The HMGB1-RAGE axis mediates traumatic brain injury-induced pulmonary dysfunction in lung transplantation

Traumatic brain injury (TBI) results in systemic inflammatory responses that affect the lung. This is especially critical in the setting of lung transplantation, where more than half of donor allografts are obtained postmortem from individuals with TBI. The mechanism by which TBI causes pulmonary dysfunction remains unclear but may involve the interaction of high-mobility group box-1 (HMGB1) protein with the receptor for advanced glycation end products (RAGE). To investigate the role of HMGB1 and RAGE in TBI-induced lung dysfunction, RAGE-sufficient (wild-type) or RAGE-deficient (RAGE(-/-)) C57BL/6 mice were subjected to TBI through controlled cortical impact and studied for cardiopulmonary injury. Compared to control animals, TBI induced systemic hypoxia, acute lung injury, pulmonary neutrophilia, and decreased compliance (a measure of the lungs' ability to expand), all of which were attenuated in RAGE(-/-) mice. Neutralizing systemic HMGB1 induced by TBI reversed hypoxia and improved lung compliance. Compared to wild-type donors, lungs from RAGE(-/-) TBI donors did not develop acute lung injury after transplantation. In a study of clinical transplantation, elevated systemic HMGB1 in donors correlated with impaired systemic oxygenation of the donor lung before transplantation and predicted impaired oxygenation after transplantation. These data suggest that the HMGB1-RAGE axis plays a role in the mechanism by which TBI induces lung dysfunction and that targeting this pathway before transplant may improve recipient outcomes after lung transplantation

Associations between drug and alcohol use, smoking, and frailty among people with HIV across the United States in the current era of antiretroviral treatment

Objective: To examine associations between frailty and drug, alcohol, and tobacco use among a large diverse cohort of people with HIV (PWH) in clinical care in the current era. Methods: PWH at 7 sites across the United States completed clinical assessments of patient-reported measures and outcomes between 2016 and 2019 as part of routine care including drug and alcohol use, smoking, and other domains. Frailty was assessed using 4 of the 5 components of the Fried frailty phenotype and PWH were categorized as not frail, pre-frail, or frail. Associations of substance use with frailty were assessed with multivariate Poisson regression. Results: Among 9336 PWH, 43% were not frail, 44% were prefrail, and 13% were frail. Frailty was more prevalent among women, older PWH, and those reporting current use of drugs or cigarettes. Current methamphetamine use (1.26: 95% CI 1.07–1.48), current (1.65: 95% CI 1.39–1.97) and former (1.21:95% CI 1.06–1.36) illicit opioid use, and former cocaine/crack use (1.17: 95% CI 1.01–1.35) were associated with greater risk of being frail in adjusted analyses. Current smoking was associated with a 61% higher risk of being frail vs. not frail (1.61: 95% CI 1.41–1.85) in adjusted analyses. Conclusions: We found a high prevalence of prefrailty and frailty among a nationally distributed cohort of PWH in care. This study identified distinct risk factors that may be associated with frailty among PWH, many of which, such as cigarette smoking and drug use, are potentially modifiable

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

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

The ATLAS trigger system for LHC Run 3 and trigger performance in 2022

The ATLAS trigger system is a crucial component of the ATLAS experiment at the LHC. It is responsible for selecting events in line with the ATLAS physics programme. This paper presents an overview of the changes to the trigger and data acquisition system during the second long shutdown of the LHC, and shows the performance of the trigger system and its components in the proton-proton collisions during the 2022 commissioning period as well as its expected performance in proton-proton and heavy-ion collisions for the remainder of the third LHC data-taking period (2022–2025)

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

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

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

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

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