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2. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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3. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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4. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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5. |
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6. |
- Cousin, E., et al.
(författare)
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Diabetes mortality and trends before 25 years of age: an analysis of the Global Burden of Disease Study 2019
- 2022
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Ingår i: Lancet Diabetes & Endocrinology. - : Elsevier BV. - 2213-8587. ; 10:3, s. 177-192
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Tidskriftsartikel (refereegranskat)abstract
- Background Diabetes, particularly type 1 diabetes, at younger ages can be a largely preventable cause of death with the correct health care and services. We aimed to evaluate diabetes mortality and trends at ages younger than 25 years globally using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods We used estimates of GBD 2019 to calculate international diabetes mortality at ages younger than 25 years in 1990 and 2019. Data sources for causes of death were obtained from vital registration systems, verbal autopsies, and other surveillance systems for 1990-2019. We estimated death rates for each location using the GBD Cause of Death Ensemble model. We analysed the association of age-standardised death rates per 100 000 population with the Socio-demographic Index (SDI) and a measure of universal health coverage (UHC) and described the variability within SDI quintiles. We present estimates with their 95% uncertainty intervals. Findings In 2019, 16 300 (95% uncertainty interval 14 200 to 18 900) global deaths due to diabetes (type 1 and 2 combined) occurred in people younger than 25 years and 73.7% (68.3 to 77.4) were classified as due to type 1 diabetes. The age-standardised death rate was 0.50 (0.44 to 0.58) per 100 000 population, and 15 900 (97.5%) of these deaths occurred in low to high-middle SDI countries. The rate was 0.13 (0.12 to 0.14) per 100 000 population in the high SDI quintile, 0.60 (0.51 to 0.70) per 100 000 population in the low-middle SDI quintile, and 0.71 (0.60 to 0.86) per 100 000 population in the low SDI quintile. Within SDI quintiles, we observed large variability in rates across countries, in part explained by the extent of UHC (r(2)=0.62). From 1990 to 2019, age-standardised death rates decreased globally by 17.0% (-28.4 to -2.9) for all diabetes, and by 21.0% (-33.0 to -5.9) when considering only type 1 diabetes. However, the low SDI quintile had the lowest decline for both all diabetes (-13.6% [-28.4 to 3.4]) and for type 1 diabetes (-13.6% [-29.3 to 8.9]). Interpretation Decreasing diabetes mortality at ages younger than 25 years remains an important challenge, especially in low and low-middle SDI countries. Inadequate diagnosis and treatment of diabetes is likely to be major contributor to these early deaths, highlighting the urgent need to provide better access to insulin and basic diabetes education and care. This mortality metric, derived from readily available and frequently updated GBD data, can help to monitor preventable diabetes-related deaths over time globally, aligned with the UN's Sustainable Development Targets, and serve as an indicator of the adequacy of basic diabetes care for type 1 and type 2 diabetes across nations. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.
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7. |
- Kinyoki, DK, et al.
(författare)
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Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017
- 2020
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Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 26:5, s. 750-759
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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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8. |
- Ramdas, S., et al.
(författare)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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9. |
- Hyde, K. D., et al.
