| 1. |
- Lind, Lars, et al.
(författare)
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Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
- 2021
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Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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| 2. |
- Bixby, H., et al.
(författare)
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Rising rural body-mass index is the main driver of the global obesity epidemic in adults
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 569:7755, s. 260-4
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Tidskriftsartikel (refereegranskat)abstract
- Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
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| 3. |
- Ramdas, S., et al.
(författare)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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| 4. |
- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 5. |
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| 6. |
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| 7. |
- Taddei, C, et al.
(författare)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Tidskriftsartikel (refereegranskat)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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| 8. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 9. |
- Blach, S., et al.
(författare)
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Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study
- 2022
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Ingår i: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 7:5, s. 396-415
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Tidskriftsartikel (refereegranskat)abstract
- Background Since the release of the first global hepatitis elimination targets in 2016, and until the COVID-19 pandemic started in early 2020, many countries and territories were making progress toward hepatitis C virus (HCV) elimination. This study aims to evaluate HCV burden in 2020, and forecast HCV burden by 2030 given current trends. Methods This analysis includes a literature review, Delphi process, and mathematical modelling to estimate HCV prevalence (viraemic infection, defined as HCV RNA-positive cases) and the cascade of care among people of all ages (age =0 years from birth) for the period between Jan 1, 2015, and Dec 31, 2030. Epidemiological data were collected from published sources and grey literature (including government reports and personal communications) and were validated among country and territory experts. A Markov model was used to forecast disease burden and cascade of care from 1950 to 2050 for countries and territories with data. Model outcomes were extracted from 2015 to 2030 to calculate population-weighted regional averages, which were used for countries or territories without data. Regional and global estimates of HCV prevalence, cascade of care, and disease burden were calculated based on 235 countries and territories. Findings Models were built for 110 countries or territories: 83 were approved by local experts and 27 were based on published data alone. Using data from these models, plus population-weighted regional averages for countries and territories without models (n=125), we estimated a global prevalence of viraemic HCV infection of 0.7% (95% UI 0.7-0.9), corresponding to 56.8 million (95% UI 55.2-67.8) infections, on Jan 1, 2020. This number represents a decrease of 6.8 million viraemic infections from a 2015 (beginning of year) prevalence estimate of 63.6 million (61.8-75.8) infections (0.9% [0.8-1.0] prevalence). By the end of 2020, an estimated 12.9 million (12.5-15.4) people were living with a diagnosed viraemic infection. In 2020, an estimated 641 000 (623 000-765 000) patients initiated treatment. Interpretation At the beginning of 2020, there were an estimated 56.8 million viraemic HCV infections globally. Although this number represents a decrease from 2015, our forecasts suggest we are not currently on track to achieve global elimination targets by 2030. As countries recover from COVID-19, these findings can help refocus efforts aimed at HCV elimination. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
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| 10. |
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| 11. |
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| 12. |
- Winkler, TW, et al.
(författare)
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Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 580-
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
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| 13. |
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| 14. |
- Do, Ron, et al.
(författare)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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| 15. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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| 16. |
- Willer, Cristen J., et al.
(författare)
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Discovery and refinement of loci associated with lipid levels
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
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Tidskriftsartikel (refereegranskat)abstract
- Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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| 17. |
- Gorski, Mathias, et al.
(författare)
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Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
- 2022
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 102:3, s. 624-639
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Tidskriftsartikel (refereegranskat)abstract
- Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
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| 18. |
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| 19. |
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| 20. |
- Teumer, A, et al.
(författare)
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Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4130-
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Tidskriftsartikel (refereegranskat)abstract
- Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.
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| 21. |
- Abu-Elyazeed, R R, et al.
