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1.
  • Aad, G., et al. (author)
  • 2011
  • swepub:Mat__t (peer-reviewed)
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2.
  • Schael, S., et al. (author)
  • Electroweak measurements in electron positron collisions at W-boson-pair energies at LEP
  • 2013
  • In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 532:4, s. 119-244
  • Research review (peer-reviewed)abstract
    • Electroweak measurements performed with data taken at the electron positron collider LEP at CERN from 1995 to 2000 are reported. The combined data set considered in this report corresponds to a total luminosity of about 3 fb(-1) collected by the four LEP experiments ALEPH, DELPHI, 13 and OPAL, at centre-of-mass energies ranging from 130 GeV to 209 GeV. Combining the published results of the four LEP experiments, the measurements include total and differential cross-sections in photon-pair, fermion-pair and four-fermion production, the latter resulting from both double-resonant WW and ZZ production as well as singly resonant production. Total and differential cross-sections are measured precisely, providing a stringent test of the Standard Model at centre-of-mass energies never explored before in electron positron collisions. Final-state interaction effects in four-fermion production, such as those arising from colour reconnection and Bose Einstein correlations between the two W decay systems arising in WW production, are searched for and upper limits on the strength of possible effects are obtained. The data are used to determine fundamental properties of the W boson and the electroweak theory. Among others, the mass and width of the W boson, m(w) and Gamma(w), the branching fraction of W decays to hadrons, B(W -> had), and the trilinear gauge-boson self-couplings g(1)(Z), K-gamma and lambda(gamma), are determined to be: m(w) = 80.376 +/- 0.033 GeV Gamma(w) = 2.195 +/- 0.083 GeV B(W -> had) = 67.41 +/- 0.27% g(1)(Z) = 0.984(-0.020)(+0.018) K-gamma - 0.982 +/- 0.042 lambda(gamma) = 0.022 +/- 0.019. (C) 2013 Elsevier B.V. All rights reserved.
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3.
  • Schael, S, et al. (author)
  • Precision electroweak measurements on the Z resonance
  • 2006
  • In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
  • Research review (peer-reviewed)abstract
    • We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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7.
  • Fuchsberger, Christian, et al. (author)
  • The genetic architecture of type 2 diabetes
  • 2016
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
  • Journal article (peer-reviewed)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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9.
  • Dunham, I, et al. (author)
  • The DNA sequence of human chromosome 22
  • 1999
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 402:6761, s. 489-495
  • Journal article (peer-reviewed)
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10.
  • Herique, A., et al. (author)
  • Direct observations of asteroid interior and regolith structure : Science measurement requirements
  • 2018
  • In: Advances in Space Research. - : Elsevier BV. - 0273-1177 .- 1879-1948. ; 62:8, s. 2141-2162
  • Journal article (peer-reviewed)abstract
    • Our knowledge of the internal structure of asteroids is, so far, indirect - relying entirely on inferences from remote sensing observations of the surface, and theoretical modeling of formation and evolution. What are the bulk properties of the regolith and deep interior? And what are the physical processes that shape asteroid internal structures? Is the composition and size distribution observed on the surface representative of the bulk? These questions are crucial to understand small bodies' history from accretion in the early Solar System to the present, and direct measurements are needed to answer these questions for the benefit of science as well as for planetary defense or exploration. Radar is one of the main instruments capable of sounding asteroids to characterize internal structure from sub-meter to global scale. In this paper, we review the science case for direct observation of the deep internal structure and regolith of a rocky asteroid of kilometer size or smaller. We establish the requirements and model dielectric properties of asteroids to outline a possible instrument suite, and highlight the capabilities of radar instrumentation to achieve these observations. We then review the expected science return including secondary objectives contributing to the determination of the gravitational field, the shape model, and the dynamical state. This work is largely inherited from MarcoPolo-R and AIDA/AIM studies.
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12.
  • Flannick, Jason, et al. (author)
  • Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
  • 2017
  • In: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
  • Journal article (peer-reviewed)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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13.
  • Manning, Alisa, et al. (author)
  • A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
  • 2017
  • In: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
  • Journal article (peer-reviewed)abstract
    • To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
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14.
