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- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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6. |
- Khatri, C, et al.
(författare)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Tidskriftsartikel (refereegranskat)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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7. |
- Fitzmauric, C., et al.
(författare)
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Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived with Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017 : A Systematic Analysis for the Global Burden of Disease Study
- 2019
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 5:12, s. 1749-1768
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data.Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning.Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence.Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs).Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.
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8. |
- Mishra, A., et al.
(författare)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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11. |
- Barucca, G., et al.
(författare)
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Study of excited Ξ baryons with the P¯ ANDA detector
- 2021
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Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
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Tidskriftsartikel (refereegranskat)abstract
- The study of baryon excitation spectra provides insight into the inner structure of baryons. So far, most of the world-wide efforts have been directed towards N∗ and Δ spectroscopy. Nevertheless, the study of the double and triple strange baryon spectrum provides independent information to the N∗ and Δ spectra. The future antiproton experiment P¯ANDA will provide direct access to final states containing a Ξ¯ Ξ pair, for which production cross sections up to μb are expected in p¯p reactions. With a luminosity of L= 10 31 cm- 2 s- 1 in the first phase of the experiment, the expected cross sections correspond to a production rate of ∼106events/day. With a nearly 4 π detector acceptance, P¯ANDA will thus be a hyperon factory. In this study, reactions of the type p¯p → Ξ¯ +Ξ∗ - as well as p¯p → Ξ¯ ∗ +Ξ- with various decay modes are investigated. For the exclusive reconstruction of the signal events a full decay tree fit is used, resulting in reconstruction efficiencies between 3 and 5%. This allows high statistics data to be collected within a few weeks of data taking.
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14. |
- Figlioli, G, et al.
(författare)
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The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
- 2019
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Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
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15. |
- Franceschini, N., et al.
(författare)
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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans. © 2018, The Author(s).
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- Kinyoki, DK, et al.
(författare)
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Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017
- 2020
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Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 26:5, s. 750-759
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Tidskriftsartikel (refereegranskat)abstract
- A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic.
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- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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19. |
- Valdes-Marquez, E., et al.
(författare)
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Relative effects of LDL-C on ischemic stroke and coronary disease A Mendelian randomization study
- 2019
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 92:11
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Tidskriftsartikel (refereegranskat)abstract
- Objective To examine the causal relevance of lifelong differences in low-density lipoprotein cholesterol (LDL-C) for ischemic stroke (IS) relative to that for coronary heart disease (CHD) using a Mendelian randomization approach. We undertook a 2-sample Mendelian randomization, based on summary data, to estimate the causal relevance of LDL-C for risk of IS and CHD. Information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels was used to estimate the causal effects of LDL-C for IS and IS subtypes (based on 12,389 IS cases from METASTROKE) and for CHD (based on 60,801 cases from CARDIoGRAMplusC4D). We then assessed the effects of LDL-C on IS and CHD for heterogeneity. A 1 mmol/L higher genetically determined LDL-C was associated with a 50% higher risk of CHD (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.32-1.68, p = 1.1 x 10(-8)). By contrast, the causal effect of LDL-C was much weaker for IS (OR 1.12, 95% CI 0.96-1.30, p = 0.14; p for heterogeneity = 2.6 x 10(-3)) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84-1.33, p = 0.64; p for heterogeneity = 8.6 x 10(-3)) when compared with that for CHD. In contrast with the consistent effects of LDL-C-lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of etiologically distinct IS subtypes may contribute to the differences observed.
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20. |
- Pulit, S. L., et al.
(författare)
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Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
- 2018
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Ingår i: Neurology-Genetics. - : Ovid Technologies (Wolters Kluwer Health). - 2376-7839. ; 4:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 x 10(-4) in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 x 10(-48)), explaining similar to 20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07,p = 0.004), but no other primary stroke subtypes (all p > 0.1). Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.
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22. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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24. |
- Chang, A. Y., et al.
