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2.
  • Abelev, B., et al. (författare)
  • Charge correlations using the balance function in Pb-Pb collisions at root s(NN)=2.76 TeV
  • 2013
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 723:4-5, s. 267-279
  • Tidskriftsartikel (refereegranskat)abstract
    • In high-energy heavy-ion collisions, the correlations between the emitted particles can be used as a probe to gain insight into the charge creation mechanisms. In this Letter, we report the first results of such studies using the electric charge balance function in the relative pseudorapidity (Delta eta) and azimuthal angle (Delta phi) in Pb-Pb collisions at root s(NN) = 2.76 TeV with the ALICE detector at the Large Hadron Collider. The width of the balance function decreases with growing centrality (i.e. for more central collisions) in both projections. This centrality dependence is not reproduced by HIJING, while AMPT, a model which incorporates strings and parton rescattering, exhibits qualitative agreement with the measured correlations in Delta phi but fails to describe the correlations in Delta eta. A thermal blast-wave model incorporating local charge conservation and tuned to describe the p(T) spectra and v(2) measurements reported by ALICE, is used to fit the centrality dependence of the width of the balance function and to extract the average separation of balancing charges at freeze-out. The comparison of our results with measurements at lower energies reveals an ordering with root s(NN): the balance functions become narrower with increasing energy for all centralities. This is consistent with the effect of larger radial flow at the LHC energies but also with the late stage creation scenario of balancing charges. However, the relative decrease of the balance function widths in Delta eta and Delta phi, with centrality from the highest SPS to the LHC energy exhibits only small differences. This observation cannot be interpreted solely within the framework where the majority of the charge is produced at a later stage in the evolution of the heavy-ion collision. (C) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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3.
  • Adam, J., et al. (författare)
  • Measurement of jet suppression in central Pb-Pb collisions at root s(NN)=2.76 TeV
  • 2015
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 746, s. 1-14
  • Tidskriftsartikel (refereegranskat)abstract
    • The transverse momentum(p(T)) spectrum and nuclear modification factor (R-AA) of reconstructed jets in 0-10% and 10-30% central Pb-Pb collisions at root s(NN) = 2.76 TeV were measured. Jets were reconstructed using the anti-k(T) jet algorithm with a resolution parameter of R = 0.2 from charged and neutral particles, utilizing the ALICE tracking detectors and Electromagnetic Calorimeter (EMCal). The jet p(T) spectra are reported in the pseudorapidity interval of \eta(jet)\ < 0.5 for 40 < p(T), jet < 120 GeV/c in 0-10% and for 30 < p(T), jet < 100 GeV/c in 10-30% collisions. Reconstructed jets were required to contain a leading charged particle with p(T) > 5 GeV/c to suppress jets constructed from the combinatorial background in Pb-Pb collisions. The leading charged particle requirement applied to jet spectra both in pp and Pb-Pb collisions had a negligible effect on the R-AA. The nuclear modification factor R-AA was found to be 0.28 +/- 0.04 in 0-10% and 0.35 +/- 0.04 in 10-30% collisions, independent of p(T), jet within the uncertainties of the measurement. The observed suppression is in fair agreement with expectations from two model calculations with different approaches to jet quenching. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V.
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4.
  • Abelev, B., et al. (författare)
  • Centrality determination of Pb-Pb collisions at root s(NN)=2.76 TeV with ALICE
  • 2013
  • Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 88:4
  • Tidskriftsartikel (refereegranskat)abstract
    • This publication describes the methods used to measure the centrality of inelastic Pb-Pb collisions at a center-of-mass energy of 2.76 TeV per colliding nucleon pair with ALICE. The centrality is a key parameter in the study of the properties of QCD matter at extreme temperature and energy density, because it is directly related to the initial overlap region of the colliding nuclei. Geometrical properties of the collision, such as the number of participating nucleons and the number of binary nucleon-nucleon collisions, are deduced from a Glauber model with a sharp impact parameter selection and shown to be consistent with those extracted from the data. The centrality determination provides a tool to compare ALICE measurements with those of other experiments and with theoretical calculations.
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5.
  • Abelev, B., et al. (författare)
  • Production of inclusive gamma(1S) and gamma(2S) in p-Pb collisions at, root S-NN=5.02 TeV
  • 2015
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 740, s. 105-117
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on the production of inclusive gamma(1S) and gamma(2S) in p-Pb collisions at root S-NN = 5.02 TeV at the LHC. The measurement is performed with the ALICE detector at backward (-4.46 < ycms < 2.96) and forward (2.03 < ycms <3.53) rapidity down to zero transverse momentum. The production cross sections of the gamma(1S) and gamma(2S) are presented, as well as the nuclear modification factor and the ratio of the forward to backward yields of gamma(1S). A suppression of the inclusive gamma(1S) yield in p-Pb collisions with respect to the yield from pp collisions scaled by the number of binary nucleon-nucleon collisions is observed at forward rapidity but not at backward rapidity. The results are compared to theoretical model calculations including nuclear shadowing or partonic energy loss effects. (C) 2014 The Authors. Published by Elsevier B.V.
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6.
  • Abelev, B., et al. (författare)
  • Centrality, rapidity and transverse momentum dependence of J/Psi suppression in Pb-Pb collisions at root(NN)-N-S=2.76TeV
  • 2014
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 734, s. 314-327
  • Tidskriftsartikel (refereegranskat)abstract
    • The inclusive J/.nuclear modification factor (R-AA) in Pb-Pb collisions at root(NN)-N-S = 2.76TeVhas been measured by ALICE as a function of centrality in the e+ e-decay channel at mid-rapidity (| y| < 0.8) and as a function of centrality, transverse momentum and rapidity in the + -decay channel at forward-rapidity (2.5 < y < 4). The J/.yields measured in Pb-Pb are suppressed compared to those in ppcollisions scaled by the number of binary collisions. The RAAintegrated over a centrality range corresponding to 90% of the inelastic Pb-Pb cross section is 0.72 - 0.06(stat.) - 0.10(syst.) at mid-rapidity and 0.58 - 0.01(stat.) - 0.09(syst.) at forward-rapidity. At low transverse momentum, significantly larger values of RAAare measured at forward-rapidity compared to measurements at lower energy. These features suggest that a contribution to the J/.yield originates from charm quark (re) combination in the deconfined partonic medium. (C) 2014 The Authors. Published by Elsevier B. V.
