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    338 research outputs found

    VIEWS AND EXPERIENCES OF YOUNG PEOPLE (11-16 years) TOWARDS MENTAL HEALTH SUPPORT IN A SCHOOL AND COMMUNITY SETTING IN THE UK

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    The University of Manchester - Institutional Repository

    Multi-ancestry GWAS reveals excitotoxicity associated with outcome after ischaemic stroke

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    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.Peer reviewe
    PubMed Central
    eScholarship - University of California
    Helsingin yliopiston digitaalinen arkisto
    Jagiellonian Univeristy Repository
    University of St. Andrews - Pure
    Fondo Bibliográfico Digital Institucional
    St Andrews Research Repository

    Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

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    'Springer Science and Business Media LLC'
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    Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease
    Kölner UniversitätsPublikationsServer
    Directory of Open Access Journals
    PubMed Central
    REPISALUD
    Universidade de Lisboa: Repositório.UL
    Diposit Digital de Documents de la UAB
    Apollo (Cambridge)
    Bangor University Research Portal
    Hal-Diderot
    Oskar Bordeaux

    The genetic architecture of the human cerebral cortex

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    Ludwig-Maximilians-Universität München
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    The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder
    Open Access LMU ( Ludwig-Maximilians-Univ. München)

    Observation of muonic Dalitz decays of chib mesons and precise spectroscopy of hidden-beauty states

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    The decays of the χb1(1P), χb2(1P), χb1(2P) and χb2(2P) mesons into the Υ(1S)μ+μ− final state are observed with a high significance using proton-proton collision data collected with the LHCb detector and corresponding to an integrated luminosity of 9 fb−1. The newly observed decays together with the Υ(2S) → Υ(1S)π+π− and Υ(3S) → Υ(2S)π+π− decay modes are used for precision measurements of the mass and mass splittings for the hidden-beauty states
    Archivio della Ricerca - Università di Pisa
    Archivio istituzionale della ricerca - Università di Cagliari
    ePubs: the open archive for STFC research publications
    Archivio istituzionale della ricerca - Università di Ferrara

    Measurement of Λ0b, Λ+c, and Λ Decay Parameters Using Λ0b →Λ+c⁢h− Decays

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    A comprehensive study of the angular distributions in the bottom-baryon decays (Formula presented), followed by (Formula presented) with (Formula presented) or (Formula presented) decays, is performed using a data sample of proton-proton collisions corresponding to an integrated luminosity of (Formula presented) collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV. The decay parameters and the associated charge-parity ((Formula presented)) asymmetries are measured, with no significant (Formula presented) violation observed. For the first time, the (Formula presented) decay parameters are measured. The most precise measurements of the decay parameters (Formula presented), (Formula presented), and (Formula presented) are obtained for (Formula presented) decays and an independent measurement of the decay parameters for the strange-baryon (Formula presented) decay is provided. The results deepen our understanding of weak decay dynamics in baryon decays
    Archivio della Ricerca - Università di Pisa
    Archivio istituzionale della ricerca - Università di Cagliari

    Measurement of the effective leptonic weak mixing angle

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    Using pp collision data at s = 13 TeV, recorded by the LHCb experiment between 2016 and 2018 and corresponding to an integrated luminosity of 5.4 fb−1, the forward-backward asymmetry in the pp → Z/γ* → μ+μ− process is measured. The measurement is carried out in ten intervals of the difference between the muon pseudorapidities, within a fiducial region covering dimuon masses between 66 and 116 GeV, muon pseudorapidities between 2.0 and 4.5 and muon transverse momenta above 20 GeV. These forward-backward asymmetries are compared with predictions, at next-to-leading order in the strong and electroweak couplings. The measured effective leptonic weak mixing angle is (Formula presented.) where the first uncertainty is statistical, the second arises from systematic uncertainties associated with the asymmetry measurement, and the third arises from uncertainties in the fit model used to extract sin2θeffl from the asymmetry measurement. This result is based on an arithmetic average of results using the CT18, MSHT20, and NNPDF31 parameterisations of the proton internal structure, and is consistent with previous measurements and with predictions from the global electroweak fit
    Archivio della Ricerca - Università di Pisa
    Archivio istituzionale della ricerca - Università di Cagliari

    Measurement of CP violation in B0 → D+D− and B0s →Ds+Ds- decays

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    A time-dependent, favour-tagged measurement of CP violation is performed with B0 → D+D− and B0 s → D+ s D− s decays, using data collected by the LHCb detector in proton-proton collisions at a centre-of-mass energy of 13 TeV corresponding to an integrated luminosity of 6 fb−1 . In B0 → D+D− decays the CP-violation parameters are measured to be SD+D− = −0.552 ± 0.100 (stat) ± 0.010 (syst), CD+D− = 0.128 ± 0.103 (stat) ± 0.010 (syst). In B0 s → D+ s D− s decays the CP-violating parameter formulation in terms of φs and |λ| results in φs = −0.086 ± 0.106 (stat) ± 0.028 (syst) rad, |λD + s D − s | = 1.145 ± 0.126 (stat) ± 0.031 (syst). These results represent the most precise single measurement of the CP-violation parameters in their respective channels. For the frst time in a single measurement, CP symmetry is observed to be violated in B0 → D+D− decays with a signifcance exceeding six standard deviations
    Archivio istituzionale della ricerca - Università di Cagliari
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    Comprehensive analysis of local and nonlocal amplitudes in the B0→ K*0μ+μ− decay

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    A comprehensive study of the local and nonlocal amplitudes contributing to the decay B0 → K*0(→ K+π−)μ+μ− is performed by analysing the phase-space distribution of the decay products. The analysis is based on pp collision data corresponding to an integrated luminosity of 8.4 fb−1 collected by the LHCb experiment. This measurement employs for the first time a model of both one-particle and two-particle nonlocal amplitudes, and utilises the complete dimuon mass spectrum without any veto regions around the narrow charmonium resonances. In this way it is possible to explicitly isolate the local and nonlocal contributions and capture the interference between them. The results show that interference with nonlocal contributions, although larger than predicted, only has a minor impact on the Wilson Coefficients determined from the fit to the data. For the local contributions, the Wilson Coefficient C9, responsible for vector dimuon currents, exhibits a 2.1σ deviation from the Standard Model expectation. The Wilson Coefficients C10, C9′ and C10′ are all in better agreement than C9 with the Standard Model and the global significance is at the level of 1.5σ. The model used also accounts for nonlocal contributions from B0→ K*0[τ+τ−→ μ+μ−] rescattering, resulting in the first direct measurement of the bsττ vector effective-coupling C9τ
    Archivio istituzionale della Ricerca - Scuola Normale Superiore
    Archivio della Ricerca - Università di Pisa
    Archivio istituzionale della ricerca - Università di Bari
    Archivio istituzionale della ricerca - Università di Cagliari
    Archivio istituzionale della ricerca - Università di Ferrara

    Search for the lepton-flavor violating decay Bs0 →φμ±τ

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    A search for the lepton-flavor violating decays Bs0→φμ±τ is presented, using a sample of proton-proton collisions at center-of-mass energies of 7, 8, and 13 TeV, collected with the LHCb detector and corresponding to a total integrated luminosity of 9 fb-1. The τ leptons are selected using decays with three charged pions. No significant excess is observed, and an upper limit on the branching fraction is determined to be B(Bs0→φμ±τ)<1.0×10-5 at 90% confidence level
    Archivio della Ricerca - Università di Pisa
    Archivio istituzionale della ricerca - Università di Cagliari
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