| 1. |
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| 2. |
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| 3. |
- Kanai, M, et al.
(författare)
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- 2023
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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. |
- Lind, Lars, et al.
(författare)
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Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
- 2021
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Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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| 6. |
- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 7. |
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| 8. |
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| 9. |
- 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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| 10. |
- Taddei, C, et al.
(författare)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Tidskriftsartikel (refereegranskat)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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| 11. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 12. |
- 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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| 13. |
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| 14. |
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| 15. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 16. |
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| 17. |
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| 18. |
- Orsini, S., et al.
(författare)
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Inner southern magnetosphere observation of Mercury via SERENA ion sensors in BepiColombo mission
- 2022
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Mercury’s southern inner magnetosphere is an unexplored region as it was not observed by earlier space missions. In October 2021, BepiColombo mission has passed through this region during its first Mercury flyby. Here, we describe the observations of SERENA ion sensors nearby and inside Mercury’s magnetosphere. An intermittent high-energy signal, possibly due to an interplanetary magnetic flux rope, has been observed downstream Mercury, together with low energy solar wind. Low energy ions, possibly due to satellite outgassing, were detected outside the magnetosphere. The dayside magnetopause and bow-shock crossing were much closer to the planet than expected, signature of a highly eroded magnetosphere. Different ion populations have been observed inside the magnetosphere, like low latitude boundary layer at magnetopause inbound and partial ring current at dawn close to the planet. These observations are important for understanding the weak magnetosphere behavior so close to the Sun, revealing details never reached before.
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| 19. |
- Hayes, A., et al.
(författare)
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A European multicentre evaluation of detection and typing methods for human enteroviruses and parechoviruses using RNA transcripts
- 2020
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Ingår i: Journal of Medical Virology. - : Wiley. - 0146-6615 .- 1096-9071. ; 92:8, s. 1065-1074
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Tidskriftsartikel (refereegranskat)abstract
- Polymerase chain reaction (PCR) detection has become the gold standard for diagnosis and typing of enterovirus (EV) and human parechovirus (HPeV) infections. Its effectiveness depends critically on using the appropriate sample types and high assay sensitivity as viral loads in cerebrospinal fluid samples from meningitis and sepsis clinical presentation can be extremely low. This study evaluated the sensitivity and specificity of currently used commercial and in-house diagnostic and typing assays. Accurately quantified RNA transcript controls were distributed to 27 diagnostic and 12 reference laboratories in 17 European countries for blinded testing. Transcripts represented the four human EV species (EV-A71, echovirus 30, coxsackie A virus 21, and EV-D68), HPeV3, and specificity controls. Reported results from 48 in-house and 15 commercial assays showed 98% detection frequencies of high copy (1000 RNA copies/5 µL) transcripts. In-house assays showed significantly greater detection frequencies of the low copy (10 copies/5 µL) EV and HPeV transcripts (81% and 86%, respectively) compared with commercial assays (56%, 50%; P = 7 × 10−5). EV-specific PCRs showed low cross-reactivity with human rhinovirus C (3 of 42 tests) and infrequent positivity in the negative control (2 of 63 tests). Most or all high copy EV and HPeV controls were successfully typed (88%, 100%) by reference laboratories, but showed reduced effectiveness for low copy controls (41%, 67%). Stabilized RNA transcripts provide an effective, logistically simple and inexpensive reagent for evaluation of diagnostic assay performance. The study provides reassurance of the performance of the many in-house assay formats used across Europe. However, it identified often substantially reduced sensitivities of commercial assays often used as point-of-care tests.
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| 20. |
- Kollhoff, A., et al.