(författare)
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Safety and immunogenicity of a glycoprotein D genital herpes vaccine in healthy girls 10-17 years of age : results from a randomised, controlled, double-blind trial
- 2013
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 31:51, s. 6136-6143
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The investigational AS04-adjuvanted herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) subunit prophylactic vaccine ('HSV vaccine'; GlaxoSmithKline Vaccines) has been shown to be well tolerated in adults, but limited data exist for pre-teen and adolescent girls, a likely target population. The primary objective of this study was to compare the occurrence of serious adverse events (SAEs) over 12 months between HSV vaccine recipients and saline recipients (placebo control group) in pre-teen and adolescent girls. The immunogenicity of the HSV vaccine was also assessed.METHODS: Healthy girls aged 10-17 years, stratified by age (10-15 years; 16-17 years), were randomised 2:1:1 to receive the HSV vaccine, a hepatitis A vaccine (Havrix™; HAV control) or placebo (saline) according to a 0-, 1-, 6-month schedule. Participants and study personnel not involved in the preparation or administration of vaccines were blinded to treatment. Safety and immunogenicity analyses were performed overall and by age (10-15 years; 16-17 years) and HSV serostatus.RESULTS: No statistically significant difference in the percentage of subjects with SAEs was observed between the HSV and saline group, or between the HSV and pooled control (HAV and saline) groups. The HSV vaccine was well tolerated, although a higher incidence of solicited local symptoms was observed in the HSV group than in the control group. Neither age nor HSV serostatus at the time of study entry had an impact on the safety profile of this vaccine. The HSV vaccine was immunogenic regardless of pre-vaccination HSV serostatus. Higher anti-gD geometric mean concentrations were observed in HSV-1 seropositive participants than in HSV-1 seronegative participants.CONCLUSION: The HSV vaccine had an acceptable safety profile, and was well tolerated and immunogenic when administered to girls aged 10-17 years regardless of age or HSV pre-vaccination serostatus.
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| 22. |
- Boy, M., et al.
(författare)
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Interactions between the atmosphere, cryosphere, and ecosystems at northern high latitudes
- 2019
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 19:3, s. 2015-2061
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Tidskriftsartikel (refereegranskat)abstract
- The Nordic Centre of Excellence CRAICC (Cryosphere-Atmosphere Interactions in a Changing Arctic Climate), funded by NordForsk in the years 2011-2016, is the largest joint Nordic research and innovation initiative to date, aiming to strengthen research and innovation regarding climate change issues in the Nordic region. CRAICC gathered more than 100 scientists from all Nordic countries in a virtual centre with the objectives of identifying and quantifying the major processes controlling Arctic warming and related feedback mechanisms, outlining strategies to mitigate Arctic warming, and developing Nordic Earth system modelling with a focus on short-lived climate forcers (SLCFs), including natural and anthropogenic aerosols. The outcome of CRAICC is reflected in more than 150 peer-reviewed scientific publications, most of which are in the CRAICC special issue of the journal Atmospheric Chemistry and Physics. This paper presents an overview of the main scientific topics investigated in the centre and provides the reader with a state-of-the-art comprehensive summary of what has been achieved in CRAICC with links to the particular publications for further detail. Faced with a vast amount of scientific discovery, we do not claim to completely summarize the results from CRAICC within this paper, but rather concentrate here on the main results which are related to feedback loops in climate change-cryosphere interactions that affect Arctic amplification.
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| 23. |
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| 24. |
- Messias, M. J, et al.
(författare)
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The Greenland Sea tracer experiment 1996–2002: Horizontal mixing and transport of Greenland Sea Intermediate Water
- 2008
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Ingår i: Progress In Oceanography. - : Elsevier BV. - 0079-6611. ; 78:1, s. 85-105
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Tidskriftsartikel (refereegranskat)abstract
- In summer 1996, a tracer release experiment using sulphur hexafluoride (SF6) was launched in the intermediate-depth waters of the central Greenland Sea (GS), to study the mixing and ventilation processes in the region and its role in the northern limb of the Atlantic overturning circulation. Here we describe the hydrographic context of the experiment, the methods adopted and the results from the monitoring of the horizontal tracer spread for the 1996–2002 period documented by 10 shipboard surveys. The tracer marked “Greenland Sea Arctic Intermediate Water” (GSAIW). This was redistributed in the gyre by variable winter convection penetrating only to mid-depths, reaching at most 1800 m depth during the strongest event observed in 2002. For the first 18 months, the tracer remained mainly in the Greenland Sea. Vigorous horizontal mixing within the Greenland Sea gyre and a tight circulation of the gyre interacting slowly with the other basins under strong topographic influences were identified. We use the tracer distributions to derive the horizontal shear at the scale of the Greenland Sea gyre, and rates of horizontal mixing at 10 and 300 km scales. Mixing rates at small scale are high, several times those observed at comparable depths at lower latitudes. Horizontal stirring at the sub-gyre scale is mediated by numerous and vigorous eddies. Evidence obtained during the tracer release suggests that these play an important role in mixing water masses to form the intermediate waters of the central Greenland Sea. By year two, the tracer had entered the surrounding current systems at intermediate depths and small concentrations were in proximity to the overflows into the North Atlantic. After 3 years, the tracer had spread over the Nordic Seas basins. Finally by year six, an intensive large survey provided an overall synoptic documentation of the spreading of the tagged GSAIW in the Nordic Seas. A circulation scheme of the tagged water originating from the centre of the GS is deduced from the horizontal spread of the tracer. We present this circulation and evaluate the transport budgets of the tracer between the GS and the surroundings basins. The overall residence time for the tagged GSAIW in the Greenland Sea was about 2.5 years. We infer an export of intermediate water of GSAIW from the GS of 1 to 1.85 Sv (1 Sv = 106 m3 s−1) for the period from September 1998 to June 2002 based on the evolution of the amount of tracer leaving the GS gyre. There is strong exchange between the Greenland Sea and Arctic Ocean via Fram Strait, but the contribution of the Greenland Sea to the Denmark Strait and Iceland Scotland overflows is modest, probably not exceeding 6% during the period under study.
