| 1. |
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| 2. |
- Aaron, F. D., et al.
(författare)
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Combined measurement and QCD analysis of the inclusive e(+/-)p scattering cross sections at HERA
- 2010
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :1
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Tidskriftsartikel (refereegranskat)abstract
- A combination is presented of the inclusive deep inelastic cross sections measured by the H1 and ZEUS Collaborations in neutral and charged current unpolarised e(+/-)p scattering at HERA during the period 1994-2000. The data span six orders of magnitude in negative four-momentum-transfer squared, Q(2), and in Bjorken x. The combination method used takes the correlations of systematic uncertainties into account, resulting in an improved accuracy. The combined data are the sole input in a NLO QCD analysis which determines a new set of parton distributions, HERAPDF1.0, with small experimental uncertainties. This set includes an estimate of the model and parametrisation uncertainties of the fit result.
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| 3. |
- Aaron, F. D., et al.
(författare)
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Events with an isolated lepton and missing transverse momentum and measurement of W production at HERA
- 2010
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; 2010:3, s. 1-19
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Tidskriftsartikel (refereegranskat)abstract
- A search for events containing an isolated electron or muon and missing trans verse momentum produced in e(+/-)p collisions is performed with the H1 and ZEUS detectors at HERA. The data were taken in the period 1994-2007 and correspond to an integrated luminosity of 0.98 fb(-1). The observed event yields are in good overall agreement with the Standard Model prediction, which is dominated by single W production. In the e(+)p data, at large hadronic transverse momentum P-T(X) > 25GeV, a total of 23 events are observed compared to a prediction of 14.0 +/- 1.9. The total single W boson production cross section is measured as 1.06 +/- 0.16 (stat.) +/- 0.07 (sys.) pb, in agreement with an Standard Model (SM) expectation of 1.26 +/- 0.19 pb.
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| 4. |
- Aaron, F. D., et al.
(författare)
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Multi-leptons with high transverse momentum at HERA
- 2009
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Ingår i: Journal of High Energy Physics. - : Springer Science and Business Media LLC. - 1029-8479. ; :10
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Tidskriftsartikel (refereegranskat)abstract
- Events with at least two high transverse momentum leptons (electrons or muons) are studied using the H1 and ZEUS detectors at HERA with an integrated luminosity of 0.94 fb(-1). The observed numbers of events are in general agreement with the Standard Model predictions. Seven di- and tri-lepton events are observed in e(+)p collision data with a scalar sum of the lepton transverse momenta above 100 GeV while 1.94 +/- 0.17 events are expected. Such events are not observed in e(-)p collisions for which 1.19 +/- 0.12 are predicted. Total visible and differential di-electron and di-muon photoproduction cross sections are extracted in a restricted phase space dominated by photon-photon collisions.
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| 5. |
- Aaron, F. D., et al.
(författare)
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Combined inclusive diffractive cross sections measured with forward proton spectrometers in deep inelastic ep scattering at HERA
- 2012
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 72:10
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Tidskriftsartikel (refereegranskat)abstract
- A combination of the inclusive diffractive cross section measurements made by the H1 and ZEUS Collaborations at HERA is presented. The analysis uses samples of diffractive deep inelastic ep scattering data at a centre-of-mass energy root s = 318 GeV where leading protons are detected by dedicated spectrometers. Correlations of systematic uncertainties are taken into account, resulting in an improved precision of the cross section measurement which reaches 6 % for the most precise points. The combined data cover the range 2.5 < Q(2) < 200 GeV2 in photon virtuality, 0.00035 < x(P) < 0.09 in proton fractional momentum loss, 0.09 < vertical bar t vertical bar < 0.55 GeV2 in squared four-momentum transfer at the proton vertex and 0.0018 < beta < 0.816 in beta = x/x(P), where x is the Bjorken scaling variable.
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| 6. |
- Abramowicz, H., et al.
(författare)
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Combination and QCD analysis of charm production cross section measurements in deep-inelastic ep scattering at HERA
- 2013
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 73:2
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Tidskriftsartikel (refereegranskat)abstract
- Measurements of open charm production cross sections in deep-inelastic ep scattering at HERA from the H1 and ZEUS Collaborations are combined. Reduced cross sections sigma(c (c) over bar)(red) for charm production are obtained in the kinematic range of photon virtuality 2.5 <= Q(2) <= 2000 GeV2 and Bjorken scaling variable 3 . 10(-5) <= x <= 5 . 10(-2). The combination method accounts for the correlations of the systematic uncertainties among the different data sets. The combined charm data together with the combined inclusive deep-inelastic scattering cross sections from HERA are used as input for a detailed NLO QCD analysis to study the influence of different heavy flavour schemes on the parton distribution functions. The optimal values of the charm mass as a parameter in these different schemes are obtained. The implications on the NLO predictions for W-+/- and Z production cross sections at the LHC are investigated. Using the fixed flavour number scheme, the running mass of the charm quark is determined.