(författare)
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The first widespread solar energetic particle event observed by Solar Orbiter on 2020 November 29
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656
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Tidskriftsartikel (refereegranskat)abstract
- Context. On 2020 November 29, the first widespread solar energetic particle (SEP) event of solar cycle 25 was observed at four widely separated locations in the inner (≲1 AU) heliosphere. Relativistic electrons as well as protons with energies > 50 MeV were observed by Solar Orbiter (SolO), Parker Solar Probe, the Solar Terrestrial Relations Observatory (STEREO)-A and multiple near-Earth spacecraft. The SEP event was associated with an M4.4 class X-ray flare and accompanied by a coronal mass ejection and an extreme ultraviolet (EUV) wave as well as a type II radio burst and multiple type III radio bursts.Aims. We present multi-spacecraft particle observations and place them in context with source observations from remote sensing instruments and discuss how such observations may further our understanding of particle acceleration and transport in this widespread event.Methods. Velocity dispersion analysis (VDA) and time shift analysis (TSA) were used to infer the particle release times at the Sun. Solar wind plasma and magnetic field measurements were examined to identify structures that influence the properties of the energetic particles such as their intensity. Pitch angle distributions and first-order anisotropies were analyzed in order to characterize the particle propagation in the interplanetary medium.Results. We find that during the 2020 November 29 SEP event, particles spread over more than 230° in longitude close to 1 AU. The particle onset delays observed at the different spacecraft are larger as the flare–footpoint angle increases and are consistent with those from previous STEREO observations. Comparing the timing when the EUV wave intersects the estimated magnetic footpoints of each spacecraft with particle release times from TSA and VDA, we conclude that a simple scenario where the particle release is only determined by the EUV wave propagation is unlikely for this event. Observations of anisotropic particle distributions at SolO, Wind, and STEREO-A do not rule out that particles are injected over a wide longitudinal range close to the Sun. However, the low values of the first-order anisotropy observed by near-Earth spacecraft suggest that diffusive propagation processes are likely involved.
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| 21. |
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| 22. |
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The Seventeenth Data Release of the Sloan Digital Sky Surveys : Complete Release of MaNGA, MaStar, and APOGEE-2 Data
- 2022
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Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics (IOP). - 0067-0049 .- 1538-4365. ; 259:2
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Tidskriftsartikel (refereegranskat)abstract
- This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 survey that publicly releases infrared spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the subsurvey Time Domain Spectroscopic Survey data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey subsurvey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated value-added catalogs. This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper, Local Volume Mapper, and Black Hole Mapper surveys.
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| 23. |
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| 24. |
- Archambault, Alexi N., et al.
(författare)
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Cumulative Burden of Colorectal Cancer Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer
- 2020
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 158:5, s. 1274-1286.e12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC.METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants.RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 x 10(-5)). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings.CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.
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| 25. |
- Pihl, E., et al.
(författare)
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Ten new insights in climate science 2020- A horizon scan
- 2020
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Ingår i: Global Sustainability. - : Cambridge University Press. - 2059-4798.
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Tidskriftsartikel (refereegranskat)abstract
- Non-technical summary We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding of Earth's sensitivity to carbon dioxide, finds that permafrost thaw could release more carbon emissions than expected and that the uptake of carbon in tropical ecosystems is weakening. Adverse impacts on human society include increasing water shortages and impacts on mental health. Options for solutions emerge from rethinking economic models, rights-based litigation, strengthened governance systems and a new social contract. The disruption caused by COVID-19 could be seized as an opportunity for positive change, directing economic stimulus towards sustainable investments. Technical summary A synthesis is made of ten fields within climate science where there have been significant advances since mid-2019, through an expert elicitation process with broad disciplinary scope. Findings include: (1) a better understanding of equilibrium climate sensitivity; (2) abrupt thaw as an accelerator of carbon release from permafrost; (3) changes to global and regional land carbon sinks; (4) impacts of climate change on water crises, including equity perspectives; (5) adverse effects on mental health from climate change; (6) immediate effects on climate of the COVID-19 pandemic and requirements for recovery packages to deliver on the Paris Agreement; (7) suggested long-term changes to governance and a social contract to address climate change, learning from the current pandemic, (8) updated positive cost-benefit ratio and new perspectives on the potential for green growth in the short- A nd long-term perspective; (9) urban electrification as a strategy to move towards low-carbon energy systems and (10) rights-based litigation as an increasingly important method to address climate change, with recent clarifications on the legal standing and representation of future generations. Social media summary Stronger permafrost thaw, COVID-19 effects and growing mental health impacts among highlights of latest climate science.
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| 26. |
- Thomas, Minta, et al.
(författare)
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Response to Li and Hopper
- 2021
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 108:3, s. 527-529
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Tidskriftsartikel (refereegranskat)
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| 27. |
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| 28. |
- Aran, A., et al.
