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Sample records for risk alleles support

  1. Common breast cancer risk alleles and risk assessment

    DEFF Research Database (Denmark)

    Näslund-Koch, C; Nordestgaard, B G; Bojesen, S E

    2017-01-01

    general population were followed in Danish health registries for up to 21 years after blood sampling. After genotyping 72 breast cancer risk loci, each with 0-2 alleles, the sum for each individual was calculated. We used the simple allele sum instead of the conventional polygenic risk score......, as it is likely more sensitive in detecting associations with risks of other endpoints than breast cancer. RESULTS: Breast cancer incidence in the 19,010 women was increased across allele sum quintiles (log-rank trend test; p=1*10(-12)), but not incidence of other cancers (p=0.41). Age- and study-adjusted hazard...... ratio for the 5(th) vs. 1(st) allele sum quintile was 1.82(95% confidence interval;1.53-2.18). Corresponding hazard ratios per allele were 1.04(1.03-1.05) and 1.05(1.02-1.08) for breast cancer incidence and mortality, similar across risk factors. In 50-year old women, the starting age for screening...

  2. A risk allele for nicotine dependence in CHRNA5 is a protective allele for cocaine dependence.

    Science.gov (United States)

    Grucza, Richard A; Wang, Jen C; Stitzel, Jerry A; Hinrichs, Anthony L; Saccone, Scott F; Saccone, Nancy L; Bucholz, Kathleen K; Cloninger, C Robert; Neuman, Rosalind J; Budde, John P; Fox, Louis; Bertelsen, Sarah; Kramer, John; Hesselbrock, Victor; Tischfield, Jay; Nurnberger, John I; Almasy, Laura; Porjesz, Bernice; Kuperman, Samuel; Schuckit, Marc A; Edenberg, Howard J; Rice, John P; Goate, Alison M; Bierut, Laura J

    2008-12-01

    A nonsynonymous coding polymorphism, rs16969968, of the CHRNA5 gene that encodes the alpha-5 subunit of the nicotinic acetylcholine receptor (nAChR) has been found to be associated with nicotine dependence. The goal of this study was to examine the association of this variant with cocaine dependence. Genetic association analysis was performed in two independent samples of unrelated case and control subjects: 1) 504 European Americans participating in the Family Study on Cocaine Dependence (FSCD) and 2) 814 European Americans participating in the Collaborative Study on the Genetics of Alcoholism (COGA). In the FSCD, there was a significant association between the CHRNA5 variant and cocaine dependence (odds ratio = .67 per allele, p = .0045, assuming an additive genetic model), but in the reverse direction compared with that previously observed for nicotine dependence. In multivariate analyses that controlled for the effects of nicotine dependence, both the protective effect for cocaine dependence and the previously documented risk effect for nicotine dependence were statistically significant. The protective effect for cocaine dependence was replicated in the COGA sample. In COGA, effect sizes for habitual smoking, a proxy phenotype for nicotine dependence, were consistent with those observed in FSCD. The minor (A) allele of rs16969968, relative to the major G allele, appears to be both a risk factor for nicotine dependence and a protective factor for cocaine dependence. The biological plausibility of such a bidirectional association stems from the involvement of nAChRs with both excitatory and inhibitory modulation of dopamine-mediated reward pathways.

  3. A strategy to discover genes that carry multi-allelic or mono-allelic risk for common diseases: A cohort allelic sums test (CAST)

    International Nuclear Information System (INIS)

    Morgenthaler, Stephan; Thilly, William G.

    2007-01-01

    A method is described to discover if a gene carries one or more allelic mutations that confer risk for any specified common disease. The method does not depend upon genetic linkage of risk-conferring mutations to high frequency genetic markers such as single nucleotide polymorphisms. Instead, the sums of allelic mutation frequencies in case and control cohorts are determined and a statistical test is applied to discover if the difference in these sums is greater than would be expected by chance. A statistical model is presented that defines the ability of such tests to detect significant gene-disease relationships as a function of case and control cohort sizes and key confounding variables: zygosity and genicity, environmental risk factors, errors in diagnosis, limits to mutant detection, linkage of neutral and risk-conferring mutations, ethnic diversity in the general population and the expectation that among all exonic mutants in the human genome greater than 90% will be neutral with regard to any effect on disease risk. Means to test the null hypothesis for, and determine the statistical power of, each test are provided. For this 'cohort allelic sums test' or 'CAST', the statistical model and test are provided as an Excel (TM) program, CASTAT (C) at http://epidemiology.mit.edu. Based on genetics, technology and statistics, a strategy of enumerating the mutant alleles carried in the exons and splice sites of the estimated ∼25,000 human genes in case cohort samples of 10,000 persons for each of 100 common diseases is proposed and evaluated: A wide range of possible conditions of multi-allelic or mono-allelic and monogenic, multigenic or polygenic (including epistatic) risk are found to be detectable using the statistical criteria of 1 or 10 ''false positive'' gene associations per 25,000 gene-disease pair-wise trials and a statistical power of >0.8. Using estimates of the distribution of both neutral and gene-inactivating nondeleterious mutations in humans and

  4. Type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases.

    Directory of Open Access Journals (Sweden)

    Rong Chen

    Full Text Available Many disease-susceptible SNPs exhibit significant disparity in ancestral and derived allele frequencies across worldwide populations. While previous studies have examined population differentiation of alleles at specific SNPs, global ethnic patterns of ensembles of disease risk alleles across human diseases are unexamined. To examine these patterns, we manually curated ethnic disease association data from 5,065 papers on human genetic studies representing 1,495 diseases, recording the precise risk alleles and their measured population frequencies and estimated effect sizes. We systematically compared the population frequencies of cross-ethnic risk alleles for each disease across 1,397 individuals from 11 HapMap populations, 1,064 individuals from 53 HGDP populations, and 49 individuals with whole-genome sequences from 10 populations. Type 2 diabetes (T2D demonstrated extreme directional differentiation of risk allele frequencies across human populations, compared with null distributions of European-frequency matched control genomic alleles and risk alleles for other diseases. Most T2D risk alleles share a consistent pattern of decreasing frequencies along human migration into East Asia. Furthermore, we show that these patterns contribute to disparities in predicted genetic risk across 1,397 HapMap individuals, T2D genetic risk being consistently higher for individuals in the African populations and lower in the Asian populations, irrespective of the ethnicity considered in the initial discovery of risk alleles. We observed a similar pattern in the distribution of T2D Genetic Risk Scores, which are associated with an increased risk of developing diabetes in the Diabetes Prevention Program cohort, for the same individuals. This disparity may be attributable to the promotion of energy storage and usage appropriate to environments and inconsistent energy intake. Our results indicate that the differential frequencies of T2D risk alleles may

  5. Type 2 Diabetes Risk Allele Loci in the Qatari Population.

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    Sarah L O'Beirne

    Full Text Available The prevalence of type 2 diabetes (T2D is increasing in the Middle East. However, the genetic risk factors for T2D in the Middle Eastern populations are not known, as the majority of studies of genetic risk for T2D are in Europeans and Asians.All subjects were ≥3 generation Qataris. Cases with T2D (n = 1,124 and controls (n = 590 were randomly recruited and assigned to the 3 known Qatari genetic subpopulations [Bedouin (Q1, Persian/South Asian (Q2 and African (Q3]. Subjects underwent genotyping for 37 single nucleotide polymorphisms (SNPs in 29 genes known to be associated with T2D in Europeans and/or Asian populations, and an additional 27 tag SNPs related to these susceptibility loci. Pre-study power analysis suggested that with the known incidence of T2D in adult Qataris (22%, the study population size would be sufficient to detect significant differences if the SNPs were risk factors among Qataris, assuming that the odds ratio (OR for T2D SNPs in Qatari's is greater than or equal to the SNP with highest known OR in other populations.Haplotype analysis demonstrated that Qatari haplotypes in the region of known T2D risk alleles in Q1 and Q2 genetic subpopulations were similar to European haplotypes. After Benjamini-Hochberg adjustment for multiple testing, only two SNPs (rs7903146 and rs4506565, both associated with transcription factor 7-like 2 (TCF7L2, achieved statistical significance in the whole study population. When T2D subjects and control subjects were assigned to the known 3 Qatari subpopulations, and analyzed individually and with the Q1 and Q2 genetic subpopulations combined, one of these SNPs (rs4506565 was also significant in the admixed group. No other SNPs associated with T2D in all Qataris or individual genetic subpopulations.With the caveats of the power analysis, the European/Asian T2D SNPs do not contribute significantly to the high prevalence of T2D in the Qatari population, suggesting that the genetic risks for T2D are

  6. Efficient computation of the joint probability of multiple inherited risk alleles from pedigree data.

    Science.gov (United States)

    Madsen, Thomas; Braun, Danielle; Peng, Gang; Parmigiani, Giovanni; Trippa, Lorenzo

    2018-06-25

    The Elston-Stewart peeling algorithm enables estimation of an individual's probability of harboring germline risk alleles based on pedigree data, and serves as the computational backbone of important genetic counseling tools. However, it remains limited to the analysis of risk alleles at a small number of genetic loci because its computing time grows exponentially with the number of loci considered. We propose a novel, approximate version of this algorithm, dubbed the peeling and paring algorithm, which scales polynomially in the number of loci. This allows extending peeling-based models to include many genetic loci. The algorithm creates a trade-off between accuracy and speed, and allows the user to control this trade-off. We provide exact bounds on the approximation error and evaluate it in realistic simulations. Results show that the loss of accuracy due to the approximation is negligible in important applications. This algorithm will improve genetic counseling tools by increasing the number of pathogenic risk alleles that can be addressed. To illustrate we create an extended five genes version of BRCAPRO, a widely used model for estimating the carrier probabilities of BRCA1 and BRCA2 risk alleles and assess its computational properties. © 2018 WILEY PERIODICALS, INC.

  7. ADHD and DAT1: Further evidence of paternal over-transmission of risk alleles and haplotype

    NARCIS (Netherlands)

    Hawi, Z.; Kent, L.; Hill, M.; Anney, R.J.; Brookes, K. J.; Barry, E.; Franke, B.; Banaschewski, T.; Buitelaar, J.; Ebstein, R.; Miranda, A.; Oades, R.D.; Roeyers, H.; Rothenberger, A.; Sergeant, J.A.; Sonuga-Barke, E.; Steinhausen, H.C.; Faraone, S.V.; Asherson, P.; Gill, M.

    2009-01-01

    We [Hawi et al. (2005); Am J Hum Genet 77:958-965] reported paternal over-transmission of risk alleles in some ADHD-associated genes. This was particularly clear in the case of the DAT1 30-UTR VNTR. In the current investigation, we analyzed three new sample comprising of 1,248 ADHD nuclear families

  8. ADHD and DAT1: further evidence of paternal over-transmission of risk alleles and haplotype.

    NARCIS (Netherlands)

    Hawi, Z.; Kent, L.; Hill, M.; Anney, R.J.; Brookes, K.J.; Barry, E.; Franke, B.; Banaschewski, T.; Buitelaar, J.K.; Ebstein, R.; Miranda, A.; Oades, R.D.; Roeyers, H.; Rothenberger, A.; Sergeant, J.A.; Sonuga-Barke, E.J.S.; Steinhausen, H.C.; Faraone, S.V.; Asherson, P.; Gill, M.

    2010-01-01

    We [Hawi et al. (2005); Am J Hum Genet 77:958-965] reported paternal over-transmission of risk alleles in some ADHD-associated genes. This was particularly clear in the case of the DAT1 3'-UTR VNTR. In the current investigation, we analyzed three new sample comprising of 1,248 ADHD nuclear families

  9. DLA Class II Alleles Are Associated with Risk for Canine Symmetrical Lupoid Onychodystropy (SLO)

    Science.gov (United States)

    Wilbe, Maria; Ziener, Martine Lund; Aronsson, Anita; Harlos, Charlotte; Sundberg, Katarina; Norberg, Elin; Andersson, Lisa; Lindblad-Toh, Kerstin; Hedhammar, Åke; Andersson, Göran; Lingaas, Frode

    2010-01-01

    Symmetrical lupoid onychodystrophy (SLO) is an immune-mediated disease in dogs affecting the claws with a suggested autoimmune aethiology. Sequence-based genotyping of the polymorphic exon 2 from DLA-DRB1, -DQA1, and -DQB1 class II loci were performed in a total of 98 SLO Gordon setter cases and 98 healthy controls. A risk haplotype (DRB1*01801/DQA1*00101/DQB1*00802) was present in 53% of cases and 34% of controls and conferred an elevated risk of developing SLO with an odds ratio (OR) of 2.1. When dogs homozygous for the risk haplotype were compared to all dogs not carrying the haplotype the OR was 5.4. However, a stronger protective haplotype (DRB1*02001/DQA1*00401/DQB1*01303, OR = 0.03, 1/OR = 33) was present in 16.8% of controls, but only in a single case (0.5%). The effect of the protective haplotype was clearly stronger than the risk haplotype, since 11.2% of the controls were heterozygous for the risk and protective haplotypes, whereas this combination was absent from cases. When the dogs with the protective haplotype were excluded, an OR of 2.5 was obtained when dogs homozygous for the risk haplotype were compared to those heterozygous for the risk haplotype, suggesting a co-dominant effect of the risk haplotype. In smaller sample sizes of the bearded collie and giant schnauzer breeds we found the same or similar haplotypes, sharing the same DQA1 allele, over-represented among the cases suggesting that the risk is associated primarily with DLA-DQ. We obtained conclusive results that DLA class II is significantly associated with risk of developing SLO in Gordon setters, thus supporting that SLO is an immune-mediated disease. Further studies of SLO in dogs may provide important insight into immune privilege of the nail apparatus and also knowledge about a number of inflammatory disorders of the nail apparatus like lichen planus, psoriasis, alopecia areata and onycholysis. PMID:20808798

  10. DLA class II alleles are associated with risk for canine symmetrical lupoid onychodystrophy [corrected](SLO.

    Directory of Open Access Journals (Sweden)

    Maria Wilbe

    Full Text Available Symmetrical lupoid onychodystrophy (SLO is an immune-mediated disease in dogs affecting the claws with a suggested autoimmune aethiology. Sequence-based genotyping of the polymorphic exon 2 from DLA-DRB1, -DQA1, and -DQB1 class II loci were performed in a total of 98 SLO Gordon setter cases and 98 healthy controls. A risk haplotype (DRB1*01801/DQA1*00101/DQB1*00802 was present in 53% of cases and 34% of controls and conferred an elevated risk of developing SLO with an odds ratio (OR of 2.1. When dogs homozygous for the risk haplotype were compared to all dogs not carrying the haplotype the OR was 5.4. However, a stronger protective haplotype (DRB1*02001/DQA1*00401/DQB1*01303, OR = 0.03, 1/OR = 33 was present in 16.8% of controls, but only in a single case (0.5%. The effect of the protective haplotype was clearly stronger than the risk haplotype, since 11.2% of the controls were heterozygous for the risk and protective haplotypes, whereas this combination was absent from cases. When the dogs with the protective haplotype were excluded, an OR of 2.5 was obtained when dogs homozygous for the risk haplotype were compared to those heterozygous for the risk haplotype, suggesting a co-dominant effect of the risk haplotype. In smaller sample sizes of the bearded collie and giant schnauzer breeds we found the same or similar haplotypes, sharing the same DQA1 allele, over-represented among the cases suggesting that the risk is associated primarily with DLA-DQ. We obtained conclusive results that DLA class II is significantly associated with risk of developing SLO in Gordon setters, thus supporting that SLO is an immune-mediated disease. Further studies of SLO in dogs may provide important insight into immune privilege of the nail apparatus and also knowledge about a number of inflammatory disorders of the nail apparatus like lichen planus, psoriasis, alopecia areata and onycholysis.

  11. Genes of the unfolded protein response pathway harbor risk alleles for primary open angle glaucoma.

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    Mary Anna Carbone

    Full Text Available The statistical power of genome-wide association (GWA studies to detect risk alleles for human diseases is limited by the unfavorable ratio of SNPs to study subjects. This multiple testing problem can be surmounted with very large population sizes when common alleles of large effects give rise to disease status. However, GWA approaches fall short when many rare alleles may give rise to a common disease, or when the number of subjects that can be recruited is limited. Here, we demonstrate that this multiple testing problem can be overcome by a comparative genomics approach in which an initial genome-wide screen in a genetically amenable model organism is used to identify human orthologues that may harbor risk alleles for adult-onset primary open angle glaucoma (POAG. Glaucoma is a major cause of blindness, which affects over 60 million people worldwide. Several genes have been associated with juvenile onset glaucoma, but genetic factors that predispose to adult onset primary open angle glaucoma (POAG remain largely unknown. Previous genome-wide analysis in a Drosophila ocular hypertension model identified transcripts with altered regulation and showed induction of the unfolded protein response (UPR upon overexpression of transgenic human glaucoma-associated myocilin (MYOC. We selected 16 orthologous genes with 62 polymorphic markers and identified in two independent human populations two genes of the UPR that harbor POAG risk alleles, BIRC6 and PDIA5. Thus, effectiveness of the UPR in response to accumulation of misfolded or aggregated proteins may contribute to the pathogenesis of POAG and provide targets for early therapeutic intervention.

  12. Genes of the unfolded protein response pathway harbor risk alleles for primary open angle glaucoma.

    Science.gov (United States)

    Carbone, Mary Anna; Chen, Yuhong; Hughes, Guy A; Weinreb, Robert N; Zabriskie, Norman A; Zhang, Kang; Anholt, Robert R H

    2011-01-01

    The statistical power of genome-wide association (GWA) studies to detect risk alleles for human diseases is limited by the unfavorable ratio of SNPs to study subjects. This multiple testing problem can be surmounted with very large population sizes when common alleles of large effects give rise to disease status. However, GWA approaches fall short when many rare alleles may give rise to a common disease, or when the number of subjects that can be recruited is limited. Here, we demonstrate that this multiple testing problem can be overcome by a comparative genomics approach in which an initial genome-wide screen in a genetically amenable model organism is used to identify human orthologues that may harbor risk alleles for adult-onset primary open angle glaucoma (POAG). Glaucoma is a major cause of blindness, which affects over 60 million people worldwide. Several genes have been associated with juvenile onset glaucoma, but genetic factors that predispose to adult onset primary open angle glaucoma (POAG) remain largely unknown. Previous genome-wide analysis in a Drosophila ocular hypertension model identified transcripts with altered regulation and showed induction of the unfolded protein response (UPR) upon overexpression of transgenic human glaucoma-associated myocilin (MYOC). We selected 16 orthologous genes with 62 polymorphic markers and identified in two independent human populations two genes of the UPR that harbor POAG risk alleles, BIRC6 and PDIA5. Thus, effectiveness of the UPR in response to accumulation of misfolded or aggregated proteins may contribute to the pathogenesis of POAG and provide targets for early therapeutic intervention.

  13. Lower Frequency of HLA-DRB1 Type 1 Diabetes Risk Alleles in Pediatric Patients with MODY.

    Science.gov (United States)

    Urrutia, Inés; Martínez, Rosa; López-Euba, Tamara; Velayos, Teresa; Martínez de LaPiscina, Idoia; Bilbao, José Ramón; Rica, Itxaso; Castaño, Luis

    2017-01-01

    The aim of this study was to determine the frequency of susceptible HLA-DRB1 alleles for type 1 diabetes in a cohort of pediatric patients with a confirmed genetic diagnosis of MODY. 160 families with a proband diagnosed with type 1 diabetes and 74 families with a molecular diagnosis of MODY (61 GCK-MODY and 13 HNF1A-MODY) were categorized at high definition for HLA-DRB1 locus. According to the presence or absence of the susceptible HLA-DRB1 alleles for type 1 diabetes, we considered three different HLA-DRB1 genotypes: 0 risk alleles (no DR3 no DR4); 1 risk allele (DR3 or DR4); 2 risk alleles (DR3 and/or DR4). Compared with type 1 diabetes, patients with MODY carried higher frequency of 0 risk alleles, OR 22.7 (95% CI: 10.7-48.6) and lower frequency of 1 or 2 risk alleles, OR 0.53 (95% CI: 0.29-0.96) and OR 0.06 (95% CI: 0.02-0.18), respectively. The frequency of HLA-DRB1 risk alleles for type 1 diabetes is significantly lower in patients with MODY. In children and adolescents with diabetes, the presence of 2 risk alleles (DR3 and/or DR4) reduces the probability of MODY diagnosis, whereas the lack of risk alleles increases it. Therefore, we might consider that HLA-DRB1 provides additional information for the selection of patients with high probability of monogenic diabetes.

  14. Lower Frequency of HLA-DRB1 Type 1 Diabetes Risk Alleles in Pediatric Patients with MODY.

    Directory of Open Access Journals (Sweden)

    Inés Urrutia

    Full Text Available The aim of this study was to determine the frequency of susceptible HLA-DRB1 alleles for type 1 diabetes in a cohort of pediatric patients with a confirmed genetic diagnosis of MODY.160 families with a proband diagnosed with type 1 diabetes and 74 families with a molecular diagnosis of MODY (61 GCK-MODY and 13 HNF1A-MODY were categorized at high definition for HLA-DRB1 locus. According to the presence or absence of the susceptible HLA-DRB1 alleles for type 1 diabetes, we considered three different HLA-DRB1 genotypes: 0 risk alleles (no DR3 no DR4; 1 risk allele (DR3 or DR4; 2 risk alleles (DR3 and/or DR4.Compared with type 1 diabetes, patients with MODY carried higher frequency of 0 risk alleles, OR 22.7 (95% CI: 10.7-48.6 and lower frequency of 1 or 2 risk alleles, OR 0.53 (95% CI: 0.29-0.96 and OR 0.06 (95% CI: 0.02-0.18, respectively.The frequency of HLA-DRB1 risk alleles for type 1 diabetes is significantly lower in patients with MODY. In children and adolescents with diabetes, the presence of 2 risk alleles (DR3 and/or DR4 reduces the probability of MODY diagnosis, whereas the lack of risk alleles increases it. Therefore, we might consider that HLA-DRB1 provides additional information for the selection of patients with high probability of monogenic diabetes.

  15. DNA Methylation Analysis of BRD1 Promoter Regions and the Schizophrenia rs138880 Risk Allele.

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    Mads Dyrvig

    Full Text Available The bromodomain containing 1 gene, BRD1 is essential for embryogenesis and CNS development. It encodes a protein that participates in histone modifying complexes and thereby regulates the expression of a large number of genes. Genetic variants in the BRD1 locus show association with schizophrenia and bipolar disorder and risk alleles in the promoter region correlate with reduced BRD1 expression. Insights into the transcriptional regulation of BRD1 and the pathogenic mechanisms associated with BRD1 risk variants, however, remain sparse. By studying transcripts in human HeLa and SH-SY5Y cells we provide evidence for differences in relative expression of BRD1 transcripts with three alternative 5' UTRs (exon 1C, 1B, and 1A. We further show that expression of these transcript variants covaries negatively with DNA methylation proportions in their upstream promoter regions suggesting that promoter usage might be regulated by DNA methylation. In line with findings that the risk allele of the rs138880 SNP in the BRD1 promoter region correlates with reduced BRD1 expression, we find that it is also associated with moderate regional BRD1 promoter hypermethylation in both adipose tissue and blood. Importantly, we demonstrate by inspecting available DNA methylation and expression data that these regions undergo changes in methylation during fetal brain development and that differences in their methylation proportions in fetal compared to postnatal frontal cortex correlate significantly with BRD1 expression. These findings suggest that BRD1 may be dysregulated in both the developing and mature brain of risk allele carriers. Finally, we demonstrate that commonly used mood stabilizers Lithium, Valproate, and Carbamazepine affect the expression of BRD1 in SH-SY5Y cells. Altogether this study indicates a link between genetic risk and epigenetic dysregulation of BRD1 which raises interesting perspectives for targeting the mechanisms pharmacologically.

  16. Human hypervariable sequences in risk assessment: rare Ha-ras alleles in cancer patients

    International Nuclear Information System (INIS)

    Krontiris, T.G.; DiMartino, N.A.; Mitcheson, H.D.; Lonergan, J.A.; Begg, C.; Parkinson, D.R.

    1987-01-01

    A variable tandem repeat (VTR) is responsible for the hyperallelism one kilobase 3' to the human c-Ha-ras-1 (Ha-ras) gene. Thirty-two distinct restriction fragments, comprising 3 allelic classes by frequency of occurrence, have thus far been detected in a sample size of approximately 800 caucasians. Rare Ha-ras alleles, 21 in all, are almost exclusively confined to the genomes of cancer patients. From their data the authors have computed the relative cancer risk associated with possession of a rare Ha-ras allele to be 27. To understand the molecular basis for this phenomenon, they have begun to clone Ha-ras fragments from nontumor DNA of cancer patients. They report here the weak activation, as detected by transfection and transformation of NIH 3T3 mouse cells, of two Ha-ras genes which were obtained from lymphocyte DNA of a melanoma patient. They have mapped the regions that confer this transforming activity to the fragment containing the VTR in one Ha-ras clone and the fragment containing gene coding sequences in the other

  17. Widespread signatures of positive selection in common risk alleles associated to autism spectrum disorder.

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    Renato Polimanti

    2017-02-01

    Full Text Available The human brain is the outcome of innumerable evolutionary processes; the systems genetics of psychiatric disorders could bear their signatures. On this basis, we analyzed five psychiatric disorders, attention deficit hyperactivity disorder, autism spectrum disorder (ASD, bipolar disorder, major depressive disorder, and schizophrenia (SCZ, using GWAS summary statistics from the Psychiatric Genomics Consortium. Machine learning-derived scores were used to investigate two natural-selection scenarios: complete selection (loci where a selected allele reached fixation and incomplete selection (loci where a selected allele has not yet reached fixation. ASD GWAS results positively correlated with incomplete-selection (p = 3.53*10-4. Variants with ASD GWAS p<0.1 were shown to have a 19%-increased probability to be in the top-5% for incomplete-selection score (OR = 1.19, 95%CI = 1.11-1.8, p = 9.56*10-7. Investigating the effect directions of minor alleles, we observed an enrichment for positive associations in SNPs with ASD GWAS p<0.1 and top-5% incomplete-selection score (permutation p<10-4. Considering the set of these ASD-positive-associated variants, we observed gene-expression enrichments for brain and pituitary tissues (p = 2.3*10-5 and p = 3*10-5, respectively and 53 gene ontology (GO enrichments, such as nervous system development (GO:0007399, p = 7.57*10-12, synapse organization (GO:0050808, p = 8.29*10-7, and axon guidance (GO:0007411, p = 1.81*10-7. Previous genetic studies demonstrated that ASD positively correlates with childhood intelligence, college completion, and years of schooling. Accordingly, we hypothesize that certain ASD risk alleles were under positive selection during human evolution due to their involvement in neurogenesis and cognitive ability.

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

    International Nuclear Information System (INIS)

    Riaz, Muhammad; Elstrodt, Fons; Hollestelle, Antoinette; Dehghan, Abbas; Klijn, Jan GM; Schutte, Mieke

    2009-01-01

    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. 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. 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. 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

  19. Probability Model of Allele Frequency of Alzheimer’s Disease Genetic Risk Factor

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    Afshin Fayyaz-Movaghar

    2016-06-01

    Full Text Available Background and Purpose: The identification of genetics risk factors of human diseases is very important. This study is conducted to model the allele frequencies (AFs of Alzheimer’s disease. Materials and Methods: In this study, several candidate probability distributions are fitted on a data set of Alzheimer’s disease genetic risk factor. Unknown parameters of the considered distributions are estimated, and some criterions of goodness-of-fit are calculated for the sake of comparison. Results: Based on some statistical criterions, the beta distribution gives the best fit on AFs. However, the estimate values of the parameters of beta distribution lead us to the standard uniform distribution. Conclusion: The AFs of Alzheimer’s disease follow the standard uniform distribution.

  20. Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers

    DEFF Research Database (Denmark)

    Antoniou, Antonis C; Spurdle, Amanda B; Sinilnikova, Olga M

    2008-01-01

    Germline mutations in BRCA1 and BRCA2 confer high risks of breast cancer. However, evidence suggests that these risks are modified by other genetic or environmental factors that cluster in families. A recent genome-wide association study has shown that common alleles at single nucleotide polymorp...

  1. Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers

    DEFF Research Database (Denmark)

    Ramus, Susan J; Antoniou, Antonis C; Kuchenbaecker, Karoline B

    2012-01-01

    Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers ...

  2. Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers

    NARCIS (Netherlands)

    Ramus, Susan J.; Antoniou, Antonis C.; Kuchenbaecker, Karoline B.; Soucy, Penny; Beesley, Jonathan; Chen, Xiaoqing; McGuffog, Lesley; Sinilnikova, Olga M.; Healey, Sue; Barrowdale, Daniel; Lee, Andrew; Thomassen, Mads; Gerdes, Anne-Marie; Kruse, Torben A.; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A.; Liljegren, Annelie; Lindblom, Annika; Olsson, Håkan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Złowocka, Elżbieta; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Cybulski, Cezary; Toloczko-Grabarek, Aleksandra; Osorio, Ana; Benitez, Javier; Duran, Mercedes; Tejada, Maria-Isabel; Hamann, Ute; Rookus, Matti; van Leeuwen, Flora E.; Aalfs, Cora M.; Meijers-Heijboer, Hanne E. J.; van Asperen, Christi J.; van Roozendaal, K. E. P.; Hoogerbrugge, Nicoline; Collée, J. Margriet; Kriege, Mieke; van der Luijt, Rob B.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Evans, D. Gareth; Lalloo, Fiona; Jacobs, Chris; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Paterson, Joan; Douglas, Fiona; Brewer, Carole; Hodgson, Shirley; Morrison, Patrick J.; Walker, Lisa; Porteous, Mary E.; Kennedy, M. John; Pathak, Harsh; Godwin, Andrew K.; Stoppa-Lyonnet, Dominique; Caux-Moncoutier, Virginie; de Pauw, Antoine; Gauthier-Villars, Marion; Mazoyer, Sylvie; Léoné, Mélanie; Calender, Alain; Lasset, Christine; Bonadona, Valérie; Hardouin, Agnès; Berthet, Pascaline; Bignon, Yves-Jean; Uhrhammer, Nancy; Faivre, Laurence; Loustalot, Catherine; Buys, Saundra; Daly, Mary; Miron, Alex; Terry, Mary Beth; Chung, Wendy K.; John, Esther M.; Southey, Melissa; Goldgar, David; Singer, Christian F.; tea, Muy-Kheng; Pfeiler, Georg; Fink-Retter, Anneliese; Hansen, Thomas v O.; Ejlertsen, Bent; Johannsson, Oskar Th; Offit, Kenneth; Kirchhoff, Tomas; Gaudet, Mia M.; Vijai, Joseph; Robson, Mark; Piedmonte, Marion; Phillips, Kelly-Anne; van Le, Linda; Hoffman, James S.; Ewart Toland, Amanda; Montagna, Marco; Tognazzo, Silvia; Imyanitov, Evgeny; Issacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Iganacio; Tornero, Eva; Navarro, Matilde; Moysich, Kirsten B.; Karlan, Beth Y.; Gross, Jenny; Olah, Edith; Vaszko, Tibor; teo, Soo-Hwang; Ganz, Patricia A.; Beattie, Mary S.; Dorfling, Cecelia M.; van Rensburg, Elizabeth J.; Diez, Orland; Kwong, Ava; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Heidemann, Simone; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorotehea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Fiebig, Britta; Schäfer, Dieter; Caldes, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomäki, Kristiina; Plante, Marie; Spurdle, Amanda B.; Neuhausen, Susan L.; Ding, Yuan Chun; Wang, Xianshu; Lindor, Noralane; Fredericksen, Zachary; Pankratz, V. Shane; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Bonanni, Bernardo; Bernard, Loris; Dolcetti, Riccardo; Papi, Laura; Ottini, Laura; Radice, Paolo; Greene, Mark H.; Mai, Phuong L.; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Pharoah, Paul D. P.; Gayther, Simon A.; Simard, Jacques; Easton, Douglas F.; Couch, Fergus J.; Chenevix-Trench, Georgia; Miedzybrodzka, Zosia; Gregory, Helen; Morrison, Patrick; Jeffers, Lisa; Ong, Kai-Ren; Hoffman, Jonathan; Donaldson, Alan; James, Margaret; Downing, Sarah; Taylor, Amy; Murray, Alexandra; Rogers, Mark T.; McCann, Emma; Barton, David; Porteous, Mary; Drummond, Sarah; Kivuva, Emma; Searle, Anne; Goodman, Selina; Hill, Kathryn; Murday, Victoria; Bradshaw, Nicola; Snadden, Lesley; Longmuir, Mark; Watt, Catherine; Gibson, Sarah; Haque, Eshika; Tobias, Ed; Duncan, Alexis; Izatt, Louise; Langman, Caroline; Whaite, Anna; Dorkins, Huw; Barwell, Julian; Serra-Feliu, Gemma; Ellis, Ian; Houghton, Catherine; Taylor, Jane; Side, Lucy; Male, Alison; Berlin, Cheryl; Eason, Jacqueline; Collier, Rebecca; Claber, Oonagh; Jobson, Irene; McLeod, Diane; Halliday, Dorothy; Durell, Sarah; Stayner, Barbara; Shanley, Susan; Rahman, Nazneen; Houlston, Richard; Bancroft, Elizabeth; D'Mello, Lucia; Page, Elizabeth; Ardern-Jones, Audrey; Kohut, Kelly; Wiggins, Jennifer; Castro, Elena; Mitra, Anita; Robertson, Lisa; Quarrell, Oliver; Bardsley, Cathryn; Goff, Sheila; Brice, Glen; Winchester, Lizzie; Eddy, Charlotte; Tripathi, Vishakha; Attard, Virginia; Lucassen, Anneke; Crawford, Gillian; McBride, Donna; Smalley, Sarah; Sinilnikova, Olga; Barjhoux, Laure; Verny-Pierre, Carole; Giraud, Sophie; Léone, Mélanie; Buecher, Bruno; Houdayer, Claude; Moncoutier, Virginie; Belotti, Muriel; Tirapo, Carole; Bressac-de-Paillerets, Brigitte; Remenieras, Audrey; Byrede, Véronique; Caron, Olivier; Lenoir, Gilbert; Urhammer, Nancy; Sobol, Hagay; Bourdon, Violaine; Noguchi, Tetsuro; Eisinger, François; Coulet, Florence; Colas, Chrystelle; Soubrier, Florent; Coupier, Isabelle; Pujol, Pascal; Peyrat, Jean-Philippe; Fournier, Joëlle; Révilliion, Françoise; Vennin, Philippe; Adenis, Claude; Rouleau, Etienne; Lidereau, Rosette; Demange, Liliane; Nogues, Catherine; Muller, Danièle; Fricker, Jean-Pierre; Barouk-Simonet, Emmanuelle; Bonnet, Françoise; Bubien, Virginie; Sevenet, Nicolas; Longy, Michel; Toulas, Christine; Guimbaud, Rosine; Gladieff, Laurence; Feillel, Viviane; Leroux, Dominique; Dreyfus, Hélène; Rebischung, Christine; Peysselon, Megalie; Coron, Fanny; Prieur, Fabienne; Lebrun, Marine; Kientz, Caroline; Frénay, Marc; Vénat-Bouvet, Laurence; Delnatte, Capucine; Mortemousque, Isabelle; Lynch, Henry T.; Snyder, Carrie L.; Hogervorst, F. B. L.; Verhoef, S.; Verheus, M.; van't Veer, L. J.; van Leeuwen, F. E.; Collée, M.; van den Ouweland, A. M. W.; Jager, A.; Hooning, M. J.; Tilanus-Linthorst, M. M. A.; Seynaeve, C.; van Asperen, C. J.; Wijnen, J. T.; Vreeswijk, M. P.; Tollenaar, R. A.; Devilee, P.; Ligtenberg, M. J.; Hoogerbrugge, N.; Ausems, M. G.; van der Luijt, R. B.; van Os, T. A.; Gille, J. J. P.; Waisfisz, Q.; Gomez-Garcia, E. B.; van Roozendaal, C. E.; Blok, Marinus J.; Caanen, B.; Oosterwijk, J. C.; van der Hout, A. H.; Mourits, M. J.; Vasen, H. F.; Thorne, Heather; Niedermayr, Eveline; Gill, Mona; Collins, Lucine; Gokgoz, Nalan; Selander, Teresa; Weerasooriya, Nayana; Karlsson, Per; Nordlilng, Margareta; Bergman, Annika; Einbeigi, Zakaria; Liedgren, Sigrun; Borg, Åke; Loman, Niklas; Soller, Maria; Jernström, Helena; Harbst, Katja; Henriksson, Karin; Arver, Brita; von Wachenfeldt, Anna; Barbany-Bustinza, Gisela; Rantala, Johanna; Grönberg, Henrik; Stattin, Eva-Lena; Emanuelsson, Monica; Ehrencrona, Hans; Rosenquist, Richard; Dahl, Niklas

    2012-01-01

    Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of

  3. Analysis of average standardized SSR allele size supports domestication of soybean along the Yellow River

    NARCIS (Netherlands)

    Li, Y.H.; Zhang, C.; Smulders, M.J.M.; Li, W.; Ma, Y.S.; Xu, Qu; Chang, R.Z.; Qiu, Li-Juan

    2013-01-01

    Soybean (Glycine max) was domesticated in China from its wild progenitor G. soja. The geographic region of domestication is, however, not exactly known. Here we employed the directional evolution of SSR (microsatellite) repeats (which mutate preferentially into longer alleles) to analyze the

  4. EOMES-positive CD4+ T cells are increased in PTPN22 (1858T) risk allele carriers.

    Science.gov (United States)

    Chemin, Karine; Ramsköld, Daniel; Diaz-Gallo, Lina-Marcela; Herrath, Jessica; Houtman, Miranda; Tandre, Karolina; Rönnblom, Lars; Catrina, Anca; Malmström, Vivianne

    2018-04-01

    The presence of the PTPN22 risk allele (1858T) is associated with several autoimmune diseases including rheumatoid arthritis (RA). Despite a number of studies exploring the function of PTPN22 in T cells, the exact impact of the PTPN22 risk allele on T-cell function in humans is still unclear. In this study, using RNA sequencing, we show that, upon TCR-activation, naïve human CD4 + T cells homozygous for the PTPN22 risk allele overexpress a set of genes including CFLAR and 4-1BB, which are important for cytotoxic T-cell differentiation. Moreover, the protein expression of the T-box transcription factor Eomesodermin (EOMES) was increased in T cells from healthy donors homozygous for the PTPN22 risk allele and correlated with a decreased number of naïve CD4 + T cells. There was no difference in the frequency of other CD4 + T-cell subsets (Th1, Th17, Tfh, Treg). Finally, an accumulation of EOMES + CD4 + T cells was observed in synovial fluid of RA patients with a more pronounced production of Perforin-1 in PTPN22 risk allele carriers. Altogether, we propose a novel mechanism of action of PTPN22 risk allele through the generation of cytotoxic CD4 + T cells and identify EOMES + CD4 + T cells as a relevant T-cell subset in RA pathogenesis. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. A genome-wide scan for common alleles affecting risk for autism

    Science.gov (United States)

    Anney, Richard; Klei, Lambertus; Pinto, Dalila; Regan, Regina; Conroy, Judith; Magalhaes, Tiago R.; Correia, Catarina; Abrahams, Brett S.; Sykes, Nuala; Pagnamenta, Alistair T.; Almeida, Joana; Bacchelli, Elena; Bailey, Anthony J.; Baird, Gillian; Battaglia, Agatino; Berney, Tom; Bolshakova, Nadia; Bölte, Sven; Bolton, Patrick F.; Bourgeron, Thomas; Brennan, Sean; Brian, Jessica; Carson, Andrew R.; Casallo, Guillermo; Casey, Jillian; Chu, Su H.; Cochrane, Lynne; Corsello, Christina; Crawford, Emily L.; Crossett, Andrew; Dawson, Geraldine; de Jonge, Maretha; Delorme, Richard; Drmic, Irene; Duketis, Eftichia; Duque, Frederico; Estes, Annette; Farrar, Penny; Fernandez, Bridget A.; Folstein, Susan E.; Fombonne, Eric; Freitag, Christine M.; Gilbert, John; Gillberg, Christopher; Glessner, Joseph T.; Goldberg, Jeremy; Green, Jonathan; Guter, Stephen J.; Hakonarson, Hakon; Heron, Elizabeth A.; Hill, Matthew; Holt, Richard; Howe, Jennifer L.; Hughes, Gillian; Hus, Vanessa; Igliozzi, Roberta; Kim, Cecilia; Klauck, Sabine M.; Kolevzon, Alexander; Korvatska, Olena; Kustanovich, Vlad; Lajonchere, Clara M.; Lamb, Janine A.; Laskawiec, Magdalena; Leboyer, Marion; Le Couteur, Ann; Leventhal, Bennett L.; Lionel, Anath C.; Liu, Xiao-Qing; Lord, Catherine; Lotspeich, Linda; Lund, Sabata C.; Maestrini, Elena; Mahoney, William; Mantoulan, Carine; Marshall, Christian R.; McConachie, Helen; McDougle, Christopher J.; McGrath, Jane; McMahon, William M.; Melhem, Nadine M.; Merikangas, Alison; Migita, Ohsuke; Minshew, Nancy J.; Mirza, Ghazala K.; Munson, Jeff; Nelson, Stanley F.; Noakes, Carolyn; Noor, Abdul; Nygren, Gudrun; Oliveira, Guiomar; Papanikolaou, Katerina; Parr, Jeremy R.; Parrini, Barbara; Paton, Tara; Pickles, Andrew; Piven, Joseph; Posey, David J; Poustka, Annemarie; Poustka, Fritz; Prasad, Aparna; Ragoussis, Jiannis; Renshaw, Katy; Rickaby, Jessica; Roberts, Wendy; Roeder, Kathryn; Roge, Bernadette; Rutter, Michael L.; Bierut, Laura J.; Rice, John P.; Salt, Jeff; Sansom, Katherine; Sato, Daisuke; Segurado, Ricardo; Senman, Lili; Shah, Naisha; Sheffield, Val C.; Soorya, Latha; Sousa, Inês; Stoppioni, Vera; Strawbridge, Christina; Tancredi, Raffaella; Tansey, Katherine; Thiruvahindrapduram, Bhooma; Thompson, Ann P.; Thomson, Susanne; Tryfon, Ana; Tsiantis, John; Van Engeland, Herman; Vincent, John B.; Volkmar, Fred; Wallace, Simon; Wang, Kai; Wang, Zhouzhi; Wassink, Thomas H.; Wing, Kirsty; Wittemeyer, Kerstin; Wood, Shawn; Yaspan, Brian L.; Zurawiecki, Danielle; Zwaigenbaum, Lonnie; Betancur, Catalina; Buxbaum, Joseph D.; Cantor, Rita M.; Cook, Edwin H.; Coon, Hilary; Cuccaro, Michael L.; Gallagher, Louise; Geschwind, Daniel H.; Gill, Michael; Haines, Jonathan L.; Miller, Judith; Monaco, Anthony P.; Nurnberger, John I.; Paterson, Andrew D.; Pericak-Vance, Margaret A.; Schellenberg, Gerard D.; Scherer, Stephen W.; Sutcliffe, James S.; Szatmari, Peter; Vicente, Astrid M.; Vieland, Veronica J.; Wijsman, Ellen M.; Devlin, Bernie; Ennis, Sean; Hallmayer, Joachim

    2010-01-01

    Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C. PMID:20663923

  6. A genome-wide scan for common alleles affecting risk for autism.

    LENUS (Irish Health Repository)

    Anney, Richard

    2010-10-15

    Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner\\'s curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.

  7. A genome-wide scan for common alleles affecting risk for autism.

    Science.gov (United States)

    Anney, Richard; Klei, Lambertus; Pinto, Dalila; Regan, Regina; Conroy, Judith; Magalhaes, Tiago R; Correia, Catarina; Abrahams, Brett S; Sykes, Nuala; Pagnamenta, Alistair T; Almeida, Joana; Bacchelli, Elena; Bailey, Anthony J; Baird, Gillian; Battaglia, Agatino; Berney, Tom; Bolshakova, Nadia; Bölte, Sven; Bolton, Patrick F; Bourgeron, Thomas; Brennan, Sean; Brian, Jessica; Carson, Andrew R; Casallo, Guillermo; Casey, Jillian; Chu, Su H; Cochrane, Lynne; Corsello, Christina; Crawford, Emily L; Crossett, Andrew; Dawson, Geraldine; de Jonge, Maretha; Delorme, Richard; Drmic, Irene; Duketis, Eftichia; Duque, Frederico; Estes, Annette; Farrar, Penny; Fernandez, Bridget A; Folstein, Susan E; Fombonne, Eric; Freitag, Christine M; Gilbert, John; Gillberg, Christopher; Glessner, Joseph T; Goldberg, Jeremy; Green, Jonathan; Guter, Stephen J; Hakonarson, Hakon; Heron, Elizabeth A; Hill, Matthew; Holt, Richard; Howe, Jennifer L; Hughes, Gillian; Hus, Vanessa; Igliozzi, Roberta; Kim, Cecilia; Klauck, Sabine M; Kolevzon, Alexander; Korvatska, Olena; Kustanovich, Vlad; Lajonchere, Clara M; Lamb, Janine A; Laskawiec, Magdalena; Leboyer, Marion; Le Couteur, Ann; Leventhal, Bennett L; Lionel, Anath C; Liu, Xiao-Qing; Lord, Catherine; Lotspeich, Linda; Lund, Sabata C; Maestrini, Elena; Mahoney, William; Mantoulan, Carine; Marshall, Christian R; McConachie, Helen; McDougle, Christopher J; McGrath, Jane; McMahon, William M; Melhem, Nadine M; Merikangas, Alison; Migita, Ohsuke; Minshew, Nancy J; Mirza, Ghazala K; Munson, Jeff; Nelson, Stanley F; Noakes, Carolyn; Noor, Abdul; Nygren, Gudrun; Oliveira, Guiomar; Papanikolaou, Katerina; Parr, Jeremy R; Parrini, Barbara; Paton, Tara; Pickles, Andrew; Piven, Joseph; Posey, David J; Poustka, Annemarie; Poustka, Fritz; Prasad, Aparna; Ragoussis, Jiannis; Renshaw, Katy; Rickaby, Jessica; Roberts, Wendy; Roeder, Kathryn; Roge, Bernadette; Rutter, Michael L; Bierut, Laura J; Rice, John P; Salt, Jeff; Sansom, Katherine; Sato, Daisuke; Segurado, Ricardo; Senman, Lili; Shah, Naisha; Sheffield, Val C; Soorya, Latha; Sousa, Inês; Stoppioni, Vera; Strawbridge, Christina; Tancredi, Raffaella; Tansey, Katherine; Thiruvahindrapduram, Bhooma; Thompson, Ann P; Thomson, Susanne; Tryfon, Ana; Tsiantis, John; Van Engeland, Herman; Vincent, John B; Volkmar, Fred; Wallace, Simon; Wang, Kai; Wang, Zhouzhi; Wassink, Thomas H; Wing, Kirsty; Wittemeyer, Kerstin; Wood, Shawn; Yaspan, Brian L; Zurawiecki, Danielle; Zwaigenbaum, Lonnie; Betancur, Catalina; Buxbaum, Joseph D; Cantor, Rita M; Cook, Edwin H; Coon, Hilary; Cuccaro, Michael L; Gallagher, Louise; Geschwind, Daniel H; Gill, Michael; Haines, Jonathan L; Miller, Judith; Monaco, Anthony P; Nurnberger, John I; Paterson, Andrew D; Pericak-Vance, Margaret A; Schellenberg, Gerard D; Scherer, Stephen W; Sutcliffe, James S; Szatmari, Peter; Vicente, Astrid M; Vieland, Veronica J; Wijsman, Ellen M; Devlin, Bernie; Ennis, Sean; Hallmayer, Joachim

    2010-10-15

    Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.

  8. A putative Alzheimer's disease risk allele in PCK1 influences brain atrophy in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Zongqi Xia

    2010-11-01

    Full Text Available Brain atrophy and cognitive dysfunction are neurodegenerative features of Multiple Sclerosis (MS. We used a candidate gene approach to address whether genetic variants implicated in susceptibility to late onset Alzheimer's Disease (AD influence brain volume and cognition in MS patients.MS subjects were genotyped for five single nucleotide polymorphisms (snps associated with susceptibility to AD: PICALM, CR1, CLU, PCK1, and ZNF224. We assessed brain volume using Brain Parenchymal Fraction (BPF measurements obtained from Magnetic Resonance Imaging (MRI data and cognitive function using the Symbol Digit Modalities Test (SDMT. Genotypes were correlated with cross-sectional BPF and SDMT scores using linear regression after adjusting for sex, age at symptom onset, and disease duration. 722 MS patients with a mean (±SD age at enrollment of 41 (±10 years were followed for 44 (±28 months. The AD risk-associated allele of a non-synonymous SNP in the PCK1 locus (rs8192708G is associated with a smaller average brain volume (P=0.0047 at the baseline MRI, but it does not impact our baseline estimate of cognition. PCK1 is additionally associated with higher baseline T2-hyperintense lesion volume (P=0.0088. Finally, we provide technical validation of our observation in a subset of 641 subjects that have more than one MRI study, demonstrating the same association between PCK1 and smaller average brain volume (P=0.0089 at the last MRI visit.Our study provides suggestive evidence for greater brain atrophy in MS patients bearing the PCK1 allele associated with AD-susceptibility, yielding new insights into potentially shared neurodegenerative process between MS and late onset AD.

  9. Increased risk for CRC in diabetic patients with the nonrisk allele of SNPs at 8q24.

    Science.gov (United States)

    Ishimaru, Shinya; Mimori, Koshi; Yamamoto, Ken; Inoue, Hiroshi; Imoto, Seiya; Kawano, Shuichi; Yamaguchi, Rui; Sato, Tetsuya; Toh, Hiroyuki; Iinuma, Hisae; Maeda, Toyoki; Ishii, Hideshi; Suzuki, Sadao; Tokudome, Shinkan; Watanabe, Masahiko; Tanaka, Jun-ichi; Kudo, Shin-ei; Sugihara, Ken-ichi; Hase, Kazuo; Mochizuki, Hidetaka; Kusunoki, Masato; Yamada, Kazutaka; Shimada, Yasuhiro; Moriya, Yoshihiro; Barnard, Graham F; Miyano, Satoru; Mori, Masaki

    2012-09-01

    Colorectal cancer (CRC) oncogenesis was considered to be determined by interactions between genetic and environmental factors. Specific interacting factors that influence CRC morbidity have yet to be fully investigated. A multi-institutional collaborative study with 1511 CRC patients and 2098 control subjects was used to compare the odds ratios for the occurrence of polymorphisms at 11 known single nucleotide polymorphisms (SNPs). TaqMan PCR and questionnaires were used to evaluate the effects of environmental exposures. Variants of rs6983267 on 8q24 were the most significant markers of risk for CRC (odds ratio 1.16, 95% confidence interval 1.06-1.27, P = 0.0015). Non-insulin-dependent diabetes mellitus (DM), a higher body mass index at age 20, and meat consumption were environmental risk factors, whereas a tuna-rich diet and vitamin intake were protective factors. The cohort of rs6983267 SNP major (T) allele at 8q24 and DM had a 1.66-fold higher risk ratio than the cohort of major allele patients without DM. We confirmed that interactions between the genetic background and environmental factors are associated with increased risk for CRC. There is a robust risk of the minor G allele at the 8q24 rs6983267 SNP; however, a major T allele SNP could more clearly reveal a correlation with CRC specifically when DM is present.

  10. Mannose-binding lectin variant alleles and the risk of arterial thrombosis in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Øhlenschlaeger, Tommy; Garred, Peter; Madsen, Hans O

    2004-01-01

    Cardiovascular disease is an important complication in patients with systemic lupus erythematosus (SLE). Variant alleles of the mannose-binding lectin gene are associated with SLE as well as with severe atherosclerosis. We determined whether mannose-binding lectin variant alleles were associated...

  11. APOL1 Risk Alleles Are Associated With More Severe Arteriosclerosis in Renal Resistance Vessels With Aging and Hypertension

    Directory of Open Access Journals (Sweden)

    Michael D. Hughson

    2016-05-01

    Discussion: With the limitation of the small number of subjects contributing to the positive results, the findings imply that APOL1 risk alleles recessively augment small-vessel arteriosclerosis in conjunction with age and hypertension. Focal segmental glomerulosclerosis was not a significant finding, indicating that in the early stages of arterionephrosclerosis, the primary pathologic influence of APOL1 genotype is vascular rather than glomerular.

  12. Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor alpha therapy

    NARCIS (Netherlands)

    Cui, Jing; Saevarsdottir, Saedis; Thomson, Brian; Padyukov, Leonid; van der Helm-van Mil, Annette H. M.; Nititham, Joanne; Hughes, Laura B.; de Vries, Niek; Raychaudhuri, Soumya; Alfredsson, Lars; Askling, Johan; Wedrén, Sara; Ding, Bo; Guiducci, Candace; Wolbink, Gert Jan; Crusius, J. Bart A.; van der Horst-Bruinsma, Irene E.; Herenius, Marieke; Weinblatt, Michael E.; Shadick, Nancy A.; Worthington, Jane; Batliwalla, Franak; Kern, Marlena; Morgan, Ann W.; Wilson, Anthony G.; Isaacs, John D.; Hyrich, Kimme; Seldin, Michael F.; Moreland, Larry W.; Behrens, Timothy W.; Allaart, Cornelia F.; Criswell, Lindsey A.; Huizinga, Tom W. J.; Tak, Paul P.; Bridges, S. Louis; Toes, Rene E. M.; Barton, Anne; Klareskog, Lars; Gregersen, Peter K.; Karlson, Elizabeth W.; Plenge, Robert M.

    2010-01-01

    OBJECTIVE: Anti-tumor necrosis factor alpha (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. METHODS: A total

  13. Common Atrial Fibrillation Risk Alleles at 4q25 Predict Recurrence after Catheter-based Atrial Fibrillation Ablation

    Science.gov (United States)

    Shoemaker, M. Benjamin; Muhammad, Raafia; Parvez, Babar; White, Brenda W.; Streur, Megan; Song, Yanna; Stubblefield, Tanya; Kucera, Gayle; Blair, Marcia; Rytlewski, Jason; Parvathaneni, Sunthosh; Nagarakanti, Rangadham; Saavedra, Pablo; Ellis, Christopher; Whalen, S. Patrick; Roden, Dan M; Darbar, Dawood

    2012-01-01

    Background Common single nucleotide polymorphisms (SNPs) at chromosome 4q25 (rs2200733, rs10033464) are associated with both lone and typical AF. Risk alleles at 4q25 have recently been shown to predict recurrence of AF after ablation in a population of predominately lone AF, but lone AF represents only 5–30% of AF cases. Objective To test the hypothesis that 4q25 AF risk alleles can predict response to AF ablation in the majority of AF cases. Methods Patients enrolled in the Vanderbilt AF Registry underwent 378 catheter-based AF ablations (median age 60 years, 71% male, 89% typical AF) between 2004 and 2011. The primary endpoint was time to recurrence of any non-sinus atrial tachyarrhythmia (atrial tachycardia, atrial flutter, or AF; [AT/AF]). Results Two-hundred AT/AF recurrences (53%) were observed. In multivariable analysis, the rs2200733 risk allele predicted a 24% shorter recurrence-free time (survival time ratio 0.76 95% confidence interval [CI] 0.6–0.95, P=0.016) compared with wild-type. The heterozygous haplotype demonstrated a 21% shorter recurrence-free time (survival time ratio = 0.79, 95% CI 0.62–0.99) and the homozygous risk allele carriers a 39% shorter recurrence-free time (survival time ratio = 0.61, 95% CI 0.37–1.0) (P=0.037). Conclusion Risk alleles at the 4q25 loci predict impaired clinical response to AF ablation in a population of predominately typical AF patients. Our findings suggest the rs2200733 polymorphism may hold promise as an as an objectively measured patient characteristic that can used as a clinical tool for selection of patients for AF ablation. PMID:23178686

  14. Enrichment of minor allele of SNPs and genetic prediction of type 2 diabetes risk in British population.

    Directory of Open Access Journals (Sweden)

    Xiaoyun Lei

    Full Text Available Type 2 diabetes (T2D is a complex disorder characterized by high blood sugar, insulin resistance, and relative lack of insulin. The collective effects of genome wide minor alleles of common SNPs, or the minor allele content (MAC in an individual, have been linked with quantitative variations of complex traits and diseases. Here we studied MAC in T2D using previously published SNP datasets and found higher MAC in cases relative to matched controls. A set of 357 SNPs was found to have the best predictive accuracy in a British population. A weighted risk score calculated by using this set produced an area under the curve (AUC score of 0.86, which is comparable to risk models built by phenotypic markers. These results identify a novel genetic risk element in T2D susceptibility and provide a potentially useful genetic method to identify individuals with high risk of T2D.

  15. Air Risk Information Support Center

    Energy Technology Data Exchange (ETDEWEB)

    Shoaf, C.R.; Guth, D.J. [Environmental Protection Agency, Washington, DC (United States)

    1990-12-31

    The Air Risk Information Support Center (Air RISC) was initiated in early 1988 by the US Environmental Protection Agency`s (EPA) Office of Health and Environmental Assessment (OHEA) and the Office of Air Quality Planning and Standards (OAQPS) as a technology transfer effort that would focus on providing information to state and local environmental agencies and to EPA Regional Offices in the areas of health, risk, and exposure assessment for toxic air pollutants. Technical information is fostered and disseminated by Air RISCs three primary activities: (1) a {open_quotes}hotline{close_quotes}, (2) quick turn-around technical assistance projects, and (3) general technical guidance projects. 1 ref., 2 figs.

  16. Collapsing glomerulopathy in a young woman with APOL1 risk alleles following acute parvovirus B19 infection: a case report investigation.

    Science.gov (United States)

    Besse, Whitney; Mansour, Sherry; Jatwani, Karan; Nast, Cynthia C; Brewster, Ursula C

    2016-09-06

    Collapsing Glomerulopathy (CG), also known as the collapsing variant of Focal Segmental Glomerulosclerosis (FSGS), is distinct in both its clinical severity and its pathophysiologic characteristics from other forms of FSGS. This lesion occurs disproportionally in patients carrying two APOL1 risk alleles, and is the classic histologic lesion resulting from Human Immunodeficiency Virus (HIV) infection of podocytes. Other viral infections, including parvovirus B19, and drugs such as interferon that perturb the immune system, have also been associated with CG. Despite significant advances, explaining such genetic and immune/infectious associations with causative mechanisms and supporting evidence has proven challenging. We report the case of a healthy (HIV-negative) pregnant 36 year-old Caribbean-American woman who presented with nephrotic syndrome and fetal demise in the setting of acute parvovirus B19 infection. A series of three renal biopsies and rapid clinical course showed progression from significant podocyte injury with mild light microscopy findings to classic viral-associated CG to ESRD in less than 3 months. Genetic analysis revealed two APOL1 G1 risk alleles. This is the first published case report of CG in the setting of acute parvovirus infection in a patient with two APOL1 risk allelles, and parvoviral proteins identified in renal epithelium on kidney biopsy. These findings support the causative role of parvovirus B19 infection in the development of CG on the background of APOL1 genetic risk.

  17. Length of FMR1 repeat alleles within the normal range does not substantially affect the risk of early menopause

    Science.gov (United States)

    Ruth, Katherine S.; Bennett, Claire E.; Schoemaker, Minouk J.; Weedon, Michael N.; Swerdlow, Anthony J.; Murray, Anna

    2016-01-01

    STUDY QUESTION Is the length of FMR1 repeat alleles within the normal range associated with the risk of early menopause? SUMMARY ANSWER The length of repeat alleles within the normal range does not substantially affect risk of early menopause. WHAT IS KNOWN ALREADY There is a strong, well-established relationship between length of premutation FMR1 alleles and age at menopause, suggesting that this relationship could continue into the normal range. Within the normal range, there is conflicting evidence; differences in ovarian reserve have been identified with FMR1 repeat allele length, but a recent population-based study did not find any association with age at menopause as a quantitative trait. STUDY DESIGN, SIZE, DURATION We analysed cross-sectional baseline survey data collected at recruitment from 2004 to 2010 from a population-based, prospective epidemiological cohort study of >110 000 women to investigate whether repeat allele length was associated with early menopause. PARTICIPANTS/MATERIALS, SETTING, METHOD We included 4333 women from the Breakthrough Generations Study (BGS), of whom 2118 were early menopause cases (menopause under 46 years) and 2215 were controls. We analysed the relationship between length of FMR1 alleles and early menopause using logistic regression with allele length as continuous and categorical variables. We also conducted analyses with the outcome age at menopause as a quantitative trait as well as appropriate sensitivity and exploratory analyses. MAIN RESULTS AND THE ROLE OF CHANCE There was no association of the shorter or longer FMR1 allele or their combined genotype with the clinically relevant end point of early menopause in our main analysis. Likewise, there were no associations with age at menopause as a quantitative trait in our secondary analysis. LIMITATIONS, REASONS FOR CAUTION Women with homozygous alleles in the normal range may have undetected FMR1 premutation alleles, although there was no evidence to suggest this. We

  18. Association of breast cancer risk with genetic variants showing differential allelic expression

    DEFF Research Database (Denmark)

    Hamdi, Yosr; Soucy, Penny; Adoue, Véronique

    2016-01-01

    There are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, cis-acting variants represent an important source of phenotypic variation. Consequently, cis-regulatory SNPs associated with differential allelic expression are functional...

  19. CYP21A2 polymorphisms in patients with autoimmune Addison's disease, and linkage disequilibrium to HLA risk alleles.

    Science.gov (United States)

    Brønstad, Ingeborg; Skinningsrud, Beate; Bratland, Eirik; Løvås, Kristian; Undlien, Dag; Sverre Husebye, Eystein; Wolff, Anette Susanne Bøe

    2014-12-01

    Steroid 21-hydroxylase, encoded by CYP21A2, is the major autoantigen in autoimmune Addison's disease (AAD). CYP21A2 is located in the region of the HLA complex on chromosome 6p21.3, which harbours several risk alleles for AAD. The objective was to investigate whether CYP21A2 gene variants confer risk of AAD independently of other risk alleles in the HLA loci. DNA samples from 381 Norwegian patients with AAD and 340 healthy controls (HC) previously genotyped for the HLA-A, -B, -DRB1, and -DQB1 and MICA loci were used for genotyping of CYP21A2. Genotyping of CYP21A2 was carried out by direct sequencing. Linkage of CYP21A2 to the HLA loci was assessed using UNPHASED version 3.0.10 and PHASE version 2.1. Heterozygotes of the single-nucleotide polymorphisms (SNPs) rs397515394, rs6467, rs6474, rs76565726 and rs6473 were detected significantly more frequently in AAD patients compared with HC (P<0.005), but all SNPs were in a linkage disequilibrium (LD) with high-risk HLA-DRB1 haplotypes. rs6472C protected against AAD (odds ratio=0.15, 95% CI (0.08-0.30), P=3.8×10(-10)). This SNP was not in an LD with HLA loci (P=0.02), but did not increase protection when considering the effect of HLA-DRB1 alleles. Mutations causing congenital adrenal hyperplasia were found in heterozygosity in <1.5% of the cases in both groups. Genetic variants of CYP21A2 associated to AAD are in LD with the main AAD risk locus HLA-DRB1, and CYP21A2 does not constitute an independent susceptibility locus. © 2014 European Society of Endocrinology.

  20. ZNF804A risk allele is associated with relatively intact gray matter volume in patients with schizophrenia.

    LENUS (Irish Health Repository)

    Donohoe, Gary

    2011-02-01

    ZNF804A rs1344706 is the first genetic risk variant to achieve genome wide significance for psychosis. Following earlier evidence that patients carrying the ZNF804A risk allele had relatively spared memory function compared to patient non-carriers, we investigated whether ZNF804A was also associated with variation in brain volume. In a sample of 70 patients and 38 healthy participants we used voxel based morphometry to compare homozygous (AA) carriers of the ZNF804A risk allele to heterozygous and homozygous (AC\\/CC) non-carriers for both whole brain volume and specific regions implicated in earlier ZNF804A studies-the dorsolateral pre-frontal cortex, the hippocampus, and the amygdala. For patients, but not for controls, we found that homozygous \\'AA\\' risk carriers had relatively larger gray matter volumes than heterozygous\\/homozygous non-carriers (AC\\/CC), particularly for hippocampal volumes. These data are consistent with our earlier behavioral data and suggest that ZNF804A is delineating a schizophrenia subtype characterized by relatively intact brain volume. Establishing if this represents a discrete molecular pathogenesis with consequences for nosology and treatment will be an important next step in understanding ZNF084A\\'s role in illness risk.

  1. Dyslexia risk variant rs600753 is linked with dyslexia-specific differential allelic expression of DYX1C1

    Directory of Open Access Journals (Sweden)

    Bent Müller

    2018-02-01

    Full Text Available Abstract An increasing number of genetic variants involved in dyslexia development were discovered during the last years, yet little is known about the molecular functional mechanisms of these SNPs. In this study we investigated whether dyslexia candidate SNPs have a direct, disease-specific effect on local expression levels of the assumed target gene by using a differential allelic expression assay. In total, 12 SNPs previously associated with dyslexia and related phenotypes were suitable for analysis. Transcripts corresponding to four SNPs were sufficiently expressed in 28 cell lines originating from controls and a family affected by dyslexia. We observed a significant effect of rs600753 on expression levels of DYX1C1 in forward and reverse sequencing approaches. The expression level of the rs600753 risk allele was increased in the respective seven cell lines from members of the dyslexia family which might be due to a disturbed transcription factor binding sites. When considering our results in the context of neuroanatomical dyslexia-specific findings, we speculate that this mechanism may be part of the pathomechanisms underlying the dyslexia-specific brain phenotype. Our results suggest that allele-specific DYX1C1 expression levels depend on genetic variants of rs600753 and contribute to dyslexia. However, these results are preliminary and need replication.

  2. Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression

    DEFF Research Database (Denmark)

    Hamdi, Yosr; Soucy, Penny; Kuchenbaeker, Karoline B

    2017-01-01

    and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. RESULTS: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most...... studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.......1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. METHODS: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast...

  3. Ovarian Cancer Susceptibility Alleles and Risk of Ovarian Cancer in BRCA1 and BRCA2 Mutation Carriers

    Science.gov (United States)

    Ramus, Susan J.; Antoniou, Antonis C; Kuchenbaecker, Karoline B.; Soucy, Penny; Beesley, Jonathan; Chen, Xiaoqing; McGuffog, Lesley; Sinilnikova, Olga M.; Healey, Sue; Barrowdale, Daniel; Lee, Andrew; Thomassen, Mads; Gerdes, Anne-Marie; Kruse, Torben A.; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A.; Liljegren, Annelie; Lindblom, Annika; Olsson, Håkan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Złowocka, Elżbieta; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Cybulski, Cezary; Toloczko-Grabarek, Aleksandra; Osorio, Ana; Benitez, Javier; Duran, Mercedes; Tejada, Maria-Isabel; Hamann, Ute; Rookus, Matti; van Leeuwen, Flora E.; Aalfs, Cora M.; Meijers-Heijboer, Hanne E.J.; van Asperen, Christi J.; van Roozendaal, K.E.P.; Hoogerbrugge, Nicoline; Collée, J. Margriet; Kriege, Mieke; van der Luijt, Rob B.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Evans, D. Gareth; Lalloo, Fiona; Jacobs, Chris; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Paterson, Joan; Douglas, Fiona; Brewer, Carole; Hodgson, Shirley; Morrison, Patrick J.; Walker, Lisa; Porteous, Mary E.; Kennedy, M. John; Pathak, Harsh; Godwin, Andrew K.; Stoppa-Lyonnet, Dominique; Caux-Moncoutier, Virginie; de Pauw, Antoine; Gauthier-Villars, Marion; Mazoyer, Sylvie; Léoné, Mélanie; Calender, Alain; Lasset, Christine; Bonadona, Valérie; Hardouin, Agnès; Berthet, Pascaline; Bignon, Yves-Jean; Uhrhammer, Nancy; Faivre, Laurence; Loustalot, Catherine; Buys, Saundra; Daly, Mary; Miron, Alex; Terry, Mary Beth; Chung, Wendy K.; John, Esther M; Southey, Melissa; Goldgar, David; Singer, Christian F; Tea, Muy-Kheng; Pfeiler, Georg; Fink-Retter, Anneliese; Hansen, Thomas v. O.; Ejlertsen, Bent; Johannsson, Oskar Th.; Offit, Kenneth; Kirchhoff, Tomas; Gaudet, Mia M.; Vijai, Joseph; Robson, Mark; Piedmonte, Marion; Phillips, Kelly-Anne; Van Le, Linda; Hoffman, James S; Toland, Amanda Ewart; Montagna, Marco; Tognazzo, Silvia; Imyanitov, Evgeny; Isaacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Ignacio; Tornero, Eva; Navarro, Matilde; Moysich, Kirsten B.; Karlan, Beth Y.; Gross, Jenny; Olah, Edith; Vaszko, Tibor; Teo, Soo-Hwang; Ganz, Patricia A.; Beattie, Mary S.; Dorfling, Cecelia M; van Rensburg, Elizabeth J; Diez, Orland; Kwong, Ava; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Heidemann, Simone; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorotehea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Fiebig, Britta; Schäfer, Dieter; Caldes, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomäki, Kristiina; Plante, Marie; Spurdle, Amanda B.; Neuhausen, Susan L.; Ding, Yuan Chun; Wang, Xianshu; Lindor, Noralane; Fredericksen, Zachary; Pankratz, V. Shane; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Bonanni, Bernardo; Bernard, Loris; Dolcetti, Riccardo; Papi, Laura; Ottini, Laura; Radice, Paolo; Greene, Mark H.; Mai, Phuong L.; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Pharoah, Paul D.P.; Gayther, Simon A.; Simard, Jacques; Easton, Douglas F.; Couch, Fergus J.; Chenevix-Trench, Georgia

    2012-01-01

    Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67–0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21–1.83) P-trend = 1.8 × 10−4, rs717852 HR = 1.25 (95% CI: 1.10–1.42) P-trend = 6.6 × 10−4, rs9303542 HR = 1.16 (95% CI: 1.02–1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81–0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10–1.42) P-trend = 6.1 × 10−4. The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer. PMID:22253144

  4. Functional consequences of the macrophage stimulating protein 689C inflammatory bowel disease risk allele.

    Directory of Open Access Journals (Sweden)

    Steven E Kauder

    Full Text Available Macrophage stimulating protein (MSP is a serum growth factor that binds to and activates the receptor tyrosine kinase, Recepteur d'Origine Nantais (RON. A non-synonymous coding variant in MSP (689C has been associated with genetic susceptibility to both Crohn's disease and ulcerative colitis, two major types of inflammatory bowel disease (IBD characterized by chronic inflammation of the digestive tract. We investigated the consequences of this polymorphism for MSP-RON pathway activity and IBD pathogenesis.RON expression patterns were examined on mouse and human cells and tissues under normal and disease conditions to identify cell types regulated by MSP-RON. Recombinant MSP variants were tested for their ability to bind and stimulate RON and undergo proteolytic activation. MSP concentrations were quantified in the serum of individuals carrying the MSP 689R and 689C alleles.In intestinal tissue, RON was primarily expressed by epithelial cells under normal and disease conditions. The 689C polymorphism had no impact on the ability of MSP to bind to or signal through RON. In a cohort of normal individuals and IBD patients, carriers of the 689C polymorphism had lower concentrations of MSP in their serum.By reducing the quantities of circulating MSP, the 689C polymorphism, or a variant in linkage disequilibrium with this polymorphism, may impact RON ligand availability and thus receptor activity. Given the known functions of RON in regulating wound healing and our analysis of RON expression patterns in human intestinal tissue, these data suggest that decreased RON activity may impact the efficiency of epithelial repair and thus underlie the increased IBD susceptibility associated with the MSP 689C allele.

  5. Rheumatoid Arthritis Risk Allele PTPRC Is Also Associated With Response to Anti–Tumor Necrosis Factor α Therapy

    Science.gov (United States)

    Cui, Jing; Saevarsdottir, Saedis; Thomson, Brian; Padyukov, Leonid; van der Helm-van Mil, Annette H. M.; Nititham, Joanne; Hughes, Laura B.; de Vries, Niek; Raychaudhuri, Soumya; Alfredsson, Lars; Askling, Johan; Wedrén, Sara; Ding, Bo; Guiducci, Candace; Wolbink, Gert Jan; Crusius, J. Bart A.; van der Horst-Bruinsma, Irene E.; Herenius, Marieke; Weinblatt, Michael E.; Shadick, Nancy A.; Worthington, Jane; Batliwalla, Franak; Kern, Marlena; Morgan, Ann W.; Wilson, Anthony G.; Isaacs, John D.; Hyrich, Kimme; Seldin, Michael F.; Moreland, Larry W.; Behrens, Timothy W.; Allaart, Cornelia F.; Criswell, Lindsey A.; Huizinga, Tom W. J.; Tak, Paul P.; Bridges, S. Louis; Toes, Rene E. M.; Barton, Anne; Klareskog, Lars; Gregersen, Peter K.; Karlson, Elizabeth W.; Plenge, Robert M.

