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

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

Comparison of Recent SnIa datasets

We rank the six latest Type Ia supernova (SnIa) datasets (Constitution (C), Union (U), ESSENCE (Davis) (E), Gold06 (G), SNLS 1yr (S) and SDSS-II (D)) in the context of the Chevalier-Polarski-Linder (CPL) parametrization $w(a)=w_0+w_1 (1-a)$, according to their Figure of Merit (FoM), their consistency with the cosmological constant ($\Lambda$CDM), their consistency with standard rulers (Cosmic Microwave Background (CMB) and Baryon Acoustic Oscillations (BAO)) and their mutual consistency. We find a significant improvement of the FoM (defined as the inverse area of the 95.4% parameter contour) with the number of SnIa of these datasets ((C) highest FoM, (U), (G), (D), (E), (S) lowest FoM). Standard rulers (CMB+BAO) have a better FoM by about a factor of 3, compared to the highest FoM SnIa dataset (C). We also find that the ranking sequence based on consistency with $\Lambda$CDM is identical with the corresponding ranking based on consistency with standard rulers ((S) most consistent, (D), (C), (E), (U), (G) least consistent). The ranking sequence of the datasets however changes when we consider the consistency with an expansion history corresponding to evolving dark energy $(w_0,w_1)=(-1.4,2)$ crossing the phantom divide line $w=-1$ (it is practically reversed to (G), (U), (E), (S), (D), (C)). The SALT2 and MLCS2k2 fitters are also compared and some peculiar features of the SDSS-II dataset when standardized with the MLCS2k2 fitter are pointed out. Finally, we construct a statistic to estimate the internal consistency of a collection of SnIa datasets. We find that even though there is good consistency among most samples taken from the above datasets, this consistency decreases significantly when the Gold06 (G) dataset is included in the sample.Comment: 13 pages, 9 figures. Included recently released SDSS-II dataset. Improved presentation. Main results unchanged. The mathematica files and datasets used for the production of the figures may be downloaded from http://leandros.physics.uoi.gr/datacomp

Nucleon Decay Searches with large Liquid Argon TPC Detectors at Shallow Depths: atmospheric neutrinos and cosmogenic backgrounds

Grand Unification of the strong, weak and electromagnetic interactions into a single unified gauge group is an extremely appealing idea which has been vigorously pursued theoretically and experimentally for many years. The detection of proton or bound-neutron decays would represent its most direct experimental evidence. In this context, we studied the physics potentialities of very large underground Liquid Argon Time Projection Chambers (LAr TPC). We carried out a detailed simulation of signal efficiency and background sources, including atmospheric neutrinos and cosmogenic backgrounds. We point out that a liquid Argon TPC, offering good granularity and energy resolution, low particle detection threshold, and excellent background discrimination, should yield very good signal over background ratios in many possible decay modes, allowing to reach partial lifetime sensitivities in the range of 1034−1035 years with exposures up to 1000 kton×year, often in quasi-background-free conditions optimal for discoveries at the few events level, corresponding to atmospheric neutrino background rejections of the order of 105. Multi-prong decay modes like e.g. p→μ−π+K+ or p→e+π+π− and channels involving kaons like e.g. p→K+ν¯, p→e+K0 and p→μ+K0 are particularly suitable, since liquid Argon imaging (...)This work was in part supported by ETH and the Swiss National Foundation. AB, AJM and SN have been supported by CICYT Grants FPA-2002-01835 and FPA-2005-07605-C02-01. SN acknowledges support from the Ramon y Cajal Programme. We thank P. Sala for help with FLUKA while she was an ETH employee

Prediction of Neutrino Fluxes in the NOMAD Experiment

The method developed for the calculation of the flux and composition of the West Area Neutrino Beam used by NOMAD in its search for neutrino oscillations is described. The calculation is based on particle production rates computed using a recent version of FLUKA and modified to take into account the cross sections measured by the SPY and NA20 experiments. These particles are propagated through the beam line taking into account the material and magnetic fields they traverse. The neutrinos produced through their decays are tracked to the NOMAD detector. The fluxes of the four neutrino flavours at NOMAD are predicted with an uncertainty of about 8% for nu(mu) and nu(e), 10% for antinu(mu), and 12% for antinu(e). The energy-dependent uncertainty achieved on the R(e, mu) prediction needed for a nu(mu)->nu(e) oscillation search ranges from 4% to 7%, whereas the overall normalization uncertainty on this ratio is 4.2%.Comment: 43 pages, 20 figures. Submitted to Nucl. Phys.

A Study of Strange Particles Produced in Neutrino Neutral Current Interactions in the NOMAD Experiment

Results of a detailed study of strange particle production in neutrino neutral current interactions are presented using the data from the NOMAD experiment. Integral yields of neutral strange particles (K0s, Lambda, Lambda-bar) have been measured. Decays of resonances and heavy hyperons with an identified K0s or Lambda in the final state have been analyzed. Clear signals corresponding to K* and Sigma(1385) have been observed. First results on the measurements of the Lambda polarization in neutral current interactions have been obtained.Comment: Accepted for publication in Nuclear Physics B as a rapid communicatio

Multiwavelength studies of MHD waves in the solar chromosphere: An overview of recent results

The chromosphere is a thin layer of the solar atmosphere that bridges the relatively cool photosphere and the intensely heated transition region and corona. Compressible and incompressible waves propagating through the chromosphere can supply significant amounts of energy to the interface region and corona. In recent years an abundance of high-resolution observations from state-of-the-art facilities have provided new and exciting ways of disentangling the characteristics of oscillatory phenomena propagating through the dynamic chromosphere. Coupled with rapid advancements in magnetohydrodynamic wave theory, we are now in an ideal position to thoroughly investigate the role waves play in supplying energy to sustain chromospheric and coronal heating. Here, we review the recent progress made in characterising, categorising and interpreting oscillations manifesting in the solar chromosphere, with an impetus placed on their intrinsic energetics.Comment: 48 pages, 25 figures, accepted into Space Science Review

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Wideband on-chip terahertz spectrometer based on a superconducting filterbank

Instrumentatio