(författare)
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Evidence for local particle acceleration in the first recurrent galactic cosmic ray depression observed by Solar Orbiter : The ion event on 19 June 2020
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656
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Tidskriftsartikel (refereegranskat)abstract
- Context. In mid-June 2020, the Solar Orbiter (SolO) mission reached its first perihelion at 0.51 au and started its cruise phase, with most of the in situ instruments operating continuously.Aims. We present the in situ particle measurements of the first proton event observed after the first perihelion obtained by the Energetic Particle Detector (EPD) suite on board SolO. The potential solar and interplanetary (IP) sources of these particles are investigated.Methods. Ion observations from similar to 20 keV to similar to 1 MeV are combined with available solar wind data from the Radio and Plasma Waves (RPW) instrument and magnetic field data from the magnetometer on board SolO to evaluate the energetic particle transport conditions and infer the possible acceleration mechanisms through which particles gain energy. We compare > 17-20 MeV ion count rate measurements for two solar rotations, along with the solar wind plasma data available from the Solar Wind Analyser (SWA) and RPW instruments, in order to infer the origin of the observed galactic cosmic ray (GCR) depressions.Results. The lack of an observed electron event and of velocity dispersion at various low-energy ion channels and the observed IP structure indicate a local IP source for the low-energy particles. From the analysis of the anisotropy of particle intensities, we conclude that the low-energy ions were most likely accelerated via a local second-order Fermi process. The observed GCR decrease on 19 June, together with the 51.8-1034.0 keV nuc(-1) ion enhancement, was due to a solar wind stream interaction region (SIR). The observation of a similar GCR decrease in the next solar rotation favours this interpretation and constitutes the first observation of a recurrent GCR decrease by SolO. The analysis of the recurrence times of this SIR suggests that it is the same SIR responsible for the He-4 events previously measured in April and May. Finally, we point out that an IP structure more complex than a common SIR cannot be discarded, mainly due to the lack of solar wind temperature measurements and the lack of a higher cadence of solar wind velocity observations.
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| 29. |
- Gerkin, RC, et al.
(författare)
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The best COVID-19 predictor is recent smell loss: a cross-sectional study
- 2020
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundCOVID-19 has heterogeneous manifestations, though one of the most common symptoms is a sudden loss of smell (anosmia or hyposmia). We investigated whether olfactory loss is a reliable predictor of COVID-19.MethodsThis preregistered, cross-sectional study used a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n=4148) or negative (C19-; n=546) COVID-19 laboratory test outcome. Logistic regression models identified singular and cumulative predictors of COVID-19 status and post-COVID-19 olfactory recovery.ResultsBoth C19+ and C19-groups exhibited smell loss, but it was significantly larger in C19+ participants (mean±SD, C19+: -82.5±27.2 points; C19-: -59.8±37.7). Smell loss during illness was the best predictor of COVID-19 in both single and cumulative feature models (ROC AUC=0.72), with additional features providing negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms, such as fever or cough. Olfactory recovery within 40 days was reported for ∼50% of participants and was best predicted by time since illness onset.ConclusionsAs smell loss is the best predictor of COVID-19, we developed the ODoR-19 tool, a 0-10 scale to screen for recent olfactory loss. Numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4<OR<10), which can be deployed when viral lab tests are impractical or unavailable.
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| 30. |
- Huyghe, Jeroen R, et al.
(författare)
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Genetic architectures of proximal and distal colorectal cancer are partly distinct
- 2021
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Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:7, s. 1325-1334
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Tidskriftsartikel (refereegranskat)abstract
- Objective: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.Design: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling.Results: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.Conclusion: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
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| 31. |
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| 32. |
- Péroux, C., et al.
