247 research outputs found
Randomized controlled phase 2 trial of hydroxychloroquine in childhood interstitial lung disease
Background
No results of controlled trials are available for any of the few treatments offered to children with interstitial lung diseases (chILD). We evaluated hydroxychloroquine (HCQ) in a phase 2, prospective, multicentre, 1:1-randomized, double-blind, placebo-controlled, parallel-group/crossover trial. HCQ (START arm) or placebo were given for 4 weeks. Then all subjects received HCQ for another 4 weeks. In the STOP arm subjects already taking HCQ were randomized to 12 weeks of HCQ or placebo (= withdrawal of HCQ). Then all subjects stopped treatment and were observed for another 12 weeks.
Results
26 subjects were included in the START arm, 9 in the STOP arm, of these four subjects participated in both arms. The primary endpoint, presence or absence of a response to treatment, assessed as oxygenation (calculated from a change in transcutaneous O 2 -saturation of â„ 5%, respiratory rate â„ 20% or level of respiratory support), did not differ between placebo and HCQ groups. Secondary endpoints including change of O 2 -saturation â„ 3%, health related quality of life, pulmonary function and 6-min-walk-test distance, were not different between groups. Finally combining all placebo and all HCQ treatment periods did not identify significant treatment effects. Overall effect sizes were small. HCQ was well tolerated, adverse events were not different between placebo and HCQ.
Conclusions
Acknowledging important shortcomings of the study, including a small study population, the treatment duration, lack of outcomes like lung function testing below age of 6 years, the small effect size of HCQ treatment observed requires careful reassessments of prescriptions in everyday practice (EudraCT-Nr.: 2013-003714-40, www.clinicaltrialsregister.eu , registered 02.07.2013)
Meta-Analysis of the Alzheimer\u27s Disease Human Brain Transcriptome and Functional Dissection in Mouse Models.
We present a consensus atlas of the human brain transcriptome in Alzheimer\u27s disease (AD), based on meta-analysis of differential gene expression in 2,114 postmortem samples. We discover 30 brain coexpression modules from seven regions as the major source of AD transcriptional perturbations. We next examine overlap with 251 brain differentially expressed gene sets from mouse models of AD and other neurodegenerative disorders. Human-mouse overlaps highlight responses to amyloid versus tau pathology and reveal age- and sex-dependent expression signatures for disease progression. Human coexpression modules enriched for neuronal and/or microglial genes broadly overlap with mouse models of AD, Huntington\u27s disease, amyotrophic lateral sclerosis, and aging. Other human coexpression modules, including those implicated in proteostasis, are not activated in AD models but rather following other, unexpected genetic manipulations. Our results comprise a cross-species resource, highlighting transcriptional networks altered by human brain pathophysiology and identifying correspondences with mouse models for AD preclinical studies
Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires
The production of tt⟠, W+bb⟠and W+cc⟠is studied in the forward region of protonâproton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fbâ1 . The W bosons are reconstructed in the decays WââÎœ , where â denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of , and is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 0.02 \mbox{fb}^{-1}. The bosons are reconstructed in the decays , where denotes muon or electron, while the and quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions
Ophthalmology