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8.
  • de Rojas, I., et al. (författare)
  • Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
  • 2021
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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10.
  • Taddei, C, et al. (författare)
  • Repositioning of the global epicentre of non-optimal cholesterol
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
  • Tidskriftsartikel (refereegranskat)abstract
    • High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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11.
  • Arndt, D. S., et al. (författare)
  • STATE OF THE CLIMATE IN 2017
  • 2018
  • Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
  • Forskningsöversikt (refereegranskat)
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13.
  • Arndt, D. S., et al. (författare)
  • State of the Climate in 2016
  • 2017
  • Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
  • Tidskriftsartikel (refereegranskat)abstract
    • In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.
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14.
  • Abbafati, Cristiana, et al. (författare)
  • 2020
  • Tidskriftsartikel (refereegranskat)
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15.
  • Chang, A. Y., et al. (författare)
  • Past, present, and future of global health financing : A review of development assistance, government, out-of-pocket, and other private spending on health for 195 countries, 1995-2050
  • 2019
  • Ingår i: The Lancet. - : Lancet Publishing Group. - 0140-6736 .- 1474-547X. ; 393:10187, s. 2233-2260
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Comprehensive and comparable estimates of health spending in each country are a key input for health policy and planning, and are necessary to support the achievement of national and international health goals. Previous studies have tracked past and projected future health spending until 2040 and shown that, with economic development, countries tend to spend more on health per capita, with a decreasing share of spending from development assistance and out-of-pocket sources. We aimed to characterise the past, present, and predicted future of global health spending, with an emphasis on equity in spending across countries. Methods: We estimated domestic health spending for 195 countries and territories from 1995 to 2016, split into three categories-government, out-of-pocket, and prepaid private health spending-and estimated development assistance for health (DAH) from 1990 to 2018. We estimated future scenarios of health spending using an ensemble of linear mixed-effects models with time series specifications to project domestic health spending from 2017 through 2050 and DAH from 2019 through 2050. Data were extracted from a broad set of sources tracking health spending and revenue, and were standardised and converted to inflation-adjusted 2018 US dollars. Incomplete or low-quality data were modelled and uncertainty was estimated, leading to a complete data series of total, government, prepaid private, and out-of-pocket health spending, and DAH. Estimates are reported in 2018 US dollars, 2018 purchasing-power parity-adjusted dollars, and as a percentage of gross domestic product. We used demographic decomposition methods to assess a set of factors associated with changes in government health spending between 1995 and 2016 and to examine evidence to support the theory of the health financing transition. We projected two alternative future scenarios based on higher government health spending to assess the potential ability of governments to generate more resources for health. Findings: Between 1995 and 2016, health spending grew at a rate of 4.00% (95% uncertainty interval 3.89-4.12) annually, although it grew slower in per capita terms (2.72% [2.61-2.84]) and increased by less than $1 per capita over this period in 22 of 195 countries. The highest annual growth rates in per capita health spending were observed in upper-middle-income countries (5.55% [5.18-5.95]), mainly due to growth in government health spending, and in lower-middle-income countries (3.71% [3.10-4.34]), mainly from DAH. Health spending globally reached $8.0 trillion (7.8-8.1) in 2016 (comprising 8.6% [8.4-8.7] of the global economy and $10.3 trillion [10.1-10.6] in purchasing-power parity-adjusted dollars), with a per capita spending of US$5252 (5184-5319) in high-income countries, $491 (461-524) in upper-middle-income countries, $81 (74-89) in lower-middle-income countries, and $40 (38-43) in low-income countries. In 2016, 0.4% (0.3-0.4) of health spending globally was in low-income countries, despite these countries comprising 10.0% of the global population. In 2018, the largest proportion of DAH targeted HIV/AIDS ($9.5 billion, 24.3% of total DAH), although spending on other infectious diseases (excluding tuberculosis and malaria) grew fastest from 2010 to 2018 (6.27% per year). The leading sources of DAH were the USA and private philanthropy (excluding corporate donations and the Bill & Melinda Gates Foundation). For the first time, we included estimates of China’s contribution to DAH ($644.7 million in 2018). Globally, health spending is projected to increase to $15.0 trillion (14.0-16.0) by 2050 (reaching 9.4% [7.6-11.3] of the global economy and $21.3 trillion [19.8-23.1] in purchasing-power parity-adjusted dollars), but at a lower growth rate of 1.84% (1.68-2.02) annually, and with continuing disparities in spending between countries. In 2050, we estimate that 0.6% (0.6-0.7) of health spending will occur in currently low-income countries, despite these countries comprising an estimated 15.7% of the global population by 2050. The ratio between per capita health spending in high-income and low-income countries was 130.2 (122.9-136.9) in 2016 and is projected to remain at similar levels in 2050 (125.9 [113.7-138.1]). The decomposition analysis identified governments’ increased prioritisation of the health sector and economic development as the strongest factors associated with increases in government health spending globally. Future government health spending scenarios suggest that, with greater prioritisation of the health sector and increased government spending, health spending per capita could more than double, with greater impacts in countries that currently have the lowest levels of government health spending. Interpretation: Financing for global health has increased steadily over the past two decades and is projected to continue increasing in the future, although at a slower pace of growth and with persistent disparities in per-capita health spending between countries. Out-of-pocket spending is projected to remain substantial outside of high-income countries. Many low-income countries are expected to remain dependent on development assistance, although with greater government spending, larger investments in health are feasible. In the absence of sustained new investments in health, increasing efficiency in health spending is essential to meet global health targets. © 2019 The Author(s).