(författare)
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MUSE-ALMA haloes VII : survey science goals & design, data processing and final catalogues
- 2022
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 516:4, s. 5618-5636
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Tidskriftsartikel (refereegranskat)abstract
- The gas cycling in the circumgalactic regions of galaxies is known to be multi-phase. The MUSE–ALMA Haloes survey gathers a large multi-wavelength observational sample of absorption and emission data with the goal to significantly advance our understanding of the physical properties of such CGM gas. A key component of the MUSE–ALMA Haloes survey is the multi-facility observational campaign conducted with VLT/MUSE, ALMA, and HST. MUSE–ALMA Haloes targets comprise 19 VLT/MUSE IFS quasar fields, including 32 zabs <0.85 strong absorbers with measured N(H I) ≥1018 cm−2 from UV-spectroscopy. We additionally use a new complementary HST medium program to characterize the stellar content of the galaxies through a 40-orbit three-band UVIS and IR WFC3 imaging. Beyond the absorber-selected targets, we detect 3658 sources all fields combined, including 703 objects with spectroscopic redshifts. This galaxy-selected sample constitutes the main focus of the current paper. We have secured millimeter ALMA observations of some of the fields to probe the molecular gas properties of these objects. Here, we present the overall survey science goals, target selection, observational strategy, data processing and source identification of the full sample. Furthermore, we provide catalogues of magnitude measurements for all objects detected in VLT/MUSE, ALMA, and HST broad-band images and associated spectroscopic redshifts derived from VLT/MUSE observations. Together, this data set provides robust characterization of the neutral atomic gas, molecular gas and stars in the same objects resulting in the baryon census of condensed matter in complex galaxy structures.
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| 33. |
- Thomas, Minta, et al.
(författare)
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Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations
- 2023
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice.
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| 34. |
- Thomas, Minta, et al.
(författare)
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Genome-wide Modeling of Polygenic Risk Score in Colorectal Cancer Risk.
- 2020
-
Ingår i: American Journal of Human Genetics. - Cambridge : Elsevier BV. - 0002-9297 .- 1537-6605. ; 107:3, s. 432-444
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Tidskriftsartikel (refereegranskat)abstract
- Accurate colorectal cancer (CRC) risk prediction models are critical for identifying individuals at low and high risk of developing CRC, as they can then be offered targeted screening and interventions to address their risks of developing disease (if they are in a high-risk group) and avoid unnecessary screening and interventions (if they are in a low-risk group). As it is likely that thousands of genetic variants contribute to CRC risk, it is clinically important to investigate whether these genetic variants can be used jointly for CRC risk prediction. In this paper, we derived and compared different approaches to generating predictive polygenic risk scores (PRS) from genome-wide association studies (GWASs) including 55,105 CRC-affected case subjects and 65,079 control subjects of European ancestry. We built the PRS in three ways, using (1) 140 previously identified and validated CRC loci; (2) SNP selection based on linkage disequilibrium (LD) clumping followed by machine-learning approaches; and (3) LDpred, a Bayesian approach for genome-wide risk prediction. We tested the PRS in an independent cohort of 101,987 individuals with 1,699 CRC-affected case subjects. The discriminatory accuracy, calculated by the age- and sex-adjusted area under the receiver operating characteristics curve (AUC), was highest for the LDpred-derived PRS (AUC = 0.654) including nearly 1.2 M genetic variants (the proportion of causal genetic variants for CRC assumed to be 0.003), whereas the PRS of the 140 known variants identified from GWASs had the lowest AUC (AUC = 0.629). Based on the LDpred-derived PRS, we are able to identify 30% of individuals without a family history as having risk for CRC similar to those with a family history of CRC, whereas the PRS based on known GWAS variants identified only top 10% as having a similar relative risk. About 90% of these individuals have no family history and would have been considered average risk under current screening guidelines, but might benefit from earlier screening. The developed PRS offers a way for risk-stratified CRC screening and other targeted interventions.
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| 35. |
- Augustin, Ramona, et al.
(författare)
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MUSE-ALMA Haloes X : the stellar masses of gas-rich absorbing galaxies
- 2024
-
Ingår i: Monthly notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 528:4, s. 6159-6166
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Tidskriftsartikel (refereegranskat)abstract
- The physical processes by which gas is accreted onto galaxies, transformed into stars, and then expelled from galaxies are of paramount importance to galaxy evolution studies. Observationally constraining each of these baryonic components in the same system, however, is challenging. Furthermore, simulations indicate that the stellar mass of galaxies is a key factor influencing CGM properties. Indeed, absorption lines detected against background quasars offer the most compelling way to study the cold gas in the circumgalactic medium (CGM). The MUSE-ALMA Haloes survey is composed of quasar fields covered with VLT/MUSE observations, comprising 32 H I absorbers at 0.2 < z < 1.4 and 79 associated galaxies, with available or upcoming molecular gas measurements from ALMA. We use a dedicated 40-orbit HST UVIS and IR WFC3 broad-band imaging campaign to characterize the stellar content of these galaxies. By fitting their spectral energy distribution, we establish they probe a wide range of stellar masses: 8.1 < log (M∗/M⊙) < 12.4. Given their star formation rates, most of these objects lie on the main sequence of galaxies. We also confirm a previously reported anticorrelation between the stellar masses and CGM hydrogen column density N (H I), indicating an evolutionary trend where higher mass galaxies are less likely to host large amounts of H I gas in their immediate vicinity up to 120 kpc. Together with other studies from the MUSE-ALMA Haloes survey, these data provide stellar masses of absorber hosts, a key component of galaxy formation and evolution, and observational constraints on the relation between galaxies and their surrounding medium.
