151 research outputs found

    Pharmacogenomic associations of adverse drug reactions in asthma: systematic review and research prioritisation

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    A systematic review of pharmacogenomic studies capturing adverse drug reactions (ADRs) related to asthma medications was undertaken, and a survey of Pharmacogenomics in Childhood Asthma (PiCA) consortia members was conducted. Studies were eligible if genetic polymorphisms were compared with suspected ADR(s) in a patient with asthma, as either a primary or secondary outcome. Five studies met the inclusion criteria. The ADRs and polymorphisms identified were change in lung function tests (rs1042713), adrenal suppression (rs591118), and decreased bone mineral density (rs6461639) and accretion (rs9896933, rs2074439). Two of these polymorphisms were replicated within the paper, but none had external replication. Priorities from PiCA consortia members (representing 15 institution in eight countries) for future studies were tachycardia (SABA/LABA), adrenal suppression/crisis and growth suppression (corticosteroids), sleep/behaviour disturbances (leukotriene receptor antagonists), and nausea and vomiting (theophylline). Future pharmacogenomic studies in asthma should collect relevant ADR data as well as markers of efficacy

    Comparison between simulated and observed LHC beam backgrounds in the ATLAS experiment at Ebeam =4 TeV

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    Results of dedicated Monte Carlo simulations of beam-induced background (BIB) in the ATLAS experiment at the Large Hadron Collider (LHC) are presented and compared with data recorded in 2012. During normal physics operation this background arises mainly from scattering of the 4 TeV protons on residual gas in the beam pipe. Methods of reconstructing the BIB signals in the ATLAS detector, developed and implemented in the simulation chain based on the \textscFluka Monte Carlo simulation package, are described. The interaction rates are determined from the residual gas pressure distribution in the LHC ring in order to set an absolute scale on the predicted rates of BIB so that they can be compared quantitatively with data. Through these comparisons the origins of the BIB leading to different observables in the ATLAS detectors are analysed. The level of agreement between simulation results and BIB measurements by ATLAS in 2012 demonstrates that a good understanding of the origin of BIB has been reached

    A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

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    Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

    The ATLAS trigger system for LHC Run 3 and trigger performance in 2022

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    The ATLAS trigger system is a crucial component of the ATLAS experiment at the LHC. It is responsible for selecting events in line with the ATLAS physics programme. This paper presents an overview of the changes to the trigger and data acquisition system during the second long shutdown of the LHC, and shows the performance of the trigger system and its components in the proton-proton collisions during the 2022 commissioning period as well as its expected performance in proton-proton and heavy-ion collisions for the remainder of the third LHC data-taking period (2022–2025)

    Search for the Zγ decay mode of new high-mass resonances in pp collisions at √s = 13 TeV with the ATLAS detector

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    This letter presents a search for narrow, high-mass resonances in the Zγ final state with the Z boson decaying into a pair of electrons or muons. The √s = 13 TeV pp collision data were recorded by the ATLAS detector at the CERN Large Hadron Collider and have an integrated luminosity of 140 fb−1. The data are found to be in agreement with the Standard Model background expectation. Upper limits are set on the resonance production cross section times the decay branching ratio into Zγ. For spin-0 resonances produced via gluon–gluon fusion, the observed limits at 95% confidence level vary between 65.5 fb and 0.6 fb, while for spin-2 resonances produced via gluon–gluon fusion (or quark–antiquark initial states) limits vary between 77.4 (76.1) fb and 0.6 (0.5) fb, for the mass range from 220 GeV to 3400 GeV

    Search for lepton-favour violation in high-mass dilepton final states using 139 fb−1 of pp collisions at √s = 13 TeV with the ATLAS detector

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    A search is performed for a heavy particle decaying into different-flavour, dilepton final states, using 139 fb−1 of proton-proton collision data at √s = 13 TeV collected in 2015–2018 by the ATLAS detector at the Large Hadron Collider. Final states with electrons, muons and hadronically decaying tau leptons are considered (eÎŒ, eτ or Ότ). No significant excess over the Standard Model predictions is observed. Upper limits on the production cross-section are set as a function of the mass of a Zâ€Č boson, a supersymmetric τ-sneutrino, and a quantum black-hole. The observed 95% CL lower mass limits obtained on a typical benchmark model Zâ€Č boson are 5.0 TeV (eÎŒ), 4.0 TeV (eτ), and 3.9 TeV (Ότ), respectively

    Measurement of the cross-sections of the electroweak and total production of a Zγ pair in association with two jets in pp collisions at √s = 13 TeV with the ATLAS detector

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    This Letter presents the measurement of the fiducial and differential cross-sections of the electroweak production of a ZÎł pair in association with two jets. The analysis uses 140 fb−1 of LHC proton–proton collision data taken at √s = 13 TeV recorded by the ATLAS detector during the years 2015–2018. Events with a Z boson candidate decaying into either an e+e− or ÎŒ+Ό− pair, a photon and two jets are selected. The electroweak component is extracted by requiring a large dijet invariant mass and by using the information about the centrality of the system and is measured with an observed and expected significance well above five standard deviations. The fiducial pp → ZÎł jj cross-section for the electroweak production is measured to be 3.6 ± 0.5 fb. The total fiducial cross-section that also includes contributions where the jets arise from strong interactions is measured to be 16.8+2.0 −1.8 fb. The results are consistent with the Standard Model predictions. Differential cross-sections are also measured using the same events and are compared with parton-shower Monte Carlo simulations. Good agreement is observed between data and predictions

    Search for heavy Higgs bosons with flavour-violating couplings in multi-lepton plus b-jets final states in pp collisions at 13 TeV with the ATLAS detector

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    A search for new heavy scalars with flavour-violating decays in final states with multiple leptons and b-tagged jets is presented. The results are interpreted in terms of a general two-Higgs-doublet model involving an additional scalar with couplings to the top-quark and the three up-type quarks (ρtt, ρtc, and ρtu). The targeted signals lead to final states with either a same-sign top-quark pair, three top-quarks, or four top-quarks. The search is based on a data sample of proton-proton collisions at √s = 13 TeV recorded with the ATLAS detector during Run 2 of the Large Hadron Collider, corresponding to an integrated luminosity of 139 fb−1. Events are categorised depending on the multiplicity of light charged leptons (electrons or muons), total lepton charge, and a deep-neural-network output to enhance the purity of each of the signals. Masses of an additional scalar boson mH between 200 − 630 GeV with couplings ρtt = 0.4, ρtc = 0.2, and ρtu = 0.2 are excluded at 95% confidence level. Additional interpretations are provided in models of R-parity violating supersymmetry, motivated by the recent flavour and (g − 2)ÎŒ anomalies
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