(författare)
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Global consortium for the classification of fungi and fungus-like taxa
- 2023
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Ingår i: MYCOSPHERE. - : Mushroom Research Foundation. - 2077-7000 .- 2077-7019. ; 14:1, s. 1960-2012
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Tidskriftsartikel (refereegranskat)abstract
- The Global Consortium for the Classification of Fungi and fungus-like taxa is an international initiative of more than 550 mycologists to develop an electronic structure for the classification of these organisms. The members of the Consortium originate from 55 countries/regions worldwide, from a wide range of disciplines, and include senior, mid-career and early-career mycologists and plant pathologists. The Consortium will publish a biannual update of the Outline of Fungi and fungus-like taxa, to act as an international scheme for other scientists. Notes on all newly published taxa at or above the level of species will be prepared and published online on the Outline of Fungi website (https://www.outlineoffungi.org/), and these will be finally published in the biannual edition of the Outline of Fungi and fungus-like taxa. Comments on recent important taxonomic opinions on controversial topics will be included in the biannual outline. For example, 'to promote a more stable taxonomy in Fusarium given the divergences over its generic delimitation', or 'are there too many genera in the Boletales?' and even more importantly, 'what should be done with the tremendously diverse 'dark fungal taxa?' There are undeniable differences in mycologists' perceptions and opinions regarding species classification as well as the establishment of new species. Given the pluralistic nature of fungal taxonomy and its implications for species concepts and the nature of species, this consortium aims to provide a platform to better refine and stabilise fungal classification, taking into consideration views from different parties. In the future, a confidential voting system will be set up to gauge the opinions of all mycologists in the Consortium on important topics. The results of such surveys will be presented to the International Commission on the Taxonomy of Fungi (ICTF) and the Nomenclature Committee for Fungi (NCF) with opinions and percentages of votes for and against. Criticisms based on scientific evidence with regards to nomenclature, classifications, and taxonomic concepts will be welcomed, and any recommendations on specific taxonomic issues will also be encouraged; however, we will encourage professionally and ethically responsible criticisms of others' work. This biannual ongoing project will provide an outlet for advances in various topics of fungal classification, nomenclature, and taxonomic concepts and lead to a community-agreed classification scheme for the fungi and fungus-like taxa. Interested parties should contact the lead author if they would like to be involved in future outlines.
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11. |
- Mishra, A., et al.
(författare)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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15. |
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16. |
- Marconi, A., et al.
(författare)
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ANDES, the high resolution spectrograph for the ELT : science case, baseline design and path to construction
- 2022
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Ingår i: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY IX. - : SPIE - International Society for Optical Engineering. - 9781510653504 - 9781510653498
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Konferensbidrag (refereegranskat)abstract
- The first generation of ELT instruments includes an optical-infrared high resolution spectrograph, indicated as ELT-HIRES and recently christened ANDES (ArmazoNes high Dispersion Echelle Spectrograph). ANDES consists of three fibre-fed spectrographs (UBV, RIZ, YJH) providing a spectral resolution of similar to 100,000 with a minimum simultaneous wavelength coverage of 0.4-1.8 mu m with the goal of extending it to 0.35-2.4 mu m with the addition of a K band spectrograph. It operates both in seeing- and diffraction-limited conditions and the fibre-feeding allows several, interchangeable observing modes including a single conjugated adaptive optics module and a small diffraction-limited integral field unit in the NIR. Its modularity will ensure that ANDES can be placed entirely on the ELT Nasmyth platform, if enough mass and volume is available, or partly in the Coude room. ANDES has a wide range of groundbreaking science cases spanning nearly all areas of research in astrophysics and even fundamental physics. Among the top science cases there are the detection of biosignatures from exoplanet atmospheres, finding the fingerprints of the first generation of stars, tests on the stability of Nature's fundamental couplings, and the direct detection of the cosmic acceleration. The ANDES project is carried forward by a large international consortium, composed of 35 Institutes from 13 countries, forming a team of more than 200 scientists and engineers which represent the majority of the scientific and technical expertise in the field among ESO member states.
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17. |
- Wang, HD, et al.
(författare)
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Global, regional, national, and selected subnational levels of stillbirths, neonatal, infant, and under-5 mortality, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015
- 2016
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Ingår i: Lancet (London, England). - : Elsevier. - 1474-547X .- 0140-6736. ; 388:10053, s. 1725-1774
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Tidskriftsartikel (refereegranskat)
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24. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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25. |
- Zillikens, M. C., et al.
(författare)
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Large meta-analysis of genome-wide association studies identifies five loci for lean body mass
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 x 10(-8)) or suggestively genome wide (p < 2.3 x 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/ near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/ near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.
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28. |
- Abellán, C., et al.
