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1.
  • Wang, H. D., et al. (författare)
  • Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970-2016: a systematic analysis for the Global Burden of Disease Study 2016
  • 2017
  • Ingår i: Lancet. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1084-1150
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016. Methods We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15-60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0.5% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Sociodemographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone. Findings Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5-24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates-a measure of relative inequality-increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86.9 years (95% UI 86.7-87.2), and for men in Singapore, at 81.3 years (78.8-83.7) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, and the gap between male and female life expectancy increased with progression to higher levels of SDI. Some countries with exceptional health performance in 1990 in terms of the difference in observed to expected life expectancy at birth had slower progress on the same measure in 2016. Interpretation Globally, mortality rates have decreased across all age groups over the past five decades, with the largest improvements occurring among children younger than 5 years. However, at the national level, considerable heterogeneity remains in terms of both level and rate of changes in age-specific mortality; increases in mortality for certain age groups occurred in some locations. We found evidence that the absolute gap between countries in age-specific death rates has declined, although the relative gap for some age-sex groups increased. Countries that now lead in terms of having higher observed life expectancy than that expected on the basis of development alone, or locations that have either increased this advantage or rapidly decreased the deficit from expected levels, could provide insight into the means to accelerate progress in nations where progress has stalled. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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2.
  • Hay, S. I., et al. (författare)
  • Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016 : A systematic analysis for the Global Burden of Disease Study 2016
  • 2017
  • Ingår i: The Lancet. - : Lancet Publishing Group. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1260-1344
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). Methods: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE difered from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. Findings: The highest globally observed HALE at birth for both women and men was in Singapore, at 75·2 years (95% uncertainty interval 71·9-78·6) for females and 72·0 years (68·8-75·1) for males. The lowest for females was in the Central African Republic (45·6 years [42·0-49·5]) and for males was in Lesotho (41·5 years [39·0-44·0]). From 1990 to 2016, global HALE increased by an average of 6·24 years (5·97-6·48) for both sexes combined. Global HALE increased by 6·04 years (5·74-6·27) for males and 6·49 years (6·08-6·77) for females, whereas HALE at age 65 years increased by 1·78 years (1·61-1·93) for males and 1·96 years (1·69-2·13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2·3% [-5·9 to 0·9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs ofset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the fve lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16·1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. Interpretation: At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs ofset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention eforts, and development assistance for health, including fnancial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support. © The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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  • Kinyoki, DK, et al. (författare)
  • Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017
  • 2020
  • Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 26:5, s. 750-759
  • Tidskriftsartikel (refereegranskat)abstract
    • A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic.
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5.
  • 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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6.
  • Reifarth, R., et al. (författare)
  • Nuclear astrophysics with radioactive ions at FAIR
  • 2016
  • Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 665:1
  • Konferensbidrag (refereegranskat)abstract
    • The nucleosynthesis of elements beyond iron is dominated by neutron captures in the s and r processes. However, 32 stable, proton-rich isotopes cannot be formed during those processes, because they are shielded from the s-process flow and r-process beta-decay chains. These nuclei are attributed to the p and rp process. For all those processes, current research in nuclear astrophysics addresses the need for more precise reaction data involving radioactive isotopes. Depending on the particular reaction, direct or inverse kinematics, forward or time-reversed direction are investigated to determine or at least to constrain the desired reaction cross sections. The Facility for Antiproton and Ion Research (FAIR) will offer unique, unprecedented opportunities to investigate many of the important reactions. The high yield of radioactive isotopes, even far away from the valley of stability, allows the investigation of isotopes involved in processes as exotic as the r or rp processes.
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7.
  • Feroci, M., et al. (författare)
  • The Large Observatory for X-ray Timing (LOFT)
  • 2012
  • Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 34:2, s. 415-444
  • Tidskriftsartikel (refereegranskat)abstract
    • High-time-resolution X-ray observations of compact objects provide direct access to strong-field gravity, to the equation of state of ultradense matter and to black hole masses and spins. A 10 m(2)-class instrument in combination with good spectral resolution is required to exploit the relevant diagnostics and answer two of the fundamental questions of the European Space Agency (ESA) Cosmic Vision Theme "Matter under extreme conditions", namely: does matter orbiting close to the event horizon follow the predictions of general relativity? What is the equation of state of matter in neutron stars? The Large Observatory For X-ray Timing (LOFT), selected by ESA as one of the four Cosmic Vision M3 candidate missions to undergo an assessment phase, will revolutionise the study of collapsed objects in our galaxy and of the brightest supermassive black holes in active galactic nuclei. Thanks to an innovative design and the development of large-area monolithic silicon drift detectors, the Large Area Detector (LAD) on board LOFT will achieve an effective area of similar to 12 m(2) (more than an order of magnitude larger than any spaceborne predecessor) in the 2-30 keV range (up to 50 keV in expanded mode), yet still fits a conventional platform and small/medium-class launcher. With this large area and a spectral resolution of < 260 eV, LOFT will yield unprecedented information on strongly curved spacetimes and matter under extreme conditions of pressure and magnetic field strength.
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8.
  • Murray, Christopher J. L., et al. (författare)
  • Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
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10.
  • van Rheenen, W, et al. (författare)
  • Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
  • 2021
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 53:12, s. 1636-
  • Tidskriftsartikel (refereegranskat)abstract
    • Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
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11.