    2013-01-01

    Objective Anti–tumor necrosis factor α (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. Methods A total of 1,283 RA patients receiving etanercept, infliximab, or adalimumab therapy were studied from among an international collaborative consortium of 9 different RA cohorts. The primary end point compared RA patients with a good treatment response according to the European League Against Rheumatism (EULAR) response criteria (n = 505) with RA patients considered to be nonresponders (n = 316). The secondary end point was the change from baseline in the level of disease activity according to the Disease Activity Score in 28 joints (ΔDAS28). Clinical factors such as age, sex, and concomitant medications were tested as possible correlates of treatment response. Thirty-one single-nucleotide polymorphisms (SNPs) associated with the risk of RA were genotyped and tested for any association with treatment response, using univariate and multivariate logistic regression models. Results Of the 31 RA-associated risk alleles, a SNP at the PTPRC (also known as CD45) gene locus (rs10919563) was associated with the primary end point, a EULAR good response versus no response (odds ratio [OR] 0.55, P = 0.0001 in the multivariate model). Similar results were obtained using the secondary end point, the ΔDAS28 (P = 0.0002). There was suggestive evidence of a stronger association in autoantibody-positive patients with RA (OR 0.55, 95% confidence interval [95% CI] 0.39–0.76) as compared with autoantibody-negative patients (OR 0.90, 95% CI 0.41–1.99). Conclusion Statistically significant associations were observed between the response to anti-TNF therapy and an RA risk allele at the PTPRC gene locus. Additional studies will be required to replicate this finding in additional patient collections

  6. Pleiotropic Associations of Allelic Variants in a 2q22 Region with Risks of Major Human Diseases and Mortality.

    Directory of Open Access Journals (Sweden)

    Alexander M Kulminski

    2016-11-01

    Full Text Available Gaining insights into genetic predisposition to age-related diseases and lifespan is a challenging task complicated by the elusive role of evolution in these phenotypes. To gain more insights, we combined methods of genome-wide and candidate-gene studies. Genome-wide scan in the Atherosclerosis Risk in Communities (ARIC Study (N = 9,573 was used to pre-select promising loci. Candidate-gene methods were used to comprehensively analyze associations of novel uncommon variants in Caucasians (minor allele frequency~2.5% located in band 2q22.3 with risks of coronary heart disease (CHD, heart failure (HF, stroke, diabetes, cancer, neurodegenerative diseases (ND, and mortality in the ARIC study, the Framingham Heart Study (N = 4,434, and the Health and Retirement Study (N = 9,676. We leveraged the analyses of pleiotropy, age-related heterogeneity, and causal inferences. Meta-analysis of the results from these comprehensive analyses shows that the minor allele increases risks of death by about 50% (p = 4.6×10-9, CHD by 35% (p = 8.9×10-6, HF by 55% (p = 9.7×10-5, stroke by 25% (p = 4.0×10-2, and ND by 100% (p = 1.3×10-3. This allele also significantly influences each of two diseases, diabetes and cancer, in antagonistic fashion in different populations. Combined significance of the pleiotropic effects was p = 6.6×10-21. Causal mediation analyses show that endophenotypes explained only small fractions of these effects. This locus harbors an evolutionary conserved gene-desert region with non-coding intergenic sequences likely involved in regulation of protein-coding flanking genes ZEB2 and ACVR2A. This region is intensively studied for mutations causing severe developmental/genetic disorders. Our analyses indicate a promising target region for interventions aimed to reduce risks of many major human diseases and mortality.

  7. Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

    OpenAIRE

    Andrulis, IL; Mulligan, AM; Schmutzler, RK; Barrowdale, D; McGuffog, L; Robson, M; Schmidt, MK; Spurdle, AB; Neuhausen, SL; Kuchenbaecker, KB

    2014-01-01

    Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRC...

  8. Preferential binding to Elk-1 by SLE-associated IL10 risk allele upregulates IL10 expression.

    Directory of Open Access Journals (Sweden)

    Daisuke Sakurai

    Full Text Available Immunoregulatory cytokine interleukin-10 (IL-10 is elevated in sera from patients with systemic lupus erythematosus (SLE correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported IL10 variant, rs3024505 located at 1 kb downstream of IL10, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA (P = 2.7×10⁻⁸, OR = 1.30, but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10, respectively, and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating IL10 expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1 detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the IL10 rs3122605-G allele

  9. Allele variants of HLA II genes DRB1 and DQB1 regarding risk for type 1 diabetes mellitus in population of Bashkortostan

    Directory of Open Access Journals (Sweden)

    Shamilevna Avzaletdinova

    2012-09-01

    Full Text Available Aims. To estimate significance of HLA II DRB1 and DRB2 allele variants for development of type 1 diabetes mellitus (T1DM in Bashkortostanpopulation (ethnical Russians, Tatar, Bashkir. Materials and methods. We analyzed DNA of 323 patients with T1DM and 683 healthy controls. DNA was derived from venous bloodsamples by phenol-chloroform extraction. DRB1 and DQB1 gene typing was performed by PCR method. Amplification products wereidentified with electrophoresis on a 1% agarose gel. Statistica for Windows v6.0 and MS Excel 98 software were applied for statisticalprocessing of acquired data. Results. Common markers of high risk for T1DM were found to be DRB1*04, DRB1*17, genotype DRB1*04/*17. On the contrary,lower risk was associated with DRB1*15 allele. In ethnical Russians lower risk of T1DM is also determined by DRB1*11 allele andDRB1*01 in Tatars. Predisposition by DQB1-alleles in Russians and Bashkir realizes only within DRB1*04/*17 genotype. However,in Tatar subpopulation DQB1*0302 is an independent risk marker of T1DM development. Conclusion. Common low risk markers for all three ethnic groups are DQB1*0301, DQB1*0602-08 alleles. Their presence negates riskof disease in all studied subpopulations even within DRB1*04/*17-genotype.

  10. The rs10993994 risk allele for prostate cancer results in clinically relevant changes in microseminoprotein-beta expression in tissue and urine.

    NARCIS (Netherlands)

    Whitaker, H.C.; Kote-Jarai, Z.; Ross-Adams, H.; Warren, A.Y.; Burge, J.; George, A.; Bancroft, E.; Jhavar, S.; Leongamornlert, D.; Tymrakiewicz, M.; Saunders, E.; Page, E.; Mitra, A.; Mitchell, G.; Lindeman, G.J.; Evans, D.G.; Blanco, I.; Mercer, C.; Rubinstein, W.S.; Clowes, V.; Douglas, F.; Hodgson, S.; Walker, L.; Donaldson, A.; Izatt, L.; Dorkins, H.; Male, A.; Tucker, K.; Stapleton, A.; Lam, J.; Kirk, J.; Lilja, H.; Easton, D.; Cooper, C.; Eeles, R.; Neal, D.E.

    2010-01-01

    BACKGROUND: Microseminoprotein-beta (MSMB) regulates apoptosis and using genome-wide association studies the rs10993994 single nucleotide polymorphism in the MSMB promoter has been linked to an increased risk of developing prostate cancer. The promoter location of the risk allele, and its ability to

  11. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast–ovarian cancer susceptibility locus

    Science.gov (United States)

    Lawrenson, Kate; Kar, Siddhartha; McCue, Karen; Kuchenbaeker, Karoline; Michailidou, Kyriaki; Tyrer, Jonathan; Beesley, Jonathan; Ramus, Susan J.; Li, Qiyuan; Delgado, Melissa K.; Lee, Janet M.; Aittomäki, Kristiina; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K.; Arver, Brita; Bandera, Elisa V.; Barile, Monica; Barkardottir, Rosa B.; Barrowdale, Daniel; Beckmann, Matthias W.; Benitez, Javier; Berchuck, Andrew; Bisogna, Maria; Bjorge, Line; Blomqvist, Carl; Blot, William; Bogdanova, Natalia; Bojesen, Anders; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Bruinsma, Fiona; Brunet, Joan; Buhari, Shaik Ahmad; Burwinkel, Barbara; Butzow, Ralf; Buys, Saundra S.; Cai, Qiuyin; Caldes, Trinidad; Campbell, Ian; Canniotto, Rikki; Chang-Claude, Jenny; Chiquette, Jocelyne; Choi, Ji-Yeob; Claes, Kathleen B. M.; Collonge-Rame, Marie- Agnès; Damette, Alexandre; Barouk-Simonet, Emmanuelle; Bonnet, Françoise; Bubien, Virginie; Sevenet, Nicolas; Longy, Michel; Berthet, Pascaline; Vaur, Dominique; Castera, Laurent; Ferrer, Sandra Fert; Bignon, Yves-Jean; Uhrhammer, Nancy; Coron, Fanny; Faivre, Laurence; Baurand, Amandine; Jacquot, Caroline; Bertolone, Geoffrey; Lizard, Sarab; Leroux, Dominique; Dreyfus, Hélène; Rebischung, Christine; Peysselon, Magalie; Peyrat, Jean-Philippe; Fournier, Joëlle; Révillion, Françoise; Adenis, Claude; Vénat-Bouvet, Laurence; Léone, Mélanie; Boutry-Kryza, Nadia; Calender, Alain; Giraud, Sophie; Verny-Pierre, Carole; Lasset, Christine; Bonadona, Valérie; Barjhoux, Laure; Sobol, Hagay; Bourdon, Violaine; Noguchi, Tetsuro; Remenieras, Audrey; Coupier, Isabelle; Pujol, Pascal; Sokolowska, Johanna; Bronner, Myriam; Delnatte, Capucine; Bézieau, Stéphane; Mari, Véronique; Gauthier-Villars, Marion; Buecher, Bruno; Rouleau, Etienne; Golmard, Lisa; Moncoutier, Virginie; Belotti, Muriel; de Pauw, Antoine; Elan, Camille; Fourme, Emmanuelle; Birot, Anne-Marie; Saule, Claire; Laurent, Maïté; Houdayer, Claude; Lesueur, Fabienne; Mebirouk, Noura; Coulet, Florence; Colas, Chrystelle; Soubrier, Florent; Warcoin, Mathilde; Prieur, Fabienne; Lebrun, Marine; Kientz, Caroline; Muller, Danièle; Fricker, Jean-Pierre; Toulas, Christine; Guimbaud, Rosine; Gladieff, Laurence; Feillel, Viviane; Mortemousque, Isabelle; Bressac-de-Paillerets, Brigitte; Caron, Olivier; Guillaud-Bataille, Marine; Cook, Linda S.; Cox, Angela; Cramer, Daniel W.; Cross, Simon S.; Cybulski, Cezary; Czene, Kamila; Daly, Mary B.; Damiola, Francesca; Dansonka-Mieszkowska, Agnieszka; Darabi, Hatef; Dennis, Joe; Devilee, Peter; Diez, Orland; Doherty, Jennifer A.; Domchek, Susan M.; Dorfling, Cecilia M.; Dörk, Thilo; Dumont, Martine; Ehrencrona, Hans; Ejlertsen, Bent; Ellis, Steve; Gregory, Helen; Miedzybrodzka, Zosia; Morrison, Patrick J.; Donaldson, Alan; Rogers, Mark T.; Kennedy, M. John; Porteous, Mary E.; Brady, Angela; Barwell, Julian; Foo, Claire; Lalloo, Fiona; Side, Lucy E.; Eason, Jacqueline; Henderson, Alex; Walker, Lisa; Cook, Jackie; Snape, Katie; Murray, Alex; McCann, Emma; Engel, Christoph; Lee, Eunjung; Evans, D. Gareth; Fasching, Peter A.; Feliubadalo, Lidia; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Foretova, Lenka; Fostira, Florentia; Foulkes, William D.; Fridley, Brooke L.; Friedman, Eitan; Frost, Debra; Gambino, Gaetana; Ganz, Patricia A.; Garber, Judy; García-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Ghoussaini, Maya; Giles, Graham G.; Glasspool, Rosalind; Godwin, Andrew K.; Goldberg, Mark S.; Goldgar, David E.; González-Neira, Anna; Goode, Ellen L.; Goodman, Marc T.; Greene, Mark H.; Gronwald, Jacek; Guénel, Pascal; Haiman, Christopher A.; Hall, Per; Hallberg, Emily; Hamann, Ute; Hansen, Thomas V. O.; Harrington, Patricia A.; Hartman, Mikael; Hassan, Norhashimah; Healey, Sue; Rookus, M. A.; van Leeuwen, F. E.; van der Kolk, L. E.; Schmidt, M. K.; Russell, N. S.; de Lange, J. L.; Wijnands, R.; Collée, J. M.; Hooning, M. J.; Seynaeve, C.; van Deurzen, C. H. M.; Obdeijn, I. M.; van Asperen, C. J.; Tollenaar, R. A. E. M.; van Cronenburg, T. C. T. E. F.; Kets, C. M.; Ausems, M. G. E. M.; van der Pol, C. C.; van Os, T. A. M.; Waisfisz, Q.; Meijers-Heijboer, H. E. J.; Gómez-Garcia, E. B.; Oosterwijk, J. C.; Mourits, M. J.; de Bock, G. H.; Vasen, H. F.; Siesling, S.; Verloop, J.; Overbeek, L. I. H.; Heitz, Florian; Herzog, Josef; Høgdall, Estrid; Høgdall, Claus K.; Hogervorst, Frans B. L.; Hollestelle, Antoinette; Hopper, John L.; Hulick, Peter J.; Huzarski, Tomasz; Imyanitov, Evgeny N.; Fox, Stephen; Kirk, Judy; Lindeman, Geoff; Price, Melanie; Bowtell, David; deFazio, Anna; Webb, Penny; Isaacs, Claudine; Ito, Hidemi; Jakubowska, Anna; Janavicius, Ramunas; Jensen, Allan; John, Esther M.; Johnson, Nichola; Kabisch, Maria; Kang, Daehee; Kapuscinski, Miroslav; Karlan, Beth Y.; Khan, Sofia; Kiemeney, Lambertus A.; Kjaer, Susanne Kruger; Knight, Julia A.; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kupryjanczyk, Jolanta; Kwong, Ava; de la Hoya, Miguel; Laitman, Yael; Lambrechts, Diether; Le, Nhu; De Leeneer, Kim; Lester, Jenny; Levine, Douglas A.; Li, Jingmei; Lindblom, Annika; Long, Jirong; Lophatananon, Artitaya; Loud, Jennifer T.; Lu, Karen; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Le Marchand, Loic; Margolin, Sara; Marme, Frederik; Massuger, Leon F. A. G.; Matsuo, Keitaro; Mazoyer, Sylvie; McGuffog, Lesley; McLean, Catriona; McNeish, Iain; Meindl, Alfons; Menon, Usha; Mensenkamp, Arjen R.; Milne, Roger L.; Montagna, Marco; Moysich, Kirsten B.; Muir, Kenneth; Mulligan, Anna Marie; Nathanson, Katherine L.; Ness, Roberta B.; Neuhausen, Susan L.; Nevanlinna, Heli; Nord, Silje; Nussbaum, Robert L.; Odunsi, Kunle; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I.; Olson, Janet E.; Olswold, Curtis; O'Malley, David; Orlow, Irene; Orr, Nick; Osorio, Ana; Park, Sue Kyung; Pearce, Celeste L.; Pejovic, Tanja; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M.; Poole, Elizabeth M.; Pylkäs, Katri; Radice, Paolo; Rantala, Johanna; Rashid, Muhammad Usman; Rennert, Gad; Rhenius, Valerie; Rhiem, Kerstin; Risch, Harvey A.; Rodriguez, Gus; Rossing, Mary Anne; Rudolph, Anja; Salvesen, Helga B.; Sangrajrang, Suleeporn; Sawyer, Elinor J.; Schildkraut, Joellen M.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Sellers, Thomas A.; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shu, Xiao-Ou; Sieh, Weiva; Singer, Christian F.; Sinilnikova, Olga M.; Slager, Susan; Song, Honglin; Soucy, Penny; Southey, Melissa C.; Stenmark-Askmalm, Marie; Stoppa-Lyonnet, Dominique; Sutter, Christian; Swerdlow, Anthony; Tchatchou, Sandrine; Teixeira, Manuel R.; Teo, Soo H.; Terry, Kathryn L.; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; Toland, Amanda Ewart; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Tseng, Chiu-chen; Tung, Nadine; Tworoger, Shelley S.; Vachon, Celine; van den Ouweland, Ans M. W.; van Doorn, Helena C.; van Rensburg, Elizabeth J.; Van't Veer, Laura J.; Vanderstichele, Adriaan; Vergote, Ignace; Vijai, Joseph; Wang, Qin; Wang-Gohrke, Shan; Weitzel, Jeffrey N.; Wentzensen, Nicolas; Whittemore, Alice S.; Wildiers, Hans; Winqvist, Robert; Wu, Anna H.; Yannoukakos, Drakoulis; Yoon, Sook-Yee; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Khanna, Kum Kum; Simard, Jacques; Monteiro, Alvaro N.; French, Juliet D.; Couch, Fergus J.; Freedman, Matthew L.; Easton, Douglas F.; Dunning, Alison M.; Pharoah, Paul D.; Edwards, Stacey L.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Gayther, Simon A.

    2016-01-01

    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10−20), ER-negative BC (P=1.1 × 10−13), BRCA1-associated BC (P=7.7 × 10−16) and triple negative BC (P-diff=2 × 10−5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10−3) and ABHD8 (P<2 × 10−3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk. PMID:27601076

  12. The rs10993994 risk allele for prostate cancer results in clinically relevant changes in microseminoprotein-beta expression in tissue and urine.

    Directory of Open Access Journals (Sweden)

    Hayley C Whitaker

    2010-10-01

    Full Text Available Microseminoprotein-beta (MSMB regulates apoptosis and using genome-wide association studies the rs10993994 single nucleotide polymorphism in the MSMB promoter has been linked to an increased risk of developing prostate cancer. The promoter location of the risk allele, and its ability to reduce promoter activity, suggested that the rs10993994 risk allele could result in lowered MSMB in benign tissue leading to increased prostate cancer risk.MSMB expression in benign and malignant prostate tissue was examined using immunohistochemistry and compared with the rs10993994 genotype. Urinary MSMB concentrations were determined by ELISA and correlated with urinary PSA, the presence or absence of cancer, rs10993994 genotype and age of onset. MSMB levels in prostate tissue and urine were greatly reduced with tumourigenesis. Urinary MSMB was better than urinary PSA at differentiating men with prostate cancer at all Gleason grades. The high risk allele was associated with heterogeneity of MSMB staining and loss of MSMB in both tissue and urine in benign prostate.These data show that some high risk alleles discovered using genome-wide association studies produce phenotypic effects with potential clinical utility. We provide the first link between a low penetrance polymorphism for prostate cancer and a potential test in human tissue and bodily fluids. There is potential to develop tissue and urinary MSMB for a biomarker of prostate cancer risk, diagnosis and disease monitoring.

  13. The rs10993994 risk allele for prostate cancer results in clinically relevant changes in microseminoprotein-beta expression in tissue and urine.

    Science.gov (United States)

    Whitaker, Hayley C; Kote-Jarai, Zsofia; Ross-Adams, Helen; Warren, Anne Y; Burge, Johanna; George, Anne; Bancroft, Elizabeth; Jhavar, Sameer; Leongamornlert, Daniel; Tymrakiewicz, Malgorzata; Saunders, Edward; Page, Elizabeth; Mitra, Anita; Mitchell, Gillian; Lindeman, Geoffrey J; Evans, D Gareth; Blanco, Ignacio; Mercer, Catherine; Rubinstein, Wendy S; Clowes, Virginia; Douglas, Fiona; Hodgson, Shirley; Walker, Lisa; Donaldson, Alan; Izatt, Louise; Dorkins, Huw; Male, Alison; Tucker, Kathy; Stapleton, Alan; Lam, Jimmy; Kirk, Judy; Lilja, Hans; Easton, Douglas; Cooper, Colin; Eeles, Rosalind; Neal, David E

    2010-10-13

    Microseminoprotein-beta (MSMB) regulates apoptosis and using genome-wide association studies the rs10993994 single nucleotide polymorphism in the MSMB promoter has been linked to an increased risk of developing prostate cancer. The promoter location of the risk allele, and its ability to reduce promoter activity, suggested that the rs10993994 risk allele could result in lowered MSMB in benign tissue leading to increased prostate cancer risk. MSMB expression in benign and malignant prostate tissue was examined using immunohistochemistry and compared with the rs10993994 genotype. Urinary MSMB concentrations were determined by ELISA and correlated with urinary PSA, the presence or absence of cancer, rs10993994 genotype and age of onset. MSMB levels in prostate tissue and urine were greatly reduced with tumourigenesis. Urinary MSMB was better than urinary PSA at differentiating men with prostate cancer at all Gleason grades. The high risk allele was associated with heterogeneity of MSMB staining and loss of MSMB in both tissue and urine in benign prostate. These data show that some high risk alleles discovered using genome-wide association studies produce phenotypic effects with potential clinical utility. We provide the first link between a low penetrance polymorphism for prostate cancer and a potential test in human tissue and bodily fluids. There is potential to develop tissue and urinary MSMB for a biomarker of prostate cancer risk, diagnosis and disease monitoring.

  14. Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction

    NARCIS (Netherlands)

    Do, Ron; Stitziel, Nathan O.; Won, Hong-Hee; Jørgensen, Anders Berg; Duga, Stefano; Angelica Merlini, Pier; Kiezun, Adam; Farrall, Martin; Goel, Anuj; Zuk, Or; Guella, Illaria; Asselta, Rosanna; Lange, Leslie A.; Peloso, Gina M.; Auer, Paul L.; Girelli, Domenico; Martinelli, Nicola; Farlow, Deborah N.; DePristo, Mark A.; Roberts, Robert; Stewart, Alexander F. R.; Saleheen, Danish; Danesh, John; Epstein, Stephen E.; Sivapalaratnam, Suthesh; Hovingh, G. Kees; Kastelein, John J.; Samani, Nilesh J.; Schunkert, Heribert; Erdmann, Jeanette; Shah, Svati H.; Kraus, William E.; Davies, Robert; Nikpay, Majid; Johansen, Christopher T.; Wang, Jian; Hegele, Robert A.; Hechter, Eliana; Marz, Winfried; Kleber, Marcus E.; Huang, Jie; Johnson, Andrew D.; Li, Mingyao; Burke, Greg L.; Gross, Myron; Liu, Yongmei; Assimes, Themistocles L.; Heiss, Gerardo; Lange, Ethan M.; Folsom, Aaron R.; Taylor, Herman A.; Olivieri, Oliviero; Hamsten, Anders; Clarke, Robert; Reilly, Dermot F.; Yin, Wu; Rivas, Manuel A.; Donnelly, Peter; Rossouw, Jacques E.; Psaty, Bruce M.; Herrington, David M.; Wilson, James G.; Rich, Stephen S.; Bamshad, Michael J.; Tracy, Russell P.; Cupples, L. Adrienne; Rader, Daniel J.; Reilly, Muredach P.; Spertus, John A.; Cresci, Sharon; Hartiala, Jaana; Tang, W. H. Wilson; Hazen, Stanley L.; Allayee, Hooman; Reiner, Alex P.; Carlson, Christopher S.; Kooperberg, Charles; Jackson, Rebecca D.; Boerwinkle, Eric; Lander, Eric S.; Schwartz, Stephen M.; Siscovick, David S.; McPherson, Ruth; Tybjaerg-Hansen, Anne; Abecasis, Goncalo R.; Watkins, Hugh; Nickerson, Deborah A.; Ardissino, Diego; Sunyaev, Shamil R.; O'Donnell, Christopher J.; Altshuler, David; Gabriel, Stacey; Kathiresan, Sekar; Gabriel, Stacey B.; Altshuler, David M.; Abecasis, Gonçalo R.; Daly, Mark J.; de Bakker, Paul I. W.; Fennell, Tim; Garimella, Kiran; Hu, Youna; Jordan, Daniel M.; Jun, Goo; Kang, Hyun Min; Lettre, Guillaume; Li, Bingshan; Newton-Cheh, Christopher H.; Padmanabhan, Sandosh; Peloso, Gina; Pulit, Sara; Reich, David; Schwartz, Steve; Scott, Laura; Stoletzki, Nina; Voight, Benjamin F.; Willer, Cristen J.; Akylbekova, Ermeg; Atwood, Larry D.; Ballantyne, Christie M.; Barbalic, Maja; Barr, R. Graham; Benjamin, Emelia J.; Bis, Joshua; Bowden, Donald W.; Brody, Jennifer; Budoff, Matthew; Burke, Greg; Buxbaum, Sarah; Carr, Jeff; Chen, Donna T.; Chen, Ida Y.; Chen, Wei-Min; Concannon, Pat; Crosby, Jacy; D'Agostino, Ralph; DeStefano, Anita L.; Dreisbach, Albert; Dupuis, Josée; Durda, J. Peter; Ellis, Jaclyn; Fornage, Myriam; Fox, Caroline S.; Fox, Ervin; Funari, Vincent; Ganesh, Santhi K.; Gardin, Julius; Goff, David; Gordon, Ora; Grody, Wayne; Guo, Xiuqing; Hall, Ira M.; Heard-Costa, Nancy L.; Heckbert, Susan R.; Heintz, Nicholas; Hickson, DeMarc; Hwang, Shih-Jen; Jacobs, David R.; Jenny, Nancy S.; Johnson, Craig W.; Kawut, Steven; Kronmal, Richard; Kurz, Raluca; Larson, Martin G.; Lawson, Mark; Lewis, Cora E.; Levy, Daniel; Li, Dalin; Lin, Honghuang; Liu, Chunyu; Liu, Jiankang; Liu, Kiang; Liu, Xiaoming; Longstreth, William T.; Loria, Cay; Lumley, Thomas; Lunetta, Kathryn; Mackey, Aaron J.; Mackey, Rachel; Manichaikul, Ani; Maxwell, Taylor; McKnight, Barbara; Meigs, James B.; Morrison, Alanna C.; Musani, Solomon K.; Mychaleckyj, Josyf C.; Nettleton, Jennifer A.; North, Kari; O'Leary, Daniel; Ong, Frank S.; Palmas, Walter; Pankow, James S.; Pankratz, Nathan D.; Paul, Shom; Perez, Marco; Person, Sharina D.; Polak, Joseph; Post, Wendy S.; Quinlan, Aaron R.; Raffel, Leslie J.; Ramachandran, Vasan S.; Reiner, Alexander P.; Rice, Kenneth; Rotter, Jerome I.; Sanders, Jill P.; Schreiner, Pamela; Seshadri, Sudha; Shea, Steve; Sidney, Stephen; Silverstein, Kevin; Smith, Nicholas L.; Sotoodehnia, Nona; Srinivasan, Asoke; Taylor, Kent; Thomas, Fridtjof; Tsai, Michael Y.; Volcik, Kelly A.; Wassel, Chrstina L.; Watson, Karol; Wei, Gina; White, Wendy; Wiggins, Kerri L.; Wilk, Jemma B.; Williams, O. Dale; Wilson, Gregory; Wolf, Phillip; Zakai, Neil A.; Hardy, John; Meschia, James F.; Nalls, Michael; Singleton, Andrew; Worrall, Brad; Barnes, Kathleen C.; Abdulhamid, Ibrahim; Accurso, Frank; Anbar, Ran; Beaty, Terri; Bigham, Abigail; Black, Phillip; Bleecker, Eugene; Buckingham, Kati; Cairns, Anne Marie; Caplan, Daniel; Chatfield, Barbara; Chidekel, Aaron; Cho, Michael; Christiani, David C.; Crapo, James D.; Crouch, Julia; Daley, Denise; Dang, Anthony; Dang, Hong; de Paula, Alicia; DeCelie-Germana, Joan; Dozor, Allen; Drumm, Mitch; Dyson, Maynard; Emerson, Julia; Emond, Mary J.; Ferkol, Thomas; Fink, Robert; Foster, Cassandra; Froh, Deborah; Gao, Li; Gershan, William; Gibson, Ronald L.; Godwin, Elizabeth; Gondor, Magdalen; Gutierrez, Hector; Hansel, Nadia N.; Hassoun, Paul M.; Hiatt, Peter; Hokanson, John E.; Howenstine, Michelle; Hummer, Laura K.; Jamal, Seema M.; Kanga, Jamshed; Kim, Yoonhee; Knowles, Michael R.; Konstan, Michael; Lahiri, Thomas; Laird, Nan; Lange, Christoph; Lin, Lin; Lin, Xihong; Louie, Tin L.; Lynch, David; Make, Barry; Martin, Thomas R.; Mathai, Steve C.; Mathias, Rasika A.; McNamara, John; McNamara, Sharon; Meyers, Deborah; Millard, Susan; Mogayzel, Peter; Moss, Richard; Murray, Tanda; Nielson, Dennis; Noyes, Blakeslee; O'Neal, Wanda; Orenstein, David; O'Sullivan, Brian; Pace, Rhonda; Pare, Peter; Parker, H. Worth; Passero, Mary Ann; Perkett, Elizabeth; Prestridge, Adrienne; Rafaels, Nicholas M.; Ramsey, Bonnie; Regan, Elizabeth; Ren, Clement; Retsch-Bogart, George; Rock, Michael; Rosen, Antony; Rosenfeld, Margaret; Ruczinski, Ingo; Sanford, Andrew; Schaeffer, David; Sell, Cindy; Sheehan, Daniel; Silverman, Edwin K.; Sin, Don; Spencer, Terry; Stonebraker, Jackie; Tabor, Holly K.; Varlotta, Laurie; Vergara, Candelaria I.; Weiss, Robert; Wigley, Fred; Wise, Robert A.; Wright, Fred A.; Wurfel, Mark M.; Zanni, Robert; Zou, Fei; Rieder, Mark J.; Green, Phil; Shendure, Jay; Akey, Joshua M.; Bustamante, Carlos D.; Crosslin, David R.; Eichler, Evan E.; Fox, P. Keolu; Fu, Wenqing; Gordon, Adam; Gravel, Simon; Jarvik, Gail P.; Johnsen, Jill M.; Kan, Mengyuan; Kenny, Eimear E.; Kidd, Jeffrey M.; Lara-Garduno, Fremiet; Leal, Suzanne M.; Liu, Dajiang J.; McGee, Sean; O'Connor, Timothy D.; Paeper, Bryan; Robertson, Peggy D.; Smith, Joshua D.; Staples, Jeffrey C.; Tennessen, Jacob A.; Turner, Emily H.; Wang, Gao; Yi, Qian; Jackson, Rebecca; Peters, Ulrike; Anderson, Garnet; Anton-Culver, Hoda; Beresford, Shirley; Bizon, Chris; Black, Henry; Brunner, Robert; Brzyski, Robert; Burwen, Dale; Caan, Bette; Carty, Cara L.; Chlebowski, Rowan; Cummings, Steven; Curb, J. David; Eaton, Charles B.; Ford, Leslie; Franceschini, Nora; Fullerton, Stephanie M.; Gass, Margery; Geller, Nancy; Howard, Barbara V.; Hsu, Li; Hutter, Carolyn M.; Ioannidis, John; Jiao, Shuo; Johnson, Karen C.; Kuller, Lewis; LaCroix, Andrea; Lakshminarayan, Kamakshi; Lane, Dorothy; Lasser, Norman; LeBlanc, Erin; Li, Kuo-Ping; Limacher, Marian; Lin, Dan-Yu; Logsdon, Benjamin A.; Hutchinson, Fred; Ludlam, Shari; Manson, JoAnn E.; Margolis, Karen; Martin, Lisa; McGowan, Joan; Monda, Keri L.; Kotchen, Jane Morley; Nathan, Lauren; Ockene, Judith; O'Sullivan, Mary Jo; Phillips, Lawrence S.; Prentice, Ross L.; Robbins, John; Robinson, Jennifer G.; Sangi-Haghpeykar, Haleh; Sarto, Gloria E.; Shumaker, Sally; Simon, Michael S.; Stefanick, Marcia L.; Stein, Evan; Tang, Hua; Taylor, Kira C.; Thomson, Cynthia A.; Thornton, Timothy A.; van Horn, Linda; Vitolins, Mara; Wactawski-Wende, Jean; Wallace, Robert; Wassertheil-Smoller, Sylvia; Zeng, Donglin; Applebaum-Bowden, Deborah; Feolo, Michael; Gan, Weiniu; Paltoo, Dina N.; Sholinsky, Phyliss; Sturcke, Anne

    2015-01-01

    Myocardial infarction (MI), a leading cause of death around the world, displays a complex pattern of inheritance(1,2). When MI occurs early in life, genetic inheritance is a major component to risk(1). Previously, rare mutations in low-density lipoprotein (LDL) genes have been shown to contribute to

  15. Allelic variations in the CYBA gene of NADPH oxidase and risk of kidney complications in patients with type 1 diabetes.

    Science.gov (United States)

    Patente, Thiago A; Mohammedi, Kamel; Bellili-Muñoz, Naïma; Driss, Fathi; Sanchez, Manuel; Fumeron, Frédéric; Roussel, Ronan; Hadjadj, Samy; Corrêa-Giannella, Maria Lúcia; Marre, Michel; Velho, Gilberto

    2015-09-01

    Oxidative stress plays a pivotal role in the pathophysiology of diabetic nephropathy, and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system is an important source of reactive oxygen species in hyperglycemic conditions in the kidney. Plasma concentration of advanced oxidation protein products (AOPP), a marker of oxidative stress, is increased in patients with diabetic nephropathy. We investigated associations of variants in the CYBA gene, encoding the regulatory subunit p22(phox) of NADPH oxidase, with diabetic nephropathy and plasma AOPP and myeloperoxidase (MPO) concentrations in type 1 diabetic patients. Seven SNPs in the CYBA region were analyzed in 1357 Caucasian subjects with type 1 diabetes from the SURGENE (n=340), GENEDIAB (n=444), and GENESIS (n=573) cohorts. Duration of follow-up was 10, 9, and 6 years, respectively. Cox proportional hazards and logistic regression analyses were used to estimate hazard ratios (HR) or odds ratios (OR) for incidence and prevalence of diabetic nephropathy. The major G-allele of rs9932581 was associated with the incidence of renal events defined as new cases of microalbuminuria or the progression to a more severe stage of nephropathy during follow-up (HR 1.59, 95% CI 1.17-2.18, P=0.003) in SURGENE. The same allele was associated with established/advanced nephropathy (OR 1.52, 95% CI 1.22-1.92, P=0.0001) and with the incidence of end-stage renal disease (ESRD) (HR 2.01, 95% CI 1.30-3.24, P=0.001) in GENEDIAB/GENESIS pooled studies. The risk allele was also associated with higher plasma AOPP concentration in subsets of SURGENE and GENEDIAB, with higher plasma MPO concentration in a subset of GENEDIAB, and with lower estimated glomerular filtration rate (eGFR) in the three cohorts. In conclusion, a functional variant in the promoter of the CYBA gene was associated with lower eGFR and with prevalence and incidence of diabetic nephropathy and ESRD in type 1 diabetic patients. These results are consistent with

  16. Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression

    DEFF Research Database (Denmark)

    Hamdi, Yosr; Soucy, Penny; Kuchenbaeker, Karoline B

    2017-01-01

    1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. METHODS: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast...... and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. RESULTS: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most...... significant SNP rs228595 p = 7 × 10(-6)). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1...

  17. A common polymorphism in the promoter region of the TNFSF4 gene is associated with lower allele-specific expression and risk of myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Massimiliano Ria

    Full Text Available BACKGROUND: The TNFSF4/TNFRSF4 system, along with several other receptor-ligand pairs, is involved in the recruitment and activation of T-cells and is therefore tentatively implicated in atherosclerosis and acute coronary syndromes. We have previously shown that genetic variants in TNFSF4 are associated with myocardial infarction (MI in women. This prompted functional studies of TNFSF4 expression. METHODS AND RESULTS: Based on a screening of the TNFSF4 genomic region, a promoter polymorphism (rs45454293 and a haplotype were identified, conceivably involved in gene regulation. The rs45454293T-allele, in agreement with the linked rs3850641G-allele, proved to be associated with increased risk of MI in women. Haplotype-specific chromatin immunoprecipitation of activated polymerase II, as a measure of transcriptional activity in vivo, suggested that the haplotype including the rs45454293 and rs3850641 polymorphisms is functionally important, the rs45454293T- and rs3850641G-alleles being associated with lower transcriptional activity in cells heterozygous for both polymorphisms. The functional role of rs45454293 on transcriptional levels of TNFSF4 was clarified by luciferase reporter assays, where the rs45454293T-allele decreased gene expression when compared with the rs45454293C-allele, while the rs3850641 SNP did not have any effect on TNFSF4 promoter activity. Electromobility shift assay showed that the rs45454293 polymorphism, but not rs3850641, affects the binding of nuclear factors, thus suggesting that the lower transcriptional activity is attributed to binding of one or more transcriptional repressor(s to the T-allele. CONCLUSIONS: Our data indicate that the TNFSF4 rs45454293T-allele is associated with lower TNFSF4 expression and increased risk of MI.

  18. Additive composite ABCG2, SLC2A9 and SLC22A12 scores of high-risk alleles with alcohol use modulate gout risk.

    Science.gov (United States)

    Tu, Hung-Pin; Chung, Chia-Min; Min-Shan Ko, Albert; Lee, Su-Shin; Lai, Han-Ming; Lee, Chien-Hung; Huang, Chung-Ming; Liu, Chiu-Shong; Ko, Ying-Chin

    2016-09-01

    The aim of the present study was to evaluate the contribution of urate transporter genes and alcohol use to the risk of gout/tophi. Eight variants of ABCG2, SLC2A9, SLC22A12, SLC22A11 and SLC17A3 were genotyped in male individuals in a case-control study with 157 gout (33% tophi), 106 asymptomatic hyperuricaemia and 295 control subjects from Taiwan. The multilocus profiles of the genetic risk scores for urate gene variants were used to evaluate the risk of asymptomatic hyperuricaemia, gout and tophi. ABCG2 Q141K (T), SLC2A9 rs1014290 (A) and SLC22A12 rs475688 (C) under an additive model and alcohol use independently predicted the risk of gout (respective odds ratio for each factor=2.48, 2.03, 1.95 and 2.48). The additive composite Q141K, rs1014290 and rs475688 scores of high-risk alleles were associated with gout risk (Pgout and tophi risk (P for interaction=0.0452, 0.0033). The synergistic effect of genetic urate score 5-6 and alcohol use indicates that these combined factors correlate with gout and tophi occurrence.

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

    Science.gov (United States)

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

    2012-03-01

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

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

    Science.gov (United States)

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

    2015-10-01

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

  1. Decision support for utility environmental risk management

    International Nuclear Information System (INIS)

    Balson, W.E.; Wilson, D.S.

    1991-01-01

    This paper reviews a number of decision support methods developed and applied by Decision Focus Incorporated to help utility personnel manage current environmental problems. This work has been performed for the Environmental Risk Analysis Program of EPRI's Environment Division, and also for a number of electric utilities across the country. These are two distinct types of decision support software tools that have been created: economic risk management and environmental risk analysis. These types differ primarily in the identification of who will make a decision. Economic risk management tools are directed primarily at decisions made by electric utilities. Environmental risk analysis tools are directed primarily at decisions made by legislative or regulatory agencies, about which a utility may wish to comment

  2. Modeling Glaucoma: Retinal Ganglion Cells Generated from Induced Pluripotent Stem Cells of Patients with SIX6 Risk Allele Show Developmental Abnormalities.

    Science.gov (United States)

    Teotia, Pooja; Van Hook, Matthew J; Wichman, Christopher S; Allingham, R Rand; Hauser, Michael A; Ahmad, Iqbal

    2017-11-01

    Glaucoma represents a group of multifactorial diseases with a unifying pathology of progressive retinal ganglion cell (RGC) degeneration, causing irreversible vision loss. To test the hypothesis that RGCs are intrinsically vulnerable in glaucoma, we have developed an in vitro model using the SIX6 risk allele carrying glaucoma patient-specific induced pluripotent stem cells (iPSCs) for generating functional RGCs. Here, we demonstrate that the efficiency of RGC generation by SIX6 risk allele iPSCs is significantly lower than iPSCs-derived from healthy, age- and sex-matched controls. The decrease in the number of RGC generation is accompanied by repressed developmental expression of RGC regulatory genes. The SIX6 risk allele RGCs display short and simple neurites, reduced expression of guidance molecules, and immature electrophysiological signature. In addition, these cells have higher expression of glaucoma-associated genes, CDKN2A and CDKN2B, suggesting an early onset of the disease phenotype. Consistent with the developmental abnormalities, the SIX6 risk allele RGCs display global dysregulation of genes which map on developmentally relevant biological processes for RGC differentiation and signaling pathways such as mammalian target of rapamycin that integrate diverse functions for differentiation, metabolism, and survival. The results suggest that SIX6 influences different stages of RGC differentiation and their survival; therefore, alteration in SIX6 function due to the risk allele may lead to cellular and molecular abnormalities. These abnormalities, if carried into adulthood, may make RGCs vulnerable in glaucoma. Stem Cells 2017;35:2239-2252. © 2017 AlphaMed Press.

  3. Shared epitope alleles remain a risk factor for anti-citrullinated proteins antibody (ACPA--positive rheumatoid arthritis in three Asian ethnic groups.

    Directory of Open Access Journals (Sweden)

    Too Chun-Lai

    Full Text Available BACKGROUND: To investigate the associations between HLA-DRB1 shared epitope (SE alleles and rheumatoid arthritis in subsets of rheumatoid arthritis defined by autoantibodies in three Asian populations from Malaysia. METHODS: 1,079 rheumatoid arthritis patients and 1,470 healthy controls were included in the study. Levels of antibodies to citrullinated proteins (ACPA and rheumatoid factors were assessed and the PCR-SSO method was used for HLA-DRB1 genotyping. RESULTS: The proportion of ACPA positivity among Malay, Chinese and Indian rheumatoid arthritis patients were 62.9%, 65.2% and 68.6%, respectively. An increased frequency of SE alleles was observed in ACPA-positive rheumatoid arthritis among the three Asian ethnic groups. HLA-DRB1*10 was highly associated with rheumatoid arthritis susceptibility in these Asian populations. HLA-DRB1*0405 was significantly associated with susceptibility to rheumatoid arthritis in Malays and Chinese, but not in Indians. HLA-DRB1*01 did not show any independent effect as a risk factor for rheumatoid arthritis in this study and HLA-DRB1*1202 was protective in Malays and Chinese. There was no association between SE alleles and ACPA- negative rheumatoid arthritis in any of the three Asian ethnic groups. CONCLUSION: The HLA-DRB1 SE alleles increase the risk of ACPA-positive rheumatoid arthritis in all three Asian populations from Malaysia.

  4. Apolipoprotein E e4 allele does not increase the risk of early postoperative delirium after major surgery.

    Science.gov (United States)

    Abelha, Fernando José; Fernandes, Vera; Botelho, Miguela; Santos, Patricia; Santos, Alice; Machado, J C; Barros, Henrique

    2012-02-01

    BACKGROUND: A relationship between patients with a genetic predisposition to and those who develop postoperative delirium has not been yet determined. The aim of this study was to determine whether there is an association between apolipoprotein E epsilon 4 allele (APOE4) and delirium after major surgery. METHODS: Of 230 intensive care patients admitted to the post anesthesia care unit (PACU) over a period of 3 months, 173 were enrolled in the study. Patients' demographics and intra- and postoperative data were collected. Patients were followed for the development of delirium using the Intensive Care Delirium Screening Checklist, and DNA was obtained at PACU admission to determine apolipoprotein E genotype. RESULTS: Fifteen percent of patients developed delirium after surgery. Twenty-four patients had one copy of APOE4. The presence of APOE4 was not associated with an increased risk of early postoperative delirium (4% vs. 17%; P = 0.088). The presence of APOE4 was not associated with differences in any studied variables. Multivariate analysis identified age [odds ratio (OR) 9.3, 95% confidence interval (CI) 2.0-43.0, P = 0.004 for age ≥65 years), congestive heart disease (OR 6.2, 95% CI 2.0-19.3, P = 0.002), and emergency surgery (OR 59.7, 95% CI 6.7-530.5, P < 0.001) as independent predictors for development of delirium. The Simplified Acute Physiology Score II (SAPS II) and The Acute Physiology and Chronic Health Evaluation II (APACHE II) were significantly higher in patients with delirium (P < 0.001 and 0.008, respectively). Hospital mortality rates of these patients was higher and they had a longer median PACU stay. CONCLUSIONS: Apolipoprotein e4 carrier status was not associated with an increased risk for early postoperative delirium. Age, congestive heart failure, and emergency surgery were independent risk factors for the development of delirium after major surgery.

  5. Association of apolipoprotein E allele {epsilon}4 with late-onset sporadic Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Lucotte, G.; David, F.; Berriche, S. [Regional Center of Neurogenetics, Reims (France)] [and others

    1994-09-15

    Apolipoprotein E, type {epsilon}4 allele (ApoE {epsilon}4), is associated with late-onset sporadic Alzheimer`s disease (AD) in French patients. The association is highly significant (0.45 AD versus 0.12 controls for {epsilon}4 allele frequencies). These data support the involvement of ApoE {epsilon}4 allele as a very important risk factor for the clinical expression of AD. 22 refs., 1 fig., 3 tabs.

  6. Allelic Variation of Risk for Anxiety Symptoms Moderates the Relation Between Adolescent Safety Behaviors and Social Anxiety Symptoms

    Science.gov (United States)

    Thomas, Sarah A.; Weeks, Justin W.; Dougherty, Lea R.; Lipton, Melanie F.; Daruwala, Samantha E.; Kline, Kathryn

    2015-01-01

    Social anxiety often develops in adolescence, and precedes the onset of depression and substance use disorders. The link between social anxiety and use of behaviors to minimize distress in social situations (i.e., safety behaviors) is strong and for some patients, this link poses difficulty for engaging in, and benefiting from, exposure-based treatment. Yet, little is known about whether individual differences may moderate links between social anxiety and safety behaviors, namely variations in genetic alleles germane to anxiety. We examined the relation between adolescent social anxiety and expressions of safety behaviors, and whether allelic variation for anxiety moderates this relation. Adolescents (n=75; ages 14–17) were recruited from two larger studies investigating measurement of family relationships or adolescent social anxiety. Adolescents completed self-report measures about social anxiety symptoms and use of safety behaviors. They also provided saliva samples to assess allelic variations for anxiety from two genetic polymorphisms (BDNF rs6265; TAQ1A rs1800497). Controlling for adolescent age and gender, we observed a significant interaction between social anxiety symptoms and allelic variation (β=0.37, t=2.41, p=.02). Specifically, adolescents carrying allelic variations for anxiety evidenced a statistically significant and relatively strong positive relation between social anxiety symptoms and safety behaviors (β=0.73), whereas adolescents not carrying allelic variation evidenced a statistically non-significant and relatively weak relation (β=0.22). These findings have important implications for treating adolescent social anxiety, in that we identified an individual difference variable that can be used to identify people who evidence a particularly strong link between use of safety behaviors and expressing social anxiety. PMID:26692635

  7. The impact of the CACNA1C risk allele on limbic structures and facial emotions recognition in bipolar disorder subjects and healthy controls.

    Science.gov (United States)

    Soeiro-de-Souza, Márcio Gerhardt; Otaduy, Maria Concepción Garcia; Dias, Carolina Zadres; Bio, Danielle S; Machado-Vieira, Rodrigo; Moreno, Ricardo Alberto

    2012-12-01

    Impairments in facial emotion recognition (FER) have been reported in bipolar disorder (BD) during all mood states. FER has been the focus of functional magnetic resonance imaging studies evaluating differential activation of limbic regions. Recently, the α1-C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene has been described as a risk gene for BD and its Met allele found to increase CACNA1C mRNA expression. In healthy controls, the CACNA1C risk (Met) allele has been reported to increase limbic system activation during emotional stimuli and also to impact on cognitive function. The aim of this study was to investigate the impact of CACNA1C genotype on FER scores and limbic system morphology in subjects with BD and healthy controls. Thirty-nine euthymic BD I subjects and 40 healthy controls were submitted to a FER recognition test battery and genotyped for CACNA1C. Subjects were also examined with a 3D 3-Tesla structural imaging protocol. The CACNA1C risk allele for BD was associated to FER impairment in BD, while in controls nothing was observed. The CACNA1C genotype did not impact on amygdala or hippocampus volume neither in BD nor controls. Sample size. The present findings suggest that a polymorphism in calcium channels interferes FER phenotype exclusively in BD and doesn't interfere on limbic structures morphology. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. The STAT4 SLE risk allele rs7574865[T] is associated with increased IL-12-induced IFN-γ production in T cells from patients with SLE.

    Science.gov (United States)

    Hagberg, Niklas; Joelsson, Martin; Leonard, Dag; Reid, Sarah; Eloranta, Maija-Leena; Mo, John; Nilsson, Magnus K; Syvänen, Ann-Christine; Bryceson, Yenan T; Rönnblom, Lars

    2018-02-23

    Genetic variants in the transcription factor STAT4 are associated with increased susceptibility to systemic lupus erythematosus (SLE) and a more severe disease phenotype. This study aimed to clarify how the SLE-associated intronic STAT4 risk allele rs7574865[T] affects the function of immune cells in SLE. Peripheral blood mononuclear cells (PBMCs) were isolated from 52 genotyped patients with SLE. Phosphorylation of STAT4 (pSTAT4) and STAT1 (pSTAT1) in response to interferon (IFN)-α, IFN-γ or interleukin (IL)-12, total levels of STAT4, STAT1 and T-bet, and frequency of IFN-γ + cells on IL-12 stimulation were determined by flow cytometry in subsets of immune cells before and after preactivation of cells with phytohaemagglutinin (PHA) and IL-2. Cellular responses and phenotypes were correlated to STAT4 risk allele carriership. Janus kinase inhibitors (JAKi) selective for TYK2 (TYK2i) or JAK2 (JAK2i) were evaluated for inhibition of IL-12 or IFN-γ-induced activation of SLE PBMCs. In resting PBMCs, the STAT4 risk allele was neither associated with total levels of STAT4 or STAT1, nor cytokine-induced pSTAT4 or pSTAT1. Following PHA/IL-2 activation, CD8 + T cells from STAT4 risk allele carriers displayed increased levels of STAT4 resulting in increased pSTAT4 in response to IL-12 and IFN-α, and an augmented IL-12-induced IFN-γ production in CD8 + and CD4 + T cells. The TYK2i and the JAK2i efficiently blocked IL-12 and IFN-γ-induced activation of PBMCs from STAT4 risk patients, respectively. T cells from patients with SLE carrying the STAT4 risk allele rs7574865[T] display an augmented response to IL-12 and IFN-α. This subset of patients may benefit from JAKi treatment. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. Risk-based emergency decision support

    International Nuclear Information System (INIS)

    Koerte, Jens

    2003-01-01

    In the present paper we discuss how to assist critical decisions taken under complex, contingent circumstances, with a high degree of uncertainty and short time frames. In such sharp-end decision regimes, standard rule-based decision support systems do not capture the complexity of the situation. At the same time, traditional risk analysis is of little use due to variability in the specific circumstances. How then, can an organisation provide assistance to, e.g. pilots in dealing with such emergencies? A method called 'contingent risk and decision analysis' is presented, to provide decision support for decisions under variable circumstances and short available time scales. The method consists of nine steps of definition, modelling, analysis and criteria definition to be performed 'off-line' by analysts, and procedure generation to transform the analysis result into an operational decision aid. Examples of pilots' decisions in response to sudden vibration in offshore helicopter transport method are used to illustrate the approach

  10. Evidence of an association between the Arg72 allele of the peptide YY and increased risk of type 2 diabetes

    DEFF Research Database (Denmark)

    Torekov, Signe S; Larsen, Lesli H; Glümer, Charlotte

    2005-01-01

    We tested the hypothesis that variants in the gene encoding the prepropeptide YY (PYY) associate with type 2 diabetes and/or obesity. Mutation analyses of DNA from 84 patients with obesity and familial type 2 diabetes identified two polymorphisms, IVS3 + 68C>T and Arg72Thr, and one rare variant......, +151C>A of PYY. The common allele of the Arg72Thr variant associated with type 2 diabetes with an allele frequency of the Arg allele of 0.667 (95% CI 0.658-0.677) among 4,639 glucose-tolerant subjects and 0.692 (0.674-0.710) among 1,326 patients with type 2 diabetes (P = 0.005, odds ratio 1.19 [95% CI...... tolerance test (OGTT) (P = 0.03), an increased area under the curve for the post-OGTT plasma glucose level (P = 0.03), and a lower insulinogenic index (P = 0.01). In conclusion, the common Arg allele of the PYY Arg72Thr variant modestly associates with type 2 diabetes and with type 2 diabetes...

  11. TNF-α -308 A allele is associated with an increased risk of distant metastasis in rectal cancer patients from Southwestern China.

    Directory of Open Access Journals (Sweden)

    Zhen Li

    Full Text Available Tumor necrosis factor-α (TNF-α, an important factor in systematic inflammation, is reportedly involved in several cancer types. The TNF-α -308 G>A (rs1800629 polymorphism in the promoter region influences TNF-α production. The association between TNF-α -308 G>A polymorphism and colorectal cancer (CRC is not fully understood, especially the connections between TNF-α -308 G>A polymorphism and clinical features of CRC. In this study, TNF-α -308 G>A polymorphism was genotyped in 1140 individuals with or without CRC from Southwestern China. In case-control studies, we found no association between TNF-α -308 G>A polymorphism and CRC risk. Analysis of the correlations between TNF-α -308 G>A polymorphism and clinical features of CRC revealed that TNF-α -308 A allele was associated with higher body mass index (BMI larger tumor size, and distant tumor metastasis in all CRC patients. Notably, rectal cancer (a subtype of CRC patients with TNF-α -308 A allele had a very high risk of distant tumor metastasis [odds ratio (OR = 4.481; 95% confidence interval (CI: 2.072-9.693; P = 0.00025]. The association between TNF-α -308 A allele and distant tumor metastasis remained even significant after adjusting all clinical characteristics (OR = 7.099; 95% CI: 2.482-20.301; P = 0.000256 in rectal cancer patients. Our results suggested that TNF-α -308 A allele was significantly associated with distant tumor metastasis in rectal cancer patients.

  12. Risk allelic load in Th2 and Th3 cytokines genes as biomarker of susceptibility to HPV-16 positive cervical cancer: a case control study

    International Nuclear Information System (INIS)

    Torres-Poveda, K.; Burguete-García, A. I.; Bahena-Román, M.; Méndez-Martínez, R.; Zurita-Díaz, M. A.; López-Estrada, G.; Delgado-Romero, K.; Peralta-Zaragoza, O.; Bermúdez-Morales, V. H.; Cantú, D.; García-Carrancá, A.; Madrid-Marina, V.

    2016-01-01

    Alterations in the host cellular immune response allow persistent infections with High-Risk Human Papillomavirus (HR-HPV) and development of premalignant cervical lesions and cervical cancer (CC). Variations of immunosuppressive cytokine levels in cervix are associated with the natural history of CC. To assess the potential role of genetic host immunity and cytokines serum levels in the risk of developing CC, we conducted a case–control study paired by age. Peripheral blood samples from patients with CC (n = 200) and hospital controls (n = 200), were used to evaluate nine biallelic SNPs of six cytokine genes of the adaptive immune system by allelic discrimination and cytokines serum levels by ELISA. After analyzing the SNP association by multivariate logistic regression adjusted by age, CC history and smoking history, three Th2 cytokines (IL-4, IL-6 and IL-10) and one Th3 (TGFB1) cytokine were significantly associated with CC. Individuals with at least one copy of the following risk alleles: T of SNP (−590C > T IL-4), C of SNP (−573G > C IL-6), A of SNP (−592C > A IL-10), T of SNP (−819C > T IL-10) and T of SNP (−509C > T TGFB1), had an adjusted odds ratio (OR) of 2.08 (95 % CI 1.475–2.934, p = 0.0001), an OR of 1.70 (95 % CI 1.208–2.404, p = 0.002), an OR of 1.87 (95 % CI 1.332–2.630, p = 0.0001), an OR of 1.67 (95 % CI 1.192–2.353, p = 0.003) and an OR of 1.91 (95 % CI 1.354–2.701, p = 0.0001), respectively, for CC. The burden of carrying two or more of these risk alleles was found to have an additive effect on the risk of CC (p trend = 0.0001). Finally, the serum levels of Th2 and Th3 cytokines were higher in CC cases than the controls; whereas IFNG levels, a Th1 cytokine, were higher in controls than CC cases. The significant associations of five SNPs with CC indicate that these polymorphisms are potential candidates for predicting the risk of development of CC, representing a risk allelic load for CC and can be used as a biomarker of

  13. The type 2 diabetes risk allele of TMEM154-rs6813195 associates with decreased beta cell function in a study of 6,486 Danes.

    Directory of Open Access Journals (Sweden)

    Marie Neergaard Harder

    Full Text Available A trans-ethnic meta-analysis of type 2 diabetes genome-wide association studies has identified seven novel susceptibility variants in or near TMEM154, SSR1/RREB1, FAF1, POU5F1/TCF19, LPP, ARL15 and ABCB9/MPHOSPH9. The aim of our study was to investigate associations between these novel risk variants and type 2 diabetes and pre-diabetic traits in a Danish population-based study with measurements of plasma glucose and serum insulin after an oral glucose tolerance test in order to elaborate on the physiological impact of the variants.Case-control analyses were performed in up to 5,777 patients with type 2 diabetes and 7,956 individuals with normal fasting glucose levels. Quantitative trait analyses were performed in up to 5,744 Inter99 participants naïve to glucose-lowering medication. Significant associations between TMEM154-rs6813195 and the beta cell measures insulinogenic index and disposition index and between FAF1-rs17106184 and 2-hour serum insulin levels were selected for further investigation in additional Danish studies and results were combined in meta-analyses including up to 6,486 Danes.We confirmed associations with type 2 diabetes for five of the seven SNPs (TMEM154-rs6813195, FAF1-rs17106184, POU5F1/TCF19-rs3130501, ARL15-rs702634 and ABCB9/MPHOSPH9-rs4275659. The type 2 diabetes risk C-allele of TMEM154-rs6813195 associated with decreased disposition index (n=5,181, β=-0.042, p=0.012 and insulinogenic index (n=5,181, β=-0.032, p=0.043 in Inter99 and these associations remained significant in meta-analyses including four additional Danish studies (disposition index n=6,486, β=-0.042, p=0.0044; and insulinogenic index n=6,486, β=-0.037, p=0.0094. The type 2 diabetes risk G-allele of FAF1-rs17106184 associated with increased levels of 2-hour serum insulin (n=5,547, β=0.055, p=0.017 in Inter99 and also when combining effects with three additional Danish studies (n=6,260, β=0.062, p=0.0040.Studies of type 2 diabetes intermediary

  14. Increased NBCn1 expression, Na+/ HCO 3 ? co-transport and intracellular pH in human vascular smooth muscle cells with a risk allele for hypertension

    OpenAIRE

    Ng, Fu Liang; Boedtkjer, Ebbe; Witkowska, Kate; Ren, Meixia; Zhang, Ruoxin; Tucker, Arthur; Aalkj?r, Christian; Caulfield, Mark J.; Ye, Shu

    2017-01-01

    Abstract Genome-wide association studies have revealed an association between variation at the SLC4A7 locus and blood pressure. SLC4A7 encodes the electroneutral Na+/ HCO 3 ? co-transporter NBCn1 which regulates intracellular pH (pH i ). We conducted a functional study of variants at this locus in primary cultures of vascular smooth muscle and endothelial cells. In both cell types, we found genotype-dependent differences for rs13082711 in DNA-nuclear protein interactions, where the risk allel...

  15. Association of MMP7 -181A→G Promoter Polymorphism with Gastric Cancer Risk: INFLUENCE OF NICOTINE IN DIFFERENTIAL ALLELE-SPECIFIC TRANSCRIPTION VIA INCREASED PHOSPHORYLATION OF cAMP-RESPONSE ELEMENT-BINDING PROTEIN (CREB).

    Science.gov (United States)

    Kesh, Kousik; Subramanian, Lakshmi; Ghosh, Nillu; Gupta, Vinayak; Gupta, Arnab; Bhattacharya, Samir; Mahapatra, Nitish R; Swarnakar, Snehasikta

    2015-06-05

    Elevated expression of matrix metalloproteinase7 (MMP7) has been demonstrated to play a pivotal role in cancer invasion. The -181A→G (rs11568818) polymorphism in the MMP7 promoter modulates gene expression and possibly affects cancer progression. Here, we evaluated the impact of -181A→G polymorphism on MMP7 promoter activity and its association with gastric cancer risk in eastern Indian case-control cohorts (n = 520). The GG genotype as compared with the AA genotype was predisposed (p = 0.02; odds ratio = 1.9, 95% confidence interval = 1.1-3.3) to gastric cancer risk. Stratification analysis showed that tobacco addiction enhanced gastric cancer risk in GG subjects when compared with AA subjects (p = 0.03, odds ratio = 2.46, and 95% confidence interval = 1.07-5.68). Meta-analysis revealed that tobacco enhanced the risk for cancer more markedly in AG and GG carriers. Activity and expression of MMP7 were significantly higher in GG than in AA carriers. In support, MMP7 promoter-reporter assays showed greater transcriptional activity toward A to G transition under basal/nicotine-induced/cAMP-response element-binding protein (CREB) overexpressed conditions in gastric adenocarcinoma cells. Moreover, nicotine (a major component of tobacco) treatment significantly up-regulated MMP7 expression due to enhanced CREB phosphorylation followed by its nuclear translocation in gastric adenocarcinoma cells. Furthermore, chromatin immunoprecipitation experiments revealed higher binding of phosphorylated CREB with the -181G than the -181A allele. Altogether, specific binding of phosphorylated CREB to the G allele-carrying promoter enhances MMP7 gene expression that is further augmented by nicotine due to increased CREB phosphorylation and thereby increases the risk for gastric cancer. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21

    Science.gov (United States)

    Adoue, Véronique; Michailidou, Kyriaki; Canisius, Sander; Lemaçon, Audrey; Droit, Arnaud; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Baynes, Caroline; Blomqvist, Carl; Bogdanova, Natalia V.; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Borresen-Dale, Anne-Lise; Brand, Judith S.; Brauch, Hiltrud; Brenner, Hermann; Broeks, Annegien; Burwinkel, Barbara; Chang-Claude, Jenny; Couch, Fergus J.; Cox, Angela; Cross, Simon S.; Czene, Kamila; Darabi, Hatef; Dennis, Joe; Devilee, Peter; Dörk, Thilo; Dos-Santos-Silva, Isabel; Eriksson, Mikael; Fasching, Peter A.; Figueroa, Jonine; Flyger, Henrik; García-Closas, Montserrat; Giles, Graham G.; Goldberg, Mark S.; González-Neira, Anna; Grenaker-Alnæs, Grethe; Guénel, Pascal; Haeberle, Lothar; Haiman, Christopher A.; Hamann, Ute; Hallberg, Emily; Hooning, Maartje J.; Hopper, John L.; Jakubowska, Anna; Jones, Michael; Kabisch, Maria; Kataja, Vesa; Lambrechts, Diether; Marchand, Loic Le; Lindblom, Annika; Lubinski, Jan; Mannermaa, Arto; Maranian, Mel; Margolin, Sara; Marme, Frederik; Milne, Roger L.; Neuhausen, Susan L.; Nevanlinna, Heli; Neven, Patrick; Olswold, Curtis; Peto, Julian; Plaseska-Karanfilska, Dijana; Pylkäs, Katri; Radice, Paolo; Rudolph, Anja; Sawyer, Elinor J.; Schmidt, Marjanka K.; Shu, Xiao-Ou; Southey, Melissa C.; Swerdlow, Anthony; Tollenaar, Rob A.E.M.; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Vachon, Celine; Van Den Ouweland, Ans M. W.; Wang, Qin; Winqvist, Robert; Investigators, kConFab/AOCS; Zheng, Wei; Benitez, Javier; Chenevix-Trench, Georgia; Dunning, Alison M.; Pharoah, Paul D. P.; Kristensen, Vessela; Hall, Per; Easton, Douglas F.; Pastinen, Tomi; Nord, Silje; Simard, Jacques

    2016-01-01

    There are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, cis-acting variants represent an important source of phenotypic variation. Consequently, cis-regulatory SNPs associated with differential allelic expression are functional candidates for further investigation as disease-causing variants. To investigate whether common variants associated with differential allelic expression were involved in breast cancer susceptibility, a list of genes was established on the basis of their involvement in cancer related pathways and/or mechanisms. Thereafter, using data from a genome-wide map of allelic expression associated SNPs, 313 genetic variants were selected and their association with breast cancer risk was then evaluated in 46,451 breast cancer cases and 42,599 controls of European ancestry ascertained from 41 studies participating in the Breast Cancer Association Consortium. The associations were evaluated with overall breast cancer risk and with estrogen receptor negative and positive disease. One novel breast cancer susceptibility locus on 4q21 (rs11099601) was identified (OR = 1.05, P = 5.6x10-6). rs11099601 lies in a 135 kb linkage disequilibrium block containing several genes, including, HELQ, encoding the protein HEL308 a DNA dependant ATPase and DNA Helicase involved in DNA repair, MRPS18C encoding the Mitochondrial Ribosomal Protein S18C and FAM175A (ABRAXAS), encoding a BRCA1 BRCT domain-interacting protein involved in DNA damage response and double-strand break (DSB) repair. Expression QTL analysis in breast cancer tissue showed rs11099601 to be associated with HELQ (P = 8.28x10-14), MRPS18C (P = 1.94x10-27) and FAM175A (P = 3.83x10-3), explaining about 20%, 14% and 1%, respectively of the variance inexpression of these genes in breast carcinomas. PMID:27792995

  17. Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21.

    Science.gov (United States)

    Hamdi, Yosr; Soucy, Penny; Adoue, Véronique; Michailidou, Kyriaki; Canisius, Sander; Lemaçon, Audrey; Droit, Arnaud; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Baynes, Caroline; Blomqvist, Carl; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Borresen-Dale, Anne-Lise; Brand, Judith S; Brauch, Hiltrud; Brenner, Hermann; Broeks, Annegien; Burwinkel, Barbara; Chang-Claude, Jenny; Couch, Fergus J; Cox, Angela; Cross, Simon S; Czene, Kamila; Darabi, Hatef; Dennis, Joe; Devilee, Peter; Dörk, Thilo; Dos-Santos-Silva, Isabel; Eriksson, Mikael; Fasching, Peter A; Figueroa, Jonine; Flyger, Henrik; García-Closas, Montserrat; Giles, Graham G; Goldberg, Mark S; González-Neira, Anna; Grenaker-Alnæs, Grethe; Guénel, Pascal; Haeberle, Lothar; Haiman, Christopher A; Hamann, Ute; Hallberg, Emily; Hooning, Maartje J; Hopper, John L; Jakubowska, Anna; Jones, Michael; Kabisch, Maria; Kataja, Vesa; Lambrechts, Diether; Le Marchand, Loic; Lindblom, Annika; Lubinski, Jan; Mannermaa, Arto; Maranian, Mel; Margolin, Sara; Marme, Frederik; Milne, Roger L; Neuhausen, Susan L; Nevanlinna, Heli; Neven, Patrick; Olswold, Curtis; Peto, Julian; Plaseska-Karanfilska, Dijana; Pylkäs, Katri; Radice, Paolo; Rudolph, Anja; Sawyer, Elinor J; Schmidt, Marjanka K; Shu, Xiao-Ou; Southey, Melissa C; Swerdlow, Anthony; Tollenaar, Rob A E M; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Vachon, Celine; Van Den Ouweland, Ans M W; Wang, Qin; Winqvist, Robert; Zheng, Wei; Benitez, Javier; Chenevix-Trench, Georgia; Dunning, Alison M; Pharoah, Paul D P; Kristensen, Vessela; Hall, Per; Easton, Douglas F; Pastinen, Tomi; Nord, Silje; Simard, Jacques

    2016-12-06

    There are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, cis-acting variants represent an important source of phenotypic variation. Consequently, cis-regulatory SNPs associated with differential allelic expression are functional candidates for further investigation as disease-causing variants. To investigate whether common variants associated with differential allelic expression were involved in breast cancer susceptibility, a list of genes was established on the basis of their involvement in cancer related pathways and/or mechanisms. Thereafter, using data from a genome-wide map of allelic expression associated SNPs, 313 genetic variants were selected and their association with breast cancer risk was then evaluated in 46,451 breast cancer cases and 42,599 controls of European ancestry ascertained from 41 studies participating in the Breast Cancer Association Consortium. The associations were evaluated with overall breast cancer risk and with estrogen receptor negative and positive disease. One novel breast cancer susceptibility locus on 4q21 (rs11099601) was identified (OR = 1.05, P = 5.6x10-6). rs11099601 lies in a 135 kb linkage disequilibrium block containing several genes, including, HELQ, encoding the protein HEL308 a DNA dependant ATPase and DNA Helicase involved in DNA repair, MRPS18C encoding the Mitochondrial Ribosomal Protein S18C and FAM175A (ABRAXAS), encoding a BRCA1 BRCT domain-interacting protein involved in DNA damage response and double-strand break (DSB) repair. Expression QTL analysis in breast cancer tissue showed rs11099601 to be associated with HELQ (P = 8.28x10-14), MRPS18C (P = 1.94x10-27) and FAM175A (P = 3.83x10-3), explaining about 20%, 14% and 1%, respectively of the variance inexpression of these genes in breast carcinomas.

  18. Common genetic variants associated with thyroid function may be risk alleles for Hashimoto's disease and Graves' disease.

    Science.gov (United States)

    Campbell, Purdey; Brix, Thomas H; Wilson, Scott G; Ward, Lynley C; Hui, Jennie; Beilby, John P; Hegedüs, Laszlo; Walsh, John P

    2015-02-14

    Recent studies have identified common genetic variants associated with TSH, free T4 and thyroid peroxidase antibodies, but it is unclear whether these differ between patients with Hashimoto's disease and Graves' disease. To examine whether 11 common genetic variants differ between Graves' disease and Hashimoto's disease. We genotyped 11 common variants in a discovery cohort of 203 Australian patients with autoimmune thyroid disease (AITD). Two variants with significant or suggestive associations were analysed in a replication cohort of 384 Danish patients. For rs753760 (PDE10A), the minor allele frequency in Graves' disease and Hashimoto's disease was 0·38 vs. 0·23, respectively, (P = 6·42 × 10 -4 ) in the discovery cohort, 0·29 vs. 0·24 (P = 0·147) in the replication cohort and 0·32 vs. 0·24 in combined analysis (P = 0·0021; all analyses adjusted for sex). In healthy controls from Busselton, the frequency was 0·29, significantly different from Hashimoto's disease but not Graves' disease. For rs4889009 (MAF gene region), the frequency of the minor G-allele in Graves' disease and Hashimoto's disease was 0·48 vs. 0·36 (P = 0·0156) in the discovery cohort, 0·48 vs. 0·34 (P = 1·83 × 10 -4 ) in the replication cohort and 0·48 vs. 0·35 in the combined analysis (P = 7·53 × 10 -6 ); in controls, the frequency was 0·38, significantly different from Graves' disease but not Hashimoto's disease. After further adjustment for smoking, associations with rs4889009 remained significant, whereas those with rs753760 were not. Common variants in PDE10A and MAF gene regions may influence whether patients with AITD develop Graves' disease or Hashimoto's disease. © 2015 John Wiley & Sons Ltd.

  19. SCREENING LOW FREQUENCY SNPS FROM GENOME WIDE ASSOCIATION STUDY REVEALS A NEW RISK ALLELE FOR PROGRESSION TO AIDS

    Science.gov (United States)

    Le Clerc, Sigrid; Coulonges, Cédric; Delaneau, Olivier; Van Manen, Danielle; Herbeck, Joshua T.; Limou, Sophie; An, Ping; Martinson, Jeremy J.; Spadoni, Jean-Louis; Therwath, Amu; Veldink, Jan H.; van den Berg, Leonard H.; Taing, Lieng; Labib, Taoufik; Mellak, Safa; Montes, Matthieu; Delfraissy, Jean-François; Schächter, François; Winkler, Cheryl; Froguel, Philippe; Mullins, James I.; Schuitemaker, Hanneke; Zagury, Jean-François

    2011-01-01

    Background Seven genome-wide association studies (GWAS) have been published in AIDS and only associations in the HLA region on chromosome 6 and CXCR6 have passed genome-wide significance. Methods We reanalyzed the data from three previously published GWAS, targeting specifically low frequency SNPs (minor allele frequency (MAF)<5%). Two groups composed of 365 slow progressors (SP) and 147 rapid progressors (RP) from Europe and the US were compared with a control group of 1394 seronegative individuals using Eigenstrat corrections. Results Of the 8584 SNPs with MAF<5% in cases and controls (Bonferroni threshold=5.8×10−6), four SNPs showed statistical evidence of association with the SP phenotype. The best result was for HCP5 rs2395029 (p=8.54×10−15, OR=3.41) in the HLA locus, in partial linkage disequilibrium with two additional chromosome 6 associations in C6orf48 (p=3.03×10−10, OR=2.9) and NOTCH4 (9.08×10−07, OR=2.32). The fourth association corresponded to rs2072255 located in RICH2 (p=3.30×10−06, OR=0.43) in chromosome 17. Using HCP5 rs2395029 as a covariate, the C6orf48 and NOTCH4 signals disappeared, but the RICH2 signal still remained significant. Conclusion Besides the already known chromosome 6 associations, the analysis of low frequency SNPs brought up a new association in the RICH2 gene. Interestingly, RICH2 interacts with BST-2 known to be a major restriction factor for HIV-1 infection. Our study has thus identified a new candidate gene for AIDS molecular etiology and confirms the interest of singling out low frequency SNPs in order to exploit GWAS data. PMID:21107268

  20. Supporting Risk Assessment: Accounting for Indirect Risk to Ecosystem Components.

    Directory of Open Access Journals (Sweden)

    Cathryn Clarke Murray

    Full Text Available The multi-scalar complexity of social-ecological systems makes it challenging to quantify impacts from human activities on ecosystems, inspiring risk-based approaches to assessments of potential effects of human activities on valued ecosystem components. Risk assessments do not commonly include the risk from indirect effects as mediated via habitat and prey. In this case study from British Columbia, Canada, we illustrate how such "indirect risks" can be incorporated into risk assessments for seventeen ecosystem components. We ask whether (i the addition of indirect risk changes the at-risk ranking of the seventeen ecosystem components and if (ii risk scores correlate with trophic prey and habitat linkages in the food web. Even with conservative assumptions about the transfer of impacts or risks from prey species and habitats, the addition of indirect risks in the cumulative risk score changes the ranking of priorities for management. In particular, resident orca, Steller sea lion, and Pacific herring all increase in relative risk, more closely aligning these species with their "at-risk status" designations. Risk assessments are not a replacement for impact assessments, but-by considering the potential for indirect risks as we demonstrate here-they offer a crucial complementary perspective for the management of ecosystems and the organisms within.

  1. Supporting Risk Assessment: Accounting for Indirect Risk to Ecosystem Components

    Science.gov (United States)

    Mach, Megan E.; Martone, Rebecca G.; Singh, Gerald G.; O, Miriam; Chan, Kai M. A.

    2016-01-01

    The multi-scalar complexity of social-ecological systems makes it challenging to quantify impacts from human activities on ecosystems, inspiring risk-based approaches to assessments of potential effects of human activities on valued ecosystem components. Risk assessments do not commonly include the risk from indirect effects as mediated via habitat and prey. In this case study from British Columbia, Canada, we illustrate how such “indirect risks” can be incorporated into risk assessments for seventeen ecosystem components. We ask whether (i) the addition of indirect risk changes the at-risk ranking of the seventeen ecosystem components and if (ii) risk scores correlate with trophic prey and habitat linkages in the food web. Even with conservative assumptions about the transfer of impacts or risks from prey species and habitats, the addition of indirect risks in the cumulative risk score changes the ranking of priorities for management. In particular, resident orca, Steller sea lion, and Pacific herring all increase in relative risk, more closely aligning these species with their “at-risk status” designations. Risk assessments are not a replacement for impact assessments, but—by considering the potential for indirect risks as we demonstrate here—they offer a crucial complementary perspective for the management of ecosystems and the organisms within. PMID:27632287

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

    Science.gov (United States)

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

    2014-01-01

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

  3. Supporting At-Risk Learners: Introduction

    Science.gov (United States)

    Hutchinson, Nancy

    2015-01-01

    In its final report, the At-risk Working Group, which reported to the Ontario Minister of Education, described at-risk secondary students as performing significantly below the provincial standard, failing to meet curriculum expectations, and being disengaged from school (O'Connor, 2003, p. 5). In this special issue, authors examine this topic,…

  4. Risk assessment in support of plant health

    DEFF Research Database (Denmark)

    Jeger, Michael; Schans, Jan; Lövei, Gabor L.

