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Sökning: WFRF:(Hart Stephen)

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1.
  • Elsik, Christine G., et al. (författare)
  • The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
  • 2009
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
  • Tidskriftsartikel (refereegranskat)abstract
    • To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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2.
  • Collier, Paul, et al. (författare)
  • The Second World War
  • 2018. - 2nd
  • Bok (refereegranskat)abstract
    • The Second World War was the most devastating conflict in human history and one which provides innumerable lessons - military, political, and moral. Across the globe, both soldier and civilian endured suffering on a scale previously unknown to humanity as nations grappled with the demands of total war.
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3.
  • Di Angelantonio, Emanuele, et al. (författare)
  • Association of Cardiometabolic Multimorbidity With Mortality : The Emerging Risk Factors Collaboration
  • 2015
  • Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 314:1, s. 52-60
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE The prevalence of cardiometabolic multimorbidity is increasing.OBJECTIVE To estimate reductions in life expectancy associated with cardiometabolic multimorbidity.DESIGN, SETTING, AND PARTICIPANTS Age-and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689 300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128 843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499 808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI).MAIN OUTCOMES AND MEASURES All-cause mortality and estimated reductions in life expectancy.RESULTS In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy.CONCLUSIONS AND RELEVANCE Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.
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4.
  • Overview of the JET results
  • 2015
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 55:10
  • Tidskriftsartikel (refereegranskat)
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5.
  • Belfrage, Henrik, et al. (författare)
  • Assessment and management of risk for intimate partner violence by police officers using the Spousal Assault Risk Assessment Guide
  • 2012
  • Ingår i: Law and human behavior. - : American Psychological Association (APA). - 0147-7307 .- 1573-661X. ; 36:1, s. 60-67
  • Tidskriftsartikel (refereegranskat)abstract
    • Intimate partner violence (IPV) is a crime that is present in all countries, seriously impacts victims, and demands a great deal of time and resources from the criminal justice system. The current study examined the use of the Spousal Assault Risk Assessment Guide, 2nd ed. (SARA; Kropp, Hart, Webster, & Eaves, 1995), a structured professional judgment risk assessment and management tool for IPV, by police officers in Sweden over a follow-up of 18 months. SARA risk assessments had significant predictive validity with respect to risk management recommendations made by police, as well as with recidivism as indexed by subsequent contacts with police. Risk management mediated the association between risk assessment and recidivism: High levels of intervention were associated with decreased recidivism in high risk cases, but with increased recidivism in low risk cases. The findings support the potential utility of police-based risk assessment and management of IPV, and in particular the belief that appropriately structured risk assessment and management decisions can prevent violence.
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6.
  • Couch, Fergus J., et al. (författare)
  • Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
  • 2016
  • Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
  • Tidskriftsartikel (refereegranskat)abstract
    • Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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7.
  • Dawed, Adem Y., et al. (författare)
  • Pharmacogenomics of GLP-1 receptor agonists : a genome- wide analysis of observational data and large randomised controlled trials
  • 2023
  • Ingår i: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 11:1, s. 33-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In the treatment of type 2 diabetes, GLP-1 receptor agonists lower blood glucose concentrations, body weight, and have cardiovascular benefits. The efficacy and side effects of GLP-1 receptor agonists vary between people. Human pharmacogenomic studies of this inter-individual variation can provide both biological insight into drug action and provide biomarkers to inform clinical decision making. We therefore aimed to identify genetic variants associated with glycaemic response to GLP-1 receptor agonist treatment. Methods:In this genome-wide analysis we included adults (aged & GE;18 years) with type 2 diabetes treated with GLP-1 receptor agonists with baseline HbA1c of 7% or more (53 mmol/mol) from four prospective observational cohorts (DIRECT, PRIBA, PROMASTER, and GoDARTS) and two randomised clinical trials (HARMONY phase 3 and AWARD). The primary endpoint was HbA1c reduction at 6 months after starting GLP-1 receptor agonists. We evaluated variants in GLP1R, then did a genome-wide association study and gene-based burden tests. Findings:4571 adults were included in our analysis, of these, 3339 (73%) were White European, 449 (10%) Hispanic, 312 (7%) American Indian or Alaskan Native, and 471 (10%) were other, and around 2140 (47%) of the participants were women. Variation in HbA1c reduction with GLP-1 receptor agonists treatment was associated with rs6923761G & RARR;A (Gly168Ser) in the GLP1R (0.08% [95% CI 0.04-0.12] or 0.9 mmol/mol lower reduction in HbA1c per serine, p=6.0 x 10-5) and low frequency variants in ARRB1 (optimal sequence kernel association test p=6.7 x 10-8), largely driven by rs140226575G & RARR;A (Thr370Met; 0.25% [SE 0.06] or 2.7 mmol/mol [SE 0.7] greater HbA1c reduction per methionine, p=5.2 x 10-6). A similar effect size for the ARRB1 Thr370Met was seen in Hispanic and American Indian or Alaska Native populations who have a higher frequency of this variant (6-11%) than in White European populations. Combining these two genes identified 4% of the population who had a 30% greater reduction in HbA1c than the 9% of the population with the worse response. Interpretation:This genome-wide pharmacogenomic study of GLP-1 receptor agonists provides novel biological and clinical insights. Clinically, when genotype is routinely available at the point of prescribing, individuals with ARRB1 variants might benefit from earlier initiation of GLP-1 receptor agonists.