(författare)
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Challenging Local Realism with Human Choices
- 2018
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 557, s. 212-216
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Tidskriftsartikel (refereegranskat)abstract
- A Bell test is a randomized trial that compares experimental observations against the philosophical worldview of local realism , in which the properties of the physical world are independent of our observation of them and no signal travels faster than light. A Bell test requires spatially distributed entanglement, fast and high-efficiency detection and unpredictable measurement settings. Although technology can satisfy the first two of these requirements, the use of physical devices to choose settings in a Bell test involves making assumptions about the physics that one aims to test. Bell himself noted this weakness in using physical setting choices and argued that human 'free will' could be used rigorously to ensure unpredictability in Bell tests. Here we report a set of local-realism tests using human choices, which avoids assumptions about predictability in physics. We recruited about 100,000 human participants to play an online video game that incentivizes fast, sustained input of unpredictable selections and illustrates Bell-test methodology. The participants generated 97,347,490 binary choices, which were directed via a scalable web platform to 12 laboratories on five continents, where 13 experiments tested local realism using photons, single atoms, atomic ensembles and superconducting devices. Over a 12-hour period on 30 November 2016, participants worldwide provided a sustained data flow of over 1,000 bits per second to the experiments, which used different human-generated data to choose each measurement setting. The observed correlations strongly contradict local realism and other realistic positions in bi-partite and tri-partite 12 scenarios. Project outcomes include closing the 'freedom-of-choice loophole' (the possibility that the setting choices are influenced by 'hidden variables' to correlate with the particle properties), the utilization of video-game methods for rapid collection of human-generated randomness, and the use of networking techniques for global participation in experimental science.
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29. |
- Butler-Laporte, G, et al.
(författare)
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Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative
- 2022
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 18:11, s. e1010367-
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Tidskriftsartikel (refereegranskat)abstract
- Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75–10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.
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30. |
- Bendo, G. J., et al.
(författare)
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The bright extragalactic ALMA redshift survey (BEARS) – II. Millimetre photometry of gravitational lens candidates
- 2023
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Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 522:2, s. 2995-3017
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Tidskriftsartikel (refereegranskat)abstract
- We present 101- and 151-GHz ALMA continuum images for 85 fields selected from Herschel observations that have 500-μm flux densities >80 mJy and 250–500-μm colours consistent with z > 2, most of which are expected to be gravitationally lensed or hyperluminous infrared galaxies. Approximately half of the Herschel 500-μm sources were resolved into multiple ALMA sources, but 11 of the 15 brightest 500-μm Herschel sources correspond to individual ALMA sources. For the 37 fields containing either a single source with a spectroscopic redshift or two sources with the same spectroscopic redshift, we examined the colour temperatures and dust emissivity indices. The colour temperatures only vary weakly with redshift and are statistically consistent with no redshift-dependent temperature variations, which generally corresponds to results from other samples selected in far-infrared, submillimetre, or millimetre bands but not to results from samples selected in optical or near-infrared bands. The dust emissivity indices, with very few exceptions, are largely consistent with a value of 2. We also compared spectroscopic redshifts to photometric redshifts based on spectral energy distribution templates designed for infrared-bright high-redshift galaxies. While the templates systematically underestimate the redshifts by ∼15 per cent, the inclusion of ALMA data decreases the scatter in the predicted redshifts by a factor of ∼2, illustrating the potential usefulness of these millimetre data for estimating photometric redshifts.
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31. |
- Hagimoto, Masato, et al.