    2012-01-01

    environmental risk assessment and the evaluation of risk reducing options. Quantitative approaches have become increasingly important during this time. The Panel has developed such methods in climatic mapping (in association with the Joint Research Councils), application of spatial spread models, re......With the establishment of the Plant Health Panel in 2006, EFSA became the body responsible for risk assessment in the plant health area for the European Union (EU). Since then more than 70 outputs have been produced dealing with the full range of organisms harmful to plant health across all crop...... types and plants in the environment. There has been an increasing trend towards producing scientific opinions which are full pest risk assessments for the whole EU territory. In its work, and as a contribution to the wider development of risk assessment methodology, the Panel has developed a series...

  5. Supporting risk-informed decisions during business process execution

    NARCIS (Netherlands)

    Conforti, R.; Leoni, de M.; La Rosa, M.; Aalst, van der W.M.P.; Salinesi, C.; Norrie, M.C.; Pastor, O.

    2013-01-01

    This paper proposes a technique that supports process participants in making risk-informed decisions, with the aim to reduce the process risks. Risk reduction involves decreasing the likelihood and severity of a process fault from occurring. Given a process exposed to risks, e.g. a financial process

  6. Apolipoprotein B levels, APOB alleles, and risk of ischemic cardiovascular disease in the general population, a review

    DEFF Research Database (Denmark)

    Benn, Marianne

    2009-01-01

    capturing the entire variation in APOB cannot be identified, and thus most polymorphisms must be evaluated separately in association studies; (3) APOB mutations and polymorphisms are associated with a range of apolipoprotein B and LDL cholesterol levels, although the magnitude of effect sizes of common...... for the E4154K polymorphism that possibly predicts a reduction in risk of ischemic cerebrovascular disease and ischemic stroke, common APOB polymorphisms with modest effect sizes on lipid levels do not predict risk of ischemic heart disease, myocardial infarction, ischemic cerebrovascular disease...

  7. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

    DEFF Research Database (Denmark)

    Lawrenson, Kate; Kar, Siddhartha; McCue, Karen

    2016-01-01

    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10(-20)), ER......'-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk....

  8. Fatigue risks in the connections of sign support structures.

    Science.gov (United States)

    2013-05-01

    This research effort develops a reliability-based approach for prescribing inspection intervals for mast-arm sign support : structures corresponding to user-specified levels of fatigue-induced fracture risk. The resulting level of risk for a : partic...

  9. Type 2 diabetes risk alleles near ADCY5, CDKAL1 and HHEX-IDE are associated with reduced birthweight

    DEFF Research Database (Denmark)

    Andersson, E A; Pilgaard, K; Pisinger, C

    2010-01-01

    The fetal insulin hypothesis suggests that variation in the fetal genotype influencing insulin secretion or action may predispose to low birthweight and type 2 diabetes. We examined associations between 25 confirmed type 2 diabetes risk variants and birthweight in individuals from the Danish Inte...

  10. A Common LPA Null Allele Associates With Lower Lipoprotein(a) Levels and Coronary Artery Disease Risk

    NARCIS (Netherlands)

    Kyriakou, Theodosios; Seedorf, Udo; Goel, Anuj; Hopewell, Jemma C.; Clarke, Robert; Watkins, Hugh; Farrall, Martin; van der Hout, A.H.

    Objective-Increased levels of lipoprotein(a) are a highly heritable risk factor for coronary artery disease (CAD). The genetic determinants of lipoprotein(a) levels are mainly because of genetic variation in the apolipoprotein(a) gene (LPA). We have tested the association of a relatively common null

  11. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

    NARCIS (Netherlands)

    K. Lawrenson (Kate); S. Kar (Siddhartha); K. McCue (Karen); Kuchenbaeker, K. (Karoline); K. Michailidou (Kyriaki); J.P. Tyrer (Jonathan); J. Beesley (Jonathan); S.J. Ramus (Susan); Li, Q. (Qiyuan); Delgado, M.K. (Melissa K.); J.M. Lee (Janet M.); K. Aittomäki (Kristiina); I.L. Andrulis (Irene); H. Anton-Culver (Hoda); Arndt, V. (Volker); B.K. Arun (Banu); B. Arver (Brita Wasteson); E.V. Bandera (Elisa); M. Barile (Monica); Barkardottir, R.B. (Rosa B.); D. Barrowdale (Daniel); M.W. Beckmann (Matthias); J. Benítez (Javier); A. Berchuck (Andrew); M. Bisogna (Maria); L. Bjorge (Line); C. Blomqvist (Carl); W.J. Blot (William); N.V. Bogdanova (Natalia); Bojesen, A. (Anders); S.E. Bojesen (Stig); M.K. Bolla (Manjeet K.); B. Bonnani (Bernardo); A.-L. Borresen-Dale (Anne-Lise); H. Brauch (Hiltrud); P. Brennan (Paul); H. Brenner (Hermann); F. Bruinsma (Fiona); J. Brunet (Joan); S.A.B.S. Buhari (Shaik Ahmad Bin Syed); B. Burwinkel (Barbara); R. Butzow (Ralf); S.S. Buys (Saundra); Q. Cai (Qiuyin); T. Caldes (Trinidad); I. Campbell (Ian); Canniotto, R. (Rikki); J. Chang-Claude (Jenny); Chiquette, J. (Jocelyne); Choi, J.-Y. (Ji-Yeob); K.B.M. Claes (Kathleen B.M.); L.S. Cook (Linda S.); A. Cox (Angela); D.W. Cramer (Daniel); S.S. Cross (Simon); C. Cybulski (Cezary); K. Czene (Kamila); M.B. Daly (Mary B.); F. Damiola (Francesca); A. Dansonka-Mieszkowska (Agnieszka); H. Darabi (Hatef); J. Dennis (Joe); P. Devilee (Peter); O. Díez (Orland); J.A. Doherty (Jennifer A.); S.M. Domchek (Susan); C.M. Dorfling (Cecilia); T. Dörk (Thilo); M. Dumont (Martine); H. Ehrencrona (Hans); B. Ejlertsen (Bent); S.D. Ellis (Steve); C. Engel (Christoph); E. Lee (Eunjung); Evans, D.G. (D. Gareth); P.A. Fasching (Peter); L. Feliubadaló (L.); J.D. Figueroa (Jonine); D. Flesch-Janys (Dieter); O. Fletcher (Olivia); H. Flyger (Henrik); L. Foretova (Lenka); F. Fostira (Florentia); W.D. Foulkes (William); B.L. Fridley (Brooke); E. Friedman (Eitan); D. Frost (Debra); Gambino, G. (Gaetana); P.A. Ganz (Patricia A.); J. Garber (Judy); M. García-Closas (Montserrat); A. Gentry-Maharaj (Aleksandra); M. Ghoussaini (Maya); G.G. Giles (Graham); R. Glasspool (Rosalind); A.K. Godwin (Andrew K.); M.S. Goldberg (Mark); D. Goldgar (David); A. González-Neira (Anna); E.L. Goode (Ellen); M.T. Goodman (Marc); M.H. Greene (Mark H.); J. Gronwald (Jacek); P. Guénel (Pascal); C.A. Haiman (Christopher A.); P. Hall (Per); Hallberg, E. (Emily); U. Hamann (Ute); T.V.O. Hansen (Thomas); P. harrington (Patricia); J.M. Hartman (Joost); N. Hassan (Norhashimah); S. Healey (Sue); P.U. Heitz; J. Herzog (Josef); E. Høgdall (Estrid); C.K. Høgdall (Claus); F.B.L. Hogervorst (Frans); A. Hollestelle (Antoinette); J.L. Hopper (John); P.J. Hulick (Peter); T. Huzarski (Tomasz); E.N. Imyanitov (Evgeny); C. Isaacs (Claudine); H. Ito (Hidemi); A. Jakubowska (Anna); R. Janavicius (Ramunas); A. Jensen (Allan); E.M. John (Esther); Johnson, N. (Nichola); M. Kabisch (Maria); D. Kang (Daehee); M.K. Kapuscinski (Miroslav K.); Karlan, B.Y. (Beth Y.); S. Khan (Sofia); L.A.L.M. Kiemeney (Bart); M. Kjaer (Michael); J.A. Knight (Julia); I. Konstantopoulou (I.); V-M. Kosma (Veli-Matti); V. Kristensen (Vessela); J. Kupryjanczyk (Jolanta); A. Kwong (Ava); M. de La Hoya (Miguel); Y. Laitman (Yael); Lambrechts, D. (Diether); N.D. Le (Nhu D.); K. De Leeneer (Kim); K.J. Lester (Kathryn); D.A. Levine (Douglas); J. Li (Jingmei); A. Lindblom (Annika); J. Long (Jirong); A. Lophatananon (Artitaya); J.T. Loud (Jennifer); K.H. Lu (Karen); J. Lubinski (Jan); A. Mannermaa (Arto); S. Manoukian (Siranoush); L. Le Marchand (Loic); S. Margolin (Sara); F. Marme (Frederick); L.F. Massuger (Leon); K. Matsuo (Keitaro); S. Mazoyer (Sylvie); L. McGuffog (Lesley); C.A. McLean (Catriona Ann); I. McNeish (Iain); A. Meindl (Alfons); U. Menon (Usha); Mensenkamp, A.R. (Arjen R.); R.L. Milne (Roger); M. Montagna (Marco); K.B. Moysich (Kirsten); K.R. Muir (K.); A.-M. Mulligan (Anna-Marie); K.L. Nathanson (Katherine); R.B. Ness (Roberta); S.L. Neuhausen (Susan); H. Nevanlinna (Heli); S. Nord (Silje); R.L. Nussbaum (Robert L.); K. Odunsi (Kunle); K. Offit (Kenneth); E. Olah; O.I. Olopade (Olufunmilayo I.); J.E. Olson (Janet); C. Olswold (Curtis); D.M. O'Malley (David M.); I. Orlow (Irene); N. Orr (Nick); A. Osorio (Ana); Park, S.K. (Sue Kyung); C.L. Pearce (Celeste); T. Pejovic (Tanja); P. Peterlongo (Paolo); G. Pfeiler (Georg); C. Phelan (Catherine); E.M. Poole (Elizabeth); K. Pykäs (Katri); P. Radice (Paolo); J. Rantala (Johanna); M.U. Rashid (Muhammad); G. Rennert (Gad); V. Rhenius (Valerie); K. Rhiem (Kerstin); H. Risch (Harvey); G.C. Rodriguez (Gustavo); M.A. Rossing (Mary Anne); Rudolph, A. (Anja); H.B. Salvesen (Helga); Sangrajrang, S. (Suleeporn); Sawyer, E.J. (Elinor J.); J.M. Schildkraut (Joellen); M.K. Schmidt (Marjanka); R.K. Schmutzler (Rita); T.A. Sellers (Thomas A.); C.M. Seynaeve (Caroline); Shah, M. (Mitul); C.-Y. Shen (Chen-Yang); X.-O. Shu (Xiao-Ou); W. Sieh (Weiva); C.F. Singer (Christian); O. Sinilnikova (Olga); S. Slager (Susan); H. Song (Honglin); Soucy, P. (Penny); M.C. Southey (Melissa); M. Stenmark-Askmalm (Marie); D. Stoppa-Lyonnet (Dominique); C. Sutter (Christian); A.J. Swerdlow (Anthony ); Tchatchou, S. (Sandrine); P.J. Teixeira; S.-H. Teo (Soo-Hwang); K.L. Terry (Kathryn); M.B. Terry (Mary Beth); M. Thomassen (Mads); M.G. Tibiletti (Maria Grazia); L. Tihomirova (Laima); S. Tognazzo (Silvia); A.E. Toland (Amanda); I.P. Tomlinson (Ian); D. Torres (Diana); T. Truong (Thérèse); C.-C. Tseng (Chiu-Chen); N. Tung (Nadine); Tworoger, S.S. (Shelley S.); C. Vachon (Celine); Van Den Ouweland, A.M.W. (Ans M.W.); Van Doorn, H.C. (Helena C.); E.J. van Rensburg (Elizabeth); L.J. van 't Veer (Laura); A. Vanderstichele (Adriaan); I. Vergote (Ignace); J. Vijai (Joseph); Wang, Q. (Qin); S. Wang-Gohrke (Shan); J.N. Weitzel (Jeffrey); N. Wentzensen (N.); A.S. Whittemore (Alice); H. Wildiers (Hans); R. Winqvist (Robert); A.H. Wu (Anna); Yannoukakos, D. (Drakoulis); S.-Y. Yoon (Sook-Yee); J-C. Yu (Jyh-Cherng); W. Zheng (Wei); Y. Zheng (Ying); Khanna, K.K. (Kum Kum); J. Simard (Jacques); A.N.A. Monteiro (Alvaro N.); J.D. French (Juliet); F.J. Couch (Fergus); M. Freedman (Matthew); D.F. Easton (Douglas F.); A.M. Dunning (Alison); P.D.P. Pharoah (Paul); S.L. Edwards (Stacey); G. Chenevix-Trench (Georgia); A.C. Antoniou (Antonis C.); S.A. Gayther (Simon); D. Bowtell (David); A. DeFazio (Anna); P. Webb (Penny); M.-A. Collonge-Rame; Damette, A. (Alexandre); E. Barouk-Simonet (Emmanuelle); F. Bonnet (Françoise); V. Bubien (Virginie); N. Sevenet (Nicolas); M. Longy (Michel); P. Berthet (Pascaline); D. Vaur (Dominique); L. Castera (Laurent); S.F. Ferrer; Y.-J. Bignon (Yves-Jean); N. Uhrhammer (Nancy); F. Coron (Fanny); L. Faivre (Laurence); Baurand, A. (Amandine); Jacquot, C. (Caroline); Bertolone, G. (Geoffrey); Lizard, S. (Sarab); D. Leroux (Dominique); H. Dreyfus (Hélène); C. Rebischung (Christine); Peysselon, M. (Magalie); J.-P. Peyrat; J. Fournier (Joëlle); F. Révillion (Françoise); C. Adenis (Claude); L. Vénat-Bouvet (Laurence); M. Léone (Mélanie); N. Boutry-Kryza (N.); A. Calender (Alain); S. Giraud (Sophie); C. Verny-Pierre (Carole); C. Lasset (Christine); V. Bonadona (Valérie); Barjhoux, L. (Laure); H. Sobol (Hagay); V. Bourdon (Violaine); Noguchi, T. (Tetsuro); A. Remenieras (Audrey); I. Coupier (Isabelle); P. Pujol (Pascal); J. Sokolowska (Johanna); M. Bronner (Myriam); C.D. Delnatte (Capucine); Bézieau, S. (Stéphane); Mari, V. (Véronique); M. Gauthier-Villars (Marion); B. Buecher (Bruno); E. Rouleau (Etienne); L. Golmard (Lisa); V. Moncoutier (Virginie); M. Belotti (Muriel); A. de Pauw (Antoine); Elan, C. (Camille); Fourme, E. (Emmanuelle); Birot, A.-M. (Anne-Marie); Saule, C. (Claire); Laurent, M. (Maïté); C. Houdayer (Claude); F. Lesueur (Fabienne); N. Mebirouk (Noura); F. Coulet (Florence); C. Colas (Chrystelle); F. Soubrier; Warcoin, M. (Mathilde); F. Prieur (Fabienne); M. Lebrun (Marine); C. Kientz (Caroline); D.W. Muller (Danièle); J.P. Fricker (Jean Pierre); C. Toulas (Christine); R. Guimbaud (Rosine); L. Gladieff (Laurence); V. Feillel (Viviane); I. Mortemousque (Isabelle); B. Bressac-de Paillerets (Brigitte); O. Caron (Olivier); M. Guillaud-Bataille (Marine); H. Gregory (Helen); Z. Miedzybrodzka (Zosia); P.J. Morrison (Patrick); A. Donaldson (Alan); M.T. Rogers (Mark); M.J. Kennedy (John); M.E. Porteous (Mary); A. Brady (A.); J. Barwell (Julian); Foo, C. (Claire); F. Lalloo (Fiona); L. Side (Lucy); J. Eason (Jacqueline); Henderson, A. (Alex); L.J. Walker (Lisa); J. Cook (Jackie); Snape, K. (Katie); A. Murray (Alexandra); E. McCann (Emma); M.A. Rookus (Matti); F.E. van Leeuwen (F.); L. van der Kolk (Lizet); M.K. Schmidt (Marjanka); N.S. Russell (Nicola); J.L. de Lange (J.); Wijnands, R.; J.M. Collée (Margriet); M.J. Hooning (Maartje); Seynaeve, C.; C.H.M. van Deurzen (Carolien); A.I.M. Obdeijn (Inge-Marie); C.J. van Asperen (Christi); R.A.E.M. Tollenaar (Rob); T.C.T.E.F. van Cronenburg; C.M. Kets; M.G.E.M. Ausems (Margreet); C. van der Pol (Carmen); T.A.M. van Os (Theo); Q. Waisfisz (Quinten); E.J. Meijers-Heijboer (Hanne); E.B. Gómez García (Encarna); J.C. Oosterwijk (Jan); M.J. Mourits (Marjan); G.H. de Bock (Geertruida); H. Vasen (Hans); Siesling, S.; Verloop, J.; L.I.H. Overbeek (Lucy); S.B. Fox (Stephen); J. Kirk (Judy); G.J. Lindeman; M. Price (Melanie)

    2016-01-01

    textabstractA locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 ×

  12. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

    DEFF Research Database (Denmark)

    Lawrenson, Kate; Kar, Siddhartha; McCue, Karen

    2016-01-01

    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10(-20)), ER-n...

  13. The apolipoprotein E epsilon4-allele and antihypertensive treatment are associated with increased risk of cerebral MRI white matter hyperintensities

    DEFF Research Database (Denmark)

    Høgh, P; Garde, Ellen; Mortensen, Erik Lykke

    2007-01-01

    ) in a community-based sample of elderly subjects. MATERIALS AND METHODS: From a cohort of 976 subjects born in 1914, APOE genotype was determined and MRI examinations were carried out in 75 subjects. WMH were rated using a standard semi-quantitative method. ANOVA and regression analyses were conducted to explore...... the relative importance of the potential risk factors. RESULTS: APOE genotype and antihypertensive treatment were significantly associated with severity of total WMH load (P Pharmaceutical treatment for arterial...

  14. Cytotoxic T lymphocyte-Associated Antigen +49G Variant Confers Risk for Anti-CCP- and Rheumatoid Factor-Positive Type of Rheumatoid Arthritis Only in Combination with CT60∗G Allele

    Directory of Open Access Journals (Sweden)

    Bernadett Farago

    2010-01-01

    Full Text Available Controversial observations have been published on the association of the cytotoxic T lymphocyte associated antigen gene's variants with rheumatoid arthritis (RA. After genotyping 428 patients and 230 matched controls, the prevalence of the CT60∗G allele was more frequent in RF- and/or anti-CCP-seropositive RApatients, compared to the healthy controls (P<.001. Regression analysis revealed that the CT60∗G allele is a possible predisposing factor for RA in these subgroups. No accumulation of the +49∗G allele was found among patients, and this variant was not found to correlate with RA. Assaying the possible genotype variations, the +49∗G-CT60∗G allelic combination was accumulated in seropositive RA-subtypes, and was associated with the risk of RA (OR=1.73, P=.001 for the whole RA-population. Although the +49∗G allele did not mean a predisposition to RA alone, in combination with CT60∗G it, also conferred risk, suggesting that the +49A/G variant is associated with the risk of RA only in certain haplotypes.

  15. Delimiting Allelic Imbalance of TYMS by Allele-Specific Analysis.

    Science.gov (United States)

    Balboa-Beltrán, Emilia; Cruz, Raquel; Carracedo, Angel; Barros, Francisco

    2015-07-01

    Allelic imbalance of thymidylate synthase (TYMS) is attributed to polymorphisms in the 5'- and 3'-untranslated region (UTR). These polymorphisms have been related to the risk of suffering different cancers, for example leukemia, breast or gastric cancer, and response to different drugs, among which are methotrexate glutamates, stavudine, and specifically 5-fluorouracil (5-FU), as TYMS is its direct target. A vast literature has been published in relation to 5-FU, even suggesting the sole use of these polymorphisms to effectively manage 5-FU dosage. Estimates of the extent to which these polymorphisms influence in TYMS expression have in the past been based on functional analysis by luciferase assays and quantification of TYMS mRNA, but both these studies, as the association studies with cancer risk or with toxicity or response to 5-FU, are very contradictory. Regarding functional assays, the artificial genetic environment created in luciferase assay and the problems derived from quantitative polymerase chain reactions (qPCRs), for example the use of a reference gene, may have distorted the results. To avoid these sources of interference, we have analyzed the allelic imbalance of TYMS by allelic-specific analysis in peripheral blood mononuclear cells (PBMCs) from patients.Allelic imbalance in PBMCs, taken from 40 patients with suspected myeloproliferative haematological diseases, was determined by fluorescent fragment analysis (for the 3'-UTR polymorphism), Sanger sequencing and allelic-specific qPCR in multiplex (for the 5'-UTR polymorphisms).For neither the 3'- nor the 5'-UTR polymorphisms did the observed allelic imbalance exceed 1.5 fold. None of the TYMS polymorphisms is statistically associated with allelic imbalance.The results acquired allow us to deny the previously established assertion of an influence of 2 to 4 fold of the rs45445694 and rs2853542 polymorphisms in the expression of TYMS and narrow its allelic imbalance to 1.5 fold, in our population

  16. Quantitative Relationship Between Cumulative Risk Alleles Based on Genome-Wide Association Studies and Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis

    Directory of Open Access Journals (Sweden)

    Satoru Kodama

    2018-01-01

    Full Text Available Many epidemiological studies have assessed the genetic risk of having undiagnosed or of developing type 2 diabetes mellitus (T2DM using several single nucleotide polymorphisms (SNPs based on findings of genome-wide association studies (GWAS. However, the quantitative association of cumulative risk alleles (RAs of such SNPs with T2DM risk has been unclear. The aim of this meta-analysis is to review the strength of the association between cumulative RAs and T2DM risk. Systematic literature searches were conducted for cross-sectional or longitudinal studies that examined odds ratios (ORs for T2DM in relation to genetic profiles. Logarithm of the estimated OR (log OR of T2DM for 1 increment in RAs carried (1-ΔRA in each study was pooled using a random-effects model. There were 46 eligible studies that included 74,880 cases among 249,365 participants. In 32 studies with a cross-sectional design, the pooled OR for T2DM morbidity for 1-ΔRA was 1.16 (95% confidence interval [CI], 1.13–1.19. In 15 studies that had a longitudinal design, the OR for incident T2DM was 1.10 (95% CI, 1.08–1.13. There was large heterogeneity in the magnitude of log OR (P < 0.001 for both cross-sectional studies and longitudinal studies. The top 10 commonly used genes significantly explained the variance in the log OR (P = 0.04 for cross-sectional studies; P = 0.006 for longitudinal studies. The current meta-analysis indicated that carrying 1-ΔRA in T2DM-associated SNPs was associated with a modest risk of prevalent or incident T2DM, although the heterogeneity in the used genes among studies requires us to interpret the results with caution.

  17. US EPA's Ecological Risk Assessment Support Center ...

    Science.gov (United States)

    BackgroundThe ERASC provides technical information and addresses scientific questions of concern or interest on topics relevant to ecological risk assessment at hazardous waste sites for EPA's Office of Solid Waste and Emergency Response (OSWER) personnel and the Office of Resource Conservation and Recovery (ORCR) staff. Requests are channeled to ERASC through the Ecological Risk Assessment Forum (ERAF). To assess emerging and complex scientific issues that require expert judgment, the ERASC relies on the expertise of scientists and engineers located throughout EPA's Office of Research and Development (ORD) labs and centers.ResponseERASC develops responses that reflect the state of the science for ecological risk assessment and also provides a communication point for the distribution of the responses to other interested parties. For further information, contact Ecology_ERASC@epa.gov or call 513-569-7940.

  18. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

    OpenAIRE

    Lawrenson, Kate; Kar, Siddhartha; McCue, Karen; Kuchenbaeker, Karoline; Michailidou, Kyriaki; Tyrer, Jonathan; Beesley, Jonathan; Ramus, Susan J.; Li, Qiyuan; Delgado, Melissa K.; Lee, Janet M.; Aittomaki, Kristiina; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker

    2016-01-01

    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10−20), ER-negative BC (P=1.1 × 10−13), BRCA1-associated BC (P=7.7 × 10−16) and triple negative BC (P-diff=2 × 10−5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10...

  19. Allelic variation at the 8q23.3 colorectal cancer risk locus functions as a cis-acting regulator of EIF3H.

    Directory of Open Access Journals (Sweden)

    Alan M Pittman

    2010-09-01

    Full Text Available Common genetic variation at human 8q23.3 is significantly associated with colorectal cancer (CRC risk. To elucidate the basis of this association we compared the frequency of common variants at 8q23.3 in 1,964 CRC cases and 2,081 healthy controls. Reporter gene studies showed that the single nucleotide polymorphism rs16888589 acts as an allele-specific transcriptional repressor. Chromosome conformation capture (3C analysis demonstrated that the genomic region harboring rs16888589 interacts with the promoter of gene for eukaryotic translation initiation factor 3, subunit H (EIF3H. We show that increased expression of EIF3H gene increases CRC growth and invasiveness thereby providing a biological mechanism for the 8q23.3 association. These data provide evidence for a functional basis for the non-coding risk variant rs16888589 at 8q23.3 and provides novel insight into the etiological basis of CRC.

  20. Increased NBCn1 expression, Na+/HCO3 co-transport and intracellular pH in human vascular smooth muscle cells with a risk allele for hypertension

    DEFF Research Database (Denmark)

    Ng, Fu Liang; Boedtkjer, Ebbe; Witkowska, Katarzyna

    2017-01-01

    cultures of vascular smooth muscle and endothelial cells. In both cell types, we found genotype-dependent differences for rs13082711 in DNA-nuclear protein interactions, where the risk allele is associated with increased SLC4A7 expression level, NBCn1 availability and function as reflected in elevated...

  1. Relationship between New Allelic Types of Helicobacter pylori vacA Gene and cagA Status and Risk of GU or DU in Iran

    Directory of Open Access Journals (Sweden)

    S Bakhti

    2015-09-01

    Full Text Available Background & objectives: Several studies have described VacA and CagA as the two important virulence determinants of Helicobacter pylori, which are associated with gastric ulcer (GU and duodenal ulcer (DU. The aim of present study was to determine the associations of the i and d regions genotypes of H. pylori vacA gene and cagA status with GU and DU risk. Methods: A total of 177 isolates were cultured from the biopsies of Iranian patients with different geographic origins and genotyped. Data were collected and analyzed. Results: Frequency of the vacA i1, i2, i1i2, d1, and d2 alleles and cagA in all patients was 42.9%, 55.4%, 1.7%, 41.8%, 58.2% and 68.4%, respectively. There was a significant difference between the frequencies of vacA i1 in isolates from GU than those from non-atrophic gastritis (p<0.05. When the GU was considered as a dependant factor by the multiple logistic regression analysis, the vacA i1 genotype was significantly associated with the age- and sex-adjusted risk for GU (p=0.006, odds ratio [OR]=3.56 95% confidence interval [CI]=1.45–8.75. Statistical analysis showed no significant association between vacA d genotype and digestive diseases. After controlling for age and sex variables, the cagA genotype remained in the final model when the DU was considered as a dependant factor by the the multiple logistic regression analysis (p=0.021, OR=3.77 95% CI=1.22-11.60. Conclusion: We have proposed that the H. pylori vacA i1 and cagA genotypes could be considered as benefit biomarkers for prediction of risk of GU and DU in Iran, respectively.

  2. Screening of the GPX3 gene identifies the "T" allele of the SNP -861A/T as a risk for ischemic stroke in young Asian Indians.

    Science.gov (United States)

    Akhter, Mohammad S; Biswas, Arijit; Rashid, Hina; Devi, Luxmi; Behari, Madhuri; Saxena, Renu

    2014-09-01

    Deficiency of plasma glutathione peroxidase (GPx-3) has been associated with platelet-dependent thrombosis. Single-nucleotide polymorphisms (SNPs) in the promoter region of GPX3 gene have been found associated with the risk for ischemic stroke in Caucasian populations. The aim of our present study was to evaluate the impact of genetic variations in the GPX3 gene and plasma GPx-3 antigen levels on ischemic stroke in young Asian Indians. One hundred patients with ischemic stroke and 200 age- and sex-matched controls were studied. Genetic analysis for the study population was done by a combination of variant screening using single-stranded conformation polymorphism and final genotyping by polymerase chain reaction-restriction fragment length polymorphism and allele-specific polymerase chain reactions. Plasma GPx-3 antigen levels were evaluated using commercial kits. Data were analyzed using genetic analysis software and statistical tools. Significantly higher GPx-3 levels were observed in controls compared with patients (controls 26.37 ± 3.66 μg/mL and patients 22.83 ± 4.57 μg/mL, P stroke phenotype (P stroke (P ischemic stroke phenotype. The -861A/T and -568T/C SNPs may show a statistically significant association with both plasma GPx-3 antigen levels and the stroke phenotype in a larger sample size. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  3. Prediction of Banking Systemic Risk Based on Support Vector Machine

    Directory of Open Access Journals (Sweden)

    Shouwei Li

    2013-01-01

    Full Text Available Banking systemic risk is a complex nonlinear phenomenon and has shed light on the importance of safeguarding financial stability by recent financial crisis. According to the complex nonlinear characteristics of banking systemic risk, in this paper we apply support vector machine (SVM to the prediction of banking systemic risk in an attempt to suggest a new model with better explanatory power and stability. We conduct a case study of an SVM-based prediction model for Chinese banking systemic risk and find the experiment results showing that support vector machine is an efficient method in such case.

  4. Support mechanisms and risk: Implications on the Nordic electricity system

    DEFF Research Database (Denmark)

    Kitzing, Lena; Ravn, Hans

    2013-01-01

    a stochastic analysis for the Nordic electricity system by conducting simulations with the energy system model Balmorel and by applying the mean-standard deviation approach of modern portfolio theory to quantify risk implications of policy instruments for an exemplary offshore wind park. The analysis reveals......Investments in renewable energy projects, such as offshore wind parks, are very much dependent on financial support. The type of policy instrument chosen for such support determines investors' exposure to market risk, and thus influences which rate of return they expect to achieve. We make...... that the two support policy schemes Feed-in Tariffs and Feed-in Premiums provide different risk-return relationships. In the investigated case, a Feed-in Premium scheme would require a 13% higher support level, because of a 6% higher exposure of investors to market risk. Our findings can help when designing...

  5. Support mechanisms for renewables: How risk exposure influences investment incentives

    Directory of Open Access Journals (Sweden)

    Lena Kitzing

    2016-06-01

    Full Text Available We analyse quantitatively how risk exposure from different support mechanisms, such as feed-in tariffs and premiums, can influence the investment incentives for private investors. We develop a net cash flow approach that takes systematic and unsystematic risks into account through cost of capital and the Capital Asset Pricing Model as well as through active liquidity management. Applying the model to a specific case, a German offshore wind park, we find that the support levels required to give adequate investment incentives are for a feed-in tariff scheme approximately 4-10% lower than for a feed-in premium scheme. The effect of differences in risk exposure from the support schemes is significant and cannot be neglected in policy making, especially when deciding between support instruments or when determining adequate support levels.

  6. Knowledge, risk, and policy support: Public perceptions of nuclear power

    International Nuclear Information System (INIS)

    Stoutenborough, James W.; Sturgess, Shelbi G.; Vedlitz, Arnold

    2013-01-01

    Nuclear energy was becoming increasingly popular as an alternative to air polluting fossil fuel technologies through the latter half of the 2000s. The tragic events of March 11, 2011 in Fukushima, Japan appear to have instantly killed any momentum the nuclear industry had gained. While unfortunate, many argue that nuclear power is still a safe alternative and that the Fukushima disaster resulted from insufficient safety regulations in Japan, a problem that does not exist in the United States. This project examines U.S. public support for nuclear energy one year after the Fukushima tragedy, seeking to understand the influence of knowledge and risk perceptions on policy support. We evaluate public support for nuclear energy policy from several perspectives using risk and attitudinal measurements that are more specific than often found in the literature to obtain a greater understanding of the connection between policy and risk. -- Highlights: •Paper evaluates US public support for nuclear energy1 year after Fukushima tragedy. •Attitudinal indicators are significant predictors of nuclear power policy support. •People more knowledgeable about energy issues are more supportive of nuclear energy. •Perceptions of risk exert varying influence on support for nuclear power. •Specific attitude and risk indicators permit nuanced insight into their influence

  7. Reduced risk of recurrent myocardial infarction in homozygous carriers of the chromosome 9p21 rs1333049 C risk allele in the contemporary percutaneous coronary intervention era: a prospective observational study

    Science.gov (United States)

    Hara, Masahiko; Sakata, Yasuhiko; Nakatani, Daisaku; Suna, Shinichiro; Usami, Masaya; Matsumoto, Sen; Ozaki, Kouichi; Nishino, Masami; Sato, Hiroshi; Kitamura, Tetsuhisa; Nanto, Shinsuke; Hamasaki, Toshimitsu; Tanaka, Toshihiro; Hori, Masatsugu; Komuro, Issei

    2014-01-01

    Objectives Chromosome 9p21 single nucleotide polymorphism (SNP) is a susceptibility variant for acute myocardial infarction (AMI) in the primary prevention setting. However, it is controversial whether this SNP is also associated with recurrent myocardial infarction (ReMI) in the secondary prevention setting. The purpose of this study is to evaluate the impact of chromosome 9p21 SNP on ReMI in patients receiving secondary prevention programmes after AMI. Design A prospective observational study. Setting Osaka Acute Coronary Insufficiency Study (OACIS) in Japan. Participants 2022 patients from the OACIS database. Interventions Genotyping of the 9p21 rs1333049 variant. Primary outcome measures ReMI event after survival discharge for 1 year. Results A total of 43 ReMI occurred during the 1 year follow-up period. Although the rs1333049 C allele had an increased susceptibility to their first AMI in an additive model when compared with 1373 healthy controls (OR 1.20, 95% CI 1.09 to 1.33, p=2.3*10−4), patients with the CC genotype had a lower incidence of ReMI at 1 year after discharge of AMI (log-rank p=0.005). The adjusted HR of the CC genotype as compared with the CG/GG genotypes was 0.20 (0.06 to 0.65, p=0.007). Subgroup analysis demonstrated that the association between the rs1333049 CC genotype and a lower incidence of 1 year ReMI was common to all subgroups. Conclusions Homozygous carriers of the rs1333049 C allele on chromosome 9p21 showed a reduced risk of 1 year ReMI in the contemporary percutaneous coronary intervention era, although the C allele had conferred susceptibility to their first AMI. PMID:25232560

  8. Social Support and Personal Agency in At-Risk Mothers

    Directory of Open Access Journals (Sweden)

    María José Rodrigo

    2011-04-01

    Full Text Available This study investigated: a mothers´ use and satisfaction with informal and formal supports in at-risk psychosocial contexts, and b the relationships between satisfaction with help and the mothers´ perception of their role (personal agency. Self-report data about the use and satisfaction with sources of help, and levels of internal control, self-efficacy, couple agreement, role difficulty and motivation for change were obtained from 519 mothers referred by Social Services and 519 non-referred mothers. Results indicated that at-risk mothers relied less upon close informal support and more on formal support than non atrisk mothers. They were also more satisfied with the formal sources of support and had lower levels of personal agency. There were beneficial effects of satisfaction with informal help and school support on several aspects of personal agency for both groups. However, satisfaction with school and social services support had a detrimental effect on couple agreement in the at-risk group. Implications of the results for providing social support to at-risk families are discussed.

  9. Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers: implications for risk prediction

    DEFF Research Database (Denmark)

    Antoniou, Antonis C; Beesley, Jonathan; McGuffog, Lesley

    2010-01-01

    The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs650495...

  10. Ribo HRM--detection of inter- and intra-species polymorphisms within ribosomal DNA by high resolution melting analysis supported by application of artificial allelic standards.

    Science.gov (United States)

    Masny, Aleksander; Jagiełło, Agata; Płucienniczak, Grażyna; Golab, Elzbieta

    2012-09-01

    Ribo HRM, a single-tube PCR and high resolution melting (HRM) assay for detection of polymorphisms in the large subunit ribosomal DNA expansion segment V, was developed on a Trichinella model. Four Trichinella species: T. spiralis (isolates ISS3 and ISS160), T. nativa (isolates ISS10 and ISS70), T. britovi (isolates ISS2 and ISS392) and T. pseudospiralis (isolates ISS13 and ISS1348) were genotyped. Cloned allelic variants of the expansion segment V were used as standards to prepare reference HRM curves characteristic for single sequences and mixtures of several cloned sequences imitating allelic composition detected in Trichinella isolates. Using the primer pair Tsr1 and Trich1bi, it was possible to amplify a fragment of the ESV and detect PCR products obtained from the genomic DNA of pools of larvae belonging to the four investigated species: T. pseudospiralis, T. spiralis, T. britovi and T. nativa, in a single tube Real-Time PCR reaction. Differences in the shape of the HRM curves of Trichinella isolates suggested the presence of differences between examined isolates of T. nativa, T. britovi and T. pseudospiralis species. No differences were observed between T. spiralis isolates. The presence of polymorphisms within the amplified ESV sequence fragment of T. nativa T. britovi and T. pseudospiralis was confirmed by sequencing of the cloned PCR products. Novel sequences were discovered and deposited in GenBank (GenBank IDs: JN971020-JN971027, JN120902.1, JN120903.1, JN120904.1, JN120906.1, JN120905.1). Screening the ESV region of Trichinella for polymorphism is possible using the genotyping assay Ribo HRM at the current state of its development. The Ribo HRM assay could be useful in phylogenetic studies of the Trichinella genus. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Support Mechanisms for Renewables: How Risk Exposure Influences Investment Incentives

    DEFF Research Database (Denmark)

    Kitzing, Lena; Weber, Christoph

    2015-01-01

    and the Capital Asset Pricing Model as well as through active liquidity management. Applying the model to a specific case, a German offshore wind park, we find that the support levels required to give adequate investment incentives are for a feed-in tariff scheme approximately 4-10% lower than for a feed......We analyse quantitatively how risk exposure from different support mechanisms, such as feed-in tariffs and premiums, can influence the investment incentives for private investors. We develop a net cash flow approach that takes systematic and unsystematic risks into account through cost of capital...

  12. Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

    NARCIS (Netherlands)

    K.B. Kuchenbaecker (Karoline); S.L. Neuhausen (Susan); M. Robson (Mark); D. Barrowdale (Daniel); L. McGuffog (Lesley); A.M. Mulligan (Anna Marie); I.L. Andrulis (Irene); A.B. Spurdle (Amanda); M.K. Schmidt (Marjanka); R.K. Schmutzler (Rita); C. Engel (Christoph); B. Wapenschmidt (Barbara); H. Nevanlinna (Heli); M. Thomassen (Mads); M.C. Southey (Melissa); P. Radice (Paolo); S.J. Ramus (Susan); S.M. Domchek (Susan); K.L. Nathanson (Katherine); A. Lee (Andrew); S. Healey (Sue); R. Nussbaum (Robert); R. Rebbeck (Timothy); B.K. Arun (Banu); M. James (Margaret); B.Y. Karlan (Beth); K.J. Lester (Kathryn); I. Cass (Ilana); M.B. Terry (Mary Beth); M.J. Daly (Mark); D. Goldgar (David); S.S. Buys (Saundra); R. Janavicius (Ramunas); L. Tihomirova (Laima); N. Tung (Nadine); C.M. Dorfling (Cecilia); E.J. van Rensburg (Elizabeth); L. Steele (Linda); T. v O Hansen (Thomas); B. Ejlertsen (Bent); A-M. Gerdes (Anne-Marie); F. Nielsen (Finn); J. Dennis (Joe); J.M. Cunningham (Julie); S. Hart (Stewart); S. Slager (Susan); A. Osorio (Ana); J. Benítez (Javier); M. Duran (Mercedes); J.N. Weitzel (Jeffrey); I. Tafur (Isaac); M. Hander (Mary); P. Peterlongo (Paolo); S. Manoukian (Siranoush); B. Peissel (Bernard); G. Roversi (Gaia); G. Scuvera (Giulietta); B. Bonnani (Bernardo); P. Mariani (Paolo); S. Volorio (Sara); R. Dolcetti (Riccardo); L. Varesco (Liliana); L. Papi (Laura); M.G. Tibiletti (Maria Grazia); G. Giannini (Giuseppe); F. Fostira (Florentia); I. Konstantopoulou (I.); J. Garber (Judy); U. Hamann (Ute); A. Donaldson (Alan); C. Brewer (Carole); C. Foo (Claire); D.G. Evans (Gareth); D. Frost (Debra); D. Eccles (Diana); F. Douglas (Fiona); A. Brady (A.); J. Cook (Jackie); M. Tischkowitz (Marc); L. Adlard; J. Barwell (Julian); K. Ong; L.J. Walker (Lisa); L. Izatt (Louise); L. Side (Lucy); M.J. Kennedy (John); M.T. Rogers (Mark); M.E. Porteous (Mary); P.J. Morrison (Patrick); R. Platte (Radka); R. Eeles (Ros); R. Davidson (Rosemarie); S. Hodgson (Shirley); S.D. Ellis (Steve); A.K. Godwin (Andrew); K. Rhiem (Kerstin); A. Meindl (Alfons); N. Ditsch (Nina); N. Arnold (Norbert); H. Plendl (Hansjoerg); D. Niederacher (Dieter); C. Sutter (Christian); D. Steinemann (Doris); N. Bogdanova-Markov (Nadja); K. Kast (Karin); R. Varon-Mateeva (Raymonda); S. Wang-Gohrke (Shan); P.A. Gehrig (Paola A.); B. Markiefka (Birgid); B. Buecher (Bruno); C. Lefol (Cédrick); D. Stoppa-Lyonnet (Dominique); E. Rouleau (Etienne); F. Prieur (Fabienne); F. Damiola (Francesca); L. Barjhoux (Laure); L. Faivre (Laurence); M. Longy (Michel); N. Sevenet (Nicolas); O. Sinilnikova (Olga); S. Mazoyer (Sylvie); V. Bonadona (Valérie); V. Caux-Moncoutier (Virginie); C. Isaacs (Claudine); T. Van Maerken (Tom); K.B.M. Claes (Kathleen B.M.); M. Piedmonte (Marion); L. Andrews (Lesley); J. Hays (John); G.C. Rodriguez (Gustavo); T. Caldes (Trinidad); M. de La Hoya (Miguel); S. Khan (Sofia); F.B.L. Hogervorst (Frans); C.M. Aalfs (Cora); J.L. de Lange (J.); E.J. Meijers-Heijboer (Hanne); A.H. van der Hout (Annemarie); J.T. Wijnen (Juul); K.E. van Roozendaal (Kees); A.R. Mensenkamp (Arjen); A.M.W. van den Ouweland (Ans); C.H.M. van Deurzen (Carolien); R.B. van der Luijt (Rob); E. Olah; O. Díez (Orland); C. Lazaro (Conxi); I. Blanco (Ignacio); A. Teulé (A.); M. Menéndez (Mireia); A. Jakubowska (Anna); J. Lubinski (Jan); C. Cybulski (Cezary); J. Gronwald (Jacek); K. Jaworska-Bieniek (Katarzyna); K. Durda (Katarzyna); A. Arason (Adalgeir); C. Maugard; P. Soucy (Penny); M. Montagna (Marco); S. Agata (Simona); P.J. Teixeira; C. Olswold (Curtis); N.M. Lindor (Noralane); V.S. Pankratz (Shane); B. Hallberg (Boubou); X. Wang (Xianshu); C. Szabo (Csilla); J. Vijai (Joseph); L. Jacobs (Lauren); M. Corines (Marina); A. Lincoln (Anne); A. Berger (Andreas); A. Fink-Retter (Anneliese); C.F. Singer (Christian); C. Rappaport (Christine); D.G. Kaulich (Daphne Gschwantler); G. Pfeiler (Georg); M.-K. Tea; C. Phelan (Catherine); P.L. Mai (Phuong); M.H. Greene (Mark); G. Rennert (Gad); E.N. Imyanitov (Evgeny); G. Glendon (Gord); A.E. Toland (Amanda); A. Bojesen (Anders); I.S. Pedersen (Inge Sokilde); U.B. Jensen; M.A. Caligo (Maria); E. Friedman (Eitan); R. Berger (Raanan); Y. Laitman (Yael); J. Rantala (Johanna); B. Arver (Brita Wasteson); N. Loman (Niklas); Å. Borg (Åke); H. Ehrencrona (Hans); O.I. Olopade (Olofunmilayo); J. Simard (Jacques); D.F. Easton (Douglas); G. Chenevix-Trench (Georgia); K. Offit (Kenneth); F.J. Couch (Fergus); A.C. Antoniou (Antonis C.); CIMBA; EMBRACE Study; Breast Cancer Family; GEMO Study Collaborators; HEBON; KConFab Investigators

    2014-01-01

    textabstractIntroduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2

  13. Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

    NARCIS (Netherlands)

    Kuchenbaecker, Karoline B.; Neuhausen, Susan L.; Robson, Mark; Barrowdale, Daniel; McGuffog, Lesley; Mulligan, Anna Marie; Andrulis, Irene L.; Spurdle, Amanda B.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Engel, Christoph; Wappenschmidt, Barbara; Nevanlinna, Heli; Thomassen, Mads; Southey, Melissa; Radice, Paolo; Ramus, Susan J.; Domchek, Susan M.; Nathanson, Katherine L.; Lee, Andrew; Healey, Sue; Nussbaum, Robert L.; Rebbeck, Timothy R.; Arun, Banu K.; James, Paul; Karlan, Beth Y.; Lester, Jenny; Cass, Ilana; Terry, Mary Beth; Daly, Mary B.; Goldgar, David E.; Buys, Saundra S.; Janavicius, Ramunas; Tihomirova, Laima; Tung, Nadine; Dorfling, Cecilia M.; van Rensburg, Elizabeth J.; Steele, Linda; v O Hansen, Thomas; Ejlertsen, Bent; Gerdes, Anne-Marie; Nielsen, Finn C.; Dennis, Joe; Cunningham, Julie; Hart, Steven; Slager, Susan; Osorio, Ana; Benitez, Javier; Duran, Mercedes; Weitzel, Jeffrey N.; Tafur, Isaac; Hander, Mary; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Roversi, Gaia; Scuvera, Giulietta; Bonanni, Bernardo; Mariani, Paolo; Volorio, Sara; Dolcetti, Riccardo; Varesco, Liliana; Papi, Laura; Tibiletti, Maria Grazia; Giannini, Giuseppe; Fostira, Florentia; Konstantopoulou, Irene; Garber, Judy; Hamann, Ute; Donaldson, Alan; Brewer, Carole; Foo, Claire; Evans, D. Gareth; Frost, Debra; Eccles, Diana; Douglas, Fiona; Brady, Angela; Cook, Jackie; Tischkowitz, Marc; Adlard, Julian; Barwell, Julian; Ong, Kai-Ren; Walker, Lisa; Izatt, Louise; Side, Lucy E.; Kennedy, M. John; Rogers, Mark T.; Porteous, Mary E.; Morrison, Patrick J.; Platte, Radka; Eeles, Ros; Davidson, Rosemarie; Hodgson, Shirley; Ellis, Steve; Godwin, Andrew K.; Rhiem, Kerstin; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Plendl, Hansjoerg; Niederacher, Dieter; Sutter, Christian; Steinemann, Doris; Bogdanova-Markov, Nadja; Kast, Karin; Varon-Mateeva, Raymonda; Wang-Gohrke, Shan; Gehrig, Andrea; Markiefka, Birgid; Buecher, Bruno; Lefol, Cédrick; Stoppa-Lyonnet, Dominique; Rouleau, Etienne; Prieur, Fabienne; Damiola, Francesca; Barjhoux, Laure; Faivre, Laurence; Longy, Michel; Sevenet, Nicolas; Sinilnikova, Olga M.; Mazoyer, Sylvie; Bonadona, Valérie; Caux-Moncoutier, Virginie; Isaacs, Claudine; van Maerken, Tom; Claes, Kathleen; Piedmonte, Marion; Andrews, Lesley; Hays, John; Rodriguez, Gustavo C.; Caldes, Trinidad; de la Hoya, Miguel; Khan, Sofia; Hogervorst, Frans B. L.; Aalfs, Cora M.; de Lange, J. L.; Meijers-Heijboer, Hanne E. J.; van der Hout, Annemarie H.; Wijnen, Juul T.; van Roozendaal, K. E. P.; Mensenkamp, Arjen R.; van den Ouweland, Ans M. W.; van Deurzen, Carolien H. M.; van der Luijt, Rob B.; Olah, Edith; Diez, Orland; Lazaro, Conxi; Blanco, Ignacio; Teulé, Alex; Menendez, Mireia; Jakubowska, Anna; Lubinski, Jan; Cybulski, Cezary; Gronwald, Jacek; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Arason, Adalgeir; Maugard, Christine; Soucy, Penny; Montagna, Marco; Agata, Simona; Teixeira, Manuel R.; Olswold, Curtis; Lindor, Noralane; Pankratz, Vernon S.; Hallberg, Emily; Wang, Xianshu; Szabo, Csilla I.; Vijai, Joseph; Jacobs, Lauren; Corines, Marina; Lincoln, Anne; Berger, Andreas; Fink-Retter, Anneliese; Singer, Christian F.; Rappaport, Christine; Kaulich, Daphne Gschwantler; Pfeiler, Georg; tea, Muy-Kheng; Phelan, Catherine M.; Mai, Phuong L.; Greene, Mark H.; Rennert, Gad; Imyanitov, Evgeny N.; Glendon, Gord; Toland, Amanda Ewart; Bojesen, Anders; Pedersen, Inge Sokilde; Jensen, Uffe Birk; Caligo, Maria A.; Friedman, Eitan; Berger, Raanan; Laitman, Yael; Rantala, Johanna; Arver, Brita; Loman, Niklas; Borg, Ake; Ehrencrona, Hans; Olopade, Olufunmilayo I.; Simard, Jacques; Easton, Douglas F.; Chenevix-Trench, Georgia; Offit, Kenneth; Couch, Fergus J.; Antoniou, Antonis C.; Perkins, Jo; Miedzybrodzka, Zosia; Gregory, Helen; Morrison, Patrick; Jeffers, Lisa; Cole, Trevor; Hoffman, Jonathan; James, Margaret; Paterson, Joan; Downing, Sarah; Taylor, Amy; Murray, Alexandra; McCann, Emma; Barton, David; Porteous, Mary; Drummond, Sarah; Kivuva, Emma; Searle, Anne; Goodman, Selina; Hill, Kathryn; Murday, Victoria; Bradshaw, Nicola; Snadden, Lesley; Longmuir, Mark; Watt, Catherine; Gibson, Sarah; Haque, Eshika; Tobias, Ed; Duncan, Alexis; Jacobs, Chris; Langman, Caroline; Dorkins, Huw; Serra-Feliu, Gemma; Ellis, Ian; Lalloo, Fiona; Taylor, Jane; Side, Lucy; Male, Alison; Berlin, Cheryl; Eason, Jacqueline; Collier, Rebecca; Claber, Oonagh; Jobson, Irene; McLeod, Diane; Halliday, Dorothy; Durell, Sarah; Stayner, Barbara; Shanley, Susan; Rahman, Nazneen; Houlston, Richard; Bancroft, Elizabeth; Page, Elizabeth; Ardern-Jones, Audrey; Kohut, Kelly; Wiggins, Jennifer; Castro, Elena; Mitra, Anita; Quarrell, Oliver; Bardsley, Cathryn; Goff, Sheila; Brice, Glen; Winchester, Lizzie; Eddy, Charlotte; Tripathi, Vishakha; Attard, Virginia; Lucassen, Anneke; Crawford, Gillian; McBride, Donna; Smalley, Sarah; Weaver, Joellen; Bove, Betsy; Sinilnikova, Olga; Verny-Pierre, Carole; Calender, Alain; Giraud, Sophie; Léone, Mélanie; Gauthier-Villars, Marion; Houdayer, Claude; Moncoutier, Virginie; Belotti, Muriel; Tirapo, Carole; de Pauw, Antoine; Bressac-de-Paillerets, Brigitte; Caron, Olivier; Bignon, Yves-Jean; Uhrhammer, Nancy; Lasset, Christine; Handallo, Sandrine; Hardouin, Agnès; Berthet, Pascaline; Sobol, Hagay; Bourdon, Violaine; Noguchi, Tetsuro; Remenieras, Audrey; Eisinger, François; Coupier, Isabelle; Pujol, Pascal; Peyrat, Jean-Philippe; Fournier, Joëlle; Révillion, Françoise; Vennin, Philippe; Adenis, Claude; Lidereau, Rosette; Demange, Liliane; Nogues, Catherine; Muller, Danièle; Fricker, Jean-Pierre; Barouk-Simonet, Emmanuelle; Bonnet, Françoise; Bubien, Virginie; Toulas, Christine; Guimbaud, Rosine; Gladieff, Laurence; Feillel, Viviane; Leroux, Dominique; Dreyfus, Hélène; Rebischung, Christine; Peysselon, Magalie; Coron, Fanny; Lebrun, Marine; Kientz, Caroline; Ferrer, Sandra Fert; Frénay, Marc; Vénat-Bouvet, Laurence; Delnatte, Capucine; Mortemousque, Isabelle; Coulet, Florence; Colas, Chrystelle; Soubrier, Florent; Sokolowska, Johanna; Bronner, Myriam; Collonge-Rame, Marie-Agnès; Damette, Alexandre; Lynch, Henry T.; Snyder, Carrie L.; Coene, Ilse; Crombez, Brecht; Segura, Pedro Perez; Romero, Atocha; Diaque, Paula; Aittomäki, Kristiina; Blomqvist, Carl; Aaltonen, Kirsimari; Muranen, Taru A.; Erkkilä, Irja; Palola, Virpi; Rookus, M. A.; Hogervorst, F. B. L.; van Leeuwen, F. E.; Verhoef, S.; Schmidt, M. K.; Wijnands, R.; Collée, J. M.; van den Ouweland, A. M. W.; Hooning, M. J.; Seynaeve, C.; van Deurzen, C. H. M.; Obdeijn, I. M.; van Asperen, C. J.; Wijnen, J. T.; Tollenaar, R. A. E. M.; Devilee, P.; van Cronenburg, T. C. T. E. F.; Kets, C. M.; Mensenkamp, A. R.; Ausems, M. G. E. M.; van der Luijt, R. B.; van Os, T. A. M.; Gille, J. J. P.; Waisfisz, Q.; Gómez-Garcia, E. B.; Blok, M. J.; Oosterwijk, J. C.; van der Hout, A. H.; Mourits, M. J.; de Bock, G. H.; Vasen, H. F.; Siesling, S.; Overbeek, L. I. H.; Papp, Janos; Vaszko, Tibor; Bozsik, Aniko; Pocza, Timea; Franko, Judit; Balogh, Maria; Domokos, Gabriella; Ferenczi, Judit; Balmaña, J.; Capella, Gabriel; Dumont, Martine; Tranchant, Martine

    2014-01-01

    Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation

  14. Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21

    NARCIS (Netherlands)

    Y. Hamdi (Yosr); Soucy, P. (Penny); Adoue, V. (Véronique); K. Michailidou (Kyriaki); S. Canisius (Sander); Lemaçon, A. (Audrey); A. Droit (Arnaud); I.L. Andrulis (Irene); H. Anton-Culver (Hoda); Arndt, V. (Volker); Baynes, C. (Caroline); C. Blomqvist (Carl); N.V. Bogdanova (Natalia); S.E. Bojesen (Stig); M.K. Bolla (Manjeet K.); B. Bonnani (Bernardo); A.-L. Borresen-Dale (Anne-Lise); J.S. Brand (Judith S.); H. Brauch (Hiltrud); Brenner, H. (Hermann); A. Broeks (Annegien); B. Burwinkel (Barbara); J. Chang-Claude (Jenny); Couch, F.J. (Fergus J.); A. Cox (Angela); S.S. Cross (Simon); K. Czene (Kamila); H. Darabi (Hatef); J. Dennis (Joe); P. Devilee (Peter); T. Dörk (Thilo); I. dos Santos Silva (Isabel); M. Eriksson (Mats); P.A. Fasching (Peter); J.D. Figueroa (Jonine); H. Flyger (Henrik); M. García-Closas (Montserrat); Giles, G.G. (Graham G.); M.S. Goldberg (Mark); A. González-Neira (Anna); G. Grenaker Alnæs (Grethe); P. Guénel (Pascal); L. Haeberle (Lothar); C.A. Haiman (Christopher); U. Hamann (Ute); Hallberg, E. (Emily); M.J. Hooning (Maartje); J.L. Hopper (John); A. Jakubowska (Anna); M. Jones (Michael); M. Kabisch (Maria); V. Kataja (Vesa); Lambrechts, D. (Diether); L. Le Marchand (Loic); A. Lindblom (Annika); J. Lubinski (Jan); A. Mannermaa (Arto); M. Maranian (Melanie); S. Margolin (Sara); Marme, F. (Frederik); R.L. Milne (Roger); S.L. Neuhausen (Susan); H. Nevanlinna (Heli); P. Neven (Patrick); C. Olswold (Curtis); J. Peto (Julian); Plaseska-Karanfilska, D. (Dijana); K. Pykäs (Katri); P. Radice (Paolo); A. Rudolph (Anja); E.J. Sawyer (Elinor); M.K. Schmidt (Marjanka); X.-O. Shu (Xiao-Ou); M.C. Southey (Melissa); A.J. Swerdlow (Anthony ); R.A.E.M. Tollenaar (Rob); I.P. Tomlinson (Ian); D. Torres (Diana); T. Truong (Thérèse); C. Vachon (Celine); A.M.W. van den Ouweland (Ans); Q. Wang (Qin); R. Winqvist (Robert); W. Zheng (Wei); J. Benítez (Javier); G. Chenevix-Trench (Georgia); A.M. Dunning (Alison); P.D.P. Pharoah (Paul); Kristensen, V. (Vessela); P. Hall (Per); D.F. Easton (Douglas); T. Pastinen (Tomi); S. Nord (Silje); J. Simard (Jacques)

    2016-01-01

    textabstractThere are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, cis-acting variants represent an important source of phenotypic variation. Consequently, cis-regulatory SNPs associated with differential allelic expression are

  15. Simplified risk model support for environmental management integration

    International Nuclear Information System (INIS)

    Eide, S.A.; Jones, J.L.; Wierman, T.E.

    1998-01-01

    This paper summarizes the process and results of human health risk assessments of the US Department of Energy (DOE) complex-wide programs for high-level waste, transuranic waste, low-level, mixed low-level waste, and spent nuclear fuel. The DOE baseline programs and alternatives for these five material types were characterized by disposition maps (material flow diagrams) and supporting information in the May 1997 report 'A Contractor Report to the Department of Energy on Environmental Baseline Programs and Integration Opportunities' (Discussion Draft). Risk analyses were performed using the Simplified Risk Model (SRM), developed to support DOE Environmental Management Integration studies. The SRM risk analyses consistently and comprehensively cover the life cycle programs for the five material types, from initial storage through final disposition. Risk results are presented at several levels: DOE complex-wide, material type program, individual DOE sites, and DOE site activities. The detailed risk results are documented in the February 1998 report 'Human Health Risk Comparisons for Environmental Management Baseline Programs and Integration Opportunities' (Discussion Draft)

  16. Making Risk Models Operational for Situational Awareness and Decision Support

    International Nuclear Information System (INIS)

    Paulson, P.R.; Coles, G.; Shoemaker, S.

    2012-01-01

    We present CARIM, a decision support tool to aid in the evaluation of plans for converting control systems to digital instruments. The model provides the capability to optimize planning and resource allocation to reduce risk from multiple safety and economic perspectives. (author)

  17. Perceptions of Social Support, Empowerment and Youth Risk Behaviors

    Science.gov (United States)

    Reininger, Belinda M.; Perez, Adriana; Flores, Maria I. Aguirre; Chen, Zhongxue; Rahbar, Mohammad H.

    2012-01-01

    This study examined the association of perceived social support and community empowerment among urban middle-school students living in Matamoros, Mexico and the risk behaviors of fighting, alcohol and tobacco use, and sexual activity. Middle school students (n = 1,181) from 32 public and private Mexican schools were surveyed. Weighted multiple…

  18. Social network, social support, and risk of incident stroke: Atherosclerosis Risk in Communities study.

    Science.gov (United States)

    Nagayoshi, Mako; Everson-Rose, Susan A; Iso, Hiroyasu; Mosley, Thomas H; Rose, Kathryn M; Lutsey, Pamela L

    2014-10-01

    Having a small social network and lack of social support have been associated with incident coronary heart disease; however, epidemiological evidence for incident stroke is limited. We assessed the longitudinal association of a small social network and lack of social support with risk of incident stroke and evaluated whether the association was partly mediated by vital exhaustion and inflammation. The Atherosclerosis Risk in Communities study measured social network and social support in 13 686 men and women (mean, 57 years; 56% women; 24% black; 76% white) without a history of stroke. Social network was assessed by the 10-item Lubben Social Network Scale and social support by a 16-item Interpersonal Support Evaluation List-Short Form. During a median follow-up of 18.6 years, 905 incident strokes occurred. Relative to participants with a large social network, those with a small social network had a higher risk of stroke (hazard ratio [95% confidence interval], 1.44 [1.02-2.04]) after adjustment for demographics, socioeconomic variables, marital status, behavioral risk factors, and major stroke risk factors. Vital exhaustion, but not inflammation, partly mediated the association between a small social network and incident stroke. Social support was unrelated to incident stroke. In this sample of US community-dwelling men and women, having a small social network was associated with excess risk of incident stroke. As with other cardiovascular conditions, having a small social network may be associated with a modestly increased risk of incident stroke. © 2014 American Heart Association, Inc.

  19. Nutrition support in hospitalised adults at nutritional risk.

    Science.gov (United States)

    Feinberg, Joshua; Nielsen, Emil Eik; Korang, Steven Kwasi; Halberg Engell, Kirstine; Nielsen, Marie Skøtt; Zhang, Kang; Didriksen, Maria; Lund, Lisbeth; Lindahl, Niklas; Hallum, Sara; Liang, Ning; Xiong, Wenjing; Yang, Xuemei; Brunsgaard, Pernille; Garioud, Alexandre; Safi, Sanam; Lindschou, Jane; Kondrup, Jens; Gluud, Christian; Jakobsen, Janus C

    2017-05-19

    The prevalence of disease-related malnutrition in Western European hospitals is estimated to be about 30%. There is no consensus whether poor nutritional status causes poorer clinical outcome or if it is merely associated with it. The intention with all forms of nutrition support is to increase uptake of essential nutrients and improve clinical outcome. Previous reviews have shown conflicting results with regard to the effects of nutrition support. To assess the benefits and harms of nutrition support versus no intervention, treatment as usual, or placebo in hospitalised adults at nutritional risk. We searched Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE (Ovid SP), Embase (Ovid SP), LILACS (BIREME), and Science Citation Index Expanded (Web of Science). We also searched the World Health Organization International Clinical Trials Registry Platform (www.who.int/ictrp); ClinicalTrials.gov; Turning Research Into Practice (TRIP); Google Scholar; and BIOSIS, as well as relevant bibliographies of review articles and personal files. All searches are current to February 2016. We include randomised clinical trials, irrespective of publication type, publication date, and language, comparing nutrition support versus control in hospitalised adults at nutritional risk. We exclude trials assessing non-standard nutrition support. We used standard methodological procedures expected by Cochrane and the Cochrane Hepato-Biliary Group. We used trial domains to assess the risks of systematic error (bias). We conducted Trial Sequential Analyses to control for the risks of random errors. We considered a P value of 0.025 or less as statistically significant. We used GRADE methodology. Our primary outcomes were all-cause mortality, serious adverse events, and health-related quality of life. We included 244 randomised clinical trials with 28,619 participants that met our inclusion criteria. We considered all trials to be at high risk of bias. Two

  20. Low Penetrance Alleles in Colorectal Cancer: the arachidonic acid pathway

    NARCIS (Netherlands)

    C.L.E. Siezen

    2006-01-01

    textabstractIn summary, we can conclude that we have successfully identified low penetrance alleles in the PPAR., PLA2G2A and ALOX15 genes, conferring differential colorectal adenoma risk, and two such alleles in the PTGS2 gene, one of which is also involved in colorectal cancer risk. These

  1. Risk of dependence associated with health, social support, and lifestyle.

    Science.gov (United States)

    Alcañiz, Manuela; Brugulat, Pilar; Guillén, Montserrat; Medina-Bustos, Antonia; Mompart-Penina, Anna; Solé-Auró, Aïda

    2015-01-01

    OBJECTIVE To analyze the prevalence of individuals at risk of dependence and its associated factors. METHODS The study was based on data from the Catalan Health Survey, Spain conducted in 2010 and 2011. Logistic regression models from a random sample of 3,842 individuals aged ≥ 15 years were used to classify individuals according to the state of their personal autonomy. Predictive models were proposed to identify indicators that helped distinguish dependent individuals from those at risk of dependence. Variables on health status, social support, and lifestyles were considered. RESULTS We found that 18.6% of the population presented a risk of dependence, especially after age 65. Compared with this group, individuals who reported dependence (11.0%) had difficulties performing activities of daily living and had to receive support to perform them. Habits such as smoking, excessive alcohol consumption, and being sedentary were associated with a higher probability of dependence, particularly for women. CONCLUSIONS Difficulties in carrying out activities of daily living precede the onset of dependence. Preserving personal autonomy and function without receiving support appear to be a preventive factor. Adopting an active and healthy lifestyle helps reduce the risk of dependence.

  2. TGFbeta1 (Leu10Pro), p53 (Arg72Pro) can predict for increased risk for breast cancer in south Indian women and TGFbeta1 Pro (Leu10Pro) allele predicts response to neo-adjuvant chemo-radiotherapy.

    Science.gov (United States)

    Rajkumar, Thangarajan; Samson, Mani; Rama, Ranganathan; Sridevi, Veluswami; Mahji, Urmila; Swaminathan, Rajaraman; Nancy, Nirmala K

    2008-11-01

    The breast cancer incidence has been increasing in the south Indian women. A case (n=250)-control (n=500) study was undertaken to investigate the role of Single Nucleotide Polymorphisms (SNP's) in GSTM1 (Present/Null); GSTP1 (Ile105Val), p53 (Arg72Pro), TGFbeta1 (Leu10Pro), c-erbB2 (Ile655Val), and GSTT1 (Null/Present) in breast cancer. In addition, the value of the SNP's in predicting primary tumor's pathologic response following neo-adjuvant chemo-radiotherapy was assessed. Genotyping was done using PCR (GSTM1, GSTT1), Taqman Allelic discrimination assay (GSTP1, c-erbB2) and PCR-CTPP (p53 and TGFbeta1). None of the gene SNP's studied were associated with a statistically significant increased risk for the breast cancer. However, combined analysis of the SNP's showed that p53 (Arg/Arg and Arg/Pro) with TGFbeta1 (Pro/Pro and Leu/Pro) were associated with greater than 2 fold increased risk for breast cancer in Univariate (P=0.01) and Multivariate (P=0.003) analysis. There was no statistically significant association for the GST family members with the breast cancer risk. TGFbeta1 (Pro/Pro) allele was found to predict complete pathologic response in the primary tumour following neo-adjuvant chemo-radiotherapy (OR=6.53 and 10.53 in Univariate and Multivariate analysis respectively) (P=0.004) and was independent of stage. This study suggests that SNP's can help predict breast cancer risk in south Indian women and that TGFbeta1 (Pro/Pro) allele is associated with a better pCR in the primary tumour.

  3. Remediation planning and risk assessment support through data fusion technology

    International Nuclear Information System (INIS)

    1996-01-01

    Coleman Research's Data Fusion Modeling (DFM) services gives one the ability to use large geophysical and hydrological data sets, which include direct and indirect measurements, to obtain a unified mathematical model of the geology and hydrology at one's site. Coleman Research (CRC) has adapted highly stable and efficient statistical inversion techniques, developed over the past 20 years, to provide a 3D site model with quantified uncertainty based on state-of-the-art modeling codes. This site model supports risk assessment and remediation planning with enhanced numerical accuracy for tradeoff studies of alternate remediation strategies. Further, DFM supports real time model updates during remediation and site investigation

  4. Intelligent Decision Support System for Bank Loans Risk Classification

    Institute of Scientific and Technical Information of China (English)

    杨保安; 马云飞; 俞莲

    2001-01-01

    Intelligent Decision Support System (IISS) for Bank Loans Risk Classification (BLRC), based on the way of integration Artificial Neural Network (ANN) and Expert System (ES), is proposed. According to the feature of BLRC, the key financial and non-financial factors are analyzed. Meanwhile, ES and Model Base (MB) which contain ANN are designed . The general framework,interaction and integration of the system are given. In addition, how the system realizes BLRC is elucidated in detail.

  5. Social support for schoolchildren at risk of social exclusion

    Directory of Open Access Journals (Sweden)

    Ivanauskiene V.

    2012-10-01

    Full Text Available Social exclusion is a wider concept than poverty and includes not only material conditions but also inability to participate in economic, social, political and cultural life. The essence of social exclusion is social relationships (more exactly breaking off relationships, which may mean not only pushing away some members of the society, but also breaking off relationships with the society from the side of a person himself/herself. The reasons of origin of social exclusion may be legal, political, economical, social and cultural. Nowadays social exclusion is predetermined by social-economic factors. According to Poviliūnas (2001, the problems of children’s social exclusion may be solved ensuring proper education, care of public health, safety and minimal life standard. Growing aggression and violence of schoolchildren and their social exclusion are nowadays an important issue of political debate and media reports. Often schoolchildren face the risk of social exclusion at school during the period of adolescence. The risk also depends on the social status of their family in the society and the relationship of the family members. The aim of the article is to identify characteristic features of schoolchildren at risk of social exclusion and analyze social support provided for them. A quantitative research was carried out to achieve the aim. The method of data collection is a questionnaire. 105 teachers working in 3 secondary schools in Lithuania participated in the research. The research results revealed that most often schoolchildren face the risk of social exclusion at school during adolescence period. They are characterized as incommunicative, unsociable, passive, and shy, do not trust others, are vulnerable, have learning problems and avoid collaborative activities. These schoolchildren usually come from families of social risk or single parent families. The support provided at school by teachers to schoolchildren at risk of social exclusion

  6. Sustainable nanotechnology decision support system: bridging risk management, sustainable innovation and risk governance

    International Nuclear Information System (INIS)

    Subramanian, Vrishali; Semenzin, Elena; Hristozov, Danail; Zabeo, Alex; Malsch, Ineke; McAlea, Eamonn; Murphy, Finbarr; Mullins, Martin; Harmelen, Toon van; Ligthart, Tom; Linkov, Igor; Marcomini, Antonio

    2016-01-01

    The significant uncertainties associated with the (eco)toxicological risks of engineered nanomaterials pose challenges to the development of nano-enabled products toward greatest possible societal benefit. This paper argues for the use of risk governance approaches to manage nanotechnology risks and sustainability, and considers the links between these concepts. Further, seven risk assessment and management criteria relevant to risk governance are defined: (a) life cycle thinking, (b) triple bottom line, (c) inclusion of stakeholders, (d) risk management, (e) benefit–risk assessment, (f) consideration of uncertainty, and (g) adaptive response. These criteria are used to compare five well-developed nanotechnology frameworks: International Risk Governance Council framework, Comprehensive Environmental Assessment, Streaming Life Cycle Risk Assessment, Certifiable Nanospecific Risk Management and Monitoring System and LICARA NanoSCAN. A Sustainable Nanotechnology Decision Support System (SUNDS) is proposed to better address current nanotechnology risk assessment and management needs, and makes. Stakeholder needs were solicited for further SUNDS enhancement through a stakeholder workshop that included representatives from regulatory, industry and insurance sectors. Workshop participants expressed the need for the wider adoption of sustainability assessment methods and tools for designing greener nanomaterials.

  7. Sustainable nanotechnology decision support system: bridging risk management, sustainable innovation and risk governance

    Energy Technology Data Exchange (ETDEWEB)

    Subramanian, Vrishali, E-mail: vrishali.subramanian@unive.it; Semenzin, Elena; Hristozov, Danail; Zabeo, Alex [University Ca’ Foscari of Venice, Department of Environmental Sciences, Informatics and Statistics (Italy); Malsch, Ineke [Malsch TechnoValuation (Netherlands); McAlea, Eamonn; Murphy, Finbarr; Mullins, Martin [University of Limerick, Kemmy Business School (Ireland); Harmelen, Toon van; Ligthart, Tom [TNO (Netherlands); Linkov, Igor; Marcomini, Antonio, E-mail: marcom@unive.it [University Ca’ Foscari of Venice, Department of Environmental Sciences, Informatics and Statistics (Italy)

    2016-04-15

    The significant uncertainties associated with the (eco)toxicological risks of engineered nanomaterials pose challenges to the development of nano-enabled products toward greatest possible societal benefit. This paper argues for the use of risk governance approaches to manage nanotechnology risks and sustainability, and considers the links between these concepts. Further, seven risk assessment and management criteria relevant to risk governance are defined: (a) life cycle thinking, (b) triple bottom line, (c) inclusion of stakeholders, (d) risk management, (e) benefit–risk assessment, (f) consideration of uncertainty, and (g) adaptive response. These criteria are used to compare five well-developed nanotechnology frameworks: International Risk Governance Council framework, Comprehensive Environmental Assessment, Streaming Life Cycle Risk Assessment, Certifiable Nanospecific Risk Management and Monitoring System and LICARA NanoSCAN. A Sustainable Nanotechnology Decision Support System (SUNDS) is proposed to better address current nanotechnology risk assessment and management needs, and makes. Stakeholder needs were solicited for further SUNDS enhancement through a stakeholder workshop that included representatives from regulatory, industry and insurance sectors. Workshop participants expressed the need for the wider adoption of sustainability assessment methods and tools for designing greener nanomaterials.