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16.
  • Fresard, Laure, et al. (författare)
  • Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
  • 2019
  • Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
  • Tidskriftsartikel (refereegranskat)abstract
    • It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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17.
  • Hudson, Lawrence N, et al. (författare)
  • The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
  • 2017
  • Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
  • Tidskriftsartikel (refereegranskat)abstract
    • The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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18.
  • Olalde, I., et al. (författare)
  • The Beaker phenomenon and the genomic transformation of northwest Europe
  • 2018
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 555:7695, s. 190-196
  • Tidskriftsartikel (refereegranskat)abstract
    • From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain's gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries.
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20.
  • Micah, Angela E., et al. (författare)
  • Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
  • 2021
  • Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
  • Forskningsöversikt (refereegranskat)abstract
    • Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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21.
  • Schellart, P., et al. (författare)
  • Detecting cosmic rays with the LOFAR radio telescope
  • 2013
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 560, s. 1-14
  • Tidskriftsartikel (refereegranskat)abstract
    • The low frequency array (LOFAR), is the first radio telescope designed with the capability to measure radio emission from cosmic-ray induced air showers in parallel with interferometric observations. In the first ~2 years of observing, 405 cosmic-ray events in the energy range of 1016−1018 eV have been detected in the band from 30−80 MHz. Each of these air showers is registered with up to ~1000 independent antennas resulting in measurements of the radio emission with unprecedented detail. This article describes the dataset, as well as the analysis pipeline, and serves as a reference for future papers based on these data. All steps necessary to achieve a full reconstruction of the electric field at every antenna position are explained, including removal of radio frequency interference, correcting for the antenna response and identification of the pulsed signal.
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22.
  • Asgekar, A., et al. (författare)
  • LOFAR detections of low-frequency radio recombination lines towards Cassiopeia A
  • 2013
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 551
  • Tidskriftsartikel (refereegranskat)abstract
    • Cassiopeia A was observed using the low-band antennas of the LOw Frequency ARray (LOFAR) with high spectral resolution. This allowed a search for radio recombination lines (RRLs) along the line-of-sight to this source. Five carbon alpha RRLs were detected in absorption between 40 and 50 MHz with a signal-to-noise ratio of >5 from two independent LOFAR data sets. The derived line velocities (v(LSR) similar to -50 km s(-1)) and integrated optical depths (similar to 13 s(-1)) of the RRLs in our spectra, extracted over the whole supernova remnant, are consistent within each LOFAR data set and with those previously reported. For the first time, we are able to extract spectra against the brightest hotspot of the remnant at frequencies below 330 MHz. These spectra show significantly higher (15-80 percent) integrated optical depths, indicating that there is small-scale angular structure of the order of similar to 1 pc in the absorbing gas distribution over the face of the remnant. We also place an upper limit of 3 x 10(-4) on the peak optical depths of hydrogen and helium RRLs. These results demonstrate that LOFAR has the desired spectral stability and sensitivity to study faint recombination lines in the decameter band.
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23.
  • Corstanje, A., et al. (författare)
  • The shape of the radio wavefront of extensive air showers as measured with LOFAR
  • 2015
  • Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 61, s. 22-31
  • Tidskriftsartikel (refereegranskat)abstract
    • Extensive air showers, induced by high energy cosmic rays impinging on the Earth’s atmosphere, produce radio emission that is measured with the LOFAR radio telescope. As the emission comes from a finite distance of a few kilometers, the incident wavefront is non-planar. A spherical, conical or hyperbolic shape of the wavefront has been proposed, but measurements of individual air showers have been inconclusive so far. For a selected high-quality sample of 161 measured extensive air showers, we have reconstructed the wavefront by measuring pulse arrival times to sub-nanosecond precision in 200 to 350 individual antennas. For each measured air shower, we have fitted a conical, spherical, and hyperboloid shape to the arrival times. The fit quality and a likelihood analysis show that a hyperboloid is the best parameterization. Using a non-planar wavefront shape gives an improved angular resolution, when reconstructing the shower arrival direction. Furthermore, a dependence of the wavefront shape on the shower geometry can be seen. This suggests that it will be possible to use a wavefront shape analysis to get an additional handle on the atmospheric depth of the shower maximum, which is sensitive to the mass of the primary particle.
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24.
  • Gong, J., et al. (författare)
  • Sex differences in dementia risk and risk factors: Individual-participant data analysis using 21 cohorts across six continents from the COSMIC consortium
  • 2023
  • Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:8, s. 3365-3378
  • Tidskriftsartikel (refereegranskat)abstract
    • IntroductionSex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno-regional groups. MethodsA total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and women-to-men ratio of hazard ratios (RHRs) for associations between RFs and all-cause dementia were derived from mixed-effect Cox models. ResultsIncident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low- and lower-middle-income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs. DiscussionDementia risk was higher in women than men, with possible variations by country-level income settings, but most RFs appear to work similarly in women and men.
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25.