  • Adlarson, Patrik, et al. (författare)
  • Exclusive measurement of the eta -> pi(+) pi(-) gamma decay
  • 2012
  • Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 707:2, s. 243-249
  • Tidskriftsartikel (refereegranskat)abstract
    • An exclusive measurement of the decay eta -> pi(+) pi(-) gamma has been performed at the WASA facility at COSY. The eta mesons were produced in the fusion reaction pd -> He-3 X at a proton beam momentum of 1.7 GeV/c. Efficiency corrected differential distributions have been extracted based on 13 960 +/- 140 events after background subtraction. The measured pion angular distribution is consistent with a relative p-wave of the two-pion system, whereas the measured photon energy spectrum was found at variance with the simplest gauge invariant matrix element of eta -> pi(+) pi(-) gamma. A parameterization of the data can be achieved by the additional inclusion of the empirical pion vector form factor multiplied by a first-order polynomial in the squared invariant mass of the pi(+) pi(-) system.
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  • Diaz Fernandez, Paloma, 1983, et al. (författare)
  • Quasifree (p, pN) scattering of light neutron-rich nuclei near N=14
  • 2018
  • Ingår i: Physical Review C. - 2469-9985 .- 2469-9993. ; 97:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: For many years, quasifree scattering reactions in direct kinematics have been extensively used to study the structure of stable nuclei, demonstrating the potential of this approach. The (RB)-B-3 collaboration has performed a pilot experiment to study quasifree scattering reactions in inverse kinematics for a stable C-12 beam. The results from that experiment constitute the first quasifree scattering results in inverse and complete kinematics. This technique has lately been extended to exotic beams to investigate the evolution of shell structure, which has attracted much interest due to changes in shell structure if the number of protons or neutrons is varied. Purpose: In this work we investigate for the first time the quasifree scattering reactions (p, pn) and (p, 2p) simultaneously for the same projectile in inverse and complete kinematics for radioactive beams with the aim to study the evolution of single-particle properties from N = 14 to N = 15. Method: The structure of the projectiles O-23, O-22, and N-21 has been studied simultaneously via (p, pn) and (p, 2p) quasifree knockout reactions in complete inverse kinematics, allowing the investigation of proton and neutron structure at the same time. The experimental data were collected at the (RB)-B-3-LAND setup at GSI at beam energies of around 400 MeV/u. Two key observables have been studied to shed light on the structure of those nuclei: the inclusive cross sections and the corresponding momentum distributions. Conclusions: The knockout reactions (p, pn) and (p, 2p) with radioactive beams in inverse kinematics have provided important and complementary information for the study of shell evolution and structure. For the (p, pn) channels, indications of a change in the structure of these nuclei moving from N = 14 to N = 15 have been observed, i.e., from the 0d(5/2) shell to the 1s(1/2). This supports previous observations of a subshell closure at N = 14 for neutron-rich oxygen isotopes and its weakening for the nitrogen isotopes.
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  • Langefeld, Carl D., et al. (författare)
  • Transancestral mapping and genetic load in systemic lupus erythematosus
  • 2017
  • Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
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14.
  • Ponnath, L., et al. (författare)
  • Measurement of nuclear interaction cross sections towards neutron-skin thickness determination
  • 2024
  • Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 855
  • Tidskriftsartikel (refereegranskat)abstract
    • The accuracy of reaction theories used to extract properties of exotic nuclei from scattering experiments is often unknown or not quantified, but of utmost importance when, e.g., constraining the equation of state of asymmetric nuclear matter from observables as the neutron-skin thickness. In order to test the Glauber multiple-scattering model, the total interaction cross section of [Formula presented] on carbon targets was measured at initial beam energies of 400, 550, 650, 800, and 1000 MeV/nucleon. The measurements were performed during the first experiment of the newly constructed R3B (Reaction with Relativistic Radioactive Beams) experiment after the start of FAIR Phase-0 at the GSI/FAIR facility with beam energies of 400, 550, 650, 800, and 1000 MeV/nucleon. The combination of the large-acceptance dipole magnet GLAD and a newly designed and highly efficient Time-of-Flight detector enabled a precise transmission measurement with several target thicknesses for each initial beam energy with an experimental uncertainty of ±0.4%. A comparison with the Glauber model revealed a discrepancy of around 3.1% at higher beam energies, which will serve as a crucial baseline for the model-dependent uncertainty in future fragmentation experiments.
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15.
  • Vandebrouck, M., et al. (författare)
  • Effective proton-neutron interaction near the drip line from unbound states in F-25,F-26
  • 2017
  • Ingår i: Physical Review C. - 2469-9985 .- 2469-9993. ; 96:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Odd-odd nuclei, around doubly closed shells, have been extensively used to study proton-neutron interactions. However, the evolution of these interactions as a function of the binding energy, ultimately when nuclei become unbound, is poorly known. The F-26 nucleus, composed of a deeply bound pi 0d(5/2) proton and an unbound v0d(3/2) neutron on top of an O-24 core, is particularly adapted for this purpose. The coupling of this proton and neutron results in a J(pi) = 1(1)(+) - 4(1)(+) multiplet, whose energies must be determined to study the influence of the proximity of the continuum on the corresponding proton-neutron interaction. The J(pi) = 1(1)(+), 2(1)(+), 4(1)(+) bound states have been determined, and only a clear identification of the J(pi) = 3(1)(+) is missing. Purpose: We wish to complete the study of the J(pi) = 1(1)(+) - 4(1)(+) multiplet in F-26, by studying the energy and width of the J(pi) = 3(1)(+) unbound state. The method was first validated by the study of unbound states in F-25, for which resonances were already observed in a previous experiment. Method: Radioactive beams of Ne-26 and Ne-27, produced at about 440AMeV by the fragment separator at the GSI facility were used to populate unbound states in F-25 and F-26 via one-proton knockout reactions on a CH2 target, located at the object focal point of the (RB)-B-3/LAND setup. The detection of emitted. rays and neutrons, added to the reconstruction of the momentum vector of the A - 1 nuclei, allowed the determination of the energy of three unbound states in F-25 and two in F-26. Results: Based on its width and decay properties, the first unbound state in F-25, at the relative energy of 49(9) keV, is proposed to be a J(pi) = 1/ 2(-) arising from a p1/2 proton- hole state. In F-26, the first resonance at 323(33) keV is proposed to be the J(pi) = 3(1)(+) member of the J(pi) = 1(1)(+) - 4(1)(+) multiplet. Energies of observed states in F-25,F-26 have been compared to calculations using the independent-particle shell model, a phenomenological shell model, and the ab initio valence-space in-medium similarity renormalization group method. Conclusions: The deduced effective proton- neutron interaction is weakened by about 30-40% in comparison to the models, pointing to the need for implementing the role of the continuum in theoretical descriptions or to a wrong determination of the atomic mass of F-26.
