363 research outputs found

    Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

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    Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

    The formation and fate of internal waves in the South China Sea

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    Internal gravity waves, the subsurface analogue of the familiar surface gravity waves that break on beaches, are ubiquitous in the ocean. Because of their strong vertical and horizontal currents, and the turbulent mixing caused by their breaking, they affect a panoply of ocean processes, such as the supply of nutrients for photosynthesis1, sediment and pollutant transport2 and acoustic transmission3; they also pose hazards for man-made structures in the ocean4. Generated primarily by the wind and the tides, internal waves can travel thousands of kilometres from their sources before breaking5, making it challenging to observe them and to include them in numerical climate models, which are sensitive to their effects6,7. For over a decade, studies8-11 have targeted the South China Sea, where the oceans' most powerful known internal waves are generated in the Luzon Strait and steepen dramatically as they propagate west. Confusion has persisted regarding their mechanism of generation, variability and energy budget, however, owing to the lack of in situ data from the Luzon Strait, where extreme flow conditions make measurements difficult. Here we use new observations and numerical models to (1) show that the waves begin as sinusoidal disturbances rather than arising from sharp hydraulic phenomena, (2) reveal the existence of >200-metre-high breaking internal waves in the region of generation that give rise to turbulence levels >10,000 times that in the open ocean, (3) determine that the Kuroshio western boundary current noticeably refracts the internal wave field emanating from the Luzon Strait, and (4) demonstrate a factor-of-two agreement between modelled and observed energy fluxes, which allows us to produce an observationally supported energy budget of the region. Together, these findings give a cradle-to-grave picture of internal waves on a basin scale, which will support further improvements of their representation in numerical climate predictions

    ϒ production in p–Pb collisions at √sNN=8.16 TeV

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    ϒ production in p–Pb interactions is studied at the centre-of-mass energy per nucleon–nucleon collision √sNN = 8.16 TeV with the ALICE detector at the CERN LHC. The measurement is performed reconstructing bottomonium resonances via their dimuon decay channel, in the centre-of-mass rapidity intervals 2.03 < ycms < 3.53 and −4.46 < ycms < −2.96, down to zero transverse momentum. In this work, results on the ϒ(1S) production cross section as a function of rapidity and transverse momentum are presented. The corresponding nuclear modification factor shows a suppression of the ϒ(1S) yields with respect to pp collisions, both at forward and backward rapidity. This suppression is stronger in the low transverse momentum region and shows no significant dependence on the centrality of the interactions. Furthermore, the ϒ(2S) nuclear modification factor is evaluated, suggesting a suppression similar to that of the ϒ(1S). A first measurement of the ϒ(3S) has also been performed. Finally, results are compared with previous ALICE measurements in p–Pb collisions at √sNN = 5.02 TeV and with theoretical calculations.publishedVersio

    (Anti-)deuteron production in pp collisions at 1as=13TeV

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    The study of (anti-)deuteron production in pp collisions has proven to be a powerful tool to investigate the formation mechanism of loosely bound states in high-energy hadronic collisions. In this paper the production of (anti-)deuterons is studied as a function of the charged particle multiplicity in inelastic pp collisions at s=13 TeV using the ALICE experiment. Thanks to the large number of accumulated minimum bias events, it has been possible to measure (anti-)deuteron production in pp collisions up to the same charged particle multiplicity (d Nch/ d \u3b7 3c 26) as measured in p\u2013Pb collisions at similar centre-of-mass energies. Within the uncertainties, the deuteron yield in pp collisions resembles the one in p\u2013Pb interactions, suggesting a common formation mechanism behind the production of light nuclei in hadronic interactions. In this context the measurements are compared with the expectations of coalescence and statistical hadronisation models (SHM)

    Multiplicity dependence of inclusive J/psi production at midrapidity in pp collisions at root s=13 TeV

