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Sökning: WFRF:(Diaz Alejandro)

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1.
  • Abelev, Betty, et al. (författare)
  • Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
  • 2013
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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2.
  • Abelev, Betty, et al. (författare)
  • Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
  • 2012
  • Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
  • Tidskriftsartikel (refereegranskat)abstract
    • The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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3.
  • 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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4.
  • Bernal, Ximena E., et al. (författare)
  • Empowering Latina scientists
  • 2019
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6429, s. 825-826
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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5.
  • Ferrando, Carlos, et al. (författare)
  • Effects of oxygen on post-surgical infections during an individualised perioperative open-lung ventilatory strategy : a randomised controlled trial
  • 2020
  • Ingår i: British Journal of Anaesthesia. - : ELSEVIER SCI LTD. - 0007-0912 .- 1471-6771. ; 124:1, s. 110-120
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We aimed to examine whether using a high fraction of inspired oxygen (FIO2) in the context of an individualised intra- and postoperative open-lung ventilation approach could decrease surgical site infection (SSI) in patients scheduled for abdominal surgery. Methods: We performed a multicentre, randomised controlled clinical trial in a network of 21 university hospitals from June 6, 2017 to July 19, 2018. Patients undergoing abdominal surgery were randomly assigned to receive a high (0.80) or conventional (0.3) FIO2 during the intraoperative period and during the first 3 postoperative hours. All patients were mechanically ventilated with an open-lung strategy, which included recruitment manoeuvres and individualised positive end-expiratory pressure for the best respiratory-system compliance, and individualised continuous postoperative airway pressure for adequate peripheral oxyhaemoglobin saturation. The primary outcome was the prevalence of SSI within the first 7 postoperative days. The secondary outcomes were composites of systemic complications, length of intensive care and hospital stay, and 6-month mortality. Results: We enrolled 740 subjects: 371 in the high FIO2 group and 369 in the low FIO2 group. Data from 717 subjects were available for final analysis. The rate of SSI during the first postoperative week did not differ between high (8.9%) and low (9.4%) FIO2 groups (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.59-1.50; P=0.90]). Secondary outcomes, such as atelectasis (7.7% vs 9.8%; RR: 0.77; 95% CI: 0.48-1.25; P=0.38) and myocardial ischaemia (0.6% [n=2] vs 0% [n=0]; P=0.47) did not differ between groups. Conclusions: An oxygenation strategy using high FIO2 compared with conventional FIO2 did not reduce postoperative SSIs in abdominal surgery. No differences in secondary outcomes or adverse events were found.
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6.
  • Abbasi, Rasha, et al. (författare)
  • IceCube search for neutrinos from GRB 221009A
  • 2023
  • Ingår i: Proceedings of 38th International Cosmic Ray Conference (ICRC 2023). - : Sissa Medialab Srl.
  • Konferensbidrag (refereegranskat)abstract
    •  GRB 221009A is the brightest Gamma Ray Burst (GRB) ever observed. The observed extremelyhigh flux of high and very-high-energy photons provide a unique opportunity to probe the predictedneutrino counterpart to the electromagnetic emission. We have used a variety of methods to searchfor neutrinos in coincidence with the GRB over several time windows during the precursor, promptand afterglow phases of the GRB. MeV scale neutrinos are studied using photo-multiplier ratescalers which are normally used to search for galactic core-collapse supernovae neutrinos. GeVneutrinos are searched starting with DeepCore triggers. These events don’t have directionallocalization, but instead can indicate an excess in the rate of events. 10 GeV - 1 TeV and >TeVneutrinos are searched using traditional neutrino point source methods which take into accountthe direction and time of events with DeepCore and the entire IceCube detector respectively. The>TeV results include both a fast-response analysis conducted by IceCube in real-time with timewindows of T0 − 1 to T0 + 2 hours and T0 ± 1 day around the time of GRB 221009A, as well asan offline analysis with 3 new time windows up to a time window of T0 − 1 to T0 + 14 days, thelongest time period we consider. The combination of observations by IceCube covers 9 ordersof magnitude in neutrino energy, from MeV to PeV, placing upper limits across the range forpredicted neutrino emission.
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7.
  • Abelev, Betty, et al. (författare)
  • Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
  • 2012
  • Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
  • Tidskriftsartikel (refereegranskat)abstract
    • We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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8.
  • Carraminana, Albert, et al. (författare)
  • Rationale and Study Design for an Individualized Perioperative Open Lung Ventilatory Strategy in Patients on One-Lung Ventilation (iPROVE-OLV)
  • 2019
  • Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : W B SAUNDERS CO-ELSEVIER INC. - 1053-0770 .- 1532-8422. ; 33:9, s. 2492-2502
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aim of this clinical trial is to examine whether it is possible to reduce postoperative complications using an individualized perioperative ventilatory strategy versus using a standard lung-protective ventilation strategy in patients scheduled for thoracic surgery requiring one-lung ventilation. Design: International, multicenter, prospective, randomized controlled clinical trial. Setting: A network of university hospitals. Participants: The study comprises 1,380 patients scheduled for thoracic surgery. Interventions: The individualized group will receive intraoperative recruitment maneuvers followed by individualized positive end-expiratory pressure (open lung approach) during the intraoperative period plus postoperative ventilatory support with high-flow nasal cannula, whereas the control group will be managed with conventional lung-protective ventilation. Measurements and Main Results: Individual and total number of postoperative complications, including atelectasis, pneumothorax, pleural effusion, pneumonia, acute lung injury; unplanned readmission and reintubation; length of stay and death in the critical care unit and in the hospital will be analyzed for both groups. The authors hypothesize that the intraoperative application of an open lung approach followed by an individual indication of high-flow nasal cannula in the postoperative period will reduce pulmonary complications and length of hospital stay in high-risk surgical patients. (C) 2019 Published by Elsevier Inc.
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9.
  • Edwards, Robert A., et al. (författare)
  • Global phylogeography and ancient evolution of the widespread human gut virus crAssphage
  • 2019
  • Ingår i: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 4:10, s. 1727-1736
  • Tidskriftsartikel (refereegranskat)abstract
    • Microbiomes are vast communities of microorganisms and viruses that populate all natural ecosystems. Viruses have been considered to be the most variable component of microbiomes, as supported by virome surveys and examples of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared with that of other environments. Here, we investigate the origin, evolution and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboration, we obtained DNA sequences of crAssphage from more than one-third of the world's countries and showed that the phylogeography of crAssphage is locally clustered within countries, cities and individuals. We also found fully colinear crAssphage-like genomes in both Old-World and New-World primates, suggesting that the association of crAssphage with primates may be millions of years old. Finally, by exploiting a large cohort of more than 1,000 individuals, we tested whether crAssphage is associated with bacterial taxonomic groups of the gut microbiome, diverse human health parameters and a wide range of dietary factors. We identified strong correlations with different clades of bacteria that are related to Bacteroidetes and weak associations with several diet categories, but no significant association with health or disease. We conclude that crAssphage is a benign cosmopolitan virus that may have coevolved with the human lineage and is an integral part of the normal human gut virome.