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| 36. |
- Bragaglia, A., et al.
(författare)
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The Gaia-ESO Survey : Target selection of open cluster stars & x22c6
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 659
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Tidskriftsartikel (refereegranskat)abstract
- Context. The Gaia-ESO Survey (GES) is a public, high-resolution spectroscopic survey, conducted with the multi-object spectrograph Fibre Large Array Multi Element Spectrograph (FLAMES) on the Very Large Telescope (European Southern Observatory, ESO, Cerro Paranal, Chile) from December 2011 to January 2018. Gaia-ESO has targeted all the main stellar components of the Milky Way, including thin and thick disc, bulge, and halo. In particular, a large sample of open clusters has been observed, from very young ones, just out of the embedded phase, to very old ones. Aims. The different kinds of clusters and stars targeted in them are useful to reach the main science goals of the open cluster part of GES, which are the study of the open cluster structure and dynamics, the use of open clusters to constrain and improve stellar evolution models, and the definition of Galactic disc properties (e.g., metallicity distribution). Methods. The Gaia-ESO Survey is organised in 19 working groups (WGs), each one being responsible for a task. We describe here the work of three of them, one in charge of the selection of the targets within each cluster or association (WG4), one responsible for defining the most probable candidate member stars (WG1), and another one in charge of the preparation of the observations (WG6). As the entire GES has been conducted before the second Gaia data release, we could not make use of the Gaia astrometry to define cluster member candidates. We made use of public and private photometry to select the stars to be observed with FLAMES, once brought on a common astrometric system (the one defined by 2MASS). Candidate target selection was based on ground-based proper motions, radial velocities, and X-ray properties when appropriate, for example, and it was mostly used to define the position of the clusters' evolutionary sequences in the colour-magnitude diagrams. Targets for GIRAFFE were then selected near the sequences in an unbiased way. We used known information on membership, when available, only for the few stars to be observed with UVES. Results. We collected spectra for 62 confirmed clusters in the main observing campaign (and a few more clusters were taken from the ESO archive). Among them are very young clusters, where the main targets are pre-main sequence stars, clusters with very hot and massive stars currently on the main sequence, intermediate-age and old clusters where evolved stars are the main targets. Our strategy of making the selection of targets as inclusive and unbiased as possible and of observing a significant and representative fraction of all possible targets permitted us to collect the largest, most accurate, and most homogeneous spectroscopic data set on open star clusters ever achieved.
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| 37. |
- Chen, Zhishan, et al.
(författare)
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Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
- 2024
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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| 38. |
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| 39. |
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| 40. |
- Maurichi, A, et al.
(författare)
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Reply to E. Hindié
- 2020
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 38:27, s. 3238-
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 41. |
- Solé Navais, Pol, et al.
(författare)
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Genetic effects on the timing of parturition and links to fetal birth weight.
- 2023
-
Ingår i: Nature genetics. - 1546-1718. ; 55:4, s. 559-567
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Tidskriftsartikel (refereegranskat)abstract
- The timing of parturition is crucial for neonatal survival and infant health. Yet, its genetic basis remains largely unresolved. We present a maternal genome-wide meta-analysis of gestational duration (n=195,555), identifying 22 associated loci (24 independent variants) and an enrichment in genes differentially expressed during labor. A meta-analysis of preterm delivery (18,797 cases, 260,246 controls) revealed six associated loci and large genetic similarities with gestational duration. Analysis of the parental transmitted and nontransmitted alleles (n=136,833) shows that 15 of the gestational duration genetic variants act through the maternal genome, whereas 7 act both through the maternal and fetal genomes and 2 act only via the fetal genome. Finally, the maternal effects on gestational duration show signs of antagonistic pleiotropy with the fetal effects on birth weight: maternal alleles that increase gestational duration have negative fetal effects on birth weight. The present study provides insights into the genetic effects on the timing of parturition and the complex maternal-fetal relationship between gestational duration and birth weight.