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| 7. |
- Cossarizza, A., et al.
(författare)
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Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
- 2019
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Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
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Tidskriftsartikel (refereegranskat)abstract
- These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
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| 8. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 9. |
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| 10. |
- Rheinbay, E, et al.
(författare)
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Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 102-
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of drivers of cancer has traditionally focused on protein-coding genes1–4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5′ region of TP53, in the 3′ untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.
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| 11. |
- Flannick, Jason, et al.
(författare)
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Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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| 12. |
- Fuchsberger, Christian, et al.
(författare)
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The genetic architecture of type 2 diabetes
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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| 13. |
- Ahearn, Thomas U., et al.
(författare)
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Common variants in breast cancer risk loci predispose to distinct tumor subtypes
- 2022
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Ingår i: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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| 14. |
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| 15. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 16. |
- 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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| 17. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 18. |
- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 19. |
- Mueller, Stefanie H., et al.
(författare)
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Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry
- 2023
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Ingår i: Genome Medicine. - : BioMed Central (BMC). - 1756-994X. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.Methods: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.Results: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 x 10(-6)) and AC058822.1 (P = 1.47 x 10(-4)), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C.Conclusions: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 x 10(-5)), demonstrating the importance of diversifying study cohorts.
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| 20. |
- Namkoong, H, et al.
(författare)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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| 21. |
- Pinto, Dalila, et al.
(författare)
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Functional impact of global rare copy number variation in autism spectrum disorders.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7304, s. 368-372
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Tidskriftsartikel (refereegranskat)abstract
- The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
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| 22. |
- Verra, L., et al.
(författare)
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Controlled Growth of the Self-Modulation of a Relativistic Proton Bunch in Plasma
- 2022
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Ingår i: Physical Review Accelerators and Beams. - : American Physical Society. - 2469-9888. ; 25:7
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Tidskriftsartikel (refereegranskat)abstract
- A long, narrow, relativistic charged particle bunch propagating in plasma is subject to the self -modulation (SM) instability. We show that SM of a proton bunch can be seeded by the wakefields driven by a preceding electron bunch. SM timing reproducibility and control are at the level of a small fraction of the modulation period. With this seeding method, we independently control the amplitude of the seed wakefields with the charge of the electron bunch and the growth rate of SM with the charge of the proton bunch. Seeding leads to larger growth of the wakefields than in the instability case.
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| 23. |
- Anney, Richard, et al.
(författare)
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A genome-wide scan for common alleles affecting risk for autism.
- 2010
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082
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Tidskriftsartikel (refereegranskat)abstract
- Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
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| 24. |
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| 25. |
- Anney, Richard, et al.
(författare)
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Individual common variants exert weak effects on the risk for autism spectrum disorders.
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:21, s. 4781-92
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Tidskriftsartikel (refereegranskat)abstract
- While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASD), the contribution of common variation to ASD risk is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating association of individual SNPs, we also sought evidence that common variants, en masse, might affect risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest p-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. By contrast, allele-scores derived from the transmission of common alleles to Stage 1 cases significantly predict case-status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele-score results, it is reasonable to conclude that common variants affect ASD risk but their individual effects are modest.
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| 26. |
- Nechaeva, T., et al.
(författare)
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Hosing of a Long Relativistic Particle Bunch in Plasma
- 2024
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 132:7
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Tidskriftsartikel (refereegranskat)abstract
- Experimental results show that hosing of a long particle bunch in plasma can be induced by wakefields driven by a short, misaligned preceding bunch. Hosing develops in the plane of misalignment, selfmodulation in the perpendicular plane, at frequencies close to the plasma electron frequency, and are reproducible. Development of hosing depends on misalignment direction, its growth on misalignment extent and on proton bunch charge. Results have the main characteristics of a theoretical model, are relevant to other plasma -based accelerators and represent the first characterization of hosing.
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| 27. |
- Verra, L., et al.
(författare)
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Development of the self-modulation instability of a relativistic proton bunch in plasma
- 2023
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Ingår i: Physics of Plasmas. - : American Institute of Physics (AIP). - 1070-664X .- 1089-7674. ; 30:8
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Tidskriftsartikel (refereegranskat)abstract
- Self-modulation is a beam-plasma instability that is useful to drive large-amplitude wakefields with bunches much longer than the plasma skin depth. We present experimental results showing that, when increasing the ratio between the initial transverse size of the bunch and the plasma skin depth, the instability occurs later along the bunch, or not at all, over a fixed plasma length because the amplitude of the initial wakefields decreases. We show cases for which self-modulation does not develop, and we introduce a simple model discussing the conditions for which it would not occur after any plasma length. Changing bunch size and plasma electron density also changes the growth rate of the instability. We discuss the impact of these results on the design of a particle accelerator based on the self-modulation instability seeded by a relativistic ionization front, such as the future upgrade of the Advanced WAKefield Experiment.
