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1.
  • Flannick, Jason, et al. (author)
  • Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
  • 2017
  • In: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
  • Journal article (peer-reviewed)abstract
    • To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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2.
  • Fuchsberger, Christian, et al. (author)
  • The genetic architecture of type 2 diabetes
  • 2016
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
  • Journal article (peer-reviewed)abstract
    • The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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3.
  • Silberzahn, Raphael, et al. (author)
  • Many analysts, one dataset : Making transparent how variations in analytical choices affect results
  • 2018
  • In: Advances in Methods and Practices in Psychological Science. - : Sage Publications. - 2515-2459 .- 2515-2467. ; 1:3, s. 337-356
  • Journal article (peer-reviewed)abstract
    • Twenty-nine teams involving 61 analysts used the same dataset to address the same research question: whether soccer referees are more likely to give red cards to dark skin toned players than light skin toned players. Analytic approaches varied widely across teams, and estimated effect sizes ranged from 0.89 to 2.93 in odds ratio units, with a median of 1.31. Twenty teams (69%) found a statistically significant positive effect and nine teams (31%) observed a non-significant relationship. Overall 29 differentanalyses used 21 unique combinations of covariates. We found that neither analysts' prior beliefs about the effect, nor their level of expertise, nor peer-reviewed quality of analysis readily explained variation in analysis outcomes. This suggests that significant variation in the results of analyses of complex data may be difficult to avoid, even by experts with honest intentions. Crowdsourcing data analysis, a strategy by which numerous research teams are recruited to simultaneously investigate the same research question, makes transparent how defensible, yet subjective analytic choices influence research results.
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4.
  • Turcot, Valerie, et al. (author)
  • Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
  • 2018
  • In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
  • Journal article (peer-reviewed)abstract
    • Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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5.
  • Bedding, Timothy R., et al. (author)
  • A multi-site campaign to measure solar-like oscillations in Procyon. II. mode frequencies
  • 2010
  • In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 713:2, s. 935-949
  • Journal article (peer-reviewed)abstract
    • We have analyzed data from a multi-site campaign to observe oscillations in the F5 star Procyon. The data consist of high-precision velocities that we obtained over more than three weeks with 11 telescopes. A new method for adjusting the data weights allows us to suppress the sidelobes in the power spectrum. Stacking the power spectrum in a so-called echelle diagram reveals two clear ridges, which we identify with even and odd values of the angular degree (l = 0 and 2, and l = 1 and 3, respectively). We interpret a strong, narrow peak at 446 mu Hz that lies close to the l = 1 ridge as a mode with mixed character. We show that the frequencies of the ridge centroids and their separations are useful diagnostics for asteroseismology. In particular, variations in the large separation appear to indicate a glitch in the sound-speed profile at an acoustic depth of similar to 1000 s. We list frequencies for 55 modes extracted from the data spanning 20 radial orders, a range comparable to the best solar data, which will provide valuable constraints for theoretical models. A preliminary comparison with published models shows that the offset between observed and calculated frequencies for the radial modes is very different for Procyon than for the Sun and other cool stars. We find the mean lifetime of the modes in Procyon to be 1.29(-0.49)(+0.55) days, which is significantly shorter than the 2-4 days seen in the Sun.
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6.
  • Bentham, James, et al. (author)
  • A century of trends in adult human height
  • 2016
  • In: eLIFE. - 2050-084X. ; 5
  • Journal article (peer-reviewed)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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7.
  • Bentham, James, et al. (author)
  • A century of trends in adult human height
  • 2016
  • In: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
  • Journal article (peer-reviewed)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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8.
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9.
  • Elberling, Bo, et al. (author)
  • Soil and Plant Community Characteristics and Dynamics at Zackenberg
  • 2008
  • In: High-arctic ecosystem dynamics in a changing climate - Ten years of monitoring and research at Zackenberg Research Station, Northeast Greenland (Advances in Ecological Research). - 0065-2504. - 9780123736659 ; 40, s. 223-248
  • Book chapter (other academic/artistic)abstract
    • Arctic soils hold large amounts of nutrients in the weatherable minerals and the soil organic matter, which slowly decompose. The decomposition processes release nutrients to the plant-available nutrient pool as well as greenhouse gases to the atmosphere. Changes in climatic conditions, for example, changes in the distribution of snow, water balance and the length of the growing season, are likely to affect the complex interactions between plants, abiotic and biotic soil processes as well as the composition of soil micro- and macro-fauna and thereby the overall decomposition rates. These interactions, in turn, will influence soil-plant functioning and vegetation composition in the short as well as in the long term. In this chapter, we report on soils and. plant communities and their distribution patterns in the valley Zackenbergdalen and focus on the detailed investigations within five dominating plant communities. These five communities are located along an ecological gradient in the landscape and are closely related to differences in water availability. They are therefore indirectly formed as a result of the distribution of landforms, redistribution of snow and drainage conditions. Each of the plant communities is closely related to specific nutrient levels and degree of soil development including soil element accumulation and translocation, for example, organic carbon. Results presented here show that different parts of the landscape have responded quite differently to the same overall climate changes the last 10 years and thus, most likely in the future too. Fens represent the wettest sites holding large reactive buried carbon stocks. A warmer climate will cause a permafrost degradation, which most likely will result in anoxic decomposition and increasing methane emissions. However, the net gas emissions at fen sites are sensitive to long-term changes in the water table level. Indeed, increasing maximum active layer depth at fen sites has been recorded together with a decreasing water level at Zackenberg. This is in line with the first signs of increasing extension of grasslands at the expense of fens. In contrast, the most exposed and dry areas have less soil carbon, and decomposition processes are periodically water limited. Here, an increase in air temperatures may increase active layer depth more than at fen sites, but water availability will be critical in determining nutrient cycling and plant production. Field manipulation experiments of increasing temperature, water supply and nutrient addition show that soil-plant interactions are sensitive to these variables. However, additional plant-specific investigations are needed before net effects of climate changes on different landscape and plant communities can be integrated in a landscape context and used to assess the net ecosystem effect of future climate scenarios.
