A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

The performance of the jet trigger for the ATLAS detector during 2011 data taking

The performance of the jet trigger for the ATLAS detector at the LHC during the 2011 data taking period is described. During 2011 the LHC provided proton–proton collisions with a centre-of-mass energy of 7 TeV and heavy ion collisions with a 2.76 TeV per nucleon–nucleon collision energy. The ATLAS trigger is a three level system designed to reduce the rate of events from the 40 MHz nominal maximum bunch crossing rate to the approximate 400 Hz which can be written to offline storage. The ATLAS jet trigger is the primary means for the online selection of events containing jets. Events are accepted by the trigger if they contain one or more jets above some transverse energy threshold. During 2011 data taking the jet trigger was fully efficient for jets with transverse energy above 25 GeV for triggers seeded randomly at Level 1. For triggers which require a jet to be identified at each of the three trigger levels, full efficiency is reached for offline jets with transverse energy above 60 GeV. Jets reconstructed in the final trigger level and corresponding to offline jets with transverse energy greater than 60 GeV, are reconstructed with a resolution in transverse energy with respect to offline jets, of better than 4 % in the central region and better than 2.5 % in the forward direction

Measurement of the View the tt production cross-section using eμ events with b-tagged jets in pp collisions at √s = 13 TeV with the ATLAS detector

This paper describes a measurement of the inclusive top quark pair production cross-section (σtt¯) with a data sample of 3.2 fb−1 of proton–proton collisions at a centre-of-mass energy of √s = 13 TeV, collected in 2015 by the ATLAS detector at the LHC. This measurement uses events with an opposite-charge electron–muon pair in the final state. Jets containing b-quarks are tagged using an algorithm based on track impact parameters and reconstructed secondary vertices. The numbers of events with exactly one and exactly two b-tagged jets are counted and used to determine simultaneously σtt¯ and the efficiency to reconstruct and b-tag a jet from a top quark decay, thereby minimising the associated systematic uncertainties. The cross-section is measured to be: σtt¯ = 818 ± 8 (stat) ± 27 (syst) ± 19 (lumi) ± 12 (beam) pb, where the four uncertainties arise from data statistics, experimental and theoretical systematic effects, the integrated luminosity and the LHC beam energy, giving a total relative uncertainty of 4.4%. The result is consistent with theoretical QCD calculations at next-to-next-to-leading order. A fiducial measurement corresponding to the experimental acceptance of the leptons is also presented

Measurement of the double-differential high-mass Drell-Yan cross section in pp collisions at √s = 8 TeV with the ATLAS detector

This paper presents a measurement of the double-differential cross section for the Drell-Yan Z/γ∗ → ℓ+ℓ− and photon-induced γγ → ℓ+ℓ− processes where ℓ is an electron or muon. The measurement is performed for invariant masses of the lepton pairs, mℓℓ, between 116 GeV and 1500 GeV using a sample of 20.3 fb−1 of pp collisions data at centre-of-mass energy of √s = 8 TeV collected by the ATLAS detector at the LHC in 2012. The data are presented double differentially in invariant mass and absolute dilepton rapidity as well as in invariant mass and absolute pseudorapidity separation of the lepton pair. The single-differential cross section as a function of mℓℓ is also reported. The electron and muon channel measurements are combined and a total experimental precision of better than 1% is achieved at low mℓℓ. A comparison to next-to-next-to-leading order perturbative QCD predictions using several recent parton distribution functions and including next-to-leading order electroweak effects indicates the potential of the data to constrain parton distribution functions. In particular, a large impact of the data on the photon PDF is demonstrated

Measurement of W± and Z-boson production cross sections in pp collisions at √s=13 TeV with the ATLAS detector

See paper for full list of authors - 17 pages plus author list + cover pages (34 pages total), 5 figures, 3 tables, submitted to Phys. Lett. B, All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2015-03/International audienceMeasurements of the $W^{\pm} \rightarrow \ell^{\pm} \nu$ and $Z \rightarrow \ell^+ \ell^-$ production cross sections (where $\ell^{\pm}=e^{\pm},\mu^{\pm}$) in proton-proton collisions at $\sqrt{s}=13$ TeV are presented using data recorded by the ATLAS experiment at the Large Hadron Collider, corresponding to a total integrated luminosity of 81 pb$^{-1}$. The total inclusive $W^{\pm}$-boson production cross sections times the single-lepton-flavour branching ratios are $\sigma_{W^+}^{tot}= 11.78 \pm 0.02 (stat) \pm 0.32 (sys) \pm 0.59 (lumi)$ nb and $\sigma_{W^-}^{tot} = 8.75 \pm 0.02 (stat) \pm 0.24 (sys) \pm 0.44 (lumi)$ nb for $W^+$ and $W^-$, respectively. The total inclusive $Z$-boson production cross section times leptonic branching ratio, within the invariant mass window $66 < m_{\ell\ell} < 116$ GeV, is $\sigma_{Z}^{tot} = 1.97 \pm 0.01 (stat) \pm 0.04 (sys) \pm 0.10 (lumi)$ nb. The $W^+$, $W^-$, and $Z$-boson production cross sections and cross-section ratios within a fiducial region defined by the detector acceptance are also measured. The cross-section ratios benefit from significant cancellation of experimental uncertainties, resulting in $\sigma_{W^+}^{fid}/\sigma_{W^-}^{fid} = 1.295 \pm 0.003 (stat) \pm 0.010 (sys)$ and $\sigma_{W^{\pm}}^{fid}/\sigma_{Z}^{fid} = 10.31 \pm 0.04 (stat) \pm 0.20 (sys)$. Theoretical predictions, based on calculations accurate to next-to-next-to-leading order for quantum chromodynamics and next-to-leading order for electroweak processes and which employ different parton distribution function sets, are compared to these measurements