(författare)
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Past, present, and future of global health financing : A review of development assistance, government, out-of-pocket, and other private spending on health for 195 countries, 1995-2050
- 2019
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Ingår i: The Lancet. - : Lancet Publishing Group. - 0140-6736 .- 1474-547X. ; 393:10187, s. 2233-2260
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Tidskriftsartikel (refereegranskat)abstract
- Background: Comprehensive and comparable estimates of health spending in each country are a key input for health policy and planning, and are necessary to support the achievement of national and international health goals. Previous studies have tracked past and projected future health spending until 2040 and shown that, with economic development, countries tend to spend more on health per capita, with a decreasing share of spending from development assistance and out-of-pocket sources. We aimed to characterise the past, present, and predicted future of global health spending, with an emphasis on equity in spending across countries. Methods: We estimated domestic health spending for 195 countries and territories from 1995 to 2016, split into three categories-government, out-of-pocket, and prepaid private health spending-and estimated development assistance for health (DAH) from 1990 to 2018. We estimated future scenarios of health spending using an ensemble of linear mixed-effects models with time series specifications to project domestic health spending from 2017 through 2050 and DAH from 2019 through 2050. Data were extracted from a broad set of sources tracking health spending and revenue, and were standardised and converted to inflation-adjusted 2018 US dollars. Incomplete or low-quality data were modelled and uncertainty was estimated, leading to a complete data series of total, government, prepaid private, and out-of-pocket health spending, and DAH. Estimates are reported in 2018 US dollars, 2018 purchasing-power parity-adjusted dollars, and as a percentage of gross domestic product. We used demographic decomposition methods to assess a set of factors associated with changes in government health spending between 1995 and 2016 and to examine evidence to support the theory of the health financing transition. We projected two alternative future scenarios based on higher government health spending to assess the potential ability of governments to generate more resources for health. Findings: Between 1995 and 2016, health spending grew at a rate of 4.00% (95% uncertainty interval 3.89-4.12) annually, although it grew slower in per capita terms (2.72% [2.61-2.84]) and increased by less than $1 per capita over this period in 22 of 195 countries. The highest annual growth rates in per capita health spending were observed in upper-middle-income countries (5.55% [5.18-5.95]), mainly due to growth in government health spending, and in lower-middle-income countries (3.71% [3.10-4.34]), mainly from DAH. Health spending globally reached $8.0 trillion (7.8-8.1) in 2016 (comprising 8.6% [8.4-8.7] of the global economy and $10.3 trillion [10.1-10.6] in purchasing-power parity-adjusted dollars), with a per capita spending of US$5252 (5184-5319) in high-income countries, $491 (461-524) in upper-middle-income countries, $81 (74-89) in lower-middle-income countries, and $40 (38-43) in low-income countries. In 2016, 0.4% (0.3-0.4) of health spending globally was in low-income countries, despite these countries comprising 10.0% of the global population. In 2018, the largest proportion of DAH targeted HIV/AIDS ($9.5 billion, 24.3% of total DAH), although spending on other infectious diseases (excluding tuberculosis and malaria) grew fastest from 2010 to 2018 (6.27% per year). The leading sources of DAH were the USA and private philanthropy (excluding corporate donations and the Bill & Melinda Gates Foundation). For the first time, we included estimates of China’s contribution to DAH ($644.7 million in 2018). Globally, health spending is projected to increase to $15.0 trillion (14.0-16.0) by 2050 (reaching 9.4% [7.6-11.3] of the global economy and $21.3 trillion [19.8-23.1] in purchasing-power parity-adjusted dollars), but at a lower growth rate of 1.84% (1.68-2.02) annually, and with continuing disparities in spending between countries. In 2050, we estimate that 0.6% (0.6-0.7) of health spending will occur in currently low-income countries, despite these countries comprising an estimated 15.7% of the global population by 2050. The ratio between per capita health spending in high-income and low-income countries was 130.2 (122.9-136.9) in 2016 and is projected to remain at similar levels in 2050 (125.9 [113.7-138.1]). The decomposition analysis identified governments’ increased prioritisation of the health sector and economic development as the strongest factors associated with increases in government health spending globally. Future government health spending scenarios suggest that, with greater prioritisation of the health sector and increased government spending, health spending per capita could more than double, with greater impacts in countries that currently have the lowest levels of government health spending. Interpretation: Financing for global health has increased steadily over the past two decades and is projected to continue increasing in the future, although at a slower pace of growth and with persistent disparities in per-capita health spending between countries. Out-of-pocket spending is projected to remain substantial outside of high-income countries. Many low-income countries are expected to remain dependent on development assistance, although with greater government spending, larger investments in health are feasible. In the absence of sustained new investments in health, increasing efficiency in health spending is essential to meet global health targets. © 2019 The Author(s).
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25. |
- Chauhan, G., et al.