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10.
  • Forchhammer, Mads C., et al. (author)
  • Zackenberg in a circumpolar context
  • 2008
  • In: Advances in Ecological Research. - 0065-2504. ; 40, s. 499-544
  • Book chapter (other academic/artistic)abstract
    • Throughout the Northern Hemisphere, changes in local and regional climate conditions are coupled to the recurring and persistent large-scale patterns of pressure and circulation anomalies spanning vast geographical areas, the so-called teleconnection patterns. Indeed, the atmospheric fluctuations described by the North Atlantic Oscillation (NAO) are closely associated with the last four decades of inter-annual variability in local snow and ice conditions observed in the Arctic. Since the NAO has also been connected with changes in the global climate, the behaviour of species, communities and other ecosystem elements at Zackenberg in relation to the NAO enables us to view these in circumpolar and global contexts. Large-scale systems like the NAO constitute the link between the global change and local climate variability to which ecosystem components respond. Here, we place selected ecosystem elements from the monitoring programme Zackenberg Basic presented in previous chapters in a circumpolar context related to NAO-mediated climatic changes. We begin by linking the local variability in winter weather conditions at Zackenberg to fluctuations in the NAO. We then proceed by linking the observed intra- and inter-annual behaviour of selected ecosystem elements to changes in the NAO. The functional ecosystem characteristics in focus are landscape gas exchange dynamics phenological patterns at different trophic levels, consumer-resource dynamics and community stability. The influence of the NAO is presented and discussed in a broader perspective based on information obtained from other arctic localities. The relation between the NAO and the Zackenberg winter weather, is nonlinear, reflecting differential effects of the NAO as the index moves between high and low phases. The inverse hyperbolic relationship found between the NAO and the amount of winter snow was also evident as non-linear response in organisms and systems to inter-annual changes in the NAO. Responses investigated included growth and reproduction in plants and animals, population dynamics and synchrony, inter-trophic interactions and community stability together with system feedback dynamics.
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11.
  • Justice, Anne E., et al. (author)
  • Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
  • 2019
  • In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
  • Journal article (peer-reviewed)abstract
    • Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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12.
  • Manning, Alisa, et al. (author)
  • A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
  • 2017
  • In: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
  • Journal article (peer-reviewed)abstract
    • To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
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13.
  • Marouli, Eirini, et al. (author)
  • Rare and low-frequency coding variants alter human adult height
  • 2017
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
  • Journal article (peer-reviewed)abstract
    • Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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14.
  • Naghavi, Mohsen, et al. (author)
  • Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
  • 2015
  • In: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
  • Journal article (peer-reviewed)abstract
    • Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
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15.
  • Nielsen, Rasmus J., et al. (author)
  • Integrated ecological–economic fisheries models—Evaluation, review and challenges for implementation
  • 2018
  • In: Fish and Fisheries. - : Wiley. - 1467-2960 .- 1467-2979. ; 19:1, s. 1-29
  • Research review (peer-reviewed)abstract
    • Marine ecosystems evolve under many interconnected and area-specific pressures. To fulfil society's intensifying and diversifying needs while ensuring ecologically sustainable development, more effective marine spatial planning and broader-scope management of marine resources is necessary. Integrated ecological–economic fisheries models (IEEFMs) of marine systems are needed to evaluate impacts and sustainability of potential management actions and understand, and anticipate ecological, economic and social dynamics at a range of scales from local to national and regional. To make these models most effective, it is important to determine how model characteristics and methods of communicating results influence the model implementation, the nature of the advice that can be provided and the impact on decisions taken by managers. This article presents a global review and comparative evaluation of 35 IEEFMs applied to marine fisheries and marine ecosystem resources to identify the characteristics that determine their usefulness, effectiveness and implementation. The focus is on fully integrated models that allow for feedbacks between ecological and human processes although not all the models reviewed achieve that. Modellers must invest more time to make models user friendly and to participate in management fora where models and model results can be explained and discussed. Such involvement is beneficial to all parties, leading to improvement of models and more effective implementation of advice, but demands substantial resources which must be built into the governance process. It takes time to develop effective processes for using IEEFMs requiring a long-term commitment to integrating multidisciplinary modelling advice into management decision-making.
