9 research outputs found

    Predictive factors and early biomarkers of response in multiple sclerosis patients treated with natalizumab

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    There are an increasing number of treatments available for multiple sclerosis (MS). The early identification of optimal responders to individual treatments is important to achieve individualized therapy. With this aim, we performed a multicenter retrospective longitudinal study including 186 MS patients treated with natalizumab who were followed for 2 years. We analyzed the following variables at recruitment: sex, current age, age at disease onset, disease duration, EDSS, number of T2 and Gd + lesions, IgG and IgM oligoclonal bands, HLA class II (DR, DRB, DQA, DQB, and DRB1*15:01), IgG and IgM antibody titers against human herpesvirus 6 (HHV-6) and the antibody response to Epstein–Barr virus (EBV) through the measurement of the anti-EBNA-1 and anti-VCA IgG titers, in relation to clinical response (no relapses or disability progression), and to NEDA-3 (no evidence of disease activity in terms of clinical response and no changes in MRI scans either) after 2-years follow-up. Baseline EDSS score, baseline EBNA-1 IgG titers and percentage change of HHV6 IgG titers between baseline and 6 month visits were significantly different in clinical responders and in NEDA-3 status (all of them remained significant in the multivariate analysis). We identified three variables for the early identification of natalizumab optimal responders in a rapid and cost-effective approach

    A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee

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    Many clinical trials have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of clinical thrombotic events. Aspirin and ticlopidine have been shown to be effective, but both have potentially serious adverse effects. Clopidogrel, a new thienopyridine derivative similar to ticlopidine, is an inhibitor of platelet aggregation induced by adenosine diphosphate. METHODS: CAPRIE was a randomised, blinded, international trial designed to assess the relative efficacy of clopidogrel (75 mg once daily) and aspirin (325 mg once daily) in reducing the risk of a composite outcome cluster of ischaemic stroke, myocardial infarction, or vascular death; their relative safety was also assessed. The population studied comprised subgroups of patients with atherosclerotic vascular disease manifested as either recent ischaemic stroke, recent myocardial infarction, or symptomatic peripheral arterial disease. Patients were followed for 1 to 3 years. FINDINGS: 19,185 patients, with more than 6300 in each of the clinical subgroups, were recruited over 3 years, with a mean follow-up of 1.91 years. There were 1960 first events included in the outcome cluster on which an intention-to-treat analysis showed that patients treated with clopidogrel had an annual 5.32% risk of ischaemic stroke, myocardial infarction, or vascular death compared with 5.83% with aspirin. These rates reflect a statistically significant (p = 0.043) relative-risk reduction of 8.7% in favour of clopidogrel (95% Cl 0.3-16.5). Corresponding on-treatment analysis yielded a relative-risk reduction of 9.4%. There were no major differences in terms of safety. Reported adverse experiences in the clopidogrel and aspirin groups judged to be severe included rash (0.26% vs 0.10%), diarrhoea (0.23% vs 0.11%), upper gastrointestinal discomfort (0.97% vs 1.22%), intracranial haemorrhage (0.33% vs 0.47%), and gastrointestinal haemorrhage (0.52% vs 0.72%), respectively. There were ten (0.10%) patients in the clopidogrel group with significant reductions in neutrophils (< 1.2 x 10(9)/L) and 16 (0.17%) in the aspirin group. INTERPRETATION: Long-term administration of clopidogrel to patients with atherosclerotic vascular disease is more effective than aspirin in reducing the combined risk of ischaemic stroke, myocardial infarction, or vascular death. The overall safety profile of clopidogrel is at least as good as that of medium-dose aspirin

    Skewness and kurtosis of mean transverse momentum fluctuations at the LHC energies

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    The first measurements of skewness and kurtosis of mean transverse momentum (〈pTâŒȘ) fluctuations are reported in Pb–Pb collisions at sNN = 5.02 TeV, Xe–Xe collisions at sNN = 5.44 TeV and pp collisions at s=5.02 TeV using the ALICE detector. The measurements are carried out as a function of system size 〈dNch/dηâŒȘ|η|<0.51/3, using charged particles with transverse momentum (pT) and pseudorapidity (η), in the range 0.2<pT<3.0 GeV/c and |η|<0.8, respectively. In Pb–Pb and Xe–Xe collisions, positive skewness is observed in the fluctuations of 〈pTâŒȘ for all centralities, which is significantly larger than what would be expected in the scenario of independent particle emission. This positive skewness is considered a crucial consequence of the hydrodynamic evolution of the hot and dense nuclear matter created in heavy-ion collisions. Furthermore, similar observations of positive skewness for minimum bias pp collisions are also reported here. Kurtosis of 〈pTâŒȘ fluctuations is found to be in good agreement with the kurtosis of Gaussian distribution, for most central Pb–Pb collisions. Hydrodynamic model calculations with MUSIC using Monte Carlo Glauber initial conditions are able to explain the measurements of both skewness and kurtosis qualitatively from semicentral to central collisions in Pb–Pb system. Color reconnection mechanism in PYTHIA8 model seems to play a pivotal role in capturing the qualitative behavior of the same measurements in pp collisions

    System-size dependence of the hadronic rescattering effect at energies available at the CERN Large Hadron Collider