Search for resonances in the mass distribution of jet pairs with one or two jets identified as b-jets in proton–proton collisions at √s=13TeV with the ATLAS detector

Searches for high-mass resonances in the dijet invariant mass spectrum with one or two jets identi-fied as b-jets are performed using an integrated luminosity of 3.2fb−1of proton–proton collisions with a centre-of-mass energy of √s=13TeVrecorded by the ATLAS detector at the Large Hadron Collider. Noevidence of anomalous phenomena is observed in the data, which are used to exclude, at 95%credibility level, excited b∗quarks with masses from 1.1TeVto 2.1TeVand leptophobic Z bosons with masses from 1.1TeVto 1.5TeV. Contributions of a Gaussian signal shape with effective cross sections ranging from approximately 0.4 to 0.001pb are also excluded in the mass range 1.5–5.0TeV

Search for TeV-scale gravity signatures in high-mass final states with leptons and jets with the ATLAS detector at sqrt [ s ] = 13TeV

A search for physics beyond the Standard Model, in final states with at least one high transverse momentum charged lepton (electron or muon) and two additional high transverse momentum leptons or jets, is performed using 3.2 fb−1 of proton–proton collision data recorded by the ATLAS detector at the Large Hadron Collider in 2015 at √s = 13 TeV. The upper end of the distribution of the scalar sum of the transverse momenta of leptons and jets is sensitive to the production of high-mass objects. No excess of events beyond Standard Model predictions is observed. Exclusion limits are set for models of microscopic black holes with two to six extra dimensions

Charged-particle distributions in √s=13 TeV pp interactions measured with the ATLAS detector at the LHC

Charged-particle distributions are measured in proton–proton collisions at a centre-of-mass energy of 13 TeV, using a data sample of nearly 9 million events, corresponding to an integrated luminosity of 170 μb−1170 μb−1, recorded by the ATLAS detector during a special Large Hadron Collider fill. The charged-particle multiplicity, its dependence on transverse momentum and pseudorapidity and the dependence of the mean transverse momentum on the charged-particle multiplicity are presented. The measurements are performed with charged particles with transverse momentum greater than 500 MeV and absolute pseudorapidity less than 2.5, in events with at least one charged particle satisfying these kinematic requirements. Additional measurements in a reduced phase space with absolute pseudorapidity less than 0.8 are also presented, in order to compare with other experiments. The results are corrected for detector effects, presented as particle-level distributions and are compared to the predictions of various Monte Carlo event generators

Search for dark matter produced in association with a hadronically decaying vector boson in pp collisions at sqrt (s) = 13 TeV with the ATLAS detector

A search is presented for dark matter produced in association with a hadronically decaying W or Z boson using 3.2 fb−1 of pp collisions at View the MathML sources=13 TeV recorded by the ATLAS detector at the Large Hadron Collider. Events with a hadronic jet compatible with a W or Z boson and with large missing transverse momentum are analysed. The data are consistent with the Standard Model predictions and are interpreted in terms of both an effective field theory and a simplified model containing dark matter

Search for high-mass new phenomena in the dilepton final state using proton–proton collisions at View the MathML sources=13TeV with the ATLAS detector

A search is conducted for both resonant and non-resonant high-mass new phenomena in dielectron and dimuon final states. The search uses View the MathML source3.2fb−1 of proton–proton collision data, collected at View the MathML sources=13TeV by the ATLAS experiment at the LHC in 2015. The dilepton invariant mass is used as the discriminating variable. No significant deviation from the Standard Model prediction is observed; therefore limits are set on the signal model parameters of interest at 95% credibility level. Upper limits are set on the cross-section times branching ratio for resonances decaying to dileptons, and the limits are converted into lower limits on the resonance mass, ranging between 2.74 TeV and 3.36 TeV, depending on the model. Lower limits on the ℓℓqqℓℓqq contact interaction scale are set between 16.7 TeV and 25.2 TeV, also depending on the mode