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10.
  • Hudson, Lawrence N, et al. (författare)
  • The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
  • 2017
  • Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
  • Tidskriftsartikel (refereegranskat)abstract
    • The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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11.
  • Hudson, Lawrence N., et al. (författare)
  • The PREDICTS database : a global database of how local terrestrial biodiversity responds to human impacts
  • 2014
  • Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:24, s. 4701-4735
  • Tidskriftsartikel (refereegranskat)abstract
    • Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
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12.
  • López-Isac, Elena, et al. (författare)
  • Brief Report : IRF4 Newly Identified as a Common Susceptibility Locus for Systemic Sclerosis and Rheumatoid Arthritis in a Cross-Disease Meta-Analysis of Genome-Wide Association Studies
  • 2016
  • Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 68:9, s. 2338-2344
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that have similar clinical and immunologic characteristics. To date, several shared SSc–RA genetic loci have been identified independently. The aim of the current study was to systematically search for new common SSc–RA loci through an interdisease meta–genome-wide association (meta-GWAS) strategy. Methods: The study was designed as a meta-analysis combining GWAS data sets of patients with SSc and patients with RA, using a strategy that allowed identification of loci with both same-direction and opposite-direction allelic effects. The top single-nucleotide polymorphisms were followed up in independent SSc and RA case–control cohorts. This allowed an increase in the sample size to a total of 8,830 patients with SSc, 16,870 patients with RA, and 43,393 healthy controls. Results: This cross-disease meta-analysis of the GWAS data sets identified several loci with nominal association signals (P < 5 × 10−6) that also showed evidence of association in the disease-specific GWAS scans. These loci included several genomic regions not previously reported as shared loci, as well as several risk factors that were previously found to be associated with both diseases. Follow-up analyses of the putatively new SSc–RA loci identified IRF4 as a shared risk factor for these 2 diseases (Pcombined = 3.29 × 10−12). Analysis of the biologic relevance of the known SSc–RA shared loci identified the type I interferon and interleukin-12 signaling pathways as the main common etiologic factors. Conclusion: This study identified a novel shared locus, IRF4, for the risk of SSc and RA, and highlighted the usefulness of a cross-disease GWAS meta-analysis strategy in the identification of common risk loci.
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13.
  • Menkveld, Albert J., et al. (författare)
  • Nonstandard Errors
  • 2024
  • Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
  • Tidskriftsartikel (refereegranskat)abstract
    • In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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15.
  • Prieto-Díaz, Rubén, et al. (författare)
  • Exploring the Effect of Halogenation in a Series of Potent and Selective A2B Adenosine Receptor Antagonists
  • 2023
  • Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 66:1, s. 890-912
  • Tidskriftsartikel (refereegranskat)abstract
    • The modulation of the A2B adenosine receptor is a promising strategy in cancer (immuno) therapy, with A2BAR antagonists emerging as immune checkpoint inhibitors. Herein, we report a systematic assessment of the impact of (di- and mono-)halogenation at positions 7 and/or 8 on both A2BAR affinity and pharmacokinetic properties of a collection of A2BAR antagonists and its study with structure-based free energy perturbation simulations. Monohalogenation at position 8 produced potent A2BAR ligands irrespective of the nature of the halogen. In contrast, halogenation at position 7 and dihalogenation produced a halogen-size-dependent decay in affinity. Eight novel A2BAR ligands exhibited remarkable affinity (Ki < 10 nM), exquisite subtype selectivity, and enantioselective recognition, with some eutomers eliciting sub-nanomolar affinity. The pharmacokinetic profile of representative derivatives showed enhanced solubility and microsomal stability. Finally, two compounds showed the capacity of reversing the antiproliferative effect of adenosine in activated primary human peripheral blood mononuclear cells.
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16.
  • Val, Cristina, et al. (författare)
  • Optimization of 2-Amino-4,6-diarylpyrimidine-5-carbonitriles as Potent and Selective A(1) Antagonists
  • 2022
  • Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 65:3, s. 2091-2106
  • Tidskriftsartikel (refereegranskat)abstract
    • We herein document a large collection of 108 2-amino-4,6-disubstituted-pyrimidine derivatives as potent, structurally simple, and highly selective A(1)AR ligands. The most attractive ligands were confirmed as antagonists of the canonical cyclic adenosine monophosphate pathway, and some pharmacokinetic parameters were preliminarily evaluated. The library, built through a reliable and efficient three-component reaction, comprehensively explored the chemical space allowing the identification of the most prominent features of the structure-activity and structure-selectivity relationships around this scaffold. These included the influence on the selectivity profile of the aromatic residues at positions R-4 and R-6 of the pyrimidine core but most importantly the prominent role to the unprecedented A(1)AR selectivity profile exerted by the methyl group introduced at the exocyclic amino group. The structure-activity relationship trends on both A(1) and A(2A)ARs were conveniently interpreted with rigorous free energy perturbation simulations, which started from the receptor-driven docking model that guided the design of these series.
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17.
  • Aad, G., et al. (författare)
  • Commissioning of the ATLAS Muon Spectrometer with cosmic rays
  • 2010
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 875-916
  • Tidskriftsartikel (refereegranskat)abstract
    • The ATLAS detector at the Large Hadron Collider has collected several hundred million cosmic ray events during 2008 and 2009. These data were used to commission the Muon Spectrometer and to study the performance of the trigger and tracking chambers, their alignment, the detector control system, the data acquisition and the analysis programs. We present the performance in the relevant parameters that determine the quality of the muon measurement. We discuss the single element efficiency, resolution and noise rates, the calibration method of the detector response and of the alignment system, the track reconstruction efficiency and the momentum measurement. The results show that the detector is close to the design performance and that the Muon Spectrometer is ready to detect muons produced in high energy proton-proton collisions.
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18.