OBJECTIVE: In the current study we aimed to identify metabolites associated with age-related macular degeneration (AMD) by performing the largest metabolome association analysis in AMD to date. In addition, we aimed to determine the effect of AMD-associated genetic variants on metabolite levels, and aimed to investigate associations between the identified metabolites and activity of the complement system, one of the main AMD-associated disease pathways. DESIGN: Case-control assocation analysis of metabolomics data. SUBJECTS: 2,267 AMD cases and 4,266 controls from five European cohorts. METHODS: Metabolomics was performed using a high-throughput H-NMR metabolomics platform, which allows the quantification of 146 metabolite measurements and 79 derivative values. Metabolome-AMD associations were studied using univariate logistic regression analyses. The effect of 52 AMD-associated genetic variants on the identified metabolites was investigated using linear regression. In addition, associations between the identified metabolites and activity of the complement pathway (defined by the C3d/C3 ratio) were investigated using linear regression. MAIN OUTCOME MEASURES: Metabolites associated with AMD RESULTS: We identified 60 metabolites that were significantly associated with AMD, including increased levels of large and extra-large HDL subclasses and decreased levels of VLDL, amino acids and citrate. Out of 52 AMD-associated genetic variants, seven variants were significantly associated with 34 of the identified metabolites. The strongest associations were identified for genetic variants located in or near genes involved in lipid metabolism (ABCA1, CETP, APOE, LIPC) with metabolites belonging to the large and extra-large HDL subclasses. In addition, 57 out of 60 metabolites were significantly associated with complement activation levels, and these associations were independent of AMD status. Increased large and extra-large HDL levels and decreased VLDL and amino acid levels were associated with increased complement activation. CONCLUSIONS: Lipoprotein levels were associated with AMD-associated genetic variants, while decreased essential amino acids may point to nutritional deficiencies in AMD. We observed strong associations between the vast majority of the AMD-associated metabolites and systemic complement activation levels, independent of AMD status. This may indicate biological interactions between the main AMD disease pathways, and suggests that multiple pathways may need to be targeted simultaneously for successful treatment of AMD
Study of the rare B-s(0) and B-0 decays into the pi(+) pi(-) mu(+) mu(-) final state
A search for the rare decays and is performed in a data set corresponding to an integrated luminosity of 3.0 fb collected by the LHCb detector in proton-proton collisions at centre-of-mass energies of 7 and 8 TeV. Decay candidates with pion pairs that have invariant mass in the range 0.5-1.3 GeV/ and with muon pairs that do not originate from a resonance are considered. The first observation of the decay and the first evidence of the decay are obtained and the branching fractions are measured to be and , where the third uncertainty is due to the branching fraction of the decay , used as a normalisation.A search for the rare decays Bs0âÏ+ÏâÎŒ+ÎŒâ and B0âÏ+ÏâÎŒ+ÎŒâ is performed in a data set corresponding to an integrated luminosity of 3.0 fbâ1 collected by the LHCb detector in protonâproton collisions at centre-of-mass energies of 7 and 8 TeV . Decay candidates with pion pairs that have invariant mass in the range 0.5â1.3 GeV/c2 and with muon pairs that do not originate from a resonance are considered. The first observation of the decay Bs0âÏ+ÏâÎŒ+ÎŒâ and the first evidence of the decay B0âÏ+ÏâÎŒ+ÎŒâ are obtained and the branching fractions, restricted to the dipion-mass range considered, are measured to be B(Bs0âÏ+ÏâÎŒ+ÎŒâ)=(8.6±1.5 (stat)±0.7 (syst)±0.7(norm))Ă10â8 and B(B0âÏ+ÏâÎŒ+ÎŒâ)=(2.11±0.51(stat)±0.15(syst)±0.16(norm))Ă10â8 , where the third uncertainty is due to the branching fraction of the decay B0âJ/Ï(âÎŒ+ÎŒâ)Kâ(892)0(âK+Ïâ) , used as a normalisation.A search for the rare decays Bs0âÏ+ÏâÎŒ+ÎŒâ and B0âÏ+ÏâÎŒ+ÎŒâ is performed in a data set corresponding to an integrated luminosity of 3.0 fbâ1 collected by the LHCb detector in protonâproton collisions at centre-of-mass energies of 7 and 8 TeV . Decay candidates with pion pairs that have invariant mass in the range 0.5â1.3 GeV/c2 and with muon pairs that do not originate from a resonance are considered. The first observation of the decay Bs0âÏ+ÏâÎŒ+ÎŒâ and the first evidence of the decay B0âÏ+ÏâÎŒ+ÎŒâ are obtained and the branching fractions, restricted to the dipion-mass range considered, are measured to be B(Bs0âÏ+ÏâÎŒ+ÎŒâ)=(8.6±1.5 (stat)±0.7 (syst)±0.7(norm))Ă10â8 and