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| 28. |
- Casey, Jillian P, et al.
(författare)
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A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder.
- 2012
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Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 131:4, s. 565-579
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
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| 29. |
- Haywood, Alan M., et al.
(författare)
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The Pliocene Model Intercomparison Project Phase 2 : large-scale climate features and climate sensitivity
- 2020
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 16:6, s. 2095-2123
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Tidskriftsartikel (refereegranskat)abstract
- The Pliocene epoch has great potential to improve our understanding of the long-term climatic and environmental consequences of an atmospheric CO2 concentration near similar to 400 parts per million by volume. Here we present the large-scale features of Pliocene climate as simulated by a new ensemble of climate models of varying complexity and spatial resolution based on new reconstructions of boundary conditions (the Pliocene Model Intercomparison Project Phase 2; PlioMIP2). As a global annual average, modelled surface air temperatures increase by between 1.7 and 5.2 degrees C relative to the pre-industrial era with a multi-model mean value of 3.2 degrees C. Annual mean total precipitation rates increase by 7 % (range: 2 %-13 %). On average, surface air temperature (SAT) increases by 4.3 degrees C over land and 2.8 degrees C over the oceans. There is a clear pattern of polar amplification with warming polewards of 60 degrees N and 60 degrees S exceeding the global mean warming by a factor of 2.3. In the Atlantic and Pacific oceans, meridional temperature gradients are reduced, while tropical zonal gradients remain largely unchanged. There is a statistically significant relationship between a model's climate response associated with a doubling in CO2 (equilibrium climate sensitivity; ECS) and its simulated Pliocene surface temperature response. The mean ensemble Earth system response to a doubling of CO2 (including ice sheet feedbacks) is 67 % greater than ECS; this is larger than the increase of 47 % obtained from the PlioMIP1 ensemble. Proxy-derived estimates of Pliocene sea surface temperatures are used to assess model estimates of ECS and give an ECS range of 2.6-4.8 degrees C. This result is in general accord with the ECS range presented by previous Intergovernmental Panel on Climate Change (IPCC) Assessment Reports.
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| 30. |
- Lunt, Daniel J., et al.
(författare)
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The DeepMIP contribution to PMIP4 : experimental design for model simulations of the EECO, PETM, and pre-PETM (version 1.0)
- 2017
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 10:2, s. 889-901
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Tidskriftsartikel (refereegranskat)abstract
- Past warm periods provide an opportunity to evaluate climate models under extreme forcing scenarios, in particular high (>800 ppmv) atmospheric CO2 concentrations. Although a post hoc intercomparison of Eocene (similar to 50 Ma) climate model simulations and geological data has been carried out previously, models of past high-CO2 periods have never been evaluated in a consistent framework. Here, we present an experimental design for climate model simulations of three warm periods within the early Eocene and the latest Paleocene (the EECO, PETM, and pre-PETM). Together with the CMIP6 pre-industrial control and abrupt 4 x CO2 simulations, and additional sensitivity studies, these form the first phase of DeepMIP - the Deep-time Model Intercomparison Project, itself a group within the wider Paleo-climate Modelling Intercomparison Project (PMIP). The experimental design specifies and provides guidance on boundary conditions associated with palaeogeography, greenhouse gases, astronomical configuration, solar constant, land surface processes, and aerosols. Initial conditions, simulation length, and output variables are also specified. Finally, we explain how the geological data sets, which will be used to evaluate the simulations, will be developed.
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| 31. |
- Abramowicz, H., et al.
(författare)
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Conceptual design report for the LUXE experiment
- 2021
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Ingår i: European Physical Journal-Special Topics. - : Springer Science and Business Media LLC. - 1951-6355 .- 1951-6401. ; 230:11, s. 2445-2560
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Tidskriftsartikel (refereegranskat)abstract
- This Conceptual Design Report describes LUXE (Laser Und XFEL Experiment), an experimental campaign that aims to combine the high-quality and high-energy electron beam of the European XFEL with a powerful laser to explore the uncharted terrain of quantum electrodynamics characterised by both high energy and high intensity. We will reach this hitherto inaccessible regime of quantum physics by analysing high-energy electron-photon and photon-photon interactions in the extreme environment provided by an intense laser focus. The physics background and its relevance are presented in the science case which in turn leads to, and justifies, the ensuing plan for all aspects of the experiment: Our choice of experimental parameters allows (i) field strengths to be probed where the coupling to charges becomes non-perturbative and (ii) a precision to be achieved that permits a detailed comparison of the measured data with calculations. In addition, the high photon flux predicted will enable a sensitive search for new physics beyond the Standard Model. The initial phase of the experiment will employ an existing 40 TW laser, whereas the second phase will utilise an upgraded laser power of 350 TW. All expectations regarding the performance of the experimental set-up as well as the expected physics results are based on detailed numerical simulations throughout.