(författare)
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Bright extragalactic ALMA redshift survey (BEARS) III: detailed study of emission lines from 71 Herschel targets
- 2023
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 521:4, s. 5508-5535
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Tidskriftsartikel (refereegranskat)abstract
- We analyse the molecular and atomic emission lines of 71 bright Herschel-selected galaxies between redshifts 1.4 and 4.6 detected by the Atacama Large Millimeter/submillimeter Array. These lines include a total of 156 CO, [C i], and H2O emission lines. For 46 galaxies, we detect two transitions of CO lines, and for these galaxies we find gas properties similar to those of other dusty star-forming galaxy (DSFG) samples. A comparison to photodissociation models suggests that most of Herschel-selected galaxies have similar interstellar medium conditions as local infrared-luminous galaxies and high-redshift DSFGs, although with denser gas and more intense far-ultraviolet radiation fields than normal star-forming galaxies. The line luminosities agree with the luminosity scaling relations across five orders of magnitude, although the star formation and gas surface density distributions (i.e. Schmidt-Kennicutt relation) suggest a different star formation phase in our galaxies (and other DSFGs) compared to local and low-redshift gas-rich, normal star-forming systems. The gas-to-dust ratios of these galaxies are similar to Milky Way values, with no apparent redshift evolution. Four of 46 sources appear to have CO line ratios in excess of the expected maximum (thermalized) profile, suggesting a rare phase in the evolution of DSFGs. Finally, we create a deep stacked spectrum over a wide rest-frame frequency (220-890 GHz) that reveals faint transitions from HCN and CH, in line with previous stacking experiments.
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32. |
- Jones, Gregory T., et al.
(författare)
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Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci
- 2017
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Ingår i: Circulation Research. - 0009-7330 .- 1524-4571. ; 120:2, s. 341-
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
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33. |
- Kousathanas, A, et al.
(författare)
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Whole-genome sequencing reveals host factors underlying critical COVID-19
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 607:7917, s. 97-
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Tidskriftsartikel (refereegranskat)abstract
- Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.
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34. |
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35. |
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36. |
- Zhou, Wei, et al.
(författare)
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Global Biobank Meta-analysis Initiative : Powering genetic discovery across human disease
- 2022
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Ingår i: Cell Genomics. - : Elsevier. - 2666-979X. ; 2:10
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Tidskriftsartikel (refereegranskat)abstract
- Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)-a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits.
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37. |
- Al-Dahan, N., et al.
(författare)
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Isomeric States In 208Hg And 209Tl Populated In Fragmentation Of 238U
- 2009
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Ingår i: Acta Physica Polonica. Series B: Elementary Particle Physics, Nuclear Physics, Statistical Physics, Theory of Relativity, Field Theory. - 0587-4254. ; 40:3, s. 871-874
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Tidskriftsartikel (refereegranskat)abstract
- The nuclear structure of neutron-rich N > 126 nuclei has been investigated following their production via relativistic projectile fragmentation of a E/A = 1 GeV U-238 beam on a Be target. The preliminary analysis indicates the presence of previously unreported isomeric states in the N = 128 isotones Hg-208 and Tl-209.
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38. |
- Al-Dahan, N., et al.
(författare)
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Nuclear Structure "Southeast" of 208Pb: Isomeric states in 208Hg and 209Tl
- 2009
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 80:6
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Tidskriftsartikel (refereegranskat)abstract
- The nuclear structure of neutron-rich N>126 nuclei has been investigated following their production via relativistic projectile fragmentation of a E/A=1 GeV U-238 beam. Metastable states in the N=128 isotones Hg-208 and Tl-209 have been identified. Delayed gamma-ray transitions are interpreted as arising from the decay of I-pi=(8(+)) and (17/2(+)) isomers, respectively. The data allow for the so far most comprehensive verification of the shell-model approach in the region determined by magic numbers Z < 82 and N>126.
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39. |
- Bacelar, A. M. Denis, et al.
(författare)
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Angular Momentum Population In Fragmentation Reactions
- 2009
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Ingår i: Acta Physica Polonica. Series B: Elementary Particle Physics, Nuclear Physics, Statistical Physics, Theory of Relativity, Field Theory. - 0587-4254. ; 40:3, s. 889-892
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Tidskriftsartikel (refereegranskat)abstract
- Neutron-deficient nuclei with N = 126 have been populated following projectile fragmentation of a U-238 beam with energy 1 GeV/A. The decay of several previously reported isomers has been measured. This will allow us to calculate high-spin isomeric ratios and compare them with model calculations to allow a better understanding of the reaction mechanism.
