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- Roselli, Carolina, et al.
(författare)
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Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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- Crawley, C, et al.
(författare)
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Outcomes for reduced-intensity allogeneic transplantation for multiple myeloma: an analysis of prognostic factors from the Chronic Leukaemia Working Party of the EBMT
- 2005
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 105:11, s. 4532-4539
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Tidskriftsartikel (refereegranskat)abstract
- We report the outcome of 229 patients who received an allograft for myeloma with reduced-intensity conditioning (RIC) regimens from 33 centers within the European Group for Blood and Marrow Transplantation (EBMT). The median age was 52 years and 64% were male. Conditioning regimens were heterogeneous, but most were fludarabine based and T cell depleted with antithymocyte globulin or alemtuzumab. Transplantation-related mortality (TRIM) at 1 year was 22%. The 3-year overall survival (OS) and progression-free survival (PFS) were 41% and 21 %, respectively. Adverse OS was associated with chemoresistant disease (relative risk [RR], 2.9), more than 1 prior transplantation (RR, 2.0), and male patients with female donors (FIR, 1.45). Adverse PFS was associated with chemoresistance (RR, 2.4) and alemtuzumab (RR, 1.8). TRM was increased with female-to-male donation (RR, 2.5) and transplantation more than 1 year from diagnosis (RR, 2.3). Grades II to IV acute graft-versus-host disease (aGvHD) occurred in 31%. Chronic GvHD was associated with better OS and PFS and were 84% and 46% for limited, 58% and 30% for extensive, and 29% and 12% in its absence suggesting that a graft-versus-myeloma effect is important. While RIC is feasible, heavily pretreated patients and patients with progressive disease do not benefit.
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- Young, William J., et al.
(författare)
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Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
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- Smith, ER, et al.
(författare)
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Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis
- 2023
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Despite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies.MethodsWe screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale.ResultsWe screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection—as compared with uninfected pregnant women—were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias.ConclusionsThis analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.
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- Álvaro, J. Javier, et al.
(författare)
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Global Cambrian trilobite palaeobiogeography assessed using parsimony analysis of endemicity
- 2013
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Ingår i: Early Palaeozoic Biogeography and Palaeogeography. - 0435-4052. - 9781862393738 ; Memoir 38:38, s. 273-296
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Bokkapitel (refereegranskat)abstract
- Palaeobiogeographical data on Cambrian trilobites obtained during the twentieth century are combined in this paper to evaluate palaeoceanographic links through c. 30 myr, once these arthropods biomineralized. Worldwide major tectonostratigraphic units are characterized at series intervals of Cambrian time and datasets of trilobite genera (629 for Cambrian Series 2, 965 for Cambrian Series 3, and 866 for the Furongian Series) are analysed using parsimony analysis of endemicity. Special attention is given to the biogeographical observations made in microcontinents and exotic terranes. The same is done for platform-basinal transects of well-known continental margins. The parsimony analysis of endemicity analysis resulted in distinct palaeogeographical area groupings among the tectonostratigraphic units. With these groupings, several palaeobiogeographical units are distinguished, which do not necessarily fit the previously proposed biogeographical realms and provinces. Their development and spatial distributions are broadly controlled by Cambrian palaeoclimates, palaeogeographical conditions (e.g. carbonate productivity and anoxic conditions) and ocean current circulation.
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- Visibile, A., et al.
(författare)
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Strain or Electronic Effects? - The influence of alkali metals on the bandgap of Cu2O
- 2020
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Ingår i: Chemical Physics Letters. - : Elsevier BV. - 0009-2614. ; 755
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Tidskriftsartikel (refereegranskat)abstract
- Using density functional theory we studied the influence of group 1 and 11 impurities on the bandgap of Cu2O. Our results show that dopants affect the bandgap through geometric and electronic effects. Geometric effects originate from the compression of adjacent Cu-O bonds while electronic effects are tightly connected to changes in the ability to delocalize electrons through 2 electron 3 center bonds. Doping with alkali metals disturbs the delocalization network and therefore results in an increased bandgap. The 2 electron 3 center bonding network is restored by Au and Ag dopants or decreased doping concentrations.
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| 21. |
- Ahlberg, P., et al.
(författare)
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Solvated CH5+ in liquid superacid
- 2001
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Ingår i: Chemistry - A European Journal. - 0947-6539 .- 1521-3765. ; 7:12, s. 2501-2510
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Tidskriftsartikel (refereegranskat)
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| 22. |
- Ahlberg, P., et al.
(författare)
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Solvated CH5+ in liquid superacid
- 2001
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Ingår i: Chemistry-a European Journal. ; 7:9, s. 1936-1943
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Tidskriftsartikel (refereegranskat)abstract
- The transition states for methane activation in liquid superacid have been studied by experimentally determined secondary kinetic deuterium isotope effects (SKIEs) and computational chemistry. For the first time, the SKIEs on hydrogen/deuterium exchange of methane have been measured by using the methane isotopologues in homogeneous liquid superacid ((HF)-H-2/ SbF5). To achieve high accuracy of the SKIEs, the rate constants for pairs of methane isotopologues were simultaneously measured in the same superacid solution by using NMR spectroscopy Density functional theory (DFT and high-level ab initio methods have been employed to model possible intermediates and transition states, assuming that the superacids involved in the exchange reactions are H2F- ions solvated by HF Only the unsolvated superacid H2F- is found to be strong enough to protonate methane. yielding the methonium ion solvated by HF as a potential energy minimum. In contrast, the (HF)(x)-solvated H2F- superacids (x = 1-4) do not appear to be strong enough to yield stable solvated methonium ions. However, such ions show up as parts of the transition slates of the exchange in which the methonium ions are solvated by (HF)(x). The calculated DFT activation barrier is in good agreement with that experimentally observed.
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- Beznosov, Pavel A., et al.
(författare)
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Morphology of the earliest reconstructable tetrapod Parmastega aelidae
- 2019
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Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 574:7779, s. 527-531
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Tidskriftsartikel (refereegranskat)abstract
- The known diversity of tetrapods of the Devonian period has increased markedly in recent decades, but their fossil record consists mostly of tantalizing fragments(1-15). The framework for interpreting the morphology and palaeobiology of Devonian tetrapods is dominated by the near complete fossils of Ichthyostega and Acanthostega; the less complete, but partly reconstructable, Ventastega and Tulerpeton have supporting roles(2,4,16-34). All four of these genera date to the late Famennian age (about 365-359 million years ago)-they are 10 million years younger than the earliest known tetrapod fragments(5,10), and nearly 30 million years younger than the oldest known tetrapod footprints(35). Here we describe Parmastega aelidae gen. et sp. nov., a tetrapod from Russia dated to the earliest Famennian age (about 372 million years ago), represented by three-dimensional material that enables the reconstruction of the skull and shoulder girdle. The raised orbits, lateral line canals and weakly ossified postcranial skeleton of P. aelidae suggest a largely aquatic, surface-cruising animal. In Bayesian and parsimony-based phylogenetic analyses, the majority of trees place Parmastega as a sister group to all other tetrapods.
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