5,488 research outputs found

    Pd-(L)1 inhibitors as monotherapy for the first-line treatment of non-small-cell lung cancer patients with high pd-l1 expression : A network meta-analysis

    Get PDF
    Altres ajuts: RocheProgrammed cell death-ligand 1 (PD-L1) has emerged as a potential biomarker for selec-tion of patients more likely to respond to immunotherapy and as a prognostic factor in non-small cell lung cancer (NSCLC). In this network meta-analysis, we aimed to evaluate the efficacy of first-line anti-PD-(L)1 monotherapy in advanced NSCLC patients with high PD-L1 expression (≥50%) compared to platinum-based chemotherapy. We also evaluated efficacy outcomes according to tumor mutational burden (TMB). To that end, we conducted a systematic review. Six clinical trials with 2111 patients were included. In head-to-head comparisons, immunotherapy showed a significant improvement in progression-free survival (PFS: HRpooled = 0.69, 95% CI: 0.52-0.90, p = 0.007), overall survival (OS: HRpooled = 0.69, 95% CI: 0.61-0.78; p < 0.001) and overall response rate (ORR) (Risk ratio (RR)pooled = 1.354, 95% CI: 1.04-1.762, p = 0.024). In the assessment of relative efficacy for PFS through indirect comparisons, pembrolizumab (results from KEYNOTE-024) ranked highest followed by cemiplimab and atezolizumab, with statistical significance determined for some of the drugs. In terms of OS, cemiplimab ranked highest followed by atezolizumab and pembrolizumab, although non-significant OS was determined for these drugs. In conclusion, PD-(L)1 inhibitor mon-otherapy improves efficacy outcomes in the first line setting of advanced NSCLC patients with high PD-L1 expression. Evaluations with longer follow up are still needed to determine the superiority of any specific drug

    Genomic Expansion of Magnetotactic Bacteria Reveals an Early Common Origin of Magnetotaxis with Lineage-specific Evolution

    Get PDF
    The origin and evolution of magnetoreception, which in diverse prokaryotes and protozoa is known as magnetotaxis and enables these microorganisms to detect Earth’s magnetic field for orientation and navigation, is not well understood in evolutionary biology. The only known prokaryotes capable of sensing the geomagnetic field are magnetotactic bacteria (MTB), motile microorganisms that biomineralize intracellular, membrane-bounded magnetic single-domain crystals of either magnetite (Fe3O4) or greigite (Fe3S4) called magnetosomes. Magnetosomes are responsible for magnetotaxis in MTB. Here we report the first large-scale metagenomic survey of MTB from both northern and southern hemispheres combined with 28 genomes from uncultivated MTB. These genomes expand greatly the coverage of MTB in the Proteobacteria, Nitrospirae, and Omnitrophica phyla, and provide the first genomic evidence of MTB belonging to the Zetaproteobacteria and “Candidatus Lambdaproteobacteria” classes. The gene content and organization of magnetosome gene clusters, which are physically grouped genes that encode proteins for magnetosome biosynthesis and organization, are more conserved within phylogenetically similar groups than between different taxonomic lineages. Moreover, the phylogenies of core magnetosome proteins form monophyletic clades. Together, these results suggest a common ancient origin of iron-based (Fe3O4 and Fe3S4) magnetotaxis in the domain Bacteria that underwent lineage-specific evolution, shedding new light on the origin and evolution of biomineralization and magnetotaxis, and expanding significantly the phylogenomic representation of MTB

    Silicon strip detectors for two-dimensional soft X-ray imaging at normal incidence

    Get PDF
    A simple prototype system for static two-dimensional soft X-ray imaging using silicon microstrip detectors irradiated at normal incidence is presented. Radiation sensors consist of single-sided silicon detectors made from 300 mum thick wafers, read by RX64 ASICs. Data acquisition and control is performed by a Windows PC workstation running dedicated LabVIEW routines, connected to the sensors through a PCI-DIO-96 interface. Two-dimensional images are obtained by scanning a lead collimator with a thin slit perpendicular to the strip axis, along the whole detector size; the several strip profiles (slices) taken at each position are then put together to form a planar image. Preliminary results are presented, illustrating the high-resolution imaging capabilities of the system with soft X-rays. (C) 2003 Elsevier B.V. All rights reserved.info:eu-repo/semantics/publishedVersio

    Measurement of the BˉDνˉ\bar{B}\to D\ell\bar{\nu} Partila Width and Form Factor Parameters

