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Sökning: WFRF:(Muino P. Conde)

  • Resultat 451-460 av 460
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451.
  • Abat, E., et al. (författare)
  • Photon reconstruction in the ATLAS Inner Detector and Liquid Argon Barrel Calorimeter at the 2004 Combined Test Beam
  • 2011
  • Ingår i: Journal of Instrumentation. - 1748-0221. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • The reconstruction of photons in the ATLAS detector is studied with data taken during the 2004 Combined Test Beam, where a full slice of the ATLAS detector was exposed to beams of particles of known energy at the CERN SPS. The results presented show significant differences in the longitudinal development of the electromagnetic shower between converted and unconverted photons as well as in the total measured energy. The potential to use the reconstructed converted photons as a means to precisely map the material of the tracker in front of the electromagnetic calorimeter is also considered. All results obtained are compared with a detailed Monte-Carlo simulation of the test-beam setup which is based on the same simulation and reconstruction tools as those used for the ATLAS detector itself.
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452.
  • Mishra, A., et al. (författare)
  • Stroke genetics informs drug discovery and risk prediction across ancestries
  • 2022
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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453.
  • Abat, E., et al. (författare)
  • Study of the response of the ATLAS central calorimeter to pions of energies from 3 to 9 GeV
  • 2009
  • Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002 .- 1872-9576. ; 607:2, s. 372-386
  • Tidskriftsartikel (refereegranskat)abstract
    • A fully instrumented slice of the ATLAS central detector was exposed to test beams from the SPS (Super Proton Synchrotron) at CERN in 2004. in this paper, the response of the central calorimeters to pions with energies in the range between 3 and 9 GeV is presented. The linearity and the resolution of the combined calorimetry (electromagnetic and hadronic calorimeters) was measured and compared to the prediction of a detector simulation program using the toolkit Geant 4. (C) 2009 Elsevier B.V. All rights reserved.
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454.
  • Abata, E., et al. (författare)
  • Study of energy response and resolution of the ATLAS barrel calorimeter to hadrons of energies from 20 to 350 GeV
  • 2010
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576 .- 0167-5087. ; 621:1-3, s. 134-150
  • Tidskriftsartikel (refereegranskat)abstract
    • A fully instrumented slice of the ATLAS detector was exposed to test beams from the SPS (Super Proton Synchrotron) at CERN in 2004. In this paper, the results of the measurements of the response of the barrel calorimeter to hadrons with energies in the range 20-350 GeV and beam impact points and angles corresponding to pseudo-rapidity values in the range 0.2-0.65 are reported. The results are compared to the predictions of a simulation program using the Geant 4 toolkit. (C) 2010 Published by Elsevier B.V.
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455.
  • Mapelli, A., et al. (författare)
  • Development of a detector (ALFA) to measure the absolute LHC luminosity at ATLAS
  • 2008
  • Ingår i: Astroparticle, Particle and Space Physics, Detectors and Medical Physics Applications - Proceedings of the 10th Conference. - 9812819088 - 9789812819086 ; , s. 984-988
  • Konferensbidrag (refereegranskat)abstract
    • The ATLAS collaboration plans to determine the absolute luminosity of the CERN LHC at Interaction Point 1 by measuring the trajectory of protons elastically scattered at very small angles (μrad). A scintillating fibre tracker system called ALFA (Absolute Luminosity For ATLAS) is proposed for this measurement. Detector modules will be placed above and below the LHC beam axis in roman pot units at a distance of 240 m on cach side of the ATLAS interaction point. They allow the detectors to approach the beam axis to millimeter distance. Overlap detectors also based on the scintillating fibre technology, will measure the precise relative position of the two detector modules, Results obtained during beam tests at DESY and at CERN validate the detectors design and demonstrate the achievable resolution. We also report about radiation hardness studies of the scintillating fibres to estimate the lifetime of the ALFA system at different operating conditions of the LHC.
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456.