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| 25. |
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| 26. |
- Helgadottir, Anna, et al.
(författare)
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Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism
- 2012
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 60:8, s. 722-729
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components. Background It is unclear whether the LPA variants rs10455872 and rs3798220, which correlate with lipoprotein(a) levels and coronary artery disease (CAD), confer susceptibility predominantly via atherosclerosis or thrombosis. Methods The 2 LPA variants were combined and examined as LPA scores for the association with ischemic stroke (and TOAST [Trial of Org 10172 in Acute Stroke Treatment] subtypes) (effective sample size [n(e)] = 9,396); peripheral arterial disease (n(e) = 5,215); abdominal aortic aneurysm (ne = 4,572); venous thromboembolism (ne = 4,607); intracranial aneurysm (ne = 1,328); CAD (n(e) = 12,716), carotid intima-media thickness (n = 3,714), and angiographic CAD severity (n = 5,588). Results LPA score was associated with ischemic stroke subtype large artery atherosclerosis (odds ratio [OR]: 1.27; p = 6.7 X 10(-4)), peripheral artery disease (OR: 1.47; p = 2.9 x 10(-14)), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 x 10(-5)), but not with the ischemic stroke subtypes cardioembolism (OR: 1.03; p = 0.69) or small vessel disease (OR: 1.06; p = 0.52). Although the LPA variants were not associated with carotid intima-media thickness, they were associated with the number of obstructed coronary vessels (p = 4.8 x 10(-12)). Furthermore, CAD cases carrying LPA risk variants had increased susceptibility to atherosclerotic manifestations outside of the coronary tree (OR: 1.26; p = 0.0010) and had earlier onset of CAD (-1.58 years/allele; p = 8.2 x 10(-8)) than CAD cases not carrying the risk variants. There was no association of LPA score with venous thromboembolism (OR: 0.97; p = 0.63) or intracranial aneurysm (OR: 0.85; p = 0.15). Conclusions LPA sequence variants were associated with atherosclerotic burden, but not with primarily thrombotic phenotypes. (J Am Coll Cardiol 2012; 60: 722-9) (C) 2012 by the American College of Cardiology Foundation
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| 27. |
- Shapiro, M, et al.
(författare)
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An Earth-system prediction initiative for the twenty-first century: An international interdisciplinary initiative to accelerate advances in knowledge, prediction, use and value of weather, climate and Earth-system information
- 2010
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Ingår i: BULLETIN OF THE AMERICAN METEOROLOGICAL SOCIETY. - 0003-0007. ; 91:10, s. 1377-1388
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Tidskriftsartikel (refereegranskat)abstract
- The necessity and benefits for establishing the international Earth-system Prediction Initiative (EPI) are discussed by scientists associated with the World Meteorological Organization (WMO) World Weather Research Programme (WWRP), World Climate Research Programme (WCRP), International Geosphere–Biosphere Programme (IGBP), Global Climate Observing System (GCOS), and natural-hazards and socioeconomic communities. The proposed initiative will provide research and services to accelerate advances in weather, climate, and Earth system prediction and the use of this information by global societies. It will build upon the WMO, the Group on Earth Observations (GEO), the Global Earth Observation System of Systems (GEOSS) and the International Council for Science (ICSU) to coordinate the effort across the weather, climate, Earth system, natural-hazards, and socioeconomic disciplines. It will require (i) advanced high-performance computing facilities, supporting a worldwide network of research and operational modeling centers, and early warning systems; (ii) science, technology, and education projects to enhance knowledge, awareness, and utilization of weather, climate, environmental, and socioeconomic information; (iii) investments in maintaining existing and developing new observational capabilities; and (iv) infrastructure to transition achievements into operational products and services.