  • Sawcer, Stephen, et al. (author)
  • Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
  • 2011
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
  • Journal article (peer-reviewed)abstract
    • Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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15.
  • Shupe, M. D., et al. (author)
  • Overview of the MOSAiC expedition : Atmosphere
  • 2022
  • In: Elementa. - : University of California Press. - 2325-1026. ; 10:1
  • Journal article (peer-reviewed)abstract
    • With the Arctic rapidly changing, the needs to observe, understand, and model the changes are essential. To support these needs, an annual cycle of observations of atmospheric properties, processes, and interactions were made while drifting with the sea ice across the central Arctic during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition from October 2019 to September 2020. An international team designed and implemented the comprehensive program to document and characterize all aspects of the Arctic atmospheric system in unprecedented detail, using a variety of approaches, and across multiple scales. These measurements were coordinated with other observational teams to explore crosscutting and coupled interactions with the Arctic Ocean, sea ice, and ecosystem through a variety of physical and biogeochemical processes. This overview outlines the breadth and complexity of the atmospheric research program, which was organized into 4 subgroups: atmospheric state, clouds and precipitation, gases and aerosols, and energy budgets. Atmospheric variability over the annual cycle revealed important influences from a persistent large-scale winter circulation pattern, leading to some storms with pressure and winds that were outside the interquartile range of past conditions suggested by long-term reanalysis. Similarly, the MOSAiC location was warmer and wetter in summer than the reanalysis climatology, in part due to its close proximity to the sea ice edge. The comprehensiveness of the observational program for characterizing and analyzing atmospheric phenomena is demonstrated via a winter case study examining air mass transitions and a summer case study examining vertical atmospheric evolution. Overall, the MOSAiC atmospheric program successfully met its objectives and was the most comprehensive atmospheric measurement program to date conducted over the Arctic sea ice. The obtained data will support a broad range of coupled-system scientific research and provide an important foundation for advancing multiscale modeling capabilities in the Arctic. 
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16.
  • van de Munckhof, A., et al. (author)
  • Outcomes of Cerebral Venous Thrombosis due to Vaccine-Induced Immune Thrombotic Thrombocytopenia After the Acute Phase
  • 2022
  • In: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 53:10, s. 3206-3210
  • Journal article (peer-reviewed)abstract
    • Background: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. Methods: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). Results: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed). Conclusions: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.
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  • Sanchez-Gonzalez, A., et al. (author)
  • Accurate prediction of X-ray pulse properties from a free-electron laser using machine learning
  • 2017
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
  • Journal article (peer-reviewed)abstract
    • Free-electron lasers providing ultra-short high-brightness pulses of X-ray radiation have great potential for a wide impact on science, and are a critical element for unravelling the structural dynamics of matter. To fully harness this potential, we must accurately know the X-ray properties: intensity, spectrum and temporal profile. Owing to the inherent fluctuations in free-electron lasers, this mandates a full characterization of the properties for each and every pulse. While diagnostics of these properties exist, they are often invasive and many cannot operate at a high-repetition rate. Here, we present a technique for circumventing this limitation. Employing a machine learning strategy, we can accurately predict X-ray properties for every shot using only parameters that are easily recorded at high-repetition rate, by training a model on a small set of fully diagnosed pulses. This opens the door to fully realizing the promise of next-generation high-repetition rate X-ray lasers.
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19.
  • Beecham, Ashley H, et al. (author)
  • Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
  • 2013
  • In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
  • Journal article (peer-reviewed)abstract
    • Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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20.
  • Journeau, C., et al. (author)
  • European Research on the Corium issues within the SARNET network of excellence
  • 2008
  • In: International Conference on Advances in Nuclear Power Plants, ICAPP 2008. - 9781605607870 ; , s. 1172-1181
  • Conference paper (peer-reviewed)abstract
    • Within SARNET, the corium topic covers all the behaviors of corium from early phase of core degradation to in or ex-vessel corium recovery with the exception of corium interaction with water, direct containment heating and fission product release. The corium topic regroups in three work packages the critical mass of competence required to improve significantly the corium behavior knowledge. The spirit of the SARNET networking is to share the knowledge, the facilities and the simulation tools for severe accidents, so to reach a better efficiency and to rationalize the R&D effort at European level. Extensive benchmarking has been launched in most of the areas of research. These benchmarks were mainly dedicated to the recalculation of experiments, while, in the next periods, a larger focus will be given to integral experiments or reactor applications. Eventually, all the knowledge will be accumulated in the ASTEC severe accident simulation code through physical model improvements and extension of validation database. This paper summarizes the progress that has been achieved in the frame of the networking activities. A special focus is placed on the melt pool and debris coolability and corium-concrete interaction, in which, the effects due to multidimensional geometries and heterogeneities has been shown, during SARNET, to play a crucial role and for which further research is still needed.