  8. Risk and uncertainty in the structure of management decision support

    International Nuclear Information System (INIS)

    Valeca, Serban Constantin

    2002-01-01

    The monograph is structured into five chapters addressing the following subject matters: 1 - The risk descriptor implied by the power systems with nuclear injection; 1.1 - Concepts and operators for describing the nuclear power risk; 1.2 - Risk approach in a holistic conception; 2 - Modelling the risk in the frame of re-engineering concept; 2.1 - Defining and interpreting the power re-engineering; 2.2 - Managerial re-engineering of power production systems; 3 - Informatics system of managing the power objectives with nuclear injection; 3.1 - Informatics systems for risk at the level of CANDU - 600 nuclear plant; 3.2. - Expert function structure applicable to the management of power objectives with nuclear injection; 4 - Assisting support in the operation of nuclear facilities; 4.1 - Assisting support system for nuclear plant operation; 4.2 - Program products for dedicated drivers; 5 - The management decision activities at the level of power systems with nuclear injection; 5.1 - Preliminaries in making power decision; 5.2 - Applications of decision models of sustainable power systems with nuclear injection; 5.3 - Re-engineering of power decision in the frame of maximal utility theory. The successful application of re-engineering concept is based on knowledge and managing capacity of design leadership and its ability of dealing the error generating sources. The main stages of implementing successfully the re-engineering are: - Replacing the pollution processes instead of adjusting measures; - Raising the designer responsibility by radical innovation of processes' architecture; - Re-designing the processes by basic changes at the level of the management functions and structures; - Raising the personnel professionalism by motivation as optimal way of improving the workers mentalities; - Accurate definition of objectives in the frame of re-engineering program; - Application of re-engineering in industrial units starting from the management level; - Selecting as general

  9. The IL-10-1082 (rs1800896) G allele is associated with a decreased risk of developing premature coronary artery disease and some IL-10 polymorphisms were associated with clinical and metabolic parameters. The GEA study.

    Science.gov (United States)

    Posadas-Sánchez, Rosalinda; Angeles-Martínez, Javier; Pérez-Hernández, Nonanzit; Rodríguez-Pérez, José Manuel; López-Bautista, Fabiola; Flores-Dominguez, Carmina; Fragoso, José Manuel; Posadas-Romero, Carlos; Vargas-Alarcón, Gilberto

    2018-06-01

    Interleukin 10 (IL-10) is an anti-inflammatory cytokine with a protective role in the formation and the development of the atherosclerotic plaque. The aim of the present study was to establish if IL-10 gene polymorphisms are associated with the development of premature coronary artery disease (pCAD) and cardiovascular risk factors in Mexican individuals. Three IL-10 gene polymorphisms [-592C/A (rs1800872), -819C/T (rs1800871), and -1082 A/G (rs1800896)] and IL-10 plasma levels were analyzed in 2266 individuals (1160 pCAD patients and 1106 healthy controls). Under recessive and co-dominant2 models, the -1082 A/G (rs1800896) G allele was associated with decreased risk of developing pCAD (OR = 0.572, P rec  = 0.022 and OR = 0.567, P cod2  = 0.023). In pCAD patients, the polymorphisms were associated with hyperinsulinemia, small and dense LDLs, hypertension, and diabetes mellitus. In the control group, the polymorphisms were associated with hypertension, hyperuricemia, and small and dense LDLs. pCAD patients have significantly higher IL-10 plasma levels than healthy controls [0.91 (0.55-1.67) pg/mL vs 0.45 (0.24-0.98) pg/mL, respectively, P < 0.0001]. Nevertheless, these levels were not associated with the genotypes analyzed in the present study. The results suggest that the IL-10-1082 A/G (rs1800896) G allele is associated with a decreased risk of developing pCAD. In patients and controls, the polymorphisms analyzed were associated with some cardiovascular risk factors. Although, in pCAD patients the IL-10 plasma levels were higher, they were not associated with the genotypes of the polymorphisms examined. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. NRC Support for the Kalinin (VVER) probabilistic risk assessment

    International Nuclear Information System (INIS)

    Bley, D.; Diamond, D.J.; Chu, T.L.; Azarm, A.; Pratt, W.T.; Johnson, D.; Szukiewicz, A.; Drouin, M.; El-Bassioni, A.; Su, T.M.

    1998-01-01

    The US Nuclear Regulatory Commission (NRC) and the Federal Nuclear and Radiation Safety Authority of the Russian Federation have been working together since 1994 to carry out a probabilistic risk assessment (PRA) of a VVER-1000 in the Russian Federation. This was a recognition by both parties that this technology has had a profound effect on the discipline of nuclear reactor safety in the West and that the technology should be transferred to others so that it can be applied to Soviet-designed plants. The NRC provided funds from the Agency for International Development and technical support primarily through Brookhaven National Laboratory and its subcontractors. The latter support was carried out through workshops, by documenting the methodology to be used in a set of guides, and through periodic review of the technical activity. The result of this effort to date includes a set of procedure guides, a draft final report on the Level 1 PRA for internal events (excluding internal fires and floods), and progress reports on the fire, flood, and seismic analysis. It is the authors belief that the type of assistance provided by the NRC has been instrumental in assuring a quality product and transferring important technology for use by regulators and operators of Soviet-designed reactors. After a thorough review, the report will be finalized, lessons learned will be applied in the regulatory and operational regimes in the Russian Federation, and consideration will be given to supporting a containment analysis in order to complete a simplified Level 2 PRA

  11. RiskChanges Spatial Decision Support system for the analysis of changing multi-hazard risk

    Science.gov (United States)

    van Westen, Cees; Zhang, Kaixi; Bakker, Wim; Andrejchenko, Vera; Berlin, Julian; Olyazadeh, Roya; Cristal, Irina

    2015-04-01

    Within the framework of the EU FP7 Marie Curie Project CHANGES and the EU FP7 Copernicus project INCREO a spatial decision support system was developed with the aim to analyse the effect of risk reduction planning alternatives on reducing the risk now and in the future, and support decision makers in selecting the best alternatives. Central to the SDSS are the stakeholders. The envisaged users of the system are organizations involved in planning of risk reduction measures, and that have staff capable of visualizing and analyzing spatial data at a municipal scale. The SDSS should be able to function in different countries with different legal frameworks and with organizations with different mandates. These could be subdivided into Civil protection organization with the mandate to design disaster response plans, Expert organizations with the mandate to design structural risk reduction measures (e.g. dams, dikes, check-dams etc), and planning organizations with the mandate to make land development plans. The SDSS can be used in different ways: analyzing the current level of risk, analyzing the best alternatives for risk reduction, the evaluation of the consequences of possible future scenarios to the risk levels, and the evaluation how different risk reduction alternatives will lead to risk reduction under different future scenarios. The SDSS is developed based on open source software and following open standards, for code as well as for data formats and service interfaces. Code development was based upon open source software as well. The architecture of the system is modular. The various parts of the system are loosely coupled, extensible, using standards for interoperability, flexible and web-based. The Spatial Decision Support System is composed of a number of integrated components. The Risk Assessment component allows to carry out spatial risk analysis, with different degrees of complexity, ranging from simple exposure (overlay of hazard and assets maps) to

  12. HLA-DRB1 Alleles as Genetic Risk Factors for the Development of Anti-MDA5 Antibodies in Patients with Dermatomyositis.

    Science.gov (United States)

    Chen, Zhiyong; Wang, Yan; Kuwana, Masataka; Xu, Xue; Hu, Wei; Feng, Xuebing; Wang, Hong; Kimura, Akinori; Sun, Lingyun

    2017-09-01

    Patients with polymyositis/dermatomyositis (PM/DM) who express anti-melanoma differentiation associated protein 5 (anti-MDA5) antibodies frequently present with interstitial lung disease (ILD). The aim of this study was to investigate the association of HLA-DRB1 with anti-MDA5 expression in PM/DM. The frequency of DRB1 alleles was compared among 70 patients with PM, 104 patients with DM, and 400 healthy controls in a Han Chinese population. Frequencies of DRB1*04:01 [17.0% vs 1.3%, corrected p value (p c ) = 3.8 × 10 -8 , OR 16.2, 95% CI 6.6-39.7] and *12:02 (42.6% vs 19.3%, p c = 0.008, OR 3.1, 95% CI 1.7-5.7) were significantly higher in anti-MDA5-positive patients with PM/DM compared with the controls. The frequencies of DRB1*04:01 (p = 5.2 × 10 -6 , OR 17.1, 95% CI 5.3-54.9) and *12:02 (p = 3.8 × 10 -4 , OR 3.1, 95% CI 1.7-5.7) in anti-MDA5-positive patients with DM-ILD were higher than in the controls, whereas the frequencies of DRB1*04:01 and *12:02 did not differ between the anti-MDA5-negative patients with DM-ILD and controls. No difference in the frequency of DRB1 alleles, other than *04:01, carrying the "shared epitope" (SE), i.e., *01:01, *01:02, *04:05, and *10:01, was observed between the controls and patients with DM stratified by the presence of anti-MDA5 and ILD. DRB1*04:01 and *12:02 confer susceptibility to anti-MDA5 antibody production in DM, which cannot be explained by the SE hypothesis.

  13. Nutrition support in hospitalised adults at nutritional risk

    DEFF Research Database (Denmark)

    Feinberg, Joshua; Nielsen, Emil Eik; Korang, Steven Kwasi

    2017-01-01

    International Clinical Trials Registry Platform (www.who.int/ictrp); ClinicalTrials.gov; Turning Research Into Practice (TRIP); Google Scholar; and BIOSIS, as well as relevant bibliographies of review articles and personal files. All searches are current to February 2016. SELECTION CRITERIA: We include...... methodology. Our primary outcomes were all-cause mortality, serious adverse events, and health-related quality of life. MAIN RESULTS: We included 244 randomised clinical trials with 28,619 participants that met our inclusion criteria. We considered all trials to be at high risk of bias. Two trials accounted...... experimental intervention (12 trials); general nutrition support (9 trials); and fortified food (2 trials). The control interventions were treatment as usual (122 trials); no intervention (107 trials); and placebo (15 trials). In 204/244 trials, the intervention lasted three days or more.We found no evidence...

  14. Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers

    NARCIS (Netherlands)

    Cox, David G.; Simard, Jacques; Sinnett, Daniel; Hamdi, Yosr; Soucy, Penny; Ouimet, Manon; Barjhoux, Laure; Verny-Pierre, Carole; McGuffog, Lesley; Healey, Sue; Szabo, Csilla; Greene, Mark H.; Mai, Phuong L.; Andrulis, Irene L.; Thomassen, Mads; Gerdes, Anne-Marie; Caligo, Maria A.; Friedman, Eitan; Laitman, Yael; Kaufman, Bella; Paluch, Shani S.; Borg, Åke; Karlsson, Per; Askmalm, Marie Stenmark; Bustinza, Gisela Barbany; Nathanson, Katherine L.; Domchek, Susan M.; Rebbeck, Timothy R.; Benítez, Javier; Hamann, Ute; Rookus, Matti A.; van den Ouweland, Ans M. W.; Ausems, Margreet G. E. M.; Aalfs, Cora M.; van Asperen, Christi J.; Devilee, Peter; Gille, Hans J. J. P.; Peock, Susan; Frost, Debra; Evans, D. Gareth; Eeles, Ros; Izatt, Louise; Adlard, Julian; Paterson, Joan; Eason, Jacqueline; Godwin, Andrew K.; Remon, Marie-Alice; Moncoutier, Virginie; van Os, T. A.; Meijers-Heijboer, H. E. J.

    2011-01-01

    Mutations in the BRCA1 gene substantially increase a woman's lifetime risk of breast cancer. However, there is great variation in this increase in risk with several genetic and non-genetic modifiers identified. The BRCA1 protein plays a central role in DNA repair, a mechanism that is particularly

  15. Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers

    DEFF Research Database (Denmark)

    Cox, David G; Simard, Jacques; Sinnett, Daniel

    2011-01-01

    Mutations in the BRCA1 gene substantially increase a woman's lifetime risk of breast cancer. However, there is great variation in this increase in risk with several genetic and non-genetic modifiers identified. The BRCA1 protein plays a central role in DNA repair, a mechanism that is particularly...

  16. Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers.

    NARCIS (Netherlands)

    Cox, D.G.; Simard, J.; Sinnett, D.; Hamdi, Y.; Soucy, P.; Ouimet, M.; Barjhoux, L.; Verny-Pierre, C.; McGuffog, L.; Healey, S.; Szabo, C.; Greene, M.H.; Mai, P.L.; Andrulis, I.L.; Thomassen, M.; Gerdes, A.M.; Caligo, M.A.; Friedman, E.; Laitman, Y.; Kaufman, B.; Paluch, S.S.; Borg, A.; Karlsson, P.; Askmalm, M.S.; Bustinza, G.B.; Nathanson, K.L.; Domchek, S.M.; Rebbeck, T.R.; Benitez, J.; Hamann, U.; Rookus, M.A.; Ouweland, A.M. van den; Ausems, M.G.; Aalfs, C.M.; Asperen, C.J. van; Devilee, P.; Gille, H.J.; Peock, S.; Frost, D.; Evans, D.G.; Eeles, R.; Izatt, L.; Adlard, J.; Paterson, J.; Eason, J.; Godwin, A.K.; Remon, M.A.; Moncoutier, V.; Gauthier-Villars, M.; Lasset, C.; Giraud, S.; Hardouin, A.; Berthet, P.; Sobol, H.; Eisinger, F.; Bressac de Paillerets, B.; Caron, O.; Delnatte, C.; Goldgar, D.; Miron, A.; Ozcelik, H.; Buys, S.; Southey, M.C.; Terry, M.B.; Singer, C.F.; Dressler, A.C.; Tea, M.K.; Hansen, T.V.; Johannsson, O.; Piedmonte, M.; Rodriguez, G.C.; Basil, J.B.; Blank, S.; Toland, A.E.; Montagna, M.; Isaacs, C.; Blanco, I.; Gayther, S.A.; Moysich, K.B.; Schmutzler, R.K.; Wappenschmidt, B.; Engel, C.; Meindl, A.; Ditsch, N.; Arnold, N.; Niederacher, D.; Sutter, C.; Gadzicki, D.; Fiebig, B.; Caldes, T.; Laframboise, R.; Nevanlinna, H.; Chen, X.; Beesley, J.; Spurdle, A.B.; Neuhausen, S.L.; Ding, Y.C.; Couch, F.J.; Wang, X.; Peterlongo, P.; Manoukian, S.; Bernard, L.; Radice, P.; Easton, D.F.; Chenevix-Trench, G.; Antoniou, A.C.; Stoppa-Lyonnet, D.; Mazoyer, S.; Sinilnikova, O.M.; Ligtenberg, M.J.L.; Hoogerbrugge, N.; et al.,

    2011-01-01

    Mutations in the BRCA1 gene substantially increase a woman's lifetime risk of breast cancer. However, there is great variation in this increase in risk with several genetic and non-genetic modifiers identified. The BRCA1 protein plays a central role in DNA repair, a mechanism that is particularly

  17. Allele coding in genomic evaluation

    Directory of Open Access Journals (Sweden)

    Christensen Ole F

    2011-06-01

    Full Text Available Abstract Background Genomic data are used in animal breeding to assist genetic evaluation. Several models to estimate genomic breeding values have been studied. In general, two approaches have been used. One approach estimates the marker effects first and then, genomic breeding values are obtained by summing marker effects. In the second approach, genomic breeding values are estimated directly using an equivalent model with a genomic relationship matrix. Allele coding is the method chosen to assign values to the regression coefficients in the statistical model. A common allele coding is zero for the homozygous genotype of the first allele, one for the heterozygote, and two for the homozygous genotype for the other allele. Another common allele coding changes these regression coefficients by subtracting a value from each marker such that the mean of regression coefficients is zero within each marker. We call this centered allele coding. This study considered effects of different allele coding methods on inference. Both marker-based and equivalent models were considered, and restricted maximum likelihood and Bayesian methods were used in inference. Results Theoretical derivations showed that parameter estimates and estimated marker effects in marker-based models are the same irrespective of the allele coding, provided that the model has a fixed general mean. For the equivalent models, the same results hold, even though different allele coding methods lead to different genomic relationship matrices. Calculated genomic breeding values are independent of allele coding when the estimate of the general mean is included into the values. Reliabilities of estimated genomic breeding values calculated using elements of the inverse of the coefficient matrix depend on the allele coding because different allele coding methods imply different models. Finally, allele coding affects the mixing of Markov chain Monte Carlo algorithms, with the centered coding being

  18. Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3

    NARCIS (Netherlands)

    Hamdi, Yosr; Soucy, Penny; Kuchenbaeker, Karoline B; Pastinen, Tomi; Droit, Arnaud; Lemaçon, Audrey; Adlard, Julian; Aittomäki, Kristiina; Andrulis, Irene L; Arason, Adalgeir; Arnold, Norbert; Arun, Banu K; Azzollini, Jacopo; Bane, Anita; Barjhoux, Laure; Barrowdale, Daniel; Benitez, Javier; Berthet, Pascaline; Blok, Marinus J; Bobolis, Kristie; Bonadona, Valérie; Bonanni, Bernardo; Bradbury, Angela R; Brewer, Carole; Buecher, Bruno; Buys, Saundra S; Caligo, Maria A; Chiquette, Jocelyne; Chung, Wendy K; Claes, Kathleen B M; Daly, Mary B; Damiola, Francesca; Davidson, Rosemarie; De la Hoya, Miguel; De Leeneer, Kim; Diez, Orland; Ding, Yuan Chun; Dolcetti, Riccardo; Domchek, Susan M; Dorfling, Cecilia M; Eccles, Diana; Eeles, Ros; Einbeigi, Zakaria; Ejlertsen, Bent; Engel, Christoph; Gareth Evans, D; Feliubadalo, Lidia; Foretova, Lenka; Fostira, Florentia; Foulkes, William D; Fountzilas, George; Friedman, Eitan; Frost, Debra; Ganschow, Pamela; Ganz, Patricia A; Garber, Judy; Gayther, Simon A; Gerdes, Anne-Marie; Glendon, Gord; Godwin, Andrew K; Goldgar, David E; Greene, Mark H; Gronwald, Jacek; Hahnen, Eric; Hamann, Ute; Hansen, Thomas V O; Hart, Steven; Hays, John L; Hogervorst, Frans B L; Hulick, Peter J; Imyanitov, Evgeny N; Isaacs, Claudine; Izatt, Louise; Jakubowska, Anna; James, Paul; Janavicius, Ramunas; Jensen, Uffe Birk; John, Esther M; Joseph, Vijai; Just, Walter; Kaczmarek, Katarzyna; Karlan, Beth Y; Kets, Carolien M; Kirk, Judy; Kriege, Mieke; Laitman, Yael; Laurent, Maïté; Lazaro, Conxi; Leslie, Goska; Lester, Jenny; Lesueur, Fabienne; Liljegren, Annelie; Loman, Niklas; Loud, Jennifer T; Manoukian, Siranoush; Mariani, Milena; Mazoyer, Sylvie; McGuffog, Lesley; Meijers-Heijboer, Hanne E J; Meindl, Alfons; Miller, Austin; Montagna, Marco; Mulligan, Anna Marie; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Nussbaum, Robert L; Olah, Edith; Olopade, Olufunmilayo I; Ong, Kai-Ren; Oosterwijk, Jan C; Osorio, Ana; Papi, Laura; Park, Sue Kyung; Pedersen, Inge Sokilde; Peissel, Bernard; Segura, Pedro Perez; Peterlongo, Paolo; Phelan, Catherine M; Radice, Paolo; Rantala, Johanna; Rappaport-Fuerhauser, Christine; Rennert, Gad; Richardson, Andrea; Robson, Mark; Rodriguez, Gustavo C; Rookus, Matti A; Schmutzler, Rita Katharina; Sevenet, Nicolas; Shah, Payal D; Singer, Christian F; Slavin, Thomas P; Snape, Katie; Sokolowska, Johanna; Sønderstrup, Ida Marie Heeholm; Southey, Melissa; Spurdle, Amanda B; Stadler, Zsofia; Stoppa-Lyonnet, Dominique; Sukiennicki, Grzegorz; Sutter, Christian; Tan, Yen; Tea, Muy-Kheng; Teixeira, Manuel R; Teulé, Alex; Teo, Soo-Hwang; Terry, Mary Beth; Thomassen, Mads; Tihomirova, Laima; Tischkowitz, Marc; Tognazzo, Silvia; Toland, Amanda Ewart; Tung, Nadine; van den Ouweland, Ans M W; van der Luijt, Rob B; van Engelen, Klaartje; van Rensburg, Elizabeth J; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Wijnen, Juul T; Rebbeck, Timothy; Chenevix-Trench, Georgia; Offit, Kenneth; Couch, Fergus J; Nord, Silje; Easton, Douglas F; Antoniou, Antonis C; Simard, Jacques

    PURPOSE: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1

  19. Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of a modifier of breast cancer risk at locus 11q22.3

    NARCIS (Netherlands)

    Y. Hamdi (Yosr); Soucy, P. (Penny); Kuchenbaeker, K.B. (Karoline B.); Pastinen, T. (Tomi); A. Droit (Arnaud); Lemaçon, A. (Audrey); J.W. Adlard (Julian); K. Aittomäki (Kristiina); I.L. Andrulis (Irene); A. Arason (Adalgeir); N. Arnold (Norbert); B.K. Arun (Banu); J. Azzollini; A.L. Bane (Anita L.); Barjhoux, L. (Laure); D. Barrowdale (Daniel); J. Benítez (Javier); P. Berthet (Pascaline); M.J. Blok (Marinus); K.A. Bobolis (Kristie A.); V. Bonadona (Valérie); B. Bonnani (Bernardo); Bradbury, A.R. (Angela R.); C. Brewer (Carole); B. Buecher (Bruno); Buys, S.S. (Saundra S.); M.A. Caligo (Maria); Chiquette, J. (Jocelyne); W. Chung (Wendy); K.B.M. Claes (Kathleen B.M.); Daly, M.B. (Mary B.); F. Damiola (Francesca); R. Davidson (Rosemarie); M. de La Hoya (Miguel); K. De Leeneer (Kim); O. Díez (Orland); Y.C. Ding (Yuan); R. Dolcetti (Riccardo); S.M. Domchek (Susan); C.M. Dorfling (Cecilia); D. Eccles (Diana); R. Eeles (Ros); Z. Einbeigi (Zakaria); B. Ejlertsen (Bent); EMBRACE; C. Engel (Christoph); Gareth Evans, D.; L. Feliubadaló (L.); L. Foretova (Lenka); F. Fostira (Florentia); Foulkes, W.D. (William D.); G. Fountzilas (George); E. Friedman (Eitan); D. Frost (Debra); P. Ganschow (Pamela); P.A. Ganz (Patricia A.); J. Garber (Judy); S.A. Gayther (Simon); GEMO Study Collaborators; A-M. Gerdes (Anne-Marie); G. Glendon (Gord); A.K. Godwin (Andrew K.); D. Goldgar (David); M.H. Greene (Mark H.); J. Gronwald (Jacek); E. Hahnen (Eric); U. Hamann (Ute); T.V.O. Hansen (Thomas); S. Hart (Stewart); J. Hays (John); HEBON; F.B.L. Hogervorst (Frans); P.J. Hulick (Peter); E.N. Imyanitov (Evgeny); C. Isaacs (Claudine); L. Izatt (Louise); A. Jakubowska (Anna); M. James (Margaret); R. Janavicius (Ramunas); U.B. Jensen; E.M. John (Esther); V. Joseph (Vijai); Just, W. (Walter); Kaczmarek, K. (Katarzyna); Karlan, B.Y. (Beth Y.); KConFab Investigators; C.M. Kets; J. Kirk (Judy); Kriege, M. (Mieke); Y. Laitman (Yael); Laurent, M. (Maïté); C. Lazaro (Conxi); Leslie, G. (Goska); K.J. Lester (Kathryn); F. Lesueur (Fabienne); A. Liljegren (Annelie); N. Loman (Niklas); J.T. Loud (Jennifer); S. Manoukian (Siranoush); Mariani, M. (Milena); S. Mazoyer (Sylvie); L. McGuffog (Lesley); E.J. Meijers-Heijboer (Hanne); A. Meindl (Alfons); A. Miller (Austin); M. Montagna (Marco); A.-M. Mulligan (Anna-Marie); K.L. Nathanson (Katherine); S.L. Neuhausen (Susan); H. Nevanlinna (Heli); R.L. Nussbaum (Robert L.); Olah, E. (Edith); O.I. Olopade (Olufunmilayo I.); K.-R. Ong (Kai-Ren); J.C. Oosterwijk (Jan); A. Osorio (Ana); L. Papi (Laura); S.K. Park (Sue K.); Pedersen, I.S. (Inge Sokilde); B. Peissel (Bernard); P.P. Segura (Pedro Perez); P. Peterlongo (Paolo); C. Phelan (Catherine); P. Radice (Paolo); J. Rantala (Johanna); Rappaport-Fuerhauser, C. (Christine); G. Rennert (Gad); A.L. Richardson (Andrea); M. Robson (Mark); G.C. Rodriguez (Gustavo); M.A. Rookus (Matti); R.K. Schmutzler (Rita); N. Sevenet (Nicolas); Shah, P.D. (Payal D.); C.F. Singer (Christian); Slavin, T.P. (Thomas P.); Snape, K. (Katie); J. Sokolowska (Johanna); Sønderstrup, I.M.H. (Ida Marie Heeholm); M.C. Southey (Melissa); A.B. Spurdle (Amanda); Stadler, Z. (Zsofia); D. Stoppa-Lyonnet (Dominique); G. Sukiennicki (Grzegorz); C. Sutter (Christian); Tan, Y. (Yen); M.-K. Tea; P.J. Teixeira; A. Teulé (A.); S.-H. Teo (Soo-Hwang); M.B. Terry (Mary Beth); M. Thomassen (Mads); L. Tihomirova (Laima); M. Tischkowitz (Marc); S. Tognazzo (Silvia); A.E. Toland (Amanda); N. Tung (Nadine); A.M.W. van den Ouweland (Ans); R.B. van der Luijt (Rob); K. van Engelen (Klaartje); E.J. van Rensburg (Elizabeth); R. Varon-Mateeva (Raymonda); B. Wapenschmidt (Barbara); J.T. Wijnen (Juul); R. Rebbeck (Timothy); G. Chenevix-Trench (Georgia); K. Offit (Kenneth); Couch, F.J. (Fergus J.); S. Nord (Silje); D.F. Easton (Douglas F.); A.C. Antoniou (Antonis C.); Simard, J. (Jacques)

    2016-01-01

    textabstractPurpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility

  20. Impact of preoperative nutritional support on clinical outcome in abdominal surgical patients at nutritional risk

    DEFF Research Database (Denmark)

    Jie, Bin; Jiang, Zhu-Ming; Nolan, Marie T

    2012-01-01

    This multicenter, prospective cohort study evaluated the effect of preoperative nutritional support in abdominal surgical patients at nutritional risk as defined by the Nutritional Risk Screening Tool 2002 (NRS-2002).......This multicenter, prospective cohort study evaluated the effect of preoperative nutritional support in abdominal surgical patients at nutritional risk as defined by the Nutritional Risk Screening Tool 2002 (NRS-2002)....

  1. Allele coding in genomic evaluation

    DEFF Research Database (Denmark)

    Standen, Ismo; Christensen, Ole Fredslund

    2011-01-01

    Genomic data are used in animal breeding to assist genetic evaluation. Several models to estimate genomic breeding values have been studied. In general, two approaches have been used. One approach estimates the marker effects first and then, genomic breeding values are obtained by summing marker...... effects. In the second approach, genomic breeding values are estimated directly using an equivalent model with a genomic relationship matrix. Allele coding is the method chosen to assign values to the regression coefficients in the statistical model. A common allele coding is zero for the homozygous...... genotype of the first allele, one for the heterozygote, and two for the homozygous genotype for the other allele. Another common allele coding changes these regression coefficients by subtracting a value from each marker such that the mean of regression coefficients is zero within each marker. We call...

  2. Clinician support and psychosocial risk factors associated with breastfeeding discontinuation.

    Science.gov (United States)

    Taveras, Elsie M; Capra, Angela M; Braveman, Paula A; Jensvold, Nancy G; Escobar, Gabriel J; Lieu, Tracy A

    2003-07-01

    Breastfeeding rates fall short of goals set in Healthy People 2010 and other national recommendations. The current, national breastfeeding continuation rate of 29% at 6 months lags behind the Healthy People 2010 goal of 50%. The objective of this study was to evaluate associations between breastfeeding discontinuation at 2 and 12 weeks postpartum and clinician support, maternal physical and mental health status, workplace issues, and other factors amenable to intervention. A prospective cohort study was conducted of low-risk mothers and infants who were in a health maintenance organization and enrolled in a randomized, controlled trial of home visits. Mothers were interviewed in person at 1 to 2 days postpartum and by telephone at 2 and 12 weeks. Logistic regression modeling was performed to assess the independent effects of the predictors of interest, adjusting for sociodemographic and other confounding variables. Of the 1163 mother-newborn pairs in the cohort, 1007 (87%) initiated breastfeeding, 872 (75%) were breastfeeding at the 2-week interview, and 646 (55%) were breastfeeding at the 12-week interview. In the final multivariate models, breastfeeding discontinuation at 2 weeks was associated with lack of confidence in ability to breastfeed at the 1- to 2-day interview (odds ratio [OR]: 2.8; 95% confidence interval [CI]: 1.02-7.6), early breastfeeding problems (OR: 1.5; 95% CI: 1.1-1.97), Asian race/ethnicity (OR: 2.6; 95% CI: 1.1-5.7), and lower maternal education (OR: 1.5; 95% CI: 1.2-1.9). Mothers were much less likely to discontinue breastfeeding at 12 weeks postpartum if they reported (during the 12-week interview) having received encouragement from their clinician to breastfeed (OR: 0.6; 95% CI: 0.4-0.8). Breastfeeding discontinuation at 12 weeks was also associated with demographic factors and maternal depressive symptoms (OR: 1.18; 95% CI: 1.01-1.37) and returning to work or school by 12 weeks postpartum (OR: 2.4; 95% CI: 1.8-3.3). Our results indicate

  3. Clonal Ordering of 17p and 5q Allelic Losses in Barrett Dysplasia and Adenocarcinoma

    Science.gov (United States)

    Blount, Patricia L.; Meltzer, Stephen J.; Yin, Jing; Huang, Ying; Krasna, Mark J.; Reid, Brian J.

    1993-04-01

    Both 17p and 5q allelic losses appear to be involved in the pathogenesis or progression of many human solid tumors. In colon carcinogenesis, there is strong evidence that the targets of the 17p and 5q allelic losses are TP53, the gene encoding p53, and APC, respectively. It is widely accepted that 5q allelic losses precede 17p allelic losses in the progression to colonic carcinoma. The data, however, supporting this proposed order are largely based on the prevalence of 17p and 5q allelic losses in adenomas and unrelated adenocarcinomas from different patients. We investigated the order in which 17p and 5q allelic losses developed during neoplastic progression in Barrett esophagus by evaluating multiple aneuploid cell populations from the same patient. Using DNA content flow cytometric cell sorting and polymerase chain reaction, 38 aneuploid cell populations from 14 patients with Barrett esophagus who had high grade dysplasia, cancer or both were evaluated for 17p and 5q allelic losses. 17p allelic losses preceded 5q allelic losses in 7 patients, both 17p and 5q allelic losses were present in all aneuploid populations of 4 patients, and only 17p (without 5q) allelic losses were present in the aneuploid populations of 3 patients. In no patient did we find that a 5q allelic loss preceded a 17p allelic loss. Our data suggest that 17p allelic losses typically occur before 5q allelic losses during neoplastic progression in Barrett esophagus.

  4. Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers.

    OpenAIRE

    Cox, D. G.; Simard, J.; Sinnett, D.; Hamdi, Y.; Soucy, P.; Ouimet, M.; Barjhoux, L.; Verny-Pierre, C.; McGuffog, L.; Healey, S.; Szabo, C.; Greene, M. H.; Mai, P. L.; Andrulis, I. L.; Thomassen, M.

    2011-01-01

    Mutations in the BRCA1 gene substantially increase a woman's lifetime risk of breast cancer. However, there is great variation in this increase in risk with several genetic and non-genetic modifiers identified. The BRCA1 protein plays a central role in DNA repair, a mechanism that is particularly instrumental in safeguarding cells against tumorigenesis. We hypothesized that polymorphisms that alter the expression and/or function of BRCA1 carried on the wild-type (non-mutated) copy of the BRCA...

  5. Knowledge management in support of enterprise risk management

    OpenAIRE

    Rodriguez, Eduardo; Edwards, John S.

    2014-01-01

    Risk management and knowledge management have so far been studied almost independently. The evolution of risk management to the holistic view of Enterprise Risk Management requires the destruction of barriers between organizational silos and the exchange and application of knowledge from different risk management areas. However, knowledge management has received little or no attention in risk management. This paper examines possible relationships between knowledge management constructs relate...

  6. 164Ile allele in the beta2-Adrenergic receptor gene is associated with risk of elevated blood pressure in women. The Copenhagen City Heart Study

    DEFF Research Database (Denmark)

    Sethi, AA; Tybjærg-Hansen, A; Jensen, Gorm Boje

    2005-01-01

    Since beta2-adrenergic receptors are important regulators of blood pressure, genetic variation in this receptor could explain risk of elevated blood pressure in selected individuals. We tested the hypothesis that Gly16Arg, Gln27Glu, and Thr164Ile in the beta2-adrenergic receptor gene associated w...

  7. Carriers of the Complex Allele HFE c.[187C>G;340+4T>C] Have Increased Risk of Iron Overload in São Miguel Island Population (Azores, Portugal).

    Science.gov (United States)

    Branco, Claudia C; Gomes, Cidália T; De Fez, Laura; Bulhões, Sara; Brilhante, Maria José; Pereirinha, Tânia; Cabral, Rita; Rego, Ana Catarina; Fraga, Cristina; Miguel, António G; Brasil, Gracinda; Macedo, Paula; Mota-Vieira, Luisa

    2015-01-01

    Iron overload is associated with acquired and genetic conditions, the most common being hereditary hemochromatosis (HH) type-I, caused by HFE mutations. Here, we conducted a hospital-based case-control study of 41 patients from the São Miguel Island (Azores, Portugal), six belonging to a family with HH type-I pseudodominant inheritance, and 35 unrelated individuals fulfilling the biochemical criteria of iron overload compatible with HH type-I. For this purpose, we analyzed the most common HFE mutations- c.845G>A [p.Cys282Tyr], c.187C>G [p.His63Asp], and c.193A>T [p.Ser65Cys]. Results revealed that the family's HH pseudodominant pattern is due to consanguineous marriage of HFE-c.845G>A carriers, and to marriage with a genetically unrelated spouse that is a -c.187G carrier. Regarding unrelated patients, six were homozygous for c.845A, and three were c.845A/c.187G compound heterozygous. We then performed sequencing of HFE exons 2, 4, 5 and their intron-flanking regions. No other mutations were observed, but we identified the -c.340+4C [IVS2+4C] splice variant in 26 (74.3%) patients. Functionally, the c.340+4C may generate alternative splicing by HFE exon 2 skipping and consequently, a protein missing the α1-domain essential for HFE/ transferrin receptor-1 interactions. Finally, we investigated HFE mutations configuration with iron overload by determining haplotypes and genotypic profiles. Results evidenced that carriers of HFE-c.187G allele also carry -c.340+4C, suggesting in-cis configuration. This data is corroborated by the association analysis where carriers of the complex allele HFE-c.[187C>G;340+4T>C] have an increased iron overload risk (RR = 2.08, 95% CI = 1.40-2.94, poverload because they will produce two altered proteins--the p.63Asp [c.187G], and the protein lacking 88 amino acids encoded by exon 2. In summary, we provide evidence that the complex allele HFE-c.[187C>G;340+4T>C] has a role, as genetic predisposition factor, on iron overload in the S

  8. Risk-Based Decision Support of Water Resource Management Alternatives

    National Research Council Canada - National Science Library

    West, Paul D; Trainor, Timothy E

    2006-01-01

    .... A model is presented that combines a new risk assessment methodology with traditional decision-making tools to enable systems engineers to capture the full spectrum of operational risks during the design process...

  9. SADA: Ecological Risk Based Decision Support System for Selective Remediation

    Science.gov (United States)

    Spatial Analysis and Decision Assistance (SADA) is freeware that implements terrestrial ecological risk assessment and yields a selective remediation design using its integral geographical information system, based on ecological and risk assessment inputs. Selective remediation ...

  10. Incorporating Allelic Dropout

    Czech Academy of Sciences Publication Activity Database

    Slovák, Dalibor

    2014-01-01

    Roč. 2, č. 1 (2014), s. 31-33 ISSN 1805-8698 Grant - others:SVV(CZ) 260034 Institutional support: RVO:67985807 Keywords : drop-out * peak height * DNA interpretation Subject RIV: IN - Informatics, Computer Science http://www.ijbh.org/ijbh2014-1.pdf

  11. A common allele on chromosome 9 associated with coronary heartdisease

    Energy Technology Data Exchange (ETDEWEB)

    McPherson, Ruth; Pertsemlidis, Alexander; Kavaslar, Nihan; Stewart, Alexandre; Roberts, Robert; Cox, David R.; Hinds, David; Pennachio, Len; Tybjaerg-Hansen, Anne; Folsom, Aaron R.; Boerwinkle,Eric; Hobbs, Helen H.; Cohen, Jonathan C.

    2007-03-01

    Coronary heart disease (CHD) is a major cause of death in Western countries. Here we used genome-wide association scanning to identify a 58 kb interval on chromosome 9 that was consistently associated with CHD in six independent samples. The interval contains no annotated genes and is not associated with established CHD risk factors such as plasma lipoproteins, hypertension or diabetes. Homozygotes for the risk allele comprise 20-25% of Caucasians and have a {approx}30-40% increased risk of CHD. These data indicate that the susceptibility allele acts through a novel mechanism to increase CHD risk in a large fraction of the population.

  12. Governance in support of integrated flood risk management? The case of Romania

    NARCIS (Netherlands)

    Vinke-de Kruijf, Joanne; Kuks, Stefanus M.M.; Augustijn, Dionysius C.M.

    2015-01-01

    Building on an existing model of governance, this paper aims to assess the supportiveness of Romania׳s structural flood risk governance context towards integrated flood risk management. We assert that a governance structure supports the development and implementation of integrated flood risk

  13. Protective effects of self-esteem and family support on suicide risk behaviors among at-risk adolescents.

    Science.gov (United States)

    Sharaf, Amira Y; Thompson, Elaine A; Walsh, Elaine

    2009-08-01

    If and how family support and self-esteem might interact to protect against adolescent suicide risk is not well understood. Hierarchical multiple regression was used to examine the moderating effect of family support on the relationship between self-esteem and suicide risk behaviors among potential high school dropouts (N = 849), using questionnaires and in-depth assessment interviews. Family support moderated the impact of self-esteem on suicide risk; the ameliorating effect of self-esteem was stronger among adolescents with low versus high family support. Self-esteem influences adolescent suicide risk behaviors for youth with low as well as high family support. Interventions designed to strengthen both self-esteem and support resources are appropriate.

  14. Screening of Nutritional Risk and Nutritional Support in General Surgery Patients: A Survey from Shanghai, China

    Science.gov (United States)

    Jia, Zhen-Yi; Yang, Jun; Tong, Da-Nian; Peng, Jia-Yuan; Zhang, Zhong-Wei; Liu, Wei-Jie; Xia, Yang; Qin, Huan-long

    2015-01-01

    To determine the prevalence of nutritional risk in surgical departments and to evaluate the impact of nutritional support on clinical outcomes. The nutritional risk in different surgical diseases and the different way of nutritional support on clinical outcomes in patients at nutritional risk remain unclear. Hospitalized patients from general surgical departments were screened using the Nutritional Risk Screening (NRS) 2002 questionnaire on admission. Data were collected on nutritional risk, complications, and length of stay (LOS). Overall, 5034 patients were recruited; the overall prevalence of nutritional risk on admission were 19.2%. The highest prevalence was found among patients with gastric cancer. At-risk patients had more complications and longer LOS than nonrisk patients. Of the at-risk patients, the complication rate was significantly lower and LOS was significantly shorter in the nutritional-support group than in the no-support group (20.9 versus 30.0%, P nutrition or who received support for 5 to 7 days, or daily support entailing 16 to 25 kcal/kg of nonprotein energy. Different surgical diseases have different levels of nutritional risk. The provision of nutritional support was associated with a lower complication rate and a shorter LOS for gastric, colorectal, and HPB cancer patients at nutritional risk. The improper use of nutritional support may not improve outcomes for at-risk patients. PMID:26011204

  15. The moderating role of social support on the relationship between impulsivity and suicide risk.

    Science.gov (United States)

    Kleiman, Evan M; Riskind, John H; Schaefer, Karen E; Weingarden, Hilary

    2012-01-01

    Suicide is the second leading cause of death among college students. There has been considerable research into risk factors for suicide, such as impulsivity, but considerably less research on protective factors. The present study examines the role that social support plays in the relationship between impulsivity and suicide risk. Participants were 169 undergraduates who completed self-report measures of impulsivity and social support. Suicide risk was assessed using an interview measure. Social support moderates the relationship between impulsivity and suicide risk, such that those who are highly impulsive are less likely to be at risk for suicide if they also have high levels of social support. Social support can be a useful buffer to suicide risk for at-risk individuals who are highly impulsive.

  16. NanoRisk - A Conceptual Decision Support Tool for Nanomaterials

    DEFF Research Database (Denmark)

    Hansen, Steffen Foss; Baun, Anders; Alstrup Jensen, K.

    2011-01-01

    Only a few risk assessment methodologies and approaches are useful for assessing the risk for professional end-users, consumers and the environment. We have developed a generic framework (NanoRiskCat) that can be used by companies and risk assessors to categorize nanomaterials considering existing...... environmental, health and safety information and known uncertainties. In NanoRiskCat’s simplest form, the final evaluation outcome for a specific nanomaterial in a given application will be communicated in the form of a short title (e.g. TiO2 in sunscreen) describing the use of the nanomaterial. This short...... to the exposure and hazard potential are green , yellow corresponding to none, possible, expected and unknown, respectively. The exposure potential was evaluated based on 1) the location of the nanomaterial and 2) a judgment of the potential of nanomaterial exposure based on the description and explanation...

  17. Computerised Genetic Risk Assessment and Decision Support in Primary Care

    Directory of Open Access Journals (Sweden)

    Andrew Coulson

    2000-09-01

    To address these issues, a new computer application called RAGs (Risk Assessment in Genetics has been designed. The system allows a doctor to create family trees and assess genetic risk of breast cancer. RAGs possesses two features that distinguish it from similar software: (a a user-centred design, which takes into account the requirements of the doctor-patient encounter; (b risk reporting using qualitative evidence for or against an increased risk, which the authors believe to be more useful and accessible than numerical probabilities are. In that the system allows for any genetic risk guideline to be implemented, it can be used with all diseases for which evaluation guidelines exist. The software may be easily modified to cater for the amount of detail required by different specialists.

  18. A risk-based model for maintenance decision support of civil structures using RAMS

    NARCIS (Netherlands)

    Viana Da Rocha, T. C.; Stipanovic, I.; Hartmann, A.; Bakker, J.

    2017-01-01

    As a cornerstone of transportation asset management, risk-based approaches have been used to support maintenance decisions of civil structures. However, ambiguous and subjective risk criteria and inconsistency on the use of risk-based approaches can lead to a fuzzy understanding of the risks

  19. Resting-State Brain and the FTO Obesity Risk Allele: Default Mode, Sensorimotor, and Salience Network Connectivity Underlying Different Somatosensory Integration and Reward Processing between Genotypes.

    Science.gov (United States)

    Olivo, Gaia; Wiemerslage, Lyle; Nilsson, Emil K; Solstrand Dahlberg, Linda; Larsen, Anna L; Olaya Búcaro, Marcela; Gustafsson, Veronica P; Titova, Olga E; Bandstein, Marcus; Larsson, Elna-Marie; Benedict, Christian; Brooks, Samantha J; Schiöth, Helgi B

    2016-01-01

    Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene are linked to obesity, but how these SNPs influence resting-state neural activation is unknown. Few brain-imaging studies have investigated the influence of obesity-related SNPs on neural activity, and no study has investigated resting-state connectivity patterns. We tested connectivity within three, main resting-state networks: default mode (DMN), sensorimotor (SMN), and salience network (SN) in 30 male participants, grouped based on genotype for the rs9939609 FTO SNP, as well as punishment and reward sensitivity measured by the Behavioral Inhibition (BIS) and Behavioral Activation System (BAS) questionnaires. Because obesity is associated with anomalies in both systems, we calculated a BIS/BAS ratio (BBr) accounting for features of both scores. A prominence of BIS over BAS (higher BBr) resulted in increased connectivity in frontal and paralimbic regions. These alterations were more evident in the obesity-associated AA genotype, where a high BBr was also associated with increased SN connectivity in dopaminergic circuitries, and in a subnetwork involved in somatosensory integration regarding food. Participants with AA genotype and high BBr, compared to corresponding participants in the TT genotype, also showed greater DMN connectivity in regions involved in the processing of food cues, and in the SMN for regions involved in visceral perception and reward-based learning. These findings suggest that neural connectivity patterns influence the sensitivity toward punishment and reward more closely in the AA carriers, predisposing them to developing obesity. Our work explains a complex interaction between genetics, neural patterns, and behavioral measures in determining the risk for obesity and may help develop individually-tailored strategies for obesity prevention.

  20. Aggregate exposure pathways in support of risk assessment

    Science.gov (United States)

    Over time, risk assessment has shifted from establishing relationships between exposure to a single chemical and a resulting adverse health outcome, to evaluating multiple chemicals and disease outcomes simultaneously. As a result, there is an increasing need to better understand...

  1. Integrating LCA and Risk Assessment for Decision Support

    DEFF Research Database (Denmark)

    Dong, Yan; Miraglia, Simona; Manzo, Stefano

    The study aims at developing a methodology using decision analysis theory and tools to find the optimal policy (or design) of the studied system, to ensure both sustainability and meanwhile manage risks.......The study aims at developing a methodology using decision analysis theory and tools to find the optimal policy (or design) of the studied system, to ensure both sustainability and meanwhile manage risks....

  2. "Homeland Defense: At Risk as a Result of Civil Support?"

    National Research Council Canada - National Science Library

    Brickhouse, Tonja

    2003-01-01

    This research effort is an attempt by the author to examine the broad area of military support to civil authorities and the potential for a significant demand on Department of Defense (DoD) resources...

  3. Handling risk attitudes for preference learning and intelligent decision support

    DEFF Research Database (Denmark)

    Franco de los Ríos, Camilo; Hougaard, Jens Leth; Nielsen, Kurt

    2015-01-01

    Intelligent decision support should allow integrating human knowledge with efficient algorithms for making interpretable and useful recommendations on real world decision problems. Attitudes and preferences articulate and come together under a decision process that should be explicitly modeled...

  4. Effects of the APOE ε2 Allele on Mortality and Cognitive Function in the Oldest Old

    DEFF Research Database (Denmark)

    Lindahl-Jacobsen, Rune; Tan, Qihua; Mengel-From, Jonas

    2013-01-01

    Some studies indicate that the APOE ε2 allele may have a protective effect on mortality and mental health among the elderly adults. We investigated the effect of the APOE ε2 allele on cognitive function and mortality in 1651 members of the virtually extinct Danish 1905 birth cohort. We found...... no protective effect of the APOE ε2 allele on mortality compared with the APOE ε3 allele. The point estimates indicated an increased protection against cognitive decline over time for persons with the APOE ε2 allele. Cognitive score did not significantly modify the mortality risk of the various APOE genotypes....... We did not find a protective effect of the APOE ε2 allele on mortality among the oldest old, but in agreement with our previous findings, we found a 22% increased mortality risk for APOE ε4 carriers. The APOE ε2 allele may be protective on cognitive decline among the oldest old....

  5. Coopetition as Support Strategy for Supply Chain Risk Management

    Directory of Open Access Journals (Sweden)

    João Batista de Camargo Junior

    2014-06-01

    Full Text Available As supply chain management research and its adoption advance, new challenges are imposed for researchers and managers. Accordingly, the supply chain risk management (SCRM has been a prominent field because it suggests strategies and action plans to mitigate these risks. On the other hand, it is observed that the coopetition concept advocates that two competing organizations can work together in some activities in the form of a strategic alliance, contributing to achieve maximum efficiency. Therefore, the purpose of this paper is to propose the extension of this concept into the activities of SCRM, treating coopetition as an action that can be added to the risk management efforts in order to make supply chains more resilient. Thus, through an exploratory literature search that uses secondary data, we drawn two propositions that deal with the possibility of adding a coopetitor to reduce risks in supply chains and on the feasibility of balanced coopetition changes the profile of a supply chain to a resilient model. Although these propositions require further empirical verification, it is believed that this is a good start for discussions about the benefits and competitive advantages that the adoption of coopetition in risk management activities in supply chains can bring to organizations.

  6. Climatology in support of climate risk management : a progress report.

    OpenAIRE

    McGregor, G.R.

    2015-01-01

    Climate risk management has emerged over the last decade as a distinct area of activity within the wider field of climatology. Its focus is on integrating climate and non-climate information in order to enhance the decision-making process in a wide range of climate-sensitive sectors of society, the economy and the environment. Given the burgeoning pure and applied climate science literature that addresses a range of climate risks, the purpose of this progress report is to provide an overview ...

  7. Plasminogen alleles influence susceptibility to invasive aspergillosis.

    Directory of Open Access Journals (Sweden)

    Aimee K Zaas

    2008-06-01

    Full Text Available Invasive aspergillosis (IA is a common and life-threatening infection in immunocompromised individuals. A number of environmental and epidemiologic risk factors for developing IA have been identified. However, genetic factors that affect risk for developing IA have not been clearly identified. We report that host genetic differences influence outcome following establishment of pulmonary aspergillosis in an exogenously immune suppressed mouse model. Computational haplotype-based genetic analysis indicated that genetic variation within the biologically plausible positional candidate gene plasminogen (Plg; Gene ID 18855 correlated with murine outcome. There was a single nonsynonymous coding change (Gly110Ser where the minor allele was found in all of the susceptible strains, but not in the resistant strains. A nonsynonymous single nucleotide polymorphism (Asp472Asn was also identified in the human homolog (PLG; Gene ID 5340. An association study within a cohort of 236 allogeneic hematopoietic stem cell transplant (HSCT recipients revealed that alleles at this SNP significantly affected the risk of developing IA after HSCT. Furthermore, we demonstrated that plasminogen directly binds to Aspergillus fumigatus. We propose that genetic variation within the plasminogen pathway influences the pathogenesis of this invasive fungal infection.

  8. Does Organizational and Coworker Support Moderate Diabetes Risk and Job Stress Among Employees?

    Science.gov (United States)

    Wolff, Marilyn B; Gay, Jennifer L; Wilson, Mark G; DeJoy, David M; Vandenberg, Robert J

    2018-05-01

    Examine the moderating role of perceived organizational and coworker support on the relationship between job stress and type 2 diabetes risk among employees. A cross-sectional survey was administered to employees at the workplace. One national retail organization. Baseline data were obtained from 1595 employees in 21 retail stores. Self-reported organizational and coworker support to encourage and fulfill job responsibilities and job stress. Diabetes risk was calculated using age, gender, race/ethnicity, blood pressure, physical activity, weight status, and self-reported diagnosed type 2 diabetes. Multilevel multiple regression was conducted to test the interaction effect of support on the association between job stress and diabetes risk. Mean age was 37.95 years (±12.03) and body mass index was 26.72 (±4.95). Three percent of participants reported diagnosed diabetes. Organizational support was positively associated with coworker support. Both were negatively associated with job stress. Organizational support, but not coworker support, moderated the relationship of job stress with diabetes risk. Participants with greater perceived organizational support had lower diabetes risk scores compared to those with lower perceived organizational support. Organizational support may be a key factor for workplaces to reduce stress and diabetes risk. Further testing of organizations' supportive role on employee health may be helpful in developing future workplace programs.

  9. Responding to and Supporting Students with Disabilities: Risk Management Considerations

    Science.gov (United States)

    Lundquist, Anne; Shackelford, Allan

    2011-01-01

    Making the "right" risk management decisions involving students with significant psychological disabilities requires a clear and comprehensive understanding of the legal obligations and duties at issue. It also requires taking into consideration the best interests of these individual students. At the same time, decision makers must focus…

  10. Risk, security and technology: governing football supporters in the twenty-first century

    NARCIS (Netherlands)

    Spaaij, R.

    2013-01-01

    This paper critically examines the security and risk management technologies that are being used to conduct and pre-empt the behaviour of football supporters. It is shown how, in the Netherlands, pre-emptive risk management in the governing of football supporters involves a dispersed and fragmented

  11. Creating Efficient Instrumentation Networks to Support Parametric Risk Transfer

    Science.gov (United States)

    Rockett, P.

    2009-04-01

    The development and institutionalisation of Catastrophe modelling during the 1990s opened the way for Catastrophe risk securitization transactions in which catastrophe risk held by insurers is transferred to the capital markets in the form of a bond. Cat Bonds have been one of the few areas of the capital markets in which the risk modelling has remained secure and the returns on the bonds have held up well through the 2008 Credit Crunch. There are three ways of structuring the loss triggers on bonds: ‘indemnity triggers' - reflecting the actual losses to the issuers; ‘index triggers' reflecting the losses to some index such as reported insurance industry loss and ‘parametric triggers' reflecting the parameters of the underlying catastrophe event itself. Indemnity triggers require that the investors trust that the insurer is reporting all their underlying exposures, while both indemnity and index losses may take 1-2 years to settle before all the claims are reported and resolved. Therefore parametric structures have many advantages, in particular in that the bond can be settled rapidly after an event. The challenge is to create parametric indices that closely reflect the actual losses to the insurer - ie that minimise ‘basis risk'. First generation parametric indices had high basis risk as they were crudely based on the magnitude of an earthquake occurring within some defined geographical box, or the intensity of a hurricane relative to the distance of the storm from some location. Second generation triggers involve taking measurements of ground motion or windspeed or flood depths at many locations and weighting each value so that the overall index closely mimics insurance loss. Cat bonds with second generation parametric triggers have been successfully issued for European Windstorm, UK Flood and California and Japan Earthquake. However the spread of second generation parametric structures is limited by the availability of suitable networks of

  12. Supporting At-Risk Learners at a Comprehensive University in ...

    African Journals Online (AJOL)

    It addresses the issue that many students who arrive at university lack the ... the work of the academic support and learning development units in higher education ... Results in both the PIRLS (Progress in International Reading Literacy Study) .... but also about “adjustments to a learning environment that requires greater ...

  13. Decision support systems for cyber-risk supervision in banks

    OpenAIRE

    Košak, Matjaž

    2016-01-01

    Cyber risk has been increasing due to fast development of information technology, increased using of smart gadgets, advanced way of communication, changing habits of users, and inventiveness of cyber criminals. Nowadays, cyber criminals are highly motivated professionals who are frequently financed by wealthy criminal organizations, or even states, and have clear goals and strategies. False working of critical systems might have important consequences for the whole society, therefore the ...

  14. Assessment of Transport Projects: Risk Analysis and Decision Support

    DEFF Research Database (Denmark)

    Salling, Kim Bang

    2008-01-01

    functions. New research proved that specifically two impacts stood out in transport project assessment, namely, travel time savings and construction costs. The final concern of this study has been the fitting of distributions, e.g. by the use of data from major databases developed in which Optimism Bias...... choosing probability distributions and performing real term data fits. The perspective of this Ph.D. study presents newer and better understanding of assigning risks within assessment of transport projects....

  15. Ergonomics Risk Assessment among support staff in Universiti Malaysia Pahang

    Science.gov (United States)

    Jusoh, Faisal; Nafis Osman Zahid, Muhammed

    2018-03-01

    Awareness of ergonomic risk assessment among workers are getting intense in many industries nowadays. It is essential since most of the workers spend 7 to 8 hours of their time in the workplaces. Previous study shown that spending too much time with static posture in sitting at workplace leads to the problem of Musculoskeletal Disorders (MSDs). The implications are not only harmful to human body but also effect the productivity. Currently, there are no scientific study conducted to assess the conditions of workers in Universiti Malaysia Pahang (UMP). Therefore, the problem of MSDs could not be justified clearly and the top management did not acknowledge this issue. This study aims to present current scenario of ergonomic risk level at UMP by using structured model. It focuses on operational staff from faculties and Human Resources Department (HRD). Initially, three types of assessments are executed based on general working condition, Cornell Muscokeletal Discomfort Questionnaire (CMDQ) and Rapid Office Strain Assessment (ROSA). Based on the findings, 90% of the respondents felt discomfort at workplace but prefer to rectify the issues by themselves. Almost 50% of them evaluated themselves in level 4-5 of discomfort level. The CMDQ result shown the discomfort area at faculties and HRD. The workplace at faculties and HRD had been assessed through ROSA and the overall result shown the risk level is medium level respectively. Therefore, further investigation is requires and improvement of workplace need to be proposed to establish good working condition.

  16. A decision support system for corporations cyber security risk management

    OpenAIRE

    Molina, Gabriela del Rocio Roldan

    2017-01-01

    This thesis presents a decision aiding system named C3-SEC (Contex-aware Corporative Cyber Security), developed in the context of a master program at Polytechnic Institute of Leiria, Portugal. The research dimension and the corresponding software development process that followed are presented and validated with an application scenario and case study performed at Universidad de las Fuerzas Armadas ESPE – Ecuador. C3-SEC is a decision aiding software intended to support cyber ri...

  17. Maternal adverse childhood experiences and antepartum risks: the moderating role of social support.

    Science.gov (United States)

    Racine, Nicole; Madigan, Sheri; Plamondon, Andre; Hetherington, Erin; McDonald, Sheila; Tough, Suzanne

    2018-03-28

    The aims of the current study were to examine the association between maternal adverse childhood experiences (ACEs) and antepartum health risks, and to investigate whether social support moderated this association. It was hypothesized that ACEs would be associated with antepartum health risks; however, social support in the prenatal period would buffer mothers from the deleterious consequences of ACEs. Data from 1994 women (mean age = 31 years) and their infants were collected from a longitudinal cohort recruited in health care offices in Alberta, Canada. Pregnant women completed questionnaires related to ACEs prior to the age of 18 and prenatal social support, and a health care professional assessed the mother's antepartum health risk. ACEs included physical, emotional, and sexual abuse, exposure to domestic violence, as well as exposure to household dysfunction such as parental substance use, mental illness, or incarceration. Regression analyses demonstrated a positive association between ACEs and antepartum health risks. However, a significant interaction between maternal ACEs and social support was also observed. Specifically, women exposed to high ACEs and low social support in pregnancy had high antepartum health risks. However, among mothers who had high ACEs but also high levels of social support, there was no association between ACEs and antepartum health risk. A history of ACEs can place mothers at risk of antepartum health complications. However, a resiliency effect was observed: women with a history of ACEs were buffered from experiencing antepartum health risks if they reported high levels of social support in pregnancy.

  18. Perceptions of risk, risk aversion, and barriers to adoption of decision support systems and integrated pest management: an introduction.

    Science.gov (United States)

    Gent, David H; De Wolf, Erick; Pethybridge, Sarah J

    2011-06-01

    Rational management of plant diseases, both economically and environmentally, involves assessing risks and the costs associated with both correct and incorrect tactical management decisions to determine when control measures are warranted. Decision support systems can help to inform users of plant disease risk and thus assist in accurately targeting events critical for management. However, in many instances adoption of these systems for use in routine disease management has been perceived as slow. The under-utilization of some decision support systems is likely due to both technical and perception constraints that have not been addressed adequately during development and implementation phases. Growers' perceptions of risk and their aversion to these perceived risks can be reasons for the "slow" uptake of decision support systems and, more broadly, integrated pest management (IPM). Decision theory provides some tools that may assist in quantifying and incorporating subjective and/or measured probabilities of disease occurrence or crop loss into decision support systems. Incorporation of subjective probabilities into IPM recommendations may be one means to reduce grower uncertainty and improve trust of these systems because management recommendations could be explicitly informed by growers' perceptions of risk and economic utility. Ultimately though, we suggest that an appropriate measure of the value and impact of decision support systems is grower education that enables more skillful and informed management decisions independent of consultation of the support tool outputs.

  19. Youth at risk of physical inactivity may benefit more from activity-related support than youth not at risk

    Directory of Open Access Journals (Sweden)

    Schmalz Dorothy L

    2006-03-01

    Full Text Available Background This study examines whether associations between activity-related support and adolescents' physical activity differ for adolescents at high versus low risk of physical inactivity. Methods: Participants included 202 middle-school-aged girls (N = 92 and boys (N = 110. Physical activity was assessed using three self-report questionnaires. Activity-related support from mothers, fathers, siblings, and peers was assessed using the Activity Support Scale. Perceived sport competence was assessed using the Physical Activity Self Description Questionnaire. Participants' height and weight were measured and used to calculate their age- and sex-adjusted Body Mass Index percentile. Participants were classified as being at high risk for physical inactivity if they fulfilled two of the following three criteria: (1 overweight; (2 female; or (3 having low perceived sport competence. Results: Activity-related support from all sources was associated with higher levels of physical activity among adolescents. A stronger association between activity support and physical activity was found for adolescents at high risk for physical inactivity in comparison to adolescents at low risk. Conclusions: Findings from this study suggest that the activity-related support from family and friends may be an effective tool in promoting physical activity among youth at risk of physical inactivity.

  20. Probabilistic risk assessment and intelligent decision support systems

    International Nuclear Information System (INIS)

    Wu, J.S.; Apostolakis, G.E.; Okrent, D.

    1989-01-01

    The purpose of this paper is to review the progress made in recent years in both the area of PRA as a support to AI applications and the area of AI applications in PRA. The emphasis is on the areas that have made some progress in the past few years, with a brief description of the methods and a discussion of the potential uses and weaknesses. Also included is a brief review of recent developments in the theory of uncertainty in the AI community that may impact uncertainty modeling in PRA. AI techniques could be applied to the related field of PRA in several ways. In this discussion, however, the scope is limited to emergency diagnosis and accident management, because these are the areas that have attracted most of the attention in recent years. The potential use of PRA as a support to these applications is discussed in detail, and this is followed by a survey of recent developments in these areas. (orig./GL)

  1. Public support for alcohol policies associated with knowledge of cancer risk.

    Science.gov (United States)

    Buykx, Penny; Gilligan, Conor; Ward, Bernadette; Kippen, Rebecca; Chapman, Kathy

    2015-04-01

    Several options are advocated by policy experts to mitigate alcohol-related harms, although the most effective strategies often have the least public support. While knowledge of tobacco-related health risks predicts support for relevant public health measures, it is not known whether knowledge of alcohol health risks is similarly associated with the acceptability of policies intended to reduce alcohol consumption and related harms. This study aims to gauge public support for a range of alcohol policies and to determine whether or not support is associated with knowledge of a long-term health risk of alcohol consumption, specifically cancer. 2482 adults in New South Wales (NSW), Australia, participated in an online survey. Logistic regression analysis was used to examine the association between demographic data, alcohol consumption, smoking status, knowledge of alcohol as a risk factor for cancer and support for alcohol-related policies. Most participants were supportive of health warnings, restricting access to internet alcohol advertising to young people, and requiring information on national drinking guidelines on alcohol containers. Almost half of participants supported a ban on sport sponsorship, while less than 41% supported price increases, volumetric taxation, or reducing the number of retail outlets. Only 47% of participants identified drinking too much alcohol as a risk factor for cancer. Knowledge of alcohol as a risk factor for cancer was a significant predictor of support for all policies, while level of alcohol consumption had a significant inverse relationship with policy support. The finding that support for alcohol management policies is associated with awareness that drinking too much alcohol may contribute to cancer could assist in the planning of future public health interventions. Improving awareness of the long term health risks of alcohol consumption may be one avenue to increasing public support for effective alcohol harm-reduction policies

  2. A generic rabies risk assessment tool to support surveillance.

    Science.gov (United States)

    Ward, Michael P; Hernández-Jover, Marta

    2015-06-01

    The continued spread of rabies in Indonesia poses a risk to human and animal populations in the remaining free islands, as well as the neighbouring rabies-free countries of Timor Leste, Papua New Guinea and Australia. Here we describe the development of a generic risk assessment tool which can be used to rapidly determine the vulnerability of rabies-free islands, so that scarce resources can be targeted to surveillance activities and the sensitivity of surveillance systems increased. The tool was developed by integrating information on the historical spread of rabies, anthropological studies, and the opinions of local animal health experts. The resulting tool is based on eight critical parameters that can be estimated from the literature, expert opinion, observational studies and information generated from routine surveillance. In the case study presented, results generated by this tool were most sensitive to the probability that dogs are present on private and fishing boats and it was predicted that rabies-infection (one infected case) might occur in a rabies-free island (upper 95% prediction interval) with a volume of 1000 boats movements. With 25,000 boat movements, the median of the probability distribution would be equal to one infected case, with an upper 95% prediction interval of six infected cases. This tool could also be used at the national-level to guide control and eradication plans. An initial recommendation from this study is to develop a surveillance programme to determine the likelihood that boats transport dogs, for example by port surveillance or regularly conducted surveys of fisherman and passenger ferries. However, the illegal nature of dog transportation from rabies-infected to rabies-free islands is a challenge for developing such surveillance. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Further Evidence for the Impact of a Genome-Wide-Supported Psychosis Risk Variant in ZNF804A on the Theory of Mind Network

    Science.gov (United States)

    Mohnke, Sebastian; Erk, Susanne; Schnell, Knut; Schütz, Claudia; Romanczuk-Seiferth, Nina; Grimm, Oliver; Haddad, Leila; Pöhland, Lydia; Garbusow, Maria; Schmitgen, Mike M; Kirsch, Peter; Esslinger, Christine; Rietschel, Marcella; Witt, Stephanie H; Nöthen, Markus M; Cichon, Sven; Mattheisen, Manuel; Mühleisen, Thomas; Jensen, Jimmy; Schott, Björn H; Maier, Wolfgang; Heinz, Andreas; Meyer-Lindenberg, Andreas; Walter, Henrik

    2014-01-01

    The single-nucleotide polymorphism (SNP) rs1344706 in ZNF804A is one of the best-supported risk variants for psychosis. We hypothesized that this SNP contributes to the development of schizophrenia by affecting the ability to understand other people's mental states. This skill, commonly referred to as Theory of Mind (ToM), has consistently been found to be impaired in schizophrenia. Using functional magnetic resonance imaging, we previously showed that in healthy individuals rs1344706 impacted on activity and connectivity of key areas of the ToM network, including the dorsomedial prefrontal cortex, temporo-parietal junction, and the posterior cingulate cortex, which show aberrant activity in schizophrenia patients, too. We aimed to replicate these results in an independent sample of 188 healthy German volunteers. In order to assess the reliability of brain activity elicited by the ToM task, 25 participants performed the task twice with an interval of 14 days showing excellent accordance in recruitment of key ToM areas. Confirming our previous results, we observed decreasing activity of the left temporo-parietal junction, dorsomedial prefrontal cortex, and the posterior cingulate cortex with increasing number of risk alleles during ToM. Complementing our replication sample with the discovery sample, analyzed in a previous report (total N=297), further revealed negative genotype effects in the left dorsomedial prefrontal cortex as well as in the temporal and parietal regions. In addition, as shown previously, rs1344706 risk allele dose positively predicted increased frontal–temporo-parietal connectivity. These findings confirm the effects of the psychosis risk variant in ZNF804A on the dysfunction of the ToM network. PMID:24247043

  4. Allele-specific MMP-3 transcription under in vivo conditions

    Energy Technology Data Exchange (ETDEWEB)

    Chaoyong, Zhu [Atherosclerosis Research Unit, King Gustav V Research Institute, Department of Medicine, Karolinska Institute, Stockholm (Sweden); Odeberg, Jacob [Atherosclerosis Research Unit, King Gustav V Research Institute, Department of Medicine, Karolinska Institute, Stockholm (Sweden); Department of Biotechnology, AlbaNova University Center, Royal Institute of Technology, Stockholm (Sweden); Hamsten, Anders [Atherosclerosis Research Unit, King Gustav V Research Institute, Department of Medicine, Karolinska Institute, Stockholm (Sweden); Eriksson, Per [Atherosclerosis Research Unit, King Gustav V Research Institute, Department of Medicine, Karolinska Institute, Stockholm (Sweden)

    2006-09-29

    A common matrix metalloproteinases-3 (MMP-3) -1612 5A/6A promoter polymorphism is associated with risk for cardiovascular disease, rheumatoid arthritis, and other diseases. Here we used the haplotype chromatin immunoprecipitation method to study allele-specific MMP-3 expression under in vivo conditions in heterozygous THP-1 cells. Pyrosequencing was used to analyse the ratio of 5A-allele to 6A-allele after chromatin immunoprecipitation using an antibody against phosphorylated active RNA polymerase II. There was no allele-specific difference in transcriptional activity during basal conditions, i.e., in unstimulated monocytic THP-1 cells. However, after stimulation of MMP-3 expression by monocyte differentiation or incubation with IL-1{beta}, the haplotype containing the 5A-allele was associated with higher transcriptional activity compared with the 6A-containing haplotype. Electromobility shift assay demonstrated increased binding of nuclear proteins to the 5A-allele after monocyte differentiation. In conclusion, the common MMP-3 5A/6A promoter polymorphism appears to be functional only during specific environmental conditions involving inflammation.

  5. FORMENTOR real-time decision support for risk management

    International Nuclear Information System (INIS)

    Pennings, R.; Gerlinger, G.; Ponamale, M.

    1995-01-01

    The supervision of complex industrial processes, such as in the chemical, nuclear or aerospace industries, is a difficult task. The FORMENTOR methodology allows the development of supervision support systems to aid operations in their tasks, especially when dealing with perturbations and hazardous situations. A FORMENTOR system presents a synthetic plant-wide view of the current situation, diagnoses the underlying causes of perturbations, predicts possible future evolutions and proposes remedial actions. For this the methodology integrates models, techniques and tools from four domains namely artificial intelligence, safety analysis, real-time computing and ergonomics. The methodological approach provides firm control over the development process while meeting the quality and technical requirements of the client; furthermore it ensures the reliability and maintainability of the obtained system

  6. Sustainable nanotechnology decision support system: bridging risk management, sustainable innovation and risk governance

    NARCIS (Netherlands)

    Subramanian, V.; Semenzin, E.; Hristozov, D.; Zabeo, A.; Malsch, I.; McAlea, E.; Murphy, F.; Mullins, M.; Harmelen, T. van; Ligthart, T.; Linkov, I.; Marcomini, A.

    2016-01-01

    The significant uncertainties associated with the (eco)toxicological risks of engineered nanomaterials pose challenges to the development of nano-enabled products toward greatest possible societal benefit. This paper argues for the use of risk governance approaches to manage nanotechnology risks and

  7. Experimental climate information services in support of risk management

    Science.gov (United States)

    Webb, R. S.; Pulwarty, R. S.; Davidson, M. A.; Shea, E. E.; Nierenberg, C.; Dole, R. M.

    2009-12-01

    Climate variability and change impact national and local economies and environments. Developing and communicating climate and climate impacts information to inform decision making requires an understanding of context, societal objectives, and identification of factors important to the management of risk. Information sensitive to changing baselines or extremes is a critical emergent need. Meeting this need requires timely production and delivery of useful climate data, information and knowledge within familiar pathways. We identify key attributes for a climate service , and the network and infrastructure to develop and coordinate the resulting services based on lessons learned in experimental implementations of climate services. "Service-type" activities already exist in many settings within federal, state, academic, and private sectors. The challenge for a climate service is to find effective implementation strategies for improving decision quality (not just meeting user needs). These strategies include upfront infrastructure investments, learning from event to event, coordinated innovation and diffusion, and highlighting common adaptation interests. Common to these strategies is the production of reliable and accessible data, analyses of emergent conditions and needs, and deliberative processes to identify appropriate entry points and uses for improved knowledge. Experimental climate services show that the development of well-structured paths among observations, projections, risk assessments and usable information requires sustained participation in “knowledge management systems” for early warning across temporal and spatial scales. Central to these systems is a collaborative framework between research and management to ensure anticipatory coordination between decision makers and information providers, allowing for emerging research findings and their attendant uncertainties to be considered. Early warnings in this context are not simply forecasts or

  8. Supportive relationships and sexual risk behavior in adolescence: an ecological-transactional approach.

    Science.gov (United States)

    Henrich, Christopher C; Brookmeyer, Kathryn A; Shrier, Lydia A; Shahar, Golan

    2006-04-01

    To examine the longitudinal associations between supportive relationships with friends and parents and sexual risk behavior in adolescence based on an ecological-transactional perspective. Analyses were conducted on 2,652 sexually active adolescents from the first two waves of the National Longitudinal Study of Adolescent Health (Add Health). African-American adolescents had lower risk for sexual risk behavior. Supportive friendships and parent connectedness interacted in predicting decreased likelihood of sexual risk behavior. Mother-child communication about sex contributed to decreased likelihood of sexual risk only for girls. There were also small reciprocal effects of sexual risk behavior on decreased relationship quality over time. To better understand the parents' role in adolescent sexual risk behavior, multiple facets of parenting, the social contexts of parenting and adolescents' peers, and the effects of adolescents' behavior on these relationships should be taken into consideration.

  9. The family health, functioning, social support and child maltreatment risk of families expecting a baby.

    Science.gov (United States)

    Lepistö, Sari; Ellonen, Noora; Helminen, Mika; Paavilainen, Eija

    2017-08-01

    To describe the family health, functioning, social support and child maltreatment risk and associations between them in families expecting a baby. Finland was one of the first countries in banning corporal punishment against children over 30 years ago. Despite of this, studies have shown that parents physically abuse their children. In addition, professionals struggle in intervention of this phenomenon. Abusive parents should be recognised and helped before actual violent behaviour. A follow-up case-control study, with a supportive intervention in the case group (families with a heightened risk) in maternity and child welfare clinics. The baseline results of families are described here. Child maltreatment risk in families expecting a baby was measured by Child Abuse Potential Inventory. The health and functioning was measured by Family Health, Functioning and Social Support Scale. Data included 380 families. A total of 78 families had increased risk for child maltreatment. Heightened risk was associated with partners' age, mothers' education, partners' father's mental health problems, mothers' worry about partners' drinking and mothers' difficulties in talking about the family's problems. Risk was associated with family functioning and health. Families with risk received a less support from maternity clinics. Families with child maltreatment risk and related factors were found. This knowledge can be applied for supporting families both during pregnancy and after the baby is born. Professionals working with families in maternity clinics need tools to recognise families with risk and aid a discussion with them about the family life situation. The Child Abuse Potential, as a part of evaluating the family life situation, seems to prove a useful tool in identifying families at risk. The results offer a valid and useful tool for recognising families with risk and provide knowledge about high-risk family situations. © 2016 John Wiley & Sons Ltd.

