean number of LR-HPV genotypes increased with number of lifetime sexual partners and decreased with education level and consistent condom use. Conclusions. This study shows a reduction in LR-HPV infection among circumcised men.

  2. A national standard for psychosocial safety climate (PSC): PSC 41 as the benchmark for low risk of job strain and depressive symptoms.

    Science.gov (United States)

    Bailey, Tessa S; Dollard, Maureen F; Richards, Penny A M

    2015-01-01

    Despite decades of research from around the world now permeating occupational health and safety (OHS) legislation and guidelines, there remains a lack of tools to guide practice. Our main goal was to establish benchmark levels of psychosocial safety climate (PSC) that would signify risk of job strain (jobs with high demands and low control) and depression in organizations. First, to justify our focus on PSC, using interview data from Australian employees matched at 2 time points 12 months apart (n = 1081), we verified PSC as a significant leading predictor of job strain and in turn depression. Next, using 2 additional data sets (n = 2097 and n = 1043) we determined benchmarks of organizational PSC (range 12-60) for low-risk (PSC at 41 or above) and high-risk (PSC at 37 or below) of employee job strain and depressive symptoms. Finally, using the newly created benchmarks we estimated the population attributable risk (PAR) and found that improving PSC in organizations to above 37 could reduce 14% of job strain and 16% of depressive symptoms in the working population. The results provide national standards that organizations and regulatory agencies can utilize to promote safer working environments and lower the risk of harm to employee mental health.

  3. Assessing the safety of physician-directed nurse-administered propofol sedation in low-risk patients undergoing endoscopy and colonoscopy

    Science.gov (United States)

    Sathananthan, Dharshan; Young, Edward; Nind, Garry; George, Biju; Ashby, Angelie; Drummond, Sharon; Redel, Kasia; Green, Neville; Singh, Rajvinder

    2017-01-01

    Background and study aims Physician-directed nurse-administered balanced propofol sedation (PhD NAPS) in patients undergoing endoscopy and/or colonoscopy is being increasingly utilized worldwide. However, this method of sedation is not universally employed in Australian hospitals due to concerns surrounding its safety. The aim of this study was to assess the safety of PhD NAPS in low-risk patients undergoing endoscopy and/or colonoscopy. Patients and methods This study was conducted at a single tertiary teaching hospital in Adelaide, Australia. It was a prospective study involving 1000 patients with an ASA score of 1 – 3 presenting with any indication for endoscopy, colonoscopy or both. A total of 981 patients (451 male) with a mean age of 53 years (range: 16 – 87) were recruited from January 2010 to October 2012. 440 endoscopies, 420 colonoscopies, and 121 combined procedures were performed. The intra-procedural adverse events (AEs) were recorded. Results There were no major intra-procedural adverse events. Minor AEs occurred in 6.42 % of patients, and resolved spontaneously or with intravenous fluid boluses in all cases. Conclusion PhD NAPS is safe when the proceduralist and nursing staff are adequately trained and strict patient selection criteria are used. PMID:28210707

  4. Routine Cysticotomy and Flushing of the Cystic Duct in Patients with Low Risk of Common Duct Stones: Can It Be Beneficial?

    Directory of Open Access Journals (Sweden)

    Piera Leon

    2017-01-01

    Full Text Available Background. Gallstone disease affects 15–20% of the general population and up to 20% of these patients present common bile duct stones. Aim. This observational study reports our experience on routine cysticotomy and flushing of the cystic duct in patients with low risk of common duct stones. Materials and Methods. We analyzed 731 patients who underwent laparoscopic cholecystectomy between September 2013 and September 2015. Results. Patients were preoperatively stratified on the clinical risk; those presenting with low preoperative risk of common bile duct stones were referred to undergo laparoscopic cholecystectomy and routine cysticotomy with bile duct flushing. Patients presenting thick bile sludge, solid debrides, and/or increased tension of bile outflow underwent unplanned cholangiography. No intraoperative complications or conversion to open technique occurred. Average follow-up time was 22,8 months (range 12 to 37. Rate of retained ductal stones accounted for 0,3%. Conclusions. Routine cysticotomy and bile flushing in our experience is a valid, simple, and not time consuming manoeuvre that can help decompressing and flushing CBD. Moreover, it is a valid tool for extending selective IOC approach in a focused manner. Further evaluations have to be conducted to evaluate risks and effectiveness of this manoeuvre.

  5. Brain Derived Neurotrophic Factor (BDNF) levels as a possible predictor of psychopathology in healthy twins at high and low risk for affective disorder.

    Science.gov (United States)

    Vinberg, Maj; Miskowiak, Kamilla; Kessing, Lars Vedel

    2014-01-01

    Brain Derived Neurotrophic Factor (BDNF) is a potential biomarker of affective disorder. However, longitudinal studies evaluating a potential predictive role of BDNF on subsequent psychopathology are lacking. The aim of this study was to investigate whether BDNF alone or in interaction with the BDNF Val66Met polymorphism predict onset of affective disorder in healthy individuals at heritable risk for affective disorder. In a high-risk study, we assessed whole blood levels of BDNF in 234 healthy monozygotic and dizygotic twins with or without a co-twin history of affective disorder (high and low risk twins, respectively). Participants were followed up longitudinally with questionnaires at 6-month intervals for mean seven years and then reassessed with a personal interview to obtain information about whether they had developed psychiatric illness. At follow-up 36 participants (15.4%) had developed psychiatric disorder. Cox regression analysis revealed that BDNF levels at baseline were not associated with onset of illness in this explorative study. Further, two-way interactions between BDNF levels and the Val66Met polymorphism or between familial risk and the Val66Met polymorphism did not predict illness onset.

  6. Normal value of functional parameters in gated myocardial perfusion SPECT in patients with low risk of coronary artery disease: emory cardiac tool box program

    Energy Technology Data Exchange (ETDEWEB)

    Kang, D. Y.; Kim, M. H.; Kim, Y. D.; Kim, D. K. [Donga University College of Medicine, Busan (Korea, Republic of)

    2002-07-01

    Absolute value of the functional data of gated myocardial perfusion SPECT is necessary to determine that individual patient is normal or not. Tc-99m MIBI gated myocardial perfusion SPECT was performed using emory cardiac tool box program. All patients (M:F=15:36, age 64{+-}10 yrs) showed normal myocardial perfusion. The patients with following characteristics were excluded; previous angina or MI, ECG change with Q wave or ST-T change, diabetes mellitus, hypercholesterolemia, typical chest pain and hypertension. In all patients, myocardial mass is 117{+-}23 g in stress gated SPECT, 106{+-}22 g in stress ungated SPECT and 102{+-}21 g in rest ungated SPECT. EDV is 90{+-}28 ml, ESV 26{+-}20 ml, SV 66{+-}21 ml, EF 73{+-}10 % and TID 1.06{+-}0.14. Myocardial mass in rest ungated SPECT is significantly different between men and women (p=0.025). Myocardial mass is significantly different between stress gated SPECT and stress ungated SPECT (p=0.000), and between stress ungated SPECT and rest ungated SPECT (p=0.003). We provide normal value of functional parameters to determine the abnormality of individual patients in patients with low risk of coronary artery disease.

  7. Mode of Delivery according to Leisure Time Physical Activity before and during Pregnancy: A Multicenter Cohort Study of Low-Risk Women.

    Science.gov (United States)

    Nielsen, Emilie Nor; Andersen, Per Kragh; Hegaard, Hanne Kristine; Juhl, Mette

    2017-01-01

    Objectives. To examine the association between maternal leisure time physical activity and mode of delivery. Study Design. Population-based multicentre cohort. From the Danish Dystocia Study, we included 2,435 nulliparous women, who delivered a singleton infant in cephalic presentation at term after spontaneous onset of labor in 2004-2005. We analysed mode of delivery according to self-reported physical activity at four stages, that is, the year before pregnancy and during first, second, and third trimester, in logistic regression models. Further, we combined physical activity measures at all four stages in one variable for a proportional odds model for cumulative logits. Main Outcome Measures. Mode of delivery (emergency caesarean section; vacuum extractor; spontaneous vaginal delivery). Results. The odds of emergency caesarean section decreased with increasing levels of physical activity with statistically significant trends at all four time stages except the third trimester. This tendency was confirmed in the proportional odds model showing 28% higher odds of a more complicated mode of delivery among women with a low activity level compared to moderately active women. Conclusions. We found increasing leisure time physical activity before and during pregnancy associated with a less complicated delivery among low-risk, nulliparous women.

  8. Impact of age, intrinsic subtype and local treatment on long-term local-regional recurrence and breast cancer mortality among low-risk breast cancer patients

    DEFF Research Database (Denmark)

    Laurberg, Tinne; Alsner, Jan; Tramm, Trine

    2017-01-01

    AIM: To evaluate the long-term prognostic impact of age, local treatment and intrinsic subtypes on the risk of local-regional recurrence (LRR) and breast cancer mortality among low-risk patients.MATERIAL AND METHODS: Cohort study with prospectively collected data, balanced five-year age groups...... no prognostic impact on the 20-year LRR risk, regardless of age. A distinct 20-year mortality pattern was observed among the younger patients: 11% of patients with LumB tumor died of breast cancer within the first five years after primary surgery, 23% of patients with Lum-HER2+ tumor died within a 5-10-year...... period, whereas patients with LumA tumor died with a constant low rate throughout the 20-year period. After 20 years of follow-up, patients with LumA tumor had breast cancer mortality comparable to that of patients with LumB tumor (20%) and lower than Lum-HER2+ tumor (39%). Among the older patients...