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| 32. |
- Axelson, Olav, 1937-, et al.
(författare)
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Regulatory toxicology and pharmacology.
- 2003
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Ingår i: International journal of occupational and environmental health. - 1077-3525 .- 2049-3967. ; 9, s. 386-389
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Tidskriftsartikel (refereegranskat)
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| 33. |
- Berntell, Ellen, et al.
(författare)
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Mid-Pliocene West African Monsoon rainfall as simulated in the PlioMIP2 ensemble
- 2021
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 17:4, s. 1777-1794
-
Tidskriftsartikel (refereegranskat)abstract
- The mid-Pliocene warm period (mPWP; ∼3.2 million years ago) is seen as the most recent time period characterized by a warm climate state, with similar to modern geography and ∼400 ppmv atmospheric CO2 concentration, and is therefore often considered an interesting analogue for near-future climate projections. Paleoenvironmental reconstructions indicate higher surface temperatures, decreasing tropical deserts, and a more humid climate in West Africa characterized by a strengthened West African Monsoon (WAM). Using model results from the second phase of the Pliocene Modelling Intercomparison Project (PlioMIP2) ensemble, we analyse changes of the WAM rainfall during the mPWP by comparing them with the control simulations for the pre-industrial period. The ensemble shows a robust increase in the summer rainfall over West Africa and the Sahara region, with an average increase of 2.5 mm/d, contrasted by a rainfall decrease over the equatorial Atlantic. An anomalous warming of the Sahara and deepening of the Saharan Heat Low, seen in >90 % of the models, leads to a strengthening of the WAM and an increased monsoonal flow into the continent. A similar warming of the Sahara is seen in future projections using both phase 3 and 5 of the Coupled Model Intercomparison Project (CMIP3 and CMIP5). Though previous studies of future projections indicate a west–east drying–wetting contrast over the Sahel, PlioMIP2 simulations indicate a uniform rainfall increase in that region in warm climates characterized by increasing greenhouse gas forcing. We note that this effect will further depend on the long-term response of the vegetation to the CO2 forcing.
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| 34. |
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| 35. |
- Feng, Ran, et al.
(författare)
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Past terrestrial hydroclimate sensitivity controlled by Earth system feedbacks
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Despite tectonic conditions and atmospheric CO2 levels (pCO2) similar to those of present-day, geological reconstructions from the mid-Pliocene (3.3-3.0 Ma) document high lake levels in the Sahel and mesic conditions in subtropical Eurasia, suggesting drastic reorganizations of subtropical terrestrial hydroclimate during this interval. Here, using a compilation of proxy data and multi-model paleoclimate simulations, we show that the mid-Pliocene hydroclimate state is not driven by direct CO2 radiative forcing but by a loss of northern high-latitude ice sheets and continental greening. These ice sheet and vegetation changes are long-term Earth system feedbacks to elevated pCO2. Further, the moist conditions in the Sahel and subtropical Eurasia during the mid-Pliocene are a product of enhanced tropospheric humidity and a stationary wave response to the surface warming pattern, which varies strongly with land cover changes. These findings highlight the potential for amplified terrestrial hydroclimate responses over long timescales to a sustained CO2 forcing.
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| 36. |
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| 37. |
- Gudbjartsson, Daniel F., et al.
(författare)
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Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:3, s. 342-347
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).
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| 38. |
- Kasliwal, Mansi M., et al.