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16.
  • Surendran, Praveen, et al. (author)
  • Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
  • 2020
  • In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
  • Journal article (peer-reviewed)abstract
    • Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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17.
  • Vos, Theo, et al. (author)
  • Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
  • 2015
  • In: The Lancet. - 1474-547X .- 0140-6736. ; 386:9995, s. 743-800
  • Journal article (peer-reviewed)abstract
    • Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. Findings Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2.4 billion and 1.6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537.6 million in 1990 to 764.8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114.87 per 1000 people to 110.31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21.1% in 1990 to 31.2% in 2013. Interpretation Ageing of the world's population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.
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18.
  • Wuttke, Matthias, et al. (author)
  • A catalog of genetic loci associated with kidney function from analyses of a million individuals
  • 2019
  • In: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
  • Journal article (peer-reviewed)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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19.
  • 2019
  • Journal article (peer-reviewed)
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20.
  • Abbott, Benjamin W., et al. (author)
  • Biomass offsets little or none of permafrost carbon release from soils, streams, and wildfire : an expert assessment
  • 2016
  • In: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 11:3
  • Journal article (peer-reviewed)abstract
    • As the permafrost region warms, its large organic carbon pool will be increasingly vulnerable to decomposition, combustion, and hydrologic export. Models predict that some portion of this release will be offset by increased production of Arctic and boreal biomass; however, the lack of robust estimates of net carbon balance increases the risk of further overshooting international emissions targets. Precise empirical or model-based assessments of the critical factors driving carbon balance are unlikely in the near future, so to address this gap, we present estimates from 98 permafrost-region experts of the response of biomass, wildfire, and hydrologic carbon flux to climate change. Results suggest that contrary to model projections, total permafrost-region biomass could decrease due to water stress and disturbance, factors that are not adequately incorporated in current models. Assessments indicate that end-of-the-century organic carbon release from Arctic rivers and collapsing coastlines could increase by 75% while carbon loss via burning could increase four-fold. Experts identified water balance, shifts in vegetation community, and permafrost degradation as the key sources of uncertainty in predicting future system response. In combination with previous findings, results suggest the permafrost region will become a carbon source to the atmosphere by 2100 regardless of warming scenario but that 65%-85% of permafrost carbon release can still be avoided if human emissions are actively reduced.
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21.
  • Arridge, Christopher S., et al. (author)
  • Uranus Pathfinder : exploring the origins and evolution of Ice Giant planets
  • 2012
  • In: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 33:2-3, s. 753-791
  • Journal article (peer-reviewed)abstract
    • The "Ice Giants" Uranus and Neptune are a different class of planet compared to Jupiter and Saturn. Studying these objects is important for furthering our understanding of the formation and evolution of the planets, and unravelling the fundamental physical and chemical processes in the Solar System. The importance of filling these gaps in our knowledge of the Solar System is particularly acute when trying to apply our understanding to the numerous planetary systems that have been discovered around other stars. The Uranus Pathfinder (UP) mission thus represents the quintessential aspects of the objectives of the European planetary community as expressed in ESA's Cosmic Vision 2015-2025. UP was proposed to the European Space Agency's M3 call for medium-class missions in 2010 and proposed to be the first orbiter of an Ice Giant planet. As the most accessible Ice Giant within the M-class mission envelope Uranus was identified as the mission target. Although not selected for this call the UP mission concept provides a baseline framework for the exploration of Uranus with existing low-cost platforms and underlines the need to develop power sources suitable for the outer Solar System. The UP science case is based around exploring the origins, evolution, and processes at work in Ice Giant planetary systems. Three broad themes were identified: (1) Uranus as an Ice Giant, (2) An Ice Giant planetary system, and (3) An asymmetric magnetosphere. Due to the long interplanetary transfer from Earth to Uranus a significant cruise-phase science theme was also developed. The UP mission concept calls for the use of a Mars Express/Rosetta-type platform to launch on a Soyuz-Fregat in 2021 and entering into an eccentric polar orbit around Uranus in the 2036-2037 timeframe. The science payload has a strong heritage in Europe and beyond and requires no significant technology developments.
  •  
22.
  • Callaghan, Terry V., et al. (author)
  • Changing snow cover and its impacts
  • 2011
  • In: Snow, Water, Ice and Permafrost in the Arctic (SWIPA). - Oslo : Arctic Monitoring and Assessment Programme. - 9788279710714 ; , s. 4:1-4:58
  • Book chapter (peer-reviewed)
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23.