  • Aad, G., et al. (författare)
  • Readiness of the ATLAS Tile Calorimeter for LHC collisions
  • 2010
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:4, s. 1193-1236
  • Tidskriftsartikel (refereegranskat)abstract
    • The Tile hadronic calorimeter of the ATLAS detector has undergone extensive testing in the experimental hall since its installation in late 2005. The readout, control and calibration systems have been fully operational since 2007 and the detector has successfully collected data from the LHC single beams in 2008 and first collisions in 2009. This paper gives an overview of the Tile Calorimeter performance as measured using random triggers, calibration data, data from cosmic ray muons and single beam data. The detector operation status, noise characteristics and performance of the calibration systems are presented, as well as the validation of the timing and energy calibration carried out with minimum ionising cosmic ray muons data. The calibration systems' precision is well below the design value of 1%. The determination of the global energy scale was performed with an uncertainty of 4%.
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19.
  • Aad, G., et al. (författare)
  • Studies of the performance of the ATLAS detector using cosmic-ray muons
  • 2011
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 71:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Muons from cosmic-ray interactions in the atmosphere provide a high-statistics source of particles that can be used to study the performance and calibration of the ATLAS detector. Cosmic-ray muons can penetrate to the cavern and deposit energy in all detector subsystems. Such events have played an important role in the commissioning of the detector since the start of the installation phase in 2005 and were particularly important for understanding the detector performance in the time prior to the arrival of the first LHC beams. Global cosmic-ray runs were undertaken in both 2008 and 2009 and these data have been used through to the early phases of collision data-taking as a tool for calibration, alignment and detector monitoring. These large datasets have also been used for detector performance studies, including investigations that rely on the combined performance of different subsystems. This paper presents the results of performance studies related to combined tracking, lepton identification and the reconstruction of jets and missing transverse energy. Results are compared to expectations based on a cosmic-ray event generator and a full simulation of the detector response.
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20.
  • Aad, G., et al. (författare)
  • The ATLAS Inner Detector commissioning and calibration
  • 2010
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 787-821
  • Tidskriftsartikel (refereegranskat)abstract
    • The ATLAS Inner Detector is a composite tracking system consisting of silicon pixels, silicon strips and straw tubes in a 2 T magnetic field. Its installation was completed in August 2008 and the detector took part in data-taking with single LHC beams and cosmic rays. The initial detector operation, hardware commissioning and in-situ calibrations are described. Tracking performance has been measured with 7.6 million cosmic-ray events, collected using a tracking trigger and reconstructed with modular pattern-recognition and fitting software. The intrinsic hit efficiency and tracking trigger efficiencies are close to 100%. Lorentz angle measurements for both electrons and holes, specific energy-loss calibration and transition radiation turn-on measurements have been performed. Different alignment techniques have been used to reconstruct the detector geometry. After the initial alignment, a transverse impact parameter resolution of 22.1 +/- 0.9 mu m and a relative momentum resolution sigma (p) /p=(4.83 +/- 0.16)x10(-4) GeV(-1)xp (T) have been measured for high momentum tracks.
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21.
  • Aad, G., et al. (författare)
  • The ATLAS Simulation Infrastructure
  • 2010
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 823-874
  • Tidskriftsartikel (refereegranskat)abstract
    • The simulation software for the ATLAS Experiment at the Large Hadron Collider is being used for large-scale production of events on the LHC Computing Grid. This simulation requires many components, from the generators that simulate particle collisions, through packages simulating the response of the various detectors and triggers. All of these components come together under the ATLAS simulation infrastructure. In this paper, that infrastructure is discussed, including that supporting the detector description, interfacing the event generation, and combining the GEANT4 simulation of the response of the individual detectors. Also described are the tools allowing the software validation, performance testing, and the validation of the simulated output against known physics processes.
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22.
  • Beaney, Thomas, et al. (författare)
  • May measurement month 2019 : The global blood pressure screening campaign of the international society of hypertension
  • 2020
  • Ingår i: Hypertension. - 0194-911X. ; 76:2, s. 333-341
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated blood pressure remains the single biggest risk factor contributing to the global burden of disease and mortality. May Measurement Month is an annual global screening campaign aiming to improve awareness of blood pressure at the individual and population level. Adults (≥18 years) recruited through opportunistic sampling were screened at sites in 92 countries during May 2019. Ideally, 3 blood pressure readings were measured for each participant, and data on lifestyle factors and comorbidities were collected. Hypertension was defined as a systolic blood pressure ≥140 mm Hg, or a diastolic blood pressure ≥90 mm Hg (mean of the second and third readings) or taking antihypertensive medication. When necessary, multiple imputation was used to estimate participants' mean blood pressure. Mixed-effects models were used to evaluate associations between blood pressure and participant characteristics. Of 1 508 130 screenees 482 273 (32.0%) had never had a blood pressure measurement before and 513 337 (34.0%) had hypertension, of whom 58.7% were aware, and 54.7% were on antihypertensive medication. Of those on medication, 57.8% were controlled to <140/90 mm Hg, and 28.9% to <130/80 mm Hg. Of all those with hypertension, 31.7% were controlled to <140/90 mm Hg, and 350 825 (23.3%) participants had untreated or inadequately treated hypertension. Of those taking antihypertensive medication, half were taking only a single drug, and 25% reported using aspirin inappropriately. This survey is the largest ever synchronized and standardized contemporary compilation of global blood pressure data. This campaign is needed as a temporary substitute for systematic blood pressure screening in many countries worldwide.
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23.
  • Bentham, James, et al. (författare)
  • A century of trends in adult human height
  • 2016
  • Ingår i: eLIFE. - 2050-084X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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24.
  • Bentham, James, et al. (författare)
  • A century of trends in adult human height
  • 2016
  • Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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25.
  • Cambronero, Maria Emilia, 1978, et al. (författare)
  • Towards a GDPR-compliant cloud architecture with data privacy controlled through sticky policies
  • 2024
  • Ingår i: PeerJ Computer Science. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Data privacy is one of the biggest challenges facing system architects at the system design stage. Especially when certain laws, such as the General Data Protection Regulation (GDPR), have to be complied with by cloud environments. In this article, we want to help cloud providers comply with the GDPR by proposing a GDPR-compliant cloud architecture. To do this, we use model-driven engineering techniques to design cloud architecture and analyze cloud interactions. In particular, we develop a complete framework, called MDCT, which includes a Unified Modeling Language profile that allows us to define specific cloud scenarios and profile validation to ensure that certain required properties are met. The validation process is implemented through the Object Constraint Language (OCL) rules, which allow us to describe the constraints in these models. To comply with many GDPR articles, the proposed cloud architecture considers data privacy and data tracking, enabling safe and secure data management and tracking in the context of the cloud. For this purpose, sticky policies associated with the data are incorporated to define permission for third parties to access the data and track instances of data access. As a result, a cloud architecture designed with MDCT contains a set of OCL rules to validate it as a GDPR-compliant cloud architecture. Our tool models key GDPR points such as user consent/withdrawal, the purpose of access, and data transparency and auditing, and considers data privacy and data tracking with the help of sticky policies.