  10. Risk analysis for decision support in electricity distribution system asset management: methods and frameworks for analysing intangible risks

    Energy Technology Data Exchange (ETDEWEB)

    Nordgaard, Dag Eirik

    2010-04-15

    During the last 10 to 15 years electricity distribution companies throughout the world have been ever more focused on asset management as the guiding principle for their activities. Within asset management, risk is a key issue for distribution companies, together with handling of cost and performance. There is now an increased awareness of the need to include risk analyses into the companies' decision making processes. Much of the work on risk in electricity distribution systems has focused on aspects of reliability. This is understandable, since it is surely an important feature of the product delivered by the electricity distribution infrastructure, and it is high on the agenda for regulatory authorities in many countries. However, electricity distribution companies are also concerned with other risks relevant for their decision making. This typically involves intangible risks, such as safety, environmental impacts and company reputation. In contrast to the numerous methodologies developed for reliability risk analysis, there are relatively few applications of structured analyses to support decisions concerning intangible risks, even though they represent an important motivation for decisions taken in electricity distribution companies. The overall objective of this PhD work has been to explore risk analysis methods that can be used to improve and support decision making in electricity distribution system asset management, with an emphasis on the analysis of intangible risks. The main contributions of this thesis can be summarised as: An exploration and testing of quantitative risk analysis (QRA) methods to support decisions concerning intangible risks; The development of a procedure for using life curve models to provide input to QRA models; The development of a framework for risk-informed decision making where QRA are used to analyse selected problems; In addition, the results contribute to clarify the basic concepts of risk, and highlight challenges

  11. Role of the B Allele of Influenza A Virus Segment 8 in Setting Mammalian Host Range and Pathogenicity.

    Science.gov (United States)

    Turnbull, Matthew L; Wise, Helen M; Nicol, Marlynne Q; Smith, Nikki; Dunfee, Rebecca L; Beard, Philippa M; Jagger, Brett W; Ligertwood, Yvonne; Hardisty, Gareth R; Xiao, Haixia; Benton, Donald J; Coburn, Alice M; Paulo, Joao A; Gygi, Steven P; McCauley, John W; Taubenberger, Jeffery K; Lycett, Samantha J; Weekes, Michael P; Dutia, Bernadette M; Digard, Paul

    2016-10-15

    burden on farming and health care sectors. Host adaptation likely involves multiple viral factors. Here, we investigated the role of IAV segment 8. Segment 8 has evolved into two distinct clades: the A and B alleles. The B-allele genes have previously been suggested to be restricted to avian virus species. We introduced a selection of avian virus A- and B-allele segment 8s into human H1N1 and H3N2 virus backgrounds and found that these reassortant viruses were fully competent in mammalian host systems. We also analyzed the currently available public data on the segment 8 gene distribution and found surprisingly little evidence for specific avian host restriction of the B-clade segment. We conclude that B-allele segment 8 genes are, in fact, capable of supporting infection in mammals and that they should be considered during the assessment of the pandemic risk of zoonotic influenza A viruses. Copyright © 2016 Turnbull et al.

  12. Elements of a Workplace Culture of Health, Perceived Organizational Support for Health, and Lifestyle Risk.

    Science.gov (United States)

    Payne, Julianne; Cluff, Laurie; Lang, Jason; Matson-Koffman, Dyann; Morgan-Lopez, Antonio

    2018-01-01

    We investigated the impact of elements of a workplace culture of health (COH) on employees' perceptions of employer support for health and lifestyle risk. We used 2013 and 2015 survey data from the National Healthy Worksite Program, a Centers for Disease Control and Prevention (CDC)-led initiative to help workplaces implement health-promoting interventions. Forty-one employers completed the CDC Worksite Health Scorecard to document organizational changes. Eight hundred twenty-five employees provided data to evaluate changes in their health and attitudes. We defined elements of a COH as environmental, policy, and programmatic supports; leadership and coworker support; employee engagement (motivational interventions); and strategic communication. Outcomes included scores of employees' perceptions of employer support for health and lifestyle risk derived from self-reported physical activity, nutrition, and tobacco use. We estimated effects using multilevel regression models. At the employee level and across time, regression coefficients show positive associations between leadership support, coworker support, employee engagement, and perceived support for health ( P leadership support in 2015 only ( P leadership and coworker support) tend to be associated with perceived support for health, while workplace elements (environmental and policy supports) are more associated with lifestyle risk. Employers need to confront relational and workplace elements together to build a COH.

  13. A sequential model to link contextual risk, perception and public support for flood adaptation policy.

    Science.gov (United States)

    Shao, Wanyun; Xian, Siyuan; Lin, Ning; Small, Mitchell J

    2017-10-01

    The economic damage from coastal flooding has dramatically increased over the past several decades, owing to rapid development in shoreline areas and possible effects of climate change. To respond to these trends, it is imperative for policy makers to understand individuals' support for flood adaptation policy. Using original survey data for all coastal counties of the United States Gulf Coast merged with contextual data on flood risk, this study investigates coastal residents' support for two adaptation policy measures: incentives for relocation and funding for educational programs on emergency planning and evacuation. Specifically, this study explores the interactive relationships among contextual flood risks, perceived flood risks and policy support for flood adaptation, with the effects of social-demographic variables being controlled. Age, gender, race and partisanship are found to significantly affect individuals' policy support for both adaptation measures. The contextual flooding risks, indicated by distance from the coast, maximum wind speed and peak height of storm surge associated with the last hurricane landfall, and percentage of high-risk flood zone per county, are shown to impact one's perceptions of risk, which in turn influence one's support for both policy measures. The key finding -risk perception mediates the impact of contextual risk conditions on public support for flood management policies - highlights the need to ensure that the public is well informed by the latest scientific, engineering and economic knowledge. To achieve this, more information on current and future flood risks and options available for mitigation as well as risk communication tools are needed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Effects of Social Support Network Size on Mortality Risk: Considerations by Diabetes Status.

    Science.gov (United States)

    Loprinzi, Paul D; Ford, M Allison

    2018-05-01

    Previous work demonstrates that social support is inversely associated with mortality risk. Less research, however, has examined the effects of the size of the social support network on mortality risk among those with and without diabetes, which was the purpose of this study. Data from the 1999-2008 National Health and Nutrition Examination Survey were used, with participants followed through 2011. This study included 1,412 older adults (≥60 years of age) with diabetes and 5,872 older adults without diabetes. The size of the social support network was assessed via self-report and reported as the number of participants' close friends. Among those without diabetes, various levels of social support network size were inversely associated with mortality risk. However, among those with diabetes, only those with a high social support network size (i.e., at least six close friends) had a reduced risk of all-cause mortality. That is, compared to those with zero close friends, those with diabetes who had six or more close friends had a 49% reduced risk of all-cause mortality (hazard ratio 0.51, 95% CI 0.27-0.94). To mitigate mortality risk, a greater social support network size may be needed for those with diabetes.

  15. A decision-support scheme for mapping endangered areas in pest risk analysis

    NARCIS (Netherlands)

    Baker, R.H.A.; Benninga, J.; Bremmer, J.; Brunel, S.; Dupin, M.; Eyre, D.; Ilieva, Z.; Jarosik, V.; Kehlenbeck, H.; Kriticos, D.J.; Makowski, D.; Pergl, J.; Reynaud, P.; Robinet, C.; Soliman, T.; Werf, van der W.; Worner, S.

    2012-01-01

    This paper describes a decision-support scheme (DSS) for mapping the area where economically important loss is likely to occur (the endangered area). It has been designed by the PRATIQUE project to help pest risk analysts address the numerous risk mapping challenges and decide on the most suitable

  16. A suite of models to support the quantitative assessment of spread in pest risk analysis

    NARCIS (Netherlands)

    Robinet, C.; Kehlenbeck, H.; Werf, van der W.

    2012-01-01

    In the frame of the EU project PRATIQUE (KBBE-2007-212459 Enhancements of pest risk analysis techniques) a suite of models was developed to support the quantitative assessment of spread in pest risk analysis. This dataset contains the model codes (R language) for the four models in the suite. Three

  17. Population differentiation in allele frequencies of obesity-associated SNPs.

    Science.gov (United States)

    Mao, Linyong; Fang, Yayin; Campbell, Michael; Southerland, William M

    2017-11-10

    Obesity is emerging as a global health problem, with more than one-third of the world's adult population being overweight or obese. In this study, we investigated worldwide population differentiation in allele frequencies of obesity-associated SNPs (single nucleotide polymorphisms). We collected a total of 225 obesity-associated SNPs from a public database. Their population-level allele frequencies were derived based on the genotype data from 1000 Genomes Project (phase 3). We used hypergeometric model to assess whether the effect allele at a given SNP is significantly enriched or depleted in each of the 26 populations surveyed in the 1000 Genomes Project with respect to the overall pooled population. Our results indicate that 195 out of 225 SNPs (86.7%) possess effect alleles significantly enriched or depleted in at least one of the 26 populations. Populations within the same continental group exhibit similar allele enrichment/depletion patterns whereas inter-continental populations show distinct patterns. Among the 225 SNPs, 15 SNPs cluster in the first intron region of the FTO gene, which is a major gene associated with body-mass index (BMI) and fat mass. African populations exhibit much smaller blocks of LD (linkage disequilibrium) among these15 SNPs while European and Asian populations have larger blocks. To estimate the cumulative effect of all variants associated with obesity, we developed the personal composite genetic risk score for obesity. Our results indicate that the East Asian populations have the lowest averages of the composite risk scores, whereas three European populations have the highest averages. In addition, the population-level average of composite genetic risk scores is significantly correlated (R 2 = 0.35, P = 0.0060) with obesity prevalence. We have detected substantial population differentiation in allele frequencies of obesity-associated SNPs. The results will help elucidate the genetic basis which may contribute to population

  18. An Integrated Web-based Decision Support System in Disaster Risk Management

    Science.gov (United States)

    Aye, Z. C.; Jaboyedoff, M.; Derron, M. H.

    2012-04-01

    Nowadays, web based decision support systems (DSS) play an essential role in disaster risk management because of their supporting abilities which help the decision makers to improve their performances and make better decisions without needing to solve complex problems while reducing human resources and time. Since the decision making process is one of the main factors which highly influence the damages and losses of society, it is extremely important to make right decisions at right time by combining available risk information with advanced web technology of Geographic Information System (GIS) and Decision Support System (DSS). This paper presents an integrated web-based decision support system (DSS) of how to use risk information in risk management efficiently and effectively while highlighting the importance of a decision support system in the field of risk reduction. Beyond the conventional systems, it provides the users to define their own strategies starting from risk identification to the risk reduction, which leads to an integrated approach in risk management. In addition, it also considers the complexity of changing environment from different perspectives and sectors with diverse stakeholders' involvement in the development process. The aim of this platform is to contribute a part towards the natural hazards and geosciences society by developing an open-source web platform where the users can analyze risk profiles and make decisions by performing cost benefit analysis, Environmental Impact Assessment (EIA) and Strategic Environmental Assessment (SEA) with the support of others tools and resources provided. There are different access rights to the system depending on the user profiles and their responsibilities. The system is still under development and the current version provides maps viewing, basic GIS functionality, assessment of important infrastructures (e.g. bridge, hospital, etc.) affected by landslides and visualization of the impact

  19. Assessment of the myostatin Q204X allele using an allelic discrimination assay

    OpenAIRE

    Sifuentes-Rincón,Ana M.; Puentes-Montiel,Herlinda E.; Moreno-Medina,Víctor R.; Rosa-Reyna,Xóchitl F. de la

    2006-01-01

    An allelic discrimination assay was designed and used to determine the genotypic and allelic frequencies of the myostatin (MSTN) gene Q204X allele from two Mexican Full-French herds. The assay is a simple high throughput genotyping method that could be applied to investigate the effect of the Q204X allele on the Charolais breed.

  20. Using prior risk-related knowledge to support risk management decisions: lessons learnt from a tunneling project.

    Science.gov (United States)

    Cárdenas, Ibsen Chivatá; Al-Jibouri, Saad S H; Halman, Johannes I M; van de Linde, Wim; Kaalberg, Frank

    2014-10-01

    The authors of this article have developed six probabilistic causal models for critical risks in tunnel works. The details of the models' development and evaluation were reported in two earlier publications of this journal. Accordingly, as a remaining step, this article is focused on the investigation into the use of these models in a real case study project. The use of the models is challenging given the need to provide information on risks that usually are both project and context dependent. The latter is of particular concern in underground construction projects. Tunnel risks are the consequences of interactions between site- and project-specific factors. Large variations and uncertainties in ground conditions as well as project singularities give rise to particular risk factors with very specific impacts. These circumstances mean that existing risk information, gathered from previous projects, is extremely difficult to use in other projects. This article considers these issues and addresses the extent to which prior risk-related knowledge, in the form of causal models, as the models developed for the investigation, can be used to provide useful risk information for the case study project. The identification and characterization of the causes and conditions that lead to failures and their interactions as well as their associated probabilistic information is assumed to be risk-related knowledge in this article. It is shown that, irrespective of existing constraints on using information and knowledge from past experiences, construction risk-related knowledge can be transferred and used from project to project in the form of comprehensive models based on probabilistic-causal relationships. The article also shows that the developed models provide guidance as to the use of specific remedial measures by means of the identification of critical risk factors, and therefore they support risk management decisions. Similarly, a number of limitations of the models are

  1. MYPLAN - A Mobile Phone Application for Supporting People at Risk of Suicide

    DEFF Research Database (Denmark)

    Skovgaard Larsen, Jette L; Frandsen, Hanne; Erlangsen, Annette

    2016-01-01

    describes MYPLAN, a mobile phone application designed to support people at risk of suicide by letting them create a safety plan. METHOD: MYPLAN was developed in collaboration with clinical psychiatric staff at Danish suicide preventive clinics. The mobile application lets the user create an individualized......BACKGROUND: Safety plans have been suggested as an intervention for people at risk of suicide. Given the impulsive character of suicidal ideation, a safety plan in the format of a mobile phone application is likely to be more available and useful than traditional paper versions. AIMS: The study......,000 times. Users at risk of suicide as well as clinical staff have provided positive feedback on the mobile application. CONCLUSION: Support via mobile phone applications might be particularly useful for younger age groups at risk of suicide as well as in areas or countries where support options are lacking...

  2. Perceptions of risk, risk aversion, and barriers to adoption of decision support systems and integrated pest management: An introduction

    Science.gov (United States)

    Rational management of plant diseases, both economically and environmentally, involves assessing risks and the costs associated with both correct and incorrect management decisions to determine when control measures are warranted. Decision support systems can help to inform users of plant disease r...

  3. Intrapersonal, interpersonal, and contextual risk factors for overprovision of partner support in marriage.

    Science.gov (United States)

    Brock, Rebecca L; Lawrence, Erika

    2014-02-01

    Recent research indicates that receiving too much support from one's spouse (i.e., overprovision of support) is actually more detrimental to marriage than not receiving enough support. The principal goal of the present study was to develop a novel framework for explaining the pathways through which couples experience overprovision of support in their marriages. Intrapersonal factors (anxious and avoidant attachment), interpersonal factors (conflict management and emotional intimacy), and contextual factors (stress originating outside of the marriage) were assessed during the transition into marriage as potential risk factors for experiencing higher levels of support overprovision during the first 5 years of marriage in a sample of 103 couples using growth curve analytic techniques. To the extent that (a) husbands were higher in avoidant attachment, (b) husbands reported greater chronic role strain, and (c) couples had lower levels of emotional intimacy, support overprovision was greater for both husbands and wives. In addition, emotional intimacy (lower levels) was a partial pathway through which husband avoidant attachment contributed to support overprovision. Finally, factors placing couples at risk for support overprovision in their marriages appear to be distinct from those increasing the risk for support underprovision. The potential for results to inform contemporary marital theories and marital preparation programs is discussed.

  4. Distribution of a pseudodeficiency allele among Tay-Sachs carriers

    Energy Technology Data Exchange (ETDEWEB)

    Tomczak, J.; Grebner, E.E. (Thomas Jefferson Univ., Philadelphia, PA (United States)); Boogen, C. (Univ. of Essen Medical School (Germany))

    1993-08-01

    Recently Triggs-Raine et al. (1992) identified a new mutation in the gene coding for the [alpha]-subunit of [beta]-hexosaminidase A (hex A), the enzyme whose deficiency causes Tay-Sachs disease. This mutation, a C[sub 739]-to-T transition in exon 7, results in an altered enzyme that is active (albeit at reduced levels) in cells but that has essentially no activity in serum. This so-called pseudodeficient allele was first detected in compound heterozygotes who also carried a Tay-Sachs disease allele and therefore had no detectable hex A in their serum but who were in good health. Carriers of this apparently benign mutation are generally indistinguishable from carriers of a lethal mutation by means of routine enzyme-based screening tests, because the product of the pseudodeficient allele is not detectable in serum and has decreased activity in cells. This suggests that some individuals who have been classified as Tay-Sachs carriers are actually carriers of the pseudodeficient allele and are not at risk to have a child affected with Tay-Sachs disease. The pseudodeficient allele may also be responsible for some inconclusive diagnoses, where leukocyte values fall below the normal range but are still above the carrier range. The fact that there are now two mutant alleles (the psuedodeficient and the adult) that are indistinguishable from the lethal infantile mutations by means of enzyme assay yet that are phenotypically very different and that together may account for as much as 12% of enzyme-defined carriers on the basis of the data here suggests that DNA analysis should be part of a comprehensive screening program. It will be particularly useful to identify the mutations in couples at risk, before they undergo prenatal diagnosis. DNA analysis will also resolve some inconclusive diagnoses.

  5. Social support, psychological vulnerability, and HIV risk among African American men who have sex with men.

    Science.gov (United States)

    Saleh, Lena D; van den Berg, Jacob J; Chambers, Christopher S; Operario, Don

    2016-05-01

    Previous research has suggested a need to understand the social-psychological factors contributing to HIV risk among African American men who have sex with men (MSM). We conducted individual in-depth interviews with 34 adult African American MSM to examine their personal experiences about: (i) sources of social support, (ii) psychological responses to the presence or absence of social support and (iii) influences of social support on sexual behaviours. The majority of participants described limited positive encouragement and lack of emotional support from family, as well as few meaningful personal relationships. Feelings of isolation and mistrust about personal relationships led many participants to avoid emotional intimacy and seek physical intimacy through sexual encounters. Findings highlight a need for multilevel interventions that enhance social support networks and address the social-psychological, emotional and interpersonal factors that contribute to HIV risk among African American MSM.

  6. Design and implementation of a risk assessment module in a spatial decision support system

    Science.gov (United States)

    Zhang, Kaixi; van Westen, Cees; Bakker, Wim

    2014-05-01

    The spatial decision support system named 'Changes SDSS' is currently under development. The goal of this system is to analyze changing hydro-meteorological hazards and the effect of risk reduction alternatives to support decision makers in choosing the best alternatives. The risk assessment module within the system is to assess the current risk, analyze the risk after implementations of risk reduction alternatives, and analyze the risk in different future years when considering scenarios such as climate change, land use change and population growth. The objective of this work is to present the detailed design and implementation plan of the risk assessment module. The main challenges faced consist of how to shift the risk assessment from traditional desktop software to an open source web-based platform, the availability of input data and the inclusion of uncertainties in the risk analysis. The risk assessment module is developed using Ext JS library for the implementation of user interface on the client side, using Python for scripting, as well as PostGIS spatial functions for complex computations on the server side. The comprehensive consideration of the underlying uncertainties in input data can lead to a better quantification of risk assessment and a more reliable Changes SDSS, since the outputs of risk assessment module are the basis for decision making module within the system. The implementation of this module will contribute to the development of open source web-based modules for multi-hazard risk assessment in the future. This work is part of the "CHANGES SDSS" project, funded by the European Community's 7th Framework Program.

  7. Support for At-Risk Girls: A School-Based Mental Health Nursing Initiative.

    Science.gov (United States)

    Adamshick, Pamela

    2015-09-01

    Mental health problems often go undiagnosed or unaddressed until a crisis or extreme event brings the problem to the forefront. Youth are particularly at risk for lack of identification and treatment in regard to mental health issues. This article describes an advanced nursing practice mental health initiative for at-risk teenage girls based on Hildegard Peplau's nursing theory, group process, and healing through holistic health approaches. A support group, RICHES, was developed with focus on core components of relationships, identity, communication, health, esteem, and support. The acronym RICHES was chosen as the name of the support group. Selected themes and issues addressed in this school-based support group are illustrated in case vignettes. Through a collaborative approach with the community and school, this practice initiative presents a unique healing process that extends knowledge in the realm of intervention with at-risk teenage girls. Further research is needed on the efficacy of support groups to modify risk factors and to address goals for primary prevention in at-risk teenage girls. © The Author(s) 2014.

  8. Revisiting support optimization at the Driskos tunnel using a quantitative risk approach

    Directory of Open Access Journals (Sweden)

    J. Connor Langford

    2016-04-01

    Full Text Available With the scale and cost of geotechnical engineering projects increasing rapidly over the past few decades, there is a clear need for the careful consideration of calculated risks in design. While risk is typically dealt with subjectively through the use of conservative design parameters, with the advent of reliability-based methods, this no longer needs to be the case. Instead, a quantitative risk approach can be considered that incorporates uncertainty in ground conditions directly into the design process to determine the variable ground response and support loads. This allows for the optimization of support on the basis of both worker safety and economic risk. This paper presents the application of such an approach to review the design of the initial lining system along a section of the Driskos twin tunnels as part of the Egnatia Odos highway in northern Greece. Along this section of tunnel, weak rock masses were encountered as well as high in situ stress conditions, which led to excessive deformations and failure of the as built temporary support. Monitoring data were used to validate the rock mass parameters selected in this area and a risk approach was used to determine, in hindsight, the most appropriate support category with respect to the cost of installation and expected cost of failure. Different construction sequences were also considered in the context of both convenience and risk cost.

  9. Rent pricing decision support mathematical model for finance leases under effective risks

    Directory of Open Access Journals (Sweden)

    Rabbani Masoud

    2015-01-01

    Full Text Available Nowadays, leasing has become an increasingly important and popular method for equipment acquisition. But, because of the rent pricing difficulties and some risks that affect the lessor and lessee's decision making, there are many people that still tend to buy equipment instead of lease it. In this paper we explore how risk can affect the leasing issue support mathematical model. For this purpose, we consider three types of risk; Credit risk, Transaction risk and Risk based pricing. In particular, our focus was on how to make decision about rent pricing in a leasing problem with different customers, various quality levels and different pricing methods. Finally, the mathematical model has been solved by Genetic Algorithm that is a search heuristic to optimize the problem. This algorithm was coded in MATLAB® R2012a to provide the best set of results.

  10. Support Vector Hazards Machine: A Counting Process Framework for Learning Risk Scores for Censored Outcomes.

    Science.gov (United States)

    Wang, Yuanjia; Chen, Tianle; Zeng, Donglin

    2016-01-01

    Learning risk scores to predict dichotomous or continuous outcomes using machine learning approaches has been studied extensively. However, how to learn risk scores for time-to-event outcomes subject to right censoring has received little attention until recently. Existing approaches rely on inverse probability weighting or rank-based regression, which may be inefficient. In this paper, we develop a new support vector hazards machine (SVHM) approach to predict censored outcomes. Our method is based on predicting the counting process associated with the time-to-event outcomes among subjects at risk via a series of support vector machines. Introducing counting processes to represent time-to-event data leads to a connection between support vector machines in supervised learning and hazards regression in standard survival analysis. To account for different at risk populations at observed event times, a time-varying offset is used in estimating risk scores. The resulting optimization is a convex quadratic programming problem that can easily incorporate non-linearity using kernel trick. We demonstrate an interesting link from the profiled empirical risk function of SVHM to the Cox partial likelihood. We then formally show that SVHM is optimal in discriminating covariate-specific hazard function from population average hazard function, and establish the consistency and learning rate of the predicted risk using the estimated risk scores. Simulation studies show improved prediction accuracy of the event times using SVHM compared to existing machine learning methods and standard conventional approaches. Finally, we analyze two real world biomedical study data where we use clinical markers and neuroimaging biomarkers to predict age-at-onset of a disease, and demonstrate superiority of SVHM in distinguishing high risk versus low risk subjects.

  11. Through ARIPAR-GIS the quantified area risk analysis supports land-use planning activities.

    Science.gov (United States)

    Spadoni, G; Egidi, D; Contini, S

    2000-01-07

    The paper first summarises the main aspects of the ARIPAR methodology whose steps can be applied to quantify the impact on a territory of major accident risks due to processing, storing and transporting dangerous substances. Then the capabilities of the new decision support tool ARIPAR-GIS, implementing the mentioned procedure, are described, together with its main features and types of results. These are clearly shown through a short description of the updated ARIPAR study (reference year 1994), in which the impact of changes due to industrial and transportation dynamics on the Ravenna territory in Italy were evaluated. The brief explanation of how results have been used by local administrations offers the opportunity to discuss about advantages of the quantitative area risk analysis tool in supporting activities of risk management, risk control and land-use planning.

  12. Social isolation, support, and capital and nutritional risk in an older sample: ethnic and gender differences

    OpenAIRE

    Locher, Julie L.; Ritchie, Christine S.; Roth, David L.; Baker, Patricia Sawyer; Bodner, Eric V.; Allman, Richard M.

    2005-01-01

    This study examines the relationships that exist between social isolation, support, and capital and nutritional risk in older black and white women and men. The paper reports on 1000 community-dwelling older adults aged 65 and older enrolled in the University of Alabama at Birmingham (UAB) Study of Aging, a longitudinal observational study of mobility among older black and white participants in the USA. Black women were at greatest nutritional risk; and black women and men were the groups mos...

  13. Risk-based analyses in support of California hazardous site remediation

    International Nuclear Information System (INIS)

    Ringland, J.T.

    1995-08-01

    The California Environmental Enterprise (CEE) is a joint program of the Department of Energy (DOE), Lawrence Livermore National Laboratory, Lawrence Berkeley Laboratory, and Sandia National Laboratories. Its goal is to make DOE laboratory expertise accessible to hazardous site cleanups in the state This support might involve working directly with parties responsible for individual cleanups or it might involve working with the California Environmental Protection Agency to develop tools that would be applicable across a broad range of sites. As part of its initial year's activities, the CEE supported a review to examine where laboratory risk and risk-based systems analysis capabilities might be most effectively applied. To this end, this study draws the following observations. The labs have a clear role in analyses supporting the demonstration and transfer of laboratory characterization or remediation technologies. The labs may have opportunities in developing broadly applicable analysis tools and computer codes for problems such as site characterization or efficient management of resources. Analysis at individual sites, separate from supporting lab technologies or prototyping general tools, may be appropriate only in limited circumstances. In any of these roles, the labs' capabilities extend beyond health risk assessment to the broader areas of risk management and risk-based systems analysis

  14. Supporting the information domains of fall-risk management in home care via health information technology.

    Science.gov (United States)

    Alhuwail, Dari; Koru, Güneş; Mills, Mary Etta

    2016-01-01

    In the United States, home care clinicians often start the episode of care devoid of relevant fall-risk information. By collecting and analyzing qualitative data from 30 clinicians in one home health agency, this case study aimed to understand how the currently adopted information technology solutions supported the clinicians' fall-risk management (FRM) information domains, and explored opportunities to adopt other solutions to better support FRM. The currently adopted electronic health record system and fall-reporting application served only some information domains with a limited capacity. Substantial improvement in addressing the FRM information domains is possible by effectively modifying the existing solutions and purposefully adopting new solutions.

  15. Geo-risk in Central Africa: integrating multi-hazards and vulnerability to support risk management

    Science.gov (United States)

    Kervyn, Francois; Nicolas, d'Oreye; Haventith, Hans-Balder; Kervyn, Matthieu; Caroline, Michellier; Trefon, Theodore; Wolff, Eleonore

    2013-04-01

    In some places, geo-hazards are a major concern for population, the assets, and the economy. This is especially the case in the East African Rift (EAR), where high volcanic and tectonic activities are sometimes coupled with geopolitical issues and dense population as in the Kivu rift area. That area is one of the most densely populated regions of Central Africa and is affected by decades of political instability and subsequent humanitarian crisis. In that region, geo-hazards are poorly assessed despite the numerous recent and historical events. Moreover, the relief of the rift also corresponds in this area to the main political boundaries, which complicates the coordination and the management of geo-hazards monitoring networks and related mitigation measures. Based on the experience acquired through several projects focused on hazard assessment and reinforcement of local monitoring capacity, the GeoRisCA project is addressing the assessment of the global risk related to the major geohazards that affect the region. Taking into account the identified factors, GeoRisCA's objective is to assess the risk from multi geohazards in a region which is subject to many (possibly combined) disasters every year and which could undergo a large impact disaster in the coming years. At regional scale, the high seismicity and the volcanic activity are the most important concerns. Possible eruptions of lethal gas in certain area around Goma, and the large number of reported and likely future mass movements as well as site-specific seismic amplification effects increase the danger at local scale. As both human lives and specific ecosystems are under threat, comprehensive methodologies are required to reliably assess multi geohazards over both short and long terms and to clearly outline and map related risk. These tools are needed by local and regional authorities as well as local and international stakeholders in management and mitigation processes. Developed methodologies in Geo

  16. Developing a caries risk registry to support caries risk assessment and management for children: A quality improvement initiative.

    Science.gov (United States)

    Ruff, Jesley C; Herndon, Jill Boylston; Horton, Roger A; Lynch, Julie; Mathwig, Dawn C; Leonard, Audra; Aravamudhan, Krishna

    2017-10-27

    Health registries are commonly used in medicine to support public health activities and are increasingly used in quality improvement (QI) initiatives. Illustrations of dental registries and their QI applications are lacking. Within dentistry, caries risk assessment implementation and documentation are vital to optimal patient care. The purpose of this article is to describe the processes used to develop a caries risk assessment registry as a QI initiative to support clinical caries risk assessment, caries prevention, and disease management for children. Developmental steps reflected Agency for Healthcare Research and Quality recommendations for planning QI registries and included engaging "champions," defining the project, identifying registry features, defining performance dashboard indicators, and pilot testing with participant feedback. We followed Standards for Quality Improvement Reporting Excellence guidelines. Registry eligibility is patients aged 0-17 years. QI tools include prompts to register eligible patients; decision support tools grounded in evidence-based guidelines; and performance dashboard reports delivered at the provider and aggregated levels at regular intervals. The registry was successfully piloted in two practices with documented caries risk assessment increasing from 57 percent to 92 percent and positive feedback regarding the potential to improve dental practice patient centeredness, patient engagement and education, and quality of care. The caries risk assessment registry demonstrates how dental registries may be used in QI efforts to promote joint patient and provider engagement, foster shared decision making, and systematically collect patient information to generate timely and actionable data to improve care quality and patient outcomes at the individual and population levels. © 2017 American Association of Public Health Dentistry.

  17. Capability-Driven Design of Business Service Ecosystem to Support Risk Governance in Regulatory Ecosystems

    Directory of Open Access Journals (Sweden)

    Christophe Feltus

    2017-04-01

    Full Text Available Risk-based regulation and risk governance gain momentum in most sectorial ecosystems, should they be the finance, the healthcare or the telecommunications ecosystems. Although there is a profusion of tools to address this issue at the corporate level, worth is to note that no solution fulfils this function at the ecosystem level yet. Therefore, in this article, the Business Service Ecosystem (BSE metamodel is semantically extended, considering the Capability as a Service (CaaS theory, in order to raise the enterprise risk management from the enterprise level up to the ecosystem level. This extension allows defining a concrete ecosystem metamodel which is afterwards mapped with an information system risk management model to support risk governance at the ecosystem level. This mapping is illustrated and validated on the basis of an application case for the Luxembourgish financial sector applied to the most important concepts from the BSE: capability, resource, service and goal.

  18. Multi Criteria Evaluation Module for RiskChanges Spatial Decision Support System

    Science.gov (United States)

    Olyazadeh, Roya; Jaboyedoff, Michel; van Westen, Cees; Bakker, Wim

    2015-04-01

    Multi-Criteria Evaluation (MCE) module is one of the five modules of RiskChanges spatial decision support system. RiskChanges web-based platform aims to analyze changes in hydro-meteorological risk and provides tools for selecting the best risk reduction alternative. It is developed under CHANGES framework (changes-itn.eu) and INCREO project (increo-fp7.eu). MCE tool helps decision makers and spatial planners to evaluate, sort and rank the decision alternatives. The users can choose among different indicators that are defined within the system using Risk and Cost Benefit analysis results besides they can add their own indicators. Subsequently the system standardizes and prioritizes them. Finally, the best decision alternative is selected by using the weighted sum model (WSM). The Application of this work is to facilitate the effect of MCE for analyzing changing risk over the time under different scenarios and future years by adopting a group decision making into practice and comparing the results by numeric and graphical view within the system. We believe that this study helps decision-makers to achieve the best solution by expressing their preferences for strategies under future scenarios. Keywords: Multi-Criteria Evaluation, Spatial Decision Support System, Weighted Sum Model, Natural Hazard Risk Management

  19. Methods and tools to support real time risk-based flood forecasting - a UK pilot application

    Directory of Open Access Journals (Sweden)

    Brown Emma

    2016-01-01

    Full Text Available Flood managers have traditionally used probabilistic models to assess potential flood risk for strategic planning and non-operational applications. Computational restrictions on data volumes and simulation times have meant that information on the risk of flooding has not been available for operational flood forecasting purposes. In practice, however, the operational flood manager has probabilistic questions to answer, which are not completely supported by the outputs of traditional, deterministic flood forecasting systems. In a collaborative approach, HR Wallingford and Deltares have developed methods, tools and techniques to extend existing flood forecasting systems with elements of strategic flood risk analysis, including probabilistic failure analysis, two dimensional flood spreading simulation and the analysis of flood impacts and consequences. This paper presents the results of the application of these new operational flood risk management tools to a pilot catchment in the UK. It discusses the problems of performing probabilistic flood risk assessment in real time and how these have been addressed in this study. It also describes the challenges of the communication of risk to operational flood managers and to the general public, and how these new methods and tools can provide risk-based supporting evidence to assist with this process.

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

    Science.gov (United States)

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

    2016-10-01

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

  1. Supporting the risk management process with land information : a case study of Australia

    NARCIS (Netherlands)

    Potts, Katie Elizabeth; Rajabifard, Abbas; Bennett, R.M.

    2017-01-01

    It is frequently argued that, at the parcel level, stakeholders are capable of and well supported in managing their land-related risks. Yet, evidence from the contemporary Australian context suggests otherwise: numerous large-scale disaster events have revealed that citizens are ill-prepared to

  2. Nutrition support can bring survival benefit to high nutrition risk gastric cancer patients who received chemotherapy.

    Science.gov (United States)

    Qiu, Miaozhen; Zhou, Yi-xin; Jin, Yin; Wang, Zi-xian; Wei, Xiao-li; Han, Hong-yu; Ye, Wen-feng; Zhou, Zhi-wei; Zhang, Dong-sheng; Wang, Feng-hua; Li, Yu-hong; Yang, Da-jun; Xu, Rui-hua

    2015-07-01

    The aim of our study is firstly to evaluate the prevalence and prognostic value of nutrition risk in gastric cancer patients and secondly to explore whether the nutrition support can prolong the survival of advanced gastric cancer patients. It contained two study periods. In the first period, we prospectively evaluated the nutritional risk of gastric adenocarcinoma patients from 2009 to 2011 using the method of European Nutritional Risk Screening (NRS) 2002. The Kaplan-Meier method and log-rank test were used to evaluate the prognostic value of high nutrition risk. The second period was between 2012 and 2013. We prospectively gave the nutrition support to stage IV gastric cancer patients whose NRS is ≥3. There were 830 patients in the first period, 50.7% patients with a NRS ≥ 3. Patients with NRS ≥ 3 presented a significantly higher percentage of stage IV diseases, elevated values of C-reactive protein, and hypoproteinemia. The median survival was significantly higher in NRS nutrition support. The median survival was 14.3 and 9.6 months for patients with and without NRS shift, respectively, P = 0.001. NRS ≥ 3 was an independent adverse prognostic factor in gastric cancer patients. For stage IV patients whose NRS ≥ 3, the nutrition support might be helpful to improve the prognosis.

  3. Bank Risk Taking and Liquidity Creation Following Regulatory Interventions and Capital Support

    NARCIS (Netherlands)

    Berger, A.N.; Bouwman, C.H.S.; Kick, T.; Schaeck, K.

    2011-01-01

    During times of bank distress, authorities often engage in regulatory interventions and provide capital support to reduce bank risk taking. An unintended effect of such actions may be a reduction in bank liquidity creation, with possible adverse consequences for the economy as a whole. This paper

  4. Bank risk taking and liquidity creation following regulatory interventions and capital support

    NARCIS (Netherlands)

    Berger, A.N.; Bouwman, C.H.S.; Kick, T.; Schaeck, K.

    2011-01-01

    During times of bank distress, authorities often engage in regulatory interventions and provide capital support to reduce bank risk taking. An unintended effect of such actions may be a reduction in bank liquidity creation, with possible adverse consequences for the economy as a whole. This paper

  5. Towards a value model for collaborative, business intelligence-supported risk assessment

    NARCIS (Netherlands)

    Liu, L.; Daniëls, H.A.M.; Johannesson, P.

    2012-01-01

    Collaborative business intelligence supports risk assessment and in return enhances management control on a business network. Nonetheless, it needs an incentive basis in the first place before it can be implemented, that is, the value model. Starting from the managerial challenges which arise from

  6. Risk reduction using DDP (Defect Detection and Prevention): Software support and software applications

    Science.gov (United States)

    Feather, M. S.

    2001-01-01

    Risk assessment and mitigation is the focus of the Defect Detection and Prevention (DDP) process, which has been applied to spacecraft technology assessments and planning, both hardware and software. DDP's major elements and their relevance to core requirement engineering concerns are summarized. The accompanying research demonstration illustrates DDP's tool support, and further customizations for application to software.

  7. Prototype of a web - based participative decision support platform in natural hazards and risk management

    NARCIS (Netherlands)

    Aye, Z.C.; Jaboyedoff, M.; Derron, M.H.; van Westen, C.J.

    2015-01-01

    This paper presents the current state and development of a prototype web-GIS (Geographic Information System) decision support platform intended for application in natural hazards and risk management, mainly for floods and landslides. This web platform uses open-source geospatial software and

  8. Decision making support of the management of technogenically contaminated territories basing on risk analysis with use of geographic information technology

    International Nuclear Information System (INIS)

    Yatsalo, B.I.; Demin, V.F.

    2002-01-01

    Overall questions of decision making support of the contaminated territories management on a basis of risk assessment were considered. Characteristics and possibilities of the applied geoinformation system of decision making support PRANA developed for the risk control and rehabilitation of contaminated territories are demonstrated. The PRANA system involves estimations of all fundamental characteristics of risk during analysis of results and contaminated territories management [ru

  9. The Integrated Medical Model: A Risk Assessment and Decision Support Tool for Space Flight Medical Systems

    Science.gov (United States)

    Kerstman, Eric; Minard, Charles; Saile, Lynn; deCarvalho, Mary Freire; Myers, Jerry; Walton, Marlei; Butler, Douglas; Iyengar, Sriram; Johnson-Throop, Kathy; Baumann, David

    2009-01-01

    The Integrated Medical Model (IMM) is a decision support tool that is useful to mission planners and medical system designers in assessing risks and designing medical systems for space flight missions. The IMM provides an evidence based approach for optimizing medical resources and minimizing risks within space flight operational constraints. The mathematical relationships among mission and crew profiles, medical condition incidence data, in-flight medical resources, potential crew functional impairments, and clinical end-states are established to determine probable mission outcomes. Stochastic computational methods are used to forecast probability distributions of crew health and medical resource utilization, as well as estimates of medical evacuation and loss of crew life. The IMM has been used in support of the International Space Station (ISS) medical kit redesign, the medical component of the ISS Probabilistic Risk Assessment, and the development of the Constellation Medical Conditions List. The IMM also will be used to refine medical requirements for the Constellation program. The IMM outputs for ISS and Constellation design reference missions will be presented to demonstrate the potential of the IMM in assessing risks, planning missions, and designing medical systems. The implementation of the IMM verification and validation plan will be reviewed. Additional planned capabilities of the IMM, including optimization techniques and the inclusion of a mission timeline, will be discussed. Given the space flight constraints of mass, volume, and crew medical training, the IMM is a valuable risk assessment and decision support tool for medical system design and mission planning.

  10. An expert panel approach to support risk-informed decision making

    International Nuclear Information System (INIS)

    Pulkkinen, U.; Simola, K.

    2000-01-01

    The report describes the expert panel methodology developed for supporting risk-informed decision making. The aim of an expert panel is to achieve a balanced utilisation of information and expertise from several disciplines in decision-making including probabilistic safety assessment as one decision criterion. We also summarise the application of the methodology in the STUK's RI-ISI (Risk-Informed In-Service Inspection) pilot study, where the expert panel approach was used to combine the deterministic information on degradation mechanisms and probabilistic information on pipe break consequences. The expert panel served both as a critical review of the preliminary results and as a decision support for the final definition of risk categories of piping. (orig.)

  11. Improvement of mutual understanding in risk communication by application of a debate support system

    International Nuclear Information System (INIS)

    Shimoda, Hiroshi; Matsuda, Koji; Ishii, Hirotake; Yoshikawa, Hidekazu

    2010-01-01

    Given the recent problem of climate change, nuclear power has become perhaps the world's most important energy source. In Japan, however, it is difficult to build new nuclear facilities. One of the reasons for such difficulty lies in problems in risk communication. In this study, a support method has been proposed to improve mutual understanding in risk communication. The authors paid especial attention at the learning effect of debating and the benefits of employing a debate support system. A laboratory experiment including 30 university students was conducted in order to evaluate the proposed method. Results showed that the use of the system could improve mutual understanding especially with respect to the factors of risk 'reduction measures' and 'accident management'. In addition, it was found that using the system and debating from 'opposite positions' could improve subjective mutual understanding; however, this practice showed no effectiveness in terms of improving objective mutual understanding. (author)

  12. Support of the management of climatic risks and chances; Unterstuetzung des Managements von Klimarisiken und -chancen

    Energy Technology Data Exchange (ETDEWEB)

    Kind, Christian; Mohns, Till [adelphi research gGmbH, Berlin (Germany); Sartorius, Christian [Fraunhofer-Institut fuer Systemtechnik und Innovationsforschung, Karlsruhe (Germany)

    2011-03-15

    The far-reaching effects of irreversible climatic changes should inform on the expected changes, risks and opportunities. The project 'Support of the management of climate risks and opportunities' contributes to this. As part of this project, an information and decision support system (DSS) is developed which should enable public and private organizations (a) to identify possible risks of climatic change; (b) to avoid possible damages from adjustments; (c) to use possible opportunities of climatic change. The authors of the contribution under consideration develop a profound, scientific basis for the structure and content of the compass-EUS. To this end, various aspects are discussed that are important for the design of such a system.

  13. Support of the management of climatic risks and chances; Unterstuetzung des Managements von Klimarisiken und -chancen

    Energy Technology Data Exchange (ETDEWEB)

    Kind, Christian; Mohns, Till [adelphi research gGmbH, Berlin (Germany); Sartorius, Christian [Fraunhofer-Institut fuer Systemtechnik und Innovationsforschung, Karlsruhe (Germany)

    2011-03-15

    The far-reaching effects of irreversible climatic changes should inform on the expected changes, risks and opportunities. The project 'Support of the management of climate risks and opportunities' contributes to this. As part of this project, an information and decision support system (DSS) is developed which should enable public and private organizations (a) to identify possible risks of climatic change; (b) to avoid possible damages from adjustments; (c) to use possible opportunities of climatic change. The authors of the contribution under consideration develop a profound, scientific basis for the structure and content of the compass-EUS. To this end, various aspects are discussed that are important for the design of such a system.

  14. Applying the Wildland Fire Decision Support System (WFDSS) to support risk-informed decision making: The Gold Pan Fire, Bitterroot National Forest, Montana, USA

    Science.gov (United States)

    Erin K. Noonan-Wright; Tonja S. Opperman

    2015-01-01

    In response to federal wildfire policy changes, risk-informed decision-making by way of improved decision support, is increasingly becoming a component of managing wildfires. As fire incidents escalate in size and complexity, the Wildland Fire Decision Support System (WFDSS) provides support with different analytical tools as fire conditions change. We demonstrate the...

  15. Support for food policy initiatives is associated with knowledge of obesity-related cancer risk factors

    Directory of Open Access Journals (Sweden)

    Wendy Watson

    2017-12-01

    Full Text Available Objectives: To investigate community support for government-led policy initiatives to positively influence the food environment, and to identify whether there is a relationship between support for food policy initiatives and awareness of the link between obesity-related lifestyle risk factors and cancer. Methods: An online survey of knowledge of cancer risk factors and attitudes to policy initiatives that influence the food environment was completed by 2474 adults from New South Wales, Australia. The proportion of participants in support of seven food policy initiatives was quantified in relation to awareness of the link between obesity, poor diet, insufficient fruit and vegetable consumption, and physical inactivity with cancer and other health conditions. Results: Overall, policies that involved taxing unhealthy foods received the least support (41.5%. Support was highest for introducing a colour-coded food labelling system (85.9%, restricting claims being made about the health benefits of foods which are, overall, unhealthy (82.6%, displaying health warning labels on unhealthy foods (78.7% and banning unhealthy food advertising that targets children (72.6%. Participants who were aware that obesity-related lifestyle factors are related to cancer were significantly more likely to support food policy initiatives than those who were unaware. Only 17.5% of participants were aware that obesity, poor diet, insufficient fruit and vegetable consumption, and physical inactivity are linked to cancer. Conclusions: There is strong support for all policies related to food labelling and a policy banning unhealthy food advertising to children. Support for food policy initiatives that positively influence the food environment was higher among those who were aware of the link between cancer and obesity-related lifestyle factors than among those who were unaware of this link. Increasing awareness of the link between obesity-related lifestyle factors and cancer

  16. Managers’ Support – A Key Driver behind Enterprise Risk Management Maturity

    Directory of Open Access Journals (Sweden)

    Sprčić Danijela Miloš

    2017-04-01

    Full Text Available Severe consequences of the global fi nancial crisis resulted in re-thinking the risk management processes and approaches, highlighting the need for a comprehensive risk management framework. Consequently, more and more companies are moving away from the Traditional “silo-based” Risk Management (TRM to a more holistic approach known as Enterprise Risk Management (ERM. This paper presents results of both exploratory and empirical research. First, we develop ERM Index that measures maturity of ERM process within the company. Then, we present empirical results on the level of maturity and determinants of risk management system development in listed Croatian companies. Research indicates low levels of ERM development: even 38 per cent of analysed companies have no elements of ERM system, from which 22 per cent do not manage corporate risks at all. Except the company’s size supported by the economies of scale argument, managers’ support is the most important determinant of ERM system maturity in Croatian companies.

  17. Incorporating stand level risk management options into forest decision support systems

    Directory of Open Access Journals (Sweden)

    Kyle Eyvindson

    2018-01-01

    Full Text Available Aim of study: To examine methods of incorporating risk and uncertainty to stand level forest decisions. Area of study: A case study examines a small forest holding from Jönköping, Sweden. Material and methods: We incorporate empirically estimated uncertainty into the simulation through a Monte Carlo approach when simulating the forest stands for the next 100 years. For the iterations of the Monte Carlo approach, errors were incorporated into the input data which was simulated according to the Heureka decision support system. Both the Value at Risk and the Conditional Value at Risk of the net present value are evaluated for each simulated stand. Main results: Visual representation of the errors can be used to highlight which decision would be most beneficial dependent on the decision maker’s opinion of the forest inventory results. At a stand level, risk preferences can be rather easily incorporated into the current forest decision support software. Research highlights: Forest management operates under uncertainty and risk. Methods are available to describe this risk in an understandable fashion for the decision maker.

  18. Decision support systems and expert systems for risk and safety analysis

    International Nuclear Information System (INIS)

    Baybutt, P.

    1986-01-01

    During the last 1-2 years, rapid developments have occurred in the development of decision support systems and expert systems to aid in decision making related to risk and safety of industrial plants. These activities are most noteworthy in the nuclear industry where numerous systems are under development with implementation often being made on personal computers. An overview of some of these developments is provided, and an example of one recently developed decision support system is given. This example deals with CADET, a system developed to aid the U.S. Nuclear Regulatory Commission in making decisions related to the topical issue of source terms resulting from degraded core accidents in light water reactors. The paper concludes with some comments on the likely directions of future developments in decision support systems and expert systems to aid in the management of risk and safety in industrial plants. (author)

  19. Fall Risk, Supports and Services, and Falls Following a Nursing Home Discharge.

    Science.gov (United States)

    Noureldin, Marwa; Hass, Zachary; Abrahamson, Kathleen; Arling, Greg

    2017-09-04

    Falls are a major source of morbidity and mortality among older adults; however, little is known regarding fall occurrence during a nursing home (NH) to community transition. This study sought to examine whether the presence of supports and services impacts the relationship between fall-related risk factors and fall occurrence post NH discharge. Participants in the Minnesota Return to Community Initiative who were assisted in achieving a community discharge (N = 1459) comprised the study sample. The main outcome was fall occurrence within 30 days of discharge. Factor analyses were used to estimate latent models from variables of interest. A structural equation model (SEM) was estimated to determine the relationship between the emerging latent variables and falls. Fifteen percent of participants fell within 30 days of NH discharge. Factor analysis of fall-related risk factors produced three latent variables: fall concerns/history; activities of daily living impairments; and use of high-risk medications. A supports/services latent variable also emerged that included caregiver support frequency, medication management assistance, durable medical equipment use, discharge location, and receipt of home health or skilled nursing services. In the SEM model, high-risk medications use and fall concerns/history had direct positive effects on falling. Receiving supports/services did not affect falling directly; however, it reduced the effect of high-risk medication use on falling (p risk of falling post NH discharge. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Application of a web-based Decision Support System in risk management

    Science.gov (United States)

    Aye, Zar Chi; Jaboyedoff, Michel; Derron, Marc-Henri

    2013-04-01

    Increasingly, risk information is widely available with the help of advanced technologies such as earth observation satellites, global positioning technologies, coupled with hazard modeling and analysis, and geographical information systems (GIS). Even though it exists, no effort will be put into action if it is not properly presented to the decision makers. These information need to be communicated clearly and show its usefulness so that people can make better informed decision. Therefore, communicating available risk information has become an important challenge and decision support systems have been one of the significant approaches which can help not only in presenting risk information to the decision makers but also in making efficient decisions while reducing human resources and time needed. In this study, the conceptual framework of an internet-based decision support system is presented to highlight its importance role in risk management framework and how it can be applied in case study areas chosen. The main purpose of the proposed system is to facilitate the available risk information in risk reduction by taking into account of the changes in climate, land use and socio-economic along with the risk scenarios. It allows the users to formulate, compare and select risk reduction scenarios (mainly for floods and landslides) through an enhanced participatory platform with diverse stakeholders' involvement in the decision making process. It is based on the three-tier (client-server) architecture which integrates web-GIS plus DSS functionalities together with cost benefit analysis and other supporting tools. Embedding web-GIS provides its end users to make better planning and informed decisions referenced to a geographical location, which is the one of the essential factors in disaster risk reduction programs. Different risk reduction measures of a specific area (local scale) will be evaluated using this web-GIS tool, available risk scenarios obtained from

  1. Supporting families in a high-risk setting: proximal effects of the SAFEChildren preventive intervention.

    Science.gov (United States)

    Tolan, Patrick; Gorman-Smith, Deborah; Henry, David

    2004-10-01

    Four hundred twenty-four families who resided in inner-city neighborhoods and had a child entering 1st grade were randomly assigned to a control condition or to a family-focused preventive intervention combined with academic tutoring. SAFEChildren, which was developed from a developmental-ecological perspective, emphasizes developmental tasks and community factors in understanding risk and prevention. Tracking of linear-growth trends through 6 months after intervention indicated an overall effect of increased academic performance and better parental involvement in school. High-risk families had additional benefits for parental monitoring, child-problem behaviors, and children's social competence. High-risk youth showed improvement in problem behaviors and social competence. Results support a family-focused intervention that addresses risk in low-income communities as managing abnormal challenges.

  2. Personal support networks, social capital, and risk of relapse among individuals treated for substance use issues.

    Science.gov (United States)

    Panebianco, Daria; Gallupe, Owen; Carrington, Peter J; Colozzi, Ivo

    2016-01-01

    The success of treatment for substance use issues varies with personal and social factors, including the composition and structure of the individual's personal support network. This paper describes the personal support networks and social capital of a sample of Italian adults after long-term residential therapeutic treatment for substance use issues, and analyses network correlates of post-treatment substance use (relapse). Using a social network analysis approach, data were obtained from structured interviews (90-120 min long) with 80 former clients of a large non-governmental therapeutic treatment agency in Italy providing voluntary residential treatments and rehabilitation services for substance use issues. Participants had concluded the program at least six months prior. Data were collected on socio-demographic variables, addiction history, current drug use status (drug-free or relapsed), and the composition and structure of personal support networks. Factors related to risk of relapse were assessed using bivariate and multivariate logistic regression models. A main goal of this study was to identify differences between the support network profiles of drug free and relapsed participants. Drug free participants had larger, less dense, more heterogeneous and reciprocal support networks, and more brokerage social capital than relapsed participants. Additionally, a lower risk of relapse was associated with higher socio-economic status, being married/cohabiting, and having network members with higher socio-economic status, who have greater occupational heterogeneity, and reciprocate support. Post-treatment relapse was found to be negatively associated with the socioeconomic status and occupational heterogeneity of ego's support network, reciprocity in the ties between ego and network members, and a support network in which the members are relatively loosely connected with one another (i.e., ego possesses "brokerage social capital"). These findings suggest the

  3. Low Family Support and Risk of Obesity among Black Youth: Role of Gender and Ethnicity.

    Science.gov (United States)

    Assari, Shervin; Caldwell, Cleopatra Howard

    2017-05-12

    Most studies on the role of family environment in developing risk of obesity among youth have focused on parenting behaviors that are directly involved in energy balance in regional, non-representative White samples. Using a national sample of ethnically diverse Black youth, the current study tested the association between low family support and risk of obesity. We also tested the heterogeneity of this association based on gender, ethnicity, and their intersection. We used data from the National Survey of American Life-Adolescent Supplement (NSAL-A), a national survey of Black adolescents in the United States. The study enrolled 1170 African American and Caribbean Black 13-17 year old youth. Obesity was defined based on the cutoff points of body mass index (BMI) appropriate for age and gender of youth. Family support was measured using a five-item measure that captured emotional and tangible social support. Age, gender, and ethnicity were also measured. Logistic regressions were utilized in the pooled sample, and also based on gender, ethnicity, and their intersection, to test the link between low family support and risk for obesity. In the pooled sample, low family support was not associated with an increased risk of obesity (OR = 1.35, 95% Confidence Interval (CI) = 0.96-1.89). The association between low family support and risk of obesity was, however, significant among African American females (OR = 1.60, 95% CI = 1.01-2.55). There was no association for African American males (OR = 1.26, 95% CI = 0.82-1.92), Caribbean Black males (OR = 0.68, 95% CI = 0.01-54.85), and Caribbean Black females (OR = 0.78, 95% CI = 0.42-1.44). In conclusion, policies and programs that enable African American families to provide additional family support may prevent obesity among African American female youth. Future research should test the efficacy of promoting family support as a tool for preventing obesity among African American female youth.

  4. The protease inhibitor PI*S allele and COPD

    DEFF Research Database (Denmark)

    Hersh, C P; Ly, N P; Berkey, C S

    2005-01-01

    In many countries, the protease inhibitor (SERPINA1) PI*S allele is more common than PI*Z, the allele responsible for most cases of chronic obstructive pulmonary disease (COPD) due to severe alpha 1-antitrypsin deficiency. However, the risk of COPD due to the PI*S allele is not clear. The current...... authors located studies that addressed the risk of COPD or measured lung function in individuals with the PI SZ, PI MS and PI SS genotypes. A separate meta-analysis for each genotype was performed. Aggregating data from six studies, the odds ratio (OR) for COPD in PI SZ compound heterozygotes compared...... with PI MM (normal) individuals was significantly increased at 3.26 (95% confidence intervals (CI): 1.24-8.57). In 17 cross-sectional and case-control studies, the OR for COPD in PI MS heterozygotes was 1.19 (95%CI: 1.02-1.38). However, PI MS genotype was not associated with COPD risk after correcting...

  5. A Regional Decision Support Scheme for Pest Risk Analysis in Southeast Asia.

    Science.gov (United States)

    Soliman, T; MacLeod, A; Mumford, J D; Nghiem, T P L; Tan, H T W; Papworth, S K; Corlett, R T; Carrasco, L R

    2016-05-01

    A key justification to support plant health regulations is the ability of quarantine services to conduct pest risk analyses (PRA). Despite the supranational nature of biological invasions and the close proximity and connectivity of Southeast Asian countries, PRAs are conducted at the national level. Furthermore, some countries have limited experience in the development of PRAs, which may result in inadequate phytosanitary responses that put their plant resources at risk to pests vectored via international trade. We review existing decision support schemes for PRAs and, following international standards for phytosanitary measures, propose new methods that adapt existing practices to suit the unique characteristics of Southeast Asia. Using a formal written expert elicitation survey, a panel of regional scientific experts was asked to identify and rate unique traits of Southeast Asia with respect to PRA. Subsequently, an expert elicitation workshop with plant protection officials was conducted to verify the potential applicability of the developed methods. Rich biodiversity, shortage of trained personnel, social vulnerability, tropical climate, agriculture-dependent economies, high rates of land-use change, and difficulties in implementing risk management options were identified as challenging Southeast Asian traits. The developed methods emphasize local Southeast Asian conditions and could help support authorities responsible for carrying out PRAs within the region. These methods could also facilitate the creation of other PRA schemes in low- and middle-income tropical countries. © 2016 Society for Risk Analysis.

  6. MYPLAN - A Mobile Phone Application for Supporting People at Risk of Suicide.

    Science.gov (United States)

    Skovgaard Larsen, Jette L; Frandsen, Hanne; Erlangsen, Annette

    2016-05-01

    Safety plans have been suggested as an intervention for people at risk of suicide. Given the impulsive character of suicidal ideation, a safety plan in the format of a mobile phone application is likely to be more available and useful than traditional paper versions. The study describes MYPLAN, a mobile phone application designed to support people at risk of suicide by letting them create a safety plan. MYPLAN was developed in collaboration with clinical psychiatric staff at Danish suicide preventive clinics. The mobile application lets the user create an individualized safety plan by filling in templates with strategies, actions, and direct links to contact persons. MYPLAN was developed in 2013 and is freely available in Denmark and Norway. It is designed for iPhone and android platforms. As of December 2015, the application has been downloaded almost 8,000 times. Users at risk of suicide as well as clinical staff have provided positive feedback on the mobile application. Support via mobile phone applications might be particularly useful for younger age groups at risk of suicide as well as in areas or countries where support options are lacking. Yet, it is important to examine the effectiveness of this type of intervention.

  7. Prototype development of a web-based participative decision support platform in risk management

    Science.gov (United States)

    Aye, Zar Chi; Olyazadeh, Roya; Jaboyedoff, Michel; Derron, Marc-Henri

    2014-05-01

    This paper discusses the proposed background architecture and prototype development of an internet-based decision support system (DSS) in the field of natural hazards and risk management using open-source geospatial software and web technologies. It is based on a three-tier, client-server architecture with the support of boundless (opengeo) framework and its client side SDK application environment using customized gxp components and data utility classes. The main purpose of the system is to integrate the workflow of risk management systematically with the diverse involvement of stakeholders from different organizations dealing with natural hazards and risk for evaluation of management measures through the active online participation approach. It aims to develop an adaptive user friendly, web-based environment that allows the users to set up risk management strategies based on actual context and data by integrating web-GIS and DSS functionality associated with process flow and other visualization tools. Web-GIS interface has been integrated within the DSS to deliver maps and provide certain geo-processing capabilities on the web, which can be easily accessible and shared by different organizations located in case study sites of the project. This platform could be envisaged not only as a common web-based platform for the centralized sharing of data such as hazard maps, elements at risk maps and additional information but also to ensure an integrated platform of risk management where the users could upload data, analyze risk and identify possible alternative scenarios for risk reduction especially for floods and landslides, either quantitatively or qualitatively depending on the risk information provided by the stakeholders in case study regions. The level of involvement, access to and interaction with the provided functionality of the system varies depending on the roles and responsibilities of the stakeholders, for example, only the experts (planners, geological

  8. Development of a Spatial Decision Support System for Analyzing Changes in Hydro-meteorological Risk

    Science.gov (United States)

    van Westen, Cees

    2013-04-01

    In the framework of the EU FP7 Marie Curie ITN Network "CHANGES: Changing Hydro-meteorological Risks, as Analyzed by a New Generation of European Scientists (http://www.changes-itn.eu)", a spatial decision support system is under development with the aim to analyze the effect of risk reduction planning alternatives on reducing the risk now and in the future, and support decision makers in selecting the best alternatives. The SDSS is one of the main outputs of the CHANGES network, which will develop an advanced understanding of how global changes, related to environmental and climate change as well as socio-economical change, may affect the temporal and spatial patterns of hydro-meteorological hazards and associated risks in Europe; how these changes can be assessed, modeled, and incorporated in sustainable risk management strategies, focusing on spatial planning, emergency preparedness and risk communication. The CHANGES network consists of 11 full partners and 6 associate partners of which 5 private companies, representing 10 European countries. The CHANGES network has hired 12 Early Stage Researchers (ESRs) and is currently hiring 3-6 researchers more for the implementation of the SDSS. The Spatial Decision Support System will be composed of a number of integrated components. The Risk Assessment component allows to carry out spatial risk analysis, with different degrees of complexity, ranging from simple exposure (overlay of hazard and assets maps) to quantitative analysis (using different hazard types, temporal scenarios and vulnerability curves) resulting into risk curves. The platform does not include a component to calculate hazard maps, and existing hazard maps are used as input data for the risk component. The second component of the SDSS is a risk reduction planning component, which forms the core of the platform. This component includes the definition of risk reduction alternatives (related to disaster response planning, risk reduction measures and

  9. Reducing the risks of diabetes complications through diabetes self-management education and support.

    Science.gov (United States)

    Kent, Dan; D'Eramo Melkus, Gail; Stuart, Patricia Mickey W; McKoy, June M; Urbanski, Patti; Boren, Suzanne Austin; Coke, Lola; Winters, Janis E; Horsley, Neil L; Sherr, Dawn; Lipman, Ruth

    2013-04-01

    People with diabetes are at risk of developing complications that contribute to substantial morbidity and mortality. In 2011, the American Association of Diabetes Educators convened an invitational Reducing Risks Symposium, during which an interdisciplinary panel of 11 thought leaders examined current knowledge about the reduction and prevention of diabetes-related risks and translated evidence into diabetes care and self-management education. Symposium participants reviewed findings from the literature and engaged in a moderated roundtable discussion. This report summarizes the discussion and presents recommendations to incorporate into practice to improve outcomes. The objective of the symposium was to develop practical advice for diabetes educators and other members of the diabetes care team regarding the reduction of diabetes-related risks. Optimal diabetes management requires patients to actively participate in their care, which occurs most effectively with a multidisciplinary team. Diabetes education is an integral part of this team approach because it not only helps the patient understand diabetes, its progression, and possible complications, but also provides guidance and encouragement to the patient to engage in proactive risk-reduction decisions for optimal health. A variety of tools are available to help the diabetes educator develop an individualized, patient-centered plan for risk reduction. More research is needed regarding intervention efficacy, best practices to improve adherence, and quantification of benefits from ongoing diabetes support in risk reduction. Diabetes educators are urged to stay abreast of evolving models of care and to build relationships with health care providers both within and beyond the diabetes care team.

  10. Derivation of endogenous equivalent values to support risk assessment and risk management decisions for an endogenous carcinogen: Ethylene oxide.

    Science.gov (United States)

    Kirman, C R; Hays, S M

    2017-12-01

    An approach is presented for ethylene oxide (EO) to derive endogenous equivalent (EE) values, which are endogenous levels normally found within the body expressed in terms of exogenous exposures. EE values can be used to support risk assessment and risk management decisions for chemicals such as EO that have both endogenous and exogenous exposure pathways. EE values were derived using a meta-analysis of data from the published literature characterizing the distribution for an EO biomarker of exposure, hemoglobin N-(2-hydroxyethyl)-valine (HEV), in unexposed populations. These levels are compared to the those reported in exposed populations (smokers, workers). Correlation between the biomarker of exposure and external exposures of EO were applied to this distribution to determine corresponding EE values, which range from 0.13 to 6.9 ppb for EO in air. These values are orders of magnitude higher than risk-based concentration values derived for EO using default methods, and are provided as a pragmatic, data-driven alternative approach to managing the potential risks from exogenous exposures to EO. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Examining spiritual support among African American and Caucasian Alzheimer's caregivers: A risk and resilience study.

    Science.gov (United States)

    Wilks, Scott E; Spurlock, Wanda R; Brown, Sandra C; Teegen, Bettina C; Geiger, Jennifer R

    2018-05-25

    Research shows African Americans at greater risk of developing Alzheimer's disease (AD) compared to the Caucasian population, suggesting African American AD caregivers are rising in numbers at a greater rate than Caucasian counterparts. Over a decade ago, an article in Geriatric Nursing revealed spiritual well-being differences among these caregiver groups. The purpose of this study was a quasi-follow-up, utilizing a larger caregiver sample to test spiritual support as a moderator via a risk-and-resilience framework. Secondary data analysis from a sample of 691 AD caregivers examined data on demographics and standardized measures of spiritual support, caregiver burden, and psychological resilience. One-third of the sample reported as African American. Resilience negatively regressed, though not significantly, on caregiving burden among both groups. Spiritual support positively, significantly impacted resilience among both groups, slightly stronger among African Americans. Spiritual support did not significantly moderate risk with either group. Implications for professional healthcare practice are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Feasibility Risk Assessment of Transport Infrastructure Projects: The CBA-DK Decision Support Model

    DEFF Research Database (Denmark)

    Salling, Kim Bang; Banister, David

    2010-01-01

    informed decision support towards decision-makers and stakeholders in terms of accumulated descending graphs. The decision support method developed in this paper aims to provide assistance in the analysis and ultimately the choice of action, while accounting for the uncertainties surrounding any transport......This paper presents the final version of the CBA-DK decision support model for assessment of transport projects. The model makes use of conventional cost-benefit analysis resulting in aggregated single point estimates and quantitative risk analysis using Monte Carlo simulation resulting in interval...... result, and the determination of suitable probability distributions. Use is made of the reference class forecasting information, such as that developed in Optimism Bias for adjustments to investment decisions that relate to all modes of transport. The CBA-DK decision support model results in more...

  13. Social Support and HIV Risks Among Migrant and Non-Migrant Market Workers in Almaty, Kazakhstan.

    Science.gov (United States)

    Mergenova, Gaukhar; Shaw, Stacey A; Terlikbayeva, Assel; Gilbert, Louisa; Gensburg, Lenore; Primbetova, Sholpan; El-Bassel, Nabila

    2017-08-01

    Migration processes are listed within the primary factors facilitating the heterosexual spread of HIV. The study examines the relationship between social support, sexual HIV risk behaviors and sexually transmitted infections (STIs) among 1342 male migrant and non-migrant market workers from Barakholka Market in Almaty, Kazakhstan. (1) higher level of perceived social support [Enhancing Recovery in Coronary Heart Disease (ENRICHD) Social Support Instrument (ESSI score)] was associated with a lower likelihood of having sex with a female sex worker (FSW) [OR = 0.952 (0.927, 0.978) p social support factors should be considered as a component of HIV and STI prevention programs for male migrant workers from Central Asia in Kazakhstan.

  14. Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots

    Czech Academy of Sciences Publication Activity Database

    Baker, C.L.; Petkova, P.; Walker, M.; Flachs, Petr; Mihola, Ondřej; Trachtulec, Zdeněk; Petkov, P.M.; Paigen, K.

    2015-01-01

    Roč. 11, č. 9 (2015), e1005512-e1005512 ISSN 1553-7390 R&D Projects: GA ČR GAP305/10/1931; GA ČR(CZ) GA14-20728S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378050 Keywords : recombination * PRDM9 * allelic competition Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.528, year: 2014

  15. Information support of monitoring of technical condition of buildings in construction risk area

    Science.gov (United States)

    Skachkova, M. E.; Lepihina, O. Y.; Ignatova, V. V.

    2018-05-01

    The paper presents the results of the research devoted to the development of a model of information support of monitoring buildings technical condition; these buildings are located in the construction risk area. As a result of the visual and instrumental survey, as well as the analysis of existing approaches and techniques, attributive and cartographic databases have been created. These databases allow monitoring defects and damages of buildings located in a 30-meter risk area from the object under construction. The classification of structures and defects of these buildings under survey is presented. The functional capabilities of the developed model and the field of it practical applications are determined.

  16. Plasma extracellular superoxide dismutase concentration, allelic variations in the SOD3 gene and risk of myocardial infarction and all-cause mortality in people with type 1 and type 2 diabetes.

    Science.gov (United States)

    Mohammedi, Kamel; Bellili-Muñoz, Naïma; Marklund, Stefan L; Driss, Fathi; Le Nagard, Hervé; Patente, Thiago A; Fumeron, Frédéric; Roussel, Ronan; Hadjadj, Samy; Marre, Michel; Velho, Gilberto

    2015-01-15

    Oxidative stress is involved in development of diabetes complications. Extracellular superoxide dismutase (EC-SOD, SOD3) is a major extracellular antioxidant enzyme and is highly expressed in arterial walls. Advanced oxidation protein products (AOPP) and 8-iso-prostaglandin (isoprostane) are markers of oxidative stress. We investigated association of SOD3 gene variants, plasma concentrations of EC-SOD, AOPP and isoprostane with myocardial infarction and mortality in diabetic patients. We studied three cohorts designed to evaluate the vascular complications of diabetes: the GENEDIAB study (469 participants with type 1 diabetes at baseline; follow-up data for 259 participants), the GENESIS study (603 participants with type 1 diabetes at baseline; follow-up data for 525 participants) and the DIABHYCAR study (3137 participants with type 2 diabetes at baseline and follow-up). Duration of follow-up was 9, 5, and 5 years, respectively. Main outcome measures were incidence of myocardial infarction, and cardiovascular and total mortality during follow-up. Six single nucleotide polymorphisms in the SOD3 locus were genotyped in the three cohorts. Plasma concentrations of EC-SOD, AOPP, and isoprostane were measured in baseline samples of GENEDIAB participants. In GENEDIAB/GENESIS pooled cohorts, the minor T-allele of rs2284659 variant was inversely associated with the prevalence at baseline (Odds Ratio 0.48, 95% CI 0.29-0.78, p = 0.004) and the incidence during follow-up of myocardial infarction (Hazard Ratio 0.58, 95% CI 0.40-0.83, p = 0.003) and with cardiovascular (HR 0.33, 95% CI 0.08-0.74, p = 0.004) and all-cause mortality (HR 0.44, 95% CI 0.21-0.73, p = 0.0006). The protective allele was associated with higher plasma EC-SOD and lower plasma AOPP concentrations in GENEDIAB. It was also inversely associated with incidence of myocardial infarction (HR 0.75, 95% CI 0.59-0.94, p = 0.01) and all-cause mortality (HR 0.87, 95% CI 0.79-0.97, p = 0

  17. Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project.

    Science.gov (United States)

    Cross, Deanna S; Ivacic, Lynn C; Stefanski, Elisha L; McCarty, Catherine A

    2010-06-17

    There is a lack of knowledge regarding the frequency of disease associated polymorphisms in populations and population attributable risk for many populations remains unknown. Factors that could affect the association of the allele with disease, either positively or negatively, such as race, ethnicity, and gender, may not be possible to determine without population based allele frequencies.Here we used a panel of 51 polymorphisms previously associated with at least one disease and determined the allele frequencies within the entire Personalized Medicine Research Project population based cohort. We compared these allele frequencies to those in dbSNP and other data sources stratified by race. Differences in allele frequencies between self reported race, region of origin, and sex were determined. There were 19544 individuals who self reported a single racial category, 19027 or (97.4%) self reported white Caucasian, and 11205 (57.3%) individuals were female. Of the 11,208 (57%) individuals with an identifiable region of origin 8337 or (74.4%) were German.41 polymorphisms were significantly different between self reported race at the 0.05 level. Stratification of our Caucasian population by self reported region of origin revealed 19 polymorphisms that were significantly different (p = 0.05) between individuals of different origins. Further stratification of the population by gender revealed few significant differences in allele frequencies between the genders. This represents one of the largest population based allele frequency studies to date. Stratification by self reported race and region of origin revealed wide differences in allele frequencies not only by race but also by region of origin within a single racial group. We report allele frequencies for our Asian/Hmong and American Indian populations; these two minority groups are not typically selected for population allele frequency detection. Population wide allele frequencies are important for the design and

  18. The American Petroleum Institute's Decision Support System for performing exposure and risk assessments

    International Nuclear Information System (INIS)

    Spence, L.R.

    1994-01-01

    The author has developed the American Petroleum Institute's (API) Exposure and Risk Assessment Decision Support System (DSS) to assist environmental professionals in estimating human exposure and risk from sites contaminated with petroleum hydrocarbons. The DSS is a valuable, user-friendly tool that can be used to (1) estimate site-specific risks, (2) identify the need for site remediation, (3) develop and negotiate site-specific cleanup levels with regulatory agencies, and (4) efficiently and effectively evaluate the effect of parameter uncertainty and variability on estimated risk. API DSS Version 1.0 consists of four modules. Specifically, the Development of Risk Scenario module allows the user to develop a conceptual model for estimating the risk. The Fate and Transport module includes a number of contaminant fate and transport models to estimate receptor point concentrations using site-specific hydrogeological and meteorological data entered by the user. The Chemical Intake and Risk Calculation module uses estimated or user-entered receptor point concentrations to estimate chemical intake by a human receptor for several different exposure routes. Finally, the Risk Presentation module allows the user to view the results of the analysis in tabular and graphical formats. The DSS includes chemical databases for 25 hydrocarbons containing transport and toxicity information. These databases may be expanded to include many additional (non-hydrocarbon) chemicals. The computational modules of the DSS can be implemented in either a deterministic or a Monte Carlo simulation mode. The latter is used to quantify the uncertainty in the exposure and risk results due to uncertainty in the input parameters

  19. Familial Risk and a Genome-Wide Supported DRD2 Variant for Schizophrenia Predict Lateral Prefrontal-Amygdala Effective Connectivity During Emotion Processing.