  • Callaghan, Terry V., et al. (author)
  • Multiple Effects of Changes in Arctic Snow Cover
  • 2011
  • In: Ambio: a Journal of Human Environment. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 40, s. 32-45
  • Journal article (peer-reviewed)abstract
    • Snow cover plays a major role in the climate, hydrological and ecological systems of the Arctic and other regions through its influence on the surface energy balance (e.g. reflectivity), water balance (e.g. water storage and release), thermal regimes (e.g. insulation), vegetation and trace gas fluxes. Feedbacks to the climate system have global consequences. The livelihoods and well-being of Arctic residents and many services for the wider population depend on snow conditions so changes have important consequences. Already, changing snow conditions, particularly reduced summer soil moisture, winter thaw events and rain-on-snow conditions have negatively affected commercial forestry, reindeer herding, some wild animal populations and vegetation. Reductions in snow cover are also adversely impacting indigenous peoples' access to traditional foods with negative impacts on human health and well-being. However, there are likely to be some benefits from a changing Arctic snow regime such as more even run-off from melting snow that favours hydropower operations.
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24.
  • Dastoor, Ashu, et al. (author)
  • Arctic mercury cycling
  • 2022
  • In: Nature Reviews Earth & Environment. - : Springer Nature. - 2662-138X. ; 3:4, s. 270-286
  • Research review (peer-reviewed)abstract
    • Anthropogenic mercury (Hg) emissions have driven marked increases in Arctic Hg levels,which are now being impacted by regional warming, with uncertain ecological consequences. This Review presents a comprehensive assessment of the present-day total Hg mass balance in the Arctic. Over 98% of atmospheric Hg is emitted outside the region and is transported to the Arctic via long-range air and ocean transport. Around two thirds of this Hg is deposited in terrestrial ecosystems, where it predominantly accumulates in soils via vegetation uptake. Rivers and coastal erosion transfer about 80 Mg year−1 of terrestrial Hg to the Arctic Ocean, in approximate balance with modelled net terrestrial Hg deposition in the region. The revised Arctic Ocean Hg mass balance suggests net atmospheric Hg deposition to the ocean and that Hg burial in inner-shelf sediments is underestimated (up to >100%), needing seasonal observations of sediment-oceanHg exchange. Terrestrial Hg mobilization pathways from soils and the cryosphere (permafrost, ice, snow and glaciers) remain uncertain. Improved soil, snowpack and glacial Hg inventories, transfer mechanisms of riverine Hg releases under accelerated glacier and soil thaw, coupled atmosphere– terrestrial modelling and monitoring of Hg in sensitive ecosystems such as fjords can help toanticipate impacts on downstream Arctic ecosystems.
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25.
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26.
  • de las Fuentes, Lisa, et al. (author)
  • Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
  • 2021
  • In: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:6, s. 2111-2125
  • Journal article (peer-reviewed)abstract
    • Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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27.
  • Docherty, Anna R, et al. (author)
  • GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
  • 2023
  • In: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
  • Journal article (peer-reviewed)abstract
    • Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
  •  
28.
  • Farnocchia, Davide, et al. (author)
  • (523599) 2003 RM: The Asteroid that Wanted to be a Comet
  • 2023
  • In: The Planetary Science Journal. - : Institute of Physics (IOP). - 2632-3338. ; 4:2
  • Journal article (peer-reviewed)abstract
    • We report a statistically significant detection of nongravitational acceleration on the subkilometer near-Earth asteroid (523599) 2003 RM. Due to its orbit, 2003 RM experiences favorable observing apparitions every 5 yr. Thus, since its discovery, 2003 RM has been extensively tracked with ground-based optical facilities in 2003, 2008, 2013, and 2018. We find that the observed plane-of-sky positions cannot be explained with a purely gravity-driven trajectory. Including a transverse nongravitational acceleration allows us to match all observational data, but its magnitude is inconsistent with perturbations typical of asteroids such as the Yarkovsky effect or solar radiation pressure. After ruling out that the orbital deviations are due to a close approach or collision with another asteroid, we hypothesize that this anomalous acceleration is caused by unseen cometary outgassing. A detailed search for evidence of cometary activity with archival and deep observations from the Panoramic Survey Telescope and Rapid Response System and the Very Large Telescope does not reveal any detectable dust production. However, the best-fitting H2O sublimation model allows for brightening due to activity consistent with the scatter of the data. We estimate the production rate required for H2O outgassing to power the acceleration and find that, assuming a diameter of 300 m, 2003 RM would require Q(H2O) similar to 10(23) molec s(-1) at perihelion. We investigate the recent dynamical history of 2003 RM and find that the object most likely originated in the mid-to-outer main belt (similar to 86% probability) as opposed to from the Jupiter-family comet region (similar to 11% probability). Further observations, especially in the infrared, could shed light on the nature of this anomalous acceleration.
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29.