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  • Vogt, N. M., et al. (author)
  • Interaction of amyloid and tau on cortical microstructure in cognitively unimpaired adults
  • 2022
  • In: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:1, s. 65-76
  • Journal article (peer-reviewed)abstract
    • Introduction: Neurite orientation dispersion and density imaging (NODDI), a multi-compartment diffusion-weighted imaging (DWI) model, may be useful for detecting early cortical microstructural alterations in Alzheimer's disease prior to cognitive impairment. Methods: Using neuroimaging (NODDI and T1-weighted magnetic resonance imaging [MRI]) and cerebrospinal fluid (CSF) biomarker data (measured using Elecsys® CSF immunoassays) from 219 cognitively unimpaired participants, we tested the main and interactive effects of CSF amyloid beta (Aβ)42/Aβ40 and phosphorylated tau (p-tau) on cortical NODDI metrics and cortical thickness, controlling for age, sex, and apolipoprotein E ε4. Results: We observed a significant CSF Aβ42/Aβ40 × p-tau interaction on cortical neurite density index (NDI), but not orientation dispersion index or cortical thickness. The directionality of these interactive effects indicated: (1) among individuals with lower CSF p-tau, greater amyloid burden was associated with higher cortical NDI; and (2) individuals with greater amyloid and p-tau burden had lower cortical NDI, consistent with cortical neurodegenerative changes. Discussion: NDI is a particularly sensitive marker for early cortical changes that occur prior to gross atrophy or development of cognitive impairment. © 2021 the Alzheimer's Association
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22.
  • Donis, Daphne, et al. (author)
  • Stratification strength and light climate explain variation in chlorophyll a at the continental scale in a European multilake survey in a heatwave summer
  • 2021
  • In: Limnology and Oceanography. - : John Wiley & Sons. - 0024-3590 .- 1939-5590. ; 66:12, s. 4314-4333
  • Journal article (peer-reviewed)abstract
    • To determine the drivers of phytoplankton biomass, we collected standardized morphometric, physical, and biological data in 230 lakes across the Mediterranean, Continental, and Boreal climatic zones of the European continent. Multilinear regression models tested on this snapshot of mostly eutrophic lakes (median total phosphorus [TP] = 0.06 and total nitrogen [TN] = 0.7 mg L-1), and its subsets (2 depth types and 3 climatic zones), show that light climate and stratification strength were the most significant explanatory variables for chlorophyll a (Chl a) variance. TN was a significant predictor for phytoplankton biomass for shallow and continental lakes, while TP never appeared as an explanatory variable, suggesting that under high TP, light, which partially controls stratification strength, becomes limiting for phytoplankton development. Mediterranean lakes were the warmest yet most weakly stratified and had significantly less Chl a than Boreal lakes, where the temperature anomaly from the long-term average, during a summer heatwave was the highest (+4 degrees C) and showed a significant, exponential relationship with stratification strength. This European survey represents a summer snapshot of phytoplankton biomass and its drivers, and lends support that light and stratification metrics, which are both affected by climate change, are better predictors for phytoplankton biomass in nutrient-rich lakes than nutrient concentrations and surface temperature.
