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2.
  • Naghavi, Mohsen, et al. (författare)
  • 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
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
  • Tidskriftsartikel (refereegranskat)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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3.
  • Forouzanfar, Mohammad H, et al. (författare)
  • Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013.
  • 2015
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
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4.
  • Vos, Theo, et al. (författare)
  • 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
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 386:9995, s. 743-800
  • Tidskriftsartikel (refereegranskat)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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5.
  • Turcot, Valerie, et al. (författare)
  • Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
  • 2018
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
  • Tidskriftsartikel (refereegranskat)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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6.
  • Wang, Haidong, et al. (författare)
  • Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015
  • 2016
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
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7.
  • Lozano, Rafael, et al. (författare)
  • 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
  • Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
  • Tidskriftsartikel (refereegranskat)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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8.
  • Stanaway, Jeffrey D., et al. (författare)
  • Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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9.
  • Adrian-Martinez, S., et al. (författare)
  • The First Combined Search For Neutrino Point-Sources In The Southern Hemisphere With The Antares And Icecube Neutrino Telescopes
  • 2016
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 823:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results of searches for point-like sources of neutrinos based on the first combined analysis of data from both the ANTARES and IceCube neutrino telescopes. The combination of both detectors, which differ in size and location, forms a window in the southern sky where the sensitivity to point sources improves by up to a factor of 2 compared with individual analyses. Using data recorded by ANTARES from 2007 to 2012, and by IceCube from 2008 to 2011, we search for sources of neutrino emission both across the southern sky and from a preselected list of candidate objects. No significant excess over background has been found in these searches, and flux upper limits for the candidate sources are presented for E-2.5 and E-2 power-law spectra with different energy cut-offs.
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10.
  • Aartsen, M. G., et al. (författare)
  • Search for astrophysical tau neutrinos in three years of IceCube data
  • 2016
  • Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 93:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The IceCube Neutrino Observatory has observed a diffuse flux of TeV-PeVastrophysical neutrinos at 5.7 sigma significance from an all-flavor search. The direct detection of tau neutrinos in this flux has yet to occur. Tau neutrinos become distinguishable from other flavors in IceCube at energies above a few hundred TeV, when the cascade from the tau neutrino charged current interaction becomes resolvable from the cascade from the tau lepton decay. This paper presents results from the first dedicated search for tau neutrinos with energies between 214 TeV and 72 PeV in the full IceCube detector. The analysis searches for IceCube optical sensors that observe two separate pulses in a single event-one from the tau neutrino interaction and a second from the tau decay. No candidate events were observed in three years of IceCube data. For the first time, a differential upper limit on astrophysical tau neutrinos is derived around the PeV energy region, which is nearly 3 orders of magnitude lower in energy than previous limits from dedicated tau neutrino searches.
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11.
  • Aartsen, M. G., et al. (författare)
  • The IceCube Neutrino Observatory : instrumentation and online systems
  • 2017
  • Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • The IceCube Neutrino Observatory is a cubic-kilometer-scale high-energy neutrino detector built into the ice at the South Pole. Construction of IceCube, the largest neutrino detector built to date, was completed in 2011 and enabled the discovery of high-energy astrophysical neutrinos. We describe here the design, production, and calibration of the IceCube digital optical module (DOM), the cable systems, computing hardware, and our methodology for drilling and deployment. We also describe the online triggering and data filtering systems that select candidate neutrino and cosmic ray events for analysis. Due to a rigorous pre-deployment protocol, 98.4% of the DOMs in the deep ice are operating and collecting data. IceCube routinely achieves a detector uptime of 99% by emphasizing software stability and monitoring. Detector operations have been stable since construction was completed, and the detector is expected to operate at least until the end of the next decade.
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12.
  • Aartsen, M. G., et al. (författare)
  • The Search For Transient Astrophysical Neutrino Emission With Icecube-Deepcore
  • 2016
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 816:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results of a search for astrophysical sources of brief transient neutrino emission using IceCube and DeepCore data acquired between 2012 May 15 and 2013 April 30. While the search methods employed in this analysis are similar to those used in previous IceCube point source searches, the data set being examined consists of a sample of predominantly sub-TeV muon-neutrinos from the Northern Sky (-5 degrees < delta < 90 degrees) obtained through a novel event selection method. This search represents a first attempt by IceCube to identify astrophysical neutrino sources in this relatively unexplored energy range. The reconstructed direction and time of arrival of neutrino events are used to search for any significant self-correlation in the data set. The data revealed no significant source of transient neutrino emission. This result has been used to construct limits at timescales ranging from roughly 1 s to 10 days for generic soft-spectra transients. We also present limits on a specific model of neutrino emission from soft jets in core-collapse supernovae.
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13.
  • Marouli, Eirini, et al. (författare)
  • Rare and low-frequency coding variants alter human adult height
  • 2017
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
  • Tidskriftsartikel (refereegranskat)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.
  •  
14.
  • Aartsen, M. G., et al. (författare)
  • All-flavour search for neutrinos from dark matter annihilations in the Milky Way with IceCube/DeepCore
  • 2016
  • Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 76:10
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the first IceCube search for a signal of dark matter annihilations in the Milky Way using all-flavour neutrino-induced particle cascades. The analysis focuses on the DeepCore sub-detector of IceCube, and uses the surrounding IceCube strings as a veto region in order to select starting events in the DeepCore volume. We use 329 live-days of data from IceCube operating in its 86-string configuration during 2011-2012. No neutrino excess is found, the final result being compatible with the background-only hypothesis. From this null result, we derive upper limits on the velocity-averaged self-annihilation cross-section, , for dark matter candidate masses ranging from 30 GeV up to 10 TeV, assuming both a cuspy and a flat-cored dark matter halo profile. For dark matter masses between 200 GeV and 10 TeV, the results improve on all previous IceCube results on , reaching a level of 10 cm s, depending on the annihilation channel assumed, for a cusped NFW profile. The analysis demonstrates that all-flavour searches are competitive with muon channel searches despite the intrinsically worse angular resolution of cascades compared to muon tracks in IceCube.
