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Sökning: WFRF:(Mathew S)

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1.
  • Kanai, M, et al. (författare)
  • 2023
  • swepub:Mat__t
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  • Niemi, MEK, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • 2021
  • swepub:Mat__t
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  • Thomas, HS, et al. (författare)
  • 2019
  • swepub:Mat__t
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  • 2019
  • Tidskriftsartikel (refereegranskat)
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  • Romagnoni, A, et al. (författare)
  • Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data
  • 2019
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10351-
  • Tidskriftsartikel (refereegranskat)abstract
    • Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.
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  • Nagaraja, Ch., et al. (författare)
  • Opening remarks
  • 2016
  • Konferensbidrag (refereegranskat)
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  • Weinstein, John N., et al. (författare)
  • The cancer genome atlas pan-cancer analysis project
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
  • Forskningsöversikt (refereegranskat)abstract
    • The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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  • Momozawa, Y, et al. (författare)
  • IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
  • 2018
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2427-
  • Tidskriftsartikel (refereegranskat)abstract
    • GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach.
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  • Sen, P, et al. (författare)
  • Vaccine hesitancy decreases in rheumatic diseases, long-term concerns remain in myositis: a comparative analysis of the COVAD surveys
  • 2023
  • Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 62:10, s. 3291-3301
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveCOVID-19 vaccines have a favorable safety profile in patients with autoimmune rheumatic diseases (AIRDs) such as idiopathic inflammatory myopathies (IIMs); however, hesitancy continues to persist among these patients. Therefore, we studied the prevalence, predictors and reasons for hesitancy in patients with IIMs, other AIRDs, non-rheumatic autoimmune diseases (nrAIDs) and healthy controls (HCs), using data from the two international COVID-19 Vaccination in Autoimmune Diseases (COVAD) e-surveys.MethodsThe first and second COVAD patient self-reported e-surveys were circulated from March to December 2021, and February to June 2022 (ongoing). We collected data on demographics, comorbidities, COVID-19 infection and vaccination history, reasons for hesitancy, and patient reported outcomes. Predictors of hesitancy were analysed using regression models in different groups.ResultsWe analysed data from 18 882 (COVAD-1) and 7666 (COVAD-2) respondents. Reassuringly, hesitancy decreased from 2021 (16.5%) to 2022 (5.1%) (OR: 0.26; 95% CI: 0.24, 0.30, P < 0.001). However, concerns/fear over long-term safety had increased (OR: 3.6; 95% CI: 2.9, 4.6, P < 0.01). We noted with concern greater skepticism over vaccine science among patients with IIMs than AIRDs (OR: 1.8; 95% CI: 1.08, 3.2, P = 0.023) and HCs (OR: 4; 95% CI: 1.9, 8.1, P < 0.001), as well as more long-term safety concerns/fear (IIMs vs AIRDs – OR: 1.9; 95% CI: 1.2, 2.9, P = 0.001; IIMs vs HCs – OR: 5.4 95% CI: 3, 9.6, P < 0.001). Caucasians [OR 4.2 (1.7–10.3)] were likely to be more hesitant, while those with better PROMIS physical health score were less hesitant [OR 0.9 (0.8–0.97)].ConclusionVaccine hesitancy has decreased from 2021 to 2022, long-term safety concerns remain among patients with IIMs, particularly in Caucasians and those with poor physical function.