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26.
  • Carrera, Caty, et al. (författare)
  • Validation of a clinical-genetics score to predict hemorrhagic transformations after rtPA.
  • 2019
  • Ingår i: Neurology. - 1526-632X. ; 93:9
  • Tidskriftsartikel (refereegranskat)abstract
    • To validate the Genot-PA score, a clinical-genetic logistic regression score that stratifies the thrombolytic therapy safety, in a new cohort of patients with stroke.We enrolled 1,482 recombinant tissue plasminogen activator (rtPA)-treated patients with stroke in Spain and Finland from 2003 to 2016. Cohorts were analyzed on the basis of ethnicity and therapy: Spanish patients treated with IV rtPA within 4.5 hours of onset (cohort A and B) or rtPA in combination with mechanical thrombectomy within 6 hours of onset (cohort C) and Finnish participants treated with IV rtPA within 4.5 hours of onset (cohort D). The Genot-PA score was calculated, and hemorrhagic transformation (HT) and parenchymal hematoma (PH) risks were determined for each score stratum.Genot-PA score was tested in 1,324 (cohort A, n = 726; B, n = 334; C, n = 54; and D, n = 210) patients who had enough information to complete the score. Of these, 213 (16.1%) participants developed HT and 85 (6.4%) developed PH. In cohorts A, B, and D, HT occurrence was predicted by the score (p = 2.02 × 10-6, p = 0.023, p = 0.033); PH prediction was associated in cohorts A through C (p = 0.012, p = 0.034, p = 5.32 × 10-4). Increased frequency of PH events from the lowest to the highest risk group was found (cohort A 4%-15.7%, cohort B 1.5%-18.2%, cohort C 0%-100%). The best odds ratio for PH prediction in the highest-risk group was obtained in cohort A (odds ratio 5.16, 95% confidence interval 1.46-18.08, p = 0.009).The Genot-PA score predicts HT in patients with stroke treated with IV rtPA. Moreover, in an exploratory study, the score was associated with PH risk in mechanical thrombectomy-treated patients.
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27.
  • Cruz, Raquel, et al. (författare)
  • Novel genes and sex differences in COVID-19 severity
  • 2022
  • Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
  • Tidskriftsartikel (refereegranskat)abstract
    • Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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28.
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29.
  • Diaz, Gonzalo Pablo Navarro, et al. (författare)
  • Actuator line model using simplified force calculation methods
  • 2023
  • Ingår i: Wind Energy Science. - : Copernicus Publications. - 2366-7443 .- 2366-7451. ; 8:3, s. 363-382
  • Tidskriftsartikel (refereegranskat)abstract
    • To simulate transient wind turbine wake interaction problems using limited wind turbine data, two new variants of the actuator line technique are proposed in which the rotor blade forces are computed locally using generic load data. The proposed models, which are extensions of the actuator disk force models proposed by Navarro Diaz et al. (2019a) and Sorensen et al. (2020), only demand thrust and power coefficients and the tip speed ratio as input parameters. In the paper the analogy between the actuator disk model (ADM) and the actuator line model (ALM) is shown, and from this a simple methodology to implement local forces in the ALM without the need for knowledge of blade geometry and local airfoil data is derived. Two simplified variants of ALMs are proposed, an analytical one based on Sorensen et al. (2020) and a numerical one based on Navarro Diaz et al. (2019a). The proposed models are compared to the ADM using analogous data, as well as to the classical ALM based on blade element theory, which provides more detailed force distributions by using airfoil data. To evaluate the local force calculation, the analysis of a partial-wake interaction case between two wind turbines is carried out for a uniform laminar inflow and for a turbulent neutral atmospheric boundary layer inflow. The computations are performed using the large eddy simulation facility in Open Source Field Operation and Manipulation (OpenFOAM), including Simulator for Wind Farm Applications (SOWFA) libraries and the reference National Renewable Energy Laboratory (NREL) 5 MW wind turbine as the test case. In the single-turbine case, computed normal and tangential force distributions along the blade showed a very good agreement between the employed models. The two new ALMs exhibited the same distribution as the ALM based on geometry and airfoil data, with minor differences due to the particular tip correction needed in the ALM. For the challenging partially impacted wake case, both the analytical and the numerical approaches manage to correctly capture the force distribution at the different regions of the rotor area, with, however, a consistent overestimation of the normal force outside the wake and an underestimation inside the wake. The analytical approach shows a slightly better performance in wake impact cases compared to the numerical one. As expected, the ALMs gave a much more detailed prediction of the higher-frequency power output fluctuations than the ADM. These promising findings open the possibility to simulate commercial wind farms in transient inflows using the ALM without having to get access to actual wind turbine and airfoil data, which in most cases are restricted due to confidentiality.
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30.
  • Diaz-Holguin, Alejandro, et al. (författare)
  • When Two Become One : Conformational Changes in FXR/RXR Heterodimers Bound to Steroidal Antagonists
  • 2023
  • Ingår i: ChemMedChem. - : John Wiley & Sons. - 1860-7179 .- 1860-7187. ; 18:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Farnesoid X receptor (FXR) is a nuclear receptor with an essential role in regulating bile acid synthesis and cholesterol homeostasis. FXR activation by agonists is explained by an alpha AF-2-trapping mechanism; however, antagonism mechanisms are diverse. We discuss microsecond molecular dynamics (MD) simulations investigating our recently reported FXR antagonists 2a and 2 h. We study the antagonist-induced conformational changes in the FXR ligand-binding domain, when compared to the synthetic (GW4064) or steroidal (chenodeoxycholic acid, CDCA) FXR agonists in the FXR monomer or FXR/RXR heterodimer r, and in the presence and absence of the coactivator. Our MD data suggest ligand-specific influence on conformations of different FXR-LBD regions, including the alpha 5/alpha 6 region, alpha AF-2, and alpha 9-11. Changes in the heterodimerization interface induced by antagonists seem to be associated with alpha AF-2 destabilization, which prevents both co-activator and co-repressor recruitment. Our results provide new insights into the conformational behaviour of FXR, suggesting that FXR antagonism/agonism shift requires a deeper assessment than originally proposed by crystal structures.