  •  
15.
  • Aartsen, M. G., et al. (författare)
  • Anisotropy In Cosmic-Ray Arrival Directions In The Southern Hemisphere Based On Six Years Of Data From The Icecube Detector
  • 2016
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 826:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The IceCube Neutrino Observatory accumulated a total of 318 billion cosmic-ray-induced muon events between 2009 May and 2015 May. This data set was used for a detailed analysis of the sidereal anisotropy in the arrival directions of cosmic rays in the TeV to PeV energy range. The observed global sidereal anisotropy features large regions of relative excess and deficit, with amplitudes of the order of 10(-3) up to about 100 TeV. A decomposition of the arrival direction distribution into spherical harmonics shows that most of the power is contained in the low-multipole (l <= 4) moments. However, higher multipole components are found to be statistically significant down to an angular scale of less than 10 degrees, approaching the angular resolution of the detector. Above 100 TeV, a change in the morphology of the arrival direction distribution is observed, and the anisotropy is characterized by a wide relative deficit whose amplitude increases with primary energy up to at least 5 PeV, the highest energies currently accessible to IceCube. No time dependence of the large-and small-scale structures is observed in the period of six years covered by this analysis. The high-statistics data set reveals more details of the properties of the anisotropy and is potentially able to shed light on the various physical processes that are responsible for the complex angular structure and energy evolution.
  •  
16.
  • Aartsen, M. G., et al. (författare)
  • Characterization of the atmospheric muon flux in IceCube
  • 2016
  • Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 78, s. 1-27
  • Tidskriftsartikel (refereegranskat)abstract
    • Muons produced in atmospheric cosmic ray showers account for the by far dominant part of the event yield in large-volume underground particle detectors. The IceCube detector, with an instrumented volume of about a cubic kilometer, has the potential to conduct unique investigations on atmospheric muons by exploiting the large collection area and the possibility to track particles over a long distance. Through detailed reconstruction of energy deposition along the tracks, the characteristics of muon bundles can be quantified, and individual particles of exceptionally high energy identified. The data can then be used to constrain the cosmic ray primary flux and the contribution to atmospheric lepton fluxes from prompt decays of short-lived hadrons. In this paper, techniques for the extraction of physical measurements from atmospheric muon events are described and first results are presented. The multiplicity spectrum of TeV muons in cosmic ray air showers for primaries in the energy range from the knee to the ankle is derived and found to be consistent with recent results from surface detectors. The single muon energy spectrum is determined up to PeV energies and shows a clear indication for the emergence of a distinct spectral component from prompt decays of short-lived hadrons. The magnitude of the prompt flux, which should include a substantial contribution from light vector meson di-muon decays, is consistent with current theoretical predictions. The variety of measurements and high event statistics can also be exploited for the evaluation of systematic effects. In the course of this study, internal inconsistencies in the zenith angle distribution of events were found which indicate the presence of an unexplained effect outside the currently applied range of detector systematics. The underlying cause could be related to the hadronic interaction models used to describe muon production in air showers.
  •  
17.
  • Aartsen, M. G., et al. (författare)
  • Determining neutrino oscillation parameters from atmospheric muon neutrino disappearance with three years of IceCube DeepCore data
  • 2015
  • Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 91:7
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a measurement of neutrino oscillations via atmospheric muon neutrino disappearance with three years of data of the completed IceCube neutrino detector. DeepCore, a region of denser IceCube instrumentation, enables the detection and reconstruction of atmospheric muon neutrinos between 10 and 100 GeV, where a strong disappearance signal is expected. The IceCube detector volume surrounding DeepCore is used as a veto region to suppress the atmospheric muon background. Neutrino events are selected where the detected Cherenkov photons of the secondary particles minimally scatter, and the neutrino energy and arrival direction are reconstructed. Both variables are used to obtain the neutrino oscillation parameters from the data, with the best fit given by Delta m(32)(2) = 2.72(-0.20)(+0.19) x 10(-3) eV(2) and sin(2)theta(23) = 0.53(-0.12)(+0.09) (normal mass ordering assumed). The results are compatible, and comparable in precision, to those of dedicated oscillation experiments.
  •  
18.
  • Aartsen, M. G., et al. (författare)
  • Improved limits on dark matter annihilation in the Sun with the 79-string IceCube detector and implications for supersymmetry
  • 2016
  • Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
  • Tidskriftsartikel (refereegranskat)abstract
    • We present an improved event-level likelihood formalism for including neutrino telescope data in global fits to new physics. We derive limits on spin-dependent dark matter-proton scattering by employing the new formalism in a re-analysis of data from the 79-string IceCube search for dark matter annihilation in the Sun, including explicit energy information for each event. The new analysis excludes a number of models in the weak-scale minimal supersymmetric standard model (MSSM) for the first time. This work is accompanied by the public release of the 79-string IceCube data, as well as an associated computer code for applying the new likelihood to arbitrary dark matter models.
  •  
19.
