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- Thomas, B., et al.
(författare)
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Global Cardiovascular and Renal Outcomes of Reduced GFR
- 2017
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Ingår i: Journal of the American Society of Nephrology. - : Ovid Technologies (Wolters Kluwer Health). - 1046-6673 .- 1533-3450. ; 28:7, s. 2167-2179
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Tidskriftsartikel (refereegranskat)abstract
- The burden of premature death and health loss from ESRD is well described. Less is known regarding the burden of cardiovascular disease attributable to reduced GFR. We estimated the prevalence of reduced GFR categories 3, 4, and 5 (not on RRT) for 188 countries at six time points from 1990 to 2013. Relative risks of cardiovascular outcomes by three categories of reduced GFR were calculated by pooled random effects meta-analysis. Results are presented as deaths for outcomes of cardiovascular disease and ESRD and as disability-adjusted life years for outcomes of cardiovascular disease, GFR categories 3, 4, and 5, and ESRD. In 2013, reduced GFR was associated with 4% of deaths worldwide, or 2.2 million deaths (95% uncertainty interval [95% UI], 2.0 to 2.4 million). More than half of these attributable deaths were cardiovascular deaths (1.2 million; 95% UI, 1.1 to 1.4 million), whereas 0.96 million (95% UI, 0.81 to 1.0 million) were ESRD-related deaths. Compared with metabolic risk factors, reduced GFR ranked below high systolic BP, high body mass index, and high fasting plasma glucose, and similarly with high total cholesterol as a risk factor for disability-adjusted life years in both developed and developing world regions. In conclusion, by 2013, cardiovascular deaths attributed to reduced GFR outnumbered ESRD deaths throughout the world. Studies are needed to evaluate the benefit of early detection of CKD and treatment to decrease these deaths.
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| 3. |
- Wilman, H. R., et al.
(författare)
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Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration
- 2019
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 71:3, s. 594-602
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p <5 × 10−8). The 2 HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. Conclusion: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. Lay summary: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart disease. We identified 3 genetic variants that are linked to an increased risk of developing higher liver iron content. We show that the same genetic variants are linked to higher risk of many diseases, but they may also be associated with some health advantages. Finally, we use genetic variants associated with waist-to-hip ratio as a tool to show that central obesity is causally associated with increased liver iron content.
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| 6. |
- Topchiev, N. P., et al.
(författare)
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The GAMMA-400 experiment : Status and prospects
- 2015
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Ingår i: Bulletin of the Russian Academy of Sciences: Physics. - 1062-8738. ; 79:3, s. 417-420
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Tidskriftsartikel (refereegranskat)abstract
- The development of the GAMMA-400 γ-ray telescope continues. The GAMMA-400 is designed to measure fluxes of γ-rays and the electron-positron cosmic-ray component possibly associated with annihilation or decay of dark matter particles; and to search for and study in detail discrete γ-ray sources, to measure the energy spectra of Galactic and extragalactic diffuse γ-rays, and to study γ-ray bursts and γ-rays from the active Sun. The energy range for measuring γ-rays and electrons (positrons) is from 100 MeV to 3000 GeV. For 100-GeV γ-rays, the γ-ray telescope has an angular resolution of ∼0.01°, an energy resolution of ∼1%, and a proton rejection factor of ∼5 × 105. The GAMMA-400 will be installed onboard the Russian Space Observatory.
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| 7. |
- Raghavan, Maanasa, et al.
(författare)
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Genomic evidence for the Pleistocene and recent population history of Native Americans
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 349:6250
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Tidskriftsartikel (refereegranskat)abstract
- Howand when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we found that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (ka) and after no more than an 8000-year isolation period in Beringia. After their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 ka, one that is now dispersed across North and South America and the other restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians (including Siberians) and, more distantly, Australo-Melanesians. Putative "Paleoamerican" relict populations, including the historical Mexican Pericues and South American Fuego-Patagonians, are not directly related to modern Australo-Melanesians as suggested by the Paleoamerican Model.
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| 8. |
- Topchiev, N. P., et al.
(författare)
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GAMMA-400 gamma-ray observatory
- 2015
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Ingår i: Proceedings of Science. - : Proceedings of Science (PoS).
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Konferensbidrag (refereegranskat)abstract
- The GAMMA-400 gamma-ray telescope with excellent angular and energy resolutions is designed to search for signatures of dark matter in the fluxes of gamma-ray emission and electrons+ positrons.Precision investigations of gamma-ray emission fromGalactic Center, Crab, Vela, Cygnus, Geminga, and other regions will be performed, as well asdiffuse gamma-rayemission,along with measurements of high-energy electron + positron and nuclei fluxes. Furthermore, it will studygamma-ray bursts and gamma-ray emission from the Sun during periods of solar activity. The energy range of GAMMA-400 is expected to be from ∼20 MeV up to TeV energies for gamma rays, up to 10 TeV for electrons + positrons, and up to 1015eV for cosmic-ray nuclei. For high-energy gamma rays with energy from 10 to 100 GeV, the GAMMA-400 angular resolution improves from 0.1° to ∼0.01° and energy resolution from 3% to ∼1%; the proton rejection factor is ∼5x105. GAMMA-400 will be installed onboardthe Russian space observatory.
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