Effect of subcutaneous methylnaltrexone on patient-reported constipation symptoms

AbstractBackgroundMethylnaltrexone, a selective peripheral acting mu-opioid receptor antagonist, alleviates the constipating effects of opioids without affecting centrally mediated analgesia.ObjectivesTo assess the effect of subcutaneous (SC) methylnaltrexone injection on patient-reported constipation symptoms and pain scores.MethodsA total of 469 subjects on opioids for chronic non-malignant pain with opioid-induced constipation were randomized to methylnaltrexone SC with once daily (QD) or every other day (QOD) dosing or placebo for 4 weeks. Constipation symptoms and pain were assessed using the patient assessment of constipation–symptoms (PAC-SYM) questionnaire and a 11-point scale, respectively, at baseline, Day 14 and Day 28. Change from baseline in PAC-SYM and pain scores were compared between methylnaltrexone and placebo arms at Day 28 using analysis of covariance, with treatment group as factor and baseline score as covariate.ResultsA majority of patients were women (60%), average age was 49 years old, and back pain (60%) was the primary pain condition. At Day 28, the methylnaltrexone SC QD group showed a significant improvement over placebo for rectal symptoms (−0.56 vs. –0.30; P < 0.05), stool symptoms (−0.76 vs. –0.43; P < 0.001) and global scores (−0.62 vs. –0.37; P < 0.001). Improvement in stool symptoms (−0.69 vs.−0.43; P < 0.05) and the global scores (−0.52 vs. –0.37; P < 0.05) were significantly greater than placebo in the methylnaltrexone QOD group. Differences in change from baseline in abdominal symptoms and pain scores between the methylnaltrexone SC QD or QOD dosing arms and placebo were not significant.ConclusionThe results of our study indicate significant improvement in constipation symptoms with methylnaltrexone QD or QOD dosing compared to placebo without a significant effect on pain scores

A search for an unexpected asymmetry in the production of e+μ− and e−μ+ pairs in proton-proton collisions recorded by the ATLAS detector at root s = 13 TeV

This search, a type not previously performed at ATLAS, uses a comparison of the production cross sections for e(+)mu(-) and e(-)mu(+) pairs to constrain physics processes beyond the Standard Model. It uses 139 fb(-1) of proton-proton collision data recorded at root s = 13 TeV at the LHC. Targeting sources of new physics which prefer final states containing e(+)mu(-) and e(-)mu(+), the search contains two broad signal regions which are used to provide model-independent constraints on the ratio of cross sections at the 2% level. The search also has two special selections targeting supersymmetric models and leptoquark signatures. Observations using one of these selections are able to exclude, at 95% confidence level, singly produced smuons with masses up to 640 GeV in a model in which the only other light sparticle is a neutralino when the R-parity-violating coupling lambda(23)(1)' is close to unity. Observations using the other selection exclude scalar leptoquarks with masses below 1880 GeV when g(1R)(eu) = g(1R)(mu c) = 1, at 95% confidence level. The limit on the coupling reduces to g(1R)(eu) = g(1R)(mu c) = 0.46 for a mass of 1420 GeV

Measurement of the nuclear modification factor for muons from charm and bottom hadrons in Pb+Pb collisions at 5.02 TeV with the ATLAS detector

Heavy-flavour hadron production provides information about the transport properties and microscopic structure of the quark-gluon plasma created in ultra-relativistic heavy-ion collisions. A measurement of the muons from semileptonic decays of charm and bottom hadrons produced in Pb+Pb and pp collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV with the ATLAS detector at the Large Hadron Collider is presented. The Pb+Pb data were collected in 2015 and 2018 with sampled integrated luminosities of 208 mu b(-1) and 38 mu b(-1), respectively, and pp data with a sampled integrated luminosity of 1.17 pb(-1) were collected in 2017. Muons from heavy-flavour semileptonic decays are separated from the light-flavour hadronic background using the momentum imbalance between the inner detector and muon spectrometer measurements, and muons originating from charm and bottom decays are further separated via the muon track's transverse impact parameter. Differential yields in Pb+Pb collisions and differential cross sections in pp collisions for such muons are measured as a function of muon transverse momentum from 4 GeV to 30 GeV in the absolute pseudorapidity interval vertical bar eta vertical bar &lt; 2. Nuclear modification factors for charm and bottom muons are presented as a function of muon transverse momentum in intervals of Pb+Pb collision centrality. The bottom muon results are the most precise measurement of b quark nuclear modification at low transverse momentum where reconstruction of B hadrons is challenging. The measured nuclear modification factors quantify a significant suppression of the yields of muons from decays of charm and bottom hadrons, with stronger effects for muons from charm hadron decays

Genetic analysis of over one million people identifies 535 novel loci for blood pressure

High blood pressure is the foremost heritable global risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits to date (systolic, diastolic, pulse pressure) in over one million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also reveal shared loci influencing lifestyle exposures. Our findings offer the potential for a precision medicine strategy for future cardiovascular disease prevention

Search for events with a pair of displaced vertices from long-lived neutral particles decaying into hadronic jets in the ATLAS muon spectrometer in collisions at

A search for events with two displaced vertices from long-lived particle (LLP) pairs using data collected by the ATLAS detector at the LHC is presented. This analysis uses 139 fb(-1) of proton-proton collision data at root s=13 TeV recorded in 2015-2018. The search employs techniques for reconstructing vertices of LLPs decaying to jets in the muon spectrometer displaced between 3 and 14 m with respect to the primary interaction vertex. The observed numbers of events are consistent with the expected background and limits for several benchmark signals are determined. For the Higgs boson with a mass of 125 GeV, the paper reports the first exclusion limits for branching fractions into neutral long-lived particles below 0.1%, while branching fractions above 10% are excluded at 95% confidence level for LLP proper lifetimes ranging from 4 cm to 72.4 m. In addition, the paper present the first results for the decay of LLPs into (tt) over bar in the ATLAS muon spectrometer

Search for Higgs boson decays into a pair of pseudoscalar particles in the final state with the ATLAS detector in collisions at

This paper presents a search for decays of the Higgs boson with a mass of 125 GeV into a pair of new pseudoscalar particles, H -&gt; aa, where one a-boson decays into a b-quark pair and the other into a muon pair. The search uses 139 fb(-1) of proton-proton collision data at a center-of-mass energy root s = 13 TeV recorded between 2015 and 2018 by the ATLAS experiment at the LHC. A narrow dimuon resonance is searched for in the invariant mass spectrum between 16 GeV and 62 GeV. The largest excess of events above the Standard Model backgrounds is observed at a dimuon invariant mass of 52 GeV and corresponds to a local (global) significance of 3.3 sigma (1.7 sigma). Upper limits at 95% confidence level are placed on the branching ratio of the Higgs boson to the bb mu mu final state, beta(H -&gt; aa -&gt; bb mu mu), and are in the range 0.2-4.0 x 10(-4), depending on the signal mass hypothesis