  •  
16.
  • Heine, M., et al. (författare)
  • Determination of the neutron-capture rate of C-17 for r-process nucleosynthesis
  • 2017
  • Ingår i: Physical Review C. - 2469-9985 .- 2469-9993. ; 95:1, s. Article no 014613 -
  • Tidskriftsartikel (refereegranskat)abstract
    • With the (RB)-B-3-LAND setup at GSI we have measured exclusive relative-energy spectra of the Coulomb dissociation of C-18 at a projectile energy around 425A MeV on a lead target, which are needed to determine the radiative neutron-capture cross sections of C-17 into the ground state of C-18. Those data have been used to constrain theoretical calculations for transitions populating excited states in C-18. This allowed to derive the astrophysical cross section sigma(n gamma)*. accounting for the thermal population of C-17 target states in astrophysical scenarios. The experimentally verified capture rate is significantly lower than those of previously obtained Hauser-Feshbach estimations at temperatures T-9
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17.
  • Boillos, J. M., et al. (författare)
  • Isotopic cross sections of fragmentation residues produced by light projectiles on carbon near
  • 2022
  • Ingår i: Physical Review C. - 2469-9993 .- 2469-9985. ; 105:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We measured 135 cross sections of residual nuclei produced in fragmentation reactions of C12, N14, and O13−16,20,22 projectiles impinging on a carbon target at kinetic energies of near 400A MeV, most of them for the first time, with the RB3/LAND setup at the GSI facility in Darmstadt (Germany). The use of this state-of-the-art experimental setup in combination with the inverse kinematics technique gave the full identification in atomic and mass numbers of fragmentation residues with a high precision. The cross sections of these residues were determined with uncertainties below 20% for most of the cases. These data are compared to other previous measurements with stable isotopes and are also used to benchmark different model calculations.
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18.
  • Graña-González, A., et al. (författare)
  • Quasi-free (p,2p) reactions in inverse kinematics for studying the fission yield dependence on temperature
  • 2023
  • Ingår i: FAIR next generation scientists - 7th Edition Workshop : FAIRness2022 - FAIRness2022. - 1824-8039. ; 419
  • Konferensbidrag (refereegranskat)abstract
    • Despite the recent experimental and theoretical progress in the investigation of the nuclear fission process, a complete description still represents a challenge in nuclear physics because it is a very complex dynamical process, whose description involves the coupling between intrinsic and collective degrees of freedom, as well as different quantum-mechanical phenomena. To improve on the existing data on nuclear fission, we produce fission reactions of heavy nuclei in inverse kinematics by using quasi-free (p,2p) scattering, which induce fission through particle-hole excitations that can range from few to ten's of MeV. The measurement of the four-momenta of the two outgoing protons allows to reconstruct the excitation energy of the fissioning compound nucleus and therefore to study the evolution of the fission yields with temperature. The realization of this kind of experiment requires a complex experimental setup, providing full isotopic identification of both fission fragments and an accurate measurement of the momenta of the two outgoing protons. This was realized recently at the GSI/FAIR facility and here some preliminary results are presented.
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19.
  •  
20.
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21.
  • Ramilowski, JA, et al. (författare)
  • Functional annotation of human long noncoding RNAs via molecular phenotyping
  • 2020
  • Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 30:7, s. 1060-1072
  • Tidskriftsartikel (refereegranskat)abstract
    • Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-to-date lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.
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22.
  • Röder, M., et al. (författare)
  • Coulomb dissociation of 20,21 N
  • 2016
  • Ingår i: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993 .- 0556-2813. ; 93:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Neutron-rich light nuclei and their reactions play an important role in the creation of chemical elements. Here, data from a Coulomb dissociation experiment on N20,21 are reported. Relativistic N20,21 ions impinged on a lead target and the Coulomb dissociation cross section was determined in a kinematically complete experiment. Using the detailed balance theorem, the N19(n,γ)N20 and N20(n,γ)N21 excitation functions and thermonuclear reaction rates have been determined. The N19(n,γ)N20 rate is up to a factor of 5 higher at T
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23.
  • Thies, Ronja, 1987, et al. (författare)
  • Systematic investigation of projectile fragmentation using beams of unstable B and C isotopes
  • 2016
  • Ingår i: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993 .- 0556-2813. ; 93:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Models describing nuclear fragmentation and fragmentation fission deliver important input for planning nuclear physics experiments and future radioactive ion beam facilities. These models are usually benchmarked against data from stable beam experiments. In the future, two-step fragmentation reactions with exotic nuclei as stepping stones are a promising tool for reaching the most neutron-rich nuclei, creating a need for models to describe also these reactions. Purpose: We want to extend the presently available data on fragmentation reactions towards the light exotic region on the nuclear chart. Furthermore, we want to improve the understanding of projectile fragmentation especially for unstable isotopes. Method: We have measured projectile fragments from C10,12-18 and B10-15 isotopes colliding with a carbon target. These measurements were all performed within one experiment, which gives rise to a very consistent data set. We compare our data to model calculations. Results: One-proton removal cross sections with different final neutron numbers (1pxn) for relativistic C10,12-18 and B10-15 isotopes impinging on a carbon target. Comparing model calculations to the data, we find that the epax code is not able to describe the data satisfactorily. Using abrabla07 on the other hand, we find that the average excitation energy per abraded nucleon needs to be decreased from 27 MeV to 8.1 MeV. With that decrease abrabla07 describes the data surprisingly well. Conclusions: Extending the available data towards light unstable nuclei with a consistent set of new data has allowed a systematic investigation of the role of the excitation energy induced in projectile fragmentation. Most striking is the apparent mass dependence of the average excitation energy per abraded nucleon. Nevertheless, this parameter, which has been related to final-state interactions, requires further study.