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31.
  • Diaz Puebla, Alejandro, et al. (författare)
  • Sizing of actuators for flight control systems and flaps integration in RAPID
  • 2015
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • The architecture of the flight control system, essentialfor all flight operations, has significantlychanged throughout the years. The first part ofthe work consists of a preliminary sizing modelof an EHA and an EMA. The second part of thework consists of the development of parametricCAD models of different types of flaps and theirintegration in RAPID. This thesis addresses theactuation system architecture of what it is namedas more electric aircraft with electrically poweredactuators. This consists of the development offlexible parametric models of flight control surfaces,being able to adapt to any wing geometryand their automatic integration in RAPID. Furthermore,it represents a first step in the developmentof an automatic tool that allows the user tochoose any possible wing control surface configuration.
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32.
  • Díaz-Sánchez, Adrian Alberto, et al. (författare)
  • Development and application of a multiplex TaqMan® real-time qPCR assay for the simultaneous detection of anaplasma marginale and theileria annulata and molecular characterization of anaplasma marginale from cattle in Western Cuba."/>
  • 2020
  • Ingår i: Ticks and Tick-borne Diseases. - : Elsevier BV. - 1877-959X .- 1877-9603. ; 11:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Anaplasmosis and theileriosis are considered the most important tick-borne diseases for livestock production worldwide, causing significant economic losses in tropical and subtropical regions. The present study was aimed to develop a multiplex TaqMan® qPCR assay to simultaneously detect Anaplasma marginale and Theileria annulata and to applied it to investigate naturally infected cattle in Cuba. The assay was highly specific, sensible, and efficient; it was more sensitive than a well-established nested PCR and detected 1 DNA copy of each target. Consistent repeatability and reproducibility within and between multiplex qPCR runs was shown. A total of 223 blood samples collected in western Cuba were analyzed for haemoparasites infection in cattle. The multiplex qPCR assay detected A. marginale in 213 samples (95.5%; CI: 95%; 91.9%–97.5%), but all samples were negative for T. annulata. Additionally, the genetic diversity of A. marginale was assessed using 16S rRNA, MSP1a and MSP4 nucleotide and protein sequences. The MSP1a tandem repeats ranged from three to five, and twelve different MSP1a tandem repeats of A. marginale were found, which presented genotypes C, E, and G in the 5ʹUTR microsatellite region. Phylogenetic analysis using the msp4 gene showed that Cuban strains were closely related to others previously reported in Mexico, Brazil and Asian countries. The multiplex qPCR described here proved to be a rapid, specific and cost-effective mean for the simultaneous detection of A. marginale and T. annulata. Further epidemiological studies using this assay will improve the surveillance of the associated diseases in regions where they are endemic.
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33.
  • Díaz-Sánchez, Adrian A., et al. (författare)
  • Molecular detection and identification of tick-borne pathogens in Equus caballus and ticks from western Cuba : [Detección e identificación molecular de patógenos transmitidos por garrapatas en Equus caballus y garrapatas del occidente de Cuba]
  • 2022
  • Ingår i: Biotecnologia Aplicada. - : Elfos Scientiae. - 0864-4551 .- 1027-2852. ; 39:2, s. 2501-2505
  • Tidskriftsartikel (refereegranskat)abstract
    • Babesia caballi, Theileria equi and several species of rickettsias are agents of vector-borne diseases that affect equines. The objective of this study was to detect infections by B. caballi and T. equi in horses and to identify rickettsias in horses and ticks in the western region of Cuba. Two nPCR assays were developed and standardized for the detection of B. caballi and T. equi. Blood samples from horses and ticks were collected. Identification by blood smear and molecular detection and identification of B. caballi, T. equi and Rickettsia spp. were carried out. Intraerythrocytic formations compatible with B. caballi and T. equi were observed. The nPCR showed that 25 % of the samples were positive for B. caballi, 73 % for T. equi and 20 % showed coinfection. The results were confirmed with the partial sequencing of the genes bc48 (B. caballi) and ema-1 (T. equi). The sequencing of the 18S rRNA gene of T. equi demonstrated the presence of at least two genotypes of T. equi isolates in Cuba. The real time qPCR assay and sequencing revealed the presence of Rickettsia amblyommatis in A. mixtum and Rickettsia felis in D. nitens.Conclusions: These results constitute the first piece of molecular evidence of B. caballi and T. equi in horses and the first report of R. felis in D. nitens in Cuba, which broadens the knowledge about the distribution of pathogens and the spectrum of potential vectors contributing to the strengthening of management and control programs.
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34.
  • Duffy, J. Emmett, et al. (författare)
  • Toward a Coordinated Global Observing System for Seagrasses and Marine Macroalgae
  • 2019
  • Ingår i: Frontiers in Marine Science. - : Frontiers Media S.A.. - 2296-7745. ; 6
  • Forskningsöversikt (refereegranskat)abstract
    • In coastal waters around the world, the dominant primary producers are benthic macrophytes, including seagrasses and macroalgae, that provide habitat structure and food for diverse and abundant biological communities and drive ecosystem processes. Seagrass meadows and macroalgal forests play key roles for coastal societies, contributing to fishery yields, storm protection, biogeochemical cycling and storage, and important cultural values. These socio-economically valuable services are threatened worldwide by human activities, with substantial areas of seagrass and macroalgal forests lost over the last half-century. Tracking the status and trends in marine macrophyte cover and quality is an emerging priority for ocean and coastal management, but doing so has been challenged by limited coordination across the numerous efforts to monitor macrophytes, which vary widely in goals, methodologies, scales, capacity, governance approaches, and data availability. Here, we present a consensus assessment and recommendations on the current state of and opportunities for advancing global marine macrophyte observations, integrating contributions from a community of researchers with broad geographic and disciplinary expertise. With the increasing scale of human impacts, the time is ripe to harmonize marine macrophyte observations by building on existing networks and identifying a core set of common metrics and approaches in sampling design, field measurements, governance, capacity building, and data management. We recommend a tiered observation system, with improvement of remote sensing and remote underwater imaging to expand capacity to capture broad-scale extent at intervals of several years, coordinated with strati fied in situ sampling annually to characterize the key variables of cover and taxonomic or functional group composition, and to provide ground-truth. A robust networked system of macrophyte observations will be facilitated by establishing best practices, including standard protocols, documentation, and sharing of resources at all stages of work flow, and secure archiving of open-access data. Because such a network is necessarily distributed, sustaining it depends on close engagement of local stakeholders and focusing on building and long-term maintenance of local capacity, particularly in the developing world. Realizing these recommendations will producemore effective, efficient, and responsive observing, a more accurate global picture of change in vegetated coastal systems, and stronger international capacity for sustaining observations.