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  • Quanz, S. P., et al. (författare)
  • Large Interferometer For Exoplanets (LIFE) I. Improved exoplanet detection yield estimates for a large mid-infrared space-interferometer mission
  • 2022
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 664
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. One of the long-term goals of exoplanet science is the atmospheric characterization of dozens of small exoplanets in order to understand their diversity and search for habitable worlds and potential biosignatures. Achieving this goal requires a space mission of sufficient scale that can spatially separate the signals from exoplanets and their host stars and thus directly scrutinize the exoplanets and their atmospheres.Aims. We seek to quantify the exoplanet detection performance of a space-based mid-infrared (MIR) nulling interferometer that measures the thermal emission of exoplanets. We study the impact of various parameters and compare the performance with that of large single-aperture mission concepts that detect exoplanets in reflected light.Methods. We have developed an instrument simulator that considers all major astrophysical noise sources and coupled it with Monte Carlo simulations of a synthetic exoplanet population around main-sequence stars within 20 pc of the Sun. This allows us to quantify the number (and types) of exoplanets that our mission concept could detect. Considering single visits only, we discuss two different scenarios for distributing 2.5 yr of an initial search phase among the stellar targets. Different apertures sizes and wavelength ranges are investigated.Results. An interferometer consisting of four 2 m apertures working in the 4–18.5 μ.m wavelength range with a total instrument throughput of 5% could detect up to ≈550 exoplanets with radii between 0.5 and 6 R⊕ with an integrated S/N ≥ 7. At least ≈160 of the detected exoplanets have radii ≤1.5 R⊕. Depending on the observing scenario, ≈25–45 rocky exoplanets (objects with radii between 0.5 and 1.5 R⊕) orbiting within the empirical habitable zone (eHZ) of their host stars are among the detections. With four 3.5 m apertures, the total number of detections can increase to up to ≈770, including ≈60–80 rocky eHZ planets. With four times 1 m apertures, the maximum detection yield is ≈315 exoplanets, including ≤20 rocky eHZ planets. The vast majority of small, temperate exoplanets are detected around M dwarfs. The impact of changing the wavelength range to 3–20 μm or 6–17 μm on the detection yield is negligible.Conclusions. A large space-based MIR nulling interferometer will be able to directly detect hundreds of small, nearby exoplanets, tens of which would be habitable world candidates. This shows that such a mission can compete with large single-aperture reflected light missions. Further increasing the number of habitable world candidates, in particular around solar-type stars, appears possible via the implementation of a multi-visit strategy during the search phase. The high median S/N of most of the detected planets will allow for first estimates of their radii and effective temperatures and will help prioritize the targets for a second mission phase to obtain high-S/N thermal emission spectra, leveraging the superior diagnostic power of the MIR regime compared to shorter wavelengths.
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  • Kattge, Jens, et al. (författare)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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  • Beal, Jacob, et al. (författare)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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  • Abazajian, Kevork, et al. (författare)
  • CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves
  • 2022
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
  • Tidskriftsartikel (refereegranskat)abstract
    • CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.
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  • Craddock, Nick, et al. (författare)
  • Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
  • Tidskriftsartikel (refereegranskat)abstract
    • Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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37.
  • Ding, Li, et al. (författare)
  • Somatic mutations affect key pathways in lung adenocarcinoma
  • 2008
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 455:7216, s. 1069-1075
  • Tidskriftsartikel (refereegranskat)abstract
    • Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
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  • Quegan, S., et al. (författare)
  • The European Space Agency BIOMASS mission: Measuring forest above-ground biomass from space
  • 2019
  • Ingår i: Remote Sensing of Environment. - : Elsevier BV. - 0034-4257. ; 227, s. 44-60
  • Tidskriftsartikel (refereegranskat)abstract
    • The primary objective of the European Space Agency's 7th Earth Explorer mission, BIOMASS, is to determine the worldwide distribution of forest above-ground biomass (AGB) in order to reduce the major uncertainties in calculations of carbon stocks and fluxes associated with the terrestrial biosphere, including carbon fluxes associated with Land Use Change, forest degradation and forest regrowth. To meet this objective it will carry, for the first time in space, a fully polarimetric P-band synthetic aperture radar (SAR). Three main products will be provided: global maps of both AGB and forest height, with a spatial resolution of 200 m, and maps of severe forest disturbance at 50 m resolution (where “global” is to be understood as subject to Space Object tracking radar restrictions). After launch in 2022, there will be a 3-month commissioning phase, followed by a 14-month phase during which there will be global coverage by SAR tomography. In the succeeding interferometric phase, global polarimetric interferometry Pol-InSAR coverage will be achieved every 7 months up to the end of the 5-year mission. Both Pol-InSAR and TomoSAR will be used to eliminate scattering from the ground (both direct and double bounce backscatter) in forests. In dense tropical forests AGB can then be estimated from the remaining volume scattering using non-linear inversion of a backscattering model. Airborne campaigns in the tropics also indicate that AGB is highly correlated with the backscatter from around 30 m above the ground, as measured by tomography. In contrast, double bounce scattering appears to carry important information about the AGB of boreal forests, so ground cancellation may not be appropriate and the best approach for such forests remains to be finalized. Several methods to exploit these new data in carbon cycle calculations have already been demonstrated. In addition, major mutual gains will be made by combining BIOMASS data with data from other missions that will measure forest biomass, structure, height and change, including the NASA Global Ecosystem Dynamics Investigation lidar deployed on the International Space Station after its launch in December 2018, and the NASA-ISRO NISAR L- and S-band SAR, due for launch in 2022. More generally, space-based measurements of biomass are a core component of a carbon cycle observation and modelling strategy developed by the Group on Earth Observations. Secondary objectives of the mission include imaging of sub-surface geological structures in arid environments, generation of a true Digital Terrain Model without biases caused by forest cover, and measurement of glacier and icesheet velocities. In addition, the operations needed for ionospheric correction of the data will allow very sensitive estimates of ionospheric Total Electron Content and its changes along the dawn-dusk orbit of the mission.