  • Oonk, J. B. R., et al. (författare)
  • Discovery of carbon radio recombination lines in absorption towards Cygnus A
  • 2014
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 437:4, s. 3506-3515
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the first detection of carbon radio recombination line absorption along the line of sight to Cygnus A. The observations were carried out with the Low Frequency Array in the 33–57 MHz range. These low-frequency radio observations provide us with a new line of sight to study the diffuse, neutral gas in our Galaxy. To our knowledge this is the first time that foreground Milky Way recombination line absorption has been observed against a bright extragalactic background source. By stacking 48 carbon α lines in the observed frequency range we detect carbon absorption with a signal-to-noise ratio of about 5. The average carbon absorption has a peak optical depth of 2 × 10−4, a line width of 10 km s−1 and a velocity of +4 km s−1 with respect to the local standard of rest. The associated gas is found to have an electron temperature Te ∼ 110 K and density ne ∼ 0.06 cm−3. These properties imply that the observed carbon α absorption likely arises in the cold neutral medium of the Orion arm of the Milky Way. Hydrogen and helium lines were not detected to a 3σ peak optical depth limit of 1.5 × 10−4 for a 4 km s−1 channel width. Radio recombination lines associated with Cygnus A itself were also searched for, but are not detected. We set a 3σ upper limit of 1.5 × 10−4 for the peak optical depth of these lines for a 4 km s−1 channel width.
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26.
  • Nelles, A., et al. (författare)
  • Calibrating the absolute amplitude scale for air showers measured at LOFAR
  • 2015
  • Ingår i: Journal of Instrumentation. - 1748-0221. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Air showers induced by cosmic rays create nanosecond pulses detectable at radio frequencies. These pulses have been measured successfully in the past few years at the LOw-Frequency ARray (LOFAR) and are used to study the properties of cosmic rays. For a complete understanding of this phenomenon and the underlying physical processes, an absolute calibration of the detecting antenna system is needed. We present three approaches that were used to check and improve the antenna model of LOFAR and to provide an absolute calibration of the whole system for air shower measurements. Two methods are based on calibrated reference sources and one on a calibration approach using the diffuse radio emission of the Galaxy, optimized for short data-sets. An accuracy of 19% in amplitude is reached. The absolute calibration is also compared to predictions from air shower simulations. These results are used to set an absolute energy scale for air shower measurements and can be used as a basis for an absolute scale for the measurement of astronomical transients with LOFAR.
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27.
  • Orrù, E., et al. (författare)
  • Wide-field LOFAR imaging of the field around the double-double radio galaxy B1834+620 : A fresh view on a restarted AGN and doubeltjes
  • 2015
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 584, s. 1-12
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The existence of double-double radio galaxies (DDRGs) is evidence for recurrent jet activity in active galactic nuclei (AGN), as expected from standard accretion models. A detailed study of these rare sources provides new perspectives for investigating the AGN duty cycle, AGN-galaxy feedback, and accretion mechanisms. Large catalogues of radio sources, on the other hand, provide statistical information about the evolution of the radio-loud AGN population out to high redshifts.Aims. Using wide-field imaging with the LOFAR telescope, we study both a well-known DDRG as well as a large number of radio sources in the field of view.Methods. We present a high resolution image of the DDRG B1834+620 obtained at 144 MHz using LOFAR commissioning data. Our image covers about 100 square degrees and contains over 1000 sources.Results. The four components of the DDRG B1834+620 have been resolved for the first time at 144 MHz. Inner lobes were found to point towards the direction of the outer lobes, unlike standard FR II sources. Polarized emission was detected at +60 rad m-2 in the northern outer lobe. The high spatial resolution allows the identification of a large number of small double-lobed radio sources; roughly 10% of all sources in the field are doubles with a separation smaller than 1′.Conclusions. The spectral fit of the four components is consistent with a scenario in which the outer lobes are still active or the jets recently switched off, while emission of the inner lobes is the result of a mix-up of new and old jet activity. From the presence of the newly extended features in the inner lobes of the DDRG, we can infer that the mechanism responsible for their formation is the bow shock that is driven by the newly launched jet. We find that the density of the small doubles exceeds the density of FR II sources with similar properties at 1.4 GHz, but this difference becomes smaller for low flux densities. Finally, we show that the significant challenges of wide-field imaging (e.g., time and frequency variation of the beam, directional dependent calibration errors) can be solved using LOFAR commissioning data, thus demonstrating the potential of the full LOFAR telescope to discover millions of powerful AGN at redshift z ~ 1.
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28.
  • Pfeffer, W. Tad, et al. (författare)
  • The Randolph Glacier Inventory : a globally complete inventory of glaciers
  • 2014
  • Ingår i: Journal of Glaciology. - 0022-1430 .- 1727-5652. ; 60:221, s. 537-552
  • Tidskriftsartikel (refereegranskat)abstract
    • The Randolph Glacier Inventory (RGI) is a globally complete collection of digital outlines of glaciers, excluding the ice sheets, developed to meet the needs of the Fifth Assessment of the Intergovernmental Panel on Climate Change for estimates of past and future mass balance. The RGI was created with limited resources in a short period. Priority was given to completeness of coverage, but a limited, uniform set of attributes is attached to each of the similar to 198 000 glaciers in its latest version, 3.2. Satellite imagery from 1999-2010 provided most of the outlines. Their total extent is estimated as 726 800 +/- 34 000 km(2). The uncertainty, about +/- 5%, is derived from careful single-glacier and basin-scale uncertainty estimates and comparisons with inventories that were not sources for the RGI. The main contributors to uncertainty are probably misinterpretation of seasonal snow cover and debris cover. These errors appear not to be normally distributed, and quantifying them reliably is an unsolved problem. Combined with digital elevation models, the RGI glacier outlines yield hypsometries that can be combined with atmospheric data or model outputs for analysis of the impacts of climatic change on glaciers. The RGI has already proved its value in the generation of significantly improved aggregate estimates of glacier mass changes and total volume, and thus actual and potential contributions to sea-level rise.
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29.