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24.
  • Atar, L., et al. (författare)
  • Quasifree (p, 2p) Reactions on Oxygen Isotopes: Observation of Isospin Independence of the Reduced Single-Particle Strength
  • 2018
  • Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 120:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Quasifree one-proton knockout reactions have been employed in inverse kinematics for a systematic study of the structure of stable and exotic oxygen isotopes at the R3B/LAND setup with incident beam energies in the range of 300-450 MeV/u. The oxygen isotopic chain offers a large variation of separation energies that allows for a quantitative understanding of single-particle strength with changing isospin asymmetry. Quasifree knockout reactions provide a complementary approach to intermediate-energy one-nucleon removal reactions. Inclusive cross sections for quasifree knockout reactions of the type OA(p,2p)NA-1 have been determined and compared to calculations based on the eikonal reaction theory. The reduction factors for the single-particle strength with respect to the independent-particle model were obtained and compared to state-of-the-art ab initio predictions. The results do not show any significant dependence on proton-neutron asymmetry.
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25.
  • Heil, M., et al. (författare)
  • A new Time-of-flight detector for the R 3 B setup
  • 2022
  • Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-601X .- 1434-6001. ; 58:12
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the design, prototype developments and test results of the new time-of-flight detector (ToFD) which is part of the R3B experimental setup at GSI and FAIR, Darmstadt, Germany. The ToFD detector is able to detect heavy-ion residues of all charges at relativistic energies with a relative energy precision σΔE/ ΔE of up to 1% and a time precision of up to 14 ps (sigma). Together with an elaborate particle-tracking system, the full identification of relativistic ions from hydrogen up to uranium in mass and nuclear charge is possible.
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26.
  • Lihtar, I., et al. (författare)
  • RELATIVISTIC COULOMB EXCITATION OF 124 Sn
  • 2024
  • Ingår i: Acta Physica Polonica B, Proceedings Supplement. - 1899-2358. ; 17:3
  • Tidskriftsartikel (refereegranskat)abstract
    • The Coulomb excitation of 124, 128, 130, 132, 134Sn isotopes in the electric field of a Pb target have been studied using the R3B setup as a part of the FAIR Phase-0 program. The experiment was motivated by the possibility of using the nuclear dipole response to infer valuable information on the slope of the symmetry energy of the nuclear equation of state. Measurements were performed in inverse kinematics at relativistic energies of 750 MeV/u and 904 MeV/u. The analysis method and preliminary results for the decay channel with a single outgoing neutron for 124Sn are reported.
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27.
  • Menkveld, Albert J., et al. (författare)
  • Nonstandard Errors
  • 2024
  • Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
  • Tidskriftsartikel (refereegranskat)abstract
    • In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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28.
  • Revel, A., et al. (författare)
  • Strong Neutron Pairing in core+4n Nuclei
  • 2018
  • Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 120:15
  • Tidskriftsartikel (refereegranskat)abstract
    • The emission of neutron pairs from the neutron-rich N=12 isotones C18 and O20 has been studied by high-energy nucleon knockout from N19 and O21 secondary beams, populating unbound states of the two isotones up to 15 MeV above their two-neutron emission thresholds. The analysis of triple fragment-n-n correlations shows that the decay N19(-1p)C18∗→C16+n+n is clearly dominated by direct pair emission. The two-neutron correlation strength, the largest ever observed, suggests the predominance of a C14 core surrounded by four valence neutrons arranged in strongly correlated pairs. On the other hand, a significant competition of a sequential branch is found in the decay O21(-1n)O20∗→O18+n+n, attributed to its formation through the knockout of a deeply bound neutron that breaks the O16 core and reduces the number of pairs.
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29.
  • Ribeiro, G., et al. (författare)
  • Structure of Be-13 studied in proton knockout from B-14
  • 2018
  • Ingår i: Physical Review C. - 2469-9985 .- 2469-9993. ; 98:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The neutron-unbound isotope Be-13 has been studied in several experiments using different reactions, different projectile energies, and different experimental setups. There is, however, no real consensus in the interpretation of the data, in particular concerning the structure of the low-lying excited states. Gathering new experimental information, which may reveal the Be-13 structure, is a challenge, particularly in light of its bridging role between Be-12, where the N = 8 neutron shell breaks down, and the Borromean halo nucleus Be-14. The purpose of the present study is to investigate the role of bound excited states in the reaction product Be-12 after proton knockout from B-14, by measuring coincidences between Be-12, neutrons, and gamma rays originating from de-excitation of states fed by neutron decay of Be-13. The Be-13 isotopes were produced in proton knockout from a 400 MeV/nucleon B-14 beam impinging on a CH2 target. The Be-12-n relative-energy spectrum d sigma/dE(fn) was obtained from coincidences between Be-12(g.s.) and a neutron, and also as threefold coincidences by adding gamma rays, from the de-excitation of excited states in Be-12. Neutron decay from the first 5/2(+) state in Be-13 to the 2(+) state in Be-12 at 2.11 MeV is confirmed. An energy independence of the proton-knockout mechanism is found from a comparison with data taken with a 35 MeV/nucleon B-14 beam. A low-lying p-wave resonance in Be-13(1/2(-)) is confirmed by comparing proton- and neutron-knockout data from B-14 and Be-14.