(författare)
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Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting
- 2019
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 92:5
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts.MethodsWe performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI.ResultsThe mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 x 10(-8); and LINC00539/ZDHHC20, p = 5.82 x 10(-9). Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p([BI]) = 9.38 x 10(-25); p([SSBI]) = 5.23 x 10(-14) for hypertension), smoking (p([BI]) = 4.4 x 10(-10); p([SSBI]) = 1.2 x 10(-4)), diabetes (p([BI]) = 1.7 x 10(-8); p([SSBI]) = 2.8 x 10(-3)), previous cardiovascular disease (p([BI]) = 1.0 x 10(-18); p([SSBI]) = 2.3 x 10(-7)), stroke (p([BI]) = 3.9 x 10(-69); p([SSBI]) = 3.2 x 10(-24)), and MRI-defined white matter hyperintensity burden (p([BI]) = 1.43 x 10(-157); p([SSBI]) = 3.16 x 10(-106)), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p 0.0022), without indication of directional pleiotropy.ConclusionIn this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.
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- Milz, Mathias, et al.
(författare)
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Validation of water vapour profiles (version 13) retrieved by the IMK/IAA scientific retrieval processor based on full resolution spectra measured by MIPAS on board Envisat
- 2009
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 2:2, s. 379-399
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Tidskriftsartikel (refereegranskat)abstract
- Vertical profiles of stratospheric water vapour measured by the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) with the full resolution mode between September 2002 and March 2004 and retrieved with the IMK/IAA scientific retrieval processor were compared to a number of independent measurements in order to estimate the bias and to validate the existing precision estimates of the MIPAS data. The estimated precision for MIPAS is 5 to 10% in the stratosphere, depending on altitude, latitude, and season. The independent instruments were: the Halogen Occultation Experiment (HALOE), the Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS), the Improved Limb Atmospheric Spectrometer-II (ILAS-II), the Polar Ozone and Aerosol Measurement (POAM III) instrument, the Middle Atmospheric Water Vapour Radiometer (MIAWARA), the Michelson Interferometer for Passive Atmospheric Sounding, balloon-borne version (MIPAS-B), the Airborne Microwave Stratospheric Observing System(AMSOS), the Fluorescent Stratospheric Hygrometer for Balloon (FLASH-B), the NOAA frostpoint hygrometer, and the Fast In Situ Hygrometer (FISH). For the in-situ measurements and the ground based, air- and balloon borne remote sensing instruments, the measurements are restricted to central and northern Europe. The comparisons to satellite-borne instruments are predominantly at mid- to high latitudes on both hemispheres. In the stratosphere there is no clear indicationof a bias in MIPAS data, because the independent measurements in some cases are drier and in some cases are moister than the MIPAS measurements. Compared to the infrared measurements of MIPAS, measurements in the ultraviolet and visible have a tendency to be high, whereas microwave measurements have a tendency to be low. Theresults of chi2-based precision validation are somewhat controversial among the comparison estimates. However, for comparison instruments whose error budget also includes errors due to uncertainties in spectrally interfering species and where good coincidences were found, the chi2 values found are in the expected range or even below. This suggests that there is no evidence of systematically underestimated MIPAS random errors.
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35. |
- Pulit, SL, et al.
(författare)
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Loci associated with ischaemic stroke and its subtypes (SiGN): a genome-wide association study.