  • De Gasperin, F., et al. (författare)
  • M 87 at metre wavelengths: the LOFAR picture
  • 2012
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 547, s. article no. 56-
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. M87 is a giant elliptical galaxy located in the centre of the Virgo cluster, which harbours a supermassive black hole of mass 6.4x10(9) M-circle dot, whose activity is responsible for the extended (80 kpc) radio lobes that surround the galaxy. The energy generated by matter falling onto the central black hole is ejected and transferred to the intra-cluster medium via a relativistic jet and morphologically complex systems of buoyant bubbles, which rise towards the edges of the extended halo. Aims. To place constraints on past activity cycles of the active nucleus, images of M 87 were produced at low radio frequencies never explored before at these high spatial resolution and dynamic range. To disentangle different synchrotron models and place constraints on source magnetic field, age and energetics, we also performed a detailed spectral analysis of M 87 extended radio-halo. Methods. We present the first observations made with the new Low-Frequency Array (LOFAR) of M 87 at frequencies down to 20 MHz. Three observations were conducted, at 15-30 MHz, 30-77 MHz and 116-162 MHz. We used these observations together with archival data to produce a low-frequency spectral index map and to perform a spectral analysis in the wide frequency range 30 MHz-10 GHz. Results. We do not find any sign of new extended emissions; on the contrary the source appears well confined by the high pressure of the intra-cluster medium. A continuous injection of relativistic electrons is the model that best fits our data, and provides a scenario in which the lobes are still supplied by fresh relativistic particles from the active galactic nuclei. We suggest that the discrepancy between the low-frequency radio-spectral slope in the core and in the halo implies a strong adiabatic expansion of the plasma as soon as it leaves the core area. The extended halo has an equipartition magnetic field strength of similar or equal to 10 mu G, which increases to similar or equal to 13 mu G in the zones where the particle flows are more active. The continuous injection model for synchrotron ageing provides an age for the halo of similar or equal to 40 Myr, which in turn provides a jet kinetic power of 6-10 x 10(44) erg s(-1).
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30.
  • Fretwell, P., et al. (författare)
  • Bedmap2 : improved ice bed, surface and thickness datasets for Antarctica
  • 2013
  • Ingår i: The Cryosphere. - : Copernicus GmbH. - 1994-0416 .- 1994-0424. ; 7:1, s. 375-393
  • Tidskriftsartikel (refereegranskat)abstract
    • We present Bedmap2, a new suite of gridded products describing surface elevation, ice-thickness and the seafloor and subglacial bed elevation of the Antarctic south of 60 degrees S. We derived these products using data from a variety of sources, including many substantial surveys completed since the original Bedmap compilation (Bedmap1) in 2001. In particular, the Bedmap2 ice thickness grid is made from 25 million measurements, over two orders of magnitude more than were used in Bedmap1. In most parts of Antarctica the subglacial landscape is visible in much greater detail than was previously available and the improved data-coverage has in many areas revealed the full scale of mountain ranges, valleys, basins and troughs, only fragments of which were previously indicated in local surveys. The derived statistics for Bedmap2 show that the volume of ice contained in the Antarctic ice sheet (27 million km(3)) and its potential contribution to sea-level rise (58 m) are similar to those of Bedmap1, but the mean thickness of the ice sheet is 4.6% greater, the mean depth of the bed beneath the grounded ice sheet is 72m lower and the area of ice sheet grounded on bed below sea level is increased by 10 %. The Bedmap2 compilation highlights several areas beneath the ice sheet where the bed elevation is substantially lower than the deepest bed indicated by Bedmap1. These products, along with grids of data coverage and uncertainty, provide new opportunities for detailed modelling of the past and future evolution of the Antarctic ice sheets.
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31.
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32.
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33.
  • Bae, J. B., et al. (författare)
  • Does parity matter in women's risk of dementia? A COSMIC collaboration cohort study
  • 2020
  • Ingår i: Bmc Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Dementia shows sex difference in its epidemiology. Childbirth, a distinctive experience of women, is associated with the risk for various diseases. However, its association with the risk of dementia in women has rarely been studied. Methods We harmonized and pooled baseline data from 11 population-based cohorts from 11 countries over 3 continents, including 14,792 women aged 60 years or older. We investigated the association between parity and the risk of dementia using logistic regression models that adjusted for age, educational level, hypertension, diabetes mellitus, and cohort, with additional analyses by region and dementia subtype. Results Across all cohorts, grand multiparous (5 or more childbirths) women had a 47% greater risk of dementia than primiparous (1 childbirth) women (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.10-1.94), while nulliparous (no childbirth) women and women with 2 to 4 childbirths showed a comparable dementia risk to primiparous women. However, there were differences associated with region and dementia subtype. Compared to women with 1 to 4 childbirths, grand multiparous women showed a higher risk of dementia in Europe (OR = 2.99, 95% CI = 1.38-6.47) and Latin America (OR = 1.49, 95% CI = 1.04-2.12), while nulliparous women showed a higher dementia risk in Asia (OR = 2.15, 95% CI = 1.33-3.47). Grand multiparity was associated with 6.9-fold higher risk of vascular dementia in Europe (OR = 6.86, 95% CI = 1.81-26.08), whereas nulliparity was associated with a higher risk of Alzheimer disease (OR = 1.91, 95% CI 1.07-3.39) and non-Alzheimer non-vascular dementia (OR = 3.47, 95% CI = 1.44-8.35) in Asia. Conclusion Parity is associated with women's risk of dementia, though this is not uniform across regions and dementia subtypes.
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34.