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30.
  • Rodriguez-Sancheza, J. L., et al. (författare)
  • Comprehensive investigation of fission yields by using spallation- and (p,2p)induced fission reactions in inverse kinematics
  • 2023
  • Ingår i: 15TH INTERNATIONAL CONFERENCE ON NUCLEAR DATA FOR SCIENCE AND TECHNOLOGY, ND2022. - 2100-014X. ; 284
  • Konferensbidrag (refereegranskat)abstract
    • In the last decades, measurements of spallation, fragmentation and Coulex induced fission reactions in inverse kinematics have provided valuable data to accurately investigate the fission dynamics and nuclear structure at large deformations of a large variety of stable and non -stable heavy nuclei. To go a step further, we propose now to induce fission by the use of quasi -free (p,2p) scattering reactions in inverse kinematics, which allows us to reconstruct the excitation energy of the compound fissioning system by using the four-momenta of the two outgoing protons. Therefore, this new approach might permit to correlate the excitation energy with the charge and mass distributions of the fission fragments and with the fission probabilities, given for the first time direct access to the simultaneous measurement of the fission yield dependence on temperature and fission barrier heights of exotic heavy nuclei, respectively. The first experiment based on this methodology was realized recently at the GM/FAIR facility and a detailed description of the experimental setup is given here.
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31.
  • van Rheenen, Wouter, et al. (författare)
  • Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis
  • 2016
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1043-1048
  • Tidskriftsartikel (refereegranskat)abstract
    • To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.
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32.
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33.
  • Syndikus, I., et al. (författare)
  • Probing the Z = 6 spin-orbit shell gap with (p,2p) quasi-free scattering reactions
  • 2020
  • Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 809
  • Tidskriftsartikel (refereegranskat)abstract
    • The evolution of the traditional nuclear magic numbers away from the valley of stability is an active field of research. Experimental efforts focus on providing key spectroscopic information that will shed light into the structure of exotic nuclei and understanding the driving mechanism behind the shell evolution. In this work, we investigate the Z=6 spin-orbit shell gap towards the neutron dripline. To do so, we employed NA(p,2p)CA−1 quasi-free scattering reactions to measure the proton component of the 21+ state of 16,18,20C. The experimental findings support the notion of a moderate reduction of the proton 1p1/2−1p3/2 spin-orbit splitting, at variance to recent claims for a prevalent Z=6 magic number towards the neutron dripline.
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34.
  • van Vollenhoven, R, et al. (författare)
  • A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS)
  • 2017
  • Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 76:3, s. 554-561
  • Tidskriftsartikel (refereegranskat)abstract
    • Treat-to-target recommendations have identified ‘remission’ as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. Therefore, we initiated a process to achieve consensus on potential definitions for remission in SLE.MethodsAn international task force of 60 specialists and patient representatives participated in preparatory exercises, a face-to-face meeting and follow-up electronic voting. The level for agreement was set at 90%.ResultsThe task force agreed on eight key statements regarding remission in SLE and three principles to guide the further development of remission definitions:1. Definitions of remission will be worded as follows: remission in SLE is a durable state characterised by …………………. (reference to symptoms, signs, routine labs).2. For defining remission, a validated index must be used, for example, clinical systemic lupus erythematosus disease activity index (SLEDAI)=0, British Isles lupus assessment group (BILAG) 2004 D/E only, clinical European consensus lupus outcome measure (ECLAM)=0; with routine laboratory assessments included, and supplemented with physician's global assessment.3. Distinction is made between remission off and on therapy: remission off therapy requires the patient to be on no other treatment for SLE than maintenance antimalarials; and remission on therapy allows patients to be on stable maintenance antimalarials, low-dose corticosteroids (prednisone ≤5 mg/day), maintenance immunosuppressives and/or maintenance biologics.The task force also agreed that the most appropriate outcomes (dependent variables) for testing the prognostic value (construct validity) of potential remission definitions are: death, damage, flares and measures of health-related quality of life.ConclusionsThe work of this international task force provides a framework for testing different definitions of remission against long-term outcomes.
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35.
  • Simpson, J., et al. (författare)
  • Evolution of structure and shapes in Er 158 to ultrahigh spin
  • 2023
  • Ingår i: Physical Review C. - 2469-9985. ; 107:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The level structure of Er158 has been studied using the Gammasphere spectrometer via the Cd114(Ca48,4n) reaction at 215 MeV with both thin (self-supporting) and thick (backed) targets. The level scheme has been considerably extended with more than 200 new transitions and six new rotational structures, including two strongly coupled high-K bands. Configuration assignments for the new structures are based on their observed alignments, B(M1)/B(E2) ratios of reduced transition probabilities, excitation energies, and comparisons with neighboring nuclei and theoretical calculations. With increasing angular momentum, this nucleus exhibits Coriolis-induced alignments of both neutrons and protons before it then undergoes a rotation-induced transition from near-prolate collective rotation to a noncollective oblate configuration. This transition occurs via the mechanism of band termination around spin 45ħ in three rotational structures. Two distinct lifetime branches, consistent with the crossing of a collective "fast"rotational structure by an energetically favored "slow"terminating sequence, are confirmed for the positive-parity states, and similar behavior is established in the negative-parity states. Weak-intensity, high-energy transitions are observed to feed into the terminating states. At the highest spins, three collective bands with high dynamic moments of inertia and large quadrupole moments were identified. These bands are interpreted as triaxial strongly deformed structures and mark a return to collectivity at ultrahigh spin.
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36.