    Science.gov (United States)

    Quarto, Tiziana; Paparella, Isabella; De Tullio, Davide; Viscanti, Giovanna; Fazio, Leonardo; Taurisano, Paolo; Romano, Raffaella; Rampino, Antonio; Masellis, Rita; Popolizio, Teresa; Selvaggi, Pierluigi; Pergola, Giulio; Bertolino, Alessandro; Blasi, Giuseppe

    2017-09-16

    The brain functional mechanisms translating genetic risk into emotional symptoms in schizophrenia (SCZ) may include abnormal functional integration between areas key for emotion processing, such as the amygdala and the lateral prefrontal cortex (LPFC). Indeed, investigation of these mechanisms is also complicated by emotion processing comprising different subcomponents and by disease-associated state variables. Here, our aim was to investigate the relationship between risk for SCZ and effective connectivity between the amygdala and the LPFC during different subcomponents of emotion processing. Thus, we first characterized with dynamic causal modeling (DCM) physiological patterns of LPFC-amygdala effective connectivity in healthy controls (HC) during implicit and explicit emotion processing. Then, we compared DCM patterns in a subsample of HC, in patients with SCZ and in healthy siblings of patients (SIB), matched for demographics. Finally, we investigated in HC association of LPFC-amygdala effective connectivity with a genome-wide supported variant increasing genetic risk for SCZ and possibly relevant to emotion processing (DRD2 rs2514218). In HC, we found that a "bottom-up" amygdala-to-LPFC pattern during implicit processing and a "top-down" LPFC-to-amygdala pattern during explicit processing were the most likely directional models of effective connectivity. Differently, implicit emotion processing in SIB, SCZ, and HC homozygous for the SCZ risk rs2514218 C allele was associated with decreased probability for the "bottom-up" as well as with increased probability for the "top-down" model. These findings suggest that task-specific anomaly in the directional flow of information or disconnection between the amygdala and the LPFC is a good candidate endophenotype of SCZ. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  20. Social Support and Sexual Risk Among Establishment-Based Female Sex Workers in Tijuana.

    Science.gov (United States)

    Choudhury, Shonali Mona; Toller Erausquin, Jennifer; Park, Kyuwon; Anglade, Debbie

    2015-08-01

    Social support can affect health outcomes of female sex workers. In this inductive feminist grounded theory study based on 20 in-depth interviews, we explore how establishment-based female sex workers in Tijuana perceive the impact of the connections among women on their lives and health. Participants elected to discuss the importance of social support from mothers, sisters, friends, and co-workers, and the empowering and disempowering aspects of these relationships. In previous studies, scholars demonstrated the efficacy of formal organization of female sex workers in promoting the mitigation of sexual and HIV risk. We show the importance of informal ties with other women. Some participants mentioned competitive relationships, others talked about cooperation and the desire for a venue to learn from one another. Social interactions with other women are especially empowering when female sex workers can openly engage in "woman talk" that may contribute to the mitigation of sexual and HIV risk. © The Author(s) 2015.

  1. Interactive Decision-Support Tool for Risk-Based Radiation Therapy Plan Comparison for Hodgkin Lymphoma

    DEFF Research Database (Denmark)

    Brodin, N. Patrik; Maraldo, Maja V.; Aznar, Marianne C.

    2014-01-01

    PURPOSE: To present a novel tool that allows quantitative estimation and visualization of the risk of various relevant normal tissue endpoints to aid in treatment plan comparison and clinical decision making in radiation therapy (RT) planning for Hodgkin lymphoma (HL). METHODS AND MATERIALS...... and a volumetric modulated arc therapy plan for a patient with mediastinal HL. CONCLUSION: This multiple-endpoint decision-support tool provides quantitative risk estimates to supplement the clinical judgment of the radiation oncologist when comparing different RT options....... of dose-response curves to drive the reoptimization of a volumetric modulated arc therapy treatment plan for an HL patient with head-and-neck involvement. We also use this decision-support tool to visualize and quantitatively evaluate the trade-off between a 3-dimensional conformal RT plan...

  2. Qualitative risk assessment of subsurface barriers in applications supporting retrieval of SST waste

    International Nuclear Information System (INIS)

    Treat, R.L.

    1994-04-01

    This report provides a brief, qualitative assessment of risks associated with the potential use of impermeable surface barriers installed around and beneath Hanford Site single-shell tanks (SSTs) to support the retrieval of wastes from those tanks. These risks are compared to qualitative assessment of costs and risks associated with a case in which barriers are not used. A quantitative assessment of costs and risks associated with these two cases will be prepared and documented in a companion report. The companion report will compare quantitatively the costs and risks of several retrieval options with varying parameters, such as effectiveness of retrieval, effectiveness of subsurface barriers, and the use of surface barriers. For ease of comparison of qualitative risks, a case in which impermeable subsurface barriers are used in conjunction with another technology to remove tank waste is referred, to in this report as the Barrier Case. A case in which waste removal technologies are used without employing a subsurface barrier is referred to as the No Barrier Case. The technologies associated with each case are described in the following sections

  3. Recent innovation of geospatial information technology to support disaster risk management and responses

    Science.gov (United States)

    Une, Hiroshi; Nakano, Takayuki

    2018-05-01

    Geographic location is one of the most fundamental and indispensable information elements in the field of disaster response and prevention. For example, in the case of the Tohoku Earthquake in 2011, aerial photos taken immediately after the earthquake greatly improved information sharing among different government offices and facilitated rescue and recovery operations, and maps prepared after the disaster assisted in the rapid reconstruction of affected local communities. Thanks to the recent development of geospatial information technology, this information has become more essential for disaster response activities. Advancements in web mapping technology allows us to better understand the situation by overlaying various location-specific data on base maps on the web and specifying the areas on which activities should be focused. Through 3-D modelling technology, we can have a more realistic understanding of the relationship between disaster and topography. Geospatial information technology can sup-port proper preparation and emergency responses against disasters by individuals and local communities through hazard mapping and other information services using mobile devices. Thus, geospatial information technology is playing a more vital role on all stages of disaster risk management and responses. In acknowledging geospatial information's vital role in disaster risk reduction, the Sendai Framework for Disaster Risk Reduction 2015-2030, adopted at the Third United Nations World Conference on Disaster Risk Reduction, repeatedly reveals the importance of utilizing geospatial information technology for disaster risk reduction. This presentation aims to report the recent practical applications of geospatial information technology for disaster risk management and responses.

  4. An integrated probabilistic risk analysis decision support methodology for systems with multiple state variables

    International Nuclear Information System (INIS)

    Sen, P.; Tan, John K.G.; Spencer, David

    1999-01-01

    Probabilistic risk analysis (PRA) methods have been proven to be valuable in risk and reliability analysis. However, a weak link seems to exist between methods for analysing risks and those for making rational decisions. The integrated decision support system (IDSS) methodology presented in this paper attempts to address this issue in a practical manner. In consists of three phases: a PRA phase, a risk sensitivity analysis (SA) phase and an optimisation phase, which are implemented through an integrated computer software system. In the risk analysis phase the problem is analysed by the Boolean representation method (BRM), a PRA method that can deal with systems with multiple state variables and feedback loops. In the second phase the results obtained from the BRM are utilised directly to perform importance and risk SA. In the third phase, the problem is formulated as a multiple objective decision making problem in the form of multiple objective reliability optimisation. An industrial example is included. The resultant solutions of a five objective reliability optimisation are presented, on the basis of which rational decision making can be explored

  5. Risk management frameworks: supporting the next generation of Murray-Darling Basin water sharing plans

    Directory of Open Access Journals (Sweden)

    G. M. Podger

    2014-09-01

    Full Text Available Water jurisdictions in Australia are required to prepare and implement water resource plans. In developing these plans the common goal is realising the best possible use of the water resources – maximising outcomes while minimising negative impacts. This requires managing the risks associated with assessing and balancing cultural, industrial, agricultural, social and environmental demands for water within a competitive and resource-limited environment. Recognising this, conformance to international risk management principles (ISO 31000:2009 have been embedded within the Murray-Darling Basin Plan. Yet, to date, there has been little strategic investment by water jurisdictions in bridging the gap between principle and practice. The ISO 31000 principles and the risk management framework that embodies them align well with an adaptive management paradigm within which to conduct water resource planning. They also provide an integrative framework for the development of workflows that link risk analysis with risk evaluation and mitigation (adaptation scenarios, providing a transparent, repeatable and robust platform. This study, through a demonstration use case and a series of workflows, demonstrates to policy makers how these principles can be used to support the development of the next generation of water sharing plans in 2019. The workflows consider the uncertainty associated with climate and flow inputs, and model parameters on irrigation and hydropower production, meeting environmental flow objectives and recreational use of the water resource. The results provide insights to the risks associated with meeting a range of different objectives.

  6. Evaluation of Lay Support in Pregnant women with Social risk (ELSIPS: a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Kenyon Sara

    2012-02-01

    Full Text Available Abstract Background Maternal, neonatal and child health outcomes are worse in families from black and ethnic minority groups and disadvantaged backgrounds. There is little evidence on whether lay support improves maternal and infant outcomes among women with complex social needs within a disadvantaged multi-ethnic population in the United Kingdom (UK. Method/Design The aim of this study is to evaluate a lay Pregnancy Outreach Worker (POW service for nulliparous women identified as having social risk within a maternity service that is systematically assessing social risks alongside the usual obstetric and medical risks. The study design is a randomised controlled trial (RCT in nulliparous women assessed as having social risk comparing standard maternity care with the addition of referral to the POW support service. The POWs work alongside community midwifery teams and offer individualised support to women to encourage engagement with services (health and social care from randomisation (before 28 weeks gestation until 6 weeks after birth. The primary outcomes have been chosen on the basis that they are linked to maternal and infant health. The two primary outcomes are engagement with antenatal care, assessed by the number of antenatal visits; and maternal depression, assessed using the Edinburgh Postnatal Depression Scale at 8-12 weeks after birth. Secondary outcomes include maternal and neonatal morbidity and mortality, routine child health assessments, including immunisation uptake and breastfeeding at 6 weeks. Other psychological outcomes (self efficacy and mother-to-infant bonding will also be collected using validated tools. A sample size of 1316 will provide 90% power (at the 5% significance level to detect increased engagement with antenatal services of 1.5 visits and a reduction of 1.5 in the average EPDS score for women with two or more social risk factors, with power in excess of this for women with any social risk factor. Analysis will

  7. The use of risk assessment to support control of Salmonella in pork

    DEFF Research Database (Denmark)

    Nauta, Maarten

    Despite the effectivity of control measures in the past decade, domestic pork was estimated to be the most important food source for salmonellosis in Denmark in 2014 (Anonymous 2015). Therefore, there is a continued focus on the identification of effective intervention measures in the pig and pork...... of salmonellosis for the Danish population. The results of these projects illustrate how quantitative microbiological risk assessments (QMRAs) can be applied to support the control of Salmonella in pork....

  8. Social Support and Its Impact on Ethnic Identity and HIV Risk among Migrant Workers.

    Science.gov (United States)

    Shehadeh, Nancy; Rubens, Muni; Attonito, Jennifer; Jennings, Terri

    2018-02-01

    Migrant workers are disproportionately affected by HIV due to poverty, social isolation, lack of access to and availability of health care services, acculturation, language barriers, constant mobility, and lack of knowledge. This study examined the impact of changes in social support on ethnic identity and HIV risk behaviors among migrant workers in South Florida. For this study, baseline and 6-month follow-up data were collected from an HIV intervention study among migrant workers in South Florida (n = 270) who reported unprotected sex in the past 30 days. The Multigroup Identity Measure was used to assess ethnic identity and the Social Provisions Scale examined the degree to which respondents' social relationships provide various dimensions of social support. Social support was a significant predictor of ethnic identity and of ethnic identity subscales, ethnic identity belonging and ethnic identity explore. There were small but statistically significant short-term changes in ethnic identity and ethnic identity subscales among the migrant workers over the 6-month time period assessed after controlling for the intervention. Future studies should be conducted over a longer period of time to better assess this relationship and possible factors to reduce HIV risk behaviors. There is a need to focus on improving the quality of health and reduce HIV and other risks experienced by this marginalized community.

  9. Prioritization of information using decision support systems for seismic risk in Bucharest city

    Science.gov (United States)

    Armas, Iuliana; Gheorghe, Diana

    2014-05-01

    Nowadays, because of the ever increasing volume of information, policymakers are faced with decision making problems. Achieving an objective and suitable decision making may become a challenge. In such situations decision support systems (DSS) have been developed. DSS can assist in the decision making process, offering support on how a decision should be made, rather than what decision should be made (Simon, 1979). This in turn potentially involves a huge number of stakeholders and criteria. Regarding seismic risk, Bucharest City is highly vulnerable (Mandrescu et al., 2007). The aim of this study is to implement a spatial decision support system in order to secure a suitable shelter in case of an earthquake occurrence in the historical centre of Bucharest City. In case of a seismic risk, a shelter is essential for sheltering people who lost their homes or whose homes are in danger of collapsing while people at risk receive first aid in the post-disaster phase. For the present study, the SMCE Module for ILWIS 3.4 was used. The methodology included structuring the problem by creating a decision tree, standardizing and weighting of the criteria. The results showed that the most suitable buildings are Tania Hotel, Hanul lui Manuc, The National Bank of Romania, The Romanian Commercial Bank and The National History Museum.

  10. Visualizing risks in cancer communication: A systematic review of computer-supported visual aids.

    Science.gov (United States)

    Stellamanns, Jan; Ruetters, Dana; Dahal, Keshav; Schillmoeller, Zita; Huebner, Jutta

    2017-08-01

    Health websites are becoming important sources for cancer information. Lay users, patients and carers seek support for critical decisions, but they are prone to common biases when quantitative information is presented. Graphical representations of risk data can facilitate comprehension, and interactive visualizations are popular. This review summarizes the evidence on computer-supported graphs that present risk data and their effects on various measures. The systematic literature search was conducted in several databases, including MEDLINE, EMBASE and CINAHL. Only studies with a controlled design were included. Relevant publications were carefully selected and critically appraised by two reviewers. Thirteen studies were included. Ten studies evaluated static graphs and three dynamic formats. Most decision scenarios were hypothetical. Static graphs could improve accuracy, comprehension, and behavioural intention. But the results were heterogeneous and inconsistent among the studies. Dynamic formats were not superior or even impaired performance compared to static formats. Static graphs show promising but inconsistent results, while research on dynamic visualizations is scarce and must be interpreted cautiously due to methodical limitations. Well-designed and context-specific static graphs can support web-based cancer risk communication in particular populations. The application of dynamic formats cannot be recommended and needs further research. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. A Decision Support System for Drinking Water Production Integrating Health Risks Assessment

    Science.gov (United States)

    Delpla, Ianis; Monteith, Donald T.; Freeman, Chris; Haftka, Joris; Hermens, Joop; Jones, Timothy G.; Baurès, Estelle; Jung, Aude-Valérie; Thomas, Olivier

    2014-01-01

    The issue of drinking water quality compliance in small and medium scale water services is of paramount importance in relation to the 98/83/CE European Drinking Water Directive (DWD). Additionally, concerns are being expressed over the implementation of the DWD with respect to possible impacts on water quality from forecast changes in European climate with global warming and further anticipated reductions in north European acid emissions. Consequently, we have developed a decision support system (DSS) named ARTEM-WQ (AwaReness Tool for the Evaluation and Mitigation of drinking Water Quality issues resulting from environmental changes) to support decision making by small and medium plant operators and other water stakeholders. ARTEM-WQ is based on a sequential risk analysis approach that includes consideration of catchment characteristics, climatic conditions and treatment operations. It provides a holistic evaluation of the water system, while also assessing human health risks of organic contaminants potentially present in treated waters (steroids, pharmaceuticals, pesticides, bisphenol-a, polychlorobiphenyls, polycyclic aromatic hydrocarbons, petrochemical hydrocarbons and disinfection by-products; n = 109). Moreover, the system provides recommendations for improvement while supporting decision making in its widest context. The tool has been tested on various European catchments and shows a promising potential to inform water managers of risks and appropriate mitigative actions. Further improvements should include toxicological knowledge advancement, environmental background pollutant concentrations and the assessment of the impact of distribution systems on water quality variation. PMID:25046634

  12. Credit Risk Evaluation Using a C-Variable Least Squares Support Vector Classification Model

    Science.gov (United States)

    Yu, Lean; Wang, Shouyang; Lai, K. K.

    Credit risk evaluation is one of the most important issues in financial risk management. In this paper, a C-variable least squares support vector classification (C-VLSSVC) model is proposed for credit risk analysis. The main idea of this model is based on the prior knowledge that different classes may have different importance for modeling and more weights should be given to those classes with more importance. The C-VLSSVC model can be constructed by a simple modification of the regularization parameter in LSSVC, whereby more weights are given to the lease squares classification errors with important classes than the lease squares classification errors with unimportant classes while keeping the regularized terms in its original form. For illustration purpose, a real-world credit dataset is used to test the effectiveness of the C-VLSSVC model.

  13. Reaching and Supporting At-Risk Community Based Seniors: Results of a Multi-church Partnership.

    Science.gov (United States)

    Ellis, Julie L; Morzinski, Jeffrey A

    2018-04-26

    The purpose of this study was to determine the impact of a nurse-led, church-based educational support group for "at-risk," older African Americans on hospitalization and emergency department use. Study nurses enrolled 81 "at-risk" older adult members of ten churches. Participants completed a trifold pamphlet identifying personal health information and support, and they attended eight monthly educational/support group sessions in their church during the 10-month intervention. Study nurses completed a risk assessment interview with each senior both pre- and post-participation. The study nurse completed post-program assessments with 64 seniors, a 79% retention rate. At the program's conclusion researchers conducted a focus group with the study RNs and used an anonymous written survey to gather participant appraisals of program elements. Neither hospitalization nor emergency department/urgent care usage was significantly different from pre- to post-program. Session attendance was moderate to high and over half of the seniors brought a family member or friend to one or more sessions. The majority of seniors initiated positive health changes (e.g., smoking cessation, weight loss, or diet changes). Participants expressed high satisfaction and expressed satisfaction to perceive that they were supporting other seniors in their community. We conclude that this intervention was successful in engaging and motivating seniors to initiate health behavior change and contributed to a health-supportive church-based community. To demonstrate a statistically significant difference in hospital and ED usage, however, a stronger intervention or a larger sample size is needed.

  14. Perceived Social Support Trajectories and the All-Cause Mortality Risk of Older Mexican American Women and Men

    Science.gov (United States)

    Hill, Terrence D.; Uchino, Bert N.; Eckhardt, Jessica L.; Angel, Jacqueline L.

    2016-01-01

    Although numerous studies of non-Hispanic whites and blacks show that social integration and social support tend to favor longevity, it is unclear whether this general pattern extends to the Mexican American population. Building on previous research, we employed seven waves of data from the Hispanic Established Populations for the Epidemiologic Study of the Elderly to examine the association between perceived social support trajectories and the all-cause mortality risk of older Mexican Americans. Growth mixture estimates revealed three latent classes of support trajectories: high, moderate, and low. Cox regression estimates indicated that older Mexican American men in the low support trajectory tend to exhibit a higher mortality risk than their counterparts in the high support trajectory. Social support trajectories were unrelated to the mortality risk of older Mexican American women. A statistically significant interaction term confirmed that social support was more strongly associated with the mortality risk of men. PMID:26966256

  15. Microangiopathic complications related to different alleles of ...

    African Journals Online (AJOL)

    Egyptian Journal of Biochemistry and Molecular Biology. Journal Home ... Microangiopathic complications related to different alleles of manganese superoxide dismutase gene in diabetes mellitus type 1. TM EL Masry ... 23(2) 2005: 155-167 ...

  16. Poor social support as a risk factor for antenatal depressive symptoms among women attending public antennal clinics in Penang, Malaysia.

    Science.gov (United States)

    Rashid, Abdul; Mohd, Rokiah

    2017-11-02

    Depression, a type of mental disorder which is portrayed by marked alterations in mood, is associated with distress and/or impaired functioning. Poor social support is an important risk factor for depression in pregnancy. An extensive literature search failed to show any published study conducted in Malaysia on antenatal depressive symptoms and the risk of poor social support on it. The aim of the study was to determine the risk of antenatal depressive symptoms due to poor social support. This cross sectional study was conducted among 3000 pregnant women attending antenatal clinics in Penang, Malaysia. Edinburgh Postnatal Depression Scale (EPDS) was used to screen for antenatal depressive symptoms and the Oslo-3 Social Support Scale (OSS-3) was used to measure social support. Odds ratio and adjusted odds ratio were used to quantify the risk of antenatal depressive symptoms due to poor social support. The prevalence of depressive symptoms was 20%. Using OSS-3 scale to gauge social support, most of the participants had moderate support (61.3%) followed by poor support (22%) and strong support (16.7%). Social support was found to be significantly associated with depressive symptoms in this study (OR 2.2, aOR 2.1, AR 45%). Considering that an expecting mother's psychological factors are important in the wellbeing of the mother and child, antenatal depression must be quickly identified. Screening pregnant women for social support can help identify women with higher risk of depression.

  17. BRAF Gene Copy Number and Mutant Allele Frequency Correlate with Time to Progression in Metastatic Melanoma Patients Treated with MAPK Inhibitors.

    Science.gov (United States)

    Stagni, Camilla; Zamuner, Carolina; Elefanti, Lisa; Zanin, Tiziana; Bianco, Paola Del; Sommariva, Antonio; Fabozzi, Alessio; Pigozzo, Jacopo; Mocellin, Simone; Montesco, Maria Cristina; Chiarion-Sileni, Vanna; De Nicolo, Arcangela; Menin, Chiara

    2018-06-01

    Metastatic melanoma is characterized by complex genomic alterations, including a high rate of mutations in driver genes and widespread deletions and amplifications encompassing various chromosome regions. Among them, chromosome 7 is frequently gained in BRAF -mutant melanoma, inducing a mutant allele-specific imbalance. Although BRAF amplification is a known mechanism of acquired resistance to therapy with MAPK inhibitors, it is still unclear if BRAF copy-number variation and BRAF mutant allele imbalance at baseline can be associated with response to treatment. In this study, we used a multimodal approach to assess BRAF copy number and mutant allele frequency in pretreatment melanoma samples from 46 patients who received MAPK inhibitor-based therapy, and we analyzed the association with progression-free survival. We found that 65% patients displayed BRAF gains, often supported by chromosome 7 polysomy. In addition, we observed that 64% patients had a balanced BRAF -mutant/wild-type allele ratio, whereas 14% and 23% patients had low and high BRAF mutant allele frequency, respectively. Notably, a significantly higher risk of progression was observed in patients with a diploid BRAF status versus those with BRAF gains [HR, 2.86; 95% confidence interval (CI), 1.29-6.35; P = 0.01] and in patients with low percentage versus those with a balanced BRAF mutant allele percentage (HR, 4.54; 95% CI, 1.33-15.53; P = 0.016). Our data suggest that quantitative analysis of the BRAF gene could be useful to select the melanoma patients who are most likely to benefit from therapy with MAPK inhibitors. Mol Cancer Ther; 17(6); 1332-40. ©2018 AACR . ©2018 American Association for Cancer Research.

  18. Application of support vector machine classifiers to preoperative risk stratification with myocardial perfusion scintigraphy

    International Nuclear Information System (INIS)

    Kasamatsu, Tomotaka; Hashimoto, Jun; Nakahara, Tadaki; Bai, Jingming; Kitamura, Naoto; Kubo, Atsushi; Iyatomi, Hitoshi; Ogawa, Koichi

    2008-01-01

    Myocardial perfusion single-photon emission computed tomography (SPECT) has been used for risk stratification before non-cardiac surgery. However, few authors have used mathematical models for evaluating the likelihood of perioperative cardiac events. This retrospective cohort study collected data of 1,351 patients referred for SPECT before non-cardiac surgery. We generated binary classifiers using support vector machine (SVM) and conventional linear models for predicting perioperative cardiac events. We used clinical and surgical risk, and SPECT findings as input data, and the occurrence of all and hard cardiac events as output data. The area under the receiver-operating characteristic curve (AUC) was calculated for assessing the prediction accuracy. The AUC values were 0.884 and 0.748 in the SVM and linear models, respectively in predicting all cardiac events with clinical and surgical risk, and SPECT variables. The values were 0.861 (SVM) and 0.677 (linear) when not using SPECT data as input. In hard events, the AUC values were 0.892 (SVM) and 0.864 (linear) with SPECT, and 0.867 (SVM) and 0.768 (linear) without SPECT. The SVM was superior to the linear model in risk stratification. We also found an incremental prognostic value of SPECT results over information about clinical and surgical risk. (author)

  19. A fuzzy logic decision support system for assessing clinical nutritional risk

    Directory of Open Access Journals (Sweden)

    Ali Mohammad Hadianfard

    2015-04-01

    Full Text Available Introduction: Studies have indicated a global high prevalence of hospital malnutrition on admission and during hospitalization. Clinical Nutritional Risk Screen (CNRS is a way to identify malnutrition and manage nutritional interventions. Several traditional and non-computer based tools have been suggested for screening nutritional risk levels. The present study was an attempt to employ a computer based fuzzy model decision support system as a nutrition-screening tool for inpatients. Method: This is an applied modeling study. The system architecture was designed based on the fuzzy logic model including input data, inference engine, and output. A clinical nutritionist entered nineteen input variables using a windows-based graphical user interface. The inference engine was involved with knowledge obtained from literature and the construction of ‘IF-THEN’ rules. The output of the system was stratification of patients into four risk levels from ‘No’ to ‘High’ where a number was also allocated to them as a nutritional risk grade. All patients (121 people admitted during implementing the system participated in testing the model. The classification tests were used to measure the CNRS fuzzy model performance. IBM SPSS version 21 was utilized as a tool for data analysis with α = 0.05 as a significance level. Results: Results showed that sensitivity, specificity, accuracy, and precision of the fuzzy model performance were 91.67% (±4.92, 76% (±7.6, 88.43% (±5.7, and 93.62% (±4.32, respectively. Instant performance on admission and very low probability of mistake in predicting malnutrition risk level may justify using the model in hospitals. Conclusion: To conclude, the fuzzy model-screening tool is based on multiple nutritional risk factors, having the capability of classifying inpatients into several nutritional risk levels and identifying the level of required nutritional intervention.

  20. Real-time 3D radiation risk assessment supporting simulation of work in nuclear environments

    International Nuclear Information System (INIS)

    Szoke, I; Louka, M N; Bryntesen, T R; Bratteli, J; Edvardsen, S T; RøEitrheim, K K; Bodor, K

    2014-01-01

    This paper describes the latest developments at the Institute for Energy Technology (IFE) in Norway, in the field of real-time 3D (three-dimensional) radiation risk assessment for the support of work simulation in nuclear environments. 3D computer simulation can greatly facilitate efficient work planning, briefing, and training of workers. It can also support communication within and between work teams, and with advisors, regulators, the media and public, at all the stages of a nuclear installation’s lifecycle. Furthermore, it is also a beneficial tool for reviewing current work practices in order to identify possible gaps in procedures, as well as to support the updating of international recommendations, dissemination of experience, and education of the current and future generation of workers. IFE has been involved in research and development into the application of 3D computer simulation and virtual reality (VR) technology to support work in radiological environments in the nuclear sector since the mid 1990s. During this process, two significant software tools have been developed, the VRdose system and the Halden Planner, and a number of publications have been produced to contribute to improving the safety culture in the nuclear industry. This paper describes the radiation risk assessment techniques applied in earlier versions of the VRdose system and the Halden Planner, for visualising radiation fields and calculating dose, and presents new developments towards implementing a flexible and up-to-date dosimetric package in these 3D software tools, based on new developments in the field of radiation protection. The latest versions of these 3D tools are capable of more accurate risk estimation, permit more flexibility via a range of user choices, and are applicable to a wider range of irradiation situations than their predecessors. (paper)

  1. Real-time 3D radiation risk assessment supporting simulation of work in nuclear environments.

    Science.gov (United States)

    Szőke, I; Louka, M N; Bryntesen, T R; Bratteli, J; Edvardsen, S T; RøEitrheim, K K; Bodor, K

    2014-06-01

    This paper describes the latest developments at the Institute for Energy Technology (IFE) in Norway, in the field of real-time 3D (three-dimensional) radiation risk assessment for the support of work simulation in nuclear environments. 3D computer simulation can greatly facilitate efficient work planning, briefing, and training of workers. It can also support communication within and between work teams, and with advisors, regulators, the media and public, at all the stages of a nuclear installation's lifecycle. Furthermore, it is also a beneficial tool for reviewing current work practices in order to identify possible gaps in procedures, as well as to support the updating of international recommendations, dissemination of experience, and education of the current and future generation of workers.IFE has been involved in research and development into the application of 3D computer simulation and virtual reality (VR) technology to support work in radiological environments in the nuclear sector since the mid 1990s. During this process, two significant software tools have been developed, the VRdose system and the Halden Planner, and a number of publications have been produced to contribute to improving the safety culture in the nuclear industry.This paper describes the radiation risk assessment techniques applied in earlier versions of the VRdose system and the Halden Planner, for visualising radiation fields and calculating dose, and presents new developments towards implementing a flexible and up-to-date dosimetric package in these 3D software tools, based on new developments in the field of radiation protection. The latest versions of these 3D tools are capable of more accurate risk estimation, permit more flexibility via a range of user choices, and are applicable to a wider range of irradiation situations than their predecessors.

  2. The role of religiosity, social support, and stress-related growth in protecting against HIV risk among transgender women.

    Science.gov (United States)

    Golub, Sarit A; Walker, Ja'nina J; Longmire-Avital, Buffie; Bimbi, David S; Parsons, Jeffrey T

    2010-11-01

    Transgender women completed questionnaires of religiosity, social support, stigma, stress-related growth, and sexual risk behavior. In a multivariate model, both social support and religious stress-related growth were significant negative predictors of unprotected anal sex, but religious behaviors and beliefs emerged as a significant positive predictor. The interaction between religious behaviors and beliefs and social support was also significant, and post-hoc analyses indicated that high-risk sex was least likely among individuals with high-levels of social support but low levels of religious behaviors and beliefs. These data have important implications for understanding factors that might protect against HIV risk for transgender women.

  3. Allele Workbench: transcriptome pipeline and interactive graphics for allele-specific expression.

    Directory of Open Access Journals (Sweden)

    Carol A Soderlund

    Full Text Available Sequencing the transcriptome can answer various questions such as determining the transcripts expressed in a given species for a specific tissue or condition, evaluating differential expression, discovering variants, and evaluating allele-specific expression. Differential expression evaluates the expression differences between different strains, tissues, and conditions. Allele-specific expression evaluates expression differences between parental alleles. Both differential expression and allele-specific expression have been studied for heterosis (hybrid vigor, where the hybrid has improved performance over the parents for one or more traits. The Allele Workbench software was developed for a heterosis study that evaluated allele-specific expression for a mouse F1 hybrid using libraries from multiple tissues with biological replicates. This software has been made into a distributable package, which includes a pipeline, a Java interface to build the database, and a Java interface for query and display of the results. The required input is a reference genome, annotation file, and one or more RNA-Seq libraries with optional replicates. It evaluates allelic imbalance at the SNP and transcript level and flags transcripts with significant opposite directional allele-specific expression. The Java interface allows the user to view data from libraries, replicates, genes, transcripts, exons, and variants, including queries on allele imbalance for selected libraries. To determine the impact of allele-specific SNPs on protein folding, variants are annotated with their effect (e.g., missense, and the parental protein sequences may be exported for protein folding analysis. The Allele Workbench processing results in transcript files and read counts that can be used as input to the previously published Transcriptome Computational Workbench, which has a new algorithm for determining a trimmed set of gene ontology terms. The software with demo files is available

  4. Abnormal segregation of alleles in CEPH pedigree DNAs arising from allele loss in lymphoblastoid DNA.

    Science.gov (United States)

    Royle, N J; Armour, J A; Crosier, M; Jeffreys, A J

    1993-01-01

    Somatic events that result in the reduction to hemi- or homozygosity at all loci affected by the event have been identified in lymphoblastoid DNA from mothers of two CEPH families. Using suitably informative probes, the allele deficiencies were detected by the abnormal transmission of alleles from grandparents to grandchildren, with the apparent absence of the alleles from the parent. Undetected somatic deficiencies in family DNAs could result in misscoring of recombination events and consequently introduce errors into linkage analysis.

  5. Comment: studies of the Pro12Ala polymorphism of the PPAR-gamma gene in the Danish MONICA cohort: homozygosity of the Ala allele confers a decreased risk of the insulin resistance syndrome

    DEFF Research Database (Denmark)

    Frederiksen, Laura; Brødbaek, Kasper; Fenger, Mogens

    2002-01-01

    with the frequency in the non-IRS group [2.8% (2.1-3.5%); P = 0.02; odds ratio, 0.24 (0.06-0.99)]. Moreover, in the total study population, homozygous carriers of the variant had lower levels of fasting serum triglyceride [1.1 +/- 0.4 mmol/liter (means +/- SD) vs. 1.4 +/- 0.9 mmol/liter; P = 0.04] and a lower...... was examined using PCR-restriction fragment length polymorphism in a phenotypically well characterized population-based sample of 2245 nondiabetic subjects. The study participants were characterized by a number of anthropometric and biochemical measurements and the European Group for the Study of Insulin...... Resistance criteria enabling a classification of the study population in an IRS group and a non-IRS group. The allelic frequency of the Pro12Ala polymorphism in the total study sample was 14% (95% confidence interval, 13-15%). Two hundred ninety-four subjects fulfilled the European Group for the Study...

  6. Prototype of a Web-based Participative Decision Support Platform in Natural Hazards and Risk Management

    Directory of Open Access Journals (Sweden)

    Zar Chi Aye

    2015-07-01

    Full Text Available This paper presents the current state and development of a prototype web-GIS (Geographic Information System decision support platform intended for application in natural hazards and risk management, mainly for floods and landslides. This web platform uses open-source geospatial software and technologies, particularly the Boundless (formerly OpenGeo framework and its client side software development kit (SDK. The main purpose of the platform is to assist the experts and stakeholders in the decision-making process for evaluation and selection of different risk management strategies through an interactive participation approach, integrating web-GIS interface with decision support tool based on a compromise programming approach. The access rights and functionality of the platform are varied depending on the roles and responsibilities of stakeholders in managing the risk. The application of the prototype platform is demonstrated based on an example case study site: Malborghetto Valbruna municipality of North-Eastern Italy where flash floods and landslides are frequent with major events having occurred in 2003. The preliminary feedback collected from the stakeholders in the region is discussed to understand the perspectives of stakeholders on the proposed prototype platform.

  7. Mutation intolerant genes and targets of FMRP are enriched for nonsynonymous alleles in schizophrenia.

    Science.gov (United States)

    Leonenko, Ganna; Richards, Alexander L; Walters, James T; Pocklington, Andrew; Chambert, Kimberly; Al Eissa, Mariam M; Sharp, Sally I; O'Brien, Niamh L; Curtis, David; Bass, Nicholas J; McQuillin, Andrew; Hultman, Christina; Moran, Jennifer L; McCarroll, Steven A; Sklar, Pamela; Neale, Benjamin M; Holmans, Peter A; Owen, Michael J; Sullivan, Patrick F; O'Donovan, Michael C

    2017-10-01

    Risk of schizophrenia is conferred by alleles occurring across the full spectrum of frequencies from common SNPs of weak effect through to ultra rare alleles, some of which may be moderately to highly penetrant. Previous studies have suggested that some of the risk of schizophrenia is attributable to uncommon alleles represented on Illumina exome arrays. Here, we present the largest study of exomic variation in schizophrenia to date, using samples from the United Kingdom and Sweden (10,011 schizophrenia cases and 13,791 controls). Single variants, genes, and gene sets were analyzed for association with schizophrenia. No single variant or gene reached genome-wide significance. Among candidate gene sets, we found significant enrichment for rare alleles (minor allele frequency [MAF] schizophrenia by excluding a role for uncommon exomic variants (0.01 ≤ MAF ≥ 0.001) that confer a relatively large effect (odds ratio [OR] > 4). We also show risk alleles within this frequency range exist, but confer smaller effects and should be identified by larger studies. © 2017 Wiley Periodicals, Inc.

  8. Consequences for diversity when animals are prioritized for conservation of the whole genome or of one specific allele

    NARCIS (Netherlands)

    Engelsma, K.A.; Veerkamp, R.F.; Calus, M.P.L.; Windig, J.J.

    2014-01-01

    When animals are selected for one specific allele, for example for inclusion in a gene bank, this may result in the loss of diversity in other parts of the genome. The aim of this study was to quantify the risk of losing diversity across the genome when targeting a single allele for conservation

  9. Statistically downscaled climate projections to support evaluating climate change risks for hydropower

    International Nuclear Information System (INIS)

    Brekke, L.

    2008-01-01

    This paper described a web-served public access archive of down-scaled climate projections developed as a tool for water managers of river and hydropower systems. The archive provided access to climate projection data at basin-relevant resolution and included an extensive compilation of down-scale climate projects designed to support risk-based adaptation planning. Downscaled translations of 112 contemporary climate projections produced using the World Climate Research Program's coupled model intercomparison project were also included. Datasets for the coupled model included temperature and precipitation, monthly time-steps, and geographic coverage for the United States and portions of Mexico and Canada. It was concluded that the archive will be used to develop risk-based studies on shifts in seasonal patterns, changes in mean annual runoff, and associated responses in water resources and hydroelectric power management. Case studies demonstrating reclamation applications of archive content and potential applications for hydroelectric power production impacts were included. tabs., figs

  10. Low supply of social support as risk factor for mortality in the older adults.

    Science.gov (United States)

    de Brito, Tábatta Renata Pereira; Nunes, Daniella Pires; Corona, Ligiana Pires; da Silva Alexandre, Tiago; de Oliveira Duarte, Yeda Aparecida

    2017-11-01

    To determine the relationship between social support and mortality in older adults, independent of other health conditions. This was a longitudinal study using the database of the 2006 SABE Study (Heath, Well-being and Aging), composed of 1413 individuals aged 60 years and over, living in São Paulo/Brazil. The present study used a questionnaire constructed for the SABE Study, which was reviewed by experts of Latin America and the Caribbean. The social network was evaluated using the variables: social support received; social support offered; number of members in the social network. The covariates included were age, gender, living arrangements, marital status, income, education, comorbidity, depressive symptoms, cognition and functional difficulties. Death as an outcome was evaluated after four years of follow-up. From a total of 1413 older adults at baseline, 268 died in a mean follow-up period of 3,9 years (SE=0,03). In the model adjusted offering social support and having networks composed of 9 or more members reduced the risk of death in the older adults. This study suggest that older adult who are offered support can benefit from mutual exchanges since reciprocity in relationships improves psychological well-being and is indicative of the quality of relationships. Thus, the older adults are part of a group of people whose role is not only to receive, but also to provide help to others, and the support offered seems to be as important as that received. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Rational risk-based decision support for drinking water well managers by optimized monitoring designs

    Science.gov (United States)

    Enzenhöfer, R.; Geiges, A.; Nowak, W.

    2011-12-01

    Advection-based well-head protection zones are commonly used to manage the contamination risk of drinking water wells. Considering the insufficient knowledge about hazards and transport properties within the catchment, current Water Safety Plans recommend that catchment managers and stakeholders know, control and monitor all possible hazards within the catchments and perform rational risk-based decisions. Our goal is to supply catchment managers with the required probabilistic risk information, and to generate tools that allow for optimal and rational allocation of resources between improved monitoring versus extended safety margins and risk mitigation measures. To support risk managers with the indispensable information, we address the epistemic uncertainty of advective-dispersive solute transport and well vulnerability (Enzenhoefer et al., 2011) within a stochastic simulation framework. Our framework can separate between uncertainty of contaminant location and actual dilution of peak concentrations by resolving heterogeneity with high-resolution Monte-Carlo simulation. To keep computational costs low, we solve the reverse temporal moment transport equation. Only in post-processing, we recover the time-dependent solute breakthrough curves and the deduced well vulnerability criteria from temporal moments by non-linear optimization. Our first step towards optimal risk management is optimal positioning of sampling locations and optimal choice of data types to reduce best the epistemic prediction uncertainty for well-head delineation, using the cross-bred Likelihood Uncertainty Estimator (CLUE, Leube et al., 2011) for optimal sampling design. Better monitoring leads to more reliable and realistic protection zones and thus helps catchment managers to better justify smaller, yet conservative safety margins. In order to allow an optimal choice in sampling strategies, we compare the trade-off in monitoring versus the delineation costs by accounting for ill

  12. The link between some alleles on human leukocyte antigen system and autism in children.

    Science.gov (United States)

    Mostafa, Gehan A; Shehab, Abeer A; Al-Ayadhi, Laila Y

    2013-02-15

    The reason behind the initiation of autoimmunity to brain in some patients with autism is not well understood. There is an association between some autoimmune disorders and specific alleles of human leukocyte antigen (HLA) system. Thus, we examined the frequency of some HLA-DRB1 alleles in 100 autistic children and 100 healthy matched-children by differential hybridization with sequence-specific oligonucleotide probes. The risk of association between acquisition or absence of these alleles and autism and also a history of autoimmune diseases in autistic relatives was studied. Autistic children had significantly higher frequency of HLA-DRB1*11 allele than controls (P<0.001). In contrast, autistic children had significantly lower frequency of HLA-DRB1*03 allele than controls (P<0.001). Acquisition of HLA-DRB1*011 and absence of HLA-DRB1*3 had significant risk for association with autism (odds ratio: 3.21 and 0.17, respectively; 95% CI: 1.65-6.31 and 0.06-0.45, respectively). HLA-DRB1*11 had a significant risk for association with a family history of autoimmunity in autistic children (odds ratio: 5.67; 95% CI: 2.07-16.3). In conclusions, the link of some HLA alleles to autism and to family history of autoimmunity indicates the possible contributing role of these alleles to autoimmunity in some autistic children. Despite a relatively small sample size, we are the first to report a probable protective association of HLA-DRB1*03 allele with autism. It warrants a replication study of a larger sample to validate the HLA-DRB1 genetic association with autism. This is important to determine whether therapeutic modulations of the immune function are legitimate avenues for novel therapy in selected cases of autism. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Estimated allele substitution effects underlying genomic evaluation models depend on the scaling of allele counts

    NARCIS (Netherlands)

    Bouwman, Aniek C.; Hayes, Ben J.; Calus, Mario P.L.

    2017-01-01

    Background: Genomic evaluation is used to predict direct genomic values (DGV) for selection candidates in breeding programs, but also to estimate allele substitution effects (ASE) of single nucleotide polymorphisms (SNPs). Scaling of allele counts influences the estimated ASE, because scaling of

  14. The Integrated Medical Model: A Risk Assessment and Decision Support Tool for Human Space Flight Missions

    Science.gov (United States)

    Kerstman, Eric L.; Minard, Charles; FreiredeCarvalho, Mary H.; Walton, Marlei E.; Myers, Jerry G., Jr.; Saile, Lynn G.; Lopez, Vilma; Butler, Douglas J.; Johnson-Throop, Kathy A.

    2011-01-01

    This slide presentation reviews the Integrated Medical Model (IMM) and its use as a risk assessment and decision support tool for human space flight missions. The IMM is an integrated, quantified, evidence-based decision support tool useful to NASA crew health and mission planners. It is intended to assist in optimizing crew health, safety and mission success within the constraints of the space flight environment for in-flight operations. It uses ISS data to assist in planning for the Exploration Program and it is not intended to assist in post flight research. The IMM was used to update Probability Risk Assessment (PRA) for the purpose of updating forecasts for the conditions requiring evacuation (EVAC) or Loss of Crew Life (LOC) for the ISS. The IMM validation approach includes comparison with actual events and involves both qualitative and quantitaive approaches. The results of these comparisons are reviewed. Another use of the IMM is to optimize the medical kits taking into consideration the specific mission and the crew profile. An example of the use of the IMM to optimize the medical kits is reviewed.

  15. A Universal Rig for Supporting Large Hammer Drills: Reduced Injury Risk and Improved Productivity.

    Science.gov (United States)

    Rempel, David; Barr, Alan

    2015-10-01

    Drilling holes into concrete with heavy hammer and rock drills is one of the most physically demanding tasks performed in commercial construction and poses risks for musculoskeletal disorders, noise induced hearing loss, hand arm vibration syndrome and silicosis. The aim of this study was to (1) use a participatory process to develop a rig to support pneumatic rock drills or large electric hammer drills in order to reduce the health risks and (2) evaluate the usability of the rig. Seven prototype rigs for supporting large hammer drills were developed and modified with feedback from commercial contractors and construction workers. The final design was evaluated by laborers and electricians (N=29) who performed their usual concrete drilling with the usual method and the new rig. Subjective regional fatigue was significantly less in the neck, shoulders, hands and arms, and lower back) when using the universal rig compared to the usual manual method. Usability ratings for the rig were significantly better than the usual method on stability, control, drilling, accuracy, and vibration. Drilling time was reduced by approximately 50% with the rig. Commercial construction contractors, laborers and electricians who use large hammer drills for drilling many holes should consider using such a rig to prevent musculoskeletal disorders, fatigue, and silicosis.

  16. Allelic genealogies in sporophytic self-incompatibility systems in plants

    DEFF Research Database (Denmark)

    Schierup, Mikkel Heide; Vekemans, Xavier; Christiansen, Freddy Bugge

    1998-01-01

    , alleles act codominantly in both pollen and style, in the SSIdom model, alleles form a dominance hierarchy, and in SSIdomcod, alleles are codominant in the style and show a dominance hierarchy in the pollen. Coalescence times of alleles rarely differ more than threefold from those under gametophytic self...

  17. Supportive interventions for enhancing dietary intake in malnourished or nutritionally at-risk adults.

    Science.gov (United States)

    Baldwin, Christine; Kimber, Katherine L; Gibbs, Michelle; Weekes, Christine Elizabeth

    2016-12-20

    Supportive interventions such as serving meals in a dining room environment or the use of assistants to feed patients are frequently recommended for the management of nutritionally vulnerable groups. Such interventions are included in many policy and guideline documents and have implications for staff time but may incur additional costs, yet there appears to be a lack of evidence for their efficacy. To assess the effects of supportive interventions for enhancing dietary intake in malnourished or nutritionally at-risk adults. We identified publications from comprehensive searches of the Cochrane Library, MEDLINE, Embase, AMED, British Nursing Index, CINAHL, SCOPUS, ISI Web of Science databases, scrutiny of the reference lists of included trials and related systematic reviews and handsearching the abstracts of relevant meetings. The date of the last search for all databases was 31 March 2013. Additional searches of CENTRAL, MEDLINE, ClinicalTrials.gov and WHO ICTRP were undertaken to September 2016. The date of the last search for these databases was 14 September 2016. Randomised controlled trials of supportive interventions given with the aim of enhancing dietary intake in nutritionally vulnerable adults compared with usual care. Three review authors and for the final search, the editor, selected trials from titles and abstracts and independently assessed eligibility of selected trials. Two review authors independently extracted data and assessed risk of bias, as well as evaluating overall quality of the evidence utilising the GRADE instrument, and then agreed as they entered data into the review. The likelihood of clinical heterogeneity amongst trials was judged to be high as trials were in populations with widely different clinical backgrounds, conducted in different healthcare settings and despite some grouping of similar interventions, involved interventions that varied considerably. We were only able, therefore, to conduct meta-analyses for the outcome measures

  18. Parenting and Family Support for Families 'at risk' - Implications from Child Abuse Reports

    Directory of Open Access Journals (Sweden)

    Ann Marie Halpenny

    2012-01-01

    Full Text Available The importance of family experiences on children’s development and wellbeing has been widely documented. Yet, recent reports generated by inquiries into child abuse and neglect in the Irish context raise disturbing questions with regard to how the severe maltreatment of children can occur within the family context. It is imperative that the messages generated from these inquiries can effectively inform policy and practice in terms of protecting children from harm and providing support to families at-risk. The present paper draws together key issues for parenting and family support for families ‘at risk’ based on the Roscommon and Monageer inquiries with a view to gaining insight into key issues which need to be addressed in terms of protecting children from harm and providing support for parents experiencing adversity. A number of implications arising from these reports are outlined and discussed. Specifically, the need to amplify the focus on support for parenting in the context of poverty and substance abuse is highlighted with a particular emphasis on developing sensitive screening and assessment for parents who may be difficult to engage with due to chronic mental health issues. The importance of accessing the voice of children within the provision of family support is also underlined in these findings. A key recommendation from these reports is that the needs, wishes and feelings of each child must be considered as well as the totality of the family situation. Moreover, the need for staff in child welfare and protection services to have access to ongoing training and professional development to meet the complex and changing needs of the children and families they are working with is also highlighted. Specifically, ongoing training for frontline staff in understanding the effects of drug and alcohol dependency, and, in particular, the effects on parenting and parent-child relationships is underscored in findings from these reports.

  19. Modelling risk aversion to support decision-making for controlling zoonotic livestock diseases.

    Science.gov (United States)

    van Asseldonk, M A P M; Bergevoet, R H M; Ge, L

    2013-12-01

    Zoonotic infectious livestock diseases are becoming a significant burden for both animal and human health and are rapidly gaining the attention of decision-makers who manage public health programmes. If control decisions have only monetary components, governments are generally regarded as being risk-neutral and the intervention strategy with the highest expected benefit (lowest expected net costs) should be preferred. However, preferences will differ and alternative intervention plans will prevail if (human) life and death outcomes are involved. A rational decision framework must therefore consider risk aversion in the decision-maker and controversial values related to public health. In the present study, risk aversion and its impact on both the utility for the monetary component and the utility for the non-monetary component is shown to be an important element when dealing with emerging zoonotic infectious livestock diseases and should not be ignored in the understanding and support of decision-making. The decision framework was applied to several control strategies for the reduction of human cases of brucellosis (Brucella melitensis) originating from sheep in Turkey.

  20. Bridging the gaps: An early integrated support collaborative for at risk mothers in rural Maine.

    Science.gov (United States)

    Morton, Jennifer; Withers, Marjorie; Konrad, Shelley Cohen; Buterbaugh, Carry; Spence, RuthAnne

    2015-01-01

    The antecedents that contribute to health disparities in maternal child health populations begin before birth and extend into the early prenatal and gestational growth periods. Mothers and infants living in rural poverty in particular are at considerable risk for problems associated with reproductive health, including pregnancy complications and premature births. The aim of this manuscript is thus two-fold, to describe the epidemiologic makeup of the community and the intervention model of the Community Caring Collaborative. Innovative models of early-integrated care for high-risk mothers and children are showing promise for long-term outcomes. They foster environments that enable mothers to trust health systems while maintaining a workforce of high functioning health workers who understand the mechanisms that underpin maternal and child health disparities. The Community Caring Collaborative in Washington County, Maine developed one such model that has made inroads in bridging such gaps. This manuscript explicates a case study of how the Community Caring Collaborative came into being and why it established the Bridging model of comprehensive care. The focus of this manuscript is thus two-fold, the community and the intervention model. The "bridging model" develops trust-based relationships between high-risk mothers with the health system and its multiple resources. Community members with advanced training provide the support and care linkages that are critical for family success. Innovative models of collaborative care impact the health of vulnerable mothers and their children working toward a marked decrease in health related disparities.

  1. Lay support for pregnant women with social risk: a randomised controlled trial

    Science.gov (United States)

    Kenyon, Sara; Jolly, Kate; Hemming, Karla; Hope, Lucy; Blissett, Jackie; Dann, Sophie-Anna; Lilford, Richard; MacArthur, Christine

    2016-01-01

    Objectives We sought evidence of effectiveness of lay support to improve maternal and child outcomes in disadvantaged families. Design Prospective, pragmatic, individually randomised controlled trial. Setting 3 Maternity Trusts in West Midlands, UK. Participants Following routine midwife systematic assessment of social risk factors, 1324 nulliparous women were assigned, using telephone randomisation, to standard maternity care, or addition of referral to a Pregnancy Outreach Worker (POW) service. Those under 16 years and teenagers recruited to the Family Nurse Partnership trial were excluded. Interventions POWs were trained to provide individual support and case management for the women including home visiting from randomisation to 6 weeks after birth. Standard maternity care (control) included provision for referring women with social risk factors to specialist midwifery services, available to both arms. Main outcome measures Primary outcomes were antenatal visits attended and Edinburgh Postnatal Depression Scale (EPDS) 8–12 weeks postpartum. Prespecified, powered, subgroup comparison was among women with 2 or more social risks. Secondary outcomes included maternal and neonatal birth outcomes; maternal self-efficacy, and mother-to-infant bonding at 8–12 weeks; child development assessment at 6 weeks, breastfeeding at 6 weeks, and immunisation uptake at 4 months, all collected from routine child health systems. Results Antenatal attendances were high in the standard care control and did not increase further with addition of the POW intervention (10.1 vs 10.1 (mean difference; MD) −0.00, 95% CI (95% CI −0.37 to 0.37)). In the powered subgroup of women with 2 or more social risk factors, mean EPDS (MD −0.79 (95% CI −1.56 to −0.02) was significantly better, although for all women recruited, no significant differences were seen (MD −0.59 (95% CI −1.24 to 0.06). Mother-to-infant bonding was significantly better in the intervention group

  2. The need for intra aortic balloon pump support following open heart surgery: risk analysis and outcome.

    LENUS (Irish Health Repository)

    Parissis, Haralabos

    2010-01-01

    BACKGROUND: The early and intermediate outcome of patients requiring intraaortic balloon pump (IABP) was studied in a cohort of 2697 adult cardiac surgical patients. METHODS: 136 patients requiring IABP (5.04%) support analysed over a 4 year period. Prospective data collection, obtained. RESULTS: The overall operative mortality was 35.3%. The "operation specific" mortality was higher on the Valve population.The mortality (%) as per time of balloon insertion was: Preoperative 18.2, Intraoperative 33.3, postoperative 58.3 (p < 0.05).The incremental risk factors for death were: Female gender (Odds Ratio (OR) = 3.87 with Confidence Intervals (CI) = 1.3-11.6), Smoking (OR = 4.88, CI = 1.23- 19.37), Preoperative Creatinine>120 (OR = 3.3, CI = 1.14-9.7), Cross Clamp time>80 min (OR = 4.16, CI = 1.73-9.98) and IABP insertion postoperatively (OR = 19.19, CI = 3.16-116.47).The incremental risk factors for the development of complications were: Poor EF (OR = 3.16, CI = 0.87-11.52), Euroscore >7 (OR = 2.99, CI = 1.14-7.88), history of PVD (OR = 4.99, CI = 1.32-18.86).The 5 years survival was 79.2% for the CABG population and 71.5% for the valve group. (Hazard ratio = 1.78, CI = 0.92-3.46). CONCLUSIONS: IABP represents a safe option of supporting the failing heart. The need for IABP especially in a high risk Valve population is associated with early unfavourable outcome, however the positive mid term results further justify its use.

  3. The need for intra aortic balloon pump support following open heart surgery: risk analysis and outcome

    Directory of Open Access Journals (Sweden)

    Apostolakis Efstratios

    2010-04-01

    Full Text Available Abstract Background The early and intermediate outcome of patients requiring intraaortic balloon pump (IABP was studied in a cohort of 2697 adult cardiac surgical patients. Methods 136 patients requiring IABP (5.04% support analysed over a 4 year period. Prospective data collection, obtained. Results The overall operative mortality was 35.3%. The "operation specific" mortality was higher on the Valve population. The mortality (% as per time of balloon insertion was: Preoperative 18.2, Intraopeartive 33.3, postoperative 58.3 (p The incremental risk factors for death were: Female gender (Odds Ratio (OR = 3.87 with Confidence Intervals (CI = 1.3-11.6, Smoking (OR = 4.88, CI = 1.23- 19.37, Preoperative Creatinine>120 (OR = 3.3, CI = 1.14-9.7, Cross Clamp time>80 min (OR = 4.16, CI = 1.73-9.98 and IABP insertion postoperatively (OR = 19.19, CI = 3.16-116.47. The incremental risk factors for the development of complications were: Poor EF (OR = 3.16, CI = 0.87-11.52, Euroscore >7 (OR = 2.99, CI = 1.14-7.88, history of PVD (OR = 4.99, CI = 1.32-18.86. The 5 years survival was 79.2% for the CABG population and 71.5% for the valve group. (Hazard ratio = 1.78, CI = 0.92-3.46. Conclusions IABP represents a safe option of supporting the failing heart. The need for IABP especially in a high risk Valve population is associated with early unfavourable outcome, however the positive mid term results further justify its use.

  4. Haptoglobin genotyping of Vietnamese: global distribution of HP del, complete deletion allele of the HP gene.

    Science.gov (United States)

    Soejima, Mikiko; Agusa, Tetsuro; Iwata, Hisato; Fujihara, Junko; Kunito, Takashi; Takeshita, Haruo; Lan, Vi Thi Mai; Minh, Tu Binh; Takahashi, Shin; Trang, Pham Thi Kim; Viet, Pham Hung; Tanabe, Shinsuke; Koda, Yoshiro

    2015-01-01

    The haptoglobin (HP) gene deletion allele (HP(del)) is responsible for anhaptoglobinemia and a genetic risk factor for anaphylaxis reaction after transfusion due to production of the anti-HP antibody. The distribution of this allele has been explored by several groups including ours. Here, we studied the frequency of HP(del) in addition to the distribution of common HP genotypes in 293 Vietnamese. The HP(del) was encountered with the frequency of 0.020. The present result suggested that this deletion allele is restricted to East and Southeast Asians. Thus, this allele seems to be a potential ancestry informative marker for these populations. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Quantitative Microbial Risk Assessment Tutorial Installation of Software for Watershed Modeling in Support of QMRA - Updated 2017

    Science.gov (United States)

    This tutorial provides instructions for accessing, retrieving, and downloading the following software to install on a host computer in support of Quantitative Microbial Risk Assessment (QMRA) modeling: • QMRA Installation • SDMProjectBuilder (which includes the Microbial ...

  6. Comprehensive risk assessment for rail transportation of dangerous goods: a validated platform for decision support

    International Nuclear Information System (INIS)

    Gheorghe, Adrian V.; Birchmeier, Juerg; Vamanu, Dan; Papazoglou, Ioannis; Kroeger, Wolfgang

    2005-01-01

    Currently, the most advanced and well documented risk assessments for the transportation of dangerous goods by railway take into account:(i)statistics-based loss of containment frequencies, (ii) specification of potential consequences for a given release situations using event tree methodology as an organisational tool and (iii) consequence calculation models to determine a risk figure known as CCDF (Complementary Cumulative Distribution Function). Such procedures for the risk assessment (including for example decision-making on preventive measures) may offer only a limited insight into the causes and sequences leading to an accident and do not allow for any kind of predictive analysis. The present work introduces an enhanced solution, and a related software platform, which attempts to integrate loss of containment causes and consequences with system's infrastructure and its environment. The solution features:(i)the use of a detailed Master Logical Diagram, including fault/event tree analysis to determine a loss of containment frequency based on different initiating events, scenarios and specific basic data, (ii) the characterization of a resulting source term following a release situation, and (iii) the calculation of various potential impacts on the neighbouring site. Results are wrapped into a CCDF format for each selected traffic segment. The risk-related results are integrated on a software platform, structured as a decision support system using intelligent maps and a variety of GIS (Geographical Information System) data processing procedures. The introduction of the hot spot approach, allows us to focus on the most risk-relevant areas and to use information on various railway infrastructure elements (e.g. points, tunnels), are the basis of the new models employed. The software is applicable to any railway transportation system, comprising its technical infrastructure, rolling stock, human actions, regulation and management procedures. It provides the

  7. RHD alleles in the Tunisian population

    Science.gov (United States)

    Ouchari, Mouna; Jemni-Yaacoub, Saloua; Chakroun, Taher; Abdelkefi, Saida; Houissa, Batoul; Hmida, Slama

    2013-01-01

    Background: A comprehensive survey of RHD alleles in Tunisia population was lacking. The aim of this study was to use a multiplex RHD typing assay for simultaneous detection of partial D especially with RHD/RHCE deoxyribonucleic acid (DNA) sequence exchange mechanism and some weak D alleles. Materials and Methods: Six RHD specific primer sets were designed to amplify RHD exons 3, 4, 5, 6, 7 and 9. DNA from 2000 blood donors (1777 D+ and 223 D-) from several regions was selected for RHD genotyping using a PCR multiplex assay. Further molecular investigations were done to characterize the RHD variants that were identified by the PCR multiplex assay. Results: In the 1777 D+ samples, only 10 individuals showed the absence of amplification of exons 4 and 5 that were subsequently identified by PCR-SSP as weak D type 4 variants. No hybrid allele was detected. In the 223 D-, RHD amplification of some exons was observed only in 5 samples: 4 individuals expressed only RHD exon 9, and one subject lacking exons 4 and 5. These samples were then screened by PCR-SSPs on d(C) ces and weak D type 4, respectively. Conclusion: The weak D type 4 appears to be the most common D variant allele. We have not found any partial D variant. Findings also indicated that RHD gene deletion is the most prevalent cause of the D- phenotype in the Tunisian population. PMID:24014941

  8. Diversity of Lactase Persistence Alleles in Ethiopia

    DEFF Research Database (Denmark)

    Jones, BL; Raga, TO; Liebert, Anke

    2013-01-01

    The persistent expression of lactase into adulthood in humans is a recent genetic adaptation that allows the consumption of milk from other mammals after weaning. In Europe, a single allele (−13910∗T, rs4988235) in an upstream region that acts as an enhancer to the expression of the lactase gene ...

  9. Enhanced low-template DNA analysis conditions and investigation of allele dropout patterns.

    Science.gov (United States)

    Hedell, Ronny; Dufva, Charlotte; Ansell, Ricky; Mostad, Petter; Hedman, Johannes

    2015-01-01

    Forensic DNA analysis applying PCR enables profiling of minute biological samples. Enhanced analysis conditions can be applied to further push the limit of detection, coming with the risk of visualising artefacts and allele imbalances. We have evaluated the consecutive increase of PCR cycles from 30 to 35 to investigate the limitations of low-template (LT) DNA analysis, applying the short tandem repeat (STR) analysis kit PowerPlex ESX 16. Mock crime scene DNA extracts of four different quantities (from around 8-84 pg) were tested. All PCR products were analysed using 5, 10 and 20 capillary electrophoresis (CE) injection seconds. Bayesian models describing allele dropout patterns, allele peak heights and heterozygote balance were developed to assess the overall improvements in EPG quality with altered PCR/CE settings. The models were also used to evaluate the impact of amplicon length, STR marker and fluorescent label on the risk for allele dropout. The allele dropout probability decreased for each PCR cycle increment from 30 to 33 PCR cycles. Irrespective of DNA amount, the dropout probability was not affected by further increasing the number of PCR cycles. For the 42 and 84 pg samples, mainly complete DNA profiles were generated applying 32 PCR cycles. For the 8 and 17 pg samples, the allele dropouts decreased from 100% using 30 cycles to about 75% and 20%, respectively. The results for 33, 34 and 35 PCR cycles indicated that heterozygote balance and stutter ratio were mainly affected by DNA amount, and not directly by PCR cycle number and CE injection settings. We found 32 and 33 PCR cycles with 10 CE injection seconds to be optimal, as 34 and 35 PCR cycles did not improve allele detection and also included CE saturation problems. We find allele dropout probability differences between several STR markers. Markers labelled with the fluorescent dyes CXR-ET (red in electropherogram) and TMR-ET (shown as black) generally have higher dropout risks compared with those

  10. Effects of Familial Attachment, Social Support, Involvement, and Self-Esteem on Youth Substance Use and Sexual Risk Taking

    Science.gov (United States)

    Peterson, Christina Hamme; Buser, Trevor J.; Westburg, Nancy G.

    2010-01-01

    A study of protective factors against substance use and sexual risk taking was conducted among 610 high-poverty urban youth. Higher levels of family attachment, social support, involvement, and self-esteem were associated with lower levels of risk behaviors. (Contains 2 tables and 1 figure.)

  11. Estimating the probability of allelic drop-out of STR alleles in forensic genetics

    DEFF Research Database (Denmark)

    Tvedebrink, Torben; Eriksen, Poul Svante; Mogensen, Helle Smidt

    2009-01-01

    In crime cases with available DNA evidence, the amount of DNA is often sparse due to the setting of the crime. In such cases, allelic drop-out of one or more true alleles in STR typing is possible. We present a statistical model for estimating the per locus and overall probability of allelic drop......-out using the results of all STR loci in the case sample as reference. The methodology of logistic regression is appropriate for this analysis, and we demonstrate how to incorporate this in a forensic genetic framework....

  12. Development of a decision analytic model to support decision making and risk communication about thrombolytic treatment.

    Science.gov (United States)

    McMeekin, Peter; Flynn, Darren; Ford, Gary A; Rodgers, Helen; Gray, Jo; Thomson, Richard G

    2015-11-11

    Individualised prediction of outcomes can support clinical and shared decision making. This paper describes the building of such a model to predict outcomes with and without intravenous thrombolysis treatment following ischaemic stroke. A decision analytic model (DAM) was constructed to establish the likely balance of benefits and risks of treating acute ischaemic stroke with thrombolysis. Probability of independence, (modified Rankin score mRS ≤ 2), dependence (mRS 3 to 5) and death at three months post-stroke was based on a calibrated version of the Stroke-Thrombolytic Predictive Instrument using data from routinely treated stroke patients in the Safe Implementation of Treatments in Stroke (SITS-UK) registry. Predictions in untreated patients were validated using data from the Virtual International Stroke Trials Archive (VISTA). The probability of symptomatic intracerebral haemorrhage in treated patients was incorporated using a scoring model from Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) data. The model predicts probabilities of haemorrhage, death, independence and dependence at 3-months, with and without thrombolysis, as a function of 13 patient characteristics. Calibration (and inclusion of additional predictors) of the Stroke-Thrombolytic Predictive Instrument (S-TPI) addressed issues of under and over prediction. Validation with VISTA data confirmed that assumptions about treatment effect were just. The C-statistics for independence and death in treated patients in the DAM were 0.793 and 0.771 respectively, and 0.776 for independence in untreated patients from VISTA. We have produced a DAM that provides an estimation of the likely benefits and risks of thrombolysis for individual patients, which has subsequently been embedded in a computerised decision aid to support better decision-making and informed consent.

  13. Baseline Risk Assessment Supporting Closure at Waste Management Area C at the Hanford Site Washington

    International Nuclear Information System (INIS)

    Singleton, Kristin M.

    2015-01-01

    contamination impacts on groundwater. Waste Management Area C is the first of the Hanford tank farms to begin the closure planning process. The current baseline risk assessment will provide valuable information for making corrective actions and closure decisions for WMA C, and will also support the planning for future tank farm soil investigation and baseline risk assessments.

  14. Risk and Performance Analyses Supporting Closure of WMA C at the Hanford Site in Southeast Washington

    International Nuclear Information System (INIS)

    Eberlein, Susan J.; Bergeron, Marcel P.; Kemp, Christopher J.; Hildebrand, R. Douglas; Aly, Alaa; Kozak, Matthew; Mehta, Sunil; Connelly, Michael

    2013-01-01

    The Office of River Protection under the U.S. Department of Energy (DOE) is pursuing closure of the Single-Shell Tank (SST) Waste Management Area (WMA) C as stipulated by the Hanford Federal Facility Agreement and Consent Order (HFFACO) under federal requirements and work tasks will be done under the State-approved closure plans and permits. An initial step in meeting the regulatory requirements is to develop a baseline risk assessment representing current conditions based on available characterization data and information collected at the WMA C location. The baseline risk assessment will be supporting a Resource Conservation and Recovery Act of 1976 (RCRA) Field Investigation (RFI)/Corrective Measures Study (CMS) for WMA closure and RCRA corrective action. Complying with the HFFACO conditions also involves developing a long-term closure Performance Assessment (PA) that evaluates human health and environmental impacts resulting from radionuclide inventories in residual wastes remaining in WMA C tanks and ancillary equipment. This PA is being developed to meet the requirements necessary for closure authorization under DOE Order 435.1 and Washington State Hazardous Waste Management Act. To meet the HFFACO conditions, the long-term closure risk analysis will include an evaluation of human health and environmental impacts from hazardous chemical inventories along with other performance Comprehensive Environmental Response, Compensation, and Liability Act Appropriate and Applicable Requirements (CERCLA ARARs) in residual wastes left in WMA C facilities after retrieval and removal. This closure risk analysis is needed to needed to comply with the requirements for permitted closure. Progress to date in developing a baseline risk assessment of WMA C has involved aspects of an evaluation of soil characterization and groundwater monitoring data collected as a part of the RFI/CMS and RCRA monitoring. Developing the long-term performance assessment aspects has involved the

  15. Risk and Performance Analyses Supporting Closure of WMA C at the Hanford Site in Southeast Washington

    Energy Technology Data Exchange (ETDEWEB)

    Eberlein, Susan J.; Bergeron, Marcel P.; Kemp, Christopher J.

    2013-11-11

    The Office of River Protection under the U.S. Department of Energy (DOE) is pursuing closure of the Single-Shell Tank (SST) Waste Management Area (WMA) C as stipulated by the Hanford Federal Facility Agreement and Consent Order (HFFACO) under federal requirements and work tasks will be done under the State-approved closure plans and permits. An initial step in meeting the regulatory requirements is to develop a baseline risk assessment representing current conditions based on available characterization data and information collected at the WMA C location. The baseline risk assessment will be supporting a Resource Conservation and Recovery Act of 1976 (RCRA) Field Investigation (RFI)/Corrective Measures Study (CMS) for WMA closure and RCRA corrective action. Complying with the HFFACO conditions also involves developing a long-term closure Performance Assessment (PA) that evaluates human health and environmental impacts resulting from radionuclide inventories in residual wastes remaining in WMA C tanks and ancillary equipment. This PA is being developed to meet the requirements necessary for closure authorization under DOE Order 435.1 and Washington State Hazardous Waste Management Act. To meet the HFFACO conditions, the long-term closure risk analysis will include an evaluation of human health and environmental impacts from hazardous chemical inventories along with other performance Comprehensive Environmental Response, Compensation, and Liability Act Appropriate and Applicable Requirements (CERCLA ARARs) in residual wastes left in WMA C facilities after retrieval and removal. This closure risk analysis is needed to needed to comply with the requirements for permitted closure. Progress to date in developing a baseline risk assessment of WMA C has involved aspects of an evaluation of soil characterization and groundwater monitoring data collected as a part of the RFI/CMS and RCRA monitoring. Developing the long-term performance assessment aspects has involved the

  16. Baseline Risk Assessment Supporting Closure at Waste Management Area C at the Hanford Site Washington

    Energy Technology Data Exchange (ETDEWEB)

    Singleton, Kristin M. [Washington River Protection Solutions LLC, Richland, WA (United States)

    2015-01-07

    contamination impacts on groundwater. Waste Management Area C is the first of the Hanford tank farms to begin the closure planning process. The current baseline risk assessment will provide valuable information for making corrective actions and closure decisions for WMA C, and will also support the planning for future tank farm soil investigation and baseline risk assessments.

  17. A multiple decision support metrics method for effective risk-informed asset management

    International Nuclear Information System (INIS)

    Liming, J.K.; Salter, J.E.

    2004-01-01

    The objective of this paper is to provide electric utilities with a concept for developing and applying effective decision support metrics via integrated risk-informed asset management (RIAM) programs for power stations and generating companies. RIAM is a process by which analysts review historical performance and develop predictive logic models and data analyses to predict critical decision support figures-of-merit (or metrics) for generating station managers and electric utility company executives. These metrics include, but are not limited to, the following: profitability, net benefit, benefit-to-cost ratio, projected return on investment, projected revenue, projected costs, asset value, safety (catastrophic facility damage frequency and consequences, etc.), power production availability (capacity factor, etc.), efficiency (heat rate), and others. RIAM applies probabilistic safety assessment (PSA) techniques and generates predictions in a probabilistic way so that metrics information can be supplied to managers in terms of probability distributions as well as point estimates. This enables the managers to apply the concept of 'confidence levels' in their critical decision-making processes. (authors)

  18. Practical application of decision support metrics for power plant risk-informed asset management

    International Nuclear Information System (INIS)

    Liming, James K.; Johnson, David H.; Kee, Ernest J.; Sun, Alice Y.; Young, Garry G.

    2003-01-01

    The objective of this paper is to provide electric utilities with a concept for developing and applying effective decision support metrics via integrated risk-informed asset management (RIAM) programs for power stations and generating companies. RIAM is a process by which analysts review historical performance and develop predictive logic models and data analyses to predict critical decision support figures-of-merit (or metrics) for generating station managers and electric utility company executives. These metrics include, but are not limited to, the following; profitability, net benefit, benefit-to-cost ratio, projected return on investment, projected revenue, projected costs, asset value, safety (catastrophic facility damage frequency and consequences, etc.), power production availability (capacity factor, etc.), efficiency (heat rate), and others. RIAM applies probabilistic safety assessment (PSA) techniques and generates predictions probabilistically so that metrics information can be supplied to managers in terms of probability distributions as well as point estimates. This enables the managers to apply the concept of 'confidence levels' in their critical decision-making processes. (author)

  19. Probabilistic safety assessment based expert systems in support of dynamic risk assessment

    International Nuclear Information System (INIS)

    Varde, P.V.; Sharma, U.L.; Marik, S.K.; Raina, V.K.; Tikku, A.C.

    2006-01-01

    Probabilistic Safety Assessment (PSA) studies are being performed, world over as part of integrated risk assessment for Nuclear Power Plants and in many cases PSA insight is utilized in support of decision making. Though the modern plants are built with inherent safety provisions, particularly to reduce the supervisory requirements during initial period into the accident, it is always desired to develop an efficient user friendly real-time operator advisory system for handling of plant transients/emergencies which would be of immense benefit for the enhancement of operational safety of the plant. This paper discusses an integrated approach for the development of operator support system. In this approach, PSA methodology and the insight obtained from PSA has been utilized for development of knowledge based or rule based experts system. While Artificial Neural Network (ANN) approach has been employed for transient identification, rule-base expert system shell environment was used for the development of diagnostic module in this system. Attempt has been made to demonstrate that this approach offers an efficient framework for addressing requirements related to handling of real-time/dynamic scenario. (author)

  20. Integrating risk analysis and multi-criteria decision support under uncertainty in electricity distribution system asset management

    International Nuclear Information System (INIS)

    Catrinu, M.D.; Nordgard, D.E.

    2011-01-01

    Asset managers in electricity distribution companies generally recognize the need and the challenge of adding structure and a higher degree of formal analysis into the increasingly complex asset management decisions. This implies improving the present asset management practice by making the best use of the available data and expert knowledge and by adopting new methods for risk analysis and decision support and nevertheless better ways to document the decisions made. This paper discusses methods for integrating risk analysis and multi-criteria decision support under uncertainty in electricity distribution system asset management. The focus is on how to include the different company objectives and risk analyses into a structured decision framework when deciding how to handle the physical assets of the electricity distribution network. This paper presents an illustrative example of decision support for maintenance and reinvestment strategies based, using expert knowledge, simplified risk analyses and multi-criteria decision analysis under uncertainty.