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40. |
- Denis Bacelar, A.M., et al.
(författare)
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The population of metastable states as a probe of relativistic-energy fragmentation reactions
- 2013
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 723:4–5, s. 302-306
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Tidskriftsartikel (refereegranskat)abstract
- Isomeric ratios have been measured for high-spin states in Po-198,200,206,208(84), At-208,209,210,211(85), Rn-210,211,212,213,214(86), Fr-208,211,212,213,214(87), Ra-210,211,212,214,215(88), and Ac-215(89) following the projectile fragmentation of a 1 AGeV U-238 beam by a Be-9 target at GSI Helmholtzzentrum fur Schwerionenforschung. The fragments were separated in the fragment separator (FRS) and identified by means of energy loss and time-of-flight techniques. They were brought to rest at the centre of the RISING gamma-ray detector array and intensities of gamma rays emitted in the decay of isomeric states with half-lives between 100 ns and 40 mu s and spin values up to 55/2 (h) over bar were used to obtain the corresponding isomeric ratios. The data are compared to theoretical isomeric ratios calculated in the framework of the abrasion-ablation model. Large experimental enhancements are obtained for high-spin isomers in comparison to expected values. (C) 2013 Elsevier B.V. All rights reserved.
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41. |
- Freitag, Daniel F., et al.
(författare)
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Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis
- 2015
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Ingår i: The Lancet Diabetes & Endocrinology. - 2213-8595. ; 3:4, s. 243-253
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Tidskriftsartikel (refereegranskat)abstract
- Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1.03 (1.02-1.04; p=3.9 x 10(-10)). Perallele odds ratios were 0.97 (0.95-0.99; p=9.9 x 10(-4)) for rheumatoid arthritis, 0.99 (0.97-1.01; p=0.47) for type 2 diabetes, 1.00 (0.98-1.02; p=0.92) for ischaemic stroke, and 1.08 (1.04-1.12; p=1.8 x 10(-5)) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1 alpha/beta inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Copyright (C) The Interleukin 1 Genetics Consortium. Open Access article distributed under the terms of CC-BY-NC-ND.
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42. |
- Al-Dahan, N., et al.
(författare)
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Structure of N≥126 Nuclei Produced in Fragmentation of 238U
- 2009
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Ingår i: Proceedings of the 13th International Symposium on Capture Gamma‐Ray Spectroscopy and Related Topics. - : AIP. - 0094-243X. ; 1090, s. 145-148
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Konferensbidrag (refereegranskat)abstract
- The nuclear structure of neutron-rich N≥126 nuclei have been investigated following their production via relativistic projectile fragmentation of a E/A=l GeV 238U beam on a Be target. The cocktail of secondary beam products were separated and identified using the GSI FRagment Separator (FRS). The nuclei of interest were implanted in a high-granularity active stopper detector set-up consisting of 6 double sided silicon strip detectors. The associated gamma-ray transitions were detected with the RISING array, consisting of 15 Euroball cluster Ge-detectors. Time-correlated gamma decays from individually identified nuclear species have been recorded, allowing the clean identification of isomeric decays.
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43. |
- Bryant, J. M., et al.
(författare)
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Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium
- 2016
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 354:6313, s. 751-757
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Tidskriftsartikel (refereegranskat)abstract
- Lung infections with Mycobacterium abscessus, a species of multidrug-resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF), in whom M. abscessus accelerates inflammatory lung damage, leading to increased morbidity and mortality. Previously, M. abscessus was thought to be independently acquired by susceptible individuals from the environment. However, using whole-genome analysis of a global collection of clinical isolates, we show that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge.
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44. |
- Grodner, E., et al.