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  • Mantzouki, Evanthia, et al. (author)
  • Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins
  • 2018
  • In: Toxins. - : MDPI. - 2072-6651. ; 10:4
  • Journal article (peer-reviewed)abstract
    • Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a) and cytotoxins (e.g., cylindrospermopsin) due to their potency. Most studies examine the relationship between individual toxin variants and environmental factors, such as nutrients, temperature and light. In summer 2015, we collected samples across Europe to investigate the effect of nutrient and temperature gradients on the variability of toxin production at a continental scale. Direct and indirect effects of temperature were the main drivers of the spatial distribution in the toxins produced by the cyanobacterial community, the toxin concentrations and toxin quota. Generalized linear models showed that a Toxin Diversity Index (TDI) increased with latitude, while it decreased with water stability. Increases in TDI were explained through a significant increase in toxin variants such as MC-YR, anatoxin and cylindrospermopsin, accompanied by a decreasing presence of MC-LR. While global warming continues, the direct and indirect effects of increased lake temperatures will drive changes in the distribution of cyanobacterial toxins in Europe, potentially promoting selection of a few highly toxic species or strains.
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  • Wevers-de Boer, K. V. C., et al. (author)
  • Four-month metacarpal bone mineral density loss predicts radiological joint damage progression after 1 year in patients with early rheumatoid arthritis: exploratory analyses from the IMPROVED study
  • 2015
  • In: Annals of the Rheumatic Diseases. - : BMJ Publishing Group. - 0003-4967 .- 1468-2060. ; 74:2, s. 341-346
  • Journal article (peer-reviewed)abstract
    • Aim To assess whether in early (rheumatoid) arthritis (RA) patients, metacarpal bone mineral density (BMD) loss after 4 months predicts radiological progression after 1 year of antirheumatic treatment. Methods Metacarpal BMD was measured 4 monthly during the first year by digital X-ray radiogrammetry (DXR-BMD) in patients participating in the IMPROVED study, a clinical trial in 610 patients with recent onset RA (2010 criteria) or undifferentiated arthritis, treated according to a remission (disease activity scoreless than1.6) steered strategy. With Sharp/van der Heijde progression greater than= 0.5 points after 1 year (yes/no) as dependent variable, univariate and multivariate logistic regression analyses were performed. Results Of 428 patients with DXR-BMD results and progression scores available, 28 (7%) had radiological progression after 1 year. Independent predictors for radiological progression were presence of baseline erosions (OR (95% CI) 6.5 (1.7 to 25)) and early DXR-BMD loss (OR (95% CI) 1.5 (1.1 to 2.0)). In 366 (86%) patients without baseline erosions, early DXR-BMD loss was the only independent predictor of progression (OR (95% CI) 2.0 (1.4 to 2.9)). Conclusions In early RA patients, metacarpal BMD loss after 4 months of treatment is an independent predictor of radiological progression after 1 year. In patients without baseline erosions, early metacarpal BMD loss is the main predictor of radiological progression.
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  • Chng, Kern Rei, et al. (author)
  • Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment
  • 2020
  • In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 26, s. 941-951
  • Journal article (peer-reviewed)abstract
    • Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (>60% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (>8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections. Spatiotemporal characterization of microbial diversity and antibiotic resistance in a tertiary-care hospital reveals broad distribution and persistence of antibiotic-resistant organisms that could cause opportunistic infections in a healthcare setting.
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29.
  • Danko, David, et al. (author)
  • A global metagenomic map of urban microbiomes and antimicrobial resistance
  • 2021
  • In: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 184:13, s. 3376-3393
  • Journal article (peer-reviewed)abstract
    • We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities.
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30.
  • Horio, M., et al. (author)
  • Oxide Fermi liquid universality revealed by electron spectroscopy
  • 2020
  • In: Physical Review B. - 2469-9969 .- 2469-9950. ; 102:24
  • Journal article (peer-reviewed)abstract
    • We present a combined soft x-ray and high-resolution vacuum-ultraviolet angle-resolved photoemission spectroscopy study of the electron-overdoped cuprate Pr1.3-xLa0.7CexCuO4 (PLCCO). Demonstration of its highly two-dimensional band structure enabled precise determination of the in-plane self-energy dominated by electron-electron scattering. Through analysis of this self-energy and the Fermi liquid cut-off energy scale, we find-in contrast to hole-doped cuprates-a momentum isotropic and comparatively weak electron correlation in PLCCO. Yet, the self-energies extracted from multiple oxide systems combine to demonstrate a logarithmic divergent relation between the quasiparticle scattering rate and mass. This constitutes a spectroscopic version of the Kadowaki-Woods relation with an important merit-the demonstration of Fermi liquid quasiparticle lifetime and mass being set by a single energy scale.