  1. Parental Support, Mental Health, and Alcohol and Marijuana Use in National and High-Risk African-American Adolescent Samples

    Directory of Open Access Journals (Sweden)

    Julie Maslowsky

    2015-01-01

    Full Text Available African-American adolescents experience disproportionate rates of negative consequences of substance use despite using substances at average or below-average rates. Due to underrepresentation of African-American adolescents in etiological literature, risk and protective processes associated with their substance use require further study. This study examines the role of parental support in adolescents’ conduct problems (CPs, depressive symptoms (DSs, and alcohol and marijuana use in a national sample and a high-risk sample of African-American adolescents. In both samples, parental support was inversely related to adolescent CPs, DSs, and alcohol and marijuana use. CPs, but not DSs, partially mediated the relation of parental support to substance use. Results were consistent across the national and high-risk samples, suggesting that the protective effect of parental support applies to African-American adolescents from a range of demographic backgrounds.

  2. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy.

    Science.gov (United States)

    Liu, Chia-Chen; Liu, Chia-Chan; Kanekiyo, Takahisa; Xu, Huaxi; Bu, Guojun

    2013-02-01

    Apolipoprotein E (Apo-E) is a major cholesterol carrier that supports lipid transport and injury repair in the brain. APOE polymorphic alleles are the main genetic determinants of Alzheimer disease (AD) risk: individuals carrying the ε4 allele are at increased risk of AD compared with those carrying the more common ε3 allele, whereas the ε2 allele decreases risk. Presence of the APOE ε4 allele is also associated with increased risk of cerebral amyloid angiopathy and age-related cognitive decline during normal ageing. Apo-E-lipoproteins bind to several cell-surface receptors to deliver lipids, and also to hydrophobic amyloid-β (Aβ) peptide, which is thought to initiate toxic events that lead to synaptic dysfunction and neurodegeneration in AD. Apo-E isoforms differentially regulate Aβ aggregation and clearance in the brain, and have distinct functions in regulating brain lipid transport, glucose metabolism, neuronal signalling, neuroinflammation, and mitochondrial function. In this Review, we describe current knowledge on Apo-E in the CNS, with a particular emphasis on the clinical and pathological features associated with carriers of different Apo-E isoforms. We also discuss Aβ-dependent and Aβ-independent mechanisms that link Apo-E4 status with AD risk, and consider how to design effective strategies for AD therapy by targeting Apo-E.

  3. Prevalence of Huntington's disease gene CAG trinucleotide repeat alleles in patients with bipolar disorder.

    Science.gov (United States)

    Ramos, Eliana Marisa; Gillis, Tammy; Mysore, Jayalakshmi S; Lee, Jong-Min; Alonso, Isabel; Gusella, James F; Smoller, Jordan W; Sklar, Pamela; MacDonald, Marcy E; Perlis, Roy H

    2015-06-01

    Huntington's disease is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms that are caused by huntingtin gene (HTT) CAG trinucleotide repeat alleles of 36 or more units. A greater than expected prevalence of incompletely penetrant HTT CAG repeat alleles observed among individuals diagnosed with major depressive disorder raises the possibility that another mood disorder, bipolar disorder, could likewise be associated with Huntington's disease. We assessed the distribution of HTT CAG repeat alleles in a cohort of individuals with bipolar disorder. HTT CAG allele sizes from 2,229 Caucasian individuals diagnosed with DSM-IV bipolar disorder were compared to allele sizes in 1,828 control individuals from multiple cohorts. We found that HTT CAG repeat alleles > 35 units were observed in only one of 4,458 chromosomes from individuals with bipolar disorder, compared to three of 3,656 chromosomes from control subjects. These findings do not support an association between bipolar disorder and Huntington's disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Social Support Networks and HIV/STI Risk Behaviors Among Latino Immigrants in a New Receiving Environment.

    Science.gov (United States)

    Althoff, Meghan D; Theall, Katherine; Schmidt, Norine; Hembling, John; Gebrekristos, Hirut T; Thompson, Michelle M; Muth, Stephen Q; Friedman, Samuel R; Kissinger, Patricia

    2017-12-01

    The objectives of this study were to: (1) describe the quantity and quality of social support networks of Latino immigrants living in a new receiving environment, and (2) determine the role such networks play in their HIV/STI risk behaviors, including substance use. Double incentivized convenience sampling was used to collect egocentric social support network data on 144 Latino immigrants. Latent class analysis was used for data reduction and to identify items best suited to measure quality and quantity of social support. Moderate and high quantity and quality of social support were protective of HIV/STI sexual risk behavior compared to low quantity and quality of support, after adjustment for gender, years in New Orleans and residing with family. Neither measure of social support was associated with binge drinking. The findings suggest that increased quantity and quality of social support decrease HIV/STI sexual risk behaviors but do not influence binge drinking. Interventions that improve the quantity and quality of social support are needed for Latino immigrants.

  5. HLA-DR alleles among Pakistani patients of coeliac disease

    International Nuclear Information System (INIS)

    Saleem, N.; Ahmed, T.A.; Bashir, M.; Ali, S.; Iqbal, M.

    2013-01-01

    Objectives: To investigate whether certain DR alleles might also contribute to the genetic susceptibility among Coeliac disease patients in Pakistan. Methods: The case-control study was conducted at the Military Hospital, Rawalpindi, from October 2011 to January 2012, and analysed 25 children diagnosed to have coeliac disease as per the criteria set by the European Society of Paediatric Gastroenterology and Nutrition, which included histopathological alterations in duodenal biopsies, clinical response to gluten withdrawal, and presence of anti-endomyseal antibodies. Patients were compared with a group of 150 healthy subjects. Dioxyribonucleic acid was extracted from peripheral blood collected in ethylenediaminetetraacetic acid.K3. Human leukocyte antigen DRB1 typing was carried out on allele level (DRB1*01 - DRB1*16) using sequence specific primers. Human leukocyte antigen type was determined by agarose gel electrophoresis and results were recorded. Phenotype frequency of various alleles among the patient group and the control group was calculated by direct counting, and significance of their association was determined by Fisher Exact Test. Results: A total of 11 (44%) female paediatric coeliac patients in age range 1-9 (mean 7.2+-4.8 years) and 14 (56%) male paediatric patients in the age range 6-14 (mean 8.6+-5.1 years) were genotyped for HLA-DRB1 loci. A statistically significant positive association of the disease with HLA-DRB1*03 (n=23; 92% versus n=31; 21% in controls, p <0.01) was observed. Conclusion: HLA-DRB1*03 is associated with increased risk of developing coeliac disease. (author)

  6. Semiparametric Allelic Tests for Mapping Multiple Phenotypes: Binomial Regression and Mahalanobis Distance.

    Science.gov (United States)

    Majumdar, Arunabha; Witte, John S; Ghosh, Saurabh

    2015-12-01

    Binary phenotypes commonly arise due to multiple underlying quantitative precursors and genetic variants may impact multiple traits in a pleiotropic manner. Hence, simultaneously analyzing such correlated traits may be more powerful than analyzing individual traits. Various genotype-level methods, e.g., MultiPhen (O'Reilly et al. []), have been developed to identify genetic factors underlying a multivariate phenotype. For univariate phenotypes, the usefulness and applicability of allele-level tests have been investigated. The test of allele frequency difference among cases and controls is commonly used for mapping case-control association. However, allelic methods for multivariate association mapping have not been studied much. In this article, we explore two allelic tests of multivariate association: one using a Binomial regression model based on inverted regression of genotype on phenotype (Binomial regression-based Association of Multivariate Phenotypes [BAMP]), and the other employing the Mahalanobis distance between two sample means of the multivariate phenotype vector for two alleles at a single-nucleotide polymorphism (Distance-based Association of Multivariate Phenotypes [DAMP]). These methods can incorporate both discrete and continuous phenotypes. Some theoretical properties for BAMP are studied. Using simulations, the power of the methods for detecting multivariate association is compared with the genotype-level test MultiPhen's. The allelic tests yield marginally higher power than MultiPhen for multivariate phenotypes. For one/two binary traits under recessive mode of inheritance, allelic tests are found to be substantially more powerful. All three tests are applied to two different real data and the results offer some support for the simulation study. We propose a hybrid approach for testing multivariate association that implements MultiPhen when Hardy-Weinberg Equilibrium (HWE) is violated and BAMP otherwise, because the allelic approaches assume HWE

  7. Psychological distress in women at risk for hereditary breast cancer: the role of family communication and perceived social support.

    Science.gov (United States)

    den Heijer, Mariska; Seynaeve, Caroline; Vanheusden, Kathleen; Duivenvoorden, Hugo J; Bartels, Carina C M; Menke-Pluymers, Marian B E; Tibben, Aad

    2011-12-01

    Hereditary breast cancer has a profound impact on individual family members and on their mutual communication and interactions. The way at-risk women cope with the threat of hereditary breast cancer may depend on the quality of family communication about hereditary breast cancer and on the perceived social support from family and friends. To examine the associations of family communication and social support with long-term psychological distress in a group of women at risk for hereditary breast cancer, who opted either for regular breast surveillance or prophylactic surgery. The study cohort consisted of 222 women at risk for hereditary breast cancer, who previously participated in a study on the psychological consequences of either regular breast cancer surveillance or prophylactic surgery. General and breast cancer specific distress, hereditary cancer-related family communication, perceived social support, and demographics were assessed. Using structural equation modelling, we found that open communication about hereditary cancer within the family was associated with less general and breast cancer specific distress. In addition, perceived support from family and friends was indirectly associated with less general and breast cancer-specific distress through open communication within the family. These findings indicate that family communication and perceived social support from friends and family are of paramount importance in the long-term adaptation to being at risk for hereditary breast cancer. Attention for these issues needs to be incorporated in the care of women at risk for hereditary breast cancer. Copyright © 2010 John Wiley & Sons, Ltd.

  8. Epidemiology of competence: a scoping review to understand the risks and supports to competence of four health professions

    Science.gov (United States)

    Glover Takahashi, Susan; Nayer, Marla

    2017-01-01

    Objectives This study examined the risks and supports to competence discussed in the literature related to occupational therapists, pharmacists, physical therapists and physicians, using epidemiology as a conceptual model. Design Articles from a scoping literature review, published from 1975 to 2014 inclusive, were included if they were about a risk or support to the professional or clinical competence of one of four health professions. Descriptive and regression analyses identified potential associations between risks and supports to competence and the location of study, type of health profession, competence life-cycle and the domain(s) of competence (organised around the CanMEDS framework). Results A total of 3572 abstracts were reviewed and 943 articles analysed. Most focused on physicians (n=810, 86.0%) and ‘practice’ (n=642, 68.0%). Fewer articles discussed risks to competence (n=418, 44.3%) than supports (n=750, 79.5%). The top four risks, each discussed in over 15% of articles, were: transitions in practice, being an international graduate, lack of clinical exposure/experience (ie, insufficient volume of procedures or patients) and age. The top two supports (over 35%) were continuing education participation and educational information/programme features. About 60% of all the articles discussed medical expert and about 25% applied to all roles. Articles focusing on residents had a greater probability of reporting on risks. Conclusions Articles about physicians were dominant. The majority of articles were written in the last decade and more discussed supports than risks to competence. An epidemiology-based conceptual model offers a helpful organising framework for exploring and explaining the competence of health professions. PMID:28864686

  9. Allele-specific deletions in mouse tumors identify Fbxw7 as germline modifier of tumor susceptibility.

    Directory of Open Access Journals (Sweden)

    Jesus Perez-Losada

    Full Text Available Genome-wide association studies (GWAS have been successful in finding associations between specific genetic variants and cancer susceptibility in human populations. These studies have identified a range of highly statistically significant associations between single nucleotide polymorphisms (SNPs and susceptibility to development of a range of human tumors. However, the effect of each SNP in isolation is very small, and all of the SNPs combined only account for a relatively minor proportion of the total genetic risk (5-10%. There is therefore a major requirement for alternative routes to the discovery of genetic risk factors for cancer. We have previously shown using mouse models that chromosomal regions harboring susceptibility genes identified by linkage analysis frequently exhibit allele-specific genetic alterations in tumors. We demonstrate here that the Fbxw7 gene, a commonly mutated gene in a wide range of mouse and human cancers, shows allele-specific deletions in mouse lymphomas and skin tumors. Lymphomas from three different F1 hybrids show 100% allele-specificity in the patterns of allelic loss. Parental alleles from 129/Sv or Spretus/Gla mice are lost in tumors from F1 hybrids with C57BL/6 animals, due to the presence of a specific non-synonymous coding sequence polymorphism at the N-terminal portion of the gene. A specific genetic test of association between this SNP and lymphoma susceptibility in interspecific backcross mice showed a significant linkage (p = 0.001, but only in animals with a functional p53 gene. These data therefore identify Fbxw7 as a p53-dependent tumor susceptibility gene. Increased p53-dependent tumor susceptibility and allele-specific losses were also seen in a mouse skin model of skin tumor development. We propose that analysis of preferential allelic imbalances in tumors may provide an efficient means of uncovering genetic variants that affect mouse and human tumor susceptibility.

  10. Do Maternal Caregiver Perceptions of Childhood Obesity Risk Factors and Obesity Complications Predict Support for Prevention Initiatives Among African Americans?

    Science.gov (United States)

    Alexander, Dayna S; Alfonso, Moya L; Cao, Chunhua; Wright, Alesha R

    2017-07-01

    Objectives African American maternal caregiver support for prevention of childhood obesity may be a factor in implementing, monitoring, and sustaining children's positive health behaviors. However, little is known about how perceptions of childhood obesity risk factors and health complications influence caregivers' support of childhood obesity prevention strategies. The objective of this study was to determine if childhood obesity risk factors and health complications were associated with maternal caregivers' support for prevention initiatives. Methods A convenience sample of maternal caregivers (N = 129, ages 22-65 years) completed the childhood obesity perceptions (COP) survey. A linear regression was conducted to determine whether perceptions about childhood obesity risk factors and subsequent health complications influenced caregivers' support for prevention strategies. Results Caregivers' perceptions of childhood obesity risk factors were moderate (M = 3.4; SD = 0.64), as were their perceptions of obesity-related health complications (M = 3.3; SD = 0.75); however, they perceived a high level of support for prevention strategies (M = 4.2; SD = 0.74). In the regression model, only health complications were significantly associated with caregiver support (β = 0.348; p obesity prevention efforts should emphasize health complications by providing education and strategies that promote self-efficacy and outcome expectations among maternal caregivers.

  11. Optimism and depression: a new look at social support as a mediator among women at risk for breast cancer.

    Science.gov (United States)

    Garner, Melissa J; McGregor, Bonnie A; Murphy, Karly M; Koenig, Alex L; Dolan, Emily D; Albano, Denise

    2015-12-01

    Breast cancer risk is a chronic stressor associated with depression. Optimism is associated with lower levels of depression among breast cancer survivors. However, to our knowledge, no studies have explored the relationship between optimism and depression among women at risk for breast cancer. We hypothesized that women at risk for breast cancer who have higher levels of optimism would report lower levels of depression and that social support would mediate this relationship. Participants (N = 199) with elevated distress were recruited from the community and completed self-report measures of depression, optimism, and social support. Participants were grouped based on their family history of breast cancer. Path analysis was used to examine the cross-sectional relationship between optimism, social support, and depressive symptoms in each group. Results indicated that the variance in depressive symptoms was partially explained through direct paths from optimism and social support among women with a family history of breast cancer. The indirect path from optimism to depressive symptoms via social support was significant (β = -.053; 90% CI = -.099 to -.011, p = .037) in this group. However, among individuals without a family history of breast cancer, the indirect path from optimism to depressive symptoms via social support was not significant. These results suggest that social support partially mediates the relationship between optimism and depression among women at risk for breast cancer. Social support may be an important intervention target to reduce depression among women at risk for breast cancer. Copyright © 2015 John Wiley & Sons, Ltd.

  12. Determination of allele frequencies in nine short tandem repeat loci ...

    African Journals Online (AJOL)

    SERVER

    2008-04-17

    Apr 17, 2008 ... the normal cellular process of replication of DNA molecules. ... probability of a certain genetic variant (alleles) occuring in ... have preservatives that hinder spoilage and are easily packaged .... Allele distribution at Nine STR.

  13. A new electrophoresis technique to separate microsatellite alleles ...

    African Journals Online (AJOL)

    A new electrophoresis technique to separate microsatellite alleles* ... African Journal of Biotechnology ... with the CEQTM 8000 Genetic Analysis System and ABI 3130xl DNA Sequencer easily separated products and determined allelic size, ...

  14. Allele specific expression and methylation in the bumblebee, Bombus terrestris

    Directory of Open Access Journals (Sweden)

    Zoë Lonsdale

    2017-09-01

    Full Text Available The social hymenoptera are emerging as models for epigenetics. DNA methylation, the addition of a methyl group, is a common epigenetic marker. In mammals and flowering plants methylation affects allele specific expression. There is contradictory evidence for the role of methylation on allele specific expression in social insects. The aim of this paper is to investigate allele specific expression and monoallelic methylation in the bumblebee, Bombus terrestris. We found nineteen genes that were both monoallelically methylated and monoallelically expressed in a single bee. Fourteen of these genes express the hypermethylated allele, while the other five express the hypomethylated allele. We also searched for allele specific expression in twenty-nine published RNA-seq libraries. We found 555 loci with allele-specific expression. We discuss our results with reference to the functional role of methylation in gene expression in insects and in the as yet unquantified role of genetic cis effects in insect allele specific methylation and expression.

  15. Comparative frequency and allelic distribution of ABO and Rh (D ...

    African Journals Online (AJOL)

    Gourab Dewan

    2015-02-18

    Feb 18, 2015 ... desh and having borders with India and Myanmar (Fig. 1). It is a hilly area with ..... calculated allelic frequencies for ABO/Rh systems previously. Therefore, allelic .... in backward caste population of Uttar Pradesh, India. Not Sci.

  16. Association mapping and favourable QTL alleles for fibre quality ...

    Indian Academy of Sciences (India)

    Cheng-Guang Dong

    A total of 201 markers were polymorphic and generated 394 allele loci, and 403 ... identified as containing favourable allele loci related to fibre quality traits. The identified .... environment. Field management followed respective local practices.

  17. Highly preferential association of NonF508del CF mutations with the M470 allele.

    Science.gov (United States)

    Ciminelli, B M; Bonizzato, A; Bombieri, C; Pompei, F; Gabaldo, M; Ciccacci, C; Begnini, A; Holubova, A; Zorzi, P; Piskackova, T; Macek, M; Castellani, C; Modiano, G; Pignatti, P F

    2007-01-01

    On the basis of previous findings on random individuals, we hypothesized a preferential association of CF causing mutations with the M allele of the M470V polymorphic site of the CFTR gene. We have determined the M/V-CF mutation haplotype in a series of 201 North East Italian and 73 Czech CF patients who were not F508del homozygotes, as F508del was already known to be fully associated with the M allele. Out of 358 not F508del CF genes, 84 carried the V allele and 274 the less common M allele. In the N-E Italian population, MM subjects have a risk of carrying a CF causing mutation 6.9x greater than VV subjects when F508del is excluded and 15.4x when F508del is included. In the Czech population a similar, although less pronounced, association is observed. Besides the possible biological significance of this association, the possibility of exploiting it for a pilot screening program has been explored in a local North East Italian population for which CF patients were characterized for their CF mutation. General M470V genotyping followed by common CF mutation screening limited to couples in which each partner carries at least one M allele would need testing only 39% of the couples, which contribute 89% of the total risk, with a cost benefit.

  18. Supported high-risk percutaneous coronary intervention with the Impella 2.5 device the Europella registry

    DEFF Research Database (Denmark)

    Sjauw, Krischan D; Konorza, Thomas; Erbel, Raimund

    2009-01-01

    OBJECTIVES: This retrospective multicenter registry evaluated the safety and feasibility of left ventricular (LV) support with the Impella 2.5 (Abiomed Europe GmbH, Aachen, Germany) during high-risk percutaneous coronary intervention (PCI). BACKGROUND: Patients with complex or high-risk coronary...... with poor LV function. The Impella 2.5, a percutaneous implantable LV assist device, might be a superior alternative to the traditionally used intra-aortic balloon pump. METHODS: The Europella registry included 144 consecutive patients who underwent a high-risk PCI. Safety and feasibility end points.......5%. Rates of myocardial infarction, stroke, bleeding requiring transfusion/surgery, and vascular complications at 30 days were 0%, 0.7%, 6.2%, and 4.0%, respectively. CONCLUSIONS: This large multicenter registry supports the safety, feasibility, and potential usefulness of hemodynamic support with Impella 2...

  19. Diet, smoking and cardiovascular risk in schizophrenia in high and low care supported housing.

    Science.gov (United States)

    Gupta, Avirup; Craig, Tom K J

    2009-01-01

    People suffering from schizophrenia have markedly increased physical morbidity and mortality. A poor diet and sedentary lifestyle make a significant contribution to this ill health. Healthcare professionals need to include assessments of diet and to promote a 'healthy living' lifestyle. To describe the dietary habits and cardiovascular risk factors of people with chronic schizophrenia living in supported accommodation and to audit the provision of cardiovascular health screening in this population. The dietary habits of 69 people with chronic schizophrenia living in community settings were assessed. Tobacco smoking, body mass indices and waist circumference were also measured. The dietary behaviour of patients living in high care settings with care staff present every day was compared with those in low care settings. Residents in both levels of care made poor dietary choices. Patients in high care were consuming more fast food than those in low care. The dietary habits of men and women in both levels of care were worse than reported by surveys of the general population in England. All patients had seen their GP in the previous year though only 3 had received diabetes screening and fewer than half had lipid profiles. People with schizophrenia do not improve their diet just by the provision of healthy food as was the case in high care settings. Secondary care services must address physical health monitoring as well as mental health if the increased mortality of patients with schizophrenia is to be addressed effectively. More effective interventions are necessary to improve and sustain a healthy diet.

  20. Genetic Stratification in Myeloid Diseases: From Risk Assessment to Clinical Decision Support Tool

    Directory of Open Access Journals (Sweden)

    Yishai Ofran

    2014-10-01

    Full Text Available Genetic aberrations have become a dominant factor in the stratification of myeloid malignancies. Cytogenetic and a few mutation studies are the backbone of risk assessment models of myeloid malignancies which are a major consideration in clinical decisions, especially patient assignment for allogeneic stem cell transplantation. Progress in our understanding of the genetic basis of the pathogenesis of myeloid malignancies and the growing capabilities of mass sequencing may add new roles for the clinical usage of genetic data. A few recently identified mutations recognized to be associated with specific diseases or clinical scenarios may soon become part of the diagnostic criteria of such conditions. Mutational studies may also advance our capabilities for a more efficient patient selection process, assigning the most effective therapy at the best timing for each patient. The clinical utility of genetic data is anticipated to advance further with the adoption of deep sequencing and next-generation sequencing techniques. We herein suggest some future potential applications of sequential genetic data to identify pending deteriorations at time points which are the best for aggressive interventions such as allogeneic stem cell transplantation. Genetics is moving from being mostly a prognostic factor to becoming a multitasking decision support tool for hematologists. Physicians must pay attention to advances in molecular hematology as it will soon be accessible and influential for most of our patients.

  1. Exploring the development of a decision support system (DSS) to prioritize engineered nanoparticles for risk assessment

    International Nuclear Information System (INIS)

    Marvin, Hans J. P.; Bouwmeester, Hans; Bakker, Martine; Kroese, E. Dinant; Meent, Dik van de; Bourgeois, Francois; Lokers, Rob; Ham, Henk van der; Verhelst, Lieke

    2013-01-01

    Engineered nanoparticles (ENPs) have gained huge commercial interest because of their unique and size-related physicochemical properties. The diversity and complexity of ENPs is increasing with the introduction of next generation nanoparticles. The current approaches are not able to assess the safety of all types and applications of ENPs. Therefore, we are developing a decision support system (DSS) that helps to identify those ENPs and applications that should get priority in the risk assessment. This DSS smartly uses existing knowledge in publicly available databases. With the aid of vocabularies, knowledge rules and logic reasoning new knowledge will be derived. In this paper, the procedure for a DSS is described. Since this system is open by design, others can re-use and extend the DSS content, and newly developed DSS tools can be easily accommodated, which will make the DSS more effective over the years. Data of newly emerging studies will be used for the validation of the DSS. The results will benefit regulating authorities and scientists focussing on the development of inherently safe ENPs

  2. Allele and genotype frequencies of -β lactoglobulin gene in Iranian ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-08-04

    Aug 4, 2009 ... Blood samples were supplied from 80 Najdi cattle and 80 buffalo from different cities of Khouzestan province. ... The allele B of β-Lactoglobulin occurred at a higher frequency than the allele A in both. Najdi cattle and buffalo. .... that of the B allele in both groups of animals studied. Expected heterozygosity ...

  3. Directional Positive Selection on an Allele of Arbitrary Dominance

    OpenAIRE

    Teshima, Kosuke M.; Przeworski, Molly

    2006-01-01

    Most models of positive directional selection assume codominance of the beneficial allele. We examine the importance of this assumption by implementing a coalescent model of positive directional selection with arbitrary dominance. We find that, for a given mean fixation time, a beneficial allele has a much weaker effect on diversity at linked neutral sites when the allele is recessive.

  4. Risk factors for development of dementia in a unique six-year cohort study. I. An exploratory, pilot study of involvement of the E4 allele of apolipoprotein E, mutations of the hemochromatosis-HFE gene, type 2 diabetes, and stroke.

    Science.gov (United States)

    Percy, Maire; Somerville, Martin J; Hicks, Mark; Garcia, Angeles; Colelli, Teresa; Wright, Emily; Kitaygorodsky, Julia; Jiang, Amy; Ho, Valerie; Parpia, Alyssa; Wong, Michael K

    2014-01-01

    Risk factors for dementia development are not well-defined. We evaluated several factors alone and in combination in a unique cohort of Caucasian volunteers over an approximately 6-year observation window using a nested case/control design. Factors included: apolipoprotein E (ApoE) gene variants (the E4 allele is the strongest confirmed genetic predisposing factor for Alzheimer's disease), the hemochromatosis-HFE gene mutations (H63D and C282Y), diabetes, and stroke. At study entry, subjects were ≥65 years of age (M ± SD = 73.0 ± 4.9), had an MMSE score ≥24, and no evidence of cerebrovascular disease or current depression. Genotyping was completed on 163 available DNA samples from three different groups at the study end: those who still had normal cognitive function; those who had developed dementia; and those with Mild Cognitive Impairment (MCI). Analyses were interpreted at the 95% confidence level without Bonferroni corrections. In the subgroup with dementia, all cases of diabetes were type 2 and present at study entry, whereas all strokes occurred during the study. The results highlight apparently synergistic interactions between genetic and medical risk factors for dementia development, gender differences in risk factors, and involvement of HFE mutations. Having E4 (i.e., either of E3/4 or E4/4), C282Y, H63D, diabetes, or stroke alone did not attain significance. Significant predisposing factors with post-hoc power ≥80% were: E4 homozygosity (E4/4)males+females, odds ratio (OR) = 56.0); E4+diabetes (males+females, OR = 13.7; E4+H63D+diabetes (females, OR = 52.0); E4+stroke (males, OR = 46.5). The importance of preventing diabetes and stroke to ward off dementia and the possible role of iron dysmetabolism in dementia are discussed.

  5. Hypermasculinity, intimate partner violence, sexual aggression, social support, and child maltreatment risk in urban, heterosexual fathers taking parenting classes.

    Science.gov (United States)

    Vasquez Guerrero, Desi Alonzo

    2009-01-01

    This study examines the relationships between hypermasculinity, sexual aggression, intimate partner violence, social support, and child maltreatment risk among heterosexual fathers completing parenting classes. Hypermasculinity scores were found to be significant predictors of study participants' reported verbal, physical, and sexual aggression toward their intimate partners. Only lack of social support, operationalized as the reported frequency of participants' conversations with friends, relatives, or neighbors about their problems, was found to be a significant predictor of child maltreatment risk. Alcohol frequency, education, and monthly income were not found to be unique, significant predictors of any dependent variables. Implications for clinical practice and research as well as limitations to the current study are discussed.

  6. Empirical study of ill-supported activities in variation risk identification and assessment in early stage product development

    DEFF Research Database (Denmark)

    Bjarklev, Kristian; Mortensen, Niels Henrik; Ebro, Martin

    2017-01-01

    medical device company by interviewing six key employees that work in the variation risk identification and assessment process. It is found that there are several ill-supported activities, and that the project teams rely heavily on tolerance experts’ assistance and experience in order to identify...... and assess the variation risk. Ill-supported activities are found to be: Balancing hardness of requirements and the screening; communicating mechanism understanding; predicting user input and internal component movement; documenting and communicating tolerance analysis; implementing robustness in the early...

  7. The Influence of Social Networks and Social Support on Health Among Older Koreans at High Risk of Depression.

    Science.gov (United States)

    Chung, Soondool; Jeon, Haesang; Song, Ahyoung

    Despite compelling evidence showing that social networks and social support are associated with depression, relatively little research is available on this topic for older Koreans at high risk of depression. This article aimed to examine the relationship among different types of social networks (family vs. friends), social support (instrumental vs. emotional), and perceived general health among older Koreans at high risk of depression. We would then test for possible differences in pathways between two age groups (60-74 years vs. 75 years and older). Using data from the 2008 Survey of Elderly Life and Welfare Need, age 60-74 years (n = 2,815) and age 75 years and older (n = 1,784) were analyzed separately. Path analyses were used to examine the relationships among social network, support, and health among Korean older adults at high risk of depression. Findings highlighted the complex associations among social networks, social support, and perceived general health within old age. Moreover, this study called attention to the negative association between instrumental support from family networks and perceived general health among older Koreans aged 60-74 years at high risk of depression. The work discussed in this article would help inform the design of much needed and effective social intervention programs for the growing number of Korean older adults with depression.

  8. A matching-allele model explains host resistance to parasites.

    Science.gov (United States)

    Luijckx, Pepijn; Fienberg, Harris; Duneau, David; Ebert, Dieter

    2013-06-17

    The maintenance of genetic variation and sex despite its costs has long puzzled biologists. A popular idea, the Red Queen Theory, is that under rapid antagonistic coevolution between hosts and their parasites, the formation of new rare host genotypes through sex can be advantageous as it creates host genotypes to which the prevailing parasite is not adapted. For host-parasite coevolution to lead to an ongoing advantage for rare genotypes, parasites should infect specific host genotypes and hosts should resist specific parasite genotypes. The most prominent genetics capturing such specificity are matching-allele models (MAMs), which have the key feature that resistance for two parasite genotypes can reverse by switching one allele at one host locus. Despite the lack of empirical support, MAMs have played a central role in the theoretical development of antagonistic coevolution, local adaptation, speciation, and sexual selection. Using genetic crosses, we show that resistance of the crustacean Daphnia magna against the parasitic bacterium Pasteuria ramosa follows a MAM. Simulation results show that the observed genetics can explain the maintenance of genetic variation and contribute to the maintenance of sex in the facultatively sexual host as predicted by the Red Queen Theory. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Investigating patients' and general practitioners' views of computerised decision support software for the assessment and management of cardiovascular risk

    Directory of Open Access Journals (Sweden)

    Anne Wilson

    2007-01-01

    Conclusion Computer decision support programs are becoming more prevalent, but little is known about their usability and acceptability to both health professionals and consumers. The complexities of cardiovascular risk assessment and management can be adequately managed with such programs. As a contemporary report this study contributes to the growing knowledge required for developers of medical software and decision support systems to better understand the needs of endusers.

  10. Combined prediction model for supply risk in nuclear power equipment manufacturing industry based on support vector machine and decision tree

    International Nuclear Information System (INIS)

    Shi Chunsheng; Meng Dapeng

    2011-01-01

    The prediction index for supply risk is developed based on the factor identifying of nuclear equipment manufacturing industry. The supply risk prediction model is established with the method of support vector machine and decision tree, based on the investigation on 3 important nuclear power equipment manufacturing enterprises and 60 suppliers. Final case study demonstrates that the combination model is better than the single prediction model, and demonstrates the feasibility and reliability of this model, which provides a method to evaluate the suppliers and measure the supply risk. (authors)

  11. Minimal support technology and in situ resource utilization for risk management of planetary spaceflight missions

    Science.gov (United States)

    Murphy, K. L.; Rygalov, V. Ye.; Johnson, S. B.

    2009-04-01

    All artificial systems and components in space degrade at higher rates than on Earth, depending in part on environmental conditions, design approach, assembly technologies, and the materials used. This degradation involves not only the hardware and software systems but the humans that interact with those systems. All technological functions and systems can be expressed through functional dependence: [Function]˜[ERU]∗[RUIS]∗[ISR]/[DR];where [ERU]efficiency (rate) of environmental resource utilization[RUIS]resource utilization infrastructure[ISR]in situ resources[DR]degradation rateThe limited resources of spaceflight and open space for autonomous missions require a high reliability (maximum possible, approaching 100%) for system functioning and operation, and must minimize the rate of any system degradation. To date, only a continuous human presence with a system in the spaceflight environment can absolutely mitigate those degradations. This mitigation is based on environmental amelioration for both the technology systems, as repair of data and spare parts, and the humans, as exercise and psychological support. Such maintenance now requires huge infrastructures, including research and development complexes and management agencies, which currently cannot move beyond the Earth. When considering what is required to move manned spaceflight from near Earth stations to remote locations such as Mars, what are the minimal technologies and infrastructures necessary for autonomous restoration of a degrading system in space? In all of the known system factors of a mission to Mars that reduce the mass load, increase the reliability, and reduce the mission’s overall risk, the current common denominator is the use of undeveloped or untested technologies. None of the technologies required to significantly reduce the risk for critical systems are currently available at acceptable readiness levels. Long term interplanetary missions require that space programs produce a craft

  12. Audit of Cardiovascular Disease Risk Factors among Supported Adults with Intellectual Disability Attending an Ageing Clinic

    Science.gov (United States)

    Wallace, Robyn A.; Schluter, Philip

    2008-01-01

    Background: Little is known about the cardiovascular disease (CVD) risk factor profile for older adults with intellectual disability (ID). As many CVD risk factors are treatable by lifestyle changes, confirmation of the risk factor profile for older adults with ID could substantially impact upon preventive health practices for this group. Method:…

  13. Analysis of the Fiscal Resources Supporting At-Risk Youth, Ages 13-24, in Hawaii

    Science.gov (United States)

    Silloway, Torey; Connors-Tadros, Lori; Dahlin, Melissa

    2012-01-01

    Hawaii's largest populations of at-risk youth include those youth who have dropped out of school, are at-risk of not completing high school, and youth who have completed school but are still not prepared for the workforce. Depending on estimates used, between 20 and 25 percent of Hawaiian youth are at risk of dropping out school. For older youth,…

  14. Percutaneous cardiopulmonary support for catheter ablation of unstable ventricular arrhythmias in high-risk patients.

    Science.gov (United States)

    Carbucicchio, Corrado; Della Bella, Paolo; Fassini, Gaetano; Trevisi, Nicola; Riva, Stefania; Giraldi, Francesco; Baratto, Francesca; Marenzi, Giancarlo; Sisillo, Erminio; Bartorelli, Antonio; Alamanni, Francesco

    2009-11-01

    In patients with severe cardiomyopathy, recurrent episodes of nontolerated ventricular tachycardia (VT) or electrical storm (ES) frequently cause acute heart failure and cardiac death; the suppression of the arrhythmia is therefore lifesaving, but feasibility of catheter ablation (CA) is precluded by the adverse hemodynamic conditions together with the characteristics of the arrhythmia that interdicts efficacious mapping. The use of the percutaneous cardiopulmonary support (CPS) for circulatory assistance may allow patient's stabilization and enhance efficacy and safety of CA in this emergency setting. 19 patients (19 males; mean age 61 +/- 6 years; chronic ischemic cardiomyopathy, eleven patients; primary dilated cardiomyopathy, six patients; arrhythmogenic right ventricular dysplasia/ cardiomyopathy, two patients) with recurrent nontolerated VT episodes undergoing CPS-assisted CA were retrospectively evaluated. Twelve patients had acute hemodynamic failure refractory to inotropic agents and ventilatory assistance, seven patients had undergone a failing nonconventional CA procedure. 14 patients presented with ES, and in twelve the procedure was undertaken under emergency conditions within 24 h from admission. Patients were ventilated under general anesthesia and assisted by a multidisciplinary team. The CPS system consisted in a Medtronic Bio-Medicus centrifugal pump and in a Maxima Plus oxygenator, a 15-F arterial cannula, and a 17-F venous cannula. Flows between 2 and 3 l/min were activated after induction of 56/62 forms of nontolerated VT, achieving hemodynamic stabilization in all patients. CA was mainly guided by conventional activation mapping and was effective in abolishing 45/56 supported VTs; in 10/19 patients all clinical VTs were suppressed by CA. Mean procedural time was 4 h and 20 min. Complete stabilization was achieved in 13 patients (68%) without VT recurrence during a 7-day in-hospital monitoring. A significant clinical improvement was observed in

  15. Applying Costs, Risks and Values Evaluation (CRAVE) methodology to Engineering Support Request (ESR) prioritization

    Science.gov (United States)

    Joglekar, Prafulla N.

    1994-01-01

    Given limited budget, the problem of prioritization among Engineering Support Requests (ESR's) with varied sizes, shapes, and colors is a difficult one. At the Kennedy Space Center (KSC), the recently developed 4-Matrix (4-M) method represents a step in the right direction as it attempts to combine the traditional criteria of technical merits only with the new concern for cost-effectiveness. However, the 4-M method was not adequately successful in the actual prioritization of ESRs for the fiscal year 1995 (FY95). This research identifies a number of design issues that should help us to develop better methods. It emphasizes that given the variety and diversity of ESR's one should not expect that a single method could help in the assessment of all ESR's. One conclusion is that a methodology such as Costs, Risks, and Values Evaluation (CRAVE) should be adopted. It also is clear that the development of methods such as 4-M requires input not only from engineers with technical expertise in ESR's but also from personnel with adequate background in the theory and practice of cost-effectiveness analysis. At KSC, ESR prioritization is one part of the Ground Support Working Teams (GSWT) Integration Process. It was discovered that the more important barriers to the incorporation of cost-effectiveness considerations in ESR prioritization lie in this process. The culture of integration, and the corresponding structure of review by a committee of peers, is not conducive to the analysis and confrontation necessary in the assessment and prioritization of ESR's. Without assistance from appropriately trained analysts charged with the responsibility to analyze and be confrontational about each ESR, the GSWT steering committee will continue to make its decisions based on incomplete understanding, inconsistent numbers, and at times, colored facts. The current organizational separation of the prioritization and the funding processes is also identified as an important barrier to the

  16. A decision support tool to prioritize risk management options for contaminated sites.

    Science.gov (United States)

    Sorvari, Jaana; Seppälä, Jyri

    2010-03-15

    The decisions on risk management (RM) of contaminated sites in Finland have typically been driven by practical factors such as time and money. However, RM is a multifaceted task that generally involves several additional determinants, e.g. performance and environmental effects of remediation methods, psychological and social factors. Therefore, we adopted a multi-criteria decision analysis approach and developed a decision support tool (DST) that is viable in decision-making in such a complex situation. The basic components of the DST are based on the Dutch REC system. However, our DST is more case-specific and allows the consideration of the type, magnitude and scale of contamination, land use, environmental conditions and socio-cultural aspects (e.g. loss of cultural heritage, image aspects). The construction of the DST was started by structuring the decision problem using a value tree. Based on this work we adopted the Multi-Attribute Value Theory (MAVT) for data aggregation. The final DST was demonstrated by two model sites for which the RM alternatives and site-specific data were created on the basis of factual remediation projects and by interviewing experts. The demonstration of the DST was carried out in a workshop where representatives of different stakeholders were requested to rank and weight the decision criteria involved. To get information on the consistency of the ranking of the RM alternatives, we used different weighting techniques (ratio estimation and pair-wise weighting) and alternative ways to treat individual respondents' weights in calculating the preference scores for each RM alternative. These dissimilar approaches resulted in some differences in the preference order of the RM alternatives. The demonstration showed that attention has to be paid to the proper description of the site, the principles of the procedure and the decision criteria. Nevertheless, the procedure proved to enable efficient communication between different stakeholders

  17. Analyzing policy support instruments and regulatory risk factors for wind energy deployment-A developers' perspective

    International Nuclear Information System (INIS)

    Luethi, Sonja; Praessler, Thomas

    2011-01-01

    A transition to a renewable energy system is high on the policy agenda in many countries. A promising energy source for a low-carbon energy future is wind. Policy-makers can attract wind energy development by providing attractive policy frameworks. This paper argues that apart from the level of financial support, both the risks stemming from the regulatory environment (legal security, administrative process and grid access) and the ability to finance projects play a critical role in determining the attractiveness of the development environment. It sheds light on how project developers trade off these different aspects and to what extent the attractiveness of a certain policy framework increases with the introduction of specific measures. Conjoint analysis is employed to provide empirical evidence on the preference of wind energy developers in the EU and the US. The analysis shows that developers' preferences are very similar across the studied regions and for different types of developers. Which policy measures could be most valuable depends on the specific existing environment. In some southeastern European countries, a reduction of administrative process duration may yield the highest utility gains, whereas, in the US, improvements in grid access regulation and an increase in remuneration levels may be more effective. - Highlights: → Paper suggests conjoint analysis as scenario tool for estimating potential effects of specific policy measures. → It provides a quantitative, empirical dataset of 119 onshore wind energy developers' preferences. → Results suggest that the aspects 'Legal security' and 'Remuneration' are important attributes. → Cluster analyses yields slightly different preferences for developers from EU and US.

  18. CHANGES SDSS: the development of a Spatial Decision Support System for analysing changing hydro-meteorological risk

    Science.gov (United States)

    van Westen, Cees; Bakker, Wim; Zhang, Kaixi; Jäger, Stefan; Assmann, Andre; Kass, Steve; Andrejchenko, Vera; Olyazadeh, Roya; Berlin, Julian; Cristal, Irina

    2014-05-01

    Within the framework of the EU FP7 Marie Curie Project CHANGES (www.changes-itn.eu) and the EU FP7 Copernicus project INCREO (http://www.increo-fp7.eu) a spatial decision support system is under development with the aim to analyse the effect of risk reduction planning alternatives on reducing the risk now and in the future, and support decision makers in selecting the best alternatives. The Spatial Decision Support System will be composed of a number of integrated components. The Risk Assessment component allows to carry out spatial risk analysis, with different degrees of complexity, ranging from simple exposure (overlay of hazard and assets maps) to quantitative analysis (using different hazard types, temporal scenarios and vulnerability curves) resulting into risk curves. The platform does not include a component to calculate hazard maps, and existing hazard maps are used as input data for the risk component. The second component of the SDSS is a risk reduction planning component, which forms the core of the platform. This component includes the definition of risk reduction alternatives (related to disaster response planning, risk reduction measures and spatial planning) and links back to the risk assessment module to calculate the new level of risk if the measure is implemented, and a cost-benefit (or cost-effectiveness/ Spatial Multi Criteria Evaluation) component to compare the alternatives and make decision on the optimal one. The third component of the SDSS is a temporal scenario component, which allows to define future scenarios in terms of climate change, land use change and population change, and the time periods for which these scenarios will be made. The component doesn't generate these scenarios but uses input maps for the effect of the scenarios on the hazard and assets maps. The last component is a communication and visualization component, which can compare scenarios and alternatives, not only in the form of maps, but also in other forms (risk

  19. SU94. Allele-Specific and Trauma-Related Epigenetic Changes in the FKBP5 Gene: Differences Between Psychotic Patients and Healthy Controls

    Science.gov (United States)

    Mihaljevic, Marina; Franic, Dusica; Soldatovic, Ivan; Andric, Sanja; Mirjanic, Tijana; Novakovic, Ivana; Adzic, Miroslav; Maric, Nadja

    2017-01-01

    5 gene in psychotic patients, which is in line with previous reports in traumatized individuals. Trauma-related demethylation in risk controls’ group supports the hypothesis that psychotic and stress-related conditions could share common neurobiological underlying mechanism, such as HPA axis dysregulation, particularly in individuals with genetic predisposition for altered stress response. References 1.Daskalakis NP, Binder EB. Schizophrenia in the spectrum of gene-stress interactions: the FKBP5 example. Schizophr Bull. 2015;41:323–329. 2.Klengel T, Mehta D, Anacker C et al. Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nat Neurosci. 2013;16:33–41.

  20. How do relationships support parenting? Effects of attachment style and social support on parenting behavior in an at-risk population.

    Science.gov (United States)

    Green, Beth L; Furrer, Carrie; McAllister, Carol

    2007-09-01

    The importance of supportive relationships for new parents has been the focus of both research and parenting interventions. Attachment style, typically viewed as a relatively stable trait reflecting one's comfort in social relationships, as well as social support, or one's perception of the social context, have both been found to be important for fostering engaged, involved parenting. Less is known, however, about how these variables work together to influence parenting behavior, especially in families at higher risk for negative child outcomes. Data were collected from 152 urban, predominantly African American, low-income parents when their children were 14 and 36 months of age. Results suggest that parents with more social support show greater increases in the frequency of positive parent-child activities over time, but that this effect is mediated by mothers' attachment style, specifically, their level of anxious/ambivalent attachment. Mothers with more social support tended to be less anxious/ambivalent about close relationships, and this in turn led to increases over time in the frequency of parent-child interactions. Mothers' tendency to avoid close relationships, however, while correlated with social support, was unrelated to changes in parenting behavior. Implications of these findings for program development, parenting, and the malleability of attachment style based on social context are discussed.

  1. Using prior risk-related knowledge to support risk management decisions: lessons learnt from a tunneling project

    NARCIS (Netherlands)

    Chivatá Cárdenas, Ibsen; Al-Jibouri, Saad H.S.; Halman, Johannes I.M.; van de Linde, W.; Kaalberg, F.

    2014-01-01

    The authors of this article have developed six probabilistic causal models for critical risks in tunnel works. The details of the models' development and evaluation were reported in two earlier publications of this journal. Accordingly, as a remaining step, this article is focused on the

  2. Assessing the Effects of Information About Global Population Growth on Risk Perceptions and Support for Mitigation and Prevention Strategies.

    Science.gov (United States)

    Dawson, Ian G J

    2018-05-16

    The human population is forecast to increase by 3-4 billion people during this century and many scientists have expressed concerns that this could increase the likelihood of certain adverse events (e.g., climate change and resource shortages). Recent research shows that these concerns are mirrored in public risk perceptions and that these perceptions correlate with a willingness to adopt mitigation behaviors (e.g., reduce resource consumption) and preventative actions (e.g., support actions to limit growth). However, little research has assessed the factors that influence risk perceptions of global population growth (GPG). To contribute to this important goal, this article presents three studies that examined how risk perceptions of GPG might be influenced by textual-visual representations (like those in media and Internet articles) of the potential effects of GPG. Study 1 found that a textual narrative that highlighted the potential negative (cf. positive) consequences of GPG led to higher perceived risk and greater willingness to adopt mitigation behaviors, but not to support preventative actions. Notably, the influence of the narratives on perceived risk was largely moderated by the participant's prior knowledge and perceptions of GPG. Contrary to expectations, studies 2 and 3 revealed, respectively, that photographs depicting GPG-related imagery and graphs depicting GPG rates had no significant effect on the perceived risk of GPG or the willingness to embrace mitigation or preventative actions. However, study 3 found that individuals with higher "graph literacy" perceived GPG as a higher risk and were more willing to adopt mitigation behaviors and support preventative actions. © 2018 Society for Risk Analysis.

  3. Cost-effectiveness Analysis of Nutritional Support for the Prevention of Pressure Ulcers in High-Risk Hospitalized Patients.

    Science.gov (United States)

    Tuffaha, Haitham W; Roberts, Shelley; Chaboyer, Wendy; Gordon, Louisa G; Scuffham, Paul A

    2016-06-01

    To evaluate the cost-effectiveness of nutritional support compared with standard care in preventing pressure ulcers (PrUs) in high-risk hospitalized patients. An economic model using data from a systematic literature review. A meta-analysis of randomized controlled trials on the efficacy of nutritional support in reducing the incidence of PrUs was conducted. Modeled cohort of hospitalized patients at high risk of developing PrUs and malnutrition simulated during their hospital stay and up to 1 year. Standard care included PrU prevention strategies, such as redistribution surfaces, repositioning, and skin protection strategies, along with standard hospital diet. In addition to the standard care, the intervention group received nutritional support comprising patient education, nutrition goal setting, and the consumption of high-protein supplements. The analysis was from a healthcare payer perspective. Key outcomes of the model included the average costs and quality-adjusted life years. Model results were tested in univariate sensitivity analyses, and decision uncertainty was characterized using a probabilistic sensitivity analysis. Compared with standard care, nutritional support was cost saving at AU $425 per patient and marginally more effective with an average 0.005 quality-adjusted life years gained. The probability of nutritional support being cost-effective was 87%. Nutritional support to prevent PrUs in high-risk hospitalized patients is cost-effective with substantial cost savings predicted. Hospitals should implement the recommendations from the current PrU practice guidelines and offer nutritional support to high-risk patients.

  4. The impact of social support on the risk of eating disorders in women exposed to intimate partner violence

    Directory of Open Access Journals (Sweden)

    Schirk DK

    2015-11-01

    Full Text Available Dana K Schirk,1 Erik B Lehman,2 Amanda N Perry,3 Rollyn M Ornstein,4 Jennifer S McCall-Hosenfeld2,5 1The Pennsylvania State University College of Medicine, 2Department of Public Health Sciences, The Pennsylvania State University College of Medicine, Hershey, 3Department of Agricultural Economics, Sociology, and Education, Division of Rural Sociology, College of Agriculture, Pennsylvania State University, University Park, 4Department of Pediatrics, 5Department of Medicine, The Pennsylvania State University College of Medicine, Hershey, PA, USA Background: Eating disorders (EDs are often found among women exposed to intimate partner violence (IPV. The role of social support (SS as a protective factor against ED among IPV-exposed women is not firmly established.Objective: The objective of this study is to determine the distribution of risk of EDs among women exposed to IPV and to examine the impact of SS on risk of ED among IPV-exposed women.Methods: Women (aged 18–64 years exposed to IPV during their lifetimes (defined by the Humiliation–Afraid–Rape–Kick instrument were recruited from primary care and domestic violence service agencies and surveyed on demographics, mood/anxiety disorders, psychosocial/community factors, and strategies used in response to IPV. The Eating Disorder Screen for Primary Care assessed the risk of ED. A modified Medical Outcomes Study Social Support Survey assessed overall functional support (scale range: 0–32; categorized into quartiles. Ordinal logistic regression examined the risk of ED based on SS, controlling for prespecified demographics (age, race/ethnicity, marital status, near-poverty level, and health-related factors significant in bivariate analyses (risky alcohol use.Results: Among 302 women with lifetime IPV, 41 (14% were at high risk, 127 (42% were at moderate risk, and 134 (44% were at low risk of an ED. In bivariate analyses, high risk of an ED was significantly more frequent among women with a

  5. Teacher-Perceived Supportive Classroom Climate Protects against Detrimental Impact of Reading Disability Risk on Peer Rejection

    Science.gov (United States)

    Kiuru, Noona; Poikkeus, Anna-Maija; Lerkkanen, Marja-Kristiina; Pakarinen, Eija; Siekkinen, Martti; Ahonen, Timo; Nurmi, Jari-Erik

    2012-01-01

    This study examined the role of a supportive classroom climate, class size, and length of teaching experience as protective factors against children's peer rejection. A total of 376 children were assessed in kindergarten for risk for reading disabilities (RD) and rated by their teachers on socially withdrawn and disruptive behaviors. The grade 1…

  6. Analysis of the risk management decisionmaking processes and the decision support systems in the wildland fire agencies

    Science.gov (United States)

    Patrick Withen

    2007-01-01

    This paper offers an analysis of the strengths, weaknesses, opportunities, and threats in the risk management process, decision support systems (DSSs), and other types of decisionmaking, including recognition primed decisionmaking, bricolage with the goal of improving DSSs and decisionmaking. DSSs may be thought of as any technology or knowledge that is used as an aid...

  7. Dispositional Affect Moderates the Stress-Buffering Effect of Social Support on Risk for Developing the Common Cold.

    Science.gov (United States)

    Janicki Deverts, Denise; Cohen, Sheldon; Doyle, William J

    2017-10-01

    The aim was to examine whether trait positive and negative affect (PA, NA) moderate the stress-buffering effect of perceived social support on risk for developing a cold subsequent to being exposed to a virus that causes mild upper respiratory illness. Analyses were based on archival data from 694 healthy adults (M age  = 31.0 years, SD = 10.7 years; 49.0% female; 64.6% Caucasian). Perceived social support and perceived stress were assessed by self-report questionnaire and trait affect by aggregating responses to daily mood items administered by telephone interview across several days. Subsequently, participants were exposed to a virus that causes the common cold and monitored for 5 days for clinical illness (infection + objective signs of illness). Two 3-way interactions emerged-Support × Stress × PA and Support × Stress × NA. The nature of these effects was such that among persons with high trait PA or low trait NA, greater social support attenuated the risk of developing a cold when under high but not low perceived stress; this stress-buffering effect did not emerge among persons with low trait PA or high trait NA. Dispositional affect might be used to identify individuals who may be most responsive to social support and support-based interventions. © 2016 Wiley Periodicals, Inc.

  8. Adolescent mental health and academic functioning: empirical support for contrasting models of risk and vulnerability.

    Science.gov (United States)

    Lucier-Greer, Mallory; O'Neal, Catherine W; Arnold, A Laura; Mancini, Jay A; Wickrama, Kandauda K A S

    2014-11-01

    Adolescents in military families contend with normative stressors that are universal and exist across social contexts (minority status, family disruptions, and social isolation) as well as stressors reflective of their military life context (e.g., parental deployment, school transitions, and living outside the United States). This study utilizes a social ecological perspective and a stress process lens to examine the relationship between multiple risk factors and relevant indicators of youth well-being, namely depressive symptoms and academic performance, as well as the mediating role of self-efficacy (N = 1,036). Three risk models were tested: an additive effects model (each risk factor uniquely influences outcomes), a full cumulative effects model (the collection of risk factors influences outcomes), a comparative model (a cumulative effects model exploring the differential effects of normative and military-related risks). This design allowed for the simultaneous examination of multiple risk factors and a comparison of alternative perspectives on measuring risk. Each model was predictive of depressive symptoms and academic performance through persistence; however, each model provides unique findings about the relationship between risk factors and youth outcomes. Discussion is provided pertinent to service providers and researchers on how risk is conceptualized and suggestions for identifying at-risk youth. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

  9. Evaluation of unit risk factors in support of the Hanford Remedial Action Environmental Impact Statement

    International Nuclear Information System (INIS)

    Strenge, D.L.; Chamberlain, P.J. II.

    1994-11-01

    This report describes the generation of unit risk factors for use with the Graphical Information System (GIS) being developed by Advanced Sciences, Inc. for the Hanford Remedial Action Environmental Impact Statement. The GIS couples information on source inventory and environmental transport with unit risk factors to estimate the potential risk from contamination at all locations on the Hanford Site. The major components of the effort to generate the unit risk factors were: determination of pollutants to include in the study, definition of media of concern, and definition of exposure assessment scenarios, methods, and parameters. The selection of pollutants was based on inventory lists which indicated the pollutants likely to be encountered at the known waste sites. The final pollutants selected included 47 chemical pollutants and 101 radionuclides. Unit risk factors have been generated for all 148 pollutants per unit initial concentration in five media: soil (per unit mass), soil (per unit area), air, groundwater, and surface water. The exposure scenarios were selected as the basis for the unit risk factor generation. The endpoint in the exposure assessment analysis is expressed as risk of developing cancer for radionuclides and carcinogenic chemicals. For noncarcinogenic chemicals, the risk endpoint is the hazard quotient. The cancer incidence and hazard quotient values are evaluated for all exposure pathways, pollutants, and scenarios. The hazard index values and unit risk values are used by the GIS to produce maps of risk for the Hanford Site

  10. The geographic spread of the CCR5 Delta32 HIV-resistance allele.

    Directory of Open Access Journals (Sweden)

    John Novembre

    2005-11-01

    Full Text Available The Delta32 mutation at the CCR5 locus is a well-studied example of natural selection acting in humans. The mutation is found principally in Europe and western Asia, with higher frequencies generally in the north. Homozygous carriers of the Delta32 mutation are resistant to HIV-1 infection because the mutation prevents functional expression of the CCR5 chemokine receptor normally used by HIV-1 to enter CD4+ T cells. HIV has emerged only recently, but population genetic data strongly suggest Delta32 has been under intense selection for much of its evolutionary history. To understand how selection and dispersal have interacted during the history of the Delta32 allele, we implemented a spatially explicit model of the spread of Delta32. The model includes the effects of sampling, which we show can give rise to local peaks in observed allele frequencies. In addition, we show that with modest gradients in selection intensity, the origin of the Delta32 allele may be relatively far from the current areas of highest allele frequency. The geographic distribution of the Delta32 allele is consistent with previous reports of a strong selective advantage (>10% for Delta32 carriers and of dispersal over relatively long distances (>100 km/generation. When selection is assumed to be uniform across Europe and western Asia, we find support for a northern European origin and long-range dispersal consistent with the Viking-mediated dispersal of Delta32 proposed by G. Lucotte and G. Mercier. However, when we allow for gradients in selection intensity, we estimate the origin to be outside of northern Europe and selection intensities to be strongest in the northwest. Our results describe the evolutionary history of the Delta32 allele and establish a general methodology for studying the geographic distribution of selected alleles.

  11. Maternal and fetal human leukocyte antigen class Ia and II alleles in severe preeclampsia and eclampsia

    DEFF Research Database (Denmark)

    Emmery, J.; Hachmon, R.; Pyo, C. W.

    2016-01-01

    and -DPB1) alleles and the risk of developing severe preeclampsia/eclampsia were investigated in a detailed and large-scale study. In total, 259 women diagnosed with severe preeclampsia or eclampsia and 260 matched control women with no preeclampsia, together with their neonates, were included in the study....... HLA genotyping for mothers and neonates was performed using next-generation sequencing. The HLA-DPB1*04:01:01G allele was significantly more frequent (Pc=0.044) among women diagnosed with severe preeclampsia/eclampsia compared with controls, and the DQA1*01:02:01G allele frequency was significantly...... lower (Pc=0.042) among newborns born by women with severe preeclampsia/eclampsia compared with controls. In mothers with severe preeclampsia/eclampsia, homozygosity was significantly more common compared with controls at the HLA-DPB1 locus (Pc=0.0028). Although the current large study shows some...

  12. Risk factors associated with default among new pulmonary TB patients and social support in six Russian regions.

    Science.gov (United States)

    Jakubowiak, W M; Bogorodskaya, E M; Borisov, S E; Borisov, E S; Danilova, I D; Danilova, D I; Kourbatova, E V; Kourbatova, E K

    2007-01-01

    Tuberculosis (TB) services in six Russian regions in which social support programmes for TB patients were implemented. To identify risk factors for default and to evaluate possible impact of social support. Retrospective study of new pulmonary smear-positive and smear-negative TB patients registered during the second and third quarters of the 2003. Data were analysed in a case-control study including default patients as cases and successfully treated patients as controls, using multivariate logistic regression modelling. A total of 1805 cases of pulmonary TB were enrolled. Default rates in the regions were 2.3-6.3%. On multivariate analysis, risk factors independently associated with default outcome included: unemployment (OR 4.44; 95%CI 2.23-8.86), alcohol abuse (OR 1.99; 95%CI 1.04-3.81), and homelessness (OR 3.49; 95%CI 1.25-9.77). Social support reduced the default outcome (OR 0.13; 95%CI 0.06-0.28), controlling for age, sex, region, residence and acid-fast bacilli (AFB) smear of sputum. Unemployment, alcohol abuse and homelessness were associated with increased default outcome among new TB patients, while social support for TB patients reduced default. Further prospective randomised studies are necessary to evaluate the impact and to determine the most cost-effective social support for improving treatment outcomes of TB in patients in Russia, especially among populations at risk of default.

  13. A pseudodeficiency allele common in non-Jewish Tay-Sachs carriers: Implications for carrier screening

    Energy Technology Data Exchange (ETDEWEB)

    Triggs-Raine, B.L.; Akerman, B.R.; Gravel, R.A. (McGill Univ.-Montreal Children' s Hospital Research Institute, Montreal, Quebec (Canada)); Mules, E.H.; Thomas, G.H.; Dowling, C.E. (Johns Hopkins School of Medicine, Baltimore, MD (United States)); Kaback, M.M.; Lim-Steele, J.S.T. (Univ. of California, San Diego, CA (United States)); Natowicz, M.R. (Eunice Kennedy Shriver Center for Mental Retardation, Waltham, MA (United States)); Grebner, E.E. (Thomas Jefferson Univ., Philadelphia, PA (United States)); Navon, R.R. (Tel-Aviv Univ., Kfar-Sava (Israel)); Welch, J.P. (Dalhousie Univ., Halifax, Nova, Scotia (Canada)); Greenberg, C.R. (Univ. of Manitoba, Winnipeg (Canada))

    1992-10-01

    Deficiency of [beta]-hexosaminidase A (Hex A) activity typically results in Tay-Sachs disease. However, healthy subjects found to be deficient in Hex A activity (i.e., pseudodeficient) by means of in vitro biochemical tests have been described. The authors analyzed the HEXA gene of one pseudodeficient subject and identified both a C[sub 739]-to-T substitution that changes Arg[sub 247][yields]Trp on one allele and a previously identified Tay-Sachs disease mutation of the second allele. Six additional pseudodeficient subjects were found to have the C[sub 739]-to-T but for none of 36 Jewish enzyme-defined carries who did not have one of three known mutations common to this group. The C[sub 739]-to-T allele, together with a [open quotes]true[close quotes] Tay-Sachs disease allele, causes Hex A pseudodeficiency. Given both the large proportion of non-Jewish carriers with this allele and that standard biochemical screening cannot differentiate between heterozygotes for the C[sub 739]-to-T mutations and Tay-Sachs disease carriers, DNA testing for this mutation in at-risk couples is essential. This could prevent unnecessary or incorrect prenatal diagnoses. 40 refs., 3 figs., 4 tabs.

  14. Allele-specific cytokine responses at the HLA-C locus, implications for psoriasis

    Science.gov (United States)

    Hundhausen, Christian; Bertoni, Anna; Mak, Rose K; Botti, Elisabetta; Di Meglio, Paola; Clop, Alex; Laggner, Ute; Chimenti, Sergio; Hayday, Adrian C; Barker, Jonathan N; Trembath, Richard C; Capon, Francesca; Nestle, Frank O

    2011-01-01

    Psoriasis is an inflammatory skin disorder that is inherited as a complex trait. Genetic studies have repeatedly highlighted HLA-C as the major determinant for psoriasis susceptibility, with the Cw*0602 allele conferring significant disease risk in a wide-range of populations. Despite the potential importance of HLA-C variation in psoriasis, either via an effect on peptide presentation or immuno-inhibitory activity, allele-specific expression patterns have not been investigated. Here, we used reporter assays to characterize two regulatory variants, which virtually abolished the response to TNF-α (rs2524094) and IFN-γ (rs10657191) in HLA-Cw*0602 and a cluster of related alleles. We validated these findings through the analysis of HLA-Cw*0602 expression in primary keratinocytes treated with TNF-α and IFN-γ. Finally, we showed that HLA-Cw*0602 transcripts are not increased in psoriatic skin lesions, despite highly elevated TNF-α levels. Thus, our findings demonstrate the presence of allele-specific differences in HLA-C expression and indicate that HLA-Cw*0602 is unresponsive to up-regulation by key pro-inflammatory cytokines in psoriasis. These data pave the way for functional studies into the pathogenic role of the major psoriasis susceptibility allele. PMID:22113476

  15. Allele-specific cytokine responses at the HLA-C locus: implications for psoriasis.

    Science.gov (United States)

    Hundhausen, Christian; Bertoni, Anna; Mak, Rose K; Botti, Elisabetta; Di Meglio, Paola; Clop, Alex; Laggner, Ute; Chimenti, Sergio; Hayday, Adrian C; Barker, Jonathan N; Trembath, Richard C; Capon, Francesca; Nestle, Frank O

    2012-03-01

    Psoriasis is an inflammatory skin disorder that is inherited as a complex trait. Genetic studies have repeatedly highlighted HLA-C as the major determinant for psoriasis susceptibility, with the Cw*0602 allele conferring significant disease risk in a wide range of populations. Despite the potential importance of HLA-C variation in psoriasis, either via an effect on peptide presentation or immuno-inhibitory activity, allele-specific expression patterns have not been investigated. Here, we used reporter assays to characterize two regulatory variants, which virtually abolished the response to tumor necrosis factor (TNF)-α (rs2524094) and IFN-γ (rs10657191) in HLA-Cw*0602 and a cluster of related alleles. We validated these findings through the analysis of HLA-Cw*0602 expression in primary keratinocytes treated with TNF-α and IFN-γ. Finally, we showed that HLA-Cw*0602 transcripts are not increased in psoriatic skin lesions, despite highly elevated TNF-α levels. Thus, our findings demonstrate the presence of allele-specific differences in HLA-C expression and indicate that HLA-Cw*0602 is unresponsive to upregulation by key proinflammatory cytokines in psoriasis. These data pave the way for functional studies into the pathogenic role of the major psoriasis susceptibility allele.

  16. CPAP treatment supported by telemedicine does not improve blood pressure in high cardiovascular risk OSA patients: a randomized, controlled trial.

    Science.gov (United States)

    Mendelson, Monique; Vivodtzev, Isabelle; Tamisier, Renaud; Laplaud, David; Dias-Domingos, Sonia; Baguet, Jean-Philippe; Moreau, Laurent; Koltes, Christian; Chavez, Léonidas; De Lamberterie, Gilles; Herengt, Frédéric; Levy, Patrick; Flore, Patrice; Pépin, Jean-Louis

    2014-11-01

    Obstructive sleep apnea (OSA) has been associated with hypertension, which is one of the intermediary mechanisms leading to increased cardiovascular morbidity. This study aimed at evaluating the effects of a combination of continuous positive airway pressure (CPAP) and telemedicine support on blood pressure (BP) reduction in high cardiovascular risk OSA patients. A multi-center randomized controlled trial that compared standard CPAP care and CPAP care and a telemedicine intervention. Sleep clinics in France. 107 adult (18-65 years old) OSA patients (AHI > 15 events/h) with a high cardiovascular risk (cardiovascular SCORE > 5% or secondary prevention). Patients were randomized to either standard care CPAP (n = 53) or CPAP and telemedicine (n = 54). Patients assigned to telemedicine were equipped with a smartphone for uploading BP measurements, CPAP adherence, sleepiness, and quality of life data; in return, they received pictograms containing health-related messages. The main outcome was home self-measured BP and secondary outcomes were cardiovascular risk evolution, objective physical activity, CPAP adherence, sleepiness and quality of life. Self-measured BP did not improve in either group (telemedicine or standard care). Patients in primary prevention showed greater BP reduction with CPAP treatment than those in secondary prevention. CPAP treatment supported by telemedicine alone did not improve blood pressure and cardiovascular risk in high cardiovascular risk OSA patients. This study emphasizes the need for diet and physical activity training programs in addition to CPAP when aiming at decreasing cardiometabolic risk factors in these patients. ClinicalTrials.gov identifier: NCT01226641.

  17. Community-Engaged Research to Identify House Parent Perspectives on Support and Risk within the House and Ball Scene

    Science.gov (United States)

    Kubicek, Katrina; Beyer, William H.; McNeeley, Miles; Weiss, George; Omni, Legendary Father Taz Ultra; Kipke, Michele D.

    2012-01-01

    This paper describes a community-engaged study with the Los Angeles House and Ball scene, in which the perspectives of the leaders of these communities are captured to better understand how the House and Ball communities may protect and/or increase its members’ risks for HIV infection. Data were collected through in-depth interviews with House parents (N=26). This study identified key features of both support (e.g., family and support; acceptance; validation and recognition) and risk (e.g., members’ struggle to maintain status in the Ballroom scene; sex work; substance use; danger of becoming too involved in the Ball community; perception and stigma of Ballroom scene within the larger gay community) within these communities. Findings are discussed in relation to framing how to leverage the supportive aspects of the House and Ball communities to design relevant HIV prevention interventions. PMID:22206442

  18. Human leukocyte antigen class I and II alleles and cervical adenocarcinoma: a pooled analysis of two epidemiologic studies

    Directory of Open Access Journals (Sweden)

    Mahboobeh eSafaeian

    2014-06-01

    Full Text Available Associations between human leukocyte antigens (HLA alleles and cervical cancer are largely representative of squamous cell carcinoma (SCC, the major histologic subtype. We evaluated the association between HLA class I (A, B, and C and class II (DRB1 and DQB1 loci and risk of cervical adenocarcinoma (ADC, a less common but aggressive histologic subtype.We pooled data from the Eastern and Western US cervical cancer studies, and evaluated the association between individual alleles and allele combinations and ADC (n=630 ADC; n=775 controls. Risk estimates were calculated for 11 a priori (based on known associations with cervical cancer regardless of histologic type and 38 non a priori common alleles, as odds ratios (OR and 95% confidence intervals (CI, adjusted for age and study. In exploratory analysis, we compared the risk associations between subgroups with HPV16 or HPV18 DNA in ADC tumor tissues in the Western US study cases and controls. Three of the a priori alleles were significantly associated with decreased risk of ADC (DRB1*13:01 (OR=0.61; 95%CI:0.41-0.93, DRB1*13:02 (OR=0.49; 95%CI:0.31-0.77, and DQB1*06:03 (OR=0.64; 95%CI:0.42-0.95; one was associated with increased risk (B*07:02(OR=1.39; 95%CI:1.07-1.79. Among alleles not previously reported, DQB1*06:04 (OR=0.46; 95%CI: 0.27-0.78 was associated with decreased risk of ADC and C*07:02 (OR=1.41; 95%CI:1.09-1.81 was associated with increased risk. We did not observe a difference by histologic subtype. ADC was most strongly associated with increased risk with B*07:02/C*07:02 alleles (OR=1.33; 95%CI:1.01-1.76 and decreased risk with DRB1*13:02/DQB1*06:04 (OR=0.41; 95%CI:0.21-0.80. Results suggest that HLA allele associations with cervical ADC are similar to those for cervical SCC. An intriguing finding was the difference in risk associated with several alleles restricted to HPV16 or HPV18 related tumors, consistent with the hypothesis that HLA recognition is HPV type specific.

  19. DQB1*06:02 allele-specific expression varies by allelic dosage, not narcolepsy status

    DEFF Research Database (Denmark)

    Weiner Lachmi, Karin; Lin, Ling; Kornum, Birgitte Rahbek

    2012-01-01

    The association of narcolepsy-cataplexy, a sleep disorder caused by the loss of hypocretin/orexin neurons in the hypothalamus, with DQA1*01:02-DQB1*06:02 is one of the tightest known single-allele human leukocyte antigen (HLA) associations. In this study, we explored genome-wide expression...

  20. Allelic database and accession divergence of a Brazilian mango collection based on microsatellite markers.

    Science.gov (United States)

    Dos Santos Ribeiro, I C N; Lima Neto, F P; Santos, C A F

    2012-12-19

    Allelic patterns and genetic distances were examined in a collection of 103 foreign and Brazilian mango (Mangifera indica) accessions in order to develop a reference database to support cultivar protection and breeding programs. An UPGMA dendrogram was generated using Jaccard's coefficients from a distance matrix based on 50 alleles of 12 microsatellite loci. The base pair number was estimated by the method of inverse mobility. The cophenetic correlation was 0.8. The accessions had a coefficient of similarity from 30 to 100%, which reflects high genetic variability. Three groups were observed in the UPGMA dendrogram; the first group was formed predominantly by foreign accessions, the second group was formed by Brazilian accessions, and the Dashehari accession was isolated from the others. The 50 microsatellite alleles did not separate all 103 accessions, indicating that there are duplicates in this mango collection. These 12 microsatellites need to be validated in order to establish a reliable set to identify mango cultivars.

  1. Analyses to support development of risk-informed separation distances for hydrogen codes and standards.

    Energy Technology Data Exchange (ETDEWEB)

    LaChance, Jeffrey L.; Houf, William G. (Sandia National Laboratories, Livermore, CA); Fluer, Inc., Paso Robels, CA; Fluer, Larry (Fluer, Inc., Paso Robels, CA); Middleton, Bobby

    2009-03-01

    The development of a set of safety codes and standards for hydrogen facilities is necessary to ensure they are designed and operated safely. To help ensure that a hydrogen facility meets an acceptable level of risk, code and standard development organizations are tilizing risk-informed concepts in developing hydrogen codes and standards.

  2. DTREEv2, a computer-based support system for the risk assessment of genetically modified plants

    NARCIS (Netherlands)

    Pertry, I.; Nothegger, C.; Sweet, J.; Kuiper, H.A.; Davies, H.; Iserentant, D.; Hull, R.; Mezzetti, B.; Messens, K.; Loose, De M.; Oliveira, de D.; Burssens, S.; Gheysen, G.; Tzotzos, G.

    2014-01-01

    Risk assessment of genetically modified organisms (GMOs) remains a contentious area and a major factor influencing the adoption of agricultural biotech. Methodologically, in many countries, risk assessment is conducted by expert committees with little or no recourse to databases and expert systems

  3. The Media and Genetically Modified Foods : Evidence in Support of Social Amplification of Risk

    NARCIS (Netherlands)

    Frewer, L.J.; Miles, S.; Marsh, R.

    2002-01-01

    Empirical examinations of the "social amplification of risk" framework are rare, partly because of the difficulties in predicting when conditions likely to result in amplification effects will occur. This means that it is difficult to examine changes in risk perception that are contemporaneous with

  4. Independent introduction of two lactase-persistence alleles into human populations reflects different history of adaptation to milk culture

    DEFF Research Database (Denmark)

    Enattah, Nabil Sabri; Jensen, Tine G K; Boyd, Mette

    2008-01-01

    the same history, probably related to the same cattle domestication event. In contrast, the compound Arab allele shows a different, highly divergent ancestral haplotype, suggesting that these two major global LP alleles have arisen independently, the latter perhaps in response to camel milk consumption....... These results support the convergent evolution of the LP in diverse populations, most probably reflecting different histories of adaptation to milk culture....