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    Measurements of the inclusive J/psi yield as a function of charged-particle pseudorapidity density dN(ch)/d eta in pp collisions at root s = 13 TeV with ALICE at the LHC are reported. The J/psi meson yield is measured at midrapidity (vertical bar y vertical bar <0.9) in the dielectron channel, for events selected based on the charged-particle multiplicity at midrapidity (vertical bar eta vertical bar <1) and at forward rapidity (-3.7 <eta <-1.7 and 2.8 <eta <5.1); both observables are normalized to their corresponding averages in minimum bias events. The increase of the normalized J/psi yield with normalized dN(ch)/d eta is significantly stronger than linear and dependent on the transverse momentum. The data are compared to theoretical predictions, which describe the observed trends well, albeit not always quantitatively. (C) 2020 European Organization for Nuclear Research. Published by Elsevier B.V.Peer reviewe

    Measurements of the production cross-section for a Z boson in association with b- or c-jets in proton–proton collisions at √s = 13 TeV with the ATLAS detector

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    This paper presents a measurement of the production cross-section of a Z boson in association with bor c-jets, in proton–proton collisions at √s = 13 TeV with the ATLAS experiment at the Large Hadron Collider using data corresponding to an integrated luminosity of 140 fb−1. Inclusive and differential cross-sections are measured for events containing a Z boson decaying into electrons or muons and produced in association with at least one b-jet, at least one c-jet, or at least two b-jets with transverse momentum pT > 20 GeV and rapidity |y| < 2.5. Predictions from several Monte Carlo generators based on next-to-leading-order matrix elements interfaced with a parton-shower simulation, with different choices of flavour schemes for initial-state partons, are compared with the measured cross-sections. The results are also compared with novel predictions, based on infrared and collinear safe jet flavour dressing algorithms. Selected Z+ ≥ 1 c-jet observables, optimized for sensitivity to intrinsic-charm, are compared with benchmark models with different intrinsic-charm fractions

    Search for non-resonant Higgs boson pair production in final states with leptons, taus, and photons in pp collisions at √s = 13 TeV with the ATLAS detector

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    A search is presented for non-resonant Higgs boson pair production, targeting the bbZZ, 4V (V = W or Z), V V τ τ , 4τ , γγV V and γγτ τ decay channels. Events are categorised based on the multiplicity of light charged leptons (electrons or muons), hadronically decaying tau leptons, and photons. The search is based on a data sample of proton-proton collisions at √s = 13 TeV recorded with the ATLAS detector during Run 2 of the Large Hadron Collider, corresponding to an integrated luminosity of 140 fb−1. No evidence of the signal is found and the observed (expected) upper limit on the cross-section for non-resonant Higgs boson pair production is determined to be 17 (11) times the Standard Model predicted cross-section at 95% confidence level under the background-only hypothesis. The observed (expected) constraints on the HHH coupling modifier, κλ, are determined to be −6.2 < κλ < 11.6 (−4.5 < κλ < 9.6) at 95% confidence level, assuming the Standard Model for the expected limits and that new physics would only affect κλ

    Measurement of vector boson production cross sections and their ratios using pp collisions at √s = 13.6 TeV with the ATLAS detector

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    Abstract available from publisher's website

    Beam-induced backgrounds measured in the ATLAS detector during local gas injection into the LHC beam vacuum

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    Inelastic beam-gas collisions at the Large Hadron Collider (LHC), within a few hundred metres of the ATLAS experiment, are known to give the dominant contribution to beam backgrounds. These are monitored by ATLAS with a dedicated Beam Conditions Monitor (BCM) and with the rate of fake jets in the calorimeters. These two methods are complementary since the BCM probes backgrounds just around the beam pipe while fake jets are observed at radii of up to several metres. In order to quantify the correlation between the residual gas density in the LHC beam vacuum and the experimental backgrounds recorded by ATLAS, several dedicated tests were performed during LHC Run 2. Local pressure bumps, with a gas density several orders of magnitude higher than during normal operation, were introduced at different locations. The changes of beam-related backgrounds, seen in ATLAS, are correlated with the local pressure variation. In addition the rates of beam-gas events are estimated from the pressure measurements and pressure bump profiles obtained from calculations. Using these rates, the efficiency of the ATLAS beam background monitors to detect beam-gas events is derived as a function of distance from the interaction point. These efficiencies and characteristic distributions of fake jets from the beam backgrounds are found to be in good agreement with results of beam-gas simulations performed with theFluka Monte Carlo programme
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