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| 42. |
- Solomonidou, A., et al.
(författare)
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Spectral and emissivity analysis of the raised ramparts around Titan's northern lakes
- 2020
-
Ingår i: Icarus. - : Academic Press. - 0019-1035 .- 1090-2643. ; 344
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Tidskriftsartikel (refereegranskat)abstract
- Some of Titan's small northern hemisphere lakes show raised rampart features (which are distinct from raised rims), and appear as SAR-bright mound-like annuli extending away from the lake for up to tens of kilometers from the shoreline. We investigate the infrared and microwave characteristics of these features using Cassini Visual and Infrared Mapping Spectrometer (VIMS) and RADAR data. A spectral comparative analysis is performed among the lakes, their ramparts, and the surrounding regions. We overcome the profound difference in spatial resolution between VIMS and SAR data by using a method that provides overlays between the spectral images and SAR, thus enabling the correct selection of VIMS pixels. The surface properties of the selected areas are obtained using a radiative transfer analysis on the selected VIMS pixels, in addition to emissivity obtained from the RADAR in radiometry mode. Analysis of these combined and co-registered data provides constraints for the formation mechanism(s) of raised ramparts. The results show that the emissivity of the raised ramparts is close to that of Titan's labyrinthic terrains and to that of empty lake floors in the northern polar regions. This is confirmed by the VIMS analysis that also shows that the infrared spectral response of the raised ramparts is very similar to that of some empty lake floors. This suggests that both areas are made from or are covered by a similar material. In addition, two out of the eight lakes with raised ramparts show spectral differences at three specific wavelengths, 1.6, 2.0, and 5.0 mu m, between the ramparts and the surrounding terrain. We hypothesize that this could be due to some component, or mixture of components in the ramparts that is less absorbent at these specific wavelengths, or it could be an effect of different grain sizes. These observations provide first insights into the possible mechanisms leading to the formation of the raised ramparts that are discussed here.
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| 43. |
- Su, Yu-Ru, et al.
(författare)
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Validation of a genetic-enhanced risk prediction model for colorectal cancer in a large community-based cohort
- 2023
-
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American association for cancer research. - 1055-9965 .- 1538-7755. ; 32:3, s. 353-362
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Polygenic risk scores (PRS) which summarize individuals' genetic risk profile may enhance targeted colorectal cancer screening. A critical step towards clinical implementation is rigorous external validations in large community-based cohorts. This study externally validated a PRS-enhanced colorectal cancer risk model comprising 140 known colorectal cancer loci to provide a comprehensive assessment on prediction performance.METHODS: The model was developed using 20,338 individuals and externally validated in a community-based cohort (n = 85,221). We validated predicted 5-year absolute colorectal cancer risk, including calibration using expected-to-observed case ratios (E/O) and calibration plots, and discriminatory accuracy using time-dependent AUC. The PRS-related improvement in AUC, sensitivity and specificity were assessed in individuals of age 45 to 74 years (screening-eligible age group) and 40 to 49 years with no endoscopy history (younger-age group).RESULTS: In European-ancestral individuals, the predicted 5-year risk calibrated well [E/O = 1.01; 95% confidence interval (CI), 0.91-1.13] and had high discriminatory accuracy (AUC = 0.73; 95% CI, 0.71-0.76). Adding the PRS to a model with age, sex, family and endoscopy history improved the 5-year AUC by 0.06 (P < 0.001) and 0.14 (P = 0.05) in the screening-eligible age and younger-age groups, respectively. Using a risk-threshold of 5-year SEER colorectal cancer incidence rate at age 50 years, adding the PRS had a similar sensitivity but improved the specificity by 11% (P < 0.001) in the screening-eligible age group. In the younger-age group it improved the sensitivity by 27% (P = 0.04) with similar specificity.CONCLUSIONS: The proposed PRS-enhanced model provides a well-calibrated 5-year colorectal cancer risk prediction and improves discriminatory accuracy in the external cohort.IMPACT: The proposed model has potential utility in risk-stratified colorectal cancer prevention.
