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Sökning: WFRF:(Hart D. Stephen)

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1.
  • Overview of the JET results
  • 2015
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 55:10
  • Tidskriftsartikel (refereegranskat)
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2.
  • 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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3.
  • 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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4.
  • 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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5.
  • Needham, Jessica F., et al. (författare)
  • Demographic composition, not demographic diversity, predicts biomass and turnover across temperate and tropical forests
  • 2022
  • Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 28, s. 2895-2909
  • Tidskriftsartikel (refereegranskat)abstract
    • The growth and survival of individual trees determine the physical structure of a forest with important consequences for forest function. However, given the diversity of tree species and forest biomes, quantifying the multitude of demographic strategies within and across forests and the way that they translate into forest structure and function remains a significant challenge. Here, we quantify the demographic rates of 1961 tree species from temperate and tropical forests and evaluate how demographic diversity (DD) and demographic composition (DC) differ across forests, and how these differences in demography relate to species richness, aboveground biomass (AGB), and carbon residence time. We find wide variation in DD and DC across forest plots, patterns that are not explained by species richness or climate variables alone. There is no evidence that DD has an effect on either AGB or carbon residence time. Rather, the DC of forests, specifically the relative abundance of large statured species, predicted both biomass and carbon residence time. Our results demonstrate the distinct DCs of globally distributed forests, reflecting biogeography, recent history, and current plot conditions. Linking the DC of forests to resilience or vulnerability to climate change, will improve the precision and accuracy of predictions of future forest composition, structure, and function.
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6.
  • Wang, Thomas J, et al. (författare)
  • Common genetic determinants of vitamin D insufficiency: a genome-wide association study.
  • 2010
  • Ingår i: Lancet. - 1474-547X. ; 376:9736, s. 180-8
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25-hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency. METHODS: We undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L. We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis. Genotype scores were constructed for confirmed variants. FINDINGS: Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts: 4p12 (overall p=1.9x10(-109) for rs2282679, in GC); 11q12 (p=2.1x10(-27) for rs12785878, near DHCR7); and 11p15 (p=3.3x10(-20) for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6.0x10(-10) for rs6013897). Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L (OR 2.47, 95% CI 2.20-2.78, p=2.3x10(-48)) or lower than 50 nmol/L (1.92, 1.70-2.16, p=1.0x10(-26)) compared with those in the lowest quartile. INTERPRETATION: Variants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency. FUNDING: Full funding sources listed at end of paper (see Acknowledgments).
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7.
  • 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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8.
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9.
  • 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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10.
  • 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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11.
  • 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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12.
  • 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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14.
  • Michel, Steven F., et al. (författare)
  • Using the HCR-20 to Predict Aggressive Behavior among Men with Schizophrenia Living in the Community: Accuracy of Prediction, General and Forensic Settings, and Dynamic Risk Factors
  • 2013
  • Ingår i: International Journal of Forensic Mental Health. - : Informa UK Limited. - 1932-9903 .- 1499-9013. ; 12:1, s. 1-13
  • Tidskriftsartikel (refereegranskat)abstract
    • The HCR-20 is widely used to assess risk of violence among patients with schizophrenia. Further understanding of the accuracy and changes over time in C and R scores is needed. Using prospectively collected data on 248 men with schizophrenia, the present study found that the HCR-20 significantly predicted aggressive behavior over 24 months. The H, C, R, HCR-20 total, and final risk judgment scores were unable to predict aggressive behavior better than chance among the general psychiatric patients in the first six months after discharge. Changes in three C items, the total R score, and in three R items significantly predicted changes in aggressive behavior.
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15.
  • Samplonius, Jelmer M., et al. (författare)
  • Strengthening the evidence base for temperature-mediated phenological asynchrony and its impacts
  • 2021
  • Ingår i: Nature Ecology and Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 5:2, s. 155-164
  • Forskningsöversikt (refereegranskat)abstract
    • Climate warming has caused the seasonal timing of many components of ecological food chains to advance. In the context of trophic interactions, the match–mismatch hypothesis postulates that differential shifts can lead to phenological asynchrony with negative impacts for consumers. However, at present there has been no consistent analysis of the links between temperature change, phenological asynchrony and individual-to-population-level impacts across taxa, trophic levels and biomes at a global scale. Here, we propose five criteria that all need to be met to demonstrate that temperature-mediated trophic asynchrony poses a growing risk to consumers. We conduct a literature review of 109 papers studying 129 taxa, and find that all five criteria are assessed for only two taxa, with the majority of taxa only having one or two criteria assessed. Crucially, nearly every study was conducted in Europe or North America, and most studies were on terrestrial secondary consumers. We thus lack a robust evidence base from which to draw general conclusions about the risk that climate-mediated trophic asynchrony may pose to populations worldwide.
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16.
  • Storey, Jennifer, et al. (författare)
  • Assessment and Management of Risk for Intimate Partner Violence by Police Officers. Using the Brief Spousal Assault Form for the Evaluation of Risk (B-SAFER).
  • 2014
  • Ingår i: Criminal justice and behavior. - : SAGE Publications. - 0093-8548 .- 1552-3594. ; 41:2, s. 256-271
  • Tidskriftsartikel (refereegranskat)abstract
    • The management of intimate partner violence (IPV) typically falls to police. For assistance, officers are increasingly using violence risk assessment tools like the Brief Spousal Assault Form for the Evaluation of Risk (B-SAFER). This study replicates the methodology of Belfrage et al. but examines the B-SAFER as used by Swedish police officers when assessing and managing IPV. Results revealed a positive relationship between risk and management. Total scores and overall risk ratings predicted recidivism (AUC [Area under the curve] = .70 and .69, respectively). Finally, a pattern where management recommendations were associated with decreased recidivism in high risk perpetrators but increased recidivism in low risk perpetrators was found. Results validate the use of the B-SAFER by police and reveal mostly comparable findings between the B-SAFER and the Spousal Assault Risk Assessment Guide, as examined by Belfrage et al., but suggest that the B-SAFER may be better suited for police.
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17.
  • Storey, Jennifer E., et al. (författare)
  • An examination of violence risk communication in practice using a structured professional judgment framework.
  • 2015
  • Ingår i: Behavioral sciences & the law (Print). - : Wiley. - 0735-3936 .- 1099-0798. ; 33:1, s. 39-55
  • Tidskriftsartikel (refereegranskat)abstract
    • The increased use of violence risk assessment tools in professional practice has sparkedthe development of best-practice guidelines for communicating about violence risk.The present study examined 166 pre-sentence reports, authored by clinicians and probationofficers, to determine the extent to which they are consistent with those guidelines.We examined the frequency with which reports contained information aboutfive topics: the presence of risk factors; the relevance of risk factors; scenarios of futureviolence; recommended management strategies; and summary risk judgments. Analysesrevealed that the topics addressed most frequently in reports were the presence ofrisk factors and recommended management strategies, but none of the five topics wasaddressed consistently, completely, or clearly in reports. This was especially the casefor probation reports. The findings highlight the need to improve practice throughbetter implementation of guidelines for risk communication. Also needed is researchon the extent to which information in risk communications is comprehended,accepted, and used by various stakeholder groups.
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