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35.
  • Fusai, Giuseppe Kito, et al. (författare)
  • Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries
  • 2023
  • Ingår i: British Journal of Surgery. - : OXFORD UNIV PRESS. - 0007-1323 .- 1365-2168.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide. Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters. Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries. Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761).
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36.
  • Garcia-Loro, Felix, et al. (författare)
  • Experimenting in PILAR federation : A common path for the future
  • 2018
  • Ingår i: PROCEEDINGS OF 2018 IEEE GLOBAL ENGINEERING EDUCATION CONFERENCE (EDUCON) - EMERGING TRENDS AND CHALLENGES OF ENGINEERING EDUCATION. - : IEEE Computer Society. - 9781538629574 ; , s. 1518-1523
  • Konferensbidrag (refereegranskat)abstract
    • The PILAR (Platform Integration of Laboratories based on the Architecture of visiR) Erasmus Plus project started in September 2016 and will last three years. The core of the PILAR project is the VISIR remote laboratory-Virtual Instruments System In Reality-. The project aims for a federation of five of the existing VISIR nodes, sharing experiments, capacity and resources among partners, and to provide access to VISIR remote lab, through PILAR consortium, to students from other educational institutions. PILAR will be the framework from which management tasks will be performed and laboratories/experiments will be shared. PILAR will also foster the Special Interest Group of VISIR under the Global Online Laboratory Consortium (GOLC) of the International Association of Online Engineering (IAOE). © 2018 IEEE.
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37.
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38.
  • Hernández-Breijo, Borja, et al. (författare)
  • Low Serum BAFF Concentration Is Associated with Response to TNF Inhibitors in Seropositive Patients with Rheumatoid Arthritis
  • 2022
  • Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 11:17
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated B-cell-activating factor (BAFF) in relation to response to treatment with TNF inhibitors (TNFis) in rheumatoid arthritis (RA). This was a longitudinal study including 158 patients with RA treated with TNFis and followed up for 6 months. Clinical response at 6 months of treatment was defined according to the EULAR criteria for good responders (GRs). BAFF concentration was measured in serum samples, collected at baseline and at 6 months. Associations with EULAR response were evaluated using univariable and multivariable logistic regression models. ROC analysis was performed to determine the optimal threshold of serum BAFF concentration associated with good EULAR response to treatment. After 6 months of TNFi treatment, 24% of patients were GRs. They had a lower BMI, lower baseline DAS28 and lower baseline serum BAFF concentration than non-responders. After 6 months of TNFi treatment, autoantibody-positive patients who attained GR had significantly lower serum BAFF concentrations compared with patients who did not. Serum BAFF < 968 pg/mL at 6 months represented the concentration likely to best discriminate between GR and non-GR at 6 months of TNFi treatment. Autoantibody-seropositive patients who had serum BAFF < 968 pg/mL at 6 months demonstrated a more than four-fold increased probability to be GRs compared with patients with higher BAFF concentrations. In conclusion, serum BAFF concentrations were associated with response to TNFis in seropositive RA patients, corroborating the importance of the B-cell compartment in RA.
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39.
  • Hernandez-Breijo, Borja, et al. (författare)
  • Serum B Cell Activating Factor Reflects Good EULAR Response to TNF Inhibition in Patients with Rheumatoid Arthritis
  • 2021
  • Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 73:Suppl. 9, s. 2586-2588
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background/Purpose: The latest breakthroughs in the pathophysiology of rheumatoid arthritis (RA) highlighted the activation of B cells as a trigger of the joint flare initiation and therefore, implicated a central role for B cells in RA pathogenesis. B cell activating factor (BAFF) is essential for B cell activation, differentiation and survival. The main objective of this study was to investigate the role of BAFF in the progression of rheumatoid arthritis during treatment with TNF inhibitors (TNFi) and its association with treatment response.Methods: This was a prospective study including 158 patients with RA initiated at the first TNFi and followed- up for 6 months (m). Disease activity was assessed using the Disease Activity Score 28 (DAS28) at baseline and 6m of treatment. Clinical response at 6m of treatment was defined according to the EULAR criteria for good responders. BAFF concentration was measured in serum samples collected at baseline and 6m. Associations between the EULAR response at 6m and clinical/serological variables were evaluated using univariable and multivariable logistic regression models. Receiver operating characteristic (ROC) analysis was performed to determine the optimal threshold of serum BAFF concentration portending EULAR response at 6m of TNFi treatment, determined as the highest Youden index.Results: After 6m of TNFi treatment, 38/158 (24%) of patients attained good EULAR response (GR). These patients had lower body mass index (BMI) (p=0.02), lower baseline DAS28 (p=0.02) and lower serum BAFF concentration at baseline and at 6m compared with patients who did not attain GR. To further investigate the role of BAFF, the cohort was stratified by anti- citrullinated protein antibody (ACPA) seropositivity. 134 (85%) patients were ACPA positive and 24 (15%) were seronegative. After 6m of TNFi treatment, seropositive patients who attained GR had lower serum BAFF concentration compared with patients who did not attain GR (median [IQR]: 793 [712- 956] pg/mL vs. 955 [808- 1176] pg/mL; p=0.006) (Figure 1). However, there were no differences in ACPA negative patients (Table 1). Therefore, the optimal threshold value for serum BAFF concentration associated with GR at 6m of TNFi treatment was evaluated in seropositive patients. Serum BAFF< 968 pg/mL at 6m represented the concentration likely to best discriminate between GR and non- GR at 6m of TNFi treatment (AUC: 0.67; 95% CI: 0.56- 0.78; p=0.009; sensitivity: 50%, specificity: 81%; PPV: 89%, NPV: 35%), yielding a positive likelihood | 2587ratio of 2.7 (Figure 2). Then, a logistic regression analysis adjusted by patient characteristics with p- value≤0.1 in univariable analysis (disease duration, BMI and baseline DAS28) was performed. We found that a serum BAFF< 968 pg/mL at 6m was significantly and independently associated with GR attainment in seropositive patients (OR: 5.28; 95% CI: 1.72- 16.17; p=0.004).Conclusion: Our results show that serum BAFF concentrations reflect clinical response to TNFi after 6m of treament, mainly in ACPA positive patients. These results suggest that BAFF may be considered a biomarker of clinical re-sponse to TNFi in patients with RA.