  • Barbaro, E., et al. (författare)
  • Free amino acids in the Arctic snow and ice core samples: Potential markers for paleoclimatic studies
  • 2017
  • Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 607, s. 454-462
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of oceanic primary production on climate variability has long been debated. Defining changes in past oceanic primary production can help understanding of the important role that marine algae have in climate variability. In ice core research methanesulfonic acid is the chemical marker commonly used for assessing changes in past primary production. However, other organic compounds such as amino acids, can be produced and emitted into the atmosphere during a phytoplankton bloom. These species can be transported and deposited onto the ice cap in polar regions. Here we investigate the correlation between the concentration of chlorophyll-a, marker of marine primary production, and amino acids present in an ice core. For the first time, free L- and D-amino acids in Arctic snow and firn samples were determined by a sensitive and selective analytical method based on liquid chromatography coupled with tandem mass spectrometry. The new method for the determination of free amino acids concentrations was applied to firn core samples collected on April 2015 from the summit of the Holtedahlfonna glacier, Svalbard (N 79'08.424, E 13'23.639, 1120 m a.s.l.). The main results of this work are summarized as follows: (1) glycine, alanine and proline, were detected and quantified in the firn core samples; (2) their concentration profiles, compared with that of the stable isotope delta O-18 ratio, show a seasonal cycling with the highest concentrations during the spring and summer time; (3) back-trajectories and Greenland Sea chlorophyll-a concentrations obtained by satellite measurements were compared with the amino acids profile obtained from ice core samples, this provided further insights into the present results. This study suggests that the amino acid concentrations in the ice samples collected from the Holtedahlfonna glaciers could reflect changes in oceanic phytoplankton abundance.
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35.
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36.
  • Kostka, Kristin, et al. (författare)
  • Unraveling COVID-19: A Large-Scale Characterization of 4.5 Million COVID-19 Cases Using CHARYBDIS.
  • 2022
  • Ingår i: Clinical epidemiology. - 1179-1349. ; 14, s. 369-384
  • Tidskriftsartikel (refereegranskat)abstract
    • Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) Characterizing Health Associated Risks and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD.We conducted a descriptive retrospective database study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11th June 2020 and are iteratively updated via GitHub. We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19, and 113,627 hospitalized with COVID-19 requiring intensive services.We aggregated over 22,000 unique characteristics describing patients with COVID-19. All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts and are readily available online. Globally, we observed similarities in the USA and Europe: more women diagnosed than men but more men hospitalized than women, most diagnosed cases between 25 and 60 years of age versus most hospitalized cases between 60 and 80 years of age. South Korea differed with more women than men hospitalized. Common comorbidities included type 2 diabetes, hypertension, chronic kidney disease and heart disease. Common presenting symptoms were dyspnea, cough and fever. Symptom data availability was more common in hospitalized cohorts than diagnosed.We constructed a global, multi-centre view to describe trends in COVID-19 progression, management and evolution over time. By characterising baseline variability in patients and geography, our work provides critical context that may otherwise be misconstrued as data quality issues. This is important as we perform studies on adverse events of special interest in COVID-19 vaccine surveillance.
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37.
  • Lo, J. W., et al. (författare)
  • Profile of and risk factors for poststroke cognitive impairment in diverse ethnoregional groups
  • 2019
  • Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 93:24
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To address the variability in prevalence estimates and inconsistencies in potential risk factors for poststroke cognitive impairment (PSCI) using a standardized approach and individual participant data (IPD) from international cohorts in the Stroke and Cognition Consortium (STROKOG) consortium. Methods We harmonized data from 13 studies based in 8 countries. Neuropsychological test scores 2 to 6 months after stroke or TIA and appropriate normative data were used to calculate standardized cognitive domain scores. Domain-specific impairment was based on percentile cutoffs from normative groups, and associations between domain scores and risk factors were examined with 1-stage IPD meta-analysis. Results In a combined sample of 3,146 participants admitted to hospital for stroke (97%) or TIA (3%), 44% were impaired in global cognition and 30% to 35% were impaired in individual domains 2 to 6 months after the index event. Diabetes mellitus and a history of stroke were strongly associated with poorer cognitive function after covariate adjustments; hypertension, smoking, and atrial fibrillation had weaker domain-specific associations. While there were no significant differences in domain impairment among ethnoracial groups, some interethnic differences were found in the effects of risk factors on cognition. Conclusions This study confirms the high prevalence of PSCI in diverse populations, highlights common risk factors, in particular diabetes mellitus, and points to ethnoracial differences that warrant attention in the development of prevention strategies.
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38.
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39.
  • Pati, Sarah G., et al. (författare)
  • Substrate and Enzyme Specificity of the Kinetic Isotope Effects Associated with the Dioxygenation of Nitroaromatic Contaminants
  • 2016
  • Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 50:13, s. 6708-6716
  • Tidskriftsartikel (refereegranskat)abstract
    • Compound-specific isotope analysis (CSIA) is a promising approach for tracking biotransformation of organic pollutants, but isotope fractionation associated with aromatic oxygenations is only poorly understood. We investigated the dioxygenation of a series of nitroaromatic compounds to the corresponding catechols by two enzymes, namely, nitrobenzene and 2-nitrotoluene dioxygenase (NBDO and 2NTDO) to elucidate the enzyme- and substrate-specificity of C and H isotope fractionation. While the apparent C-13- and H-2-kinetic isotope effects of nitrobenzene, nitrotoluene isomers, 2,6-dinitrotoluene, and naphthalene dioxygenation by NBDO varied considerably, the correlation of C and H isotope fractionation revealed a common mechanism for nitrobenzene and nitrotoluenes. Similar observations were made for the dioxygenation of these substrates by 2NTDO. Evaluation of reaction kinetics, isotope effects, and commitment-to-catalysis based on experiment and theory showed that rates of dioxygenation are determined by the enzymatic O-2 activation and aromatic C oxygenation. The contribution of enzymatic O-2 activation to the reaction rate varies for different nitroaromatic substrates of NBDO and 2NTDO. Because aromatic dioxygenation by nonheme iron dioxygenases is frequently the initial step of biodegradation, O-2 activation kinetics may also have been responsible for the minor isotope fractionation reported for the oxygenation of other aromatic contaminants.