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40.
  • Andreoni, Igor, et al. (författare)
  • Target-of-opportunity Observations of Gravitational-wave Events with Vera C. Rubin Observatory
  • 2022
  • Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 260:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The discovery of the electromagnetic counterpart to the binary neutron star (NS) merger GW170817 has opened the era of gravitational-wave multimessenger astronomy. Rapid identification of the optical/infrared kilonova enabled a precise localization of the source, which paved the way to deep multiwavelength follow-up and its myriad of related science results. Fully exploiting this new territory of exploration requires the acquisition of electromagnetic data from samples of NS mergers and other gravitational-wave sources. After GW170817, the frontier is now to map the diversity of kilonova properties and provide more stringent constraints on the Hubble constant, and enable new tests of fundamental physics. The Vera C. Rubin Observatory's Legacy Survey of Space and Time can play a key role in this field in the 2020s, when an improved network of gravitational-wave detectors is expected to reach a sensitivity that will enable the discovery of a high rate of merger events involving NSs (∼tens per year) out to distances of several hundred megaparsecs. We design comprehensive target-of-opportunity observing strategies for follow-up of gravitational-wave triggers that will make the Rubin Observatory the premier instrument for discovery and early characterization of NS and other compact-object mergers, and yet unknown classes of gravitational-wave events.
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  • Bangalore, Sripal, et al. (författare)
  • Management of Coronary Disease in Patients with Advanced Kidney Disease.
  • 2020
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 382:17, s. 1608-1618
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease.METHODS: We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest.RESULTS: At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P = 0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P = 0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P = 0.03).CONCLUSIONS: Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).
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  • Ganesh, S, et al. (författare)
  • Whole exome sequencing in dense families suggests genetic pleiotropy amongst Mendelian and complex neuropsychiatric syndromes
  • 2022
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1, s. 21128-
  • Tidskriftsartikel (refereegranskat)abstract
    • Whole Exome Sequencing (WES) studies provide important insights into the genetic architecture of serious mental illness (SMI). Genes that are central to the shared biology of SMIs may be identified by WES in families with multiple affected individuals with diverse SMI (F-SMI). We performed WES in 220 individuals from 75 F-SMI families and 60 unrelated controls. Within pedigree prioritization employed criteria of rarity, functional consequence, and sharing by ≥ 3 affected members. Across the sample, gene and gene-set-wide case–control association analysis was performed with Sequence Kernel Association Test (SKAT). In 14/16 families with ≥ 3 sequenced affected individuals, we identified a total of 78 rare predicted deleterious variants in 78 unique genes shared by ≥ 3 members with SMI. Twenty (25%) genes were implicated in monogenic CNS syndromes in OMIM (OMIM-CNS), a fraction that is a significant overrepresentation (Fisher’s Exact test OR = 2.47, p = 0.001). In gene-set SKAT, statistically significant association was noted for OMIM-CNS gene-set (SKAT-p = 0.005) but not the synaptic gene-set (SKAT-p = 0.17). In this WES study in F-SMI, we identify private, rare, protein altering variants in genes previously implicated in Mendelian neuropsychiatric syndromes; suggesting pleiotropic influences in neurodevelopment between complex and Mendelian syndromes.
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43.