(författare)
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Hindered Gamow-Teller Decay to the Odd-Odd N=Z 62Ga: Absence of Proton-Neutron T=0 Condensate in A=62
- 2014
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Ingår i: Physical Review Letters. - 1079-7114. ; 113:9
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Tidskriftsartikel (refereegranskat)abstract
- Search for a new kind of superfluidity built on collective proton-neutron pairs with aligned spin is performed studying the Gamow-Teller decay of the T=1, Jπ=0+ ground state of Ge62 into excited states of the odd-odd N=Z nucleus Ga62. The experiment is performed at GSI Helmholtzzentrum für Schwerionenforschung with the Ge62 ions selected by the fragment separator and implanted in a stack of Si-strip detectors, surrounded by the RISING Ge array. A half-life of T1/2=82.9(14) ms is measured for the Ge62 ground state. Six excited states of Ga62, populated below 2.5 MeV through Gamow-Teller transitions, are identified. Individual Gamow-Teller transition strengths agree well with theoretical predictions of the interacting shell model and the quasiparticle random phase approximation. The absence of any sizable low-lying Gamow-Teller strength in the reported beta-decay experiment supports the hypothesis of a negligible role of coherent T=0 proton-neutron correlations in Ga62.
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45. |
- Morales, A. I., et al.
(författare)
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beta-delayed gamma-ray spectroscopy of Au-203,Au-204 and Pt200-202
- 2013
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 88:1
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Tidskriftsartikel (refereegranskat)abstract
- The beta decay of five heavy, neutron-rich nuclei, Pt-203,Pt-204 and Ir200-202, has been investigated following relativistic cold fragmentation reactions of lead projectiles using the FRS + RISING setup at GSI. This paper reports on the study of the low-lying states in the decay daughter nuclei Au-203,Au-204 and Pt200-202. The characteristic gamma rays for each nucleus have been determined using beta-delayed gamma-ray spectroscopy. Tentative level schemes, relative intensities, and apparent beta feedings are provided. These data are compared with shell-model calculations, which indicate a substantial contribution to the total beta strength from high-energy first-forbidden beta-decay transitions in this mass region.
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46. |
- Morales, A. I., et al.
(författare)
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beta -Delayed gamma -Ray Spectroscopy of Heavy Neutron Rich Nuclei "South" of Lead
- 2009
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Ingår i: Acta Physica Polonica B. - 0587-4254. ; 40:3, s. 867-870
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Konferensbidrag (refereegranskat)abstract
- Relativistic projectile fragmentation of a Pb-208 primary beam has been used to produce neutron-rich nuclei with proton-holes relative to the Z = 82 shell closure, i.e., "south" of Pb. beta-delayed gamma-ray spectroscopy allows to investigate the structural properties of such nuclei with A similar to 195 -> 205. The current work presents transitions de-exciting excited states in Au-204, which are the first spectroscopic information on this N = 125 isotone.
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47. |
- Morales, A I, et al.
(författare)
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Half-Life Systematics across the N=126 Shell Closure: Role of First-Forbidden Transitions in the β Decay of Heavy Neutron-Rich Nuclei.
- 2014
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Ingår i: Physical Review Letters. - 1079-7114. ; 113:2
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Tidskriftsartikel (refereegranskat)abstract
- This Letter reports on a systematic study of β-decay half-lives of neutron-rich nuclei around doubly magic ^{208}Pb. The lifetimes of the 126-neutron shell isotone ^{204}Pt and the neighboring ^{200-202}Ir, ^{203}Pt, ^{204}Au are presented together with other 19 half-lives measured during the "stopped beam" campaign of the rare isotope investigations at GSI collaboration. The results constrain the main nuclear theories used in calculations of r-process nucleosynthesis. Predictions based on a statistical macroscopic description of the first-forbidden β strength reveal significant deviations for most of the nuclei with N<126. In contrast, theories including a fully microscopic treatment of allowed and first-forbidden transitions reproduce more satisfactorily the trend in the measured half-lives for the nuclei in this region, where the r-process pathway passes through during β decay back to stability.