  9. ‘ACTIVE LABOR’ DURATION AND DILATION RATES AMONG LOW-RISK, NULLIPAROUS WOMEN WITH SPONTANEOUS LABOR ONSET: A SYSTEMATIC REVIEW

    Science.gov (United States)

    Neal, Jeremy L.; Lowe, Nancy K.; Ahijevych, Karen L.; Patrick, Thelma E.; Cabbage, Lori A.; Corwin, Elizabeth J.

    2009-01-01

    Objective Laboring women are often admitted to labor units under criteria commonly associated with the onset of active phase labor, i.e., cervical dilatation of 3–5 cm in the presence of regular contractions. Beginning with these criteria through complete dilatation, this systematic review describes labor duration and cervical dilation rates among low-risk, nulliparous women with spontaneous labor onset. Methods Studies published in English (1990–2008) were identified via MEDLINE and CINAHL searches. Data were abstracted and weighted ‘active labor’ durations (i.e., from 3–5 cm through complete dilatation) and linear dilation rates were calculated. Results Eighteen studies (n = 7009) reported mean ‘active labor’ duration. The weighted mean duration was 6.0 hrs and the calculated dilation rate was 1.2 cm/hr. These findings closely parallel those found at the median. At the statistical limits, the weighted ‘active labor’ duration was 13.4 hrs (mean + 2 SD) and the dilation rate was 0.6 cm/hr (mean − 2 SD). Conclusions Nulliparous women with spontaneous labor onset have longer ‘active’ labors and, hence, slower dilation rates than are traditionally associated with active labor when commonly used criteria are applied as the starting point. Revision of existing active labor expectations and/or criteria used to prospectively identify active phase onset is warranted. PMID:20630357

  10. Can a Gleason 6 or Less Microfocus of Prostate Cancer in One Biopsy and Prostate-Specific Antigen Level Archetype of Low-Risk Prostate Disease?

    Science.gov (United States)

    Taverna, Gianluigi; Benecchi, Luigi; Grizzi, Fabio; Seveso, Mauro; Giusti, Guido; Piccinelli, Alessandro; Benetti, Alessio; Colombo, Piergiuseppe; Minuti, Francesco; Graziotti, Pierpaolo

    2012-01-01

    Prostate cancer (PC) remains a cause of death worldwide. Here we investigate whether a single microfocus of PC at the biopsy (graded as Gleason 6 or less, ≤5% occupancy) and the PSA archetype of low-risk prostate disease. 4500 consecutive patients were enrolled. Among them, 134 patients with a single micro-focus of PC were followed up, and the parameters influencing the biochemical relapse (BR) were analysed. Out of 134 patients, 94 had clinically significant disease, specifically in 74.26% of the patients with PSA <10 ng/mL. Positive surgical margins and the extracapsular invasion were found in 29.1% and 51.4% patients, respectively. BR was observed in 29.6% of the patients. Cox regression evidenced a correlation between the BR and Gleason grade at the retropubic radical prostatectomy (RRP), capsular invasion, and the presence of positive surgical margins. Multivariate regression analysis showed a statistically significant correlation between the presence of surgical margins at the RRP and BR. Considering a single micro-focus of PC at the biopsy and PSA serum level <10 ng/mL, clinically significant disease was found in 74.26% patients and only positive surgical margins are useful for predicting the BR.

  11. Adult attachment interviews of women from low-risk, poverty, and maltreatment risk samples: comparisons between the hostile/helpless and traditional AAI coding systems.

    Science.gov (United States)

    Frigerio, Alessandra; Costantino, Elisabetta; Ceppi, Elisa; Barone, Lavinia

    2013-01-01

    The main aim of this study was to investigate the correlates of a Hostile-Helpless (HH) state of mind among 67 women belonging to a community sample and two different at-risk samples matched on socio-economic indicators, including 20 women from low-SES population (poverty sample) and 15 women at risk for maltreatment being monitored by the social services for the protection of juveniles (maltreatment risk sample). The Adult Attachment Interview (AAI) protocols were reliably coded blind to the samples' group status. The rates of HH classification increased in relation to the risk status of the three samples, ranging from 9% for the low-risk sample to 60% for the maltreatment risk sample to 75% for mothers in the maltreatment risk sample who actually maltreated their infants. In terms of the traditional AAI classification system, 88% of the interviews from the maltreating mothers were classified Unresolved/Cannot Classify (38%) or Preoccupied (50%). Partial overlapping between the 2 AAI coding systems was found, and discussion concerns the relevant contributions of each AAI coding system to understanding of the intergenerational transmission of maltreatment.

  12. Breast Stimulation in Low-Risk Primigravidas at Term: Does It Aid in Spontaneous Onset of Labour and Vaginal Delivery? A Pilot Study

    Directory of Open Access Journals (Sweden)

    Nilanchali Singh

    2014-01-01

    Full Text Available Aims. The aim of the study was to elicit the safety and efficacy of breast stimulation as an intervention to prevent postdatism and as an aid in spontaneous onset of labour. Methods. Primigravidas with cephalic presentation, without any high-risk factor, were recruited between 36 to 38 weeks of gestation. 200 patients were recruited and randomized into two groups (n = 100. Breast stimulation was advised to one group but not to the other group. Bishop’s scoring was done at 38 weeks and repeated at 39 weeks of gestation. Maternal and fetal outcomes were compared in two groups. Result. Bishop’s score changed from 3.12 (±1.01 to 3.9 (±1.08 in control group and from 3.02 (±0.82 to 6.08 (±1.29 in breast stimulation group after one week (P value < 0.0001. The period of gestation at delivery was 39.5 (±2.3 weeks in control group and 39.2 (±2.8 weeks in intervention group (P value: 0.044. There were increased chances of vaginal delivery in intervention group (P value: 0.046. Duration of labor, hyperstimulation, presence of meconium stained liquor, postpartum hemorrhage, and neonatal outcomes were similar in both groups. Conclusion. Breast stimulation in low-risk primigravidas helps in cervical ripening and increases chances of vaginal delivery.

  13. Codetection of Trichomonas vaginalis and Candida albicans by PCR in urine samples in a low-risk population attended in a clinic first level in central Veracruz, Mexico.

    Science.gov (United States)

    López-Monteon, A; Gómez-Figueroa, F S; Ramos-Poceros, G; Guzmán-Gómez, D; Ramos-Ligonio, A

    2013-01-01

    The aim of this study is to estimate the prevalence of Trichomonas vaginalis and Candida albicans in low-risk patients treated at a first level clinic (primary health care represents the first level of contact of individuals, families, and the community with the system national health). Using a cross-sectional study in patients treated in clinical laboratory of the Sanitary District no. 7 of the city of Orizaba during the months June-July, 252 urine samples were collected for the identification of T. vaginalis and C. albicans by PCR. Furthermore, we analyzed the sociodemographic characteristics of the studied population. We observed an overall prevalence of 23.41% (95% CI 22.10-24.72) for T. vaginalis and 38.88% (95% CI 37.73-40.03) for C. albicans. There was also presence of coinfection in 14.28% (95% CI 13.10-15.46), which was associated with the presence of pain. Most of the positive cases were observed in women house-maker (80%, 95% CI 50.36-48.98). The results of this study provide evidence that the majority of positive cases observed in the studied population are presented in an asymptomatic form and usually are not associated with any risk factor.

  14. Measurement of coronary calcium scores by electron beam computed tomography or exercise testing as initial diagnostic tool in low-risk patients with suspected coronary artery disease

    Energy Technology Data Exchange (ETDEWEB)

    Geluk, Christiane A.; Perik, Patrick J.; Tio, Rene A.; Goette, Marco J.W.; Hillege, Hans L.; Zijlstra, Felix [University Medical Center Groningen, Thoraxcenter, Department of Cardiology, Groningen (Netherlands); Dikkers, Riksta; Vliegenthart, Rozemarijn; Houwers, Janneke B.; Willems, Tineke P.; Oudkerk, Matthijs [University Medical Center Groningen, Department of Radiology, Groningen (Netherlands)

    2008-02-15

    We determined the efficiency of a screening protocol based on coronary calcium scores (CCS) compared with exercise testing in patients with suspected coronary artery disease (CAD), a normal ECG and troponin levels. Three-hundred-and-four patients were enrolled in a screening protocol including CCS by electron beam computed tomography (Agatston score), and exercise testing. Decision-making was based on CCS. When CCS{>=}400, coronary angiography (CAG) was recommended. When CCS<10, patients were discharged. Exercise tests were graded as positive, negative or nondiagnostic. The combined endpoint was defined as coronary event or obstructive CAD at CAG. During 12{+-}4 months, CCS{>=}400, 10-399 and <10 were found in 42, 103 and 159 patients and the combined endpoint occurred in 24 (57%), 14 (14%) and 0 patients (0%), respectively. In 22 patients (7%), myocardial perfusion scintigraphy was performed instead of exercise testing due to the inability to perform an exercise test. A positive, nondiagnostic and negative exercise test result was found in 37, 76 and 191 patients, and the combined endpoint occurred in 11 (30%), 15 (20%) and 12 patients (6%), respectively. Receiver-operator characteristics analysis showed that the area under the curve of 0.89 (95% CI: 0.85-0.93) for CCS was superior to 0.69 (95% CI: 0.61-0.78) for exercise testing (P<0.0001). In conclusion, measurement of CCS is an appropriate initial screening test in a well-defined low-risk population with suspected CAD. (orig.)