  • Lessard, Christopher J., et al. (författare)
  • Identification of IRF8, TMEM39A, and IKZF3-ZPBP2 as Susceptibility Loci for Systemic Lupus Erythematosus in a Large-Scale Multiracial Replication Study
  • 2012
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 90:4, s. 648-660
  • Tidskriftsartikel (refereegranskat)abstract
    • Systemic lupus erythematosus (SLE) is a chronic heterogeneous autoimmune disorder characterized by the loss of tolerance to self-antigens and dysregulated interferon responses. The etiology of SLE is complex, involving both heritable and environmental factors. Candidate-gene studies and genome-wide association (GWA) scans have been successful in identifying new loci that contribute to disease susceptibility; however, much of the heritable risk has yet to be identified. In this study, we sought to replicate 1,580 variants showing suggestive association with SLE in a previously published GWA scan of European Americans; we tested a multiethnic population consisting of 7,998 SLE cases and 7,492 controls of European, African American, Asian, Hispanic, Gullah, and Amerindian ancestry to find association with the disease. Several genes relevant to immunological pathways showed association with SLE. Three loci exceeded the genome-wide significance threshold: interferon regulatory factor 8 (IRF8; rs11644034; p(meta-Euro) = 2.08 x 10(-10)), transmembrane protein 39A (TMEM39A; rs1132200; p(meta-all) 8.62 x 10(-9)), and 17q21 (rs1453560; p(meta-all) = 3.48 x 10(-10)) between IKAROS family of zinc finger 3 (AIOLOS; IKZF3) and zona pellucida binding protein 2 (ZPBP2). Fine mapping, resequencing, imputation, and haplotype analysis of IRF8 indicated that three independent effects tagged by rs8046526, rs450443, and rs4843869, respectively, were required for risk in individuals of European ancestry. Eleven additional replicated effects (5 x 10(-8) < p(meta-Euro) < 9.99 x 10(-5)) were observed with CFHR1, CADM2, LOC730109/IL12A, LPP, LOC63920, SLU7, ADAMTSL1, C10orf64, OR8D4 FAM19A2, and STXBP6. The results of this study increase the number of confirmed SLE risk loci and identify others warranting further investigation.
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37.
  • Namjou, B., et al. (författare)
  • Evaluation of the TREX1 gene in a large multi-ancestral lupus cohort
  • 2011
  • Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 12:4, s. 270-279
  • Tidskriftsartikel (refereegranskat)abstract
    • Systemic lupus erythematosus (SLE) is a prototypic autoimmune disorder with a complex pathogenesis in which genetic, hormonal and environmental factors have a role. Rare mutations in the TREX1 gene, the major mammalian 3'-5' exonuclease, have been reported in sporadic SLE cases. Some of these mutations have also been identified in a rare pediatric neurological condition featuring an inflammatory encephalopathy known as Aicardi-Goutieres syndrome (AGS). We sought to investigate the frequency of these mutations in a large multi-ancestral cohort of SLE cases and controls. A total of 40 single-nucleotide polymorphisms (SNPs), including both common and rare variants, across the TREX1 gene, were evaluated in similar to 8370 patients with SLE and similar to 7490 control subjects. Stringent quality control procedures were applied, and principal components and admixture proportions were calculated to identify outliers for removal from analysis. Population-based case-control association analyses were performed. P-values, false-discovery rate q values, and odds ratios (OR) with 95% confidence intervals (CI) were calculated. The estimated frequency of TREX1 mutations in our lupus cohort was 0.5%. Five heterozygous mutations were detected at the Y305C polymorphism in European lupus cases but none were observed in European controls. Five African cases incurred heterozygous mutations at the E266G polymorphism and, again, none were observed in the African controls. A rare homozygous R114H mutation was identified in one Asian SLE patient, whereas all genotypes at this mutation in previous reports for SLE were heterozygous. Analysis of common TREX1 SNPs (minor allele frequency (MAF)>10%) revealed a relatively common risk haplotype in European SLE patients with neurological manifestations, especially seizures, with a frequency of 58% in lupus cases compared with 45% in normal controls (P = 0.0008, OR = 1.73, 95% CI = 1.25-2.39). Finally, the presence or absence of specific autoantibodies in certain populations produced significant genetic associations. For example, a strong association with anti-nRNP was observed in the European cohort at a coding synonymous variant rs56203834 (P = 2.99E-13, OR = 5.2, 95% CI = 3.18-8.56). Our data confirm and expand previous reports and provide additional support for the involvement of TREX1 in lupus pathogenesis. Genes and Immunity (2011) 12, 270-279; doi:10.1038/gene.2010.73; published online 27 January 2011
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38.
  • Adrianto, Indra, et al. (författare)
  • Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus
  • 2011
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:3, s. 253-258
  • Tidskriftsartikel (refereegranskat)abstract
    • Systemic lupus erythematosus (SLE, MIM152700) is an autoimmune disease characterized by self-reactive antibodies resulting in systemic inflammation and organ failure. TNFAIP3, encoding the ubiquitin-modifying enzyme A20, is an established susceptibility locus for SLE. By fine mapping and genomic re-sequencing in ethnically diverse populations, we fully characterized the TNFAIP3 risk haplotype and identified a TT>A polymorphic dinucleotide (deletion T followed by a T to A transversion) associated with SLE in subjects of European (P = 1.58 x 10(-8), odds ratio = 1.70) and Korean (P = 8.33 x 10(-10), odds ratio = 2.54) ancestry. This variant, located in a region of high conservation and regulatory potential, bound a nuclear protein complex composed of NF-kappa B subunits with reduced avidity. Further, compared with the non-risk haplotype, the haplotype carrying this variant resulted in reduced TNFAIP3 mRNA and A20 protein expression. These results establish this TT>A variant as the most likely functional polymorphism responsible for the association between TNFAIP3 and SLE.
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39.
