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Träfflista för sökning "WFRF:(Hart Nigel) "

Sökning: WFRF:(Hart Nigel)

  • Resultat 1-9 av 9
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1.
  • Evangelou, Evangelos, et al. (författare)
  • Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22
  • 2011
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group. - 1468-2060. ; 70:2, s. 349-355
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in older people. It is characterised by changes in joint structure, including degeneration of the articular cartilage, and its aetiology is multifactorial with a strong postulated genetic component. Methods A meta-analysis was performed of four genome-wide association (GWA) studies of 2371 cases of knee OA and 35 909 controls in Caucasian populations. Replication of the top hits was attempted with data from 10 additional replication datasets. Results With a cumulative sample size of 6709 cases and 44 439 controls, one genome-wide significant locus was identified on chromosome 7q22 for knee OA (rs4730250, p = 9.2 x 10(-9)), thereby confirming its role as a susceptibility locus for OA. Conclusion The associated signal is located within a large (500 kb) linkage disequilibrium block that contains six genes: PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, beta), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like) and BCAP29 (B cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.
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2.
  • Ferrario, Marco M, et al. (författare)
  • The contribution of educational class in improving accuracy of cardiovascular risk prediction across European regions : the MORGAM Project Cohort Component
  • 2014
  • Ingår i: Heart. - : BMJ Publishing Group. - 1355-6037 .- 1468-201X. ; 100:15, s. 1179-1187
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To assess whether educational class, an index of socioeconomic position, improves the accuracy of the SCORE cardiovascular disease (CVD) risk prediction equation.Methods In a pooled analysis of 68 455 40-64-year-old men and women, free from coronary heart disease at baseline, from 47 prospective population-based cohorts from Nordic countries (Finland, Denmark, Sweden), the UK (Northern Ireland, Scotland), Central Europe (France, Germany, Italy) and Eastern Europe (Lithuania, Poland) and Russia, we assessed improvements in discrimination and in risk classification (net reclassification improvement (NRI)) when education was added to models including the SCORE risk equation.Results The lowest educational class was associated with higher CVD mortality in men (pooled age-adjusted HR=1.64, 95% CI 1.42 to 1.90) and women (HR=1.31, 1.02 to 1.68). In men, the HRs ranged from 1.3 (Central Europe) to 2.1 (Eastern Europe and Russia). After adjustment for the SCORE risk, the association remained statistically significant overall, in the UK and Eastern Europe and Russia. Education significantly improved discrimination in all European regions and classification in Nordic countries (clinical NRI=5.3%) and in Eastern Europe and Russia (NRI=24.7%). In women, after SCORE risk adjustment, the association was not statistically significant, but the reduced number of deaths plays a major role, and the addition of education led to improvements in discrimination and classification in the Nordic countries only.Conclusions We recommend the inclusion of education in SCORE CVD risk equation in men, particularly in Nordic and East European countries, to improve social equity in primary prevention. Weaker evidence for women warrants the need for further investigations.
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3.
  • Rose, Peter W., et al. (författare)
  • Development of a survey instrument to investigate the primary care factors related to differences in cancer diagnosis between international jurisdictions
  • 2014
  • Ingår i: BMC Family Practice. - : BioMed Central. - 1471-2296 .- 1471-2296. ; 15, s. 1-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Survival rates following a diagnosis of cancer vary between countries. The International Cancer Benchmarking Partnership (ICBP), a collaboration between six countries with primary care led health services, was set up in 2009 to investigate the causes of these differences. Module 3 of this collaboration hypothesised that an association exists between the readiness of primary care physicians (PCP) to investigate for cancer - the 'threshold' risk level at which they investigate or refer to a specialist for consideration of possible cancer - and survival for that cancer (lung, colorectal and ovarian). We describe the development of an international survey instrument to test this hypothesis. Methods: The work was led by an academic steering group in England. They agreed that an online survey was the most pragmatic way of identifying differences between the jurisdictions. Research questions were identified through clinical experience and expert knowledge of the relevant literature. A survey comprising a set of direct questions and five clinical scenarios was developed to investigate the hypothesis. The survey content was discussed and refined concurrently and repeatedly with international partners. The survey was validated using an iterative process in England. Following validation the survey was adapted to be relevant to the health systems operating in other jurisdictions and translated into Danish, Norwegian and Swedish, and into Canadian and Australian English. Results: This work has produced a survey with face, content and cross cultural validity that will be circulated in all six countries. It could also form a benchmark for similar surveys in countries with similar health care systems. Conclusions: The vignettes could also be used as educational resources. This study is likely to impact on healthcare policy and practice in participating countries.
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4.
  • Rose, Peter W., et al. (författare)
  • Explaining variation in cancer survival between 11 jurisdictions in the International Cancer Benchmarking Partnership : a primary care vignette survey
  • 2015
  • Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055 .- 2044-6055. ; 5:5, s. 1-14
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The International Cancer Benchmarking Partnership (ICBP) is a collaboration between 6 countries and 12 jurisdictions with similar primary care-led health services. This study investigates primary care physician (PCP) behaviour and systems that may contribute to the timeliness of investigating for cancer and subsequently, international survival differences. Design: A validated survey administered to PCPs via the internet set out in two parts: direct questions on primary care structure and practice relating to cancer diagnosis, and clinical vignettes, assessing management of scenarios relating to the diagnosis of lung, colorectal or ovarian cancer. Participants: 2795 PCPs in 11 jurisdictions: New South Wales and Victoria (Australia), British Columbia, Manitoba, Ontario (Canada), England, Northern Ireland, Wales (UK), Denmark, Norway and Sweden. Primary and secondary outcome measures: Analysis compared the cumulative proportion of PCPs in each jurisdiction opting to investigate or refer at each phase for each vignette with 1-year survival, and conditional 5-year survival rates for the relevant cancer and jurisdiction. Logistic regression was used to explore whether PCP characteristics or system differences in each jurisdiction affected the readiness to investigate. Results: 4 of 5 vignettes showed a statistically significant correlation (p<0.05 or better) between readiness to investigate or refer to secondary care at the first phase of each vignette and cancer survival rates for that jurisdiction. No consistent associations were found between readiness to investigate and selected PCP demographics, practice or health system variables. Conclusions: We demonstrate a correlation between the readiness of PCPs to investigate symptoms indicative of cancer and cancer survival rates, one of the first possible explanations for the variation in cancer survival between ICBP countries. No specific health system features consistently explained these findings. Some jurisdictions may consider lowering thresholds for PCPs to investigate for cancer-either directly, or by specialist referral, to improve outcomes.
