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- Gergei, Ingrid, et al.
(författare)
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GWAS META-analysis followed by MENDELIAN randomisation revealed potential control mechanisms for circulating α-klotho levels.
- 2022
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 31:5, s. 792-802
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Tidskriftsartikel (refereegranskat)abstract
- The protein α-Klotho acts as transmembrane the co-receptor for fibroblast growth factor 23 (FGF-23) and is a key regulator of phosphate homeostasis. However, α-Klotho also exists in a circulating form, with pleiotropic, but incompletely understood functions and regulation. Therefore, we undertook a GWAS meta-analysis followed by Mendelian randomisation (MR) of circulating α-Klotho levels.Plasma α-Klotho levels were measured by ELISA in the LURIC and ALSPAC (mothers) cohorts, followed by a GWAS meta-analysis in 4376 individuals across the two cohorts.Six signals at five loci were associated with circulating α-Klotho levels at genome-wide significance (p<5×10-8), namely ABO, KL, FGFR1, and two post-translational modification genes, B4GALNT3 and CHST9. Together, these loci explained >9% of the variation in circulating α-Klotho levels. MR analyses revealed no causal relationships between α-Klotho and renal function, FGF-23-dependent factors such as vitamin D and phosphate levels, or bone mineral density. The screening for genetic correlations with other phenotypes, followed by targeted MR suggested causal effects of liability of Crohn's disease risk [IVW beta=0.059 (95% CI 0.026, 0.093)] and low-density lipoprotein cholesterol (LDL-C) levels [-0.198, (-0.332, -0.063)] on α-Klotho.Our GWAS findings suggest that two enzymes involved in post-translational modification, B4GALNT3 and CHST9, contribute to genetic influences on α-Klotho levels, presumably by affecting protein turnover and stability. Subsequent evidence from MR analyses on α-Klotho levels suggest regulation by mechanisms besides phosphate-homeostasis and raise the possibility of cross-talk with FGF19- and FGF21-dependent pathways, respectively.
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| 2. |
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| 3. |
- Thomas, Sinju, et al.
(författare)
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Effects of material properties of band-gap-graded Cu(In,Ga)Se-2 thin films on the onset of the quantum efficiency spectra of corresponding solar cells
- 2022
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Ingår i: Progress in Photovoltaics. - : John Wiley & Sons. - 1062-7995 .- 1099-159X. ; 30:10, s. 1238-1246
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Tidskriftsartikel (refereegranskat)abstract
- Polycrystalline Cu(In,Ga)Se-2 (CIGSe) thin-film solar cells exhibit gradual onset in their external quantum efficiency (EQE) spectra whose shape can be affected by various CIGSe material properties. Apart from influences on the charge-carrier collection, a broadening of the EQE onset leads to enhanced radiative losses in open-circuit voltage (V-oc). In the present work, Gaussian broadening of parameters describing the EQE onset of thin-film solar cells, represented by the standard deviation, sigma(total), was evaluated to study the impacts of the effective band-gap energy, the electron diffusion length, and the Ga/In gradient in the CIGSe absorber. It is shown that sigma(total) can be disentangled into contributions of these material properties, in addition to a residual component sigma(residual). Effectively, sigma(total) depends only on a contribution related to the Ga/In gradient as well as on sigma(residual). The present work highlights the connection of this compositional gradient, the microstructure in the polycrystalline CIGSe absorber, and the luminescence emission with the residual component sigma(residual). It is demonstrated that a flat band-gap with no compositional gradient in the bulk of the CIGSe absorber is essential to obtain the lowest sigma(total) values and thus result in lower recombination losses and gains in V-oc.
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| 4. |
- Thorogood, Margaret, et al.
(författare)
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The Nkateko health service trial to improve hypertension management in rural South Africa : study protocol for a randomised controlled trial
- 2014
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 15, s. 435-
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Tidskriftsartikel (refereegranskat)abstract
- Background: South Africa has a high and rising prevalence of hypertension. Many affected individuals are not using medication, and few have controlled blood pressure. Until recently, primary care clinics focused on maternal and child health and management of acute conditions, but new government initiatives have shifted the focus to chronic diseases, including HIV/AIDS and hypertension.Methods/Design: The Nkateko trial will test the effectiveness of clinic-based lay health workers (LHWs) in supporting hypertension management. It is a pragmatic, cluster randomised controlled trial based in the Agincourt subdistrict of northeast South Africa, and it is underpinned by long-term health and demographic surveillance. Eight primary care facilities, with their catchment communities, are randomised to usual care or the addition of LHWs focused on chronic care. All clinics (intervention and control) will be provided with a clerk to collect information on clinic attendees and will match them to preexisting surveillance records. Intervention clinics will have LHWs working alongside nursing staff and focusing on health care for people with chronic conditions, particularly hypertension. The LHWs will be supported by an implementation manager, who will work with clinic staff to develop the most effective role for the LHWs. Control clinics will continue to provide usual care. The primary outcome will be the change between two population surveys conducted before and after the intervention in the proportion of the population with uncontrolled hypertension and a risk profile indicating at least moderate risk of cardiovascular disease. A process evaluation will be based on a realist approach using patient exit interviews, clinic observations and interviews with health professionals, LHWs and patients to document the intervention and its implementation.Discussion: There are challenges in the design of this trial. Assessing change through population surveys may reduce measurable effects; however, we feel this is appropriate because we aim to attract those who currently do not use clinics, and we hope to improve care for clinic users. Clinics were randomised at an open meeting because we were concerned that a remote process of randomisation would not be trusted by the community. We are constantly working to achieve an effective balance between the intervention and process evaluations.
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