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  • Mahajan, Anubha, et al. (author)
  • Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus.
  • 2015
  • In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 11:1
  • Journal article (peer-reviewed)abstract
    • Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights.
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32.
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33.
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34.
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35.
  • Steinbach, C, et al. (author)
  • Detection of the Book Isomer from the OH-stretch Spectroscopy of Size Selected Water Hexamers.
  • 2004
  • In: Physical Chemistry Chemical Physics. ; 6, s. 3320-3324
  • Journal article (peer-reviewed)abstract
    • The vibrational OH-stretch spectrum of size selected water hexamer clusters has been measured for cluster temperatures between 40 and 60 K. By comparison with temperature dependent calculations the spectra were identified to be those of the book isomer. This result is in good agreement with recent predictions of the equilibrium isomer distributions in this temperature range.
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36.
  • Steinbach, C, et al. (author)
  • Infrared Predissociation Spectroscopy of Large Water Clusters: a Unique Probe of Cluster Surfaces.
  • 2004
  • In: J. Physical Chemistry A. ; 108, s. 6165-6174
  • Journal article (peer-reviewed)abstract
    • The vibrational OH-stretch spectra of large water clusters were measured by photofragment spectroscopy after the absorption of pulsed tunable infrared radiation in the frequency range from 3000 to 3800 cm-1. The mean size of the clusters from = 20 to 1960 was measured by threshold photoionization of the water clusters doped with sodium atoms. The largest abundance of the fragments was that of water hexamers. The fragment intensities are measured for different excitation energies and different cluster temperatures as function of the cluster size. For the selected sizes = 48, 111, 631, and 1960 complete OH-stretch spectra have been measured. The comparison with calculations revealed that the method is mainly sensitive to the outer cluster surface which has for all sizes an amorphous structure dominated by 3-coordinated and to a lesser extent also by 4-coordinated molecules. The intensity of the hexamer fragments goes through a maximum at n = 70 and drops to n = 300 where it levels off with a different slope. This behavior is attributed to the number of available connected 3-coordinated water molecules and the influence of the emerging 4-coordinated molecules in these clusters.
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37.
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38.
  • Thumann, B. F., et al. (author)
  • Cross-sectional associations between objectively measured sleep characteristics and body mass index in European children and adolescents
  • 2021
  • In: Sleep Medicine. - : Elsevier BV. - 1389-9457. ; 84, s. 32-39
  • Journal article (peer-reviewed)abstract
    • Background: Short sleep duration has been found to be associated with a higher risk for overweight and obesity. However, previous studies have mainly relied on subjective measures of sleep duration and other sleep characteristics (eg quality, timing) have often been neglected. Therefore, we aimed to investigate associations between several, mainly objectively measured sleep characteristics and body mass index (BMI). Further, we aimed to identify distinct sleep subtypes based on these sleep characteristics and to study their association with BMI. Methods: Children aged 9-16 years participating in the European I.Family study (N = 559, 51.2% girls, 32.9% overweight/obese) wore an accelerometer for one week on their wrist and recorded their daily wake-up and lights-off times in a sleep diary. Information on sleep duration, sleep efficiency and sleep latency was derived. To identify sleep subtypes, we conducted a latent class analysis using all five sleep variables. Associations between single sleep variables, sleep subtype and age- and sex-specific BMI z-score were investigated using linear mixed-effects regression models to accommodate clustering among siblings. Results: No statistically significant associations were observed between the single sleep variables (sleep duration, sleep efficiency, sleep latency, wake-up and lights-off times) and BMI z-score. Four sleep subtypes were identified and children were assigned to one of the groups based on their highest probability for latent group membership: "early birds" (17.5% of the sample), "short sleep duration" (14.7%), "optimal sleep" (47.6%) and "poor sleep quality" (20.2%). Sleep subtype was not associated with BMI z-score. Conclusions: Using objective sleep data, we did not find convincing evidence for associations between the sleep variables under investigation and BMI. (C) 2021 Elsevier B.V. All rights reserved.
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39.
  • Allentoft, Morten E., et al. (author)
  • Population genomics of post-glacial western Eurasia
  • 2024
  • In: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
  • Journal article (peer-reviewed)abstract
    • Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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40.