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    International audienceThe first measurements of K*(892)0 resonance production as a function of charged-particle multiplicity in Xe-Xe collisions at sNN=5.44 TeV and pp collisions ats=5.02 TeV using the ALICE detector are presented. The resonance is reconstructed at midrapidity (|y| &lt; 0.5) using the hadronic decay channel K*0 →K±π∓. Measurements of transverse-momentum integrated yield, mean transverse-momentum, nuclear modification factor of K*0, and yield ratios of resonance to stable hadron (K*0/K) are compared across different collision systems (pp, p-Pb, Xe-Xe, and Pb-Pb) at similar collision energies to investigate how the production of K*0 resonances depends on the size of the system formed in these collisions. The hadronic rescattering effect is found to be independent of the size of colliding systems and mainly driven by the produced charged-particle multiplicity, which is a proxy of the volume of produced matter at the chemical freeze-out. In addition, the production yields of K*0 in Xe-Xe collisions are utilized to constrain the dependence of the kinetic freeze-out temperature on the system size using the hadron resonance gas–partial chemical equilibrium model

    Pseudorapidity dependence of anisotropic flow and its decorrelations using long-range multiparticle correlations in Pb–Pb and Xe–Xe collisions

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    The pseudorapidity dependence of elliptic (v2), triangular (v3), and quadrangular (v4) flow coefficients of charged particles measured in Pb–Pb collisions at a centre-of-mass energy per nucleon pair of sNN=5.02TeV and in Xe–Xe collisions at sNN=5.44TeV with ALICE at the LHC are presented. The measurements are performed in the pseudorapidity range −3.5<η<5 for various centrality intervals using two- and multi-particle cumulants with the subevent method. The flow probability density function (p.d.f.) is studied with the ratio of flow coefficient v2 calculated with four- and two-particle cumulant, and suggests that the variance of flow p.d.f. is independent of pseudorapidity. The decorrelation of the flow vector in the longitudinal direction is probed using two-particle correlations. The results measured with respect to different reference regions in pseudorapidity exhibit differences, argued to be a result of saturating decorrelation effect above a certain pseudorapidity separation, in contrast to previous publications which assign this observation to non-flow effects. The results are compared to 3+1 dimensional hydrodynamic and the AMPT transport model calculations. Neither of the models is able to simultaneously describe the pseudorapidity dependence of measurements of anisotropic flow and its fluctuations. The results presented in this work highlight shortcomings in our current understanding of initial conditions and subsequent system expansion in the longitudinal direction. Therefore, they provide input for its improvement

    Measurement of the fraction of jet longitudinal momentum carried by <math display="inline"><msubsup><mi mathvariant="normal">Λ</mi><mi>c</mi><mo>+</mo></msubsup></math> baryons in <math display="inline"><mi>p</mi><mi>p</mi></math> collisions

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    International audienceRecent measurements of charm-baryon production in hadronic collisions have questioned the universality of charm-quark fragmentation across different collision systems. In this work the fragmentation of charm quarks into charm baryons is probed, by presenting the first measurement of the longitudinal jet momentum fraction carried by Λc+ baryons, z∄ch, in hadronic collisions. The results are obtained in proton-proton (pp) collisions at s=13  TeV at the LHC, with Λc+ baryons and charged (track-based) jets reconstructed in the transverse momentum intervals of 3≀pTΛc+&lt;15  GeV/c and 7≀pTjet ch&lt;15  GeV/c, respectively. The z∄ch distribution is compared to a measurement of D0-tagged charged jets in pp collisions as well as to pythia 8 simulations. The data hints that the fragmentation of charm quarks into charm baryons is softer with respect to charm mesons, in the measured kinematic interval, as predicted by hadronization models which include color correlations beyond leading-color in the string formation

    Charged-particle production as a function of the relative transverse activity classifier in pp, p−-Pb, and Pb−-Pb collisions at the LHC

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    International audienceMeasurements of charged-particle production in pp, p−-Pb, and Pb−-Pb collisions in the toward, away, and transverse regions with the ALICE detector are discussed. These regions are defined event-by-event relative to the azimuthal direction of the charged trigger particle, which is the reconstructed particle with the largest transverse momentum (pTtrigp_{\mathrm{T}}^{\rm trig}) in the range 8<pTtrig<158<p_{\mathrm{T}}^{\rm trig}<15 GeV/c/c. The toward and away regions contain the primary and recoil jets, respectively; both regions are accompanied by the underlying event (UE). In contrast, the transverse region perpendicular to the direction of the trigger particle is dominated by the so-called UE dynamics, and includes also contributions from initial- and final-state radiation. The relative transverse activity classifier, RT=NchT/⟹NchT⟩R_{\mathrm{T}}=N_{\mathrm{ch}}^{\mathrm{T}}/\langle N_{\mathrm{ch}}^{\mathrm{T}}\rangle, is used to group events according to their UE activity, where NchTN_{\mathrm{ch}}^{\mathrm{T}} is the charged-particle multiplicity per event in the transverse region and ⟹NchT⟩\langle N_{\mathrm{ch}}^{\mathrm{T}}\rangle is the mean value over the whole analysed sample. The energy dependence of the RTR_{\mathrm{T}} distributions in pp collisions at s=2.76\sqrt{s}=2.76, 5.02, 7, and 13 TeV is reported, exploring the Koba-Nielsen-Olesen (KNO) scaling properties of the multiplicity distributions. The first measurements of charged-particle pTp_{\rm T} spectra as a function of RTR_{\mathrm{T}} in the three azimuthal regions in pp, p−-Pb, and Pb−-Pb collisions at sNN=5.02\sqrt{s_{\rm NN}}=5.02 TeV are also reported. Data are compared with predictions obtained from the event generators PYTHIA 8 and EPOS LHC. This set of measurements is expected to contribute to the understanding of the origin of collective-like effects in small collision systems (pp and p−-Pb)
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