  • Farnocchia, Davide, et al. (author)
  • The Second International Asteroid Warning Network Timing Campaign: 2005 LW3
  • 2023
  • In: The Planetary Science Journal. - : Institute of Physics (IOP). - 2632-3338. ; 4:11
  • Journal article (peer-reviewed)abstract
    • The Earth close approach of near-Earth asteroid 2005 LW3 on 2022 November 23 represented a good opportunity for a second observing campaign to test the timing accuracy of astrometric observation. With 82 participating stations, the International Asteroid Warning Network collected 1046 observations of 2005 LW3 around the time of the close approach. Compared to the previous timing campaign targeting 2019 XS, some individual observers were able to significantly improve the accuracy of their reported observation times. In particular, U.S. surveys achieved good timing performance. However, no broad, systematic improvement was achieved compared to the previous campaign, with an overall negative bias persisting among the different observers. The calibration of observing times and the mitigation of timing errors should be important future considerations for observers and orbit computers, respectively.
  •  
30.
  • Fedorets, Grigori, et al. (author)
  • Establishing Earth's Minimoon Population through Characterization of Asteroid 2020 CD3
  • 2020
  • In: Astronomical Journal. - : Institute of Physics (IOP). - 0004-6256 .- 1538-3881. ; 160:6
  • Journal article (peer-reviewed)abstract
    • We report on our detailed characterization of Earth's second known temporary natural satellite, or minimoon, asteroid 2020 CD3. An artificial origin can be ruled out based on its area-to-mass ratio and broadband photometry, which suggest that it is a silicate asteroid belonging to the S or V complex in asteroid taxonomy. The discovery of 2020 CD3 allows for the first time a comparison between known minimoons and theoretical models of their expected physical and dynamical properties. The estimated diameter of (+0.4, -0.2) m and geocentric capture approximately a decade after the first known minimoon, 2006 RH120, are in agreement with theoretical predictions. The capture duration of 2020 CD3 of at least 2.7 yr is unexpectedly long compared to the simulation average, but it is in agreement with simulated minimoons that have close lunar encounters, providing additional support for the orbital models. 2020 CD3's atypical rotation period, significantly longer than theoretical predictions, suggests that our understanding of meter-scale asteroids needs revision. More discoveries and a detailed characterization of the population can be expected with the forthcoming Vera C. Rubin Observatory Legacy Survey of Space and Time.
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31.
  • Feitosa, Mary F., et al. (author)
  • Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
  • 2018
  • In: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
  • Journal article (peer-reviewed)abstract
    • Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
  •  
32.
  • Friedman, Ran, et al. (author)
  • Understanding Conformational Dynamics of Complex Lipid Mixtures Relevant to Biology
  • 2018
  • In: Journal of Membrane Biology. - : Springer. - 0022-2631 .- 1432-1424. ; 251:5-6, s. 609-631
  • Research review (peer-reviewed)abstract
    • This is a perspective article entitled "Frontiers in computational biophysics: understanding conformational dynamics of complex lipid mixtures relevant to biology" which is following a CECAM meeting with the same name.
  •  
33.
  • Hallberg, Eric, et al. (author)
  • Sensilla and Proprioceptors
  • 2003
  • In: Handbook of Zoology, Vol. IV. Part 36. Lepidoptera, moths and butterflies. Vol. 2., Morphology, physiology, and development.. - 3110162105 ; , s. 267-288
  • Book chapter (other academic/artistic)abstract
    • Abstract is not available
  •  
34.
  • Hjorth Larsen, Ask, et al. (author)
  • The atomic simulation environment-a Python library for working with atoms
  • 2017
  • In: Journal of Physics. - : Institute of Physics Publishing (IOPP). - 0953-8984 .- 1361-648X. ; 29:27
  • Research review (peer-reviewed)abstract
    • The atomic simulation environment (ASE) is a software package written in the Python programming language with the aim of setting up, steering, and analyzing atomistic simulations. In ASE, tasks are fully scripted in Python. The powerful syntax of Python combined with the NumPy array library make it possible to perform very complex simulation tasks. For example, a sequence of calculations may be performed with the use of a simple 'for-loop' construction. Calculations of energy, forces, stresses and other quantities are performed through interfaces to many external electronic structure codes or force fields using a uniform interface. On top of this calculator interface, ASE provides modules for performing many standard simulation tasks such as structure optimization, molecular dynamics, handling of constraints and performing nudged elastic band calculations.
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35.
  • Hudson, Lawrence N, et al. (author)
  • The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
  • 2017
  • In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
  • Journal article (peer-reviewed)abstract
    • The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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36.