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48. |
- Rolo, M. Da Rocha, et al.
(författare)
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A custom readout electronics for the BESIII CGEM detector
- 2017
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Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- For the upgrade of the inner tracker of the BESIII spectrometer, planned for 2018, a lightweight tracker based on an innovative Cylindrical Gas Electron Multiplier (CGEM) detector is now under development. The analogue readout of the CGEM enables the use of a charge centroid algorithm to improve the spatial resolution to better than 130 mu m while loosening the pitch strip to 650 mu m, which allows to reduce the total number of channels to about 10 000. The channels are readout by 160 dedicated integrated 64-channel front-end ASICs, providing a time and charge measurement and featuring a fully-digital output. The energy measurement is extracted either from the time-over-threshold (ToT) or the 10-bit digitisation of the peak amplitude of the signal. The time of the event is generated by quad-buffered low-power TDCs, allowing for rates in excess of 60 kHz per channel. The TDCs are based on analogue interpolation techniques and produce a time stamp (or two, if working in ToT mode) of the event with a time resolution better than 50 ps. The front-end noise, based on a CSA and a two-stage complex conjugated pole shapers, dominate the channel intrinsic time jitter, which is less than 5 ns r.m.s. The time information of the hit can be used to reconstruct the track path, operating the detector as a small TPC and hence improving the position resolution when the distribution of the cloud, due to large incident angle or magnetic field, is very broad. Event data is collected by an off-detector motherboard, where each GEM-ROC readout card handles 4 ASIC carrier FEBs (512 channels). Configuration upload and data readout between the off-detector electronics and the VME-based data collector cards are managed by bi-directional fibre optical links. This paper covers the design of a custom front-end electronics for the readout of the new inner tracker of the BESIII experiment, addressing the relevant design aspects of the detector electronics and the front-end ASIC for the CGEM readout, and reviewing the first silicon results of the chip prototype.
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49. |
- Bianco, Federica B., et al.
(författare)
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Optimization of the Observing Cadence for the Rubin Observatory Legacy Survey of Space and Time : A Pioneering Process of Community-focused Experimental Design
- 2022
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 258:1
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Tidskriftsartikel (refereegranskat)abstract
- Vera C. Rubin Observatory is a ground-based astronomical facility under construction, a joint project of the National Science Foundation and the U.S. Department of Energy, designed to conduct a multipurpose 10 yr optical survey of the Southern Hemisphere sky: the Legacy Survey of Space and Time. Significant flexibility in survey strategy remains within the constraints imposed by the core science goals of probing dark energy and dark matter, cataloging the solar system, exploring the transient optical sky, and mapping the Milky Way. The survey's massive data throughput will be transformational for many other astrophysics domains and Rubin's data access policy sets the stage for a huge community of potential users. To ensure that the survey science potential is maximized while serving as broad a community as possible, Rubin Observatory has involved the scientific community at large in the process of setting and refining the details of the observing strategy. The motivation, history, and decision-making process of this strategy optimization are detailed in this paper, giving context to the science-driven proposals and recommendations for the survey strategy included in this Focus Issue.
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50. |
- Efe, C., et al.
(författare)
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Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients With Autoimmune Hepatitis
- 2017
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565 .- 1542-7714. ; 15:12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Predniso(lo) ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH. METHODS: We performed a retrospective study of data (from 19 centers in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6-190 mo). Patients were categorized according to their response to SOC. Patients in group 1 (n = 108) had a complete response to the SOC, but were switched to second-line therapy as a result of side effects of predniso(lo) ne or azathioprine, whereas patients in group 2 (n = 93) had not responded to SOC. RESULTS: There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P = .639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P = .682). Significantly more group 2 patients given tacrolimus compared with MMF had a complete response (56.5% vs 34%, respectively; P = .029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P = .472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal. CONCLUSIONS: Long-term therapy with MMF or tacrolimus generally was well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous nonresponder patients compared with MMF.
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