B(B0âÏ+ÏâÎŒ+ÎŒâ)=(2.11±0.51(stat)±0.15(syst)±0.16(norm))Ă10â8 , where the third uncertainty is due to the branching fraction of the decay B0âJ/Ï(âÎŒ+ÎŒâ)Kâ(892)0(âK+Ïâ) , used as a normalisation.A search for the rare decays and is performed in a data set corresponding to an integrated luminosity of 3.0 fb collected by the LHCb detector in proton-proton collisions at centre-of-mass energies of 7 and 8 TeV. Decay candidates with pion pairs that have invariant mass in the range 0.5-1.3 GeV/ and with muon pairs that do not originate from a resonance are considered. The first observation of the decay and the first evidence of the decay are obtained and the branching fractions, restricted to the dipion-mass range considered, are measured to be and , where the third uncertainty is due to the branching fraction of the decay , used as a normalisation
Angular analysis of the B-0 -> K*(0) e(+) e(-) decay in the low-q(2) region
An angular analysis of the decay is performed using a data sample, corresponding to an integrated luminosity of 3.0 {\mbox{fb}^{-1}}, collected by the LHCb experiment in collisions at centre-of-mass energies of 7 and 8 TeV during 2011 and 2012. For the first time several observables are measured in the dielectron mass squared () interval between 0.002 and 1.120. The angular observables and which are related to the polarisation and to the lepton forward-backward asymmetry, are measured to be and , where the first uncertainty is statistical and the second systematic. The angular observables and which are sensitive to the photon polarisation in this range, are found to be and . The results are consistent with Standard Model predictions.An angular analysis of the B â K^{*}^{0} e e decay is performed using a data sample, corresponding to an integrated luminosity of 3.0 fb, collected by the LHCb experiment in pp collisions at centre-of-mass energies of 7 and 8 TeV during 2011 and 2012. For the first time several observables are measured in the dielectron mass squared (q) interval between 0.002 and 1.120 GeV /c. The angular observables F and A which are related to the K^{*}^{0} polarisation and to the lepton forward-backward asymmetry, are measured to be F = 0.16 ± 0.06 ± 0.03 and A â=â0.10â±â0.18â±â0.05, where the first uncertainty is statistical and the second systematic. The angular observables A and A which are sensitive to the photon polarisation in this q range, are found to be A â=âââ0.23â±â0.23â±â0.05 and A â=â0.14â±â0.22â±â0.05. The results are consistent with Standard Model predictions.An angular analysis of the decay is performed using a data sample, corresponding to an integrated luminosity of 3.0 {\mbox{fb}^{-1}}, collected by the LHCb experiment in collisions at centre-of-mass energies of 7 and 8 TeV during 2011 and 2012. For the first time several observables are measured in the dielectron mass squared () interval between 0.002 and 1.120. The angular observables and which are related to the polarisation and to the lepton forward-backward asymmetry, are measured to be and , where the first uncertainty is statistical and the second systematic. The angular observables and which are sensitive to the photon polarisation in this range, are found to be and . The results are consistent with Standard Model predictions
Observation of the B0 â Ï0Ï0 decay from an amplitude analysis of B0 â (Ï+Ïâ)(Ï+Ïâ) decays
Protonâproton collision data recorded in 2011 and 2012 by the LHCb experiment, corresponding to an integrated luminosity of 3.0 fbâ1 , are analysed to search for the charmless B0âÏ0Ï0 decay. More than 600 B0â(Ï+Ïâ)(Ï+Ïâ) signal decays are selected and used to perform an amplitude analysis, under the assumption of no CP violation in the decay, from which the B0âÏ0Ï0 decay is observed for the first time with 7.1 standard deviations significance. The fraction of B0âÏ0Ï0 decays yielding a longitudinally polarised final state is measured to be fL=0.745â0.058+0.048(stat)±0.034(syst) . The B0âÏ0Ï0 branching fraction, using the B0âÏKâ(892)0 decay as reference, is also reported as B(B0âÏ0Ï0)=(0.94±0.17(stat)±0.09(syst)±0.06(BF))Ă10â6
Measurement of the (eta c)(1S) production cross-section in proton-proton collisions via the decay (eta c)(1S) -> p(p)over-bar
