Bronchodilator tolerance and rebound bronchoconstriction during regular inhaled β -agonist treatment

AbstractThere is uncertainty about the development of airway tolerance to β -agonists and the phenomenon of rebound bronchoconstriction on β -agonist withdrawal. We have recently completed a study of the regular terbutaline and budesonide treatment in asthma. We report our observations on the effect of starting and stopping terbutaline treatment on morning and evening peak flows.The study was a randomized four-way, double-dummy, cross-over comparison of regular inhaled terbutaline (500–1000 μ g four times daily), budesonide, combined treatment and matching placebo. Each treatment was given for 6 weeks following a 4 week single-blind placebo washout. Ipratropium was used for symptom relief. No other asthma medication was permitted during either the treatment or wash-out periods. Evaluable data were obtained from 52 subjects for both placebo and terbutaline treatment. Changes in mean morning and evening peak flows during terbutaline treatment were compared to the baseline peak flows during the last 2 weeks of the preceding washout. The peak flow changes on stopping terbutaline were also analysed.Mean morning peak flow was not significantly different during terbutaline treatment when compared to either baseline or placebo treatment. Evening peak flows were significantly higher during terbutaline treatment [mean increase 23·1l min−1(95%CI=18·8, 27·4)]. Analysis of the peak flow changes on a day-by-day basis revealed an initial increase in morning peak flows for the first 2 days of treatment of 19·2 and 13·4l min−1[increases of 25·0 and 17·3l min−1in comparison with the corresponding values during placebo (P<0·01)] followed by a return to baseline. The increase in evening peak flows was also greater for the first 2 days of treatment than for the remainder of the treatment period (P<0·01). On ceasing terbutaline treatment there was a fall in mean morning peak flow below the baseline on the following morning of 21·6l min−1(P<0·05 compared to placebo).The temporary increase in morning peak flows and greater than expected rise in evening peak flows for the first 2 days of treatment suggest the development of tolerance to the bronchodilator effect of terbutaline. Similarly, the fall in morning peak flows on treatment withdrawal suggests rebound bronchoconstriction. These effects are likely to be mediated by downregulation of the β -receptor during treatment. The clinical significance of these changes is uncertain in view of the stability of overall asthma control during terbutaline treatment, but sudden withdrawal of β -agonist treatment could conceivably lead to a deterioration in asthma control

Spatiotemporal multi-resolution approximation of the Amari type neural field model

Neural fields are spatially continuous state variables described by integro-differential equations, which are well suited to describe the spatiotemporal evolution of cortical activations on multiple scales. Here we develop a multi-resolution approximation (MRA) framework for the integro-difference equation (IDE) neural field model based on semi-orthogonal cardinal B-spline wavelets. In this way, a flexible framework is created, whereby both macroscopic and microscopic behavior of the system can be represented simultaneously. State and parameter estimation is performed using the expectation maximization (EM) algorithm. A synthetic example is provided to demonstrate the framework

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

Measurements of multijet event isotropies using optimal transport with the ATLAS detector

A measurement of novel event shapes quantifying the isotropy of collider events is performed in 140 fb−1 of proton-proton collisions with s√ = 13 TeV centre-of-mass energy recorded with the ATLAS detector at CERN’s Large Hadron Collider. These event shapes are defined as the Wasserstein distance between collider events and isotropic reference geometries. This distance is evaluated by solving optimal transport problems, using the ‘Energy-Mover’s Distance’. Isotropic references with cylindrical and circular symmetries are studied, to probe the symmetries of interest at hadron colliders. The novel event-shape observables defined in this way are infrared- and collinear-safe, have improved dynamic range and have greater sensitivity to isotropic radiation patterns than other event shapes. The measured event-shape variables are corrected for detector effects, and presented in inclusive bins of jet multiplicity and the scalar sum of the two leading jets’ transverse momenta. The measured distributions are provided as inputs to future Monte Carlo tuning campaigns and other studies probing fundamental properties of QCD and the production of hadronic final states up to the TeV-scale

Measurement of Zγγ production in pp collisions at s√=13 TeV with the ATLAS detector

Cross-sections for the production of a Z boson in association with two photons are measured in proton–proton collisions at a centre-of-mass energy of 13 TeV. The data used correspond to an integrated luminosity of 139 fb−1 recorded by the ATLAS experiment during Run 2 of the LHC. The measurements use the electron and muon decay channels of the Z boson, and a fiducial phase-space region where the photons are not radiated from the leptons. The integrated Z(→ℓℓ)γγ cross-section is measured with a precision of 12% and differential cross-sections are measured as a function of six kinematic variables of the Zγγ system. The data are compared with predictions from MC event generators which are accurate to up to next-to-leading order in QCD. The cross-section measurements are used to set limits on the coupling strengths of dimension-8 operators in the framework of an effective field theory