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| 28. |
- van der Harst, Pim, et al.
(författare)
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Seventy-five genetic loci influencing the human red blood cell
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
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Tidskriftsartikel (refereegranskat)abstract
- Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
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| 29. |
- Gretarsdottir, Solveig, et al.
(författare)
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Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:8, s. 71-692
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Tidskriftsartikel (refereegranskat)abstract
- We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 x 10(-10). In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 x 10(-5)), peripheral arterial disease (OR = 1.14, P = 3.9 x 10(-5)) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases-that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival.
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| 30. |
- Holdsworth, D. L., et al.
(författare)
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TESS Cycle 2 observations of roAp stars with 2-min cadence data
- 2024
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 527:4, s. 9548-9580
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of a systematic search of the Transiting Exoplanet Survey Satellite (TESS) 2-min cadence data for new rapidly oscillating Ap (roAp) stars observed during the Cycle 2 phase of its mission. We find seven new roAp stars previously unreported as such and present the analysis of a further 25 roAp stars that are already known. Three of the new stars show multiperiodic pulsations, while all new members are rotationally variable stars, leading to almost 70 per cent (22) of the roAp stars presented being α2 CVn-type variable stars. We show that targeted observations of known chemically peculiar stars are likely to overlook many new roAp stars, and demonstrate that multiepoch observations are necessary to see pulsational behaviour changes. We find a lack of roAp stars close to the blue edge of the theoretical roAp instability strip, and reaffirm that mode instability is observed more frequently with precise, space-based observations. In addition to the Cycle 2 observations, we analyse TESS data for all-known roAp stars. This amounts to 18 further roAp stars observed by TESS. Finally, we list six known roAp stars that TESS is yet to observe. We deduce that the incidence of roAp stars amongst the Ap star population is just 5.5 per cent, raising fundamental questions about the conditions required to excite pulsations in Ap stars. This work, coupled with our previous work on roAp stars in Cycle 1 observations, presents the most comprehensive, homogeneous study of the roAp stars in the TESS nominal mission, with a collection of 112 confirmed roAp stars in total.
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| 31. |
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| 32. |
- Olafsson, S, et al.
(författare)
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Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations
- 2017
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Ingår i: NPJ genomic medicine. - : Springer Science and Business Media LLC. - 2056-7944. ; 2, s. 24-
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Tidskriftsartikel (refereegranskat)abstract
- A meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 × 10−7, 4.3 × 10−9) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.
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| 33. |
- Olsen, Are, 1972, et al.
(författare)
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Overview of the Nordic Seas CARINA data and salinity measurements
- 2009
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Ingår i: Earth System Science Data Discussions. - 1866-3591. ; 2, s. 1-25
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Tidskriftsartikel (refereegranskat)abstract
- Water column data of carbon and carbon relevant hydrographic and hydrochemical parameters from 188 previously non-publicly available cruises in the Arctic, Atlantic, and Southern Ocean have been retrieved and merged into a new database: CARINA (CARbon IN the Atlantic). The data have been subject to rigorous quality control (QC) in order to ensure highest possible quality and consistency. The data for most of the parameters included were examined in order to quantify systematic biases in the reported values, i.e. secondary quality control. Significant biases have been corrected for in the data products, i.e. the three merged files with measured, calculated and interpolated values for each of the three CARINA regions; the Arctic Mediterranean Seas (AMS), the Atlantic (ATL) and the Southern Ocean (SO). With the adjustments the CARINA database is consistent both internally as well as with GLODAP (Key et al., 2004) and is suitable for accurate assessments of, for example, oceanic carbon inventories and uptake rates and for model validation. The Arctic Mediterranean Seas includes the Arctic Ocean and the Nordic Seas, and the quality control was carried out separately in these two areas. This contribution provides an overview of the CARINA data from the Nordic Seas and summarises the findings of the QC of the salinity data. One cruise had salinity data that were of questionable quality, and these have been removed from the data product. An evaluation of the consistency of the quality controlled salinity data suggests that they are consistent to at least 0.05.
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| 34. |
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| 35. |
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| 36. |
- Kular, L, et al.
