Using observational data to emulate a randomized trial of dynamic treatment switching strategies

BACKGROUND: When a clinical treatment fails or shows suboptimal results, the question of when to switch to another treatment arises. Treatment switching strategies are often dynamic because the time of switching depends on the evolution of an individual's time-varying covariates. Dynamic strategies can be directly compared in randomized trials. For example, HIV-infected individuals receiving antiretroviral therapy could be randomized to switching therapy within 90 days of HIV-1 RNA crossing above a threshold of either 400 copies/ml (tight-control strategy) or 1000 copies/ml (loose-control strategy).METHODS: We review an approach to emulate a randomized trial of dynamic switching strategies using observational data from the Antiretroviral Therapy Cohort Collaboration, the Centers for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration. We estimated the comparative effect of tight-control vs. loose-control strategies on death and AIDS or death via inverse-probability weighting.RESULTS: Of 43 803 individuals who initiated an eligible antiretroviral therapy regimen in 2002 or later, 2001 met the baseline inclusion criteria for the mortality analysis and 1641 for the AIDS or death analysis. There were 21 deaths and 33 AIDS or death events in the tight-control group, and 28 deaths and 41 AIDS or death events in the loose-control group. Compared with tight control, the adjusted hazard ratios (95% confidence interval) for loose control were 1.10 (0.73, 1.66) for death, and 1.04 (0.86, 1.27) for AIDS or death.CONCLUSIONS: Although our effective sample sizes were small and our estimates imprecise, the described methodological approach can serve as an example for future analyses

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

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

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

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

Search for heavy Majorana neutrinos in e±e± and e±μ± final states via WW scattering in pp collisions at √s = 13 TeV with the ATLAS detector

A search for heavy Majorana neutrinos in scattering of same-sign W boson pairs in proton–proton collisions at √s = 13 TeV at the LHC is reported. The dataset used corresponds to an integrated luminosity of 140 fb−1, collected with the ATLAS detector during 2015–2018. The search is performed in final states including a same-sign ee or eμ pair and at least two jets with large invariant mass and a large rapidity difference. No significant excess of events with respect to the Standard Model background predictions is observed. The results are interpreted in a benchmark scenario of the Phenomenological Type-I Seesaw model. New constraints are set on the values of the |VeN|2 and |VeN V*μN| parameters for heavy Majorana neutrino masses between 50 GeV and 20 TeV, where VℓN is the matrix element describing the mixing of the heavy Majorana neutrino mass eigenstate with the Standard Model neutrino of flavour ℓ = e, μ. The sensitivity to the Weinberg operator is investigated and constraints on the effective ee and eμ Majorana neutrino masses are reported. The statistical combination of the ee and eμ channels with the previously published μμ channel is performed

Search for dark mesons decaying to top and bottom quarks in proton-proton collisions at √s = 13 TeV with the ATLAS detector

A search for dark mesons originating from strongly-coupled, SU(2) dark favor symmetry conserving models and decaying gaugephobically to pure Standard Model final states containing top and bottom quarks is presented. The search targets fully hadronic final states and final states with exactly one electron or muon and multiple jets. The analyzed data sample corresponds to an integrated luminosity of 140 fb−1 of proton-proton collisions collected at √s = 13 TeV with the ATLAS detector at the Large Hadron Collider. No significant excess over the Standard Model background expectation is observed and the results are used to set the first direct constraints on this type of model. The two-dimensional signal space of dark pion masses mπD and dark rho-meson masses mρD is scanned. For mπD /mρD = 0.45, dark pions with masses mπD < 940 GeV are excluded at the 95% CL, while for mπD /mρD = 0.25 masses mπD < 740 GeV are excluded

Combination of searches for Higgs boson decays into a photon and a massless dark photon using pp collisions at √s = 13 TeV with the ATLAS detector

A combination of searches for Higgs boson decays into a visible photon and a massless dark photon (H → γγd) is presented using 139 fb−1 of proton-proton collision data at a centre-of-mass energy of √s = 13 TeV recorded by the ATLAS detector at the Large Hadron Collider. The observed (expected) 95% confidence level upper limit on the Standard Model Higgs boson decay branching ratio is determined to be B(H → γγd) < 1.3% (1.5)%. The search is also sensitive to higher-mass Higgs bosons decaying into the same final state. The observed (expected) 95% confidence level limit on the cross-section times branching ratio ranges from 16 fb (20 fb) for mH = 400 GeV to 1.0 fb (1.5 fb) for mH = 3 TeV. Results are also interpreted in the context of a minimal simplified model

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

Abstract available from publisher's website