  • Jenniskens, Peter, et al. (author)
  • The impact and recovery of asteroid 2018 LA
  • 2021
  • In: Meteoritics and Planetary Science. - : John Wiley & Sons. - 1086-9379 .- 1945-5100. ; 56:4, s. 844-893
  • Journal article (peer-reviewed)abstract
    • The June 2, 2018 impact of asteroid 2018 LA over Botswana is only the second asteroid detected in space prior to impacting over land. Here, we report on the successful recovery of meteorites. Additional astrometric data refine the approach orbit and define the spin period and shape of the asteroid. Video observations of the fireball constrain the asteroid's position in its orbit and were used to triangulate the location of the fireball's main flare over the Central Kalahari Game Reserve. Twenty‐three meteorites were recovered. A consortium study of eight of these classifies Motopi Pan as an HED polymict breccia derived from howardite, cumulate and basaltic eucrite, and diogenite lithologies. Before impact, 2018 LA was a solid rock of ~156 cm diameter with high bulk density ~2.85 g cm−3, a relatively low albedo pV ~ 0.25, no significant opposition effect on the asteroid brightness, and an impact kinetic energy of ~0.2 kt. The orbit of 2018 LA is consistent with an origin at Vesta (or its Vestoids) and delivery into an Earth‐impacting orbit via the ν6 resonance. The impact that ejected 2018 LA in an orbit toward Earth occurred 22.8 ± 3.8 Ma ago. Zircons record a concordant U‐Pb age of 4563 ± 11 Ma and a consistent 207Pb/206Pb age of 4563 ± 6 Ma. A much younger Pb‐Pb phosphate resetting age of 4234 ± 41 Ma was found. From this impact chronology, we discuss what is the possible source crater of Motopi Pan and the age of Vesta's Veneneia impact basin.
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37.
  • Kassebaum, Nicholas J., et al. (author)
  • Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015
  • 2016
  • In: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1603-1658
  • Journal article (peer-reviewed)abstract
    • Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
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38.
  • Kraja, Aldi T., et al. (author)
  • New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475000 Individuals
  • 2017
  • In: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1942-325X .- 1942-3268. ; 10:5
  • Journal article (peer-reviewed)abstract
    • Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association.Methods and Results - Here, we augment the sample with 140886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, approximate to 475000), and the other in the subset of individuals of European descent (approximate to 423000). Twenty-one SNVs were genome-wide significant (P<5x10(-8) ) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant.Conclusions - We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.
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39.
  • Lotze, Heike K., et al. (author)
  • Global ensemble projections reveal trophic amplification of ocean biomass declines with climate change
  • 2019
  • In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:26, s. 12907-12912
  • Journal article (peer-reviewed)abstract
    • While the physical dimensions of climate change are now routinely assessed through multimodel intercomparisons, projected impacts on the global ocean ecosystem generally rely on individual models with a specific set of assumptions. To address these single-model limitations, we present standardized ensemble projections from six global marine ecosystem models forced with two Earth system models and four emission scenarios with and without fishing. We derive average biomass trends and associated uncertainties across the marine food web. Without fishing, mean global animal biomass decreased by 5% (+/- 4% SD) under low emissions and 17% (+/- 11% SD) under high emissions by 2100, with an average 5% decline for every 1 degrees C of warming. Projected biomass declines were primarily driven by increasing temperature and decreasing primary production, and were more pronounced at higher trophic levels, a process known as trophic amplification. Fishing did not substantially alter the effects of climate change. Considerable regional variation featured strong biomass increases at high latitudes and decreases at middle to low latitudes, with good model agreement on the direction of change but variable magnitude. Uncertainties due to variations in marine ecosystem and Earth system models were similar. Ensemble projections performed well compared with empirical data, emphasizing the benefits of multimodel inference to project future outcomes. Our results indicate that global ocean animal biomass consistently declines with climate change, and that these impacts are amplified at higher trophic levels. Next steps for model development include dynamic scenarios of fishing, cumulative human impacts, and the effects of management measures on future ocean biomass trends.
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40.
  • Lozano, Rafael, et al. (author)
  • Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • In: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
  • Journal article (peer-reviewed)abstract
    • Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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41.
  • Lund, Line Naomi, et al. (author)
  • Exploring variation in binding of Protein A and Protein G to immunoglobulin type G by isothermal titration calorimetry
  • 2011
  • In: Journal of Molecular Recognition. - : Wiley. - 1099-1352 .- 0952-3499. ; 24:6, s. 945-952
  • Journal article (peer-reviewed)abstract
    • Bacterial Protein A (PrtA) and Protein G (PrtG) are widely used for affinity purification of antibodies. An understanding of how PrtA and PrtG bind to different isotypes of immunoglobulin type G (IgG) and to their corresponding Fc fragments is essential for the development of PrtA and PrtG mimetic ligands and for the establishment of generic processes for the purification of various antibodies. In this paper, the interactions between the two IgG-binding proteins and IgG of two different subclasses, IgG1 and IgG4, as well as their analogous Fc fragments have been studied by isothermal titration calorimetry. The results indicate that both protein ligands bind IgG and Fc fragments strongly with Ka values in the range of 10(7)-10(8) M(-1) and for both ligands, the interaction with both IgG isotypes is enthalpically driven though entropically unfavorable. Moreover, variation in the standard entropic and standard enthalpic contribution to binding between the two isotypes as well as between IgG and Fc fragment implies that the specific interaction with PrtA varies according to IgG isotype. In contrast to PrtA, PrtG bound to F(ab')(2) fragment with a Ka value of 5.1 x 10(5) M(-1); thus underscoring the usefulness of PrtA as a preferred ligand for generic antibody purification processes. Copyright (C) 2011 John Wiley & Sons, Ltd.