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41.
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42.
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43.
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44.
  • Arvidsson, Daniel, 1974, et al. (author)
  • Reexamination of Accelerometer Calibration with Energy Expenditure as Criterion: VO2net Instead of MET for Age-Equivalent Physical Activity Intensity
  • 2019
  • In: Sensors. - : MDPI AG. - 1424-8220. ; 19:15
  • Journal article (peer-reviewed)abstract
    • Accelerometer calibration for physical activity (PA) intensity is commonly performed using Metabolic Equivalent of Task (MET) as criterion. However, MET is not an age-equivalent measure of PA intensity, which limits the use of MET-calibrated accelerometers for age-related PA investigations. We investigated calibration using VO2net (VO2gross - VO2stand; mL.min(-1).kg(-1)) as criterion compared to MET (VO2gross/VO2rest) and the effect on assessment of free-living PA in children, adolescents and adults. Oxygen consumption and hip/thigh accelerometer data were collected during rest, stand and treadmill walk and run. Equivalent speed (Speed(eq)) was used as indicator of the absolute speed (Speed(abs)) performed with the same effort in individuals of different body size/age. The results showed that VO2net was higher in younger age-groups for Speedabs, but was similar in the three age-groups for Speed(eq). MET was lower in younger age-groups for both Speed(abs) and Speed(eq). The same VO2net-values respective MET-values were applied to all age-groups to develop accelerometer PA intensity cut-points. Free-living moderate-and-vigorous PA was 216, 115, 74 and 71 min/d in children, adolescents, younger and older adults with VO2net-calibration, but 140, 83, 74 and 41 min/d with MET-calibration, respectively. In conclusion, VO2net calibration of accelerometers may provide age-equivalent measures of PA intensity/effort for more accurate age-related investigations of PA in epidemiological research.
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45.
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46.
  • Benabdallah, Nadia, et al. (author)
  • Beyond Average : a-Particle Distribution and Dose Heterogeneity in Bone Metastatic Prostate Cancer
  • 2024
  • In: Journal of Nuclear Medicine. - 0161-5505. ; 65:2, s. 245-251
  • Journal article (peer-reviewed)abstract
    • a-particle emitters are emerging as a potent modality for disseminated cancer therapy because of their high linear energy transfer and localized absorbed dose profile. Despite great interest and pharmaceutical development, there is scant information on the distribution of these agents at the scale of the a-particle pathlength. We sought to determine the distribution of clinically approved [223Ra]RaCl2 in bone metastatic castration-resistant prostate cancer at this resolution, for the first time to our knowledge, to inform activity distribution and dose at the near-cell scale. Methods: Biopsy specimens and blood were collected from 7 patients 24 h after administration. 223Ra activity in each sample was recorded, and the microstructure of biopsy specimens was analyzed by micro-CT. Quantitative autoradiography and histopathology were segmented and registered with an automated procedure. Activity distributions by tissue compartment and dosimetry calculations based on the MIRD formalism were performed. Results: We revealed the activity distribution differences across and within patient samples at the macro- and microscopic scales. Microdistribution analysis confirmed localized high-activity regions in a background of low-activity tissue. We evaluated heterogeneous a-particle emission distribution concentrated at bone–tissue interfaces and calculated spatially nonuniform absorbed-dose profiles. Conclusion: Primary patient data of radiopharmaceutical therapy distribution at the small scale revealed that 223Ra uptake is nonuniform. Dose estimates present both opportunities and challenges to enhance patient outcomes and are a first step toward personalized treatment approaches and improved understanding of a-particle radiopharmaceutical therapies.
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47.