  15. Softness and potential to cause rebreathing: Differences in bedding used by infants at high and low risk for sudden infant death syndrome.

    Science.gov (United States)

    Kemp, J S; Livne, M; White, D K; Arfken, C L

    1998-02-01

    This study was carried out to determine whether bedding used by infants, who are at either high or low risk for sudden infant death syndrome (SIDS), differs in physical properties favoring rebreathing of exhaled gases. We compared softness and limitation of carbon dioxide dispersal by bedding, using a mechanical model. A questionnaire was used to describe sociodemographic risk factors and sleep practices; bedding was studied in homes with a model positioned where each infant was found sleeping that morning. The groups differed with respect to five sociodemographic risk factors (p values all < or = 0.0001). In addition, infants at higher risk were more likely to have been placed to sleep prone (46%, p = 0.02) by parents who were less likely to be aware of the risk associated with the prone position (62% aware, p = 0.005). Infants at higher risk had softer bedding (p < 0.0001, 54.1+/-17.2 cm2 vs 33.7+/-7.7 cm2 in contact with model), which caused more limitation of carbon dioxide dispersal (p = 0.008; CO2 retained, 0.60%+/-0.15% vs 0.34%+/-0.05%). A series of infants who are at high risk for SIDS because of sociodemographic factors more often sleep on bedding that has physical properties favoring rebreathing, and their parents are less often aware of the risk associated with prone sleeping.

  16. Performance of motor sequences in children at heightened vs. low risk for ASD: A longitudinal study from 18 to 36 months of age

    Directory of Open Access Journals (Sweden)

    VALENTINA eFOCAROLI

    2016-05-01

    Full Text Available Recent research shows that motor difficulties are a prominent component of the behavioral profile of autism spectrum disorder (ASD and are also apparent from early in development in infants who have an older sibling with ASD (High Risk; HR. Delays have been reported for HR infants who do and who do not receive an eventual diagnosis of ASD. A growing body of prospective studies has focused on the emergence of early motor skills primarily during the first year of life. To date, however, relatively little work has examined motor skills in the second and third years. Thus, the present research was designed to investigate motor performance in object transport tasks longitudinally in HR and LR (Low Risk children between the ages of 18 and 36 months. Participants (15 HR children and 14 LR children were observed at 18, 24, and 36 months. Children completed two motor tasks, the Ball Task and the Block Task, each of which included two conditions that varied in terms of the precision demands of the goal action. Kinematic data were acquired via two magneto inertial sensors worn on each wrist. In the Block Task, HR children reached more slowly (i.e., mean acceleration was lower compared to LR children. This finding is in line with growing evidence of early delays in fine motor skills in HR children and suggests that vulnerabilities in motor performance may persist into the preschool years in children at risk for ASD.

  17. Processing of No-Release Variants in Connected Speech

    Science.gov (United States)

    LoCasto, Paul C.; Connine, Cynthia M.

    2011-01-01

    The cross modal repetition priming paradigm was used to investigate how potential lexically ambiguous no-release variants are processed. In particular we focus on segmental regularities that affect the variant's frequency of occurrence (voicing of the critical segment) and phonological context in which the variant occurs (status of the following…

  18. Rare ADH Variant Constellations are Specific for Alcohol Dependence

    OpenAIRE

    Zuo, Lingjun; Zhang, Heping; Malison, Robert T; Li, Chiang-shan R.; Zhang, Xiang-Yang; Wang, Fei; Lu, Lingeng; Lu, Lin; Wang, Xiaoping; Krystal, John H.; Zhang, Fengyu; Deng, Hong-Wen; Luo, Xingguang

    2012-01-01

    Aims: Some of the well-known functional alcohol dehydrogenase (ADH) gene variants (e.g. ADH1B*2, ADH1B*3 and ADH1C*2) that significantly affect the risk of alcohol dependence are rare variants in most populations. In the present study, we comprehensively examined the associations between rare ADH variants [minor allele frequency (MAF)

  19. GenOVa: a computer program to generate orientational variants

    OpenAIRE

    Cayron, Cyril

    2007-01-01

    A computer program called GenOVa, written in Python, calculates the orientational variants, the operators (special types of misorientations between variants) and the composition table associated with a groupoid structure. The variants can be represented by three-dimensional shapes or by pole figures.

  20. Variants in CUL4B are Associated with Cerebral Malformations

    NARCIS (Netherlands)

    Vulto-van Silfhout, Anneke T.; Nakagawa, Tadashi; Bahi-Buisson, Nadia; Haas, Stefan A.; Hu, Hao; Bienek, Melanie; Vissers, Lisenka E. L. M.; Gilissen, Christian; Tzschach, Andreas; Busche, Andreas; Muesebeck, Joerg; Rump, Patrick; Mathijssen, Inge B.; Avela, Kristiina; Somer, Mirja; Doagu, Fatma; Philips, Anju K.; Rauch, Anita; Baumer, Alessandra; Voesenek, Krysta; Poirier, Karine; Vigneron, Jacqueline; Amram, Daniel; Odent, Sylvie; Nawara, Magdalena; Obersztyn, Ewa; Lenart, Jacek; Charzewska, Agnieszka; Lebrun, Nicolas; Fischer, Ute; Nillesen, Willy M.; Yntema, Helger G.; Jarvela, Irma; Ropers, Hans-Hilger; de Vries, Bert B. A.; Brunner, Han G.; van Bokhoven, Hans; Raymond, F. Lucy; Willemsen, Michel A. A. P.; Chelly, Jamel; Xiong, Yue; Barkovich, A. James; Kalscheuer, Vera M.; Kleefstra, Tjitske; de Brouwer, Arjan P. M.

    2015-01-01

    Variants in cullin 4B (CUL4B) are a known cause of syndromic X-linked intellectual disability. Here, we describe an additional 25 patients from 11 families with variants in CUL4B. We identified nine different novel variants in these families and confirmed the pathogenicity of all nontruncating varia

  1. Variants in CUL4B are associated with cerebral malformations

    NARCIS (Netherlands)

    Vulto-van Silfhout, A.T.; Nakagawa, T.; Bahi-Buisson, N.; Haas, S.A.; Hu, H; Bienek, M.; Vissers, L.E.L.M.; Gilissen, C.F.H.A.; Tzschach, A.; Busche, A.; Musebeck, J.; Rump, P.; Mathijssen, I.B.; Avela, K.; Somer, M.; Doagu, F.; Philips, A.K.; Rauch, A.; Baumer, A.; Voesenek, K.E.J.; Poirier, K.; Vigneron, J.; Amram, D.; Odent, S.; Nawara, M.; Obersztyn, E.; Lenart, J.; Charzewska, A.; Lebrun, N.; Fischer, U.; Nillesen, W.M.; Yntema, H.G.; Jarvela, I.; Ropers, H.H.; Vries, B. de; Brunner, H.G.; Bokhoven, H. van; Raymond, F.L.; Willemsen, M.A.A.P.; Chelly, J.; Xiong, Y.; Barkovich, A.J.; Kalscheuer, V.M.; Kleefstra, T.; Brouwer, A.P.M. de

    2015-01-01

    Variants in cullin 4B (CUL4B) are a known cause of syndromic X-linked intellectual disability. Here, we describe an additional 25 patients from 11 families with variants in CUL4B. We identified nine different novel variants in these families and confirmed the pathogenicity of all nontruncating varia

  2. The power of multiplexed functional analysis of genetic variants.

    Science.gov (United States)

    Gasperini, Molly; Starita, Lea; Shendure, Jay

    2016-10-01

    New technologies have recently enabled saturation mutagenesis and functional analysis of nearly all possible variants of regulatory elements or proteins of interest in single experiments. Here we discuss the past, present, and future of such multiplexed (functional) assays for variant effects (MAVEs). MAVEs provide detailed insight into sequence-function relationships, and they may prove critical for the prospective clinical interpretation of genetic variants.

  3. Processing of No-Release Variants in Connected Speech

    Science.gov (United States)

    LoCasto, Paul C.; Connine, Cynthia M.

    2011-01-01

    The cross modal repetition priming paradigm was used to investigate how potential lexically ambiguous no-release variants are processed. In particular we focus on segmental regularities that affect the variant's frequency of occurrence (voicing of the critical segment) and phonological context in which the variant occurs (status of the following…

  4. Wham: Identifying Structural Variants of Biological Consequence.

    Science.gov (United States)

    Kronenberg, Zev N; Osborne, Edward J; Cone, Kelsey R; Kennedy, Brett J; Domyan, Eric T; Shapiro, Michael D; Elde, Nels C; Yandell, Mark

    2015-12-01

    Existing methods for identifying structural variants (SVs) from short read datasets are inaccurate. This complicates disease-gene identification and efforts to understand the consequences of genetic variation. In response, we have created Wham (Whole-genome Alignment Metrics) to provide a single, integrated framework for both structural variant calling and association testing, thereby bypassing many of the difficulties that currently frustrate attempts to employ SVs in association testing. Here we describe Wham, benchmark it against three other widely used SV identification tools-Lumpy, Delly and SoftSearch-and demonstrate Wham's ability to identify and associate SVs with phenotypes using data from humans, domestic pigeons, and vaccinia virus. Wham and all associated software are covered under the MIT License and can be freely downloaded from github (https://github.com/zeeev/wham), with documentation on a wiki (http://zeeev.github.io/wham/). For community support please post questions to https://www.biostars.org/.