Search for direct production of winos and higgsinos in events with two same-charge leptons or three leptons in pp collision data at √s = 13 TeV with the ATLAS detector

A search for supersymmetry targeting the direct production of winos and higgsinos is conducted in final states with either two leptons (e or µ) with the same electric charge, or three leptons. The analysis uses 139 fb−1 of pp collision data at √s = 13 TeV collected with the ATLAS detector during Run 2 of the Large Hadron Collider. No significant excess over the Standard Model expectation is observed. Simplified and complete models with and without R-parity conservation are considered. In topologies with intermediate states including either W h or W Z pairs, wino masses up to 525 GeV and 250 GeV are excluded, respectively, for a bino of vanishing mass. Higgsino masses smaller than 440 GeV are excluded in a natural R-parity-violating model with bilinear terms. Upper limits on the production cross section of generic events beyond the Standard Model as low as 40 ab are obtained in signal regions optimised for these models and also for an R-parity-violating scenario with baryon-number-violating higgsino decays into top quarks and jets. The analysis significantly improves sensitivity to supersymmetric models and other processes beyond the Standard Model that may contribute to the considered final states

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

Inclusive-photon production and its dependence on photon isolation in pp collisions at s√ = 13 TeV using 139 fb−1 of ATLAS data

Measurements of differential cross sections are presented for inclusive isolated-photon production in pp collisions at a centre-of-mass energy of 13 TeV provided by the LHC and using 139 fb−1 of data recorded by the ATLAS experiment. The cross sections are measured as functions of the photon transverse energy in different regions of photon pseudorapidity. The photons are required to be isolated by means of a fixed-cone method with two different cone radii. The dependence of the inclusive-photon production on the photon isolation is investigated by measuring the fiducial cross sections as functions of the isolation-cone radius and the ratios of the differential cross sections with different radii in different regions of photon pseudorapidity. The results presented in this paper constitute an improvement with respect to those published by ATLAS earlier: the measurements are provided for different isolation radii and with a more granular segmentation in photon pseudorapidity that can be exploited in improving the determination of the proton parton distribution functions. These improvements provide a more in-depth test of the theoretical predictions. Next-to-leading-order QCD predictions from JETPHOX and SHERPA and next-to-next-to-leading-order QCD predictions from NNLOJET are compared to the measurements, using several parameterisations of the proton parton distribution functions. The measured cross sections are well described by the fixed-order QCD predictions within the experimental and theoretical uncertainties in most of the investigated phase-space region

Measurements of Zγ+jets differential cross sections in pp collisions at s√ = 13 TeV with the ATLAS detector

Differential cross-section measurements of Zγ production in association with hadronic jets are presented, using the full 139 fb−1 dataset of s√ = 13 TeV proton–proton collisions collected by the ATLAS detector during Run 2 of the LHC. Distributions are measured using events in which the Z boson decays leptonically and the photon is usually radiated from an initial-state quark. Measurements are made in both one and two observables, including those sensitive to the hard scattering in the event and others which probe additional soft and collinear radiation. Different Standard Model predictions, from both parton-shower Monte Carlo simulation and fixed-order QCD calculations, are compared with the measurements. In general, good agreement is observed between data and predictions from MATRIX and MiNNLOPS, as well as next-to-leading-order predictions from MADGRAPH5_AMC@NLO and SHERPA

Search for heavy resonances decaying into a Z or W boson and a Higgs boson in final states with leptons and b-jets in 139 fb−1 of pp collisions at s√ = 13 TeV with the ATLAS detector

This article presents a search for new resonances decaying into a Z or W boson and a 125 GeV Higgs boson h, and it targets the νν¯¯¯bb¯¯, ℓ+ℓ−bb¯¯, or ℓ±νbb¯¯ final states, where ℓ = e or μ, in proton-proton collisions at s√ = 13 TeV. The data used correspond to a total integrated luminosity of 139 fb−1 collected by the ATLAS detector during Run 2 of the LHC at CERN. The search is conducted by examining the reconstructed invariant or transverse mass distributions of Zh or Wh candidates for evidence of a localised excess in the mass range from 220 GeV to 5 TeV. No significant excess is observed and 95% confidence-level upper limits between 1.3 pb and 0.3 fb are placed on the production cross section times branching fraction of neutral and charged spin-1 resonances and CP-odd scalar bosons. These limits are converted into constraints on the parameter space of the Heavy Vector Triplet model and the two-Higgs-doublet model