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40.
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41.
  • Vega, Carmen P., et al. (författare)
  • Surface mass balance and water stable isotopes derived from firn cores on three ice rises, Fimbul Ice Shelf, Antarctica
  • 2016
  • Ingår i: The Cryosphere Discussions. - : Copernicus GmbH. - 1994-0432 .- 1994-0440 .- 1994-0424. ; 10:6, s. 2763-2777
  • Tidskriftsartikel (refereegranskat)abstract
    • Three shallow firn cores were retrieved in the austral summers of 2011/12 and 2013/14 on the ice rises Kupol Ciolkovskogo (KC), Kupol Moskovskij (KM), and Blaskimen Island (BI), all part of Fimbul Ice Shelf (FIS) in western Dronning Maud Land (DML), Antarctica. The cores were dated back to 1958 (KC), 1995 (KM), and 1996 (BI) by annual layer counting using high-resolution oxygen isotope (delta O-18) data, and by identifying volcanic horizons using non-sea-salt sulfate (nssSO(4)(2-)) data. The water stable isotope records show that the atmospheric signature of the annual snow accumulation cycle is well preserved in the firn column, especially at KM and BI. We are able to determine the annual surface mass balance (SMB), as well as the mean SMB values between identified volcanic horizons. Average SMB at the KM and BI sites (0.68 and 0.70 mw.e.yr(-1)) was higher than at the KC site (0.24 mw.e.yr(-1)), and there was greater temporal variability as well. Trends in the SMB and delta O-18 records from the KC core over the period of 1958-2012 agree well with other previously investigated cores in the area, thus the KC site could be considered the most representative of the climate of the region. Cores from KM and BI appear to be more affected by local meteorological conditions and surface topography. Our results suggest that the ice rises are suitable sites for the retrieval of longer firn and ice cores, but that BI has the best preserved seasonal cycles of the three records and is thus the most optimal site for high-resolution studies of temporal variability of the climate signal. Deuterium ex-cess data suggest a possible effect of seasonal moisture transport changes on the annual isotopic signal. In agreement with previous studies, large-scale atmospheric circulation patterns most likely provide the dominant influence on water stable isotope ratios preserved at the core sites.
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42.
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43.
  • Barg, Sebastian, et al. (författare)
  • The stimulatory action of tolbutamide on Ca2+-dependent exocytosis in pancreatic beta cells is mediated by a 65-kDa mdr-like P-glycoprotein
  • 1999
  • Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 96:10, s. 5539-5544
  • Tidskriftsartikel (refereegranskat)abstract
    • Intracellular application of the sulfonylurea tolbutamide during whole-cell patch-clamp recordings stimulated exocytosis >5-fold when applied at a cytoplasmic Ca2+ concentration of 0.17 microM. This effect was not detectable in the complete absence of cytoplasmic Ca2+ and when exocytosis was elicited by guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS). The stimulatory action could be antagonized by the sulfonamide diazoxide, by the Cl--channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), by intracellular application of the antibody JSB1 [originally raised against a 170-kDa multidrug resistance (mdr) protein], and by tamoxifen (an inhibitor of the mdr- and volume-regulated Cl- channels). Immunocytochemistry and Western blot analyses revealed that JSB1 recognizes a 65-kDa protein in the secretory granules. This protein exhibited no detectable binding of sulfonylureas and is distinct from the 140-kDa sulfonylurea high-affinity sulfonylurea receptors also present in the granules. We conclude that (i) tolbutamide stimulates Ca2+-dependent exocytosis secondary to its binding to a 140-kDa high-affinity sulfonylurea receptor in the secretory granules; and (ii) a granular 65-kDa mdr-like protein mediates the action. The processes thus initiated culminate in the activation of a granular Cl- conductance. We speculate that the activation of granular Cl- fluxes promotes exocytosis (possibly by providing the energy required for membrane fusion) by inducing water uptake and an increased intragranular hydrostatic pressure.
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44.
  • Barker, CJ, et al. (författare)
  • XPR1 Mediates the Pancreatic β-Cell Phosphate Flush
  • 2021
  • Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 70:1, s. 111-118
  • Tidskriftsartikel (refereegranskat)abstract
    • Glucose-stimulated insulin secretion is the hallmark of the pancreatic β-cell, a critical player in the regulation of blood glucose concentration. In 1974, the remarkable observation was made that an efflux of intracellular inorganic phosphate (Pi) accompanied the events of stimulated insulin secretion. The mechanism behind this “phosphate flush,” its association with insulin secretion, and its regulation have since then remained a mystery. We recapitulated the phosphate flush in the MIN6m9 β-cell line and pseudoislets. We demonstrated that knockdown of XPR1, a phosphate transporter present in MIN6m9 cells and pancreatic islets, prevented this flush. Concomitantly, XPR1 silencing led to intracellular Pi accumulation and a potential impact on Ca2+ signaling. XPR1 knockdown slightly blunted first-phase glucose-stimulated insulin secretion in MIN6m9 cells, but had no significant impact on pseudoislet secretion. In keeping with other cell types, basal Pi efflux was stimulated by inositol pyrophosphates, and basal intracellular Pi accumulated following knockdown of inositol hexakisphosphate kinases. However, the glucose-driven phosphate flush occurred despite inositol pyrophosphate depletion. Finally, while it is unlikely that XPR1 directly affects exocytosis, it may protect Ca2+ signaling. Thus, we have revealed XPR1 as the missing mediator of the phosphate flush, shedding light on a 45-year-old mystery.
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45.
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46.