  • Anghinolfi, F., et al. (författare)
  • Hadron beam test of a scintillating fibre tracker system for elastic scattering and luminosity measurement in ATLAS
  • 2007
  • Ingår i: Journal of Instrumentation. - 1748-0221. ; 2
  • Tidskriftsartikel (refereegranskat)abstract
    • A scintillating fibre tracker is proposed to measure elastic proton scattering at very small angles in the ATLAS experiment at CERN. The tracker will be located in so-called Roman Pot units at a distance of 240 m on each side of the ATLAS interaction point. An initial validation of the design choices was achieved in a beam test at DESY in a relatively low energy electron beam and using slow off-the-shelf electronics. Here we report on the results from a second beam test experiment carried out at CERN, where new detector prototypes were tested in a high energy hadron beam, using the first version of the custom designed front-end electronics. With a spatial resolution of 25 mu m an adequate tracking performance was obtained, under conditions which are similar to the situation at the LHC. In addition, the alignment method using so-called overlap detectors was studied and shown to have the expected precision.
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457.
  • Heitsch, L., et al. (författare)
  • Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome
  • 2021
  • Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 52:1, s. 132-141
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose: Large-scale observational studies of acute ischemic stroke (AIS) promise to reveal mechanisms underlying cerebral ischemia. However, meaningful quantitative phenotypes attainable in large patient populations are needed. We characterize a dynamic metric of AIS instability, defined by change in National Institutes of Health Stroke Scale score (NIHSS) from baseline to 24 hours baseline to 24 hours (NIHSSbaseline - NIHSS24hours = Delta NIHSS6-24h), to examine its relevance to AIS mechanisms and long-term outcomes. Methods: Patients with NIHSS prospectively recorded within 6 hours after onset and then 24 hours later were enrolled in the GENISIS study (Genetics of Early Neurological Instability After Ischemic Stroke). Stepwise linear regression determined variables that independently influenced Delta NIHSS6-24h. In a subcohort of tPA (alteplase)-treated patients with large vessel occlusion, the influence of early sustained recanalization and hemorrhagic transformation on Delta NIHSS6-24h was examined. Finally, the association of Delta NIHSS6-24h with 90-day favorable outcomes (modified Rankin Scale score 0-2) was assessed. Independent analysis was performed using data from the 2 NINDS-tPA stroke trials (National Institute of Neurological Disorders and Stroke rt-PA). Results: For 2555 patients with AIS, median baseline NIHSS was 9 (interquartile range, 4-16), and median Delta NIHSS6-24h was 2 (interquartile range, 0-5). In a multivariable model, baseline NIHSS, tPA-treatment, age, glucose, site, and systolic blood pressure independently predicted Delta NIHSS6-24h (R-2=0.15). In the large vessel occlusion subcohort, early sustained recanalization and hemorrhagic transformation increased the explained variance (R-2=0.27), but much of the variance remained unexplained. Delta NIHSS6-24h had a significant and independent association with 90-day favorable outcome. For the subjects in the 2 NINDS-tPA trials, Delta NIHSS3-24h was similarly associated with 90-day outcomes. Conclusions: The dynamic phenotype, Delta NIHSS6-24h, captures both explained and unexplained mechanisms involved in AIS and is significantly and independently associated with long-term outcomes. Thus, Delta NIHSS6-24h promises to be an easily obtainable and meaningful quantitative phenotype for large-scale genomic studies of AIS.
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458.
  • Mola-Caminal, M., et al. (författare)
  • PATJ Low Frequency Variants Are Associated With Worse Ischemic Stroke Functional Outcome A Genome-Wide Meta-Analysis
  • 2019
  • Ingår i: Circulation research. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7330 .- 1524-4571. ; 124:1, s. 114-120
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale: Ischemic stroke is among the leading causes of adult disability. Part of the variability in functional outcome after stroke has been attributed to genetic factors but no locus has been consistently associated with stroke outcome. Objective: Our aim was to identify genetic loci influencing the recovery process using accurate phenotyping to produce the largest GWAS (genome-wide association study) in ischemic stroke recovery to date. Methods and Results: A 12-cohort, 2-phase (discovery-replication and joint) meta-analysis of GWAS included anterior-territory and previously independent ischemic stroke cases. Functional outcome was recorded using 3-month modified Rankin Scale. Analyses were adjusted for confounders such as discharge National Institutes of Health Stroke Scale. A gene-based burden test was performed. The discovery phase (n=1225) was followed by open (n=2482) and stringent joint-analyses (n=1791). Those cohorts with modified Rankin Scale recorded at time points other than 3-month or incomplete data on previous functional status were excluded in the stringent analyses. Novel variants in PATJ (Pals1-associated tight junction) gene were associated with worse functional outcome at 3-month after stroke. The top variant was rs76221407 (G allele, beta=0.40, P=1.70x10-9). Conclusions: Our results identify a set of common variants in PATJ gene associated with 3-month functional outcome at genome-wide significance level. Future studies should examine the role of PATJ in stroke recovery and consider stringent phenotyping to enrich the information captured to unveil additional stroke outcome loci.