  • Aartsen, M. G., et al. (författare)
  • PINGU : a vision for neutrino and particle physics at the South Pole
  • 2017
  • Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 44:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The Precision IceCube Next Generation Upgrade (PINGU) is a proposed low-energy in-fill extension to the IceCube Neutrino Observatory. With detection technology modeled closely on the successful IceCube example, PINGU will provide a 6 Mton effective mass for neutrino detection with an energy threshold of a few GeV. With an unprecedented sample of over 60 000 atmospheric neutrinos per year in this energy range, PINGU will make highly competitive measurements of neutrino oscillation parameters in an energy range over an order of magnitude higher than long-baseline neutrino beam experiments. PINGU will measure the mixing parameters theta(23) and Delta m(32)(2), including the octant of theta(23) for a wide range of values, and determine the neutrino mass ordering at 3 sigma median significance within five years of operation. PINGU's high precision measurement of the rate of nu(T) appearance will provide essential tests of the unitarity of the 3 x 3 PMNS neutrino mixing matrix. PINGU will also improve the sensitivity of searches for low mass dark matter in the Sun, use neutrino tomography to directly probe the composition of the Earth's core, and improve IceCube's sensitivity to neutrinos from Galactic supernovae. Reoptimization of the PINGU design has permitted substantial reduction in both cost and logistical requirements while delivering performance nearly identical to configurations previously studied.
  •  
20.
  • Aartsen, M. G., et al. (författare)
  • Search for dark matter annihilation in the Galactic Center with IceCube-79
  • 2015
  • Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 75:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The Milky Way is expected to be embedded in a halo of dark matter particles, with the highest density in the central region, and decreasing density with the halo-centric radius. Dark matter might be indirectly detectable at Earth through a flux of stable particles generated in dark matter annihilations and peaked in the direction of the Galactic Center. We present a search for an excess flux of muon (anti-) neutrinos from dark matter annihilation in the Galactic Center using the cubic-kilometer-sized IceCube neutrino detector at the South Pole. There, the Galactic Center is always seen above the horizon. Thus, new and dedicated veto techniques against atmospheric muons are required to make the southern hemisphere accessible for IceCube. We used 319.7 live-days of data from IceCube operating in its 79-string configuration during 2010 and 2011. No neutrino excess was found and the final result is compatible with the background. We present upper limits on the self-annihilation cross-section, < sAv >, for WIMP masses ranging from 30GeV up to 10TeV, assuming cuspy (NFW) and flat-cored (Burkert) dark matter halo profiles, reaching down to similar or equal to 4 . 10(-24) cm(3) s(-1), and similar or equal to 2.6 . 10(-23) cm(3) s(-1) for the nu(nu) over bar channel, respectively.
  •  
21.
  • Aartsen, M. G., et al. (författare)
  • Searches for relativistic magnetic monopoles in IceCube
  • 2016
  • Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 76:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Various extensions of the Standard Model motivate the existence of stable magnetic monopoles that could have been created during an early high-energy epoch of the Universe. These primordial magnetic monopoles would be gradually accelerated by cosmic magnetic fields and could reach high velocities that make them visible in Cherenkov detectors such as IceCube. Equivalently to electrically charged particles, magnetic monopoles produce direct and indirect Cherenkov light while traversing through matter at relativistic velocities. This paper describes searches for relativistic (nu >= 0.76 c) and mildly relativistic (nu >= 0.51 c) monopoles, each using one year of data taken in 2008/2009 and 2011/2012, respectively. No monopole candidate was detected. For a velocity above 0.51 c the monopole flux is constrained down to a level of 1.55 x 10(-18) cm(-2) s(-1) sr(-1). This is an improvement of almost two orders of magnitude over previous limits.
  •  
22.
  • Aartsen, M. G., et al. (författare)
  • Searches for Sterile Neutrinos with the IceCube Detector
  • 2016
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 117:7
  • Tidskriftsartikel (refereegranskat)abstract
    • The IceCube neutrino telescope at the South Pole has measured the atmospheric muon neutrino spectrum as a function of zenith angle and energy in the approximate 320 GeV to 20 TeV range, to search for the oscillation signatures of light sterile neutrinos. No evidence for anomalous nu(mu) or (nu) over bar (mu) disappearance is observed in either of two independently developed analyses, each using one year of atmospheric neutrino data. New exclusion limits are placed on the parameter space of the 3 + 1 model, in which muon antineutrinos experience a strong Mikheyev-Smirnov-Wolfenstein-resonant oscillation. The exclusion limits extend to sin(2)2 theta(24) <= 0.02 at Delta m(2) similar to 0.3 eV(2) at the 90% confidence level. The allowed region from global analysis of appearance experiments, including LSND and MiniBooNE, is excluded at approximately the 99% confidence level for the global best-fit value of vertical bar U-e4 vertical bar(2).
  •  
23.
  • Aartsen, M. G., et al. (författare)
  • The Contribution Of Fermi-2Lac Blazars To Diffuse Tev-Pev Neutrino Flux
  • 2017
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 835:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The recent discovery of a diffuse cosmic neutrino flux extending up to PeV energies raises the question of which astrophysical sources generate this signal. Blazars are one class of extragalactic sources which may produce such high-energy neutrinos. We present a likelihood analysis searching for cumulative neutrino emission from blazars in the 2nd Fermi-LAT AGN catalog (2LAC) using IceCube neutrino data set 2009-12, which was optimized for the detection of individual sources. In contrast to those in previous searches with IceCube, the populations investigated contain up to hundreds of sources, the largest one being the entire blazar sample in the 2LAC catalog. No significant excess is observed, and upper limits for the cumulative flux from these populations are obtained. These constrain the maximum contribution of 2LAC blazars to the observed astrophysical neutrino flux to 27% or less between around 10 TeV and 2 PeV, assuming the equipartition of flavors on Earth and a single power-law spectrum with a spectral index of -2.5. We can still exclude the fact that 2LAC blazars (and their subpopulations) emit more than 50% of the observed neutrinos up to a spectral index as hard as -2.2 in the same energy range. Our result takes into account the fact that the neutrino source count distribution is unknown, and it does not assume strict proportionality of the neutrino flux to the measured 2LAC gamma-ray signal for each source. Additionally, we constrain recent models for neutrino emission by blazars.