  •  
42.
  • Mahajan, Anubha, et al. (author)
  • Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
  • 2018
  • In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
  • Journal article (peer-reviewed)abstract
    • We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
  •  
43.
  • Marconi, A., et al. (author)
  • ANDES, the high resolution spectrograph for the ELT : science case, baseline design and path to construction
  • 2022
  • In: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY IX. - : SPIE - International Society for Optical Engineering. - 9781510653504 - 9781510653498
  • Conference paper (peer-reviewed)abstract
    • The first generation of ELT instruments includes an optical-infrared high resolution spectrograph, indicated as ELT-HIRES and recently christened ANDES (ArmazoNes high Dispersion Echelle Spectrograph). ANDES consists of three fibre-fed spectrographs (UBV, RIZ, YJH) providing a spectral resolution of similar to 100,000 with a minimum simultaneous wavelength coverage of 0.4-1.8 mu m with the goal of extending it to 0.35-2.4 mu m with the addition of a K band spectrograph. It operates both in seeing- and diffraction-limited conditions and the fibre-feeding allows several, interchangeable observing modes including a single conjugated adaptive optics module and a small diffraction-limited integral field unit in the NIR. Its modularity will ensure that ANDES can be placed entirely on the ELT Nasmyth platform, if enough mass and volume is available, or partly in the Coude room. ANDES has a wide range of groundbreaking science cases spanning nearly all areas of research in astrophysics and even fundamental physics. Among the top science cases there are the detection of biosignatures from exoplanet atmospheres, finding the fingerprints of the first generation of stars, tests on the stability of Nature's fundamental couplings, and the direct detection of the cosmic acceleration. The ANDES project is carried forward by a large international consortium, composed of 35 Institutes from 13 countries, forming a team of more than 200 scientists and engineers which represent the majority of the scientific and technical expertise in the field among ESO member states.
  •  
44.
  • Marconi, A., et al. (author)
  • EELT-HIRES the high-resolution spectrograph for the E-ELT
  • 2016
  • In: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY VI. - : SPIE. - 9781510601963
  • Conference paper (peer-reviewed)abstract
    • The first generation of E-ELT instruments will include an optical infrared High Resolution Spectrograph, conventionally indicated as EELT-HIRES, which will be capable of providing unique breakthroughs in the fields of exoplanets, star and planet formation, physics and evolution of stars and galaxies, cosmology and fundamental physics. A 2-year long phase A study for EELT-HIRES has just started and will be performed by a consortium composed of institutes and organisations from Brazil, Chile, Denmark, France, Germany, Italy, Poland, Portugal, Spain, Sweden, Switzerland and United Kingdom. In this paper we describe the science goals and the preliminary technical concept for EELT-HIRES which will be developed during the phase A, as well as its planned development and consortium organisation during the study.
  •  
45.
  • Marconi, Alessandro, et al. (author)
  • ELT-HIRES, the high resolution spectrograph for the ELT : Phase A study and path to construction
  • 2020
  • In: Ground-based and Airborne Instrumentation for Astronomy VIII. - : SPIE - International Society for Optical Engineering. - 9781510636828 - 9781510636811
  • Conference paper (peer-reviewed)abstract
    • HIRES is the high-resolution spectrograph of the European Extremely Large Telescope at optical and near-infrared wavelengths. It consists of three fibre-fed spectrographs providing a wavelength coverage of 0.4-1.8 µm (goal 0.35-2.4 µm) at a spectral resolution of 100,000. The fibre-feeding allows HIRES to have several, interchangeable observing modes including a SCAO module and a small diffraction-limited IFU in the NIR. Therefore, it will be able to operate both in seeing- and diffraction-limited modes. Its modularity will ensure that HIRES can be placed entirely on the Nasmyth platform, if enough mass and volume is available, or part on the Nasmyth and part in the Coud`e room. ELT-HIRES has a wide range of science cases spanning nearly all areas of research in astrophysics and even fundamental physics. Among the top science cases there are the detection of biosignatures from exoplanet atmospheres, finding the fingerprints of the first generation of stars (PopIII), tests on the stability of Nature’s fundamental couplings, and the direct detection of the cosmic acceleration. The HIRES consortium is composed of more than 30 institutes from 14 countries, forming a team of more than 200 scientists and engineers.
  •  
46.
  •  
47.