- 2016
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Ingår i: The Lancet. Neurology. - 1474-4465. ; 15:2, s. 174-84
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of disease-associated loci through genome-wide association studies (GWAS) is the leading genetic approach to the identification of novel biological pathways underlying diseases in humans. Until recently, GWAS in ischaemic stroke have been limited by small sample sizes and have yielded few loci associated with ischaemic stroke. We did a large-scale GWAS to identify additional susceptibility genes for stroke and its subtypes.To identify genetic loci associated with ischaemic stroke, we did a two-stage GWAS. In the first stage, we included 16851 cases with state-of-the-art phenotyping data and 32473 stroke-free controls. Cases were aged 16 to 104 years, recruited between 1989 and 2012, and subtypes of ischaemic stroke were recorded by centrally trained and certified investigators who used the web-based protocol, Causative Classification of Stroke (CCS). We constructed case-control strata by identifying samples that were genotyped on nearly identical arrays and were of similar genetic ancestral background. We cleaned and imputed data by use of dense imputation reference panels generated from whole-genome sequence data. We did genome-wide testing to identify stroke-associated loci within each stratum for each available phenotype, and we combined summary-level results using inverse variance-weighted fixed-effects meta-analysis. In the second stage, we did in-silico lookups of 1372 single nucleotide polymorphisms identified from the first stage GWAS in 20941 cases and 364736 unique stroke-free controls. The ischaemic stroke subtypes of these cases had previously been established with the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification system, in accordance with local standards. Results from the two stages were then jointly analysed in a final meta-analysis.We identified a novel locus (G allele at rs12122341) at 1p13.2 near TSPAN2 that was associated with large artery atherosclerosis-related stroke (first stage odds ratio [OR] 1·21, 95% CI 1·13-1·30, p=4·50×10(-8); joint OR 1·19, 1·12-1·26, p=1·30×10(-9)). Our results also supported robust associations with ischaemic stroke for four other loci that have been reported in previous studies, including PITX2 (first stage OR 1·39, 1·29-1·49, p=3·26×10(-19); joint OR 1·37, 1·30-1·45, p=2·79×10(-32)) and ZFHX3 (first stage OR 1·19, 1·11-1·27, p=2·93×10(-7); joint OR 1·17, 1·11-1·23, p=2·29×10(-10)) for cardioembolic stroke, and HDAC9 (first stage OR 1·29, 1·18-1·42, p=3·50×10(-8); joint OR 1·24, 1·15-1·33, p=4·52×10(-9)) for large artery atherosclerosis stroke. The 12q24 locus near ALDH2, which has previously been associated with all ischaemic stroke but not with any specific subtype, exceeded genome-wide significance in the meta-analysis of small artery stroke (first stage OR 1·20, 1·12-1·28, p=6·82×10(-8); joint OR 1·17, 1·11-1·23, p=2·92×10(-9)). Other loci associated with stroke in previous studies, including NINJ2, were not confirmed.Our results suggest that all ischaemic stroke-related loci previously implicated by GWAS are subtype specific. We identified a novel gene associated with large artery atherosclerosis stroke susceptibility. Follow-up studies will be necessary to establish whether the locus near TSPAN2 can be a target for a novel therapeutic approach to stroke prevention. In view of the subtype-specificity of the associations detected, the rich phenotyping data available in the Stroke Genetics Network (SiGN) are likely to be crucial for further genetic discoveries related to ischaemic stroke.US National Institute of Neurological Disorders and Stroke, National Institutes of Health.
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36. |
- Evangelou, Evangelos, et al.
(författare)
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Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
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37. |
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38. |
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39. |
- Chauhan, Swarup, et al.
(författare)
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MIPAS reduced spectral resolution UTLS-1 mode measurements of temperature, O3, HNO3, N2O, H2O and relative humidity over ice: retrievals and comparison to MLS
- 2009
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; :2, s. 337-353
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Tidskriftsartikel (refereegranskat)abstract
- During several periods since 2005 the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) on Envisat has performed observations dedicated to the region of the upper troposphere/lower stratosphere (UTLS). For the duration of November/December 2005 global distributions of temperature and several trace gases from MIPAS UTLS-1 mode measurements have been retrieved using the IMK/IAA (Institut für Meteorologie und Klimaforschung/Instituto de Astrofísica de Andalucía) scientific processor. In the UTLS region a vertical resolution of 3 km for temperaure, 3 to 4 km for H2O, 2.5 to 3 km for O3, 3.5 km for HNO3 and 3.5 to 2.5 km for N2O has been achieved. The retrieved temperature, H2O, O3, HNO3, N2O, and relative humidity over ice are intercompared with the Microwave Limb Sounder (MLS/Aura) v2.2 data in the pressure range 316 to 0.68 hPa, 316 to 0.68 hPa, 215 to 0.68 hPa, 215 to 3.16 hPa, 100 to 1 hPa and 316 to 10 hPa, respectively. In general, MIPAS and MLS temperatures are biased within ±4 K over the whole pressure and latitude range. Systematic, latitude-independent differences of −2 to −4 K (MIPAS-MLS) at 121 hPa are explained by previously observed biases in the MLS v2.2 temperature retrievals. Temperature differences of −4 K up to 12 K above 10.0 hPa are present both in MIPAS and MLS with respect to ECMWF (European Centre for Medium-Range Weather Forecasts) and are likely due to deficiencies of the ECMWF analysis data. MIPAS and MLS stratospheric volume mixing ratios (vmr) of H2O are biased within ±1 ppmv, with indication of oscillations between 146 and 26 hPa in the MLS dataset. Tropical upper tropospheric values of relative humidity over ice measured by the two instruments differ by ±20% in the pressure range ~146 to 68 hPa. These differences are mainly caused by the MLS temperature biases. Ozone mixing ratios agree within 0.5 ppmv (10 to 20%) between 68 and 14 hPa. At pressures smaller than 10 hPa, MIPAS O3 vmr are higher than MLS by an average of 0.5 ppmv (10%). General agreement between MIPAS and MLS HNO3 is within the range of −1.0 (−10%) to 1.0 ppbv (20%). MIPAS HNO3 is 1.0 ppbv (10%) higher compared to MLS between 46 hPa and 10 hPa over the Northern Hemisphere. Over the tropics at 31.6 hPa MLS shows a low bias of more than 1 ppbv (>50%). In general, MIPAS and MLS N2O vmr agree within 20 to 40 ppbv (20 to 40%). Differences in the range between 100 to 21 hPa are attributed to a known 20% positive bias in MIPAS N2O data.
