| 1. |
- Gorski, Mathias, et al.
(författare)
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Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
- 2021
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 99:4, s. 926-939
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Tidskriftsartikel (refereegranskat)abstract
- Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
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| 2. |
- Schäpke, Niko Alexander, 1977, et al.
(författare)
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Jointly experimenting for transformation?: Shaping real-world laboratories by comparing them
- 2018
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Ingår i: GAIA. - 2625-5413 .- 0940-5550. ; 27, s. 85-96
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Tidskriftsartikel (refereegranskat)abstract
- Real-world laboratories (RwLs, German Reallabore) belong to a family of increasingly popular experimental and transdisciplinary research approaches at the science-society interface. As these approaches in general, and RwLs in particular, often lack clear definitions of key characteristics and their operationalization, we make two contributions in this article. First, we identify five core characteristics of RwLs: contribution to transformation, experimental methods, transdisciplinary research mode, scalability and transferability of results, as well as scientific and societal learning and reflexivity. Second, we compare RwLs to similar research approaches according to the five characteristics. In this way, we provide an orientation on experimental and transdisciplin ary research for societal transformations, and reveal the contributions of this type of research in supporting societal change. Our findings enable learning across the different approaches and highlight their complementarities, with a particular focus on RwLs.
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| 3. |
- Fox, Sydney, et al.
(författare)
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Physical characteristics of microplastic particles and potential for global atmospheric transport: A meta-analysis
- 2024
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Ingår i: Environmental Pollution. - 0269-7491 .- 1873-6424. ; 342
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Forskningsöversikt (refereegranskat)abstract
- Recent interest in microplastic pollution of natural environments has brought forth samples which confirm the pollutant's omnipresence in a variety of ecosystems. This includes locations furthest removed from human activity. Atmospheric transport and deposition are suspected as the primary transport pathway to these remote locations. The factors most influential on participation in atmospheric transport are yet to be determined. This meta-analysis aims to identify patterns that exist between physical characteristics of microplastic particles and their potential for atmospheric transport. Our review addresses the following questions: Which characteristics of microplastic particles promote atmospheric transport and deposition into remote regions, and how significant are these factors in determining distance transported from their sources? This article analyzes commonly reported physical attributes– shape, polymer composition and color– from studies in urban and remote areas. The analysis of 68 studies, composed of data from 2078 samples, shows higher occurrence of microplastic particles in remote samples with fiber shapes, polyester compositions, and red, blue, and transparent colors. This meta-analysis is the first to identify patterns between physical properties of microplastic particles and extent of their participation in atmospheric transport to global remote locations.
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| 4. |
- Sakornsakolpat, Phuwanat, et al.
(författare)
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Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 494-505
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 x 10-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.
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| 7. |
- Wanner, Matthias, et al.
(författare)
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Towards a Cyclical Concept of Real-World Laboratories A Transdisciplinary Research Practice for Sustainability Transitions
- 2018
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Ingår i: DISP. - : Informa UK Limited. - 0251-3625 .- 2166-8604. ; 54:2, s. 94-114
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Tidskriftsartikel (refereegranskat)abstract
- The transformative research approach of Real-World Laboratories (RWL) has recently attracted attention in German sustainability science. Some definitions and understandings have been published, but guidelines and procedural quality criteria for establishing and running a RWL are still missing. To address this gap, this article has two aims. First, it aims to derive key components of RWLs from the current discourse on RWLs and similar, but more elaborated research approaches. Second, it aims to transfer these key components into a comprehensive research practice. This practice is illustrated by the RWL process in the project "Well-being Transformation Wuppertal" (WTW). Methodologically, the article builds on a review of RWL-related approaches for collaborative, intervention-oriented research. This includes transition management, transdisciplinary process models and action research. Based on this review, eight key components for RWLs are proposed. They position RWLs as a normatively framed approach that aims to contribute to local action for sustainable development and the empowerment of change agents. The approach uses transdisciplinary methods of knowledge integration and engages in cyclical real-world interventions within certain spatial and content-related boundaries. The components are transferred into a flow-chart, detailing process steps, aims, responsibilities and overall principles for putting RWLs into practice. Thus, a hitherto missing tool for designing and running RWLs is provided. Then, the RWL in the district of Mirke, Wuppertal, is used as an empirical example to illustrate the application of the flowchart and related key components. Consecutive discussions centre on the different roles of researchers and practitioners in the research process, as well as the relevance of an underlying theory of change for effective interventions. Finally, critical reflection, application and amendment of the proposed flowchart are encouraged.
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