PD1-based DNA vaccine amplifies HIV-1 GAG-specific CD8+ T cells in mice

Viral vector-based vaccines that induce protective CD8+ T cell immunity can prevent or control pathogenic SIV infections, but issues of preexisting immunity and safety have impeded their implementation in HIV-1. Here, we report the development of what we believe to be a novel antigen-targeting DNA vaccine strategy that exploits the binding of programmed death-1 (PD1) to its ligands expressed on dendritic cells (DCs) by fusing soluble PD1 with HIV-1 GAG p24 antigen. As compared with non-DC-targeting vaccines, intramuscular immunization via electroporation (EP) of the fusion DNA in mice elicited consistently high frequencies of GAG-specific, broadly reactive, polyfunctional, long-lived, and cytotoxic CD8+ T cells and robust anti-GAG antibody titers. Vaccination conferred remarkable protection against mucosal challenge with vaccinia GAG viruses. Soluble PD1-based vaccination potentiated CD8+ T cell responses by enhancing antigen binding and uptake in DCs and activation in the draining lymph node. It also increased IL-12-producing DCs and engaged antigen cross-presentation when compared with anti-DEC205 antibody-mediated DC targeting. The high frequency of durable and protective GAG-specific CD8+ T cell immunity induced by soluble PD1-based vaccination suggests that PD1-based DNA vaccines could potentially be used against HIV-1 and other pathogens.published_or_final_versio

Search for the Zγ decay mode of new high-mass resonances in pp collisions at √s = 13 TeV with the ATLAS detector

This letter presents a search for narrow, high-mass resonances in the Zγ final state with the Z boson decaying into a pair of electrons or muons. The √s = 13 TeV pp collision data were recorded by the ATLAS detector at the CERN Large Hadron Collider and have an integrated luminosity of 140 fb−1. The data are found to be in agreement with the Standard Model background expectation. Upper limits are set on the resonance production cross section times the decay branching ratio into Zγ. For spin-0 resonances produced via gluon–gluon fusion, the observed limits at 95% confidence level vary between 65.5 fb and 0.6 fb, while for spin-2 resonances produced via gluon–gluon fusion (or quark–antiquark initial states) limits vary between 77.4 (76.1) fb and 0.6 (0.5) fb, for the mass range from 220 GeV to 3400 GeV

Search for heavy Higgs bosons with flavour-violating couplings in multi-lepton plus b-jets final states in pp collisions at 13 TeV with the ATLAS detector

A search for new heavy scalars with flavour-violating decays in final states with multiple leptons and b-tagged jets is presented. The results are interpreted in terms of a general two-Higgs-doublet model involving an additional scalar with couplings to the top-quark and the three up-type quarks (ρtt, ρtc, and ρtu). The targeted signals lead to final states with either a same-sign top-quark pair, three top-quarks, or four top-quarks. 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 139 fb−1. Events are categorised depending on the multiplicity of light charged leptons (electrons or muons), total lepton charge, and a deep-neural-network output to enhance the purity of each of the signals. Masses of an additional scalar boson mH between 200 − 630 GeV with couplings ρtt = 0.4, ρtc = 0.2, and ρtu = 0.2 are excluded at 95% confidence level. Additional interpretations are provided in models of R-parity violating supersymmetry, motivated by the recent flavour and (g − 2)μ anomalies

Search for a new heavy scalar particle decaying into a Higgs boson and a new scalar singlet in final states with one or two light leptons and a pair of τ-leptons with the ATLAS detector

A search for a new heavy scalar particle X decaying into a Standard Model (SM) Higgs boson and a new singlet scalar particle S is presented. The search uses a proton-proton (pp) collision data sample with an integrated luminosity of 140 fb−1 recorded at a centre-of-mass energy of s√ = 13 TeV with the ATLAS detector at the Large Hadron Collider. The most sensitive mass parameter space is explored in X mass ranging from 500 to 1500 GeV, with the corresponding S mass in the range 200–500 GeV. The search selects events with two hadronically decaying τ-lepton candidates from H → τ+τ− decays and one or two light leptons (ℓ = e, μ) from S → VV (V = W, Z) decays while the remaining V boson decays hadronically or to neutrinos. A multivariate discriminant based on event kinematics is used to separate the signal from the background. No excess is observed beyond the expected SM background and 95% confidence level upper limits between 72 fb and 542 fb are derived on the cross-section σ(pp → X → SH) assuming the same SM-Higgs boson-like decay branching ratios for the S → VV decay. Upper limits on the visible cross-sections σ(pp → X → SH → WWττ) and σ(pp → X → SH → ZZττ) are also set in the ranges 3–26 fb and 6–33 fb, respectively