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| 44. |
- Vaughan, A., et al.
(författare)
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Regolith of the Crater Floor Units, Jezero Crater, Mars : Textures, Composition, and Implications for Provenance
- 2023
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Ingår i: Journal of Geophysical Research - Planets. - : John Wiley and Sons Inc. - 2169-9097 .- 2169-9100. ; 128:3
-
Tidskriftsartikel (refereegranskat)abstract
- A multi-instrument study of the regolith of Jezero crater floor units by the Perseverance rover has identified three types of regolith: fine-grained, coarse-grained, and mixed-type. Mastcam-Z, Wide Angle Topographic Sensor for Operations and eNgineering, and SuperCam Remote Micro Imager were used to characterize the regolith texture, particle size, and roundedness where possible. Mastcam-Z multispectral and SuperCam laser-induced breakdown spectroscopy data were used to constrain the composition of the regolith types. Fine-grained regolith is found surrounding bedrock and boulders, comprising bedforms, and accumulating on top of rocks in erosional depressions. Spectral and chemical data show it is compositionally consistent with pyroxene and a ferric-oxide phase. Coarse-grained regolith consists of 1–2 mm well-sorted gray grains that are found concentrated around the base of boulders and bedrock, and armoring bedforms. Its chemistry and spectra indicate it is olivine-bearing, and its spatial distribution and roundedness indicate it has been transported, likely by saltation-induced creep. Coarse grains share similarities with the olivine grains observed in the Séítah formation bedrock, making that unit a possible source for these grains. Mixed-type regolith contains fine- and coarse-grained regolith components and larger rock fragments. The rock fragments are texturally and spectrally similar to bedrock within the Máaz and Séítah formations, indicating origins by erosion from those units, although they could also be a lag deposit from erosion of an overlying unit. The fine- and coarse-grained types are compared to their counterparts at other landing sites to inform global, regional, and local inputs to regolith formation within Jezero crater. The regolith characterization presented here informs the regolith sampling efforts underway by Perseverance. © 2023. The Authors.
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| 45. |
- Weng, S., et al.
(författare)
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MUSE-ALMA Haloes – VIII. Statistical study of circumgalactic medium gas
- 2023
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 519:1, s. 931-947
-
Tidskriftsartikel (refereegranskat)abstract
- The distribution of gas and metals in the circumgalactic medium (CGM) plays a critical role in how galaxies evolve. The MUSE-ALMA Haloes survey combines MUSE, ALMA, and HST observations to constrain the properties of the multiphase gas in the CGM and the galaxies associated with the gas probed in absorption. In this paper, we analyse the properties of galaxies associated with 32 strong HI Ly-α absorbers at redshift 0.2 ≲ z ≲ 1.4. We detect 79 galaxies within ±500 kms−1 of the absorbers in our 19 MUSE fields. These associated galaxies are found at physical distances from 5.7 kpc and reach star formation rates as low as 0.1 M⊙ yr−1. The significant number of associated galaxies allows us to map their physical distribution on the Δv and b plane. Building on previous studies, we examine the physical and nebular properties of these associated galaxies and find the following: (i) 27/32 absorbers have galaxy counterparts and more than 50 per cent of the absorbers have two or more associated galaxies, (ii) the HIHI column density of absorbers is anticorrelated with the impact parameter (scaled by virial radius) of the nearest galaxy as expected from simulations, (iii) the metallicity of associated galaxies is typically larger than the absorber metallicity, which decreases at larger impact parameters. It becomes clear that while strong HIHI absorbers are typically associated with more than a single galaxy, we can use them to statistically map the gas and metal distribution in the CGM.
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| 46. |
- Keilholz, U., et al.