(författare)
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Kilonova Luminosity Function Constraints Based on Zwicky Transient Facility Searches for 13 Neutron Star Merger Triggers during O3
- 2020
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 905:2
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Tidskriftsartikel (refereegranskat)abstract
- We present a systematic search for optical counterparts to 13 gravitational wave (GW) triggers involving at least one neutron star during LIGO/Virgo's third observing run (O3). We searched binary neutron star (BNS) and neutron star black hole (NSBH) merger localizations with the Zwicky Transient Facility (ZTF) and undertook follow-up with the Global Relay of Observatories Watching Transients Happen (GROWTH) collaboration. The GW triggers had a median localization area of 4480 deg(2), a median distance of 267 Mpc, and false-alarm rates ranging from 1.5 to 10(-25) yr(-1). The ZTF coverage in the g and r bands had a median enclosed probability of 39%, median depth of 20.8 mag, and median time lag between merger and the start of observations of 1.5 hr. The O3 follow-up by the GROWTH team comprised 340 UltraViolet/Optical/InfraRed (UVOIR) photometric points, 64 OIR spectra, and three radio images using 17 different telescopes. We find no promising kilonovae (radioactivity-powered counterparts), and we show how to convert the upper limits to constrain the underlying kilonova luminosity function. Initially, we assume that all GW triggers are bona fide astrophysical events regardless of false-alarm rate and that kilonovae accompanying BNS and NSBH mergers are drawn from a common population; later, we relax these assumptions. Assuming that all kilonovae are at least as luminous as the discovery magnitude of GW170817 (-16.1 mag), we calculate that our joint probability of detecting zero kilonovae is only 4.2%. If we assume that all kilonovae are brighter than -16.6 mag (the extrapolated peak magnitude of GW170817) and fade at a rate of 1 mag day(-1) (similar to GW170817), the joint probability of zero detections is 7%. If we separate the NSBH and BNS populations based on the online classifications, the joint probability of zero detections, assuming all kilonovae are brighter than -16.6 mag, is 9.7% for NSBH and 7.9% for BNS mergers. Moreover, no more than <57% (<89%) of putative kilonovae could be brighter than -16.6 mag assuming flat evolution (fading by 1 mag day(-1)) at the 90% confidence level. If we further take into account the online terrestrial probability for each GW trigger, we find that no more than <68% of putative kilonovae could be brighter than -16.6 mag. Comparing to model grids, we find that some kilonovae must have M-ej M, X-lan > 10(-4), or > 30 degrees to be consistent with our limits. We look forward to searches in the fourth GW observing run; even 17 neutron star mergers with only 50% coverage to a depth of -16 mag would constrain the maximum fraction of bright kilonovae to <25%.
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| 39. |
- Lai, Ian-Lin, et al.
(författare)
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Gas outflow and dust transport of comet 67P/Churyumov-Gerasimenko
- 2016
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Ingår i: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 462, s. S533-S546
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Tidskriftsartikel (refereegranskat)abstract
- Because of the diurnal thermal cycle and the irregular shape of the nucleus, gas outflow of comet 67P/Churyumov-Gerasimenko could be highly anisotropic as indicated by the colliminated dust jet structures on the sunlit side. Based on the OSIRIS imaging observations of the outgassing effect, a simple model of surface sublimation can be constructed by taking into account the dependence on the solar insolation. With preliminary information on the time variability of the global gas production rate, a sequence of gas coma models can be generated at different epochs before and after perihelion. We also investigate different patterns of dust particle dynamics under the influences of nuclear rotation and gas drag. From these considerations, a consistent picture of the spatial distribution of dusty materials across the surface of comet 67P as it moves around the perihelion can be developed. It is found that because of the redeposition of the ejected dust from the Southern hemisphere to the Northern hemisphere during the southern summer season the Hapi region could gain up to 0.4 m while the Wosret region would lose up to 1.8 m of dust mantle per orbit.
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| 40. |
- Lunt, Daniel J., et al.
(författare)
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DeepMIP : model intercomparison of early Eocene climatic optimum (EECO) large-scale climate features and comparison with proxy data
- 2021
-
Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 17:1, s. 203-227
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Tidskriftsartikel (refereegranskat)abstract
- We present results from an ensemble of eight climate models, each of which has carried out simulations of the early Eocene climate optimum (EECO, similar to 50 million years ago). These simulations have been carried out in the framework of the Deep-Time Model Intercomparison Project (DeepMIP; http://www.deepmip.org , last access: 10 January 2021); thus, all models have been configured with the same paleogeographic and vegetation boundary conditions. The results indicate that these non-CO2 boundary conditions contribute between 3 and 5 degrees C to Eocene warmth. Compared with results from previous studies, the DeepMIP simulations generally show a reduced spread of the global mean surface temperature response across the ensemble for a given atmospheric CO2 concentration as well as an increased climate sensitivity on average. An energy balance analysis of the model ensemble indicates that global mean warming in the Eocene compared with the preindustrial period mostly arises from decreases in emissivity due to the elevated CO2 concentration (and associated water vapour and long-wave cloud feedbacks), whereas the reduction in the Eocene in terms of the meridional temperature gradient is primarily due to emissivity and albedo changes owing to the non-CO2 boundary conditions (i.e. the removal of the Antarctic ice sheet and changes in vegetation). Three of the models (the Community Earth System Model, CESM; the Geophysical Fluid Dynamics Laboratory, GFDL, model; and the Norwegian Earth System Model, NorESM) show results that are consistent with the proxies in terms of the global mean temperature, meridional SST gradient, and CO2, without prescribing changes to model parameters. In addition, many of the models agree well with the first-order spatial patterns in the SST proxies. However, at a more regional scale, the models lack skill. In particular, the modelled anomalies are substantially lower than those indicated by the proxies in the southwest Pacific; here, modelled continental surface air temperature anomalies are more consistent with surface air temperature proxies, implying a possible inconsistency between marine and terrestrial temperatures in either the proxies or models in this region. Our aim is that the documentation of the large-scale features and model-data comparison presented herein will pave the way to further studies that explore aspects of the model simulations in more detail, for example the ocean circulation, hydrological cycle, and modes of variability, and encourage sensitivity studies to aspects such as paleogeography, orbital configuration, and aerosols.