    Full text link
    We have studied the decay BˉDνˉ\bar{B} \to D\ell\bar{\nu}, where =eorμ\ell=e or \mu. From a fit to the differential decay rate dΓ/dwd\Gamma/dw we measure the rate normalization FD(1)Vcb{\cal F}_D(1)|V_{cb}| and form factor slope ρ^D2\hat{\rho}^2_D, and, using measured values of τB\tau_B, find Γ(BˉDνˉ)=(12.0±0.9±2.1)ns1\Gamma(\bar{B} \to D\ell\bar{\nu}) = (12.0 \pm 0.9 \pm 2.1) ns^{-1}. The resulting branching fractions are B(Bˉ0D+νˉ)=(1.87±0.15±0.32){\cal B}(\bar{B}^0 \to D^+\ell^-\bar{\nu})=(1.87 \pm 0.15 \pm 0.32)% and B(BD0νˉ)=(1.94±0.15±0.34){\cal B}(B^- \to D^0\ell^-\bar{\nu})=(1.94 \pm 0.15 \pm 0.34)%. The form factor parameters are in agreement with those measured in BˉDνˉ\bar{B} \to D^*\ell\bar{\nu} decays, as predicted by heavy quark effective theory.Comment: 11 pages, postscript file also available through http://w4.lns.cornell.edu/public/CLN

    Investigation of Semileptonic BB Meson Decay to P-Wave Charm Mesons

    Full text link
    We have studied semileptonic BB meson decays with a P-wave charm meson in the final state using 3.29 x 10^6 B\bar{B} events collected by the CLEO~II detector at the Cornell Electron-positron Storage Ring. We find a value for the exclusive semileptonic product branching fraction: Br(B^- -> D_1^0 l^- \bar{\nu}) x Br(D_1^0 -> D^{*+}\pi^-) = (0.373 \pm 0.085 \pm 0.052 \pm 0.024)% and an upper limit for Br(B^- -> D_2^{*0} l^- \bar{\nu}) x Br(D_2^{*0} -> D^{*+}\pi^-) < 0.16%$ (90% C.L.). These results indicate that at least 20% of the total B^- semileptonic rate is unaccounted for by the observed exclusive decays, B^- -> D^0 l^- \bar{\nu}, B^- -> D^{*0} l^- \bar{\nu}, B^- -> D_1^0 l^- \bar{\nu}, and B^- -> D_2^{*0} l^- \bar{\nu}.Comment: 10 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

    Study of Gluon versus Quark Fragmentation in Υggγ\Upsilon\to gg\gamma and e+eqqˉγe^{+}e^{-}\to q\bar{q}\gamma Events at \sqrt{s}=10 GeV

    Full text link
    Using data collected with the CLEO II detector at the Cornell Electron Storage Ring, we determine the ratio R(chrg) for the mean charged multiplicity observed in Upsilon(1S)->gggamma events, to the mean charged multiplicity observed in e+e- -> qqbar gamma events. We find R(chrg)=1.04+/-0.02+/-0.05 for jet-jet masses less than 7 GeV.Comment: 15 pages, postscript file also available through http://w4.lns.cornell.edu/public/CLN

    Operations of and Future Plans for the Pierre Auger Observatory

    Full text link
    Technical reports on operations and features of the Pierre Auger Observatory, including ongoing and planned enhancements and the status of the future northern hemisphere portion of the Observatory. Contributions to the 31st International Cosmic Ray Conference, Lodz, Poland, July 2009.Comment: Contributions to the 31st ICRC, Lodz, Poland, July 200

    Evidence for a mixed mass composition at the `ankle' in the cosmic-ray spectrum

    Get PDF
    We report a first measurement for ultra-high energy cosmic rays of the correlation between the depth of shower maximum and the signal in the water Cherenkov stations of air-showers registered simultaneously by the fluorescence and the surface detectors of the Pierre Auger Observatory. Such a correlation measurement is a unique feature of a hybrid air-shower observatory with sensitivity to both the electromagnetic and muonic components. It allows an accurate determination of the spread of primary masses in the cosmic-ray flux. Up till now, constraints on the spread of primary masses have been dominated by systematic uncertainties. The present correlation measurement is not affected by systematics in the measurement of the depth of shower maximum or the signal in the water Cherenkov stations. The analysis relies on general characteristics of air showers and is thus robust also with respect to uncertainties in hadronic event generators. The observed correlation in the energy range around the `ankle' at lg(E/eV)=18.519.0\lg(E/{\rm eV})=18.5-19.0 differs significantly from expectations for pure primary cosmic-ray compositions. A light composition made up of proton and helium only is equally inconsistent with observations. The data are explained well by a mixed composition including nuclei with mass A>4A > 4. Scenarios such as the proton dip model, with almost pure compositions, are thus disfavoured as the sole explanation of the ultrahigh-energy cosmic-ray flux at Earth.Comment: Published version. Added journal reference and DOI. Added Report Numbe
    corecore