  • Nesvorný, David, et al. (author)
  • NEOMOD: A New Orbital Distribution Model for Near-Earth Objects
  • 2023
  • In: Astronomical Journal. - : Institute of Physics (IOP). - 0004-6256 .- 1538-3881. ; 166:2
  • Journal article (peer-reviewed)abstract
    • Near-Earth Objects (NEOs) are a transient population of small bodies with orbits near or in the terrestrial planet region. They represent a mid-stage in the dynamical cycle of asteroids and comets, which starts with their removal from the respective source regions—the main belt and trans-Neptunian scattered disk—and ends as bodies impact planets, disintegrate near the Sun, or are ejected from the solar system. Here we develop a new orbital model of NEOs by numerically integrating asteroid orbits from main-belt sources and calibrating the results on observations of the Catalina Sky Survey. The results imply a size-dependent sampling of the main belt with the ν 6 and 3:1 resonances producing ≃30% of NEOs with absolute magnitudes H = 15 and ≃80% of NEOs with H = 25. Hence, the large and small NEOs have different orbital distributions. The inferred flux of H < 18 bodies into the 3:1 resonance can be sustained only if the main-belt asteroids near the resonance drift toward the resonance at the maximal Yarkovsky rate (≃2 × 10−4 au Myr−1 for diameter D = 1 km and semimajor axis a = 2.5 au). This implies obliquities θ ≃ 0° for a < 2.5 au and θ ≃ 180° for a > 2.5 au, both in the immediate neighborhood of the resonance (the same applies to other resonances as well). We confirm the size-dependent disruption of asteroids near the Sun found in previous studies. An interested researcher can use the publicly available NEOMOD Simulator to generate user-defined samples of NEOs from our model.
  •  
48.
  • Post, Eric, et al. (author)
  • Ecological Dynamics Across the Arctic Associated with Recent Climate Change
  • 2009
  • In: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 325:5946, s. 1355-1358
  • Research review (peer-reviewed)abstract
    • At the close of the Fourth International Polar Year, we take stock of the ecological consequences of recent climate change in the Arctic, focusing on effects at population, community, and ecosystem scales. Despite the buffering effect of landscape heterogeneity, Arctic ecosystems and the trophic relationships that structure them have been severely perturbed. These rapid changes may be a bellwether of changes to come at lower latitudes and have the potential to affect ecosystem services related to natural resources, food production, climate regulation, and cultural integrity. We highlight areas of ecological research that deserve priority as the Arctic continues to warm.
  •  
49.
  • Post, Eric, et al. (author)
  • The polar regions in a 2°C warmer world
  • 2019
  • In: Science Advances. - : American Association for the Advancement of Science. - 2375-2548. ; 5:12
  • Research review (peer-reviewed)abstract
    • Over the past decade, the Arctic has warmed by 0.75°C, far outpacing the global average, while Antarctic temperatures have remained comparatively stable. As Earth approaches 2°C warming, the Arctic and Antarctic may reach 4°C and 2°C mean annual warming, and 7°C and 3°C winter warming, respectively. Expected consequences of increased Arctic warming include ongoing loss of land and sea ice, threats to wildlife and traditional human livelihoods, increased methane emissions, and extreme weather at lower latitudes. With low biodiversity, Antarctic ecosystems may be vulnerable to state shifts and species invasions. Land ice loss in both regions will contribute substantially to global sea level rise, with up to 3 m rise possible if certain thresholds are crossed. Mitigation efforts can slow or reduce warming, but without them northern high latitude warming may accelerate in the next two to four decades. International cooperation will be crucial to foreseeing and adapting to expected changes.
  •  
50.
  • Racine, Eric, et al. (author)
  • Can Neuroscience contribute to practical ethics? : A critical review and discussion of the methodological and translational challenges of the neuroscience of ethics
  • 2017
  • In: Bioethics. - : Wiley. - 0269-9702 .- 1467-8519. ; 2017:31, s. 328-337
  • Journal article (peer-reviewed)abstract
    • Neuroethics is an interdisciplinary field that arose in response to novel ethical challenges posed by advances in neuroscience. Historically, neuroethics has provided an opportunity to synergize different disciplines, notably proposing a two-way dialogue between an "ethics of neuroscience" and a "neuroscience of ethics". However, questions surface as to whether a "neuroscience of ethics" is a useful and unified branch of research and whether it can actually inform or lead to theoretical insights and transferable practical knowledge to help resolve ethical questions. In this article, we examine why the neuroscience of ethics is a promising area of research and summarize what we have learned so far regarding its most promising goals and contributions. We then review some of the key methodological challenges which may have hindered the use of results generated thus far by the neuroscience of ethics. Strategies are suggested to address these challenges and improve the quality of research and increase neuroscience's usefulness for applied ethics and society at large. Finally, we reflect on potential outcomes of a neuroscience of ethics and discuss the different strategies that could be used to support knowledge transfer to help different stakeholders integrate knowledge from the neuroscience of ethics. 
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