The production of the state in proton-proton collisions is probed via its decay to the final state with the LHCb detector, in the rapidity range GeV/c. The cross-section for prompt production of mesons relative to the prompt cross-section is measured, for the first time, to be at a centre-of-mass energy TeV using data corresponding to an integrated luminosity of 0.7 fb, and at TeV using 2.0 fb. The uncertainties quoted are, in order, statistical, systematic, and that on the ratio of branching fractions of the and decays to the final state. In addition, the inclusive branching fraction of -hadron decays into mesons is measured, for the first time, to be , where the third uncertainty includes also the uncertainty on the inclusive branching fraction from -hadron decays. The difference between the and meson masses is determined to be MeV/c.The production of the state in proton-proton collisions is probed via its decay to the final state with the LHCb detector, in the rapidity range . The cross-section for prompt production of mesons relative to the prompt cross-section is measured, for the first time, to be at a centre-of-mass energy using data corresponding to an integrated luminosity of 0.7Â fb , and at using 2.0Â fb . The uncertainties quoted are, in order, statistical, systematic, and that on the ratio of branching fractions of the and decays to the final state. In addition, the inclusive branching fraction of -hadron decays into mesons is measured, for the first time, to be , where the third uncertainty includes also the uncertainty on the inclusive branching fraction from -hadron decays. The difference between the and meson masses is determined to be .The production of the state in proton-proton collisions is probed via its decay to the final state with the LHCb detector, in the rapidity range GeV/c. The cross-section for prompt production of mesons relative to the prompt cross-section is measured, for the first time, to be at a centre-of-mass energy TeV using data corresponding to an integrated luminosity of 0.7 fb, and at TeV using 2.0 fb. The uncertainties quoted are, in order, statistical, systematic, and that on the ratio of branching fractions of the and decays to the final state. In addition, the inclusive branching fraction of -hadron decays into mesons is measured, for the first time, to be , where the third uncertainty includes also the uncertainty on the inclusive branching fraction from -hadron decays. The difference between the and meson masses is determined to be MeV/c
Measurement of asymmetries and polarisation fractions in decays
An angular analysis of the decay is performed using collisions corresponding to an integrated luminosity of collected by the LHCb experiment at a centre-of-mass energy TeV. A combined angular and mass analysis separates six helicity amplitudes and allows the measurement of the longitudinal polarisation fraction for the decay. A large scalar contribution from the and resonances is found, allowing the determination of additional asymmetries. Triple product and direct asymmetries are determined to be compatible with the Standard Model expectations. The branching fraction is measured to be
Search for the lepton flavour violating decay tau(-) -> mu(-)mu(+)mu(-)
A search for the lepton flavour violating decay is performed with the LHCb experiment. The data sample corresponds to an integrated luminosity of 1.0 fb of proton-proton collisions at a centre-of-mass energy of 7 TeV and 2.0 fb at 8 TeV. No evidence is found for a signal, and a limit is set at 90% confidence level on the branching fraction, .A search for the lepton flavour violating decay Ï â ÎŒ ÎŒ ÎŒ is performed with the LHCb experiment. The data sample corresponds to an integrated luminosity of 1.0 fb of proton-proton collisions at a centre-of-mass energy of 7 TeV and 2.0 fb at 8 TeV. No evidence is found for a signal, and a limit is set at 90% confidence level on the branching fraction, .A search for the lepton flavour violating decay is performed with the LHCb experiment. The data sample corresponds to an integrated luminosity of of proton-proton collisions at a centre-of-mass energy of and at . No evidence is found for a signal, and a limit is set at confidence level on the branching fraction,
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