(författare)
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DNA methylation as a mediator of HLA-DRB1*15:01 and a protective variant in multiple sclerosis
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2397-
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Tidskriftsartikel (refereegranskat)abstract
- The human leukocyte antigen (HLA) haplotype DRB1*15:01 is the major risk factor for multiple sclerosis (MS). Here, we find that DRB1*15:01 is hypomethylated and predominantly expressed in monocytes among carriers of DRB1*15:01. A differentially methylated region (DMR) encompassing HLA-DRB1 exon 2 is particularly affected and displays methylation-sensitive regulatory properties in vitro. Causal inference and Mendelian randomization provide evidence that HLA variants mediate risk for MS via changes in the HLA-DRB1 DMR that modify HLA-DRB1 expression. Meta-analysis of 14,259 cases and 171,347 controls confirms that these variants confer risk from DRB1*15:01 and also identifies a protective variant (rs9267649, p < 3.32 × 10−8, odds ratio = 0.86) after conditioning for all MS-associated variants in the region. rs9267649 is associated with increased DNA methylation at the HLA-DRB1 DMR and reduced expression of HLA-DRB1, suggesting a modulation of the DRB1*15:01 effect. Our integrative approach provides insights into the molecular mechanisms of MS susceptibility and suggests putative therapeutic strategies targeting a methylation-mediated regulation of the major risk gene.
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| 37. |
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| 38. |
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| 39. |
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| 40. |
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| 41. |
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| 42. |
- Arnalds, U. B., et al.
(författare)
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A magnetron sputtering system for the preparation of patterned thin films and in situ thin film electrical resistance measurements
- 2007
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 78:10, s. 103901-
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Tidskriftsartikel (refereegranskat)abstract
- We describe a versatile three gun magnetron sputtering system with a custom made sample holder for in situ electrical resistance measurements, both during film growth and ambient changes on film electrical properties. The sample holder allows for the preparation of patterned thin film structures, using up to five different shadow masks without breaking vacuum. We show how the system is used to monitor the electrical resistance of thin metallic films during growth and to study the thermodynamics of hydrogen uptake in metallic thin films. Furthermore, we demonstrate the growth of thin film capacitors, where patterned films are created using shadow masks.
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| 43. |
- Borgstrom, F., et al.
(författare)
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Health economic aspects of vertebral augmentation procedures
- 2015
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 26:4, s. 1239-1249
-
Forskningsöversikt (refereegranskat)abstract
- We reviewed all peer-reviewed papers analysing the cost-effectiveness of vertebroplasty and balloon kyphoplasty for osteoporotic vertebral compression fractures. In general, the procedures appear to be cost effective but are very dependent upon model input details. Better data, rather than new models, are needed to answer outstanding questions. Vertebral augmentation procedures (VAPs), including vertebroplasty (VP) and balloon kyphoplasty (BKP), seek to stabilise fractured vertebral bodies and reduce pain. The aim of this paper is to review current literature on the cost-effectiveness of VAPs as well as to discuss the challenges for economic evaluation in this research area. A systematic literature search was conducted to identify existing published studies on the cost-effectiveness of VAPs in patients with osteoporosis. Only peer-reviewed published articles that fulfilled the criteria of being regarded as full economic evaluations including both morbidity and mortality in the outcome measure in the form of quality-adjusted life years (QALYs) were included. The search identified 949 studies, of which four (0.4 %) were identified as relevant with one study added later. The reviewed studies differed widely in terms of study design, modelling framework and data used, yielding different results and conclusions regarding the cost-effectiveness of VAPs. Three out of five studies indicated in the base case results that VAPs were cost effective compared to non-surgical management (NSM). The five main factors that drove the variations in the cost-effectiveness between the studies were time horizon, quality of life effect of treatment, offset time of the treatment effect, reduced number of bed days associated with VAPs and mortality benefit with treatment. The cost-effectiveness of VAPs is uncertain. In answering the remaining questions, new cost-effectiveness analysis will yield limited benefit. Rather, studies that can reduce the uncertainty in the underlying data, especially regarding the long-term clinical outcomes of VAPs, should be conducted.
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| 44. |
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| 45. |
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| 46. |
- Gylfason, Kristinn B., 1978-, et al.