  •  
24.
  • Aartsen, M. G., et al. (författare)
  • The Detection Of A Sn Iin In Optical Follow-Up Observations Of Icecube Neutrino Events
  • 2015
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 811:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The IceCube neutrino observatory pursues a follow-up program selecting interesting neutrino events in real-time and issuing alerts for electromagnetic follow-up observations. In 2012 March, the most significant neutrino alert during the first three years of operation was issued by IceCube. In the follow-up observations performed by the Palomar Transient Factory (PTF), a Type IIn supernova (SN IIn) PTF12csy was found 0.degrees 2 away from the neutrino alert direction, with an error radius of 0.degrees 54. It has a redshift of z = 0.0684, corresponding to a luminosity distance of about 300 Mpc and the Pan-STARRS1 survey shows that its explosion time was at least 158 days (in host galaxy rest frame) before the neutrino alert, so that a causal connection is unlikely. The a posteriori significance of the chance detection of both the neutrinos and the SN at any epoch is 2.2 sigma within IceCube's 2011/12 data acquisition season. Also, a complementary neutrino analysis reveals no long-term signal over the course of one year. Therefore, we consider the SN detection coincidental and the neutrinos uncorrelated to the SN. However, the SN is unusual and interesting by itself: it is luminous and energetic, bearing strong resemblance to the SN IIn 2010jl, and shows signs of interaction of the SN ejecta with a dense circumstellar medium. High-energy neutrino emission is expected in models of diffusive shock acceleration, but at a low, non-detectable level for this specific SN. In this paper, we describe the SN PTF12csy and present both the neutrino and electromagnetic data, as well as their analysis.
  •  
25.
  • Aartsen, M. G., et al. (författare)
  • A Combined Maximum-Likelihood Analysis Of The High-Energy Astrophysical Neutrino Flux Measured With Icecube
  • 2015
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 809:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Evidence for an extraterrestrial flux of high-energy neutrinos has now been found in multiple searches with the IceCube detector. The first solid evidence was provided by a search for neutrino events with deposited energies greater than or similar to 30 TeV and interaction vertices inside the instrumented volume. Recent analyses suggest that the extraterrestrial flux extends to lower energies and is also visible with throughgoing, nu(mu)-induced tracks from the Northern Hemisphere. Here, we combine the results from six different IceCube searches for astrophysical neutrinos in a maximum-likelihood analysis. The combined event sample features high-statistics samples of shower-like and track-like events. The data are fit in up to three observables: energy, zenith angle, and event topology. Assuming the astrophysical neutrino flux to be isotropic and to consist of equal flavors at Earth, the all-flavor spectrum with neutrino energies between 25 TeV and 2.8 PeV is well described by an unbroken power law with best-fit spectral index -2.50 +/- 0.09 and a flux at 100 TeV of (6.7(-1.2)(+1.1)) x 10(-18) GeV-1 s(-1) sr(-1) cm(-2). Under the same assumptions, an unbroken power law with index -2 is disfavored with a significance of 3.8 sigma (p = 0.0066%) with respect to the best fit. This significance is reduced to 2.1 sigma (p = 1.7%) if instead we compare the best fit to a spectrum with index -2 that has an exponential cut-off at high energies. Allowing the electron-neutrino flux to deviate from the other two flavors, we find a nu(e) fraction of 0.18 +/- 0.11 at Earth. The sole production of electron neutrinos, which would be characteristic of neutron-decay-dominated sources, is rejected with a significance of 3.6 sigma ( p = 0.014%).
  •  
26.
  • Aartsen, M. G., et al. (författare)
  • An All-Sky Search For Three Flavors Of Neutrinos From Gamma-Ray Bursts With The Icecube Neutrino Observatory
  • 2016
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 824:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results and methodology of a search for neutrinos produced in the decay of charged pions created in interactions between protons and gamma-rays during the prompt emission of 807 gamma-ray bursts (GRBs) over the entire sky. This three-year search is the first in IceCube for shower-like Cherenkov light patterns from electron, muon, and tau neutrinos correlated with GRBs. We detect five low-significance events correlated with five GRBs. These events are consistent with the background expectation from atmospheric muons and neutrinos. The results of this search in combination with those of IceCube's four years of searches for track-like Cherenkov light patterns from muon neutrinos correlated with Northern-Hemisphere GRBs produce limits that tightly constrain current models of neutrino and ultra high energy cosmic ray production in GRB fireballs.
  •  
27.
  • Aartsen, M. G., et al. (författare)
  • Evidence for Astrophysical Muon Neutrinos from the Northern Sky with IceCube
  • 2015
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 115:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Results from the IceCube Neutrino Observatory have recently provided compelling evidence for the existence of a high energy astrophysical neutrino flux utilizing a dominantly Southern Hemisphere data set consisting primarily of nu(e) and nu(tau) charged-current and neutral-current ( cascade) neutrino interactions. In the analysis presented here, a data sample of approximately 35 000 muon neutrinos from the Northern sky is extracted from data taken during 659.5 days of live time recorded between May 2010 and May 2012. While this sample is composed primarily of neutrinos produced by cosmic ray interactions in Earth's atmosphere, the highest energy events are inconsistent with a hypothesis of solely terrestrial origin at 3.7 sigma significance. These neutrinos can, however, be explained by an astrophysical flux per neutrino flavor at a level of Phi(E-nu) = 9.9(-3.4)(+3.9) x 10(-19) GeV-1 cm(-2) sr(-1) s(-1) (E-nu/100 TeV)(-2), consistent with IceCube's Southern-Hemisphere-dominated result. Additionally, a fit for an astrophysical flux with an arbitrary spectral index is performed. We find a spectral index of 2.2(-0.2)(+0.2), which is also in good agreement with the Southern Hemisphere result.