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40. |
- Franceschini, N, et al.
(författare)
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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 5141-
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Tidskriftsartikel (refereegranskat)abstract
- Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
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41. |
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42. |
- Singh, G., et al.
(författare)
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Nicotine-based surface active ionic liquids: Synthesis, self-assembly and cytotoxicity studies
- 2017
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 1095-7103 .- 0021-9797. ; 496, s. 278-289
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Tidskriftsartikel (refereegranskat)abstract
- New ester-functionalized surface active ionic liquids (SAILS) based on nicotine, [C(n)ENic][Br] (n = 8, 10 and 12), with bromide counterions have been synthesized, characterized and investigated for their self assembly behavior in aqueous medium. Conductivity measurements in aqueous solutions of the investigated SAILs have provided information about their critical micelle concentration (cmc), and degree of counterion binding (16), where cmc was found to be 2-3-fold lower than homologous SAILs or conventional cationic surfactants. The inherent fluorescence of SAILs in the absence of any external fluorescent probe have shed light on cmc as well as interactions prevailing between the monomers in micelle at molecular level. The thermodynamic parameters related to micellization have been deduced from isothermal titration calorimetry (ITC) and conductivity measurements. H-1 NMR, spin-lattice (T-1) relaxation time and 2D H-1-H-1 ROESY measurements have been exploited to get detailed account of internal structure of micelle. The size and shape of the micelles have been explored using dynamic light scattering (DLS) and transmission electron microscopy (TEM) measurements. The synthesized SAILs have been found to be non-cytotoxic towards C6-Glioma cell line, which adds to the possible utility of these SAILs for diverse biological applications.
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43. |
- Wain, Louise V., et al.
(författare)
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Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney
- 2017
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 70:3, s. e4-e19
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
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44. |
- Antel, C., et al.
(författare)
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Feebly-interacting particles : FIPs 2022 Workshop Report
- 2023
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Ingår i: European Physical Journal C. - : Springer. - 1434-6044 .- 1434-6052. ; 83:12
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Forskningsöversikt (refereegranskat)abstract
- Particle physics today faces the challenge of explaining the mystery of dark matter, the origin of matter over anti-matter in the Universe, the origin of the neutrino masses, the apparent fine-tuning of the electro-weak scale, and many other aspects of fundamental physics. Perhaps the most striking frontier to emerge in the search for answers involves new physics at mass scales comparable to familiar matter, below the GeV-scale, or even radically below, down to sub-eV scales, and with very feeble interaction strength. New theoretical ideas to address dark matter and other fundamental questions predict such feebly interacting particles (FIPs) at these scales, and indeed, existing data provide numerous hints for such possibility. A vibrant experimental program to discover such physics is under way, guided by a systematic theoretical approach firmly grounded on the underlying principles of the Standard Model. This document represents the report of the FIPs 2022 workshop, held at CERN between the 17 and 21 October 2022 and aims to give an overview of these efforts, their motivations, and the decadal goals that animate the community involved in the search for FIPs.
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45. |
- Athanasaki, G., et al.