(författare)
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In-situ resistivity measurements during growth of ultra-thin Cr_0.7Mo_0.3
- 2006
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Ingår i: Thin Solid Films. - : Elsevier. - 0040-6090 .- 1879-2731. ; 515:2, s. 583-586
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Tidskriftsartikel (refereegranskat)abstract
- The growth of ultra-thin, lattice matched, Cr0.7Mo0.3 films on an MgO substrate, in a dc magnetron discharge, was investigated by in situ measurements in order to determine the minimum thickness of a continuous layer. The thickness dependence of the resistivity shows a coalescence thickness of less than two monolayers indicating layer by layer growth of the films. We compare the resistivity of the films to a combination of the Fuchs- Sondheimer and the Mayadas-Shatzkes models, assuming a thickness dependence of grain size. The model indicates that grain size increases with increasing growth temperature.
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| 47. |
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| 48. |
- Hátún, Hjálmar, et al.
(författare)
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An inflated subpolar gyre blows life toward the northeastern Atlantic
- 2016
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Ingår i: Progress in Oceanography. - 0079-6611. ; 147, s. 49-66
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Tidskriftsartikel (refereegranskat)abstract
- Deep convection in the Labrador and Irminger Seas inflates the cold and low-saline subpolar gyre, which is a rich nutrient and zooplankton source for the surrounding warmer waters of subtropical origin. The zooplankton abundances on the south Iceland shelf show characteristic sub-decadal variability, which closely reflect the oceanic abundances of the ecologically most important zooplankton species – Calanus finmarchicus. Much higher abundances of this species are observed during years when the winter mixed layer depths (MLD) in the Labrador-Irminger Sea, and over the Reykjanes Ridge are deep. Furthermore, a tight relationship is identified between on-shelf zooplankton abundances and lateral shifts of the biologically productive subarctic front southwest of Iceland. Thus, we suggest that northeastward expansion of the subpolar gyre results in biologically productive periods in the waters southwest of Iceland – both oceanic and on the shelf. In addition to local atmospheric forcing, we find that the MLD and frontal position are also impacted by remote heat losses and convection in the Labrador Sea, through northward advection of unstable mode waters. The sub-decadal oceanic and on-shelf biological production peaks are possibly predictable by half a year (local winter convection to subsequent summer production), and the advective time-lag from the Labrador Sea might induce an even longer predictability horizon (up to 1.5 years).
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| 49. |
- Hatun, H., et al.
(författare)
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The subpolar gyre regulates silicate concentrations in the North Atlantic
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- The North Atlantic is characterized by diatom-dominated spring blooms that results in significant transfer of carbon to higher trophic levels and the deep ocean. These blooms are terminated by limiting silicate concentrations in summer. Numerous regional studies have demonstrated phytoplankton community shifts to lightly-silicified diatoms and non-silicifying plankton at the onset of silicate limitation. However, to understand basin-scale patterns in ecosystem and climate dynamics, nutrient inventories must be examined over sufficient temporal and spatial scales. Here we show, from a new comprehensive compilation of data from the subpolar Atlantic Ocean, clear evidence of a marked pre-bloom silicate decline of 1.5-2 mu M throughout the winter mixed layer during the last 25 years. This silicate decrease is primarily attributed to natural multi-decadal variability through decreased winter convection depths since the mid-1990s, a weakening and retraction of the subpolar gyre and an associated increased influence of nutrient-poor water of subtropical origin. Reduced Arctic silicate import and the projected hemispheric-scale climate change-induced weakening of vertical mixing may have acted to amplify the recent decline. These marked fluctuations in pre-bloom silicate inventories will likely have important consequences for the spatial and temporal extent of diatom blooms, thus impacting ecosystem productivity and ocean-atmosphere climate dynamics.
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| 50. |
- Helgadottir, Anna, et al.
(författare)
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Genome-wide analysis yields new loci associating with aortic valve stenosis
- 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
- Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (OR) = 1.20, P = 1.2 × 10-22) and on chromosome 2q22 in TEX41 (rs1830321; OR = 1.15, P = 1.8 × 10-13). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR = 1.28, P = 6.6 × 10-10) and aortic root diameter (P = 1.30 × 10-8), and rs1830321 associates with BAV (OR = 1.12, P = 5.3 × 10-3) and coronary artery disease (OR = 1.05, P = 9.3 × 10-5). The results implicate both cardiac developmental abnormalities and atherosclerosis-like processes in the pathogenesis of AS. We show that several pathways are shared by CAD and AS. Causal analysis suggests that the shared risk factors of Lp(a) and non-high-density lipoprotein cholesterol contribute substantially to the frequent co-occurence of these diseases.
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