  5. Discussing and managing hematologic germ line variants.

    Science.gov (United States)

    Kohlmann, Wendy; Schiffman, Joshua D

    2016-11-24

    With the introduction of genomic technologies, more hereditary cancer syndromes with hematologic malignancies are being described. Up to 10% of hematologic malignancies in children and adults may be the result of an underlying inherited genetic risk. Managing these patients with hereditary hematologic malignancies, including familial leukemia, remains a clinical challenge because there is little information about these relatively rare disorders. This article covers some of the issues related to the diagnosis and interpretation of variants associated with hereditary hematologic malignancies, including the importance of an accurate family history in interpreting genetic variants associated with disease. The challenges of screening other family members and offering the most appropriate early malignancy detection is also discussed. We now have a good opportunity to better define hereditary cancer syndromes with associated hematologic malignancies and contribute to clinically effective guidelines.

  6. Wham: Identifying Structural Variants of Biological Consequence.

    Directory of Open Access Journals (Sweden)

    Zev N Kronenberg

    2015-12-01

    Full Text Available Existing methods for identifying structural variants (SVs from short read datasets are inaccurate. This complicates disease-gene identification and efforts to understand the consequences of genetic variation. In response, we have created Wham (Whole-genome Alignment Metrics to provide a single, integrated framework for both structural variant calling and association testing, thereby bypassing many of the difficulties that currently frustrate attempts to employ SVs in association testing. Here we describe Wham, benchmark it against three other widely used SV identification tools-Lumpy, Delly and SoftSearch-and demonstrate Wham's ability to identify and associate SVs with phenotypes using data from humans, domestic pigeons, and vaccinia virus. Wham and all associated software are covered under the MIT License and can be freely downloaded from github (https://github.com/zeeev/wham, with documentation on a wiki (http://zeeev.github.io/wham/. For community support please post questions to https://www.biostars.org/.

  7. Interactions between genetic variants and breast cancer risk factors in the breast and prostate cancer cohort consortium.

    Science.gov (United States)

    Campa, Daniele; Kaaks, Rudolf; Le Marchand, Loïc; Haiman, Christopher A; Travis, Ruth C; Berg, Christine D; Buring, Julie E; Chanock, Stephen J; Diver, W Ryan; Dostal, Lucie; Fournier, Agnes; Hankinson, Susan E; Henderson, Brian E; Hoover, Robert N; Isaacs, Claudine; Johansson, Mattias; Kolonel, Laurence N; Kraft, Peter; Lee, I-Min; McCarty, Catherine A; Overvad, Kim; Panico, Salvatore; Peeters, Petra H M; Riboli, Elio; Sanchez, Maria José; Schumacher, Fredrick R; Skeie, Guri; Stram, Daniel O; Thun, Michael J; Trichopoulos, Dimitrios; Zhang, Shumin; Ziegler, Regina G; Hunter, David J; Lindström, Sara; Canzian, Federico

    2011-08-17

    Recently, several genome-wide association studies have identified various genetic susceptibility loci for breast cancer. Relatively little is known about the possible interactions between these loci and the established risk factors for breast cancer. To assess interactions between single-nucleotide polymorphisms (SNPs) and established risk factors, we prospectively collected DNA samples and questionnaire data from 8576 breast cancer case subjects and 11 892 control subjects nested within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3). We genotyped 17 germline SNPs (FGFR2-rs2981582, FGFR2-rs3750817, TNRC9-rs3803662, 2q35-rs13387042, MAP3K1-rs889312, 8q24-rs13281615, CASP8-rs1045485, LSP1-rs3817198, COL1A1-rs2075555, COX11-rs6504950, RNF146-rs2180341, 6q25-rs2046210, SLC4A7-rs4973768, NOTCH2-rs11249433, 5p12-rs4415084, 5p12-rs10941679, RAD51L1-rs999737), and odds ratios were estimated by logistic regression to confirm previously reported associations with breast cancer risk. We performed likelihood ratio test to assess interactions between 17 SNPs and nine established risk factors (age at menarche, parity, age at menopause, use of hormone replacement therapy, family history, height, body mass index, smoking status, and alcohol consumption), and a correction for multiple testing of 153 tests (adjusted P value threshold = .05/153 = 3 × 10(-4)) was done. Case-case comparisons were performed for possible differential associations of polymorphisms by subgroups of tumor stage, estrogen and progesterone receptor status, and age at diagnosis. All statistical tests were two-sided. We confirmed the association of 14 SNPs with breast cancer risk (P(trend) = 2.57 × 10(-3) -3.96 × 10(-19)). Three SNPs (LSP1-rs3817198, COL1A1-rs2075555, and RNF146-rs2180341) did not show association with breast cancer risk. After accounting for multiple testing, no statistically significant interactions were detected between the 17 SNPs and the nine risk

  8. Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants.

    Directory of Open Access Journals (Sweden)

    Mengmeng Du

    Full Text Available Genome-wide association studies (GWAS have identified many common single nucleotide polymorphisms (SNPs associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs. We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33. We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s.

  9. Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants

    Science.gov (United States)

    Gala, Manish; Abecasis, Goncalo; Bezieau, Stephane; Brenner, Hermann; Butterbach, Katja; Caan, Bette J.; Carlson, Christopher S.; Casey, Graham; Chang-Claude, Jenny; Conti, David V.; Curtis, Keith R.; Duggan, David; Gallinger, Steven; Haile, Robert W.; Harrison, Tabitha A.; Hayes, Richard B.; Hoffmeister, Michael; Hopper, John L.; Hudson, Thomas J.; Jenkins, Mark A.; Küry, Sébastien; Le Marchand, Loic; Leal, Suzanne M.; Newcomb, Polly A.; Nickerson, Deborah A.; Potter, John D.; Schoen, Robert E.; Schumacher, Fredrick R.; Seminara, Daniela; Slattery, Martha L.; Hsu, Li; Chan, Andrew T.; White, Emily; Berndt, Sonja I.; Peters, Ulrike

    2016-01-01

    Genome-wide association studies (GWAS) have identified many common single nucleotide polymorphisms (SNPs) associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs). We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33). We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s). PMID:27379672

  10. Unusual variant of Cantrell′s pentalogy?

    Directory of Open Access Journals (Sweden)

    Kumar Basant

    2008-01-01

    Full Text Available A 12-hour-old male infant presented with prolapsed abdominal content through a defect on left side of chest wall with respiratory distress. A thorough clinical examination suggested absence of ectopia cordis, abdominal wall defect, and any bony anomaly. The child expired after 6 hours of admission because of respiratory distress and electrolyte imbalance. Is congenital defect of chest wall associated with diaphragmatic hernia without ectopia cordis and omphalocele, an unusual variant of Cantrell′s pentalogy?

  11. Variant position of the medial plantar nerve

    OpenAIRE

    Astik RB; Dave UH; Gajendra KS

    2011-01-01

    Knowledge of variation of position of the medial plantar nerve is important for the forefoot surgeon for plantar reconstruction, local injection therapy and an excision of interdigital neuroma. During routine dissection of 50-year-old female cadaver, we found the medial plantar nerve and vessels variably located between plantar aponeurosis and the muscles of the first layer of the sole of the right foot. Due to this variant position, the medial plantar nerve and vessels lose their protection ...

  12. Small colony variants and their clinical significance

    Directory of Open Access Journals (Sweden)

    Venkataramana Venkataramana

    2016-01-01

    Full Text Available Among the many factors that contribute to bacterial colonization, persistence and development of infection, the ability of microorganisms to form small colony variants (SCVs assumes great significance. Although bacteria require intrinsic virulence factors to cause pathogenesis, some of them regularly evolve mechanisms to evade immune mechanisms, become resistant to antibiotics, and sustain in the human/animal cells to cause chronic infections. This mini review highlights the recent advances in the study of SCVs.

  13. Unusual variant of Cantrell′s pentalogy?

    OpenAIRE

    Kumar Basant; Sharma S.; Kandpal Deepak; Agrawal L

    2008-01-01

    A 12-hour-old male infant presented with prolapsed abdominal content through a defect on left side of chest wall with respiratory distress. A thorough clinical examination suggested absence of ectopia cordis, abdominal wall defect, and any bony anomaly. The child expired after 6 hours of admission because of respiratory distress and electrolyte imbalance. Is congenital defect of chest wall associated with diaphragmatic hernia without ectopia cordis and omphalocele, an unusual variant of Cantr...