  • Blanco, A., et al. (författare)
  • Performance of timing resistive plate chambers with relativistic neutrons from 300 to 1500 MeV
  • 2015
  • Ingår i: Journal of Instrumentation. - : IOP Publishing. - 1748-0221. ; 10:2
  • Tidskriftsartikel (refereegranskat)abstract
    • A prototype composed of four resistive plate chamber layers has been exposed to quasi-monoenergetic neutrons produced from a deuteron beam of varying energy (300 to 1500 AMeV) in experiment S406 at GSI, Darmstad, Germany. Each layer, with an active area of about 2000 × 500 mm2, is made of modules containing the active gaps, all in multigap construction. Each gap is defined by 0.3 mm nylon mono-filaments positioned between 2.85 mm thick float glass electrodes. The modules are operated in avalanche mode with a non-flammable gas mixture composed of 90% C2H2F4 and 10% SF6. The signals are readout by a pick-up electrode formed by 15 copper strips (per layer), spaced at a pitch of 30 mm, connected at both sides to timing front end electronics. Measurements of the time of flight jitter of neutrons, in the mentioned energy range, point to a contribution of the resistive plate chamber in the order of 150 ps, independent of the neutron energy.
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40.
  • Hurst, A. M., et al. (författare)
  • Measurement of the sign of the spectroscopic quadrupole moment for the 2(1)(+) state in Se-70: No evidence for oblate shape
  • 2007
  • Ingår i: Physical Review Letters. - 1079-7114. ; 98:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Using a method whereby molecular and atomic ions are independently selected, an isobarically pure beam of Se-70 ions was postaccelerated to an energy of 206 MeV using REX-ISOLDE. Coulomb-excitation yields for states in the beam and target nuclei were deduced by recording deexcitation gamma rays in the highly segmented MINIBALL gamma-ray spectrometer in coincidence with scattered particles in a silicon detector. At these energies, the Coulomb-excitation yield for the first 2(+) state is expected to be strongly sensitive to the sign of the spectroscopic quadrupole moment through the nuclear reorientation effect. Experimental evidence is presented here for a prolate shape for the first 2(+) state in Se-70, reopening the question over whether there are, as reported earlier, deformed oblate shapes near to the ground state in the light selenium isotopes.
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41.
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42.
  • Kottyan, Leah C., et al. (författare)
  • The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share.
  • 2015
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:2, s. 582-596
  • Tidskriftsartikel (refereegranskat)abstract
    • Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögrens syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.
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43.
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44.
  • Lessard, Christopher J., et al. (författare)
  • Identification of a Systemic Lupus Erythematosus Susceptibility Locus at 11p13 between PDHX and CD44 in a Multiethnic Study
  • 2011
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 88:1, s. 83-91
  • Tidskriftsartikel (refereegranskat)abstract
    • Systemic lupus erythematosus (SLE) is considered to be the prototypic autoimmune disease, with a complex genetic architecture influenced by environmental factors. We sought to replicate a putative association at 11p13 not yet exceeding genome-wide significance (p < 5 x 10(-8)) identified in a genome-wide association study (GWAS). Our GWA scan identified two intergenic SNPs located between PDHX and CD44 showing suggestive evidence of association with SLE in cases of European descent (rs2732552, p = 0.004, odds ratio [OR] = 0.78; rs387619, p = 0.003, OR = 0.78). The replication cohort consisted of >15,000 subjects, including 3562 SLE cases and 3491 controls of European ancestry, 1527 cases and 1811 controls of African American (AA) descent, and 1265 cases and 1260 controls of Asian origin. We observed robust association at both rs2732552 (p = 9.03 x 10(-8), OR = 0.83) and rs387619 (p = 7.7 x 10(-7), OR = 0.83) in the European samples with p(meta) = 1.82 x 10(-9) for rs2732552. The AA and Asian SLE cases also demonstrated association at rs2732552 (p = 5 x 10(-3), OR = 0.81 and p = 4.3 x 10(-4), OR = 0.80, respectively). A meta-analysis of rs2732552 for all racial and ethnic groups studied produced p(meta) = 2.36 x 10(-13). This locus contains multiple regulatory sites that could potentially affect expression and functions of CD44, a cell-surface glycoprotein influencing immunologic, inflammatory, and oncologic phenotypes, or PDHX, a subunit of the pyruvate dehydrogenase complex.
  •  
45.
  • Machado, J., et al. (författare)
  • Performance of timing Resistive Plate Chambers with protons from 200 to 800 MeV
  • 2015
  • Ingår i: Journal of Instrumentation. - 1748-0221. ; 10:1, s. C01043-
  • Tidskriftsartikel (refereegranskat)abstract
    • A prototype composed of four resistive plate chamber layers has been exposed to quasi-monoenergetic protons produced from a deuteron beam of varying energy (200 to 800 AMeV) in experiment S406 at GSI, Darmstadt, Germany. The aim of the experiment is to characterize the response of the prototype to protons in this energy range, which deposit from 1.75 to 6 times more energy than minimum ionizing particles. Each layer, with an active area of about 2000 × 500 mm 2 , is made of modules containing the active gaps, all in multigap construction. Each gap is defined by 0.3 mm nylon mono-filaments positioned between 2.85 mm thick float glass electrodes. The modules are operated in avalanche mode with a non-flammable gas mixture composed of 90% C 2 H 2 F 4 and 10% SF 6 . The signals are readout by a pick-up electrode formed by 15 copper strips (per layer), spaced at a pitch of 30 mm, connected at both sides to timing front end electronics. Results show an uniform efficiency close to 100% along with a timing resolution of around 60 ps on the entire 2000 × 500 mm 2 area.
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46.
  •  
47.
