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Sökning: WFRF:(Stafford Jean)

  • Resultat 1-5 av 5
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1.
  • Pattaro, Cristian, et al. (författare)
  • Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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2.
  • Postmus, Iris, et al. (författare)
  • Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.
  • 2014
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.
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3.
  • Bai, Xuemei, et al. (författare)
  • Defining and advancing a systems approach for sustainable cities
  • 2016
  • Ingår i: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435 .- 1877-3443. ; 23, s. 69-78
  • Forskningsöversikt (refereegranskat)abstract
    • The sustainable development of cities is increasingly recognized as crucial to meeting collectively agreed sustainability goals at local, regional and global scales, and more broadly to securing human well-being worldwide. The UN Sustainable Development Goals (SDGs) include a goal on cities (Goal 11), with most other goals and targets have urban applications and multi scalar implications for their implementation. Further, the interdependencies - including synergies and trade-offs among the various SDGs are greater in cities, presenting both challenges and opportunities. A systems approach is urgently needed in urban research and policy analysis, but such an approach rarely features in current analysis or urban decision-making for various reasons. This paper explores four questions: why a systems approach is necessary, what defines such an approach, why has this rarely been adopted in practice, and what can be done to promote its use. We argue that a systems approach can reveal unrecognized opportunities to maximize co-benefits and synergies, guide management of inevitable trade-offs, and therefore inform prioritisation and successful solutions. We present four key issues for the effective implementation of the SDGs and the New Urban Agenda, which emerged from UN Habitat III Conference, namely: (a) a radical redesign of the multilateral institutional setup on urban issues; (b) promoting regenerative culture, behaviour, and design; (c) exploring ways to finance a systems approach; and (d) a new and enhanced role for science in sustainable development. The latter issue could be addressed through Future Earth's Urban Knowledge-Action Network, which aims at co-designing and co-producing cutting-edge and actionable knowledge for sustainable cities bringing together researchers and urban decision-makers and practitioners.
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4.
  • Maddock, Jane, et al. (författare)
  • Social health and change in cognitive capability among older adults : findings from four European longitudinal studies
  • 2023
  • Ingår i: Gerontology. - 0304-324X .- 1423-0003. ; 69:11, s. 1330-1346
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: In this study we examine whether social health markers measured at baseline are associated with differences in cognitive capability and in the rate of cognitive decline over an 11-to-18-year period among older adults and compare results across studies. Methods: We applied an integrated data analysis approach to 16,858 participants (mean age 65 years; 56% female) from the National Survey for Health and Development (NSHD), the English Longitudinal Study of Aging (ELSA), the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), and the Rotterdam Study. We used multilevel models to examine social health in relation to cognitive capability and the rate of cognitive decline. Results: Pooled estimates show distinct relationships between markers of social health and cognitive domains e.g., a large network size (& GE;6 people vs none) was associated with higher executive function (0.17 SD[95%CI:0.0, 0.34], I2=27%) but not with memory (0.08 SD[95%CI: -0.02, 0.18], I2=19%). We also observed pooled associations between being married or cohabiting, having a large network size and participating in social activities with slower decline in cognitive capability, however estimates were close to zero e.g., 0.01SD/year [95%CI: 0.01 to 0.02] I2=19% for marital status and executive function. There were clear study-specific differences: results for average processing speed were the most homogenous and results for average memory were the most heterogenous. Conclusion: Overall, markers of good social health have a positive association with cognitive capability. However, we found differential associations between specific markers of social health and cognitive domains and differences between studies. These findings highlight the importance of examining between study differences and considering context specificity of findings in developing and deploying any interventions
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5.
  • Norström, Albert, et al. (författare)
  • Principles for knowledge co-production in sustainability research
  • 2020
  • Ingår i: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 3:3, s. 182-190
  • Tidskriftsartikel (refereegranskat)abstract
    • Research practice, funding agencies and global science organizations suggest that research aimed at addressing sustainability challenges is most effective when 'co-produced' by academics and non-academics. Co-production promises to address the complex nature of contemporary sustainability challenges better than more traditional scientific approaches. But definitions of knowledge co-production are diverse and often contradictory. We propose a set of four general principles that underlie high-quality knowledge co-production for sustainability research. Using these principles, we offer practical guidance on how to engage in meaningful co-productive practices, and how to evaluate their quality and success. Research addressing sustainability issues is more effective if 'co-produced' by academics and non-academics, but definitions of co-production vary. This Perspective presents four knowledge co-production principles for sustainability research and guides on how to engage in co-productive practices.
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