  14. Association of genetic variants with diabetic nephropathy

    Institute of Scientific and Technical Information of China (English)

    Saliha; Rizvi; Syed; Tasleem; Raza; Farzana; Mahdi

    2014-01-01

    Diabetic nephropathy accounts for the most serious microvascular complication of diabetes mellitus. It is suggested that the prevalence of diabetic nephropathy will continue to increase in future posing a major challenge to the healthcare system resulting in increased morbidity and mortality. It occurs as a result of interaction between both genetic and environmental factors in individuals with both type 1 and type 2 diabetes. Genetic susceptibility has been proposed as an important factor for the development and progression of diabetic nephropathy, and various research efforts are being executed worldwide to identify the susceptibility gene for diabetic nephropathy. Numerous single nucleotide polymorphisms have been found in various genes giving rise to various gene variants which have been found to play a major role in genetic susceptibility to diabetic nephropathy. The risk of developing diabetic nephropathy is increased several times by inheriting risk alleles at susceptibility loci of various genes like ACE, IL, TNF-α, COL4A1, e NOS, SOD2, APOE, GLUT, etc. The identification of these genetic variants at a biomarker level could thus, allow the detection of those individuals at high risk for diabetic nephropathy which could thus help in the treatment, diagnosis and early prevention of the disease. The present review discusses about the various gene variants found till date to be associated with diabetic nephropathy.

  15. Primary Aldosteronism and ARMC5 Variants

    Science.gov (United States)

    Zilbermint, Mihail; Xekouki, Paraskevi; Faucz, Fabio R.; Berthon, Annabel; Gkourogianni, Alexandra; Schernthaner-Reiter, Marie Helene; Batsis, Maria; Sinaii, Ninet; Quezado, Martha M.; Merino, Maria; Hodes, Aaron; Abraham, Smita B.; Libé, Rossella; Assié, Guillaume; Espiard, Stéphanie; Drougat, Ludivine; Ragazzon, Bruno; Davis, Adam; Gebreab, Samson Y.; Neff, Ryan; Kebebew, Electron; Bertherat, Jérôme; Lodish, Maya B.

    2015-01-01

    Context: Primary aldosteronism is one of the leading causes of secondary hypertension, causing significant morbidity and mortality. A number of genetic defects have recently been identified in primary aldosteronism, whereas we identified mutations in ARMC5, a tumor-suppressor gene, in cortisol-producing primary macronodular adrenal hyperplasia. Objective: We investigated a cohort of 56 patients who were referred to the National Institutes of Health for evaluation of primary aldosteronism for ARMC5 defects. Methods: Patients underwent step-wise diagnosis, with measurement of serum aldosterone and plasma renin activity followed by imaging, saline suppression and/or oral salt loading tests, plus adrenal venous sampling. Cortisol secretion was also evaluated; unilateral or bilateral adrenalectomy was performed, if indicated. DNA, protein, and transfection studies in H295R cells were conducted by standard methods. Results: We identified 12 germline ARMC5 genetic alterations in 20 unrelated and two related individuals in our cohort (39.3%). ARMC5 sequence changes in 6 patients (10.7%) were predicted to be damaging by in silico analysis. All affected patients carrying a variant predicted to be damaging were African Americans (P = .0023). Conclusions: Germline ARMC5 variants may be associated with primary aldosteronism. Additional cohorts of patients with primary aldosteronism and metabolic syndrome, particularly African Americans, should be screened for ARMC5 sequence variants because these may underlie part of the known increased predisposition of African Americans to low renin hypertension. PMID:25822102

  16. Warty Carcinoma Penis: An Uncommon Variant

    Science.gov (United States)

    Ghosh, Arnab; Shrestha, Santosh; Ghartimagar, Dilasma; Narasimhan, Raghavan; Talwar, OP

    2017-01-01

    Penile carcinoma frequency varies widely in different parts of the world and comprises 1–10% of all the malignancies in males. Majority of the cases of penile carcinoma are squamous cell carcinoma of penis comprising 60% to 70% of all cases. Warty carcinoma of penis is an unusual neoplasm and a variant of penile squamous cell carcinoma comprising 5%–10% of all the variants. The other histological variants include basaloid, verrucous, papillary, sarcomatous, mixed, and adenosquamous carcinoma. The various histological entities with an exophytic papillary lesions including warty carcinoma are together referred to as the “verruciform” group of neoplasms. The warty carcinoma has to be differentiated from these lesions and is typically distinguished by histological features of hyperkeratosis, arborescent papillomatosis, acanthosis, and prominent koilocytosis with nuclear pleomorphism. We present a case of 65-year-old male with growth measuring 6 × 4 cm in the penis who underwent total penectomy and was diagnosed as warty carcinoma penis. PMID:28154768

  17. Association of genetic variants with diabetic nephropathy.

    Science.gov (United States)

    Rizvi, Saliha; Raza, Syed Tasleem; Mahdi, Farzana

    2014-12-15

    Diabetic nephropathy accounts for the most serious microvascular complication of diabetes mellitus. It is suggested that the prevalence of diabetic nephropathy will continue to increase in future posing a major challenge to the healthcare system resulting in increased morbidity and mortality. It occurs as a result of interaction between both genetic and environmental factors in individuals with both type 1 and type 2 diabetes. Genetic susceptibility has been proposed as an important factor for the development and progression of diabetic nephropathy, and various research efforts are being executed worldwide to identify the susceptibility gene for diabetic nephropathy. Numerous single nucleotide polymorphisms have been found in various genes giving rise to various gene variants which have been found to play a major role in genetic susceptibility to diabetic nephropathy. The risk of developing diabetic nephropathy is increased several times by inheriting risk alleles at susceptibility loci of various genes like ACE, IL, TNF-α, COL4A1, eNOS, SOD2, APOE, GLUT, etc. The identification of these genetic variants at a biomarker level could thus, allow the detection of those individuals at high risk for diabetic nephropathy which could thus help in the treatment, diagnosis and early prevention of the disease. The present review discusses about the various gene variants found till date to be associated with diabetic nephropathy.

  18. Genetic variants associated with Crohn's disease

    Directory of Open Access Journals (Sweden)

    Michail S

    2013-07-01

    Full Text Available Sonia Michail,1 Gilberto Bultron,1 R William DePaolo2 1The University of Southern California, Children's Hospital of Los Angeles, Los Angeles, CA, USA; 2Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA Abstract: Crohn's disease is an immune-related disorder characterized by inflammation of the gastrointestinal mucosa, which can occur in any area throughout the digestive tract. This life-long disease commonly presents with abdominal pain, diarrhea, vomiting, and weight loss. While the exact etiology of this disease is largely unknown, it is thought to arise from an interaction between microbial, immunological, and environmental factors in a genetically susceptible host, whereby the immune system attacks the intestine as it cross reacts against gut microbial antigens. The study of genetic variants associated with Crohn's disease has shed light on our understanding of disease pathophysiology. A large number of genetic variants identified in Crohn's disease are related to genes targeting microbial recognition and bacterial wall sensing, the most common being NOD2/CARD15 gene. This review will discuss the recent advance in our knowledge of genetic variants of this disease and how they influence the disease course and prognosis. Keywords: Crohn's disease, genetics, autophagy

  19. Splicing analysis of 14 BRCA1 missense variants classifies nine variants as pathogenic

    DEFF Research Database (Denmark)

    Ahlborn, Lise B; Dandanell, Mette; Steffensen, Ane Y;

    2015-01-01

    needed to classify whether these uncertain variants are pathogenic or benign. In this study, we investigated 14 BRCA1 variants by in silico splicing analysis and mini-gene splicing assay. All 14 alterations were missense variants located within the BRCT domain of BRCA1 and had previously been examined...... by functional analysis at the protein level. Results from a validated mini-gene splicing assay indicated that nine BRCA1 variants resulted in splicing aberrations leading to truncated transcripts and thus can be considered pathogenic (c.4987A>T/p.Met1663Leu, c.4988T>A/p.Met1663Lys, c.5072C>T/p.Thr1691Ile, c...... to have no or an uncertain effect on the protein level, whereas one variant (c.5072C>T/p.Thr1691Ile) were shown to have a strong effect on the protein level as well. In conclusion, our study emphasizes that in silico splicing prediction and mini-gene splicing analysis are important for the classification...

  20. String Variant Alias Extraction Method using Ensemble Learner

    Directory of Open Access Journals (Sweden)

    P.Selvaperumal

    2016-02-01

    Full Text Available String variant alias names are surnames which are string variant form of the primary name. Extracting string variant aliases are important in tasks such as information retrieval, information extraction, and name resolution etc. String variant alias extraction involves candidate alias name extraction and string variant alias validation. In this paper, string variant aliases are first extracted from the web and then using seven different string similarity metrics as features, candidate aliases are validated using ensemble classifier random forest. Experiments were conducted using string variant name-alias dataset containing name-alias data for 15 persons containing 30 name-alias pairs. Experimental results show that the proposed method outperforms other similar methods in terms of accuracy.

  1. DNA-polymorphisms and plasma levels of vascular disease risk factors in Greenland Inuit--is there a relation with the low risk of cardiovascular disease in the Inuit?

    DEFF Research Database (Denmark)

    Maat, M de; Bladbjerg, E-M; Johansen, L G

    1999-01-01

    Greenland Inuit are a population with a low risk of cardiovascular disease. Recently, we stated that frequencies of potentially high risk alleles of the apolipoproteins, fibrinogen, factor V, glycoprotein IIIa and factor VII (FVII) genes have different allele frequencies in the Inuit when compare...

  2. The LENTE Study: The Effectiveness of Prophylactic Intramuscular Oxytocin in the Third Stage of Labor Among Low-Risk Women in Primary Care Midwifery Practice: A Randomized Controlled Trial

    NARCIS (Netherlands)

    Jans, S.M.P.J.; Herschderfer, K.C.; Diem, M.T. van; Aitink, M.; Rijnders, M.; Pal-de Bruin, K. van der; Buitendijk, S.E.