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459.
  • Ibanez, L., et al. (författare)
  • Multi-ancestry GWAS reveals excitotoxicity associated with outcome after ischaemic stroke
  • 2022
  • Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:7, s. 2394-2406
  • Tidskriftsartikel (refereegranskat)abstract
    • During the first hours after stroke onset, neurological deficits can be highly unstable: some patients rapidly improve, while others deteriorate. This early neurological instability has a major impact on long-term outcome. Here, we aimed to determine the genetic architecture of early neurological instability measured by the difference between the National Institutes of Health Stroke Scale (NIHSS) within 6 h of stroke onset and NIHSS at 24 h. A total of 5876 individuals from seven countries (Spain, Finland, Poland, USA, Costa Rica, Mexico and Korea) were studied using a multi-ancestry meta-analyses. We found that 8.7% of NIHSS at 24 h of variance was explained by common genetic variations, and also that early neurological instability has a different genetic architecture from that of stroke risk. Eight loci (1p21.1, 1q42.2, 2p25.1, 2q31.2, 2q33.3, 5q33.2, 7p21.2 and 13q31.1) were genome-wide significant and explained 1.8% of the variability suggesting that additional variants influence early change in neurological deficits. We used functional genomics and bioinformatic annotation to identify the genes driving the association from each locus. Expression quantitative trait loci mapping and summary data-based Mendelian randomization indicate that ADAM23 (log Bayes factor = 5.41) was driving the association for 2q33.3. Gene-based analyses suggested that GRIA1 (log Bayes factor = 5.19), which is predominantly expressed in the brain, is the gene driving the association for the 5q33.2 locus. These analyses also nominated GNPAT (log Bayes factor = 7.64) ABCB5 (log Bayes factor = 5.97) for the 1p21.1 and 7p21.1 loci. Human brain single-nuclei RNA-sequencing indicates that the gene expression of ADAM23 and GRIA1 is enriched in neurons. ADAM23, a presynaptic protein and GRIA1, a protein subunit of the AMPA receptor, are part of a synaptic protein complex that modulates neuronal excitability. These data provide the first genetic evidence in humans that excitotoxicity may contribute to early neurological instability after acute ischaemic stroke. Ibanez et al. perform a multi-ancestry meta-analysis to investigate the genetic architecture of early stroke outcomes. Two of the eight genome-wide significant loci identified-ADAM23 and GRIA1-are involved in synaptic excitability, suggesting that excitotoxicity contributes to neurological instability after ischaemic stroke.
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460.
  • Muino, E., et al. (författare)
  • RP11-362K2.2:RP11-767I20.1 Genetic Variation Is Associated with Post-Reperfusion Therapy Parenchymal Hematoma. A GWAS Meta-Analysis
  • 2021
  • Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 10:14
  • Tidskriftsartikel (refereegranskat)abstract
    • Stroke is one of the most common causes of death and disability. Reperfusion therapies are the only treatment available during the acute phase of stroke. Due to recent clinical trials, these therapies may increase their frequency of use by extending the time-window administration, which may lead to an increase in complications such as hemorrhagic transformation, with parenchymal hematoma (PH) being the more severe subtype, associated with higher mortality and disability rates. Our aim was to find genetic risk factors associated with PH, as that could provide molecular targets/pathways for their prevention/treatment and study its genetic correlations to find traits sharing genetic background. We performed a GWAS and meta-analysis, following standard quality controls and association analysis (fastGWAS), adjusting age, NIHSS, and principal components. FUMA was used to annotate, prioritize, visualize, and interpret the meta-analysis results. The total number of patients in the meta-analysis was 2034 (216 cases and 1818 controls). We found rs79770152 having a genome-wide significant association (beta 0.09, p-value 3.90 x 10(-8)) located in the RP11-362K2.2:RP11-767I20.1 gene and a suggestive variant (rs13297983: beta 0.07, p-value 6.10 x 10(-8)) located in PCSK5 associated with PH occurrence. The genetic correlation showed a shared genetic background of PH with Alzheimer's disease and white matter hyperintensities. In addition, genes containing the ten most significant associations have been related to aggregated amyloid-beta, tau protein, white matter microstructure, inflammation, and matrix metalloproteinases.
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