  • Guralnik, B., et al. (författare)
  • OSL-thermochronometry using bedrock quartz : A note of caution
  • 2015
  • Ingår i: Quaternary Geochronology. - : Elsevier BV. - 1871-1014 .- 1878-0350. ; 25, s. 37-48
  • Tidskriftsartikel (refereegranskat)abstract
    • Optically stimulated luminescence (OSL) thermochronometry is an emerging application, whose capability to record sub-Million-year thermal histories is of increasing interest to a growing number of subdisciplines of Quaternary research. However, several recent studies have encountered difficulties both in extraction of OSL signals from bedrock quartz, and in their thermochronometric interpretation, thus highlighting the need for a methodological benchmark. Here, we investigate the characteristic OSL signals from quartz samples across all major types of bedrock and covering a wide range of chemical purities. High ratios of infrared to blue stimulated luminescence (IRSL/BLSL), an insensitive 'fast' OSL component, and anomalously short recombination lifetimes seen in time-resolved luminescence (TROSL), are often encountered in quartz from crystalline (magmatic and metamorphic) bedrock, and may hamper successful OSL dating. Furthermore, even when the desirable signal is present, its concentration might be indistinguishable from its environmental steady-state prediction, thus preventing its conversion to a cooling or heating history. We explore the saturation properties and the thermal activation parameters of various OSL signals in quartz to outline the capabilities and limitations for their use in low-temperature thermochronometry.
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  • Held, Claes, et al. (författare)
  • Physical activity levels, ownership of goods promoting sedentary behaviour and risk of myocardial infarction: results of the INTERHEART study
  • 2012
  • Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 33:4, s. 452-466
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: To evaluate the association between occupational and leisure-time physical activity (PA), ownership of goods promoting sedentary behaviour, and the risk of myocardial infarction (MI) in different socio-economic populations of the world. Studies in developed countries have found low PA as a risk factor for cardiovascular disease; however, the protective effect of occupational PA is less certain. Moreover, ownership of goods promoting sedentary behaviour may be associated with an increased risk. METHODS: In INTERHEART, a case-control study of 10 043 cases of first MI and 14 217 controls who did not report previous angina or physical disability completed a questionnaire on work and leisure-time PA. RESULTS: Subjects whose occupation involved either light [multivariable-adjusted odds ratio (OR) 0.78, confidence interval (CI) 0.71-0.86] or moderate (OR 0.89, CI 0.80-0.99) PA were at a lower risk of MI, whereas those who did heavy physical labour were not (OR 1.02, CI 0.88-1.19), compared with sedentary subjects. Mild exercise (OR 0.87, CI 0.81-0.93) as well as moderate or strenuous exercise (OR 0.76, CI 0.69-0.82) was protective. The effect of PA was observed across countries with low, middle, and high income. Subjects who owned both a car and a television (TV) (multivariable-adjusted OR 1.27, CI 1.05-1.54) were at higher risk of MI compared with those who owned neither. CONCLUSION: Leisure-time PA and mild-to-moderate occupational PA, but not heavy physical labour, were associated with a reduced risk, while ownership of a car and TV was associated with an increased risk of MI across all economic regions.
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  • Journeau, C., et al. (författare)
  • European Research on the Corium issues within the SARNET network of excellence
  • 2008
  • Ingår i: International Conference on Advances in Nuclear Power Plants, ICAPP 2008. - 9781605607870 ; , s. 1172-1181
  • Konferensbidrag (refereegranskat)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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47.
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48.
  • O’Reilly, Catherine M., et al. (författare)
  • Rapid and highly variable warming of lake surface waters around the globe
  • 2015
  • Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 42:24
  • Tidskriftsartikel (refereegranskat)abstract
    • In this first worldwide synthesis of in situ and satellite-derived lake data, we find that lake summer surface water temperatures rose rapidly (global mean = 0.34°C decade−1) between 1985 and 2009. Our analyses show that surface water warming rates are dependent on combinations of climate and local characteristics, rather than just lake location, leading to the counterintuitive result that regional consistency in lake warming is the exception, rather than the rule. The most rapidly warming lakes are widely geographically distributed, and their warming is associated with interactions among different climatic factors—from seasonally ice-covered lakes in areas where temperature and solar radiation are increasing while cloud cover is diminishing (0.72°C decade−1) to ice-free lakes experiencing increases in air temperature and solar radiation (0.53°C decade−1). The pervasive and rapid warming observed here signals the urgent need to incorporate climate impacts into vulnerability assessments and adaptation efforts for lakes.
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49.
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50.
  • Sawcer, Stephen, et al. (författare)
  • Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
  • 2011
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
  • Tidskriftsartikel (refereegranskat)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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