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40.
  • Holmqvist, Staffan, et al. (författare)
  • Generation of human pluripotent stem cell reporter lines for the isolation of and reporting on astrocytes generated from ventral midbrain and ventral spinal cord neural progenitors.
  • 2015
  • Ingår i: Stem Cell Research. - : Elsevier BV. - 1876-7753 .- 1873-5061. ; 15:1, s. 203-220
  • Tidskriftsartikel (refereegranskat)abstract
    • Astrocytes play a critical role during the development and the maintenance of the CNS in health and disease. Yet, their lack of accessibility from fetuses and from the brain of diseased patients has hindered our understanding of their full implication in developmental and pathogenic processes. Human pluripotent stem cells (PSCs) are an alternative source to obtain large quantities of astrocytes in vitro, for mechanistic studies of development and disease. However, these studies often require highly pure populations of astrocytes, which are not always achieved, depending on the PSC lines and protocols used. Here, we describe the generation and characterization of human PSC reporter lines expressing TagRFP driven by the ABC1D region of the human GFAP promoter, as new cellular model for generating homogenous population of astrocytes generated from CNS regionally defined PSC-derived neural progenitors. GFAABC1D::TagRFP-expressing astrocytes can be purified by fluorescent-activated cell sorting and maintain a bright expression for several additional weeks. These express canonical astrocyte markers NF1A, S100β, CX43, GLAST, GS and CD44. These new cellular models, from which highly pure populations of fluorescence-expressing astrocytes can be obtained, provide a new platform for studies where pure or fluorescently labeled astrocyte populations are necessary, for example to assess pro-inflammatory cytokine and chemokine release in response to specific treatment, and uptake and degradation of fluorescently labeled pathogenic proteins, as reported in this study.
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41.
  • Marto, João Pedro, et al. (författare)
  • Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.
  • 2023
  • Ingår i: Neurology. - 1526-632X. ; 100:7
  • Tidskriftsartikel (refereegranskat)abstract
    • COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT).Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60).Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis.The study was registered under ClinicalTrials.gov identifier NCT04895462.
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42.
  • Mendoza-Coto, Alejandro, et al. (författare)
  • Cluster self-assembly condition for arbitrary interaction potentials
  • 2021
  • Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 17:4, s. 915-923
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a sufficient criterion for the emergence of cluster phases in an ensemble of interacting classical particles with repulsive two-body interactions. Through a zero-temperature analysis in the low density region we determine the relevant characteristics of the interaction potential that make the energy of a two-particle cluster-crystal become smaller than that of a simple triangular lattice in two dimensions. The method leads to a mathematical condition for the emergence of cluster crystals in terms of the sum of Fourier components of a regularized interaction potential, which can be in principle applied to any arbitrary shape of interactions. We apply the formalism to several examples of bounded and unbounded potentials with and without cluster-forming ability. In all cases, the emergence of self-assembled cluster crystals is well captured by the presented analytic criterion and verified with known results from molecular dynamics simulations at vanishingly temperatures. Our work generalises known results for bounded potentials to repulsive potentials of arbitrary shape.
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43.
  • Mendoza-Coto, Alejandro, et al. (författare)
  • Ground-state phase diagram of ultrasoft bosons
  • 2021
  • Ingår i: Physical Review A: covering atomic, molecular, and optical physics and quantum information. - : American Physical Society (APS). - 2469-9926 .- 2469-9934. ; 104:1
  • Tidskriftsartikel (refereegranskat)abstract
    • In two-dimensional bosonic systems ultrasoft interactions develop an interesting phenomenology that ultimately leads to the appearance of supersolid phases in free space conditions. While suggested in early theoretical works and despite many further analytical efforts, the appearance of these exotic phases as well as the detailed shape of the ground-state phase diagrams have not been established yet. Here we develop a variational mean-field calculation for a generic quantum system with cluster-forming interactions. We show that by including the restriction of a fixed integer number of particles per cluster the ground-state phase diagram can be obtained in great detail. The great detail includes the determination of coexistence regimes of crystals of different occupancy as well as crystals with superfluid phases. To illustrate the application of the method we consider the softened van der Waals potential, for which the phase diagram is known via quantum Monte Carlo simulations. For densities other than that corresponding to the single-particle crystal, our results show very good quantitative agreement with the simulations regarding the location of the superfluid transitions. Additionally, the phase diagrams suggest that the solid-superfluid coexistence could be a reliable marker to locate supersolidity.
  •  
44.
  • Mendoza-Coto, Alejandro, et al. (författare)
  • On the mechanism behind the inverse melting in systems with competing interactions
  • 2019
  • Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • The competition between a short range attractive interaction and a nonlocal repulsive interaction promote the appearance of modulated phases. In this work we present the microscopic mechanisms leading to the emergence of inverse transitions in such systems by considering a thorough mean-field analysis of a variety of minimal models with different competing interactions. We identify the specific connections between the characteristic energy of the homogeneous and modulated phases and the observed reentrant behaviors in the phase diagram. In particular, we find that reentrance is appreciable when the characteristic energy cost of the homogeneous and modulated phases are comparable to each other, and for systems in which the local order parameter is limited. In the asymptotic limit of high energy cost of the homogeneous phase we observe that the degree of reentrance decreases exponentially with the ratio of the characteristic energy cost of homogeneous and modulated phases. These mean-field results are confronted with Langevin simulations of an effective coarse grained model, confirming the expected extension of the reentrance in the phase diagram. These results shed new light on many systems undergoing inverse melting transitions by qualitatively improving the understanding of the interplay of entropy and energy around the inverse melting points.
  •  
45.