(författare)
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ESMO consensus conference recommendations on the management of metastatic melanoma: under the auspices of the ESMO Guidelines Committee
- 2020
-
Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 31:11, s. 1435-1448
-
Tidskriftsartikel (refereegranskat)abstract
- The European Society for Medical Oncology (ESMO) held a consensus conference on melanoma on 5-7 September 2019 in Amsterdam, The Netherlands. The conference included a multidisciplinary panel of 32 leading experts in the management of melanoma. The aim of the conference was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where available evidence is either limited or conflicting. The main topics identified for discussion were (i) the management of locoregional disease; (ii) targeted versus immunotherapies in the adjuvant setting; (iii) targeted versus immunotherapies for the first-line treatment of metastatic melanoma; (iv) when to stop immunotherapy or targeted therapy in the metastatic setting; and (v) systemic versus local treatment for brain metastases. The expert panel was divided into five working groups to each address questions relating to one of the five topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the results relating to the management of metastatic melanoma, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.
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| 47. |
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| 48. |
- Marques-Chaves, R., et al.
(författare)
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No correlation of the Lyman continuum escape fraction with spectral hardness
- 2022
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 663
-
Tidskriftsartikel (refereegranskat)abstract
- The properties that govern the production and escape of hydrogen-ionizing photons (Lyman continuum, LyC; with energies > 13.6 eV) in star-forming galaxies are still poorly understood, but they are key to identifying and characterizing the sources that reionized the Universe. Here we empirically explore the relation between the hardness of ionizing radiation and the LyC leakage in a large sample of low-z star-forming galaxies from the recent Hubble Space Telescope Low-z Lyman Continuum Survey. Using Sloan Digital Sky Survey stacks and deep X-shooter observations, we investigate the hardness of the ionizing spectra (QHe+/QH) between 54.4 eV (He+) and 13.6 eV (H) from the optical recombination lines He II 4686 Å and Hβ 4861 Å for galaxies with LyC escape fractions spanning a wide range, fesc(LyC) ≃ 0−90%. We find that the observed intensity of He II/Hβ is primarily driven by variations in the metallicity, but is not correlated with LyC leakage. Both very strong (esc(LyC)> ≃ 0.5) and nonleakers (esc(LyC)> ≃ 0) present similar observed intensities of He II and Hβ at comparable metallicity, between ≃0.01 and ≃0.02 for 12 + log(O/H)> 8.0 and < 8.0, respectively. Our results demonstrate that QHe+/QH does not correlate with fesc(LyC), which implies that strong LyC emitters do not show harder ionizing spectra than nonleakers at similar metallicity.
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| 49. |
- Michielin, O., et al.
(författare)
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ESMO consensus conference recommendations on the management of locoregional melanoma: under the auspices of the ESMO Guidelines Committee
- 2020
-
Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 31:11, s. 1449-1461
-
Tidskriftsartikel (refereegranskat)abstract
- The European Society for Medical Oncology (ESMO) held a consensus conference on melanoma on 5-7 September 2019 in Amsterdam, The Netherlands. The conference included a multidisciplinary panel of 32 leading experts in the management of melanoma. The aim of the conference was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where available evidence is either limited or conflicting. The main topics identified for discussion were: (i) the management of locoregional disease; (ii) targeted versus immunotherapies in the adjuvant setting; (iii) targeted versus immunotherapies for the first-line treatment of metastatic melanoma; (iv) when to stop immunotherapy or targeted therapy in the metastatic setting; and (v) systemic versus local treatment of brain metastases. The expert panel was divided into five working groups in order to each address questions relating to one of the five topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the results relating to the management of locoregional melanoma, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.
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| 50. |
- Neville, S. L., et al.
(författare)
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The structural basis of bacterial manganese import
- 2021
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:32
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Tidskriftsartikel (refereegranskat)abstract
- Metal ions are essential for all forms of life. In prokaryotes, ATP-binding cassette (ABC) permeases serve as the primary import pathway for many micronutrients including the first-row transition metal manganese. However, the structural features of ionic metal transporting ABC permeases have remained undefined. Here, we present the crystal structure of the manganese transporter PsaBC from Streptococcus pneumoniae in an open-inward conformation. The type II transporter has a tightly closed transmembrane channel due to "extracellular gating" residues that prevent water permeation or ion reflux. Below these residues, the channel contains a hitherto unreported metal coordination site, which is essential for manganese translocation. Mutagenesis of the extracellular gate perturbs manganese uptake, while coordination site mutagenesis abolishes import. These structural features are highly conserved in metal-specific ABC transporters and are represented throughout the kingdoms of life. Collectively, our results define the structure of PsaBC and reveal the features required for divalent cation transport.
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