  •  
28.
  • Aartsen, M. G., et al. (författare)
  • Measurement of the Atmospheric nu(e) Spectrum with IceCube
  • 2015
  • Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 91:12
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a measurement of the atmospheric nu(e) spectrum at energies between 0.1 and 100 TeV using data from the first year of the complete IceCube detector. Atmospheric nu(e) originate mainly from the decays of kaons produced in cosmic-ray air showers. This analysis selects 1078 fully contained events in 332 days of live time, and then identifies those consistent with particle showers. A likelihood analysis with improved event selection extends our previous measurement of the conventional v(e) fluxes to higher energies. The data constrain the conventional nu(e) flux to be 1.3(-0.3)(+0.4) times a baseline prediction from a Honda's calculation, including the knee of the cosmic-ray spectrum. A fit to the kaon contribution (xi) to the neutrino flux finds a kaon component that is xi = 1.3(-0.4)(+0.5) times the baseline value. The fitted/measured prompt neutrino flux from charmed hadron decays strongly depends on the assumed astrophysical flux and shape. If the astrophysical component follows a power law, the result for the prompt flux is 0.0(-0.0)(+3.0) times a calculated flux based on the work by Enberg, Reno, and Sarcevic.
  •  
29.
  • Aartsen, M. G., et al. (författare)
  • Neutrino oscillation studies with IceCube-DeepCore
  • 2016
  • Ingår i: Nuclear Physics B. - : Elsevier BV. - 0550-3213 .- 1873-1562. ; 908, s. 161-177
  • Tidskriftsartikel (refereegranskat)abstract
    • IceCube, a gigaton-scale neutrino detector located at the South Pole, was primarily designed to search for astrophysical neutrinos with energies of PeV and higher. This goal has been achieved with the detection of the highest energy neutrinos to date. At the other end of the energy spectrum, the DeepCore extension lowers the energy threshold of the detector to approximately 10 GeV and opens the door for oscillation studies using atmospheric neutrinos. An analysis of the disappearance of these neutrinos has been completed, with the results produced being complementary with dedicated oscillation experiments. Following a review of the detector principle and performance, the method used to make these calculations, as well as the results, is detailed. Finally, the future prospects of IceCube-DeepCore and the next generation of neutrino experiments at the South Pole (IceCube-Gen2, specifically the PINGU sub-detector) are briefly discussed.
  •  
30.
  • Aartsen, M. G., et al. (författare)
  • Searches for small-scale anisotropies from neutrino point sources with three years of IceCube data
  • 2015
  • Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 66, s. 39-52
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, IceCube found evidence for a diffuse signal of astrophysical neutrinos in an energy range of similar to 60 TeV to the PeV-scale [1]. The origin of those events, being a key to understanding the origin of cosmic rays, is still an unsolved question. So far, analyses have not succeeded to resolve the diffuse signal into point-like sources. Searches including a maximum-likelihood-ratio test, based on the reconstructed directions and energies of the detected down- and up-going neutrino candidates, were also performed on IceCube data leading to the exclusion of bright point sources. In this paper, we present two methods to search for faint neutrino point sources in three years of IceCube data, taken between 2008 and 2011. The first method is an autocorrelation test, applied separately to the northern and southern sky. The second method is a multipole analysis, which expands the measured data in the northern hemisphere into spherical harmonics and uses the resulting expansion coefficients to separate signal from background. With both methods, the results are consistent with the background expectation with a slightly more sparse spatial distribution, corresponding to an underfluctuation. Depending on the assumed number of sources, the resulting upper limit on the flux per source in the northern hemisphere for an E-2 energy spectrum ranges from similar to 1.5. 10(-8) GeV/cm(2) s(-1), in the case of one assumed source, to similar to 4. 10(-10) GeV/cm(2) s(-1), in the case of 3500 assumed sources.
  •  
31.
  • Aartsen, M. G., et al. (författare)
  • SEARCHES FOR TIME-DEPENDENT NEUTRINO SOURCES WITH ICECUBE DATA FROM 2008 TO 2012
  • 2015
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 807:1
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper searches for flaring astrophysical neutrino sources and sources with periodic emission with the IceCube neutrino telescope are presented. In contrast to time-integrated searches, where steady emission is assumed, the analyses presented here look for a time-dependent signal of neutrinos using the information from the neutrino arrival times to enhance the discovery potential. A search was performed for correlations between neutrino arrival times and directions, as well as neutrino emission following time-dependent light curves, sporadic emission, or periodicities of candidate sources. These include active galactic nuclei, soft gamma-ray repeaters, supernova remnants hosting pulsars, microquasars, and X-ray binaries. The work presented here updates and extends previously published results to a longer period that covers 4 years. of data from 2008 April 5 to 2012 May 16, including the first year of operation of the completed 86 string detector. The analyses did not find any significant time-dependent point sources of neutrinos, and the results were used to set upper limits on the neutrino flux from source candidates.
  •  
32.
  • Kehoe, Laura, et al. (författare)
  • Make EU trade with Brazil sustainable
  • 2019
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
33.