    2016-01-01

    Purpose: To test third stage management of labor for low-risk women comparing routine prophylactic intramuscular oxytocin management versus modified expectant management. Study designN: Randomized controlled multicenter trial in primary care midwifery practice. Major findings: 32.4% of women in the

  3. Is there any association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low-risk localized prostate cancer?

    Directory of Open Access Journals (Sweden)

    Omer Gokhan Doluoglu

    2016-04-01

    Full Text Available ABSTRACT Purpose We investigated the association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low-risk localized prostate cancer. Materials and Methods The data of 440 patients who had undergone prostate biopsies due to high PSA levels and suspicious digital rectal examination findings were reviewed retrospectively. The patients were divided into two groups based on the presence of accompanying NIH IV prostatitis. The exclusion criteria were as follows: Gleason score>6, PSA level>20ng/mL, >2 positive cores, >50% cancerous tissue per biopsy, urinary tract infection, urological interventions at least 1 week previously (cystoscopy, urethral catheterization, or similar procedure, history of prostate biopsy, and history of androgen or 5-alpha reductase use. All patient's age, total PSA and free PSA levels, ratio of free to total PSA, PSA density and prostate volume were recorded. Results In total, 101 patients were included in the study. Histopathological examination revealed only PCa in 78 (77.2% patients and PCa+NIH IV prostatitis in 23 (22.7% patients. The median total PSA level was 7.4 (3.5–20.0 ng/mL in the PCa+NIH IV prostatitis group and 6.5 (0.6–20.0 ng/mL in the PCa group (p=0.67. The PSA level was≤10ng/mL in 60 (76.9% patients in the PCa group and in 16 (69.6% patients in the PCa+NIH IV prostatitis group (p=0.32. Conclusions Our study showed no statistically significant difference in PSA levels between patients with and without NIH IV prostatitis accompanying PCa.

  4. Is there any association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low-risk localized prostate cancer?

    Science.gov (United States)

    Doluoglu, Omer Gokhan; Ceylan, Cavit; Kilinc, Fatih; Gazel, Eymen; Resorlu, Berkan; Odabas, Oner

    2016-01-01

    ABSTRACT Purpose We investigated the association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low-risk localized prostate cancer. Materials and Methods The data of 440 patients who had undergone prostate biopsies due to high PSA levels and suspicious digital rectal examination findings were reviewed retrospectively. The patients were divided into two groups based on the presence of accompanying NIH IV prostatitis. The exclusion criteria were as follows: Gleason score>6, PSA level>20ng/mL, >2 positive cores, >50% cancerous tissue per biopsy, urinary tract infection, urological interventions at least 1 week previously (cystoscopy, urethral catheterization, or similar procedure), history of prostate biopsy, and history of androgen or 5-alpha reductase use. All patient's age, total PSA and free PSA levels, ratio of free to total PSA, PSA density and prostate volume were recorded. Results In total, 101 patients were included in the study. Histopathological examination revealed only PCa in 78 (77.2%) patients and PCa+NIH IV prostatitis in 23 (22.7%) patients. The median total PSA level was 7.4 (3.5–20.0) ng/mL in the PCa+NIH IV prostatitis group and 6.5 (0.6–20.0) ng/mL in the PCa group (p=0.67). The PSA level was≤10ng/mL in 60 (76.9%) patients in the PCa group and in 16 (69.6%) patients in the PCa+NIH IV prostatitis group (p=0.32). Conclusions Our study showed no statistically significant difference in PSA levels between patients with and without NIH IV prostatitis accompanying PCa. PMID:27256190

  5. Effect of ultra-low dose and standard heparin locks on early tunnelled dialysis catheter outcomes in low-risk dialysis patients.

    Science.gov (United States)

    Renaud, Claude J; Lim, Eng Kuang; Tho, Samuel J; Yeoh, Lee Ying

    2015-02-01

    Initial heparin locks instilled after tunnelled dialysis catheter (TDC) insertion can leak causing systemic anticoagulation and also promote staphyloccocal biofilm formation, predisposing to catheter-related infection (CRI). The 1000 U/mL concentration is thus advocated as the optimal dose for preventing catheter bleeding and malfunction. The effect of lower heparin concentrations on further lowering these complications is not known. We compared early TDC outcomes between a non-standard ultra-low (500 U/mL) and standard initial heparin locks (1000 and 5000 U/mL). This was a retrospective study on prospectively collected data on 238 de novo internal jugular TDCs placed by nephrologists. Cases were categorized into groups 1, 2 and 3, according to initial heparin lock: 500 [n = 30], 1000 [n = 180] and 5000 U/mL [n = 28] respectively. Bleeding and malfunction within 24 h of TDC insertion, 30 days CRI-free catheter survival and the effects of clinical and laboratory factors on bleeding were evaluated. Bleeding events were similar in groups 1, 2 and 3 (7 vs 14 vs 13%, respectively, P = 0.61). Malfunction was only seen in group 2 (3.3%). Thirty-day CRI-free catheter survival was comparable (96 vs 98 vs 97%, respectively, P = 0.22), giving a cumulative CRI rate of 0.76/1000 catheter days. All CRIs were staphylococcal. Univariate analysis did not reveal any significant predictors of catheter bleeding. Immediate TDC bleeding, malfunction and CRI rate are not influenced by heparin lock concentrations ≤5000 U/mL in this low-risk cohort. However this needs to be corroborated in higher risk patients. © 2014 Asian Pacific Society of Nephrology.

  6. Comparison of MACT and 5Fu+ACT-D chemotherapy regimens in the treatment of low-risk gestational trophoblastic neoplasia.

    Science.gov (United States)

    Wang, Yu; Miao, Jin-Wei; Wang, Tong; Wang, Yan; Wu, Yu-Mei; Kong, Wei-Min; Su, Li; Duan, Wei

    2016-04-01

    The study aimed to compare the efficacy of methotrexate (MTX) cervical injections + actinomycin-D (ACT-D)(MACT) and 5-fluorouracil (5-Fu) + actinomycin-D (5-Fu plus ACT-D) chemotherapy regimens for low-risk gestational trophoblastic neoplasia (LR-GTN). Clinical data from 66 LR-GTN patients, admitted to the Beijing Obstetrics and Gynecology Hospital from January 2010 to April 2012, were analysed retrospectively. In total, 32 patients were treated with a MACT therapeutic regimen and the remaining 34 with a 5Fu + ACT-D therapeutic regimen. Complete remission rates (CR), duration of treatment, hospital stay and toxicity effects were compared. There was no statistical difference in CR for the MACT (90.63%) or the 5-Fu plus ACT-D (100%) therapeutic regimens (p = 0.0676) or in the duration of treatment [MACT (3.50) or 5-Fu plus ACT-D (3.71; p = 0.2021)]. Moreover, the hospital stay in the 5-Fu plus ACT-D group (32.88 days) was significantly longer than for the MACT group (22.09 days; p < 0.001). Furthermore, the degree of myelosuppression, nausea and vomiting, diarrhoea, stomatitis and alopecia was more severe in the 5Fu + ACT-D group (p < 0.01). However, there was no statistical difference in the severity of liver function damage between the two groups. A shorter hospital stay, lower hospitalization cost and slightly more toxic effects were observed in LR-GTN patients treated with the MACT therapeutic regimen. We suggest that the MACT regimen should be used as first-line chemotherapy for LR-GTN.

  7. Low risk of late intracranial complications in mild traumatic brain injury patients using oral anticoagulation after an initial normal brain computed tomography scan: education instead of hospitalization.

    Science.gov (United States)

    Schoonman, G G; Bakker, D P; Jellema, K

    2014-07-01

    Mild traumatic brain injury (mTBI) is a common neurological disorder. Whether oral anticoagulation (OAC) use is a risk factor for secondary deterioration in mTBI patients after a normal computed tomography (CT) scan is unclear. Therefore data were retrospectively collected on patients with mTBI who used OAC to determine the incidence of secondary clinical deterioration after an initial normal head CT scan. This was a retrospective single-centre patient record study. All patients with an mTBI who presented at the emergency department between January 2007 and October 2011 were selected. Inclusion criteria were mTBI and at least 1 week of OAC use resulting in an international normalized radio > 1.1. CT scans were re-evaluated for this study. A total of 211 mTBI patients using OAC and with an initial CT scan without abnormalities were included in the analysis. In five patients a secondary deterioration was found. One patient developed a subdural hematoma after 15 h of clinical observation. The other four patients became symptomatic between 2 and 28 days after trauma. A low risk of secondary deterioration within 24 h in mTBI patients taking OAC with a normal first head CT scan was found. Our study does not support the recommendation of the current guidelines that these patients should be clinically observed for at least 24 h. The fact that in our series the majority of secondary deteriorations occurred between 2 and 28 days after trauma underscores the importance of patient instructions upon discharge from the hospital. © 2014 The Author(s) European Journal of Neurology © 2014 EAN.

  8. Miscarriage after a normal scan at 12-14 gestational weeks in women at low risk of carrying a fetus with chromosomal anomaly according to nuchal translucency screening.