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8.
  • Dixon-Suen, Suzanne C, et al. (författare)
  • Physical activity, sedentary time and breast cancer risk : a Mendelian randomisation study
  • 2022
  • Ingår i: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 56:20, s. 1157-1170
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.METHODS: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.RESULTS: Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).CONCLUSION: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.
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9.
  • Gatner, Dylan T., et al. (författare)
  • Comparing the lexical similarity of the triarchic model of psychopathy to contemporary models of psychopathy
  • 2018
  • Ingår i: Journal of personality. - : Wiley. - 0022-3506 .- 1467-6494. ; 86:4, s. 577-589
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The triarchic model of psychopathy (Patrick, Fowles, & Krueger, 2009) posits that psychopathic personality comprises three domains: boldness, meanness, and disinhibition. The present study aimed to clarify conceptual overlap between contemporary definitions of psychopathy, with particular emphasis given to the relevance of boldness (i.e., social dominance, venturesomeness, emotional resiliency)-a topic of recent debate. Method: Undergraduate students (N=439) compared the lexical similarity of triarchic domains with two contemporary models of psychopathy: the Comprehensive Assessment of Psychopathic Personality (CAPP; Cooke, Hart, Logan, & Michie, 2012) and the Five-Factor Model of psychopathy (FFM; Widiger & Lynam, 1998). Results: From a content validity perspective, meanness and disinhibition were lexically similar to both the CAPP and FFM psychopathy, whereas boldness was less strongly associated with these models. Meanness showed the strongest lexical similarity in comparison with past prototypicality ratings of the CAPP and FFM psychopathy. Conclusions: These findings bear implications for defining and comparing conceptualizations of psychopathy that underpin its assessment. 
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10.
  • Gatner, Dylan T., et al. (författare)
  • Examining the Incremental and Interactive Effects of Boldness With Meanness and Disinhibition Within the Triarchic Model of Psychopathy
  • 2016
  • Ingår i: Personality Disorders. - : American Psychological Association (APA). - 1949-2715 .- 1949-2723. ; 7:3, s. 259-268
  • Tidskriftsartikel (refereegranskat)abstract
    • The triarchic model of psychopathy (Patrick, Fowles, & Krueger, 2009) comprises 3 phenotypic domains: Meanness, Disinhibition, and Boldness. Ongoing controversy surrounds the relevance of Boldness in the conceptualization and assessment of psychopathy. In the current study, undergraduate students (N = 439) completed the Triarchic Psychopathy Measure (Patrick, 2010) to examine the association between Boldness and a host of theoretically relevant external criteria. Boldness was generally unrelated to either prosocial or harmful criteria. Boldness rarely provided incremental value above or interacted with Meanness and Disinhibition with respect to external criteria. Curvilinear effects of Boldness rarely emerged. The findings suggest that Boldness might not be a central construct in the definition of psychopathic personality disorder. Implications for the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 2013) psychopathic specifier are discussed.
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