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5.
  • Siegmann, Susanne, et al. (författare)
  • Naked mole-rats (Heterocephalus glaber) do not specialise in cooperative tasks
  • 2021
  • Ingår i: Ethology. - : John Wiley & Sons. - 0179-1613 .- 1439-0310. ; 127:10, s. 850-864
  • Tidskriftsartikel (refereegranskat)abstract
    • It has been proposed that naked mole-rat (Heterocephalus glaber) societies resemble those of eusocial insects by showing a division of labour among non-breeding individuals. Earlier studies suggested that non-breeders belong to distinct castes that specialise permanently or temporarily in specific cooperative tasks. In contrast, recent research on naked mole-rats has shown that behavioural phenotypes are continuously distributed across non-breeders and that mole-rats exhibit considerable behavioural plasticity suggesting that individuals may not specialise permanently in work tasks. However, it is currently unclear whether individuals specialise temporarily and whether there is a sex bias in cooperative behaviour among non-breeders. Here, we show that non-breeding individuals vary in overall cooperative investment, but do not specialise in specific work tasks. Within individuals, investment into specific cooperative tasks such as nest building, food carrying and burrowing is positively correlated, and there is no evidence that individuals show trade-offs between these cooperative behaviours. Non-breeding males and females do not differ in their investment in cooperative behaviours and show broadly similar age and body mass related differences in cooperative behaviours. Our results suggest that non-breeding naked mole-rats vary in their overall contribution to cooperative behaviours and that some of this variation may be explained by differences in age and body mass. Our data provide no evidence for temporary specialisation, as found among some eusocial insects and suggest that the behavioural organisation of naked mole-rats resembles that of other cooperatively breeding vertebrates more than that of eusocial insect species.
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6.
  • Styrkarsdottir, Unnur, et al. (författare)
  • Severe osteoarthritis of the hand associates with common variants within the ALDH1A2 gene and with rare variants at 1p31.
  • 2014
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1546-1718. ; 46:5, s. 498-502
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteoarthritis is the most common form of arthritis and is a major cause of pain and disability in the elderly. To search for sequence variants that confer risk of osteoarthritis of the hand, we carried out a genome-wide association study (GWAS) in subjects with severe hand osteoarthritis, using variants identified through the whole-genome sequencing of 2,230 Icelanders. We found two significantly associated loci in the Icelandic discovery set: at 15q22 (frequency of 50.7%, odds ratio (OR) = 1.51, P = 3.99 × 10(-10)) in the ALDH1A2 gene and at 1p31 (frequency of 0.02%, OR = 50.6, P = 9.8 × 10(-10)). Among the carriers of the variant at 1p31 is a family with several members in whom the risk allele segregates with osteoarthritis. The variants within the ALDH1A2 gene were confirmed in replication sets from The Netherlands and the UK, yielding an overall association of OR = 1.46 and P = 1.1 × 10(-11) (rs3204689).
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7.
  • Thompson, Robin N., et al. (författare)
  • Key questions for modelling COVID-19 exit strategies
  • 2020
  • Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - 0962-8452 .- 1471-2954. ; 287:1932
  • Tidskriftsartikel (refereegranskat)abstract
    • Combinations of intense non-pharmaceutical interventions (lockdowns) were introduced worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement exit strategies that relax restrictions while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but the challenge of designing optimal exit strategies in the face of ongoing transmission is unprecedented. Here, we report discussions from the Isaac Newton Institute 'Models for an exit strategy' workshop (11-15 May 2020). A diverse community of modellers who are providing evidence to governments worldwide were asked to identify the main questions that, if answered, would allow for more accurate predictions of the effects of different exit strategies. Based on these questions, we propose a roadmap to facilitate the development of reliable models to guide exit strategies. This roadmap requires a global collaborative effort from the scientific community and policymakers, and has three parts: (i) improve estimation of key epidemiological parameters; (ii) understand sources of heterogeneity in populations; and (iii) focus on requirements for data collection, particularly in low-to-middle-income countries. This will provide important information for planning exit strategies that balance socio-economic benefits with public health.
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8.
  • Thomson, Suzanne E., et al. (författare)
  • Bioengineered nerve conduits and wraps for peripheral nerve repair of the upper limb
  • 2017
  • Ingår i: Cochrane Database of Systematic Reviews. - : Wiley-Blackwell. - 1361-6137. ; 2017:3
  • Forskningsöversikt (refereegranskat)abstract
    • This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess and compare the effects and complication rates of licensed bioengineered nerve conduits or wraps for surgical repair of traumatic peripheral nerve injuries of the upper limb. To compare effects and complications against the current gold surgical standard (nerve autograft).
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9.
  • 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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