    Science.gov (United States)

    Westin, M; Källén, K; Saltvedt, S; Almström, H; Grunewald, C; Valentin, L

    2007-10-01

    To estimate the risk of second-trimester miscarriage in women with low risk of carrying a fetus with chromosomal abnormality, according to nuchal translucency (NT) screening, and to determine whether NT thickness or other factors affect the risk. The study population comprised 14 278 singleton pregnancies with a risk of Down syndrome < 1:250 at NT scan, and where no fetal karyotyping was performed < 25 weeks. Risk factors for miscarriage were investigated by logistic regression. The median risk of Down syndrome was 1 : 3138 (range 1 : 9651-1 : 251) and median NT was 1.7 (range 0.4-3.0) mm. The miscarriage rate was 0.5% (77/14 278; 95% CI 0.4-0.6). After having controlled for maternal age, we found the number of previous deliveries and miscarriages to independently predict miscarriage: odds ratio (OR) for each previous delivery 1.48, 95% CI 1.22-1.94, P < 0.0001; OR for each previous miscarriage 1.34, 95% CI 1.07-1.68, P = 0.01. Excluding women with any previous miscarriage and adjusting for parity, we found a U-shaped relationship between maternal age and miscarriage (P = 0.04). In singleton pregnancies with estimated risk of Down syndrome < 1:250 according to NT screening at 12-14 weeks, the spontaneous fetal loss rate before 25 weeks is likely to be around 0.5%. NT thickness up to 3 mm does not seem to affect the risk of miscarriage in such pregnancies. Instead, the risk seems to increase with number of previous miscarriages and deliveries, and possibly the risk is highest in the youngest and oldest women. Copyright (c) 2007 ISUOG

  9. Combination of vibroacoustic stimulation and acute variables of mFBP as a simple assessment method of low-risk fetuses.

    Science.gov (United States)

    Petrović, Oleg; Finderle, Aleks; Prodan, Mirko; Skunca, Elvira; Prpić, Igor; Zaputović, Sanja

    2009-02-01

    To observe a rate of fetal breathing and gross body movement appearance as physiologic reactions to the external vibroacoustic stimulation (VAS) and to establish a rapid and reliable antepartal method for accurate selecting of non-compromised fetuses in the low-risk population. Actual condition of 742-term and near-term structurally normal and otherwise healthy singleton fetuses with favourable outcome was assessed by previously established combination of the modified fetal biophysical profile and VAS. Only inactive fetuses at the beginning of the testing were included in the study. The combined biophysical testing has been started by a transabdominal real-time ultrasound examination, followed by vibroacoustic stimulus applied over the fetal head for 5 s during fetal quiescence. Fetal breathing and gross body movements were observed with particular attention in each case at measured time intervals from the application of external VAS until the moment at which either the first 60-s episode of breathing movements or all three fetal gross body movements were detected. Obtained results have been presented numerically in 5-min periods and cumulative percentages. After the external VAS, 84.5% of studied fetuses successfully manifested their normal breathing or gross body movements in the first 5 min of the modified biophysical testing. Furthermore, approximately 96% of them were able to demonstrate at least one of these two biophysical activities after 6-7 min. Because of its simplicity, non-invasiveness, independence of precise gestational dating, reproducibility and immediate individual results, ultrasonographic observation of normal fetal breathing and/or gross body movements after the external VAS stands a real chance to become a nearly optimal antenatal test for accurate and rapid information of actual non-compromised fetal condition. Authors strongly believe that the described antenatal method should represent a rather efficient assessment procedure of fetal well

  10. Measurement of hepatitis B virus core-related antigen is valuable for identifying patients who are at low risk of lamivudine resistance.

    Science.gov (United States)

    Tanaka, Eiji; Matsumoto, Akihiro; Suzuki, Fumitaka; Kobayashi, Mariko; Mizokami, Masashi; Tanaka, Yasuhito; Okanoue, Takeshi; Minami, Masahito; Chayama, Kazuaki; Imamura, Michio; Yatsuhashi, Hiroshi; Nagaoka, Shinya; Yotsuyanagi, Hiroshi; Kawata, Sumio; Kimura, Tatsuji; Maki, Noboru; Iino, Shiro; Kiyosawa, Kendo

    2006-02-01

    The clinical usefulness of hepatitis B virus core-related antigen (HBVcrAg) assay was compared with that of HBV DNA assay in predicting the occurrence of lamivudine resistance in patients with chronic hepatitis B. Of a total of 81 patients who were treated with lamivudine, 25 (31%) developed lamivudine resistance during a median follow-up period of 19.3 months. The pretreatment positive rate of HBe antigen, or pretreatment levels of HBVcrAg or HBV DNA did not differ between patients with and without lamivudine resistance. Levels of both HBVcrAg and HBV DNA decreased after the initiation of lamivudine administration; however, the level of HBVcrAg decreased significantly more slowly than that of HBV DNA. The occurrence of lamivudine resistance was significantly less frequent in the 56 patients whose HBV DNA level was less than 2.6 log copy/ml at 6 months of treatment than in the remaining 25 patients. The cumulative rate of lamivudine resistance was as high as 70% within 2 years in the latter group, while it was only 28% in the former group. Lamivudine resistance did not occur during the follow-up period in the 19 patients whose HBVcrAg level was less than 4.6 log U/ml at 6 months of treatment, while it did occur in 50% of the remaining patients within 2 years. These results suggest that measurement of HBV DNA is valuable for identifying patients who are at high risk of developing lamivudine resistance, and that, conversely, measurement of HBVcrAg is valuable for identifying those who are at low risk of lamivudine resistance.

  11. Gene panels to help identify subgroups at high and low risk of CHD among those randomized to antihypertensive treatment: The GenHAT Study

    Science.gov (United States)

    Lynch, Amy I.; Eckfeldt, John H.; Davis, Barry R.; Ford, Charles E.; Boerwinkle, Eric; Leiendecker-Foster, Catherine; Arnett, Donna K.

    2012-01-01

    Objective To identify panels of genetic variants that predict treatment-related coronary heart disease (CHD) outcomes in hypertensive patients on one of four different classes of initial antihypertensive treatment. The goal was to identify subgroups of people based on their genetic profile who benefit most from a particular treatment. Methods Candidate genetic variants (n=78) were genotyped in 39,114 participants from GenHAT, ancillary to ALLHAT. ALLHAT randomized hypertensive participants (>=55 years) to one of four treatments (amlodipine, chlorthalidone, doxazosin, lisinopril). The primary outcome was fatal CHD or non-fatal MI (mean follow-up=4.9 years). A pharmacogenetic panel was derived within each of the four treatment groups. ROC curves estimated the discrimination rate between those with and without a CHD event, based on the addition of the genetic panel risk score. Results For each treatment group, we identified a panel of genetic variants that collectively improved prediction of CHD to a small but statistically significant extent. Chlorthalidone (A): NOS3, rs3918226; SELE, rs5361; ICAM1, rs1799969; AGT, rs5051; GNAS, rs7121; ROC comparison p=.004; Amlodipine (B): MMP1, rs1799750; F5, rs6025; NPPA, rs5065; PDE4D, rs6450512; MMP9, rs2274756; ROC comparison p=.006; Lisinopril (C): AGT, rs5051; PON1, rs705379; MMP12, rs652438; F12, rs1801020; GP1BA, rs6065; PDE4D, rs27653; ROC comparison p=.01; Doxazosin (D): F2, rs1799963; PAI1, rs1799768; MMP7, rs11568818; AGT, rs5051; ACE, rs4343; MMP2, rs243865; ROC comparison p=.007. Each panel was tested for a pharmacogenetic effect; panels A, B and D showed such evidence (p=.009, .006, and .001 respectively), panel C did not (p=.09). Conclusion Because each panel was associated with CHD in a specific treatment group but not the others, this research provides evidence that it may be possible to use gene panel scores as a tool to better assess antihypertensive treatment choices to reduce CHD risk in hypertensive

  12. Economic evaluation of birth care in low-risk women. A comparison between a midwife-led birth unit and a standard obstetric unit within the same hospital in Norway. A randomised controlled trial.

    Science.gov (United States)

    Bernitz, Stine; Aas, Eline; Øian, Pål

    2012-10-01

    to investigate the cost-effectiveness in birth care for low-risk women, in an alongside midwife-led unit (MU) compared to a standard obstetric unit (SCU) within the same hospital. economic evaluation based on the findings of a randomised trial, randomising participants either into the MU or SCU. The hospital's activity-based costing system CPP was used to estimate costs, as no data on complete resource use exists. the Department of Obstetrics and Gynaecology, Østfold Hospital Trust, Norway. the study population consists of 1,110 consenting healthy women, assessed to be at low-risk at spontaneous onset of labour. effect measures; avoided caesarean sections, instrumental vaginal deliveries, complications requiring treatment in the operating room, epidural analgesia and oxytocin augmentation. Costs (€) were calculated by costs per day multiplied with length of stay, added costs for procedures performed outside the units. The results are expressed in incremental cost-effectiveness ratios (ICER) with SCU as comparator. total costs per stay were significantly lower for women at the MU (€1,672) compared to the SCU (€1,950, pcosts and reduction in clinical procedures) for all effect measures. Based on the sensitivity analysis, allocating low-risk women to MU significantly reduced costs, but was not a dominant strategy for all outcomes. the MU is more cost-effective than the SCU for low-risk women without prelabour preference for level of birth care provided equal capacity at the units. it is cost-effective to organise birth care for low-risk women in a separate midwife-led unit. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. cis-Expression QTL analysis of established colorectal cancer risk variants in colon tumors and adjacent normal tissue.