  • Petri, M., et al. (författare)
  • Structure of C-16: Testing shell model and ab initio approaches
  • 2012
  • Ingår i: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 86:4, s. Art. no. 044329-
  • Tidskriftsartikel (refereegranskat)abstract
    • Excited states in C-16 were populated via the Be-9(N-17,C-16+gamma)X one-proton knockout reaction. The lifetime of the 2(1)(+) state in C-16 was measured using the recoil distance method. The extracted lifetime of tau(+)(21) = 11.4(-0.9)(+0.8)(stat) +/- 0.7(syst(B rho))(-1.5)(+0.0)(syst(feeding)) ps yields a deduced B(E2;2(1)(+) -> 0(1)(+)) = 4.21(-0.26)(+0.34)(stat)(-0.24)(+0.28)(syst(B rho))(-0.00)(+0.64)(syst(feeding)) e(2)fm(4) value in good agreement with a previous measurement. The one-proton knockout cross section is used to extract the proton amplitude of the C-16 2(1)(+) state, which confirms the neutron dominant character of this state. Gamma-ray branching ratios between the 2(2)(+) state and the 2(1)(+) and ground states were also determined. The results are compared with p-sd shell model and no-core shell model (with NN and NN + NNN) calculations. The inclusion of three-body forces are essential in order for the no-core shell model calculations to reproduce the experimental findings on the gamma-ray branching ratios.
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48.
  • Barber, Megan R.W., et al. (författare)
  • Economic Evaluation of Damage Accrual in an International Systemic Lupus Erythematosus Inception Cohort Using a Multistate Model Approach
  • 2020
  • Ingår i: Arthritis Care and Research. - : Wiley. - 2151-464X .- 2151-4658. ; 72:12, s. 1800-1808
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: There is a paucity of data regarding health care costs associated with damage accrual in systemic lupus erythematosus. The present study was undertaken to describe costs associated with damage states across the disease course using multistate modeling. Methods: Patients from 33 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. Annual data on demographics, disease activity, damage (SLICC/American College of Rheumatology Damage Index [SDI]), hospitalizations, medications, dialysis, and selected procedures were collected. Ten-year cumulative costs (Canadian dollars) were estimated by multiplying annual costs associated with each SDI state by the expected state duration using a multistate model. Results: A total of 1,687 patients participated; 88.7% were female, 49.0% were white, mean ± SD age at diagnosis was 34.6 ± 13.3 years, and mean time to follow-up was 8.9 years (range 0.6–18.5 years). Mean annual costs were higher for those with higher SDI scores as follows: $22,006 (Canadian) (95% confidence interval [95% CI] $16,662, $27,350) for SDI scores ≥5 versus $1,833 (95% CI $1,134, $2,532) for SDI scores of 0. Similarly, 10-year cumulative costs were higher for those with higher SDI scores at the beginning of the 10-year interval as follows: $189,073 (Canadian) (95% CI $142,318, $235,827) for SDI scores ≥5 versus $21,713 (95% CI $13,639, $29,788) for SDI scores of 0. Conclusion: Patients with the highest SDI scores incur 10-year cumulative costs that are ~9-fold higher than those with the lowest SDI scores. By estimating the damage trajectory and incorporating annual costs, data on damage can be used to estimate future costs, which is critical knowledge for evaluating the cost-effectiveness of novel therapies.
  •  
49.
  • Bianco, L., et al. (författare)
  • Discovery of W-157 and Os-161
  • 2010
  • Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 690:1, s. 15-18
  • Tidskriftsartikel (refereegranskat)abstract
    • The nuclides W-157 and Os-161 have been discovered ill reactions of Ni-58 ion beams with a Cd-106 target. The Os-161 alpha-decay energy and half-life were 6890 +/- 12 keV and 640 +/- 60 mu s. The daughter W-157 nuclei beta-decayed with a half-life of 275 +/- 40 ms, populating both low-lying alpha-decaying states in Ta-157, which is consistent with a 7/2(-) ground state in W-157. Fine structure observed in the alpha decay of Os-161 places the lowest excited state in W-157 with 1(pi) = 9/2(-) at 318 +/- 30 key. The branching ratio of 5.5(-2.2)(+3.1)% indicates that Os-161 also has a 7/2(-) ground state. Shell-model calculations analysing the effects of monopole shifts and a tensor force on the relative energies of 2f(7/2) and 1h(9/2) neutron states in N = 83 isotones are presented. (C) 2010 Elsevier B.V. All rights reserved.
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50.
  • Cloutier, B. Tessier, et al. (författare)
  • Breast Cancer in Systemic Lupus Erythematosus
  • 2013
  • Ingår i: Oncology. - : S. Karger AG. - 1423-0232 .- 0030-2414. ; 85:2, s. 117-121
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Evidence points to a decreased breast cancer risk in systemic lupus erythematosus (SLE). We analyzed data from a large multisite SLE cohort, linked to cancer registries. Methods: Information on age, SLE duration, cancer date, and histology was available. We analyzed information on histological type and performed multivariate logistic regression analyses of histological types according to age, SLE duration, and calendar year. Results: We studied 180 breast cancers in the SLE cohort. Of the 155 cases with histology information, 11 were referred to simply as 'carcinoma not otherwise specified'. In the remaining 144 breast cancers, the most common histological type was ductal carcinoma (n = 95; 66%) followed by lobular adenocarcinoma (n = 11; 8%), 15 cancers were of mixed histology, and the remaining ones were special types. In our regression analyses, the independent risk factors for lobular versus ductal carcinoma was age [odds ratio (OR) 1.07, 95% confidence interval (Cl) 1.01-1.14] and for the 'special' subtypes it was age (OR 1.06, 95% Cl 1.01-1.10) and SLE duration (OR 1.05, 95% CI 1.00-1.11). Conclusions: Generally, up to 80% of breast cancers are ductal carcinomas. Though our results are not definitive, in the breast cancers that occur in SLE, there may be a slight decrease in the ductal histological type. In our analyses, age and SLE duration were independent predictors of histological status. Copyright (C) 2013 S. Karger AG, Basel
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