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- Winkler, TW, et al.
(författare)
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Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 580-
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
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- Bergström, Anna, 1983-, et al.
(författare)
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The use of the PARIHS framework in implementation research and practice-a citation analysis of the literature
- 2020
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Ingår i: Implementation science : IS. - : Springer Science and Business Media LLC. - 1748-5908. ; 15:1
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: The Promoting Action on Research Implementation in Health Services (PARIHS) framework was developed two decades ago and conceptualizes successful implementation (SI) as a function (f) of the evidence (E) nature and type, context (C) quality, and the facilitation (F), [SI = f (E,C,F)]. Despite a growing number of citations of theoretical frameworks including PARIHS, details of how theoretical frameworks are used remains largely unknown. This review aimed to enhance the understanding of the breadth and depth of the use of the PARIHS framework. METHODS: This citation analysis commenced from four core articles representing the key stages of the framework's development. The citation search was performed in Web of Science and Scopus. After exclusion, we undertook an initial assessment aimed to identify articles using PARIHS and not only referencing any of the core articles. To assess this, all articles were read in full. Further data extraction included capturing information about where (country/countries and setting/s) PARIHS had been used, as well as categorizing how the framework was applied. Also, strengths and weaknesses, as well as efforts to validate the framework, were explored in detail. RESULTS: The citation search yielded 1613 articles. After applying exclusion criteria, 1475 articles were read in full, and the initial assessment yielded a total of 367 articles reported to have used the PARIHS framework. These articles were included for data extraction. The framework had been used in a variety of settings and in both high-, middle-, and low-income countries. With regard to types of use, 32% used PARIHS in planning and delivering an intervention, 50% in data analysis, 55% in the evaluation of study findings, and/or 37% in any other way. Further analysis showed that its actual application was frequently partial and generally not well elaborated. CONCLUSIONS: In line with previous citation analysis of the use of theoretical frameworks in implementation science, we also found a rather superficial description of the use of PARIHS. Thus, we propose the development and adoption of reporting guidelines on how framework(s) are used in implementation studies, with the expectation that this will enhance the maturity of implementation science.
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- Gorski, Mathias, et al.
(författare)
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Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
- 2022
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 102:3, s. 624-639
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Tidskriftsartikel (refereegranskat)abstract
- Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
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| 6. |
- Hultquist, Gunnar, et al.
(författare)
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Corrosion of copper in distilled water without O-2 and the detection of produced hydrogen
- 2015
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Ingår i: Corrosion Science. - : Elsevier BV. - 0010-938X .- 1879-0496. ; 95, s. 162-167
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Tidskriftsartikel (refereegranskat)abstract
- This paper reports on hydrogen pressures measured during similar to 19,000 h immersion of copper in oxygen-free liquid distilled water. Copper corrosion products have been examined ex-situ by SEM and characterized by XPS and SIMS. XPS strongly indicates a corrosion product containing both oxygen and hydrogen. SIMS shows that oxygen is mainly present in the outer 0.3 mu m surface region and that hydrogen penetrates to depths well below the corrosion product. Thermal desorption spectroscopy shows that the reaction product formed near room-temperature is less stable than that formed in air at 350 degrees C.
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