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- Lumbers, R. T., et al.
(författare)
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The genomics of heart failure: design and rationale of the HERMES consortium
- 2021
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Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822. ; 8:6, s. 5531-5541
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Tidskriftsartikel (refereegranskat)abstract
- Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model. Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
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- Shah, S, et al.
(författare)
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Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 163-
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Tidskriftsartikel (refereegranskat)abstract
- Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
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- Thacher, Jesse D., et al.
(författare)
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Occupational noise exposure and risk of incident stroke: a pooled study of five Scandinavian cohorts
- 2022
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Ingår i: OCCUPATIONAL AND ENVIRONMENTAL MEDICINE. - : BMJ. - 1351-0711 .- 1470-7926. ; 79:9, s. 594-601
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To investigate the association between occupational noise exposure and stroke incidence in a pooled study of five Scandinavian cohorts (NordSOUND). Methods We pooled and harmonised data from five Scandinavian cohorts resulting in 78 389 participants. We obtained job data from national registries or questionnaires and recoded these to match a job-exposure matrix developed in Sweden, which specified the annual average daily noise exposure in five exposure classes (L-Aeq8h): <70, 70-74, 75-79, 80-84, >= 85 dB(A). We identified residential address history and estimated 1-year average road traffic noise at baseline. Using national patient and mortality registers, we identified 7777 stroke cases with a median follow-up of 20.2 years. Analyses were conducted using Cox proportional hazards models adjusting for individual and area-level potential confounders. Results Exposure to occupational noise at baseline was not associated with overall stroke in the fully adjusted models. For ischaemic stroke, occupational noise was associated with HRs (95% CI) of 1.08 (0.98 to 1.20), 1.09 (0.97 to 1.24) and 1.06 (0.92 to 1.21) in the 75-79, 80-84 and >= 85 dB(A) exposure groups, compared with <70 dB(A), respectively. In subanalyses using time-varying occupational noise exposure, we observed an indication of higher stroke risk among the most exposed (>= 85 dB(A)), particularly when restricting analyses to people exposed to occupational noise within the last year (HR: 1.27; 95% CI: 0.99 to 1.63). Conclusions We found no association between occupational noise and risk of overall stroke after adjustment for confounders. However, the non-significantly increased risk of ischaemic stroke warrants further investigation.
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- Andersson, Tomas, et al.
(författare)
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Photon energy influence on valence photoelectron spectra of silver clusters
- 2012
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Ingår i: Journal of Physics, Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 388:15, s. 152028-
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Tidskriftsartikel (refereegranskat)abstract
- Silver clusters in the size range of ∼102 constituent atoms have been studied using photoelectron spec-troscopy. The 5s and 4d valence bands have been probed with 40 and 60.5 eV photon energies. Differences in the valence band spectral features have been observed and are discussed in view of earlier results on copper clusters and in terms of differences in mean free path for electrons of different energies.
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| 6. |
- Brandhorst, Heide, 1962-, et al.
(författare)
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A new oxygen carrier for improved long-term storage of human pancreata before islet isolation
- 2010
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 89:2, s. 155-60
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pancreas oxygenation during cold storage has been established in islet isolation and transplantation to prevent ischemic tissue damage using perfluorodecalin (PFD) as hyperoxygen carrier. However, studies in humans and pigs provided conflicting results about the efficiency of PFD for pancreas oxygenation. The aim of this study was to compare PFD with a newly developed oxygen carrier composed of perfluorohexyloctane and polydimethylsiloxane 5 (F6H8S5) for long-term storage of human pancreata.METHODS: After 24-hr storage in preoxygenated PFD or F6H8S5, pancreata were processed using Liberase HI for pancreas dissociation and a Ficoll gradient for islet purification. Islet quality assessment was performed measuring glucose-stimulated insulin release, viability, islet ATP content, and posttransplant function in diabetic nude mice.RESULTS: Compared with PFD, F6H8S5 significantly increased the intrapancreatic partial oxygen pressure and islet ATP content. This corresponded to an increase of islet yield, recovery after culture, glucose stimulation index, viability, and improved graft function in diabetic nude mice.CONCLUSIONS: The present findings indicate clearly that F6H8S5 improves isolation outcome after prolonged ischemia compared with PFD. This observation seems to be related to the significant lipophilicity and almost pancreas-specific density of F6H8S5. Moreover, these characteristics facilitate pancreas shipment without using custom-made transport vessels as required for PFD.
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- Carlsen, Hanne Krage, et al.
(författare)
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Incident cardiovascular disease and long-term exposure to source-specific air pollutants in a Swedish cohort
- 2022
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 209
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Tidskriftsartikel (refereegranskat)abstract
- Background: Air pollution is associated with cardiovascular morbidity and mortality, but its role in the development of congestive heart failure (CHF) and the role of different pollution sources in cardiovascular disease remain uncertain. Methods: Participants were enrolled in the Malmö Diet and Cancer cohort in 1991–1996 with information on lifestyle and clinical indicators of cardiovascular disease. The cohort participants were followed through registers until 2016. Annual total and local source-specific concentrations of particulate matter less than 10 μm and 2.5 μm (PM10 and PM2.5), black carbon (BC), and nitrogen oxides (NOx) from traffic, residential heating, and industry were assigned to each participant's address throughout the study period. Cox proportional hazards models adjusted for possible confounders was used to estimate associations between air pollution 1–5 years prior to outcomes of incident CHF, fatal myocardial infarction (MI), major adverse coronary events (MACE), and ischemic stroke. Results: Air pollution exposure levels (mean annual exposures to PM2.5 of 11 μg/m3 and NOx of 26 μg/m3) within the cohort were moderate in terms of environmental standards. After adjusting for confounders, we observed statistically significant associations between NOx and CHF (hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.01–1.22) and NOx and fatal MI (HR 1.10, 95%CI 1.01–1.20) per interquartile range (IQR) of 9.6 μg/m3. In fully adjusted models, the estimates were similar, but the precision worse. In stratified analyses, the associations were stronger in males, ever-smokers, older participants, and those with baseline carotid artery plaques. Locally emitted and traffic-related air pollutants generally showed positive associations with CHF and fatal MI. There were no associations between air pollution and MACE or stroke. Discussion/conclusion: In an area with low to moderate air pollution exposure, we observed significant associations of long-term residential NOx with increased risk of incident CHF and fatal MI, but not with coronary events and stroke. © 2022
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