  • Björn, Lars Olof, et al. (author)
  • Effects of ozone depletion and increased ultraviolet-B radiation on northern vegetation
  • 1999
  • In: Polar Research. - : Norwegian Polar Institute. - 0800-0395 .- 1751-8369. ; 18:2, s. 331-337
  • Journal article (peer-reviewed)abstract
    • The stratospheric ozone layer has been depleted at high and mid-latitudes as a consequence of man's pollution of the atmosphere, and this results in increasing ultraviolet-B radiation at ground level. We investigate the effects of further radiation increases on plants and ecosystems by irradiating natural sub-Arctic and Arctic vegetation with artificial W-B radiation in field experiments extending over several years. Our experimental sites are located at Abisko, in northern Sweden (68 degrees N), and Adventdalen, on the island of Spitsbergen (78 degrees N). Additional UV-B induced interspecific differences in plant response in terms of reduced (or, in one case, increased) growth, changed morphology and changed pigment content. In some cases effects seem to be accumulated from one year to another. Plant litter decomposition is retarded. We are also studying how UV-B enhancement may affect the interaction between species. In some experiments we combine UV-B enhancement with changes in other factors: carbon dioxide concentration, water availability, and temperature. In some cases the effect of radiation enhancement is modified, or even reversed, by such changes. Over a four year period we did not find any significant radiation induced change in species composition, but based on the effects on individual plant species, such changes can be expected to take place over a longer time.
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48.
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49.
  • Breau, B., et al. (author)
  • Longitudinal association of childhood physical activity and physical fitness with physical activity in adolescence: insights from the IDEFICS/I.Family study
  • 2022
  • In: International Journal of Behavioral Nutrition and Physical Activity. - : Springer Science and Business Media LLC. - 1479-5868. ; 19:1
  • Journal article (peer-reviewed)abstract
    • Background: This study aimed to examine associations of early childhood physical fitness and physical activity (PA) with PA during later childhood/early adolescence while accounting for gender differences. Methods: We selected data of N = 4329 children from the IDEFICS/I. Family cohort (age 2.4-11.7 years) with data on baseline fitness and accelerometer measurements. At baseline, physical fitness tests were conducted including Flamingo balance, Backsaver sit and reach, Handgrip strength, Standing Long Jump, 40-m sprint and 20-m Shuttle run (to estimate cardio-respiratory fitness levels). PA was measured with Actigraph accelerometers over 3 days at baseline (ActiTrainer or GT1M) and 7 days at follow-up (GT3X). Evenson cutpoints were used to determine moderate-to-vigorous PA (MVPA) time, and children with >= 60mins/day of average MVPA were deemed as having met WHO guidelines at baseline and follow-up. Linear and logistic regressions were performed to examine longitudinal associations between meeting WHO guidelines, MVPA, and physical fitness tests at baseline with meeting WHO guidelines and MVPA at follow-up. Models were conducted on the entire sample, the sex-stratified sample, and stratified by sex and pubertal status at follow-up. Results: Results showed that meeting WHO guidelines for MVPA at baseline was positively associated with MVPA (Standardized Beta (B) = 0.13, 95%CI:(5.6;11.1)) and meeting WHO guidelines at follow-up for the entire sample (OR = 2.1, 95%CI:(1.5; 3.14), and stratified by males (OR = 2.5, 95%CI:(1.5; 4.1)) and females (OR = 1.8, 95%CI:(1.0; 3.2)). This was also found for both male pre/early pubertal and pubertal groups but only in the female pre/early pubertal group, and not the female pubertal group (MVPA: B = .00, 95%CI:(- 6.1; 5.6), WHO: OR = 0.61, 95%CI:(0.23;1.6)). Models indicated that Standing Long jump, 40-m sprint, Shuttle run and Flamingo balance at baseline were associated with MVPA and meeting the guidelines at follow-up. Conclusions: Meeting WHO guidelines and certain fitness tests at baseline were strongly associated with MVPA and meeting WHO guidelines at follow-up, but this association varied with sex and pubertal status. Consequently, these findings underline the importance of ensuring sufficient physical activity in terms of quality and quantity for children at the earliest stages of life.
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50.
  • Buck, Brenda J., et al. (author)
  • The emerging field of medical geology in brief : some examples
  • 2016
  • In: Environmental Earth Sciences. - : Springer Science and Business Media LLC. - 1866-6280 .- 1866-6299. ; 75:6
  • Journal article (peer-reviewed)abstract
    • Emerging medical problems present medical practitioners with many difficult challenges. Emergent disciplines may offer the medical community new opportunities to address a range of these diseases. One such emerging discipline is medical geology, a science that is dealing with the influence of natural environmental factors on the geographical distribution of health in humans and animals. It involves the study of the processes and causes of diseases and also the use research findings to present solutions to health problems.
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