  • Mendoza-Coto, Alejandro, et al. (författare)
  • Topological phase diagrams of the frustrated Ising ferromagnet
  • 2020
  • Ingår i: Physical Review B. - : American Physical Society (APS). - 2469-9950 .- 2469-9969. ; 101:17
  • Tidskriftsartikel (refereegranskat)abstract
    • The emergence of complex modulated structures in the magnetization pattern of thin films is a well-established experimental phenomenology caused by the frustrating effects of competing interactions. Using a coarse-grained version of the Ising ferromagnet with dipolar interactions, we develop a method that uses the information from the microscopic Hamiltonian to predict the specific topological phases present in the temperature-external magnetic field phase diagram. This is done by the combination of mean-field variational calculations and the renormalization group equations from the classical theory of two-dimensional melting. In this framework, we are able to distinguish when the orientational and translational symmetries are broken, discriminating between the ordered and disordered states of the system for all temperatures and fields. We observe that the reentrance developed by the H-T phase diagrams in the regime of weak dipolar interactions is directly related with the appearance of anomalous topological transitions. These results motivate the realization of new experiments on magnetic thin films in order to explore the topological properties of the magnetic textures, allowing to identify new exotic phases in these materials.
  •  
46.
  • Miranda-Pastoriza, Dario, et al. (författare)
  • Exploring Non-orthosteric Interactions with a Series of Potent and Selective A(3) Antagonists
  • 2022
  • Ingår i: ACS Medicinal Chemistry Letters. - : American Chemical Society (ACS). - 1948-5875. ; 13:2, s. 243-249
  • Tidskriftsartikel (refereegranskat)abstract
    • : A library of potent and highly A3AR selective pyrimidinebased compounds was designed to explore non-orthosteric interactions within this receptor. Starting from a prototypical orthosteric A3AR antagonist (ISVY130), the structure-based design explored functionalized residues at the exocyclic amide L1 region and aimed to provide additional interactions outside the A3AR orthosteric site. The novel ligands were assembled through an efficient and succinct synthetic approach, resulting in compounds that retain the A3AR potent and selective profile while improving the solubility of the original scaffold. The experimentally demonstrated tolerability of the L1 region to structural functionalization was further assessed by molecular dynamics simulations, giving hints of the non-orthosteric interactions explored by these series. The results pave the way to explore newly functionalized A3AR ligands, including covalent drugs and molecular probes for diagnostic and delivery purposes.
  •  
47.
  • Navarro Diaz, Gonzalo, et al. (författare)
  • Full wind rose wind farm simulation including wake and terrain effects for energy yield assessment
  • 2021
  • Ingår i: Energy. - : Elsevier. - 0360-5442 .- 1873-6785. ; 237
  • Tidskriftsartikel (refereegranskat)abstract
    • In this work, CFD simulation along with the site complete wind rose are used for the first time to estimate a key magnitude for the project development of a wind farm, the capacity factor, which is directly related with the energy yield. The large computational cost that restricted CFD simulation for such a task is drastically reduced by means of a novel interpolation-extrapolation methodology, requiring the simulation of only three inlet velocities for each wind rose sector. This methodology is based on the velocity at met mast and results of the reference velocity for each wind turbine from pre-simulated cases, which are then used to compute a wide range of cases not explicitly simulated. A comparative study is carried out, in which the measured capacity factor of an onshore wind farm in the Argentinean Patagonia is compared against different solution approaches. In the particular case of this wind farm, it is found that the separate effects of wakes and terrain produce errors in the opposite sense, and results very close to the measured value are achieved when both are considered. Also, the increase in the number of simulated direction sectors from 16 to 32 does not significantly change the results. (c) 2021 Elsevier Ltd. All rights reserved.
  •  
48.
  • Padilla-Morales, Benjamin, et al. (författare)
  • Sexual size dimorphism in mammals is associated with changes in the size of gene families related to brain development
  • 2024
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • In mammals, sexual size dimorphism often reflects the intensity of sexual selection, yet its connection to genomic evolution remains unexplored. Gene family size evolution can reflect shifts in the relative importance of different molecular functions. Here, we investigate the associate between brain development gene repertoire to sexual size dimorphism using 124 mammalian species. We reveal significant changes in gene family size associations with sexual size dimorphism. High levels of dimorphism correlate with an expansion of gene families enriched in olfactory sensory perception and a contraction of gene families associated with brain development functions, many of which exhibited particularly high expression in the human adult brain. These findings suggest a relationship between intense sexual selection and alterations in gene family size. These insights illustrate the complex interplay between sexual dimorphism, gene family size evolution, and their roles in mammalian brain development and function, offering a valuable understanding of mammalian genome evolution.
  •  
49.
  • Phillips, Helen R. P., et al. (författare)
  • Global distribution of earthworm diversity
  • 2019
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 366:6464, s. 480-
  • Tidskriftsartikel (refereegranskat)abstract
    • Soil organisms, including earthworms, are a key component of terrestrial ecosystems. However, little is known about their diversity, their distribution, and the threats affecting them. We compiled a global dataset of sampled earthworm communities from 6928 sites in 57 countries as a basis for predicting patterns in earthworm diversity, abundance, and biomass. We found that local species richness and abundance typically peaked at higher latitudes, displaying patterns opposite to those observed in aboveground organisms. However, high species dissimilarity across tropical locations may cause diversity across the entirety of the tropics to be higher than elsewhere. Climate variables were found to be more important in shaping earthworm communities than soil properties or habitat cover. These findings suggest that climate change may have serious implications for earthworm communities and for the functions they provide.
  •  
50.
  • Quinones-Espin, Alejandro Ernesto, et al. (författare)
  • Automatic detection of breast masses using deep learning with YOLO approach
  • 2023
  • Ingår i: Health and Technology. - : SPRINGER HEIDELBERG. - 2190-7188 .- 2190-7196. ; 13:6, s. 915-923
  • Tidskriftsartikel (refereegranskat)abstract
    • IntroductionBreast cancer is the most common malignant tumor among women. Mammography is the specific type of X-ray recommended to examine the breasts. However, they are difficult to interpret due to the size of the lesions, shape, indefinite borders, and low contrast of the masses with respect to healthy tissue, mainly in very dense breasts. Computer-aided detection (CAD) systems increase the efficiency of diagnoses and reduce the workload of specialists.PurposeA CAD system that uses artificial intelligence (AI) based on "You Only Look Once" (YOLO), with two models YOLOv5x and YOLOv5s, is tested for the detection of breast nodules from mammography.MethodTransfer learning and data augmentation techniques were applied. Image sets for training and validation were created from an international database (Vindr-Mammo). The network was trained and validated, and for the best model obtained, an external test was performed from a second database belonguing to "The Mammographic Image Analysis Society" (MIAS Database).ResultsThe best model was obtained with YOLOv5x. This reached a maximum sensitivity of 80% in internal validation and 72% with external test data.ConclusionYOLOv5x and YOLOv5s models showed potential for the task of detecting masses from mammographies.
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