  • Bolton-Maggs, P. H. B., et al. (författare)
  • Difficulties and pitfalls in the laboratory diagnosis of bleeding disorders
  • 2012
  • Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 18, s. 66-72
  • Tidskriftsartikel (refereegranskat)abstract
    • . von Willebrand disease (VWD) is the most common inherited bleeding disorder, but variable severity and several classification types mean that diagnosis is often not straightforward. In many countries, the assays are not readily available and/or are not well standardized. The latest methods and the basis of VWD are discussed here, together with information from the international quality assessment programme (IEQAS). Factor XIII deficiency is a rare, but important bleeding disorder, which may be missed or diagnosed late. A discussion and update on this diagnosis is considered in the final section of our review.
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47.
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48.
  • Caruso, Tancredi, et al. (författare)
  • Assessing soil ecosystem processes – biodiversity relationships in a nature reserve in Central Europe
  • 2018
  • Ingår i: Plant and Soil. - : Springer Science and Business Media LLC. - 0032-079X .- 1573-5036. ; 424:1-2, s. 491-501
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aims: Plant diversity – ecosystem processes relationships are essential to our understanding of ecosystem functioning. We aimed at disentangling the nature of such relationships in a mesotrophic grassland that was highly heterogeneous with regards to nutrient availability. Methods: Rather than targeting primary productivity, like most existing reports do, we focused our study on belowground ecosystem processes. We tested three, largely mutually exclusive, hypotheses of ecosystem processes relationships: the redundancy hypothesis, the insurance hypothesis and the centrifugal model hypothesis. We sampled the grassland twice within a single plant growing season in a spatially explicit way and assayed the soil for nitrification, urease activity, relative bacterial activity and a microbial community profile based on respiration while we simultaneously assessed plant diversity. Results: Results supported the centrifugal model. We justify the lack of support for the other two hypotheses on the basis of having conducted an observational study in an environmentally heterogeneous site. Conclusions: The centrifugal model hypothesis appears to be a very good predictive model for explaining diversity in observational, heterogeneous studies. The specific study represents one of the few observational studies that consider measures of ecosystem functioning other than primary productivity.
  •  
49.
  • Cervin, Jakob, et al. (författare)
  • GM1 ganglioside-independent intoxication by Cholera toxin
  • 2018
  • Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 14:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Cholera toxin (CT) enters and intoxicates host cells after binding cell surface receptors via its B subunit (CTB). We have recently shown that in addition to the previously described binding partner ganglioside GM1, CTB binds to fucosylated proteins. Using flow cytometric analysis of primary human jejunal epithelial cells and granulocytes, we now show that CTB binding correlates with expression of the fucosylated Lewis X (LeX) glycan. This binding is competitively blocked by fucosylated oligosaccharides and fucose-binding lectins. CTB binds the LeX glycan in vitro when this moiety is linked to proteins but not to ceramides, and this binding can be blocked by mAb to LeX. Inhibition of glycosphingolipid synthesis or sialylation in GM1-deficient C6 rat glioma cells results in sensitization to CT-mediated intoxication. Finally, CT gavage produces an intact diarrheal response in knockout mice lacking GM1 even after additional reduction of glycosphingolipids. Hence our results show that CT can induce toxicity in the absence of GM1 and support a role for host glycoproteins in CT intoxication. These findings open up new avenues for therapies to block CT action and for design of detoxified enterotoxin-based adjuvants.
  •  
50.
  • Chaitanya, Lakshmi, et al. (författare)
  • Collaborative EDNAP exercise on the IrisPlex system for DNA based prediction of human eye colour
  • 2014
  • Ingår i: Forensic Science International. - : Elsevier. - 1872-4973 .- 1878-0326. ; 11, s. 241-251
  • Tidskriftsartikel (refereegranskat)abstract
    • The IrisPlex system is a DNA-based test system for the prediction of human eye colour from biological samples and consists of a single forensically validated multiplex genotyping assay together with a statistical prediction model that is based on genotypes and phenotypes from thousands of individuals. IrisPlex predicts blue and brown human eye colour with, on average, >94% precision accuracy using six of the currently most eye colour informative single nucleotide polymorphisms (HERC2 rs12913832, OCA2 rs1800407, SLC24A4 rs12896399, SLC45A2 (MATP) rs16891982, TYR rs1393350, and IRF4 rs12203592) according to a previous study, while the accuracy in predicting non-blue and non-brown eye colours is considerably lower. In an effort to vigorously assess the IrisPlex system at the international level, testing was performed by 21 laboratories in the context of a collaborative exercise divided into three tasks and organised by the European DNA Profiling (EDNAP) Group of the International Society of Forensic Genetics (ISFG). Task 1 involved the assessment of 10 blood and saliva samples provided on FTA cards by the organising laboratory together with eye colour phenotypes; 99.4% of the genotypes were correctly reported and 99% of the eye colour phenotypes were correctly predicted. Task 2 involved the assessment of 5 DNA samples extracted by the host laboratory from simulated casework samples, artificially degraded, and provided to the participants in varying DNA concentrations. For this task, 98.7% of the genotypes were correctly determined and 96.2% of eye colour phenotypes were correctly inferred. For Tasks 1 and 2 together, 99.2% (1875) of the 1890 genotypes were correctly generated and of the 15 (0.8%) incorrect genotype calls, only 2 (0.1%) resulted in incorrect eye colour phenotypes. The voluntary Task 3 involved participants choosing their own test subjects for IrisPlex genotyping and eye colour phenotype inference, while eye photographs were provided to the organising laboratory and judged; 96% of the eye colour phenotypes were inferred correctly across 100 samples and 19 laboratories. The high success rates in genotyping and eye colour phenotyping clearly demonstrate the reproducibility and the robustness of the IrisPlex assay as well as the accuracy of the IrisPlex model to predict blue and brown eye colour from DNA. Additionally, this study demonstrates the ease with which the IrisPlex system is implementable and applicable across forensic laboratories around the world with varying pre-existing experiences.
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