  • Wang, Haidong, et al. (författare)
  • Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015 : the Global Burden of Disease Study 2015.
  • 2016
  • Ingår i: The lancet. HIV. - : Elsevier. - 2352-3018. ; 3:8, s. e361-e387
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.METHODS: For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification.FINDINGS: Global HIV incidence reached its peak in 1997, at 3·3 million new infections (95% uncertainty interval [UI] 3·1-3·4 million). Annual incidence has stayed relatively constant at about 2·6 million per year (range 2·5-2·8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38·8 million (95% UI 37·6-40·4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1·8 million deaths (95% UI 1·7-1·9 million) in 2005, to 1·2 million deaths (1·1-1·3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections.INTERPRETATION: Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030.
  •  
34.
  • Aartsen, M. G., et al. (författare)
  • Atmospheric and astrophysical neutrinos above 1 TeV interacting in IceCube
  • 2015
  • Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 91:2, s. 022001-
  • Tidskriftsartikel (refereegranskat)abstract
    • The IceCube Neutrino Observatory was designed primarily to search for high-energy (TeV-PeV) neutLrinos produced in distant astrophysical objects. A search for. greater than or similar to 100 TeV neutrinos interacting inside the instrumented volume has recently provided evidence for an isotropic flux of such neutrinos. At lower energies, IceCube collects large numbers of neutrinos from the weak decays of mesons in cosmic-ray air showers. Here we present the results of a search for neutrino interactions inside IceCube's instrumented volume between 1 TeV and 1 PeV in 641 days of data taken from 2010-2012, lowering the energy threshold for neutrinos from the southern sky below 10 TeV for the first time, far below the threshold of the previous high-energy analysis. Astrophysical neutrinos remain the dominant component in the southern sky down to a deposited energy of 10 TeV. From these data we derive new constraints on the diffuse astrophysical neutrino spectrum, Phi(v) = 2.06(-0.3)(+0.4) x 10(-18) (E-v = 10(5) GeV)-2.46 +/- 0.12GeV-1 cm(-2) sr(-1) s(-1) for 25 TeV < E-v < 1.4 PeV, as well as the strongest upper limit yet on the flux of neutrinos from charmed-meson decay in the atmosphere, 1.52 times the benchmark theoretical prediction used in previous IceCube results at 90% confidence.
  •  
35.
  • Aartsen, M. G., et al. (författare)
  • Development of a general analysis and unfolding scheme and its application to measure the energy spectrum of atmospheric neutrinos with IceCube
  • 2015
  • Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 75:3
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the development and application of a generic analysis scheme for the measurement of neutrino spectra with the IceCube detector. This scheme is based on regularized unfolding, preceded by an event selection which uses a Minimum Redundancy Maximum Relevance algorithm to select the relevant variables and a random forest for the classification of events. The analysis has been developed using IceCube data from the 59-string configuration of the detector. 27,771 neutrino candidates were detected in 346 days of livetime. A rejection of 99.9999 % of the atmospheric muon background is achieved. The energy spectrum of the atmospheric neutrino flux is obtained using the TRUEE unfolding program. The unfolded spectrum of atmospheric muon neutrinos covers an energy range from 100 GeV to 1 PeV. Compared to the previous measurement using the detector in the 40-string configuration, the analysis presented here, extends the upper end of the atmospheric neutrino spectrum by more than a factor of two, reaching an energy region that has not been previously accessed by spectral measurements.
  •  
36.
  • Aartsen, M. G., et al. (författare)
  • Flavor Ratio of Astrophysical Neutrinos above 35 TeV in IceCube
  • 2015
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 114:17
  • Tidskriftsartikel (refereegranskat)abstract
    • A diffuse flux of astrophysical neutrinos above 100 TeV has been observed at the IceCube Neutrino Observatory. Here we extend this analysis to probe the astrophysical flux down to 35 TeV and analyze its flavor composition by classifying events as showers or tracks. Taking advantage of lower atmospheric backgrounds for showerlike events, we obtain a shower-biased sample containing 129 showers and 8 tracks collected in three years from 2010 to 2013. We demonstrate consistency with the (f(e) : f(mu) : f(tau))(circle plus) approximate to (1 : 1 : 1)(circle plus) flavor ratio at Earth commonly expected from the averaged oscillations of neutrinos produced by pion decay in distant astrophysical sources. Limits are placed on nonstandard flavor compositions that cannot be produced by averaged neutrino oscillations but could arise in exotic physics scenarios. A maximally tracklike composition of (0 : 1 : 0)(circle plus) is excluded at 3.3 sigma, and a purely showerlike composition of (1 : 0 : 0)(circle plus) is excluded at 2.3 sigma.
  •  
37.
  • Aartsen, M. G., et al. (författare)
  • Lowering Icecube'S Energy Threshold For Point Source Searches In The Southern Sky
  • 2016
  • Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 824:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Observation of a point source of astrophysical neutrinos would be a "smoking gun" signature of a cosmic-ray accelerator. While IceCube has recently discovered a diffuse flux of astrophysical neutrinos, no localized point source has been observed. Previous IceCube searches for point sources in the southern sky were restricted by either an energy threshold above a few hundred TeV or poor neutrino angular resolution. Here we present a search for southern sky point sources with greatly improved sensitivities to neutrinos with energies below 100 TeV. By selecting charged-current nu(mu) interacting inside the detector, we reduce the atmospheric background while retaining efficiency for astrophysical neutrino-induced events reconstructed with sub-degree angular resolution. The new event sample covers three years of detector data and leads to a factor of 10 improvement in sensitivity to point sources emitting below 100 TeV in the southern sky. No statistically significant evidence of point sources was found, and upper limits are set on neutrino emission from individual sources. A posteriori analysis of the highest-energy (similar to 100 TeV) starting event in the sample found that this event alone represents a 2.8 sigma deviation from the hypothesis that the data consists only of atmospheric background.