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| 41. |
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| 42. |
- Oldeman, Arthur M., et al.
(författare)
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Reduced El Niño variability in the mid-Pliocene according to the PlioMIP2 ensemble
- 2021
-
Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 17:6, s. 2427-2450
-
Tidskriftsartikel (refereegranskat)abstract
- The mid-Pliocene warm period (3.264–3.025 Ma) is the most recent geological period during which atmospheric CO2 levels were similar to recent historical values (∼400 ppm). Several proxy reconstructions for the mid-Pliocene show highly reduced zonal sea surface temperature (SST) gradients in the tropical Pacific Ocean, indicating an El Niño-like mean state. However, past modelling studies do not show these highly reduced gradients. Efforts to understand mid-Pliocene climate dynamics have led to the Pliocene Model Intercomparison Project (PlioMIP). Results from the first phase (PlioMIP1) showed clear El Niño variability (albeit significantly reduced) and did not show the greatly reduced time-mean zonal SST gradient suggested by some of the proxies.In this work, we study El Niño–Southern Oscillation (ENSO) variability in the PlioMIP2 ensemble, which consists of additional global coupled climate models and updated boundary conditions compared to PlioMIP1. We quantify ENSO amplitude, period, spatial structure and “flavour”, as well as the tropical Pacific annual mean state in mid-Pliocene and pre-industrial simulations. Results show a reduced ENSO amplitude in the model-ensemble mean (−24 %) with respect to the pre-industrial, with 15 out of 17 individual models showing such a reduction. Furthermore, the spectral power of this variability considerably decreases in the 3–4-year band. The spatial structure of the dominant empirical orthogonal function shows no particular change in the patterns of tropical Pacific variability in the model-ensemble mean, compared to the pre-industrial. Although the time-mean zonal SST gradient in the equatorial Pacific decreases for 14 out of 17 models (0.2 ∘C reduction in the ensemble mean), there does not seem to be a correlation with the decrease in ENSO amplitude. The models showing the most “El Niño-like” mean state changes show a similar ENSO amplitude to that in the pre-industrial reference, while models showing more “La Niña-like” mean state changes generally show a large reduction in ENSO variability. The PlioMIP2 results show a reasonable agreement with both time-mean proxies indicating a reduced zonal SST gradient and reconstructions indicating a reduced, or similar, ENSO variability.
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| 43. |
- Thompson, EJ, et al.
(författare)
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Long COVID burden and risk factors in 10 UK longitudinal studies and electronic health records
- 2022
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 3528-
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Tidskriftsartikel (refereegranskat)abstract
- The frequency of, and risk factors for, long COVID are unclear among community-based individuals with a history of COVID-19. To elucidate the burden and possible causes of long COVID in the community, we coordinated analyses of survey data from 6907 individuals with self-reported COVID-19 from 10 UK longitudinal study (LS) samples and 1.1 million individuals with COVID-19 diagnostic codes in electronic healthcare records (EHR) collected by spring 2021. Proportions of presumed COVID-19 cases in LS reporting any symptoms for 12+ weeks ranged from 7.8% and 17% (with 1.2 to 4.8% reporting debilitating symptoms). Increasing age, female sex, white ethnicity, poor pre-pandemic general and mental health, overweight/obesity, and asthma were associated with prolonged symptoms in both LS and EHR data, but findings for other factors, such as cardio-metabolic parameters, were inconclusive.
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| 44. |
- Auyeung, T. W., et al.