    Directory of Open Access Journals (Sweden)

    Lenora W M Loo

    Full Text Available Genome-wide association studies (GWAS have identified 19 risk variants associated with colorectal cancer. As most of these risk variants reside outside the coding regions of genes, we conducted cis-expression quantitative trait loci (cis-eQTL analyses to investigate possible regulatory functions on the expression of neighboring genes. Forty microsatellite stable and CpG island methylator phenotype-negative colorectal tumors and paired adjacent normal colon tissues were used for genome-wide SNP and gene expression profiling. We found that three risk variants (rs10795668, rs4444235 and rs9929218, using near perfect proxies rs706771, rs11623717 and rs2059252, respectively were significantly associated (FDR q-value ≤0.05 with expression levels of nearby genes (<2 Mb up- or down-stream. We observed an association between the low colorectal cancer risk allele (A for rs10795668 at 10p14 and increased expression of ATP5C1 (q = 0.024 and between the colorectal cancer high risk allele (C for rs4444235 at 14q22.2 and increased expression of DLGAP5 (q = 0.041, both in tumor samples. The colorectal cancer low risk allele (A for rs9929218 at 16q22.1 was associated with a significant decrease in expression of both NOL3 (q = 0.017 and DDX28 (q = 0.046 in the adjacent normal colon tissue samples. Of the four genes, DLGAP5 and NOL3 have been previously reported to play a role in colon carcinogenesis and ATP5C1 and DDX28 are mitochondrial proteins involved in cellular metabolism and division, respectively. The combination of GWAS findings, prior functional studies, and the cis-eQTL analyses described here suggest putative functional activities for three of the colorectal cancer GWAS identified risk loci as regulating the expression of neighboring genes.

  14. A new variant selection criterion for twin variants in titanium alloys. Pt. 2

    Energy Technology Data Exchange (ETDEWEB)

    Schuman, Christophe [Laboratoire d' Etude des Microstructures et de Mecanique des Materiaux, LEM3, CNRS 7239, Universite Paul Verlaine - Metz, Ile du Saulcy, Metz (France); Bao, Lei; Lecomte, Jean Sebastien; Zhang, Yudong; Raulot, Jean Marc; Philippe, Marie Jeanne; Esling, Claude [LEM3, CNRS 7239, Universite Paul Verlaine - Metz, Ile du Saulcy, Metz (France)

    2012-05-15

    A new selection criterion to explain the activation of the twinning variant is proposed. This criterion is based on the calculation of the deformation energy to create a primary twin. The calculation takes into account the effect of the grain size using a Hall-Petch type relation. This criterion allows to obtain a very good prediction for the twin family selection and twin variant selection. The calculations are compared with the experimental results obtained on T40 (ASTM grade 2) deformed by Channel Die compression. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  15. Mutation Update: The Spectra of Nebulin Variants and Associated Myopathies

    Science.gov (United States)

    Lehtokari, Vilma-Lotta; Kiiski, Kirsi; Sandaradura, Sarah A.; Laporte, Jocelyn; Repo, Pauliina; Frey, Jennifer A.; Donner, Kati; Marttila, Minttu; Saunders, Carol; Barth, Peter G.; den Dunnen, Johan T.; Beggs, Alan H.; Clarke, Nigel F.; North, Kathryn N.; Laing, Nigel G.; Romero, Norma B.; Winder, Thomas L.; Pelin, Katarina; Wallgren-Pettersson, Carina

    2015-01-01

    A mutation update on the nebulin gene (NEB) is necessary because of recent developments in analysis methodology, the identification of increasing numbers and novel types of variants, and a widening in the spectrum of clinical and histological phenotypes associated with this gigantic, 183 exons containing gene. Recessive pathogenic variants in NEB are the major cause of nemaline myopathy (NM), one of the most common congenital myopathies. Moreover, pathogenic NEB variants have been identified in core-rod myopathy and in distal myopathies. In this update, we present the disease-causing variants in NEB in 159 families, 143 families with NM, and 16 families with NM-related myopathies. Eighty-eight families are presented here for the first time. We summarize 86 previously published and 126 unpublished variants identified in NEB. Furthermore, we have analyzed the NEB variants deposited in the Exome Variant Server (http://evs.gs.washington.edu/EVS/), identifying that pathogenic variants are a minor fraction of all coding variants (~7%). This indicates that nebulin tolerates substantial changes in its amino acid sequence, providing an explanation as to why variants in such a large gene result in relatively rare disorders. Lastly, we discuss the difficulties of drawing reliable genotype–phenotype correlations in NEB-associated disease. PMID:25205138

  16. XVCL: XML-based Variant Configuration Language

    DEFF Research Database (Denmark)

    Jarzabek, Stan; Basset, Paul; Zhang, Hongyu;

    2003-01-01

    XVCL (XML-based Variant Configuration Language) is a meta-programming technique and tool that provides effective reuse mechanisms. XVCL is an open source software developed at the National University of Singapore. Being a modern and versatile version of Bassett's frames, a technology that has...... achieved substantial gains in industry, the underlying principles of the XVCL have been thoroughly tested in practice. We envision many other applications in software and non-software domains, as we can apply XVCL to any domain that can be represented as a collection of textual documents....

  17. Clinical variants of idiopathic torsion dystonia.

    Science.gov (United States)

    Fahn, S

    1989-06-01

    Some patients with dystonic movements and postures not known to be caused by environmental or degenerative disorders can be segregated from classical-appearing idiopathic torsion dystonia on the basis of distinctive clinical and pharmacologic features. Many of them should be considered within the family of dystonia, as clinical variants of idiopathic torsion dystonia, while others are better classified as being part of other families of dyskinesias. In the former group are paradoxical dystonia, myoclonic dystonia, diurnal dystonia, and dopa-responsive dystonia. The latter group consists of dystonic tics and the various entities comprising paroxysmal dystonia, namely kinesigenic, nonkinesigenic and hypnogenic dystonia.

  18. Space-variant polarized Airy beam

    CERN Document Server

    Chen, Hao

    2015-01-01

    We experimentally generate an Airy beam with polarization structure while keeping its original amplitude and phase profile intact. This class of Airy beam preserves the acceleration properties. By monitoring their initial polarization structure we have provided insight concerning the self-healing mechanism of Airy beams. We investigate both theoretically and experimentally the self-healing polarization properties of the space-variant polarized Airy beams. Amplitude as well as the polarization structure tends to reform during propagation in spite of the severe truncation of the beam by finite apertures.

  19. Pitfalls and variants in pediatric chest imaging.

    Science.gov (United States)

    García Asensio, D; Fernández Martín, M

    2016-05-01

    Most pitfalls in the interpretation of pediatric chest imaging are closely related with the technique used and the characteristics of pediatric patients. To obtain a quality image that will enable the correct diagnosis, it is very important to use an appropriate technique. It is important to know how technical factors influence the image and to be aware of the possible artifacts that can result from poor patient cooperation. Moreover, radiologists need to be familiar with the normal anatomy in children, with the classic radiologic findings, and with the anatomic and developmental variants to avoid misinterpreting normal findings as pathological.

  20. Variant position of the medial plantar nerve

    Directory of Open Access Journals (Sweden)

    Astik RB

    2011-01-01

    Full Text Available Knowledge of variation of position of the medial plantar nerve is important for the forefoot surgeon for plantar reconstruction, local injection therapy and an excision of interdigital neuroma. During routine dissection of 50-year-old female cadaver, we found the medial plantar nerve and vessels variably located between plantar aponeurosis and the muscles of the first layer of the sole of the right foot. Due to this variant position, the medial plantar nerve and vessels lose their protection from the muscles of the first layer of the sole of the foot and became vulnerable for compression.

  1. Performance comparison of various time variant filters

    Energy Technology Data Exchange (ETDEWEB)

    Kuwata, M. [JEOL Engineering Co. Ltd., Akishima, Tokyo (Japan); Husimi, K.

    1996-07-01

    This paper describes the advantage of the trapezoidal filter used in semiconductor detector system comparing with the other time variant filters. The trapezoidal filter is the compose of a rectangular pre-filter and a gated integrator. We indicate that the best performance is obtained by the differential-integral summing type rectangular pre-filter. This filter is not only superior in performance, but also has the useful feature that the rising edge of the output waveform is linear. We introduce an example of this feature used in a high-energy experiment. (author)

  2. [Necrobiosis lipoidica. Variants on a theme].

    Science.gov (United States)

    Geissler, E; Laaff, H; Technau, K; Bruckner-Tuderman, L; Nashan, D

    2011-08-01

    A 69-year-old patient presented with different skin lesions all of which belonged to group of necrobiosis lipoidica. The initial histologic diagnosis was actinic granuloma O'Brien. A subsequent biopsy was interpreted as granulomatous necrobiosis lipoidica. The history of these necrobiotic variants is reviewed and exemplarily depicted with this case. Necrobiosis lipoidica is part of the spectrum of granulomatous skin disorders. Although its etiology is unclear, an association with diabetes mellitus is often discussed. Multiple therapeutic options exist, but standardized guidelines for treatment are missing.

  3. Oral fibrolipoma: A rare histological variant

    Directory of Open Access Journals (Sweden)

    Treville Pereira

    2014-01-01

    Full Text Available Lipomas are benign soft tissue mesenchymal neoplasms. Fibrolipoma is a histological variant of lipoma that mostly affects the buccal mucosa and causes functional and cosmetic disabilities. The diagnosis and differentiation of fibrolipoma with clinically similar lesion