  •  
38.
  • Aartsen, M. G., et al. (författare)
  • Multipole analysis of IceCube data to search for dark matter accumulated in the Galactic halo
  • 2015
  • Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 75:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Dark matter which is bound in the Galactic halo might self-annihilate and produce a flux of stable final state particles, e. g. high energy neutrinos. These neutrinos can be detected with IceCube, a cubic-kilometer sized Cherenkov detector. Given IceCube's large field of view, a characteristic anisotropy of the additional neutrino flux is expected. In this paper we describe a multipole method to search for such a large-scale anisotropy in IceCube data. This method uses the expansion coefficients of a multipole expansion of neutrino arrival directions and incorporates signal-specific weights for each expansion coefficient. We apply the technique to a high-purity muon neutrino sample from the Northern Hemisphere. The final result is compatible with the null-hypothesis. As no signal was observed, we present limits on the self-annihilation cross-section averaged over the relative velocity distribution down to 1.9x10(-23) cm(3) s(-1) for a dark matter particle mass of 700-1,000 GeV and direct annihilation into nu(nu) over bar. The resulting exclusion limits come close to exclusion limits from gamma-ray experiments, that focus on the outer Galactic halo, for high dark matter masses of a few TeV and hard annihilation channels.
  •  
39.
  • Aartsen, M. G., et al. (författare)
  • Search for Prompt Neutrino Emission from Gamma-Ray Bursts with IceCube
  • 2015
  • Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 805:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present constraints derived from a search of four years of IceCube data for a prompt neutrino flux from gammaray bursts (GRBs). A single low-significance neutrino, compatible with the atmospheric neutrino background, was found in coincidence with one of the 506 observed bursts. Although GRBs have been proposed as candidate sources for ultra-high-energy cosmic rays, our limits on the neutrino flux disfavor much of the parameter space for the latest models. We also find that no more than similar to 1% of the recently observed astrophysical neutrino flux consists of prompt emission from GRBs that are potentially observable by existing satellites.
  •  
40.
  • Aartsen, M. G., et al. (författare)
  • The IceProd framework : Distributed data processing for the IceCube neutrino observatory
  • 2015
  • Ingår i: Journal of Parallel and Distributed Computing. - : Elsevier BV. - 0743-7315 .- 1096-0848. ; 75, s. 198-211
  • Tidskriftsartikel (refereegranskat)abstract
    • IceCube is a one-gigaton instrument located at the geographic South Pole, designed to detect cosmic neutrinos, identify the particle nature of dark matter, and study high-energy neutrinos themselves. Simulation of the IceCube detector and processing of data require a significant amount of computational resources. This paper presents the first detailed description of IceProd, a lightweight distributed management system designed to meet these requirements. It is driven by a central database in order to manage mass production of simulations and analysis of data produced by the IceCube detector. IceProd runs as a separate layer on top of other middleware and can take advantage of a variety of computing resources, including grids and batch systems such as CREAM, HTCondor, and PBS. This is accomplished by a set of dedicated daemons that process job submission in a coordinated fashion through the use of middleware plugins that serve to abstract the details of job submission and job management from the framework. (C) 2014 Elsevier Inc. All rights reserved.
  •  
41.
  • Evangelou, Evangelos, et al. (författare)
  • Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
  • 2018
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
  • Tidskriftsartikel (refereegranskat)abstract
    • High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
  •  
42.
  • Justice, Anne E., et al. (författare)
  • Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
  • 2019
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
  • Tidskriftsartikel (refereegranskat)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.
  •  
43.
  • Schmidt, Amand F., et al. (författare)
  • Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9
  • 2019
  • Ingår i: BMC Cardiovascular Disorders. - : BMC. - 1471-2261 .- 1471-2261. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
  •  
44.
  • Wain, Louise V., et al. (författare)
  • Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney
  • 2017
  • Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 70:3, s. e4-e19
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
  •  
45.
  • Hollestelle, Antoinette, et al. (författare)
  • No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
  • 2016
  • Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
  •  
46.
  • Kyu, Hmwe H, et al. (författare)
  • Global and National Burden of Diseases and Injuries Among Children and Adolescents Between 1990 and 2013 : Findings From the Global Burden of Disease 2013 Study.