(författare)
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Design and development of gas diffusion layers with pore forming agent for proton exchange membrane fuel cells at various relative humidity conditions
- 2021
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Ingår i: International journal of hydrogen energy. - : Elsevier BV. - 0360-3199 .- 1879-3487. ; 46:9, s. 6835-6844
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Tidskriftsartikel (refereegranskat)abstract
- Membrane electrode assemblies are developed by incorporating gas diffusion layers (GDL) to improve the lower and higher relative humidity performance of proton exchange membrane fuel cells (PEMFCs). In the present study, gas diffusion layer samples containing microporous layers, are fabricated using carbon paper substrate, PUREBLACK® carbon powder and polyethylene glycol as pore forming agent. The GDLs are studied in single cell fuel cell, to evaluate the effect of porosity of the micro-porous layer on the performance at different operating relative humidity conditions and compared with commercial GDLs. Scanning electron microscopy and contact angle measurements indicate crack-free surface morphology and hydrophobic characteristics of the PUREBLACK® based GDLs, respectively. By varying the wt. % of PEG, fuel cell performance is evaluated under relative humidity conditions of 60 and 100% using H2/O2 and H2/Air at 70 °C and the durability is also evaluated for the GDL samples without and with 30% PEG. The fuel cell performance of the GDL with 30% pore forming agent (with a pore volume of 1.72 cc.g−1) exhibited higher performance (444 and 432 mW cm−2 at 60 and 100% RH conditions, respectively using H2 and air) compared to that without pore forming agent (436 and 397 mW cm−2).
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46. |
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47. |
- Chauhan, Ravendra P., et al.
(författare)
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Systematic Review of Important Viral Diseases in Africa in Light of the 'One Health' Concept
- 2020
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Ingår i: Pathogens. - : MDPI AG. - 2076-0817. ; 9:4
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Forskningsöversikt (refereegranskat)abstract
- Emerging and re-emerging viral diseases are of great public health concern. The recent emergence of Severe Acute Respiratory Syndrome (SARS) related coronavirus (SARS-CoV-2) in December 2019 in China, which causes COVID-19 disease in humans, and its current spread to several countries, leading to the first pandemic in history to be caused by a coronavirus, highlights the significance of zoonotic viral diseases. Rift Valley fever, rabies, West Nile, chikungunya, dengue, yellow fever, Crimean-Congo hemorrhagic fever, Ebola, and influenza viruses among many other viruses have been reported from different African countries. The paucity of information, lack of knowledge, limited resources, and climate change, coupled with cultural traditions make the African continent a hotspot for vector-borne and zoonotic viral diseases, which may spread globally. Currently, there is no information available on the status of virus diseases in Africa. This systematic review highlights the available information about viral diseases, including zoonotic and vector-borne diseases, reported in Africa. The findings will help us understand the trend of emerging and re-emerging virus diseases within the African continent. The findings recommend active surveillance of viral diseases and strict implementation of One Health measures in Africa to improve human public health and reduce the possibility of potential pandemics due to zoonotic viruses.
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48. |
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49. |
- Debette, Stéphanie, et al.
(författare)
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Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 47, s. 78-83
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Tidskriftsartikel (refereegranskat)abstract
- Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year)1. Minor cervical traumas, infection, migraine and hypertension are putative risk factors1–3, and inverse associations with obesity and hypercholesterolemia are described3,4. No confirmed genetic susceptibility factors have been identified using candidate gene approaches5. We performed genome-wide association studies (GWAS) in 1 1,393 CeAD cases and 1 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69–0.82; P = 4.46 × 1 10−10), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 1 × 1 10−3; combined P = 1 1.00 × 1 10−1111). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction6–9. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.
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50. |
- Elrashdy, Fatma, et al.
(författare)
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Autoimmunity roots of the thrombotic events after COVID-19 vaccination
- 2021
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Ingår i: Autoimmunity Reviews. - : Elsevier. - 1568-9972 .- 1873-0183. ; 20:11
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Forskningsöversikt (refereegranskat)abstract
- Although vaccination represents the most promising way to stop or contain the coronavirus disease 2019 (COVID-19) pandemic and safety and effectiveness of available vaccines were proven, a small number of individuals who received anti-SARS-CoV-2 vaccines developed a prothrombotic syndrome. Vaccine-induced immune thrombotic thrombocytopenia (VITT) can be triggered by the adenoviral vector-based vaccine, whereas lipid nanoparticle-mRNA-based vaccines can induce rare cases of deep vein thrombosis (DVT). Although the main pathogenic mechanisms behind this rare phenomenon have not yet been identified, both host and vaccine factors might be involved, with pathology at least in part being related to the vaccine-triggered autoimmune reaction. In this review, we are considering some aspects related to pathogenesis, major risk factors, as well as peculiarities of diagnosis and treatment of this rare condition.
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