(författare)
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Sleep Duration and Disturbances Were Associated With Testosterone Level, Muscle Mass, and Muscle Strength-A Cross-Sectional Study in 1274 Older Men
- 2015
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Ingår i: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610. ; 16:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Testosterone level follows a circadian rhythm. However, whether sleep duration and disturbances can affect testosterone level, muscle mass, and strength remains unknown. Objective: To examine the relationship of sleep duration and disturbances to testosterone level, muscle mass, muscle strength, and walking speed. Participants and methods: We recruited 1274 community-dwelling men older than 65 years of age. Their early morning testosterone level was assayed by mass spectrometry. A sleep questionnaire was administered to enquire about their reported sleep duration, prolonged sleep latency (>0.5 hour), and subjective insomnia complaint. Muscle mass was measured by dual-energy x-ray absorptiometry. Testosterone level, muscle mass, handgrip strength, and walking speed were tested against sleep duration and disturbances. Results: Testosterone increased with increasing sleep duration up to 9.9 hours, after which it decreased, giving rise to an inverted U-shaped relationship (P for quadratic trend < .05). A similar inverted U-shaped relationship occurred between sleep duration and muscle mass and function. Earlier go-to-bed time, despite being associated with a higher testosterone level (P < .05), was associated with weaker grip strength (P < .05). Earlier wake-up time was associated with higher muscle mass (P < .05) but neither grip strength nor walking speed. Neither prolonged sleep latency nor insomnia was associated with testosterone levels. However, prolonged sleep latency was associated with lower muscle mass (P < .05), weaker grip strength (P < .05), and slower walking speed (P < .001). Insomnia, on the other hand was associated with weaker grip strength (P < .05) and slower walking speed (P < .001) but not muscle mass. Conclusions: Sleep duration and disturbances can affect testosterone level, muscle mass, and its function. Whether optimization of sleep can ameliorate age-associated decline in sex hormone and muscle performance warrants further studies. (C) 2015 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
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| 45. |
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| 46. |
- Burke, Michael J., et al.
(författare)
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Transplant Outcomes for Children with T Cell Acute Lymphoblastic Leukemia in Second Remission : A Report from the Center for International Blood and Marrow Transplant Research
- 2015
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 21:12, s. 2154-2159
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Tidskriftsartikel (refereegranskat)abstract
- Survival for children with relapsed T cell acute lymphoblastic leukemia (T-ALL) is poor when treated with chemotherapy alone, and outcomes after allogeneic hematopoietic cell transplantation (HCT) is not well described. Two hundred twenty-nine children with T-ALL in second complete remission (CR2) received an HCT after myeloablative conditioning between 2000 and 2011 and were reported to the Center for International Blood and Marrow Transplant Research. Median age was 10 years (range, 2 to 18). Donor source was umbilical cord blood (26%), matched sibling bone marrow (38%), or unrelated bone marrow/peripheral blood (36%). Acute (grades II to IV) and chronic graft-versus-host disease occurred in, respectively, 35% (95% confidence interval [CI], 27% to 45%) and 26% (95% CI, 20% to 33%) of patients. Transplant-related mortality at day 100 and 3-year relapse rates were 13% (95% CI, 9% to 18%) and 30% (95% CI, 24% to 37%), respectively. Three-year overall survival and disease-free survival rates were 48% (95% CI, 41% to 55%) and 46% (95% CI, 39% to 52%), respectively. In multivariate analysis, patients with bone marrow relapse, with or without concurrent extramedullary relapse before HCT, were most likely to relapse (hazard ratio, 3.94; P =.005) as compared with isolated extramedullary disease. In conclusion, HCT for pediatric T-ALL in CR2 demonstrates reasonable and durable outcomes, and consideration for HCT is warranted. (c) 2015 American Society for Blood and Marrow Transplantation.
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| 47. |
- Cramwinckel, Margot J., et al.
(författare)
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Global and Zonal-Mean Hydrological Response to Early Eocene Warmth
- 2023
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Ingår i: Paleoceanography and Paleoclimatology. - 2572-4517 .- 2572-4525. ; 38:6
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Tidskriftsartikel (refereegranskat)abstract
- Earth's hydrological cycle is expected to intensify in response to global warming, with a wet-gets-wetter, dry-gets-drier response anticipated over the ocean. Subtropical regions (similar to 15 degrees-30 degrees N/S) are predicted to become drier, yet proxy evidence from past warm climates suggests these regions may be characterized by wetter conditions. Here we use an integrated data-modeling approach to reconstruct global and zonal-mean rainfall patterns during the early Eocene (similar to 56-48 million years ago). The Deep-Time Model Intercomparison Project (DeepMIP) model ensemble indicates that the mid-(30 degrees-60 degrees N/S) and high-latitudes (>60 degrees N/S) are characterized by a thermodynamically dominated hydrological response to warming and overall wetter conditions. The tropical band (0 degrees-15 degrees N/S) is also characterized by wetter conditions, with several DeepMIP models simulating narrowing of the Inter-Tropical Convergence Zone. However, the latter is not evident from the proxy data. The subtropics are characterized by negative precipitation-evaporation anomalies (i.e., drier conditions) in the DeepMIP models, but there is surprisingly large inter-model variability in mean annual precipitation (MAP). Intriguingly, we find that models with weaker meridional temperature gradients (e.g., CESM, GFDL) are characterized by a reduction in subtropical moisture divergence, leading to an increase in MAP. These model simulations agree more closely with our new proxy-derived precipitation reconstructions and other key climate metrics and imply that the early Eocene was characterized by reduced subtropical moisture divergence. If the meridional temperature gradient was even weaker than suggested by those DeepMIP models, circulation-induced changes may have outcompeted thermodynamic changes, leading to wetter subtropics. This highlights the importance of accurately reconstructing zonal temperature gradients when reconstructing past rainfall patterns. As the world warms, the atmosphere is able to hold more moisture however, this moisture will not fall evenly across the globe. Some regions are expected to become wetter, whereas other regions will become drier. This is the basis of the familiar paradigm wet-gets-wetter, dry-gets-drier and is largely supported by future model projections. However, evidence from the geological record contradicts this hypothesis and suggests that a warmer world could be characterized by wetter (rather than drier) subtropics. Here, we use an integrated data-modeling approach to investigate the hydrological response to warming during an ancient warm interval (the early Eocene, 56-48 million years ago). We show that models with weaker latitudinal temperature gradients are characterized by a reduction in subtropical moisture divergence. However, this was not sufficient to induce subtropical wetting. If the meridional temperature gradient was weaker than suggested by the models, circulation-induced changes may have lead to wetter subtropics. This work shows that the latitudinal temperature gradient is a key factor that influences hydroclimate in the subtropics, especially in past warm climates.
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| 48. |
- de Nooijer, Wesley, et al.
(författare)
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Evaluation of Arctic warming in mid-Pliocene climate simulations
- 2020
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 16:6, s. 2325-2341
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Tidskriftsartikel (refereegranskat)abstract
- Palaeoclimate simulations improve our understanding of the climate, inform us about the performance of climate models in a different climate scenario, and help to identify robust features of the climate system. Here, we analyse Arctic warming in an ensemble of 16 simulations of the mid-Pliocene Warm Period (mPWP), derived from the Pliocene Model Intercomparison Project Phase 2 (PlioMIP2). The PlioMIP2 ensemble simulates Arctic (60-90 degrees N) annual mean surface air temperature (SAT) increases of 3.7 to 11.6 degrees C compared to the pre-industrial period, with a multimodel mean (MMM) increase of 7.2 degrees C. The Arctic warming amplification ratio relative to global SAT anomalies in the ensemble ranges from 1.8 to 3.1 (MMM is 2.3). Sea ice extent anomalies range from -3.0 to -10.4 x 10(6) km(2), with a MMM anomaly of -5.6 x 10 6 km(2), which constitutes a decrease of 53 % compared to the pre-industrial period. The majority (11 out of 16) of models simulate summer seaice-free conditions (<= 1 x 10(6) km(2)) in their mPWP simulation. The ensemble tends to underestimate SAT in the Arctic when compared to available reconstructions, although the degree of underestimation varies strongly between the simulations. The simulations with the highest Arctic SAT anomalies tend to match the proxy dataset in its current form better. The ensemble shows some agreement with reconstructions of sea ice, particularly with regard to seasonal sea ice. Large uncertainties limit the confidence that can be placed in the findings and the compatibility of the different proxy datasets. We show that while reducing uncertainties in the reconstructions could decrease the SAT data-model discord substantially, further improvements are likely to be found in enhanced boundary conditions or model physics. Lastly, we compare the Arctic warming in the mPWP to projections of future Arctic warming and find that the PlioMIP2 ensemble simulates greater Arctic amplification than CMIP5 future climate simulations and an increase instead of a decrease in Atlantic Meridional Overturning Circulation (AMOC) strength compared to pre-industrial period. The results highlight the importance of slow feedbacks in equilibrium climate simulations, and that caution must be taken when using simulations of the mPWP as an analogue for future climate change.
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- Lee, Jui-Chi, et al.
(författare)
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Geomorphological mapping of comet 67P/Churyumov-Gerasimenko's Southern hemisphere
- 2016
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 462, s. S573-S592
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Tidskriftsartikel (refereegranskat)abstract
- In 2015 May, the Southern hemisphere of comet 67P/Churyumov-Gerasimenko became visible by the OSIRIS cameras on-board the Rosetta spacecraft. The resolution was high enough to carry out a detailed analysis of the surface morphology, which is quite different from the Northern hemisphere. Previous works show that fine particle deposits are the most extensive geological unit in the Northern hemisphere. In contrast, the Southern hemisphere is dominated by outcropping consolidated terrain. In this work, we provide geomorphological maps of the Southern hemisphere with the distinction of both geological units and linear features. The geomorphological maps described in this study allow us to gain a better understanding of the processes shaping the comet nucleus and the distribution of primary structures such as fractures and strata.
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