  5. Family support is not a risk factor of negative self-esteem in HIV/AIDS women

    Directory of Open Access Journals (Sweden)

    Jean Valeria

    2015-04-01

    Full Text Available Background Women with HIV/AIDS (WLWHA have a complex psychosocial burden and a tendency to negative self-esteem, possibly resulting in mental and emotional problems. They need family support to deal with the HIV/AIDS infection and its psychosocial burden. The purpose of this study was to determine chacteristics of family support, self-esteem, and depression of WLWHA and the relationship between family support and self-esteem and depression. Method This was a cross-sectional study of 99 WLWHA infected through their husbands/partners, with no history of drug abuse. The data was taken by a consecutive sampling of two proportions test at Dharmais Cancer Hospital from November 2013 – January 2014. The instruments comprised a demographic questionnaire, the Rosenberg Self-Esteem questionnaire, the Hamilton Depression Rating Scale (HDRS, and a family support questionnaire. The data was analyzed by binary logistic regression. Results There were 99 respondents with mean age of 36 years, of whom 44.4% were high school graduates, 54.5% unemployed, and 91.9% had HIV/AIDS for more than a year. Binary logistic regression analysis showed no significant relationship between family support and self-esteem (p=0.700 and depression (p=0.396. Good family support has a protective effect of 1.3 times (OR=0.772; 95%CI: 0.138-3.770 towards increasing self-esteem, whereas poor family support increases the risk of depression 1.5 times (OR=1.477; 95%CI: 0.598-3.645 in WLWHA infected with HIV/AIDS from their husband/partner. Conclusions Good family support tend to have a protective effect towards increasing self-esteem, whereas poor family support increases the risk of depression in WLWHA infected with HIV/AIDS from their husband/partner.

  6. Beliefs, barriers, social support, and environmental influences related to diabetes risk behaviours among women with a history of gestational diabetes.

    Science.gov (United States)

    Razee, Husna; van der Ploeg, Hidde P; Blignault, Ilse; Smith, Ben J; Bauman, Adrian E; McLean, Mark; Wah Cheung, N

    2010-08-01

    Women with previous gestational diabetes mellitus (GDM) are at increased risk of developing type 2 diabetes; this risk is higher in non-Caucasian women. This study explored the beliefs, attitudes, social support, environmental influences and other factors related to diabetes risk behaviours among Arabic, Cantonese/Mandarin, and English speaking women with recent GDM. Women living in the Sydney metropolitan area (Australia) who had GDM 6-36 months previously were included. In-depth semi-structured telephone interviews on women's experiences and perceptions of GDM and the lifestyle risk factors for developing type 2 diabetes were conducted in the language participants spoke at home (n=20 Arabic, 20 Cantonese/Mandarin, 17 English). Data were analysed for underlying themes using NVivo software. Mental distress, role perceptions, social support and cultural expectations were major issues related to women's struggles to find the right balance between the large proportion of household and child care responsibilities and leading a healthy lifestyle. Women's ability to follow a healthy lifestyle is embedded in their psychological wellbeing and the social and cultural context of their lives. The study highlights the need for a holistic approach that ensures personal support and access to services as well as lifestyle specific programs.

  7. RISICO: A decision support system (DSS) for dynamic wildfire risk evaluation in Italy

    Science.gov (United States)

    D'Andrea, Mirko; Fiorucci, Paolo; Gaetani, Francesco; Negro, Dario

    2010-05-01

    The system RISICO provides Italian Civil Protection Department (DPC) with daily wildland fire risk forecast maps relevant to the whole national territory since 2003. RISICO support the activities relating to Italian national forest fires warning system and National fires fighting air fleet. The RISICO system has a complex software architecture based on a framework able to manage geospatial data as well as time dependent information (e.g, Numerical Weather Prediction, real time meteorological observations, and satellite data). Within the system semi-physical models, able to simulate in space and time the variability of the fuel moisture content, are implemented. This parameter represents the main variable related with the ignition of a fire. Based on this information and introducing information on topography and wind field the model provides the rate of spread and the linear intensity of a potential fire generated by accidental or deliberate ignition. The model takes into account the vegetation patterns, in terms of fuel load and flammability. It needs territorial and meteorological data. Territorial data used by the system are vegetation cover and topography. Meteorological data are mainly represented by Numerical Weather Prediction (Limited Area model). Meteorological data provided in real time by a meteorological network are also used by the model as well as satellite data (e.g., vegetation index, snow cover). The output information are provided on a web-gis based system according with the OGC-INSPIRE standard. In 2007 the system has been improved introducing some changes both in the model structure and its functionality. Spatial resolution is increased up to 100m in the implementation at regional level. The fine fuel moisture model has been changed, introducing the FFMC of the CFFDRS with some slightly differences. In addition, a different nominal rate of spread (no-wind on flat terrain) has been introduced for each different class of vegetation. The operational

  8. Association of primary biliary cirrhosis with the allele HLA-DPB1*0301 in a German population.

    Science.gov (United States)

    Mella, J G; Roschmann, E; Maier, K P; Volk, B A

    1995-02-01

    The major histocompatibility complex class II alleles at the HLA-DPB1 locus were investigated in 32 German Caucasoid patients with primary biliary cirrhosis (PBC) and compared with those from 47 normal control patients using molecular genotyping techniques. The second exon of the HLA-DPB1 gene was amplified by polymerase chain reaction (PCR) and hybridized with 25 sequence-specific oligonucleotides (SSOs) to assign the HLA-DPB1 alleles on the basis of known sequence variations, according to the protocols of the Eleventh International Histocompatibility Workshop. A strong association of PBC was found with the allele HLA-DPB1*0301. The allele HLA DPB1*0301 was present in 50% (16 of 32) of the patients with PBC compared with 13% (6 of 47) of normal controls (P corrected < .015), whereas the other HLA-DPB1 alleles showed no significant differences in both groups. The relative risk (RR) estimate for the allele HLA-DPB1*0301 was 6.8 (95% confidence limits: 2.27 to 20.57). In summary, this study clearly demonstrates an association of PBC with the HLA-DPB1*0301 allele in German Caucasoids and may add new data to the immunogenetic background of PBC, suggesting a contribution of the HLA-DPB1 gene to the genetic susceptibility of the disease.

  9. Nitric oxide synthase gene G298 allele

    International Nuclear Information System (INIS)

    Nagib El-Kilany, Galal E.; Nayel, Ehab; Hazzaa, Sahar

    2004-01-01

    Background: Nitric oxide (NO) has an important effect on blood pressure, arterial wall, and the basal release of endothelial NO in hypertension (HPN) may be reduced. Until now, there is no solid data revealing the potential role of the polymorphism of the nitric oxide synthase gene (NOS) in patients with HPN and microvascular angina. Aim: The aim of the present study is to investigate the gene of endothelial nitric oxide synthase (eNOS), as the polymorphism of this gene may be a putative candidate for HPN and initiate the process of atherosclerosis. Methods: Sixty participants were recruited for this study; 50 were hypertensive patients complaining of chest pain [30 of them have electrocardiogram (EKG) changes of ischemia], 20 had isolated HPN, and 10 healthy volunteers served as control. All patients underwent stress myocardial perfusion imaging (MPI) and coronary angiography. Genotyping of eNOS for all patients and controls was performed. The linkages between HPN, microvascular angina and eNOS gene polymorphism were investigated. Results: MPI and coronary angiography revealed that 15 patients had chest pain with true ischemia and reversible myocardial perfusion defects (multiple and mild) but normal epicardial coronary arteries (microvascular angina), while 15 patients had significant coronary artery disease (CAD), and 20 hypertensive patients showed normal perfusion scan and coronary angiography. The prevalence of the NOS G 298 allele was higher in the hypertensive group with microvascular angina (documented by MPI) than it was among the control participants (P<.005). The eNOS allele was significantly higher in the hypertensive group than in the control participants, but there was no significant difference in homozygote mutants among hypertensive participants, x-syndrome and patients with CAD. Conclusion: eNOS gene polymorphism is proved to be an important etiology in microvascular angina (x-syndrome) among hypertensive patients. In addition, the eNOS mutant

  10. New technologies for the support of risk management. A systems-engineering point of view for the creation of risk information systems

    International Nuclear Information System (INIS)

    Beroggi, G.E.G.

    1995-01-01

    Within the framework of the poly project, the partial project 'Methodical Fundamentals and Computer Supported Risk Management' has developed two RISs (Risk Information Systems). The aim of the present book is to present the viewpoints gained in these new technologies and model formation attempts with which new RISs can be conceived and created. Because of the numerous new attempts, a compromise had to be made between the breadth and depth of the discussions whereby the breadth was preferred; which means that the aim is to define the broad range of RIS development as comprehensively as possible. The reader is meant to be motivated to think about the new technologies and their role in risk management. figs., tabs., refs

  11. Family Support in Prevention Programs for Children at Risk for Emotional/Behavioral Problems

    Science.gov (United States)

    Cavaleri, Mary A.; Olin, S. Serene; Kim, Annie; Hoagwood, Kimberly E.; Burns, Barbara J.

    2011-01-01

    We conducted a review of empirically based prevention programs to identify prevalence and types of family support services within these programs. A total of 238 articles published between 1990 and 2011 that included a family support component were identified; 37 met criteria for inclusion. Following the Institute of Medicine's typology, prevention…

  12. Integrating climatic and fuels information into National Fire Risk Decision Support Tools

    Science.gov (United States)

    W. Cooke; V. Anantharaj; C. Wax; J. Choi; K. Grala; M. Jolly; G.P. Dixon; J. Dyer; D.L. Evans; G.B. Goodrich

    2007-01-01

    The Wildland Fire Assessment System (WFAS) is a component of the U.S. Department of Agriculture, Forest Service Decision Support Systems (DSS) that support fire potential modeling. Fire potential models for Mississippi and for Eastern fire environments have been developed as part of a National Aeronautic and Space Agency-funded study aimed at demonstrating the utility...

  13. Genome-Wide Supported Risk Variants in MIR137, CACNA1C, CSMD1, DRD2, and GRM3 Contribute to Schizophrenia Susceptibility in Pakistani Population

    DEFF Research Database (Denmark)

    Fatima, Ambrin; Farooq, Muhammad; Abdullah, Uzma

    2017-01-01

    calculated using SPSS. RESULTS: A significant difference in the genotype and allele frequencies for rs4765905, rs1076560 and rs6465084 were found between the patients and controls (p=0.000). CONCLUSION: This study provides substantial evidence supporting the role of CACNA1C, GRM3 and DRD2 as schizophrenia...

  14. Analyses in support of risk-informed natural gas vehicle maintenance facility codes and standards :

    Energy Technology Data Exchange (ETDEWEB)

    Ekoto, Isaac W.; Blaylock, Myra L.; LaFleur, Angela Christine; LaChance, Jeffrey L.; Horne, Douglas B.

    2014-03-01

    Safety standards development for maintenance facilities of liquid and compressed gas fueled large-scale vehicles is required to ensure proper facility design and operation envelopes. Standard development organizations are utilizing risk-informed concepts to develop natural gas vehicle (NGV) codes and standards so that maintenance facilities meet acceptable risk levels. The present report summarizes Phase I work for existing NGV repair facility code requirements and highlights inconsistencies that need quantitative analysis into their effectiveness. A Hazardous and Operability study was performed to identify key scenarios of interest. Finally, scenario analyses were performed using detailed simulations and modeling to estimate the overpressure hazards from HAZOP defined scenarios. The results from Phase I will be used to identify significant risk contributors at NGV maintenance facilities, and are expected to form the basis for follow-on quantitative risk analysis work to address specific code requirements and identify effective accident prevention and mitigation strategies.

  15. Organizational leadership, health risk screening, individually tailored programs, and supportive workplace culture might reduce presenteeism

    NARCIS (Netherlands)

    E. Steultjens; E. Baker; N. Aas; W. Randi

    2012-01-01

    To determine if Workplace Health Promotion programs (WHPs) are effective in improving presenteeism. The secondary objective was to identify characteristics of successful programmes and potential risk factors for presenteeism. The Cochrane Library, Medline and other electronic databases were searched

  16. Human Reliability Analysis in Support of Risk Assessment for Positive Train Control

    Science.gov (United States)

    2003-06-01

    This report describes an approach to evaluating the reliability of human actions that are modeled in a probabilistic risk assessment : (PRA) of train control operations. This approach to human reliability analysis (HRA) has been applied in the case o...

  17. A Bayesian Network methodology for railway risk, safety and decision support

    OpenAIRE

    Mahboob, Qamar

    2014-01-01

    For railways, risk analysis is carried out to identify hazardous situations and their consequences. Until recently, classical methods such as Fault Tree Analysis (FTA) and Event Tree Analysis (ETA) were applied in modelling the linear and logically deterministic aspects of railway risks, safety and reliability. However, it has been proven that modern railway systems are rather complex, involving multi-dependencies between system variables and uncertainties about these dependencies. For train ...

  18. A risk based model supporting long term maintenance and reinvestment strategy decision making

    Energy Technology Data Exchange (ETDEWEB)

    Sand, Kjell; Montard, Julien; Tremoen, Tord H.

    2010-02-15

    This Technical Report is a product from the project Risk-Based Distribution System Asset Management (short: RISK DSAM) - Work Package 3 Risk exposure on company/strategic level. In the report a concept for portfolio distribution system asset management is presented. The approach comprises four main steps: 1. Decide the asset base. 2. Divide the asset base into relevant archetypes. 3. Develop or select relevant maintenance and reinvestment strategies for the different archetypes. 4. Estimate risks and costs for each archetype for the relevant strategies. For the different steps guidelines are given and a proposal for implementation of the concept is given in terms of a proposed IT system architecture.To evaluate the feasibility of such a concept, a prototype was developed in by using Visual Basic macros in Excel using real technical data from a small DSO. The experience from using the prototype shows that the concept is realistic. All assets are included and depending of the ambition of the risk analysis both simple simulation models and more advanced might be embedded. Presentations of the concept for a utility engineers have receive positive feedback indicating that the concept is regarded as a practical way to develop risk based asset management strategies for the asset fleet. It should be noted that the concept should be applied on a company strategic level and is thus not designed to be applied for a specific project or asset decisions. For this, more detailed models with area specific information, topology etc. are needed. (Author)

  19. Investment Decision Support for Engineering Projects Based on Risk Correlation Analysis

    Directory of Open Access Journals (Sweden)

    Yan Liu

    2012-01-01

    Full Text Available Investment decisions are usually made on the basis of the subjective judgments of experts subjected to the information gap during the preliminary stages of a project. As a consequence, a series of errors in risk prediction and/or decision-making will be generated leading to out of control investment and project failure. In this paper, the variable fuzzy set theory and intelligent algorithms integrated with case-based reasoning are presented. The proposed algorithm manages the numerous fuzzy concepts and variable factors of a project and also sets up the decision-making process in accordance with past cases and experiences. Furthermore, it decreases the calculation difficulty and reduces the decision-making reaction time. Three types of risk correlations combined with different characteristics of engineering projects are summarized, and each of these correlations is expounded at the project investment decision-making stage. Quantitative and qualitative change theories of variable fuzzy sets are also addressed for investment risk warning. The approach presented in this paper enables the risk analysis in a simple and intuitive manner and realizes the integration of objective and subjective risk assessments within the decision-makers' risk expectation.

  20. Experiences in reconciling risk management and restorative justice: how circles of support and accountability work restoratively in the risk society.

    Science.gov (United States)

    Hannem, Stacey

    2013-03-01

    Circles of Support and Accountability (COSA) is a restorative justice-based model that originated in Canada in the mid-1990s for the postincarceration reintegration of those who have offended sexually. Although the roots of COSA are in restorative justice philosophy, the program has also found favour, to some degree, with organisations such as police services and corrections that are traditionally concerned more with protecting community safety than with the ideals of restorative justice. Informed by the author's research and personal experience as a COSA volunteer, and analysis of recent and historical representations of COSA, this article explores theoretically how the development of the COSA initiative has been influenced by the seemingly disparate concerns of both the restorative justice and community protection movements, and examines the importance of balancing these paradigms in the everyday practices of circles.

  1. FY12 ARRA-NRAP Report – Studies to Support Risk Assessment of Geologic Carbon Sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Cantrell, Kirk J.; Shao, Hongbo; Thompson, C. J.; Zhong, Lirong; Jung, Hun Bok; Um, Wooyong

    2011-09-27

    This report summarizes results of research conducted during FY2012 to support the assessment of environmental risks associated with geologic carbon dioxide (CO2) sequestration and storage. Several research focus areas are ongoing as part of this project. This includes the quantification of the leachability of metals and organic compounds from representative CO2 storage reservoir and caprock materials, the fate of metals and organic compounds after release, and the development of a method to measure pH in situ under supercritical CO2 (scCO2) conditions. Metal leachability experiments were completed on 6 different rock samples in brine in equilibrium with scCO2 at representative geologic reservoir conditions. In general, the leaching of RCRA metals and other metals of concern was found to be limited and not likely to be a significant issue (at least, for the rocks tested). Metals leaching experiments were also completed on 1 rock sample with scCO2 containing oxygen at concentrations of 0, 1, 5, and 10% to simulate injection of CO2 originating from the oxy-fuel combustion process. Significant differences in the leaching behavior of certain metals were observed when oxygen is present in the CO2. These differences resulted from oxidation of sulfides, release of sulfate, ferric iron and other metals, and subsequent precipitation of iron oxides and some sulfates such as barite. Experiments to evaluate the potential for mobilization of organic compounds from representative reservoir materials and cap rock and their fate in porous media (quartz sand) have been conducted. Results with Fruitland coal and Gothic shale indicate that lighter organic compounds were more susceptible to mobilization by scCO2 compared to heavier compounds. Alkanes demonstrated very low extractability by scCO2. No significant differences were observed between the extractability of organic compounds by dry or water saturated scCO2. Reaction equilibrium appears to have been reached by 96 hours. When

  2. A rare FANCA gene variation as a breast cancer susceptibility allele in an Iranian population.

    Science.gov (United States)

    Abbasi, Sakineh; Rasouli, Mina

    2017-06-01

    Fanconi Anemia (FA) is an autosomal recessive syndrome characterized by congenital abnormalities, progressive bone marrow failure and Fanconi anemia complementation group A (FANCA) is also a potential breast and ovarian cancer susceptibility gene. A novel allele with tandem duplication of 13 base pair sequence in promoter region was identified. To investigate whether the 13 base pair sequence of tandem duplication in promoter region of the FANCA gene is of high penetrance in patients with breast cancer and to determine if the presence of the duplicated allele was associated with an altered risk of breast cancer, the present study screened DNA in blood samples from 304 breast cancer patients and 295 normal individuals as controls. The duplication allele had a frequency of 35.4 and 21.2% in patients with breast cancer and normal controls, respectively. There was a significant increase in the frequency of the duplication allele in patients with familial breast cancer compared with controls (45.1%, P=0.001). Furthermore, the estimated risk of breast cancer in individuals with a homozygote [odds ratio (OR), 4.093; 95% confidence intervals (CI), 1.957‑8.561] or heterozygote duplicated genotype (OR, 3.315; 95% CI, 1.996‑5.506) was higher compared with the corresponding normal homozygote genotype. In conclusion, the present study indicated that the higher the frequency of the duplicated allele, the higher the risk of breast cancer. To the best of our knowledge, the present study is the first to report FANCA gene duplication in patients with breast cancer.

  3. Allele Frequency - JSNP | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available nd 39 SNPs are assayed in three (POP_*) and two (RIKEN_japanese_*) panels, respectively. Derived from Flat f... assay (JBIC-allele and RIKEN_japanese_*), TaqMan assay (RIKEN-allele) or direct sequencing / allelic discri...unteers under informed consent RIKEN_japanese_normal_weight - 711 unrelated japanese normal weight volunteer...s ( body mass index RIKEN_japanese_obese - 796 unrelated japanese obese patients

  4. Nurturing transdisciplinary research - lessons from live experiments in prioritising and supporting novel risk science (Invited)

    Science.gov (United States)

    Rees, J.; Armstrong, C.; Barclay, J.; Moores, A.; Whitaker, D.

    2013-12-01

    The benefits of specialization over the last 150 years have meant that science has evolved within several distinct disciplines, such as physical, social or environmental. These have generated their own cultures, languages, agendas, institutions, measures of success and cohorts of suitably branded scientists. However, we increasingly see that society and the environment are exposed to many complex, interdependent and rapidly changing risks - not only from natural hazards, but also those associated with fast expanding and ageing populations, highly interconnected and interdependent economies, rapid climate change, and increasingly limited resources. Risks derived from such interacting drivers commonly generate non-linear effects or repercussions and future risks may be very different to those of today; significantly, they span many traditional science disciplines. We thus need to have a fresh look at transdisciplinary risk science, bring in novel ideas and new blood. But what are the best practical ways of sowing the seeds and fertilizing such approaches? The presentation describes novel practical steps to achieve this, all related to building and resourcing transdisciplinary research which incorporates natural hazard science within the UK over the last 5 years. These comprise instruments to prioritise science gaps and provide funding for transdisciplinary research by a) Academic research funders - the Research Councils UK (RCUK) Risk Research Network and current research programmes; b) Government and non-governmental research funders - the Living with Environmental Change Initiative, and the UK Flooding and coastal erosion risk management research strategy - and the UK Collaborative for Development Science sponsored Disasters Research Group; and c) Business funding - through integrated risk modelling for the insurance industry. Whilst young, all these initiatives are healthy and seek to build a portfolio of small scale initiatives that will breed success and develop

  5. Database for the ampC alleles in Acinetobacter baumannii.

    Directory of Open Access Journals (Sweden)

    Nabil Karah

    Full Text Available Acinetobacter baumannii is a troublesome opportunistic pathogen with a high capacity for clonal dissemination. We announce the establishment of a database for the ampC locus in A. baumannii, in which novel ampC alleles are differentiated based on the occurrence of ≥ 1 nucleotide change, regardless of whether it is silent or missense. The database is openly accessible at the pubmlst platform for A. baumannii (http://pubmlst.org/abaumannii/. Forty-eight distinctive alleles of the ampC locus have so far been identified and deposited in the database. Isolates from clonal complex 1 (CC1, according to the Pasteur multilocus sequence typing scheme, had a variety of the ampC locus alleles, including alleles 1, 3, 4, 5, 6, 7, 8, 13, 14, 17, and 18. On the other hand, isolates from CC2 had the ampC alleles 2, 3, 19, 20, 21, 22, 23, 24, 26, 27, 28, and 46. Allele 3 was characteristic for sequence types ST3 or ST32. The ampC alleles 10, 16, and 25 were characteristic for CC10, ST16, and CC25, respectively. Our study points out that novel gene databases, in which alleles are numbered based on differences in their nucleotide identities, should replace traditional records that use amino acid substitutions to define new alleles.

  6. Disentangling the influence of value predispositions and risk/benefit perceptions on support for nanotechnology among the American public.

    Science.gov (United States)

    Kim, Jiyoun; Yeo, Sara K; Brossard, Dominique; Scheufele, Dietram A; Xenos, Michael A

    2014-05-01

    Using nanotechnology as a case study, this article explores (1) how people's perceptions of benefits and risks are related to their approval of nanotechnology, (2) which information-processing factors contribute to public risk/benefit perceptions, and (3) whether individuals' predispositions (i.e., deference to scientific authority and ideology) may moderate the relationship between cognitive processing and risk perceptions of the technology. Results indicate that benefit perceptions positively affect public support for nanotechnology; perceptions of risk tend to be more influenced by systematic processing than by heuristic cues, whereas both heuristic and systematic processing influence benefit perceptions. People who are more liberal-minded tend to be more affected by systematic processing when thinking about the benefits of nanotechnology than those who are more conservative. Compared to less deferent individuals, those who are more deferent to scientific authority tend to be less influenced by systematic processing when making judgments about the benefits and risks of nanotechnology. Implications are discussed. © 2013 Society for Risk Analysis.

  7. The Microcephalin Ancestral Allele in a Neanderthal Individual

    Science.gov (United States)

    Lari, Martina; Rizzi, Ermanno; Milani, Lucio; Corti, Giorgio; Balsamo, Carlotta; Vai, Stefania; Catalano, Giulio; Pilli, Elena; Longo, Laura; Condemi, Silvana; Giunti, Paolo; Hänni, Catherine; De Bellis, Gianluca; Orlando, Ludovic; Barbujani, Guido; Caramelli, David

    2010-01-01

    Background The high frequency (around 0.70 worlwide) and the relatively young age (between 14,000 and 62,000 years) of a derived group of haplotypes, haplogroup D, at the microcephalin (MCPH1) locus led to the proposal that haplogroup D originated in a human lineage that separated from modern humans >1 million years ago, evolved under strong positive selection, and passed into the human gene pool by an episode of admixture circa 37,000 years ago. The geographic distribution of haplogroup D, with marked differences between Africa and Eurasia, suggested that the archaic human form admixing with anatomically modern humans might have been Neanderthal. Methodology/Principal Findings Here we report the first PCR amplification and high- throughput sequencing of nuclear DNA at the microcephalin (MCPH1) locus from Neanderthal individual from Mezzena Rockshelter (Monti Lessini, Italy). We show that a well-preserved Neanderthal fossil dated at approximately 50,000 years B.P., was homozygous for the ancestral, non-D, allele. The high yield of Neanderthal mtDNA sequences of the studied specimen, the pattern of nucleotide misincorporation among sequences consistent with post-mortem DNA damage and an accurate control of the MCPH1 alleles in all personnel that manipulated the sample, make it extremely unlikely that this result might reflect modern DNA contamination. Conclusions/Significance The MCPH1 genotype of the Monti Lessini (MLS) Neanderthal does not prove that there was no interbreeding between anatomically archaic and modern humans in Europe, but certainly shows that speculations on a possible Neanderthal origin of what is now the most common MCPH1 haplogroup are not supported by empirical evidence from ancient DNA. PMID:20498832

  8. The microcephalin ancestral allele in a Neanderthal individual.

    Directory of Open Access Journals (Sweden)

    Martina Lari

    Full Text Available BACKGROUND: The high frequency (around 0.70 worldwide and the relatively young age (between 14,000 and 62,000 years of a derived group of haplotypes, haplogroup D, at the microcephalin (MCPH1 locus led to the proposal that haplogroup D originated in a human lineage that separated from modern humans >1 million years ago, evolved under strong positive selection, and passed into the human gene pool by an episode of admixture circa 37,000 years ago. The geographic distribution of haplogroup D, with marked differences between Africa and Eurasia, suggested that the archaic human form admixing with anatomically modern humans might have been Neanderthal. METHODOLOGY/PRINCIPAL FINDINGS: Here we report the first PCR amplification and high-throughput sequencing of nuclear DNA at the microcephalin (MCPH1 locus from Neanderthal individual from Mezzena Rockshelter (Monti Lessini, Italy. We show that a well-preserved Neanderthal fossil dated at approximately 50,000 years B.P., was homozygous for the ancestral, non-D, allele. The high yield of Neanderthal mtDNA sequences of the studied specimen, the pattern of nucleotide misincorporation among sequences consistent with post-mortem DNA damage and an accurate control of the MCPH1 alleles in all personnel that manipulated the sample, make it extremely unlikely that this result might reflect modern DNA contamination. CONCLUSIONS/SIGNIFICANCE: The MCPH1 genotype of the Monti Lessini (MLS Neanderthal does not prove that there was no interbreeding between anatomically archaic and modern humans in Europe, but certainly shows that speculations on a possible Neanderthal origin of what is now the most common MCPH1 haplogroup are not supported by empirical evidence from ancient DNA.

  9. U.S. Support for Baltic Republic Membership in NATO: What Ends, What Risks

    National Research Council Canada - National Science Library

    Meyer, Kent

    2000-01-01

    .... President Clinton has declared, through the U.S. National Security Strategy, his administration's support for NATO enlargement to well qualified democracies regardless of geography or history, including those in northeastern Europe. U.S...

  10. Ecotoxicogenomics to Support Ecological Risk Assessment: A Case Study with Bisphenol A in Fish

    Science.gov (United States)

    Toxicogenomic approaches are being increasingly applied in the field of ecotoxicology. Given the growing availability of ecotoxicogenomic data, the Agency and the broader scientific community are actively engaged in considering how best to use those data to support ecological ris...

  11. A Two-Layer Least Squares Support Vector Machine Approach to Credit Risk Assessment

    Science.gov (United States)

    Liu, Jingli; Li, Jianping; Xu, Weixuan; Shi, Yong

    Least squares support vector machine (LS-SVM) is a revised version of support vector machine (SVM) and has been proved to be a useful tool for pattern recognition. LS-SVM had excellent generalization performance and low computational cost. In this paper, we propose a new method called two-layer least squares support vector machine which combines kernel principle component analysis (KPCA) and linear programming form of least square support vector machine. With this method sparseness and robustness is obtained while solving large dimensional and large scale database. A U.S. commercial credit card database is used to test the efficiency of our method and the result proved to be a satisfactory one.

  12. Risks Associated with Fresh Whole Blood and Red Blood Cell Transfusions in a Combat Support Hospital

    National Research Council Canada - National Science Library

    Spinella, Philip C; Perkins, Jeremy G; Grathwohl, Kurt W; Repine, Thomas; Beekley, Alec C; Sebesta, James; Jenkins, Donald; Azarow, Kenneth; Holcomb, John B

    2007-01-01

    .... Between April 2004 and December 2004, FWB was prescreened only at one combat support hospital for human immunodeficiency virus, hepatitis C virus, and hepatitis B surface antigen before transfusion...

  13. Risk-informed profitability-based analysis support of nuclear power station balance-of-plant change management

    Energy Technology Data Exchange (ETDEWEB)

    Liming, J.K. [EQE International, Inc., An ABS Group Company, Irvine, CA (United States); Kee, E.J.; Grantom, C.R.; Richards, A.M. [STP Nuclear Operating Company, Wadsworth, TX (United States)

    2001-07-01

    In this paper, a three-phased method is proposed for the STP Nuclear Operating Company (STPNOC) Risk and Reliability Analysis Section (RRA) to perform analyses and decision-making support for the STPNOC Balance-of-Plant (BOP)Task Force in managing change to simultaneously optimize plant safety and maximize long-term return-on-asset (or profitability) for the South Texas Project Electric Generating Station (STPEGS). (authors)

  14. Risk stratification in patients with advanced heart failure requiring biventricular assist device support as a bridge to cardiac transplantation.

    Science.gov (United States)

    Cheng, Richard K; Deng, Mario C; Tseng, Chi-hong; Shemin, Richard J; Kubak, Bernard M; MacLellan, W Robb

    2012-08-01

    Prior studies have identified risk factors for survival in patients with end-stage heart failure (HF) requiring left ventricular assist device (LVAD) support. However, patients with biventricular HF may represent a unique cohort. We retrospectively evaluated a consecutive cohort of 113 adult, end-stage HF patients at University of California Los Angeles Medical Center who required BIVAD support between 2000 and 2009. Survival to transplant was 66.4%, with 1-year actuarial survival of 62.8%. All patients were Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Level 1 or 2 and received Thoratec (Pleasanton, CA) paracorporeal BIVAD as a bridge to transplant. Univariate analyses showed dialysis use, ventilator use, extracorporal membrane oxygenation use, low cardiac output, preserved LV ejection fraction (restrictive physiology), normal-to-high sodium, low platelet count, low total cholesterol, low high-density and high-density lipoprotein, low albumin, and elevated aspartate aminotransferase were associated with increased risk of death. We generated a scoring system for survival to transplant. Our final model, with age, sex, dialysis, cholesterol, ventilator, and albumin, gave a C-statistic of 0.870. A simplified system preserved a C-statistic of 0.844. Patients were divided into high-risk or highest-risk groups (median respective survival, 367 and 17 days), with strong discrimination between groups for death. We have generated a scoring system that offers high prognostic ability for patients requiring BIVAD support and hope that it may assist in clinical decision making. Further studies are needed to prospectively validate our scoring system. Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  15. Risk-informed profitability-based analysis support of nuclear power station balance-of-plant change management

    International Nuclear Information System (INIS)

    Liming, J.K.; Kee, E.J.; Grantom, C.R.; Richards, A.M.

    2001-01-01

    In this paper, a three-phased method is proposed for the STP Nuclear Operating Company (STPNOC) Risk and Reliability Analysis Section (RRA) to perform analyses and decision-making support for the STPNOC Balance-of-Plant (BOP)Task Force in managing change to simultaneously optimize plant safety and maximize long-term return-on-asset (or profitability) for the South Texas Project Electric Generating Station (STPEGS). (authors)

  16. Effect of peer support on prevention of postnatal depression among high risk women: multisite randomised controlled trial.

    Science.gov (United States)

    Dennis, C-L; Hodnett, E; Kenton, L; Weston, J; Zupancic, J; Stewart, D E; Kiss, A

    2009-01-15

    To evaluate the effectiveness of telephone based peer support in the prevention of postnatal depression. Multisite randomised controlled trial. Seven health regions across Ontario, Canada. 701 women in the first two weeks postpartum identified as high risk for postnatal depression with the Edinburgh postnatal depression scale and randomised with an internet based randomisation service. Proactive individualised telephone based peer (mother to mother) support, initiated within 48-72 hours of randomisation, provided by a volunteer recruited from the community who had previously experienced and recovered from self reported postnatal depression and attended a four hour training session. Edinburgh postnatal depression scale, structured clinical interview-depression, state-trait anxiety inventory, UCLA loneliness scale, and use of health services. After web based screening of 21 470 women, 701 (72%) eligible mothers were recruited. A blinded research nurse followed up more than 85% by telephone, including 613 at 12 weeks and 600 at 24 weeks postpartum. At 12 weeks, 14% (40/297) of women in the intervention group and 25% (78/315) in the control group had an Edinburgh postnatal depression scale score >12 (chi(2)=12.5, P<0.001; number need to treat 8.8, 95% confidence interval 5.9 to 19.6; relative risk reduction 0.46, 95% confidence interval 0.24 to 0.62). There was a positive trend in favour of the intervention group for maternal anxiety but not loneliness or use of health services. For ethical reasons, participants identified with clinical depression at 12 weeks were referred for treatment, resulting in no differences between groups at 24 weeks. Of the 221 women in the intervention group who received and evaluated their experience of peer support, over 80% were satisfied and would recommend this support to a friend. Telephone based peer support can be effective in preventing postnatal depression among women at high risk. ISRCTN 68337727.

  17. Modeling Decision Support and Uncertainty using @RISK: The COSIMA-ROAD Model

    DEFF Research Database (Denmark)

    Salling, Kim Bang; Leleur, Steen

    This paper concerns a newly developed software model called COSIMA-ROAD for project evaluation in the Danish road sector. COSIMA-ROAD is developed as a combined effort in co-operation between the Danish Road Directorate and the Technical University of Denmark. The applied case study is developed...... by the Danish Road Directorate. The main purpose of this paper is primarily to describe how @RISK is used in COSIMA-ROAD. First the two main modules of COSIMA-ROAD are described as respectively a traditional cost-benefit analysis (deterministic point estimate) and a risk analysis using Monte Carlo Simulation...

  18. A 24-h a la carte food service as support for patients at nutritional risk

    DEFF Research Database (Denmark)

    Munk, T; Seidelin, Winnie; Rosenbom, E

    2013-01-01

    Undernutrition and insufficient energy and protein intake is a common problem in hospitalised patients. The aim of this pilot study was to investigate whether a novel hospital menu would be an effective strategy for increasing nutritional intake in patients at nutritional risk.......Undernutrition and insufficient energy and protein intake is a common problem in hospitalised patients. The aim of this pilot study was to investigate whether a novel hospital menu would be an effective strategy for increasing nutritional intake in patients at nutritional risk....

  19. Risk Communication in EPA's Controlled Inhalation Exposure Studies and in Support.

    Science.gov (United States)

    Resnik, David

    2017-01-01

    On March 28, 2017, the National Academy of Sciences, Engineering, and Medicine (NASEM) released a much-anticipated report on the Environmental Protection Agency's controlled human inhalation exposure studies. This essay reviews the ethical controversies that led to the genesis of the report, summarizes its key findings, and comments on its approach to informing human subjects about the risks of inhalation exposure studies. NASEM's report makes a valuable contribution to our understanding of the scientific and ethical issues involved in conducting human inhalation exposure studies. Its definition of "reasonably foreseeable risks" provides useful guidance to investigators, research participants, and institutional review board members.

  20. System robustness analysis in support of flood and drought risk management

    CERN Document Server

    Mens, MJP

    2015-01-01

    Floods and droughts have an increasing impact on societies worldwide. It is unlikely that the provision of flood protection infrastructure and reservoirs will eliminate this problem, especially as extreme events are expected to increase in probability and magnitude as a result of climate change. For this reason, the focus of water management has shifted to a risk-based approach in recent years; but this also has its limitations.This book examines system robustness as a new perspective on flood and drought risk management. The concept of robustness is familiar from other areas, such as engineer

  1. Friendships and Family Support Reduce Subsequent Depressive Symptoms in At-Risk Adolescents.

    Directory of Open Access Journals (Sweden)

    Anne-Laura van Harmelen

    Full Text Available Early life stress (ELS consists of child family adversities (CFA: negative experiences that happened within the family environment and/or peer bullying. ELS plays an important role in the development of adolescent depressive symptoms and clinical disorders. Identifying factors that may reduce depressive symptoms in adolescents with ELS may have important public mental health implications.We used structural equation modelling and examined the impact of adolescent friendships and/or family support at age 14 on depressive symptoms at age 17 in adolescents exposed to ELS before age 11. To this end, we used structural equation modelling in a community sample of 771 adolescents (322 boys and 477 girls from a 3 year longitudinal study. Significant paths in the model were followed-up to test whether social support mediated or moderated the association between ELS and depressive symptoms at age 17.We found that adolescent social support in adolescence is negatively associated with subsequent depressive symptoms in boys and girls exposed to ELS. Specifically, we found evidence for two mediational pathways: In the first pathway family support mediated the link between CFA and depressive symptoms at age 17. Specifically, CFA was negatively associated with adolescent family support at age 14, which in turn was negatively associated with depressive symptoms at age 17. In the second pathway we found that adolescent friendships mediated the path between peer bullying and depressive symptoms. Specifically, relational bullying was negatively associated with adolescent friendships at age 14, which in turn were negatively associated with depressive symptoms at age 17. In contrast, we did not find a moderating effect of friendships and family support on the association between CFA and depressive symptoms.Friendships and/or family support in adolescence mediate the relationship between ELS and late adolescent depressive symptoms in boys and girls. Therefore

  2. Tumor transcriptome sequencing reveals allelic expression imbalances associated with copy number alterations.

    Directory of Open Access Journals (Sweden)

    Brian B Tuch

    Full Text Available Due to growing throughput and shrinking cost, massively parallel sequencing is rapidly becoming an attractive alternative to microarrays for the genome-wide study of gene expression and copy number alterations in primary tumors. The sequencing of transcripts (RNA-Seq should offer several advantages over microarray-based methods, including the ability to detect somatic mutations and accurately measure allele-specific expression. To investigate these advantages we have applied a novel, strand-specific RNA-Seq method to tumors and matched normal tissue from three patients with oral squamous cell carcinomas. Additionally, to better understand the genomic determinants of the gene expression changes observed, we have sequenced the tumor and normal genomes of one of these patients. We demonstrate here that our RNA-Seq method accurately measures allelic imbalance and that measurement on the genome-wide scale yields novel insights into cancer etiology. As expected, the set of genes differentially expressed in the tumors is enriched for cell adhesion and differentiation functions, but, unexpectedly, the set of allelically imbalanced genes is also enriched for these same cancer-related functions. By comparing the transcriptomic perturbations observed in one patient to his underlying normal and tumor genomes, we find that allelic imbalance in the tumor is associated with copy number mutations and that copy number mutations are, in turn, strongly associated with changes in transcript abundance. These results support a model in which allele-specific deletions and duplications drive allele-specific changes in gene expression in the developing tumor.

  3. The Decision Support Matrix (DSM) Approach to Reducing Risk of Flooding and Water Pollution in Farmed Landscapes

    Science.gov (United States)

    Hewett, Caspar J. M.; Quinn, Paul; Wilkinson, Mark

    2014-05-01

    Intense farming plays a key role in contributing to problems such as increased flood risk, soil erosion and poor water quality. This means that there is great potential for agricultural practitioners to play a major part in reducing multiple risks through better land-use management. Greater understanding by farmers, land managers, practitioners and policy-makers of the ways in which farmed landscapes contribute to risks and the ways in which those risks might be mitigated can be an essential component in improving practice. The Decision Support Matrix (DSM) approach involves the development of a range of visualization and communication tools to help compare the risks associated with different farming practices and explore options to manage runoff. DSMs are simple decision support systems intended for use by the non-expert which combine expert hydrological evidence with local knowledge of runoff patterns. They are developed through direct engagement with stakeholders, ensuring that the examples and language used makes sense to end-users. A key element of the tools is that they show the current conditions of the land and describe extremes of land-use management within a hydrological and agricultural land-management context. The tools include conceptual models of a series of pre-determined runoff scenarios, providing the end-user with a variety of potential land management practices and runoff management options. Visual examples of different farming practices are used to illustrate the impact of good and bad practice on specific problems such as nutrient export or risk of flooding. These show both how current conditions cause problems downstream and how systems are vulnerable to changes in climate and land-use intensification. The level of risk associated with a particular land management option is represented by a mapping on a two- or three-dimensional matrix. Interactive spreadsheet-based tools are developed in which multiple questions allow the user to explore

  4. High-risk medical devices, children and the FDA: regulatory challenges facing pediatric mechanical circulatory support devices.

    Science.gov (United States)

    Almond, Christopher S D; Chen, Eric A; Berman, Michael R; Less, Joanne R; Baldwin, J Timothy; Linde-Feucht, Sarah R; Hoke, Tracey R; Pearson, Gail D; Jenkins, Kathy; Duncan, Brian W; Zuckerman, Bram D

    2007-01-01

    Pediatric mechanical circulatory support is a critical unmet need in the United States. Infant- and child-sized ventricular assist devices are currently being developed largely through federal contracts and grants through the National Heart, Lung, and Blood Institute (NHLBI). Human testing and marketing of high-risk devices for children raises epidemiologic and regulatory issues that will need to be addressed. Leaders from the US Food and Drug Administration (FDA), NHLBI, academic pediatric community, and industry convened in January 2006 for the first FDA Workshop on the Regulatory Process for Pediatric Mechanical Circulatory Support Devices. The purpose was to provide the pediatric community with an overview of the federal regulatory process for high-risk medical devices and to review the challenges specific to the development and regulation of pediatric mechanical circulatory support devices. Pediatric mechanical circulatory support present significant epidemiologic, logistic, and financial challenges to industry, federal regulators, and the pediatric community. Early interactions with the FDA, shared appreciation of challenges, and careful planning will be critical to avoid unnecessary delays in making potentially life-saving devices available for children. Collaborative efforts to address these challenges are warranted.

  5. Suicide ideation among high-risk adolescent females: Examining the interplay between parasympathetic regulation and friendship support

    Science.gov (United States)

    GILETTA, MATTEO; HASTINGS, PAUL D.; RUDOLPH, KAREN D.; BAUER, DANIEL J.; NOCK, MATTHEW K.; PRINSTEIN, MITCHELL J.

    2018-01-01

    Poor physiological self-regulation has been proposed as a potential biological vulnerability for adolescent suicidality. This study tested this hypothesis by examining the effect of parasympathetic stress responses on future suicide ideation. In addition, drawing from multilevel developmental psychopathology theories, the interplay between parasympathetic regulation and friendship support, conceptualized as an external source of regulation, was examined. At baseline, 132 adolescent females (M age = 14.59, SD = 1.39) with a history of mental health concerns participated in an in vivo interpersonal stressor (a laboratory speech task) and completed self-report measures of depressive symptoms and perceived support within a close same-age female friendship. Respiratory sinus arrhythmia (RSA) was measured before and during the speech task. Suicide ideation was assessed at baseline and at 3, 6, and 9 months follow-up. The results revealed that females with greater relative RSA decreases to the laboratory stressor were at higher risk for reporting suicide ideation over the subsequent 9 months. Moreover, parasympathetic responses moderated the effect of friendship support on suicide ideation; among females with mild changes or higher relative increases in RSA, but not more pronounced RSA decreases, friendship support reduced risk for future suicide ideation. Findings highlight the crucial role of physiological and external regulation sources as protective factors for youth suicidality. PMID:28031059

  6. Framework for Modeling High-Impact, Low-Frequency Power Grid Events to Support Risk-Informed Decisions

    Energy Technology Data Exchange (ETDEWEB)

    Veeramany, Arun; Unwin, Stephen D.; Coles, Garill A.; Dagle, Jeffery E.; Millard, W. David; Yao, Juan; Glantz, Clifford S.; Gourisetti, Sri Nikhil Gup

    2015-12-03

    grid modernization activities. The availability of a grid HILF risk model, integrated across multi-hazard domains which, when interrogated, can support transparent, defensible and effective decisions, is an attractive prospect among these communities. In this report, we document an integrated HILF risk framework intended to inform the development of risk models. These models would be based on the systematic and comprehensive (to within scope) characterization of hazards to the level of detail required for modeling risk, identification of the stressors associated with the hazards (i.e., the means of impacting grid and supporting infrastructure), characterization of the vulnerability of assets to these stressors and the probabilities of asset compromise, the grid’s dynamic response to the asset failures, and assessment of subsequent severities of consequence with respect to selected impact metrics, such as power outage duration and geographic reach. Specifically, the current framework is being developed to;1. Provide the conceptual and overarching technical paradigms for the development of risk models; 2. Identify the classes of models required to implement the framework - providing examples of existing models, and also identifying where modeling gaps exist; 3. Identify the types of data required, addressing circumstances under which data are sparse and the formal elicitation of informed judgment might be required; and 4. Identify means by which the resultant risk models might be interrogated to form the necessary basis for risk management.

  7. Risk information in support of cost estimates for the Baseline Environmental Management Report (BEMR). Section 1

    International Nuclear Information System (INIS)

    Gelston, G.M.; Jarvis, M.F.; Warren, B.R.; Von Berg, R.

    1995-06-01

    The Pacific Northwest Laboratory (PNL)(1) effort on the overall Baseline Environmental Management Report (BEMR) project consists of four installation-specific work components performed in succession. These components include (1) development of source terms, 92) collection of data and preparation of environmental settings reports, (3) calculation of unit risk factors, and (4) utilization of the unit risk factors in Automated Remedial Action Methodology (ARAM) for computation of target concentrations and cost estimates. This report documents work completed for the Nevada Test Site, Nevada, for components 2 and 3. The product of this phase of the BEMR project is the development of unit factors (i.e., unit transport factors, unit exposure factors, and unit risk factors). Thousands of these unit factors are gene rated and fill approximately one megabyte of computer information per installation. The final unit risk factors (URF) are transmitted electronically to BEMR-Cost task personnel as input to a computer program (ARAM). Abstracted files and exhibits of the URF information are included in this report. These visual formats are intended to provide a sample of the final task deliverable (the URF files) which can be easily read without a computer

  8. Sight Word Recognition among Young Children At-Risk: Picture-Supported vs. Word-Only

    Science.gov (United States)

    Meadan, Hedda; Stoner, Julia B.; Parette, Howard P.

    2008-01-01

    A quasi-experimental design was used to investigate the impact of Picture Communication Symbols (PCS) on sight word recognition by young children identified as "at risk" for academic and social-behavior difficulties. Ten pre-primer and 10 primer Dolch words were presented to 23 students in the intervention group and 8 students in the…

  9. Data development technical support document for the aircraft crash risk analysis methodology (ACRAM) standard

    International Nuclear Information System (INIS)

    Kimura, C.Y.; Glaser, R.E.; Mensing, R.W.; Lin, T.; Haley, T.A.; Barto, A.B.; Stutzke, M.A.

    1996-01-01

    The Aircraft Crash Risk Analysis Methodology (ACRAM) Panel has been formed by the US Department of Energy Office of Defense Programs (DOE/DP) for the purpose of developing a standard methodology for determining the risk from aircraft crashes onto DOE ground facilities. In order to accomplish this goal, the ACRAM panel has been divided into four teams, the data development team, the model evaluation team, the structural analysis team, and the consequence team. Each team, consisting of at least one member of the ACRAM plus additional DOE and DOE contractor personnel, specializes in the development of the methodology assigned to that team. This report documents the work performed by the data development team and provides the technical basis for the data used by the ACRAM Standard for determining the aircraft crash frequency. This report should be used to provide the generic data needed to calculate the aircraft crash frequency into the facility under consideration as part of the process for determining the aircraft crash risk to ground facilities as given by the DOE Standard Aircraft Crash Risk Assessment Methodology (ACRAM). Some broad guidance is presented on how to obtain the needed site-specific and facility specific data but this data is not provided by this document

  10. Risk Assessment supporting the decision on the initial selection of supplemental ILAW technologies

    Energy Technology Data Exchange (ETDEWEB)

    MANN, F. M.

    2003-09-29

    A risk assessment on the long-term environmental impact of various potential waste forms was conducted at the request of the Hanford Site's Mission Acceleration Initiative Team. These potential waste forms (bulk vitrification, cast stone, and steam reformer) may treat some of the low-activity waste currently planned to be treated at the Waste Treatment Plant.

  11. Digital Risk Inventory and Evaluation (RIE) : a Dutch approach offering valuable support for small business owners

    NARCIS (Netherlands)

    Meeuwsen, J.M.

    2008-01-01

    The Dutch Working Conditions Act requires employers to perform a Risk Inventory and Evaluation (RIE). Until recently, small business owners (SMEs) in particular were unhappy about this rather time-consuming obligation. However, the introduction of digital RIE instruments disseminated through the web

  12. Supporting healthcare professionals to encourage patients to decrease cardiovascular risk attributable to physical inactivity

    NARCIS (Netherlands)

    Drs. Barbara Sassen

    2011-01-01

    The consequences of cardiovascular diseases are substantial and include increasing numbers of morbidity and mortality. With a population getting more and more inactive and having a sedentary lifestyle, the risk for cardiovascular disease and type 2 diabetes rises. This dissertation reports on people

  13. Supporting nanomaterial risk assessment by case studies of nano-titanium dioxide using comprehensive environmental assessment

    Science.gov (United States)

    Here we describe a comprehensive environmental assessment (CEA) approach for two case studies of nano-titanium dioxide (nano-TiO2) in real world applications: water treatment and sunscreen. CEA combines a product life cycle framework with the risk assessment paradigm.

  14. AllelicImbalance: An R/ bioconductor package for detecting, managing, and visualizing allele expression imbalance data from RNA sequencing

    DEFF Research Database (Denmark)

    Gådin, Jesper R.; van't Hooft, Ferdinand M.; Eriksson, Per

    2015-01-01

    the possible biases. Results: We present AllelicImblance, a software program that is designed to detect, manage, and visualize allelic imbalances comprehensively. The purpose of this software is to allow users to pose genetic questions in any RNA sequencing experiment quickly, enhancing the general utility...... of RNA sequencing. The visualization features can reveal notable, non-trivial allelic imbalance behavior over specific regions, such as exons. Conclusions: The software provides a complete framework to perform allelic imbalance analyses of aligned RNA sequencing data, from detection to visualization...

  15. Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots.

    Science.gov (United States)

    Baker, Christopher L; Petkova, Pavlina; Walker, Michael; Flachs, Petr; Mihola, Ondrej; Trachtulec, Zdenek; Petkov, Petko M; Paigen, Kenneth

    2015-09-01

    Genetic recombination during meiosis functions to increase genetic diversity, promotes elimination of deleterious alleles, and helps assure proper segregation of chromatids. Mammalian recombination events are concentrated at specialized sites, termed hotspots, whose locations are determined by PRDM9, a zinc finger DNA-binding histone methyltransferase. Prdm9 is highly polymorphic with most alleles activating their own set of hotspots. In populations exhibiting high frequencies of heterozygosity, questions remain about the influences different alleles have in heterozygous individuals where the two variant forms of PRDM9 typically do not activate equivalent populations of hotspots. We now find that, in addition to activating its own hotspots, the presence of one Prdm9 allele can modify the activity of hotspots activated by the other allele. PRDM9 function is also dosage sensitive; Prdm9+/- heterozygous null mice have reduced numbers and less active hotspots and increased numbers of aberrant germ cells. In mice carrying two Prdm9 alleles, there is allelic competition; the stronger Prdm9 allele can partially or entirely suppress chromatin modification and recombination at hotspots of the weaker allele. In cell cultures, PRDM9 protein variants form functional heteromeric complexes which can bind hotspots sequences. When a heteromeric complex binds at a hotspot of one PRDM9 variant, the other PRDM9 variant, which would otherwise not bind, can still methylate hotspot nucleosomes. We propose that in heterozygous individuals the underlying molecular mechanism of allelic suppression results from formation of PRDM9 heteromers, where the DNA binding activity of one protein variant dominantly directs recombination initiation towards its own hotspots, effectively titrating down recombination by the other protein variant. In natural populations with many heterozygous individuals, allelic competition will influence the recombination landscape.

  16. Detecting differential allelic expression using high-resolution melting curve analysis: application to the breast cancer susceptibility gene CHEK2

    Directory of Open Access Journals (Sweden)

    Sinilnikova Olga

    2011-05-01

    Full Text Available Abstract Background The gene CHEK2 encodes a checkpoint kinase playing a key role in the DNA damage pathway. Though CHEK2 has been identified as an intermediate breast cancer susceptibility gene, only a small proportion of high-risk families have been explained by genetic variants located in its coding region. Alteration in gene expression regulation provides a potential mechanism for generating disease susceptibility. The detection of differential allelic expression (DAE represents a sensitive assay to direct the search for a functional sequence variant within the transcriptional regulatory elements of a candidate gene. We aimed to assess whether CHEK2 was subject to DAE in lymphoblastoid cell lines (LCLs from high-risk breast cancer patients for whom no mutation in BRCA1 or BRCA2 had been identified. Methods We implemented an assay based on high-resolution melting (HRM curve analysis and developed an analysis tool for DAE assessment. Results We observed allelic expression imbalance in 4 of the 41 LCLs examined. All four were carriers of the truncating mutation 1100delC. We confirmed previous findings that this mutation induces non-sense mediated mRNA decay. In our series, we ruled out the possibility of a functional sequence variant located in the promoter region or in a regulatory element of CHEK2 that would lead to DAE in the transcriptional regulatory milieu of freely proliferating LCLs. Conclusions Our results support that HRM is a sensitive and accurate method for DAE assessment. This approach would be of great interest for high-throughput mutation screening projects aiming to identify genes carrying functional regulatory polymorphisms.

  17. Ecological models in support of regulatory risk assessments of pesticides: developing a strategy for the future.

    Science.gov (United States)

    Forbes, Valery E; Hommen, Udo; Thorbek, Pernille; Heimbach, Fred; Van den Brink, Paul J; Wogram, Jörn; Thulke, Hans-Hermann; Grimm, Volker

    2009-01-01

    This brief communication reports on the main findings of the LEMTOX workshop, held from 9 to 12 September 2007, at the Helmholtz Centre for Environmental Research (UFZ) in Leipzig, Germany. The workshop brought together a diverse group of stakeholders from academia, regulatory authorities, contract research organizations, and industry, representing Europe, the United States, and Asia, to discuss the role of ecological modeling in risk assessments of pesticides, particularly under the European regulatory framework. The following questions were addressed: What are the potential benefits of using ecological models in pesticide registration and risk assessment? What obstacles prevent ecological modeling from being used routinely in regulatory submissions? What actions are needed to overcome the identified obstacles? What recommendations should be made to ensure good modeling practice in this context? The workshop focused exclusively on population models, and discussion was focused on those categories of population models that link effects on individuals (e.g., survival, growth, reproduction, behavior) to effects on population dynamics. The workshop participants concluded that the overall benefits of ecological modeling are that it could bring more ecology into ecological risk assessment, and it could provide an excellent tool for exploring the importance of, and interactions among, ecological complexities. However, there are a number of challenges that need to be overcome before such models will receive wide acceptance for pesticide risk assessment, despite having been used extensively in other contexts (e.g., conservation biology). The need for guidance on Good Modeling Practice (on model development, analysis, interpretation, evaluation, documentation, and communication), as well as the need for case studies that can be used to explore the added value of ecological models for risk assessment, were identified as top priorities. Assessing recovery potential of exposed

  18. Flood Risk and Probabilistic Benefit Assessment to Support Management of Flood-Prone Lands: Evidence From Candaba Floodplains, Philippines

    Science.gov (United States)

    Juarez, A. M.; Kibler, K. M.; Sayama, T.; Ohara, M.

    2016-12-01

    Flood management decision-making is often supported by risk assessment, which may overlook the role of coping capacity and the potential benefits derived from direct use of flood-prone land. Alternatively, risk-benefit analysis can support floodplain management to yield maximum socio-ecological benefits for the minimum flood risk. We evaluate flood risk-probabilistic benefit tradeoffs of livelihood practices compatible with direct human use of flood-prone land (agriculture/wild fisheries) and nature conservation (wild fisheries only) in Candaba, Philippines. Located north-west to Metro Manila, Candaba area is a multi-functional landscape that provides a temporally-variable mix of possible land uses, benefits and ecosystem services of local and regional value. To characterize inundation from 1.3- to 100-year recurrence intervals we couple frequency analysis with rainfall-runoff-inundation modelling and remotely-sensed data. By combining simulated probabilistic floods with both damage and benefit functions (e.g. fish capture and rice yield with flood intensity) we estimate potential damages and benefits over varying probabilistic flood hazards. We find that although direct human uses of flood-prone land are associated with damages, for all the investigated magnitudes of flood events with different frequencies, the probabilistic benefits ( 91 million) exceed risks by a large margin ( 33 million). Even considering risk, probabilistic livelihood benefits of direct human uses far exceed benefits provided by scenarios that exclude direct "risky" human uses (difference of 85 million). In addition, we find that individual coping strategies, such as adapting crop planting periods to the flood pulse or fishing rather than cultivating rice in the wet season, minimize flood losses ( 6 million) while allowing for valuable livelihood benefits ($ 125 million) in flood-prone land. Analysis of societal benefits and local capacities to cope with regular floods demonstrate the

  19. A carbon risk prediction model for Chinese heavy-polluting industrial enterprises based on support vector machine

    International Nuclear Information System (INIS)

    Zhou, Zhifang; Xiao, Tian; Chen, Xiaohong; Wang, Chang

    2016-01-01

    Chinese heavy-polluting industrial enterprises, especially petrochemical or chemical industry, labeled low carbon efficiency and high emission load, are facing the tremendous pressure of emission reduction under the background of global shortage of energy supply and constrain of carbon emission. However, due to the limited amount of theoretic and practical research in this field, problems like lacking prediction indicators or models, and the quantified standard of carbon risk remain unsolved. In this paper, the connotation of carbon risk and an assessment index system for Chinese heavy-polluting industrial enterprises (eg. coal enterprise, petrochemical enterprises, chemical enterprises et al.) based on support vector machine are presented. By using several heavy-polluting industrial enterprises’ related data, SVM model is trained to predict the carbon risk level of a specific enterprise, which allows the enterprise to identify and manage its carbon risks. The result shows that this method can predict enterprise’s carbon risk level in an efficient, accurate way with high practical application and generalization value.

  20. Main areas for the sociological support of organizational risks diagnostics and prevention in the internal affairs bodies

    Directory of Open Access Journals (Sweden)

    T H Dzhanteev

    2016-12-01

    Full Text Available The article considers the use of theoretical and applied sociological studies to identify and prevent negative consequences of the organizational risks in the internal affairs bodies, such as: insufficient quality of the organizational structure; failures in the design of organizational structures; poor coordination and regulation; inconsistency of resources provision; mistakes in the selection and placement of personnel; shortcomings in the organization of interaction with the public; incorrect definition of the needs of citizens in the field of law enforcement; poor quality of law enforcement services; inadequate training of personnel for the interaction with citizens. The author describes the role of the sociological support in the diagnostics of organizational risks, and pays particular attention to the factors contributing to the occurrence of undesirable situations and to the cause-and-effect relationships between various events associated with the risks. The article emphasizes the exceptional importance of forecasting negative consequences of risk situations and developing measures to minimize negative effects of organizational risks in law enforcement in general and in the internal affairs bodies in particular.

  1. [Risk management of hospital infections as a supporting tool for the improvement of hospital quality - some European examples].

    Science.gov (United States)

    Sitek, Mateusz; Witczak, Izabela; Kiedik, Dorota

    Prevention and control of nosocomial infections is one of the main pillars of security in each medical facility. This affects the quality of services and helps to minimize the economic losses incurred as a result of such infections. (Prolonged hospitalization, expensive antibiotic therapies, court costs of damages). Nosocomial infections occur in every medical facility in the hospitals in terms of risk of infection compared to other medicinal entities are at greater risk of environmental (number of hospitalizations for one bed, the amount of disinfectants, etc.). The number and diverse category of employment of medical and auxiliary, which should meet certain standards for the prevention of hospital infections, has an impact on the incidence of infection. It is impossible to eliminate hospital-acquired infections, but can be limited by appropriate measures, ranging from monitoring through the use of risk management methods, which are one of the elements supporting the improvement of the quality of medical entities. Hospital infection is a threat not only for patients but also for workers exposed to the risk of so-called occupational exposure. A comprehensive approach including elements of active surveillance and effective monitoring can help to minimize the risk of nosocomial infections.

  2. Higher FKBP5, COMT, CHRNA5, and CRHR1 allele burdens are associated with PTSD and interact with trauma exposure: implications for neuropsychiatric research and treatment

    Directory of Open Access Journals (Sweden)

    Boscarino JA

    2012-03-01

    Full Text Available Joseph A Boscarino1,2, Porat M Erlich1,3, Stuart N Hoffman4, Xiaopeng Zhang51Center for Health Research, Geisinger Clinic, Danville, PA, 2Department of Psychiatry, 3Department of Medicine, Temple University School of Medicine, Philadelphia, PA, 4Department of Neurology, 5Department of Anesthesiology, Geisinger Clinic, Danville, PA, USAObjective: The study aim was to assess the cumulative burden of polymorphisms located within four genetic loci previously associated with posttraumatic stress disorder (PTSD among outpatients at risk for PTSD.Methods: Diagnostic interviews were completed and DNA samples collected among 412 pain patients to determine if FKBP5 (rs9470080, COMT (rs4680, CHRNA5 (rs16969968, and CRHR1 (rs110402 single nucleotide polymorphisms were cumulatively associated with increased risk for PTSD.Results: In bivariate analyses, it was found that a count of specific PTSD risk alleles located within FKBP5, COMT, CHRNA5, and CRHR1 genetic loci (allele range = 0–6, mean count = 2.92, standard deviation = 1.36 was associated with lifetime (t [409] = 3.430, P = 0.001 and early onset PTSD (t [409] = 4.239, P = 0.000028. In logistic regression, controlling for demographic factors, personality traits, and trauma exposures, this risk allele count remained associated with both lifetime (odds ratio = 1.49, P = 0.00158 and early onset PTSD (odds ratio = 2.36, P = 0.000093. Interaction effects were also detected, whereby individuals with higher risk allele counts and higher trauma exposures had an increased risk of lifetime PTSD (allele count × high trauma, P = 0.026 and early onset PTSD (allele count × high trauma, P = 0.016 in these logistic regressions. Those with no or few risk alleles appeared resilient to PTSD, regardless of exposure history.Conclusion: A cumulative risk allele count involving four single nucleotide polymorphisms located within the FKBP5, COMT, CHRNA5, and CRHR1 genes are associated with PTSD. Level of trauma exposure

  3. Transthyretin levels: Potential biomarker for monitoring nutritional support efficacy and clinical complications risk in patients receiving parenteral nutrition.

    Science.gov (United States)

    Borges de Oliveira Nascimento Freitas, Renata Germano; Hessel, Gabriel; Junqueira Vasques, Ana Carolina; Negrão Nogueira, Roberto José

    2018-04-01

    Nutritional support is an effective strategy to restore or maintain nutritional status, to reduce clinical complications, hospitalization period and the morbidity/mortality risk of hospitalized patients. So, a good marker is important to evaluate the nutritional support. This study aims to evaluate the evolution of transthyretin levels in patients receiving parenteral nutrition (PN) during 14 days. Longitudinal study of 88 hospitalized patients. The assessments and samples were taken during the first 72 h (T0), on the 7th day (T7) and 14th day (T14) of PN. This study was approved by the Ethics Committee of the School of Medical Sciences at UNICAMP (No 538/2011). The C-reactive protein (CRP) levels were high and albumin and transthyretin levels were low at baseline. From T0 to T14, only transthyretin increased (p = 0.03). According to the receiver operation characteristic (ROC) curve, we found that the transthyretin had some improvement when the CRP levels were less than 10.4 mg/dl (T7). According to the CRP/albumin ratio, all patients classified as without risk for complications were discharged from the hospital. In addition, we observed that patients with transthyretin reduction had a concomitant higher risk for complications according to their ratio CRP/albumin (p = 0.03). CRP/albumin ratio was associated with the evolution of transthyretin levels. Transthyretin values showed significant improvement in the 14 days of PN. Especially, less inflamed patients (ie CRP less than 10.4 mg/dl) improved their transthyretin levels. So, CRP value at day 7 that predicts the transthyretin and transthyretin is a good biomarker for classification of nutritional support and clinical complications risk in patients receiving PN. Copyright © 2017 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

  4. Literature review of baseline information to support the risk assessment of RNAi-based GM plants

    Czech Academy of Sciences Publication Activity Database

    Pačes, Jan; Nic, M.; Novotný, T.; Svoboda, Petr

    2017-01-01

    Roč. 14, č. 6 (2017), č. článku 1246E. ISSN 2397-8325 Institutional support: RVO:68378050 Keywords : miRNA, , ,, , , * RNAi * siRNA * Dicer * Argonaute * dsRNA * off-targeting Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Cell biology

  5. Risk Aversion and Support for Merit Pay: Theory and Evidence from Minnesota's Q Comp Program

    Science.gov (United States)

    Nadler, Carl; Wiswall, Matthew

    2011-01-01

    Recent research attributes the lack of merit pay in teaching to the resistance of teachers. This article examines whether the structure of merit pay affects the types of teachers who support it. We develop a model of the relative utility teachers receive from merit pay versus the current fixed schedule of raises. We show that if teachers are risk…

  6. Aging Parents with Adult Mentally Retarded Children: Family Risk Factors and Sources of Support.

    Science.gov (United States)

    Seltzer, Marsha Mailick; Krauss, Marty Wyngaarden

    1989-01-01

    Predictors of 4 indices of well-being (physical health, life satisfaction, burden, and parenting stress) were examined among 203 aging mothers of mentally retarded adults living at home. Predictive variables examined include maternal characteristics, retarded adult's characteristics, family social climate, mother's social support network, and…

  7. Children of Mentally Ill Parents Participating in Preventive Support Groups: Parental Diagnoses and Child Risk

    NARCIS (Netherlands)

    Santvoort, F. van; Hosman, C.M.H.; Doesum, K.T.M. van; Janssens, J.M.A.M.

    2014-01-01

    In the Netherlands, preventive support groups are offered to children of mentally ill parents. Given the variety of parental diagnoses it might be questionable if offering a standardized program for all these children is the most effective response. While no overall knowledge exists about the type

  8. Usage Patterns of Communication Interfaces for Social Support among At-Risk Adolescents

    Science.gov (United States)

    Passig, David

    2014-01-01

    Social and interpersonal support has mostly been carried out face-to-face. However, the internet was able, in the last couple of decades, to facilitate social interactions through a range of computer-mediated communication (CMC) interfaces--from email applications, chat-rooms, forums, instant messages (IM), short text messages (SMS), social…

  9. Physiologically Based Toxicokinetic Modelling as a Tool to Support Risk Assessment: Three Case Studies

    Directory of Open Access Journals (Sweden)

    Hans Mielke

    2012-01-01

    Full Text Available In this contribution we present three case studies of physiologically based toxicokinetic (PBTK modelling in regulatory risk assessment. (1 Age-dependent lower enzyme expression in the newborn leads to bisphenol A (BPA blood levels which are near the levels of the tolerated daily intake (TDI at the oral exposure as calculated by EFSA. (2 Dermal exposure of BPA by receipts, car park tickets, and so forth, contribute to the exposure towards BPA. However, at the present levels of dermal exposure there is no risk for the adult. (3 Dermal exposure towards coumarin via cosmetic products leads to external exposures of two-fold the TDI. PBTK modeling helped to identify liver peak concentration as the metric for liver toxicity. After dermal exposure of twice the TDI, the liver peak concentration was lower than that present after oral exposure with the TDI dose. In the presented cases, PBTK modeling was useful to reach scientifically sound regulatory decisions.

  10. Evidence to support IL-13 as a risk locus for psoriatic arthritis but not psoriasis vulgaris.

    LENUS (Irish Health Repository)

    Bowes, John

    2011-06-01

    There is great interest in the identification of genetic factors that differentiate psoriatic arthritis (PsA) from psoriasis vulgaris (PsV), as such discoveries could lead to the identification of distinct underlying aetiological pathways. Recent studies identified single nucleotide polymorphisms (SNPs) in the interleukin 13 (IL-13) gene region as risk factors for PsV. Further investigations in one of these studies found the effect to be primarily restricted to PsA, thus suggesting the discovery of a specific genetic risk factor for PsA. Given this intriguing evidence, association to this gene was investigated in large collections of PsA and PsV patients and healthy controls.

  11. Risk by use of hearing protectors--expert programme supports SMEs in appropriate selection and use.

    Science.gov (United States)

    Liedtke, M

    2005-01-01

    Comprehensive protection by use of PPE against the hazards at work requires more than proper selection based on the protection level needed: The PPE user directive (Council Directive 89/656/EEC, Official Journal of the European Communities L 393, 30/12/1989 p.0018 - 0028) requires an assessment of personal protective equipment itself, which has to consider the risks which may be introduced by use of PPE or use of combinations of PPE. As an example risks which may be introduced by use of hearing protectors are described. Assistance in the assessment required by PPE user directive (Council Directive 89/656/EEC, Official Journal of the European Communities L 393, 30/12/1989 p. 0018 - 0028) and in selection and use of hearing protectors with regard to this assessment is presented.

  12. A Framework to Expand and Advance Probabilistic Risk Assessment to Support Small Modular Reactors

    Energy Technology Data Exchange (ETDEWEB)

    Curtis Smith; David Schwieder; Robert Nourgaliev; Cherie Phelan; Diego Mandelli; Kellie Kvarfordt; Robert Youngblood

    2012-09-01

    During the early development of nuclear power plants, researchers and engineers focused on many aspects of plant operation, two of which were getting the newly-found technology to work and minimizing the likelihood of perceived accidents through redundancy and diversity. As time, and our experience, has progressed, the realization of plant operational risk/reliability has entered into the design, operation, and regulation of these plants. But, to date, we have only dabbled at the surface of risk and reliability technologies. For the next generation of small modular reactors (SMRs), it is imperative that these technologies evolve into an accepted, encompassing, validated, and integral part of the plant in order to reduce costs and to demonstrate safe operation. Further, while it is presumed that safety margins are substantial for proposed SMR designs, the depiction and demonstration of these margins needs to be better understood in order to optimize the licensing process.

  13. Estimating and testing the effect of allelic recombination on the ...

    African Journals Online (AJOL)

    Jane

    2011-01-21

    Jan 21, 2011 ... The significance of the correlation coefficient as well as the fitted regression model was obtained using. Analysis of Variance method. Key words: Allele, genotype, regression, correlation, F-ratio, analysis of variance. INTRODUCTION .... while if the allelic replacement is being made on an Aa individual the ...

  14. Comparison of bovine lymphocyte antigen DRB3.2 allele ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-08-04

    Aug 4, 2008 ... The bovine lymphocyte antigen (BoLA-DRB3) gene encodes cell ... alleles were more resistant to clinical mastitis. ... DRB3.2 allele pattern in two Iranian Holstein cow .... observed and the number of immune parameters with.

  15. Evolutionary dynamics of sporophytic self-incompatibility alleles in plants

    DEFF Research Database (Denmark)

    Schierup, Mikkel Heide; Vekemans, Xavier; Christiansen, Freddy Bugge

    1997-01-01

    codominantly in both pollen and style (SSIcod), in the second, alleles form a dominance hierarchy in pollen and style (SSIdom). In the third model, alleles interact codominantly in the style and form a dominance hierarchy in the pollen (SSIdomcod). The SSIcod model behaves similarly to the model...

  16. Human minisatellite alleles detectable only after PCR amplification.

    Science.gov (United States)

    Armour, J A; Crosier, M; Jeffreys, A J

    1992-01-01

    We present evidence that a proportion of alleles at two human minisatellite loci is undetected by standard Southern blot hybridization. In each case the missing allele(s) can be identified after PCR amplification and correspond to tandem arrays too short to detect by hybridization. At one locus, there is only one undetected allele (population frequency 0.3), which contains just three repeat units. At the second locus, there are at least five undetected alleles (total population frequency 0.9) containing 60-120 repeats; they are not detected because these tandem repeats give very poor signals when used as a probe in standard Southern blot hybridization, and also cross-hybridize with other sequences in the genome. Under these circumstances only signals from the longest tandemly repeated alleles are detectable above the nonspecific background. The structures of these loci have been compared in human and primate DNA, and at one locus the short human allele containing three repeat units is shown to be an intermediate state in the expansion of a monomeric precursor allele in primates to high copy number in the longer human arrays. We discuss the implications of such loci for studies of human populations, minisatellite isolation by cloning, and the evolution of highly variable tandem arrays.

  17. Comparative frequency and allelic distribution of ABO and Rh (D ...

    African Journals Online (AJOL)

    Background: Allelic distribution of major blood groups (ABO and rhesus) has not been defined in Bangladeshi population. Determinants of blood group frequency in this region have not been studied properly. Aim: To determine ABO and rhesus blood group frequency and allelic distribution in a multiethnic area of ...

  18. Apolipoprotein E4 allele does not influence serum triglyceride ...

    African Journals Online (AJOL)

    This study investigated how the APOε4 allele affects the serum triglyceride response after a fatmeal in apparently healthy black South African young adults. Sixty students were successfully screened for APOE genotype using Restriction Fragment Length Polymorphism (RFLP) and were divided into four groups; the ε2 allele ...

  19. Safety Risk Knowledge Elicitation in Support of Aeronautical R and D Portfolio Management: A Case Study

    Science.gov (United States)

    Shih, Ann T.; Ancel, Ersin; Jones, Sharon Monica; Reveley, Mary S.; Luxhoj, James T.

    2012-01-01

    Aviation is a problem domain characterized by a high level of system complexity and uncertainty. Safety risk analysis in such a domain is especially challenging given the multitude of operations and diverse stakeholders. The Federal Aviation Administration (FAA) projects that by 2025 air traffic will increase by more than 50 percent with 1.1 billion passengers a year and more than 85,000 flights every 24 hours contributing to further delays and congestion in the sky (Circelli, 2011). This increased system complexity necessitates the application of structured safety risk analysis methods to understand and eliminate where possible, reduce, and/or mitigate risk factors. The use of expert judgments for probabilistic safety analysis in such a complex domain is necessary especially when evaluating the pro