Measurement of the cross-sections of the electroweak and total production of a Zγ pair in association with two jets in pp collisions at √s = 13 TeV with the ATLAS detector

This Letter presents the measurement of the fiducial and differential cross-sections of the electroweak production of a Zγ pair in association with two jets. The analysis uses 140 fb−1 of LHC proton–proton collision data taken at √s = 13 TeV recorded by the ATLAS detector during the years 2015–2018. Events with a Z boson candidate decaying into either an e+e− or μ+μ− pair, a photon and two jets are selected. The electroweak component is extracted by requiring a large dijet invariant mass and by using the information about the centrality of the system and is measured with an observed and expected significance well above five standard deviations. The fiducial pp → Zγ jj cross-section for the electroweak production is measured to be 3.6 ± 0.5 fb. The total fiducial cross-section that also includes contributions where the jets arise from strong interactions is measured to be 16.8+2.0 −1.8 fb. The results are consistent with the Standard Model predictions. Differential cross-sections are also measured using the same events and are compared with parton-shower Monte Carlo simulations. Good agreement is observed between data and predictions

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Search for lepton-favour violation in high-mass dilepton final states using 139 fb−1 of pp collisions at √s = 13 TeV with the ATLAS detector

A search is performed for a heavy particle decaying into different-flavour, dilepton final states, using 139 fb−1 of proton-proton collision data at √s = 13 TeV collected in 2015–2018 by the ATLAS detector at the Large Hadron Collider. Final states with electrons, muons and hadronically decaying tau leptons are considered (eμ, eτ or μτ). No significant excess over the Standard Model predictions is observed. Upper limits on the production cross-section are set as a function of the mass of a Z′ boson, a supersymmetric τ-sneutrino, and a quantum black-hole. The observed 95% CL lower mass limits obtained on a typical benchmark model Z′ boson are 5.0 TeV (eμ), 4.0 TeV (eτ), and 3.9 TeV (μτ), respectively

Search for non-resonant production of semi-visible jets using Run 2 data in ATLAS

Semi-visible jets, with a significant contribution to the event's missing transverse momentum, can arise in strongly interacting dark sectors. This results in an event topology where one of the jets can be aligned with the direction of the missing transverse momentum. The first search for semi-visible jets produced via a t-channel mediator exchange is presented. The analysis uses proton-proton collisions with an integrated luminosity of 139 fb−1 and a centre-of-mass energy of 13 TeV, collected with the ATLAS detector during the Run 2 of the LHC. No excess over Standard Model predictions is observed. Assuming a coupling strength of unity between the mediator, a Standard Model quark and a dark quark, mediator masses up to 2.7 TeV are excluded at the 95% confidence level. Upper limits on the coupling strength are also derived

Combination of searches for heavy spin-1 resonances using 139 fb−1 of proton-proton collision data at √s = 13 TeV with the ATLAS detector

A combination of searches for new heavy spin-1 resonances decaying into diferent pairings of W, Z, or Higgs bosons, as well as directly into leptons or quarks, is presented. The data sample used corresponds to 139 fb−1 of proton-proton collisions at √s = 13 TeV collected during 2015–2018 with the ATLAS detector at the CERN Large Hadron Collider. Analyses selecting quark pairs (qq, bb, tt¯, and tb) or third-generation leptons (τν and τ τ ) are included in this kind of combination for the frst time. A simplifed model predicting a spin-1 heavy vector-boson triplet is used. Cross-section limits are set at the 95% confdence level and are compared with predictions for the benchmark model. These limits are also expressed in terms of constraints on couplings of the heavy vector-boson triplet to quarks, leptons, and the Higgs boson. The complementarity of the various analyses increases the sensitivity to new physics, and the resulting constraints are stronger than those from any individual analysis considered. The data exclude a heavy vector-boson triplet with mass below 5.8 TeV in a weakly coupled scenario, below 4.4 TeV in a strongly coupled scenario, and up to 1.5 TeV in the case of production via vector-boson fusion