  • 2016
  • Ingår i: JAMA pediatrics. - : American Medical Association (AMA). - 2168-6203 .- 2168-6211. ; 170:3, s. 267-287
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE: The literature focuses on mortality among children younger than 5 years. Comparable information on nonfatal health outcomes among these children and the fatal and nonfatal burden of diseases and injuries among older children and adolescents is scarce.OBJECTIVE: To determine levels and trends in the fatal and nonfatal burden of diseases and injuries among younger children (aged <5 years), older children (aged 5-9 years), and adolescents (aged 10-19 years) between 1990 and 2013 in 188 countries from the Global Burden of Disease (GBD) 2013 study.EVIDENCE REVIEW: Data from vital registration, verbal autopsy studies, maternal and child death surveillance, and other sources covering 14 244 site-years (ie, years of cause of death data by geography) from 1980 through 2013 were used to estimate cause-specific mortality. Data from 35 620 epidemiological sources were used to estimate the prevalence of the diseases and sequelae in the GBD 2013 study. Cause-specific mortality for most causes was estimated using the Cause of Death Ensemble Model strategy. For some infectious diseases (eg, HIV infection/AIDS, measles, hepatitis B) where the disease process is complex or the cause of death data were insufficient or unavailable, we used natural history models. For most nonfatal health outcomes, DisMod-MR 2.0, a Bayesian metaregression tool, was used to meta-analyze the epidemiological data to generate prevalence estimates.FINDINGS: Of the 7.7 (95% uncertainty interval [UI], 7.4-8.1) million deaths among children and adolescents globally in 2013, 6.28 million occurred among younger children, 0.48 million among older children, and 0.97 million among adolescents. In 2013, the leading causes of death were lower respiratory tract infections among younger children (905 059 deaths; 95% UI, 810 304-998 125), diarrheal diseases among older children (38 325 deaths; 95% UI, 30 365-47 678), and road injuries among adolescents (115 186 deaths; 95% UI, 105 185-124 870). Iron deficiency anemia was the leading cause of years lived with disability among children and adolescents, affecting 619 (95% UI, 618-621) million in 2013. Large between-country variations exist in mortality from leading causes among children and adolescents. Countries with rapid declines in all-cause mortality between 1990 and 2013 also experienced large declines in most leading causes of death, whereas countries with the slowest declines had stagnant or increasing trends in the leading causes of death. In 2013, Nigeria had a 12% global share of deaths from lower respiratory tract infections and a 38% global share of deaths from malaria. India had 33% of the world's deaths from neonatal encephalopathy. Half of the world's diarrheal deaths among children and adolescents occurred in just 5 countries: India, Democratic Republic of the Congo, Pakistan, Nigeria, and Ethiopia.CONCLUSIONS AND RELEVANCE: Understanding the levels and trends of the leading causes of death and disability among children and adolescents is critical to guide investment and inform policies. Monitoring these trends over time is also key to understanding where interventions are having an impact. Proven interventions exist to prevent or treat the leading causes of unnecessary death and disability among children and adolescents. The findings presented here show that these are underused and give guidance to policy makers in countries where more attention is needed.
  •  
47.
  • Wang, Li-San, et al. (författare)
  • Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
  • 2015
  • Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
  •  
48.
  • ODonnell, Michael, et al. (författare)
  • Registered Replication Report: Dijksterhuis and van Knippenberg (1998)
  • 2018
  • Ingår i: Perspectives on Psychological Science. - : SAGE PUBLICATIONS LTD. - 1745-6916 .- 1745-6924. ; 13:2, s. 268-294
  • Tidskriftsartikel (refereegranskat)abstract
    • Dijksterhuis and van Knippenberg (1998) reported that participants primed with a category associated with intelligence (professor) subsequently performed 13% better on a trivia test than participants primed with a category associated with a lack of intelligence (soccer hooligans). In two unpublished replications of this study designed to verify the appropriate testing procedures, Dijksterhuis, van Knippenberg, and Holland observed a smaller difference between conditions (2%-3%) as well as a gender difference: Men showed the effect (9.3% and 7.6%), but women did not (0.3% and -0.3%). The procedure used in those replications served as the basis for this multilab Registered Replication Report. A total of 40 laboratories collected data for this project, and 23 of these laboratories met all inclusion criteria. Here we report the meta-analytic results for those 23 direct replications (total N = 4,493), which tested whether performance on a 30-item general-knowledge trivia task differed between these two priming conditions (results of supplementary analyses of the data from all 40 labs, N = 6,454, are also reported). We observed no overall difference in trivia performance between participants primed with the professor category and those primed with the hooligan category (0.14%) and no moderation by gender.
  •  
49.
  • Mokdad, Ali H., et al. (författare)
  • Adolescent health in the Eastern Mediterranean Region : findings from the global burden of disease 2015 study
  • 2018
  • Ingår i: International Journal of Public Health. - : SPRINGER BASEL AG. - 1661-8556 .- 1661-8564. ; 63, s. 79-96
  • Tidskriftsartikel (refereegranskat)abstract
    • The 22 countries of the East Mediterranean Region (EMR) have large populations of adolescents aged 10-24 years. These adolescents are central to assuring the health, development, and peace of this region. We described their health needs. Using data from the Global Burden of Disease Study 2015 (GBD 2015), we report the leading causes of mortality and morbidity for adolescents in the EMR from 1990 to 2015. We also report the prevalence of key health risk behaviors and determinants. Communicable diseases and the health consequences of natural disasters reduced substantially between 1990 and 2015. However, these gains have largely been offset by the health impacts of war and the emergence of non-communicable diseases (including mental health disorders), unintentional injury, and self-harm. Tobacco smoking and high body mass were common health risks amongst adolescents. Additionally, many EMR countries had high rates of adolescent pregnancy and unmet need for contraception. Even with the return of peace and security, adolescents will have a persisting poor health profile that will pose a barrier to socioeconomic growth and development of the EMR.
  •  
50.
  • Schmidt, Amand F., et al. (författare)
  • PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study
  • 2017
  • Ingår i: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 5:2, s. 97-105
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way off sets their substantial benefi ts. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely eff ects of PCSK9 inhibitors on diabetes risk. Methods In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA 1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. Findings Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0.09 mmol/L, 95% CI 0.02 to 0.15), bodyweight (1.03 kg, 0.24 to 1.82), waist-to-hip ratio (0.006, 0.003 to 0.010), and an odds ratio for type diabetes of 1.29 (1.11 to 1.50). Based on the collected data, we did not identify associations with HbA 1c (0.03%, -0.01 to 0.08), fasting insulin (0.00%, -0.06 to 0.07), and BMI (0.11 kg/m(2), -0.09 to 0.30). Interpretation PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefi ts of PCSK9 inhibitor treatment, as was previously done for statins.
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