The use of β2-agonist therapy before hospital attendance for severe asthma exacerbations: a post-hoc analysis

Background: Patterns of inhaled β2-agonist therapy use during severe asthma exacerbations before hospital attendance are poorly understood. Aims: To assess β2-agonist use prior to hospital attendance. Methods: We undertook an exploratory post hoc analysis of data from a 6-month clinical trial of 303 patients randomised to combination budesonide/formoterol inhaler according to a Single combination inhaler as Maintenance And Reliever Therapy regimen (‘SMART’) or fixed-dose budesonide/formoterol with salbutamol as reliever (‘Standard’). Patterns of β2-agonist use for 14 days before hospital attendance with a severe asthma exacerbation were determined by electronic monitoring of inhaler use. Results: There were 22 hospital attendances in 16 patients during the study. Seven and nine hospital attendances were eligible for analysis in the SMART and Standard groups, respectively. In both regimens, β2-agonist use increased before hospital attendance, with a median (range) maximum daily number of actuations of 14 (9 to 63) budesonide/formoterol in SMART and 46 (6 to 95) salbutamol in Standard with 4 (0 to 10) budesonide/formoterol actuations on the day of maximal salbutamol use. There was delay in obtaining medical review despite high β2-agonist use, in 9/16 patients. Different patterns of use were observed, including repeated days of no inhaled corticosteroid despite marked salbutamol use, which occurred in 3/9 patients in the Standard group. Conclusions: Delay in obtaining medical review in association with high β2-agonist use is common in patients before hospital presentation with severe exacerbations of asthma. The SMART regimen reduced nonadherence with inhaled corticosteroid therapy during severe exacerbations

Precision measurement of CPCP violation in Bs0→J/ψK+K−B_s^0 \to J/\psi K^+K^- decays

The time-dependent $CP$ asymmetry in $B_s^0 \to J/\psi K^+K^-$ decays is measured using $pp$ collision data, corresponding to an integrated luminosity of $3.0$fb$^{-1}$, collected with the LHCb detector at centre-of-mass energies of $7$ and $8$TeV. In a sample of 96 000 $B_s^0 \to J/\psi K^+K^-$ decays, the $CP$-violating phase $\phi_s$ is measured, as well as the decay widths $\Gamma_{L}$ and $\Gamma_{H}$ of the light and heavy mass eigenstates of the $B_s^0-\bar{B}_s^0$ system. The values obtained are $\phi_s = -0.058 \pm 0.049 \pm 0.006$ rad, $\Gamma_s \equiv (\Gamma_{L}+\Gamma_{H})/2 = 0.6603 \pm 0.0027 \pm 0.0015$ps$^{-1}$, and$\Delta\Gamma_s \equiv \Gamma_{L} - \Gamma_{H} = 0.0805 \pm 0.0091 \pm 0.0032$ps$^{-1}$, where the first uncertainty is statistical and the second systematic. These are the most precise single measurements of those quantities to date. A combined analysis with $B_s^{0} \to J/\psi \pi^+\pi^-$ decays gives $\phi_s = -0.010 \pm 0.039$rad. All measurements are in agreement with the Standard Model predictions. For the first time the phase $\phi_s$ is measured independently for each polarisation state of the $K^+K^-$ system and shows no evidence for polarisation dependence.Comment: 6 figure

Study of J/ψ production and cold nuclear matter effects in pPb collisions at sNN \sqrt{{{s_{NN }}}} = 5 TeV

The production of J/psi mesons with rapidity 1.5 < y < 4.0 or 5.0 < y < 2.5 and transverse momentum PT < 14 GeV/e is studied with the LHCb detector in proton-lead collisions at a nucleon-nucleon centre-of-mass energy, root(NN)-N-S = 5 TeV. The J/psi mesons are reconstructed using the dimuon decay mode. The analysis is based on a data sample corresponding to an integrated luminosity of about 1.6 nb-1. For the first time the nuclear modification factor and forward-backward production ratio are determined separately for prompt J/psi mesons and J/psi from b-hadron decays. Clear suppression of prompt J/psi production with respect to proton-proton collisions at large rapidity is observed, while the production of J/psi from b-hadron decays is less suppressed. These results show good agreement with available theoretical predictions. The measurement shows that cold nuclear matter effects are important for interpretations of the related quark-gluon plasma signatures in heavy-ion collisions

Genetic predisposition to increased blood cholesterol and triglyceride lipid levels and risk of Alzheimer Disease: a Mendelian Randomization Analysis

Background Although altered lipid metabolism has been extensively implicated in the pathogenesis of Alzheimer disease (AD) through cell biological, epidemiological, and genetic studies, the molecular mechanisms linking cholesterol and AD pathology are still not well understood and contradictory results have been reported. We have used a Mendelian randomization approach to dissect the causal nature of the association between circulating lipid levels and late onset AD (LOAD) and test the hypothesis that genetically raised lipid levels increase the risk of LOAD. Methods and Findings We included 3,914 patients with LOAD, 1,675 older individuals without LOAD, and 4,989 individuals from the general population from six genome wide studies drawn from a white population (total n = 10,578). We constructed weighted genotype risk scores (GRSs) for four blood lipid phenotypes (high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], triglycerides, and total cholesterol) using well-established SNPs in 157 loci for blood lipids reported by Willer and colleagues (2013). Both full GRSs using all SNPs associated with each trait at p<5×10−8 and trait specific scores using SNPs associated exclusively with each trait at p<5×10−8 were developed. We used logistic regression to investigate whether the GRSs were associated with LOAD in each study and results were combined together by meta-analysis. We found no association between any of the full GRSs and LOAD (meta-analysis results: odds ratio [OR] = 1.005, 95% CI 0.82–1.24, p = 0.962 per 1 unit increase in HDL-c; OR = 0.901, 95% CI 0.65–1.25, p = 0.530 per 1 unit increase in LDL-c; OR = 1.104, 95% CI 0.89–1.37, p = 0.362 per 1 unit increase in triglycerides; and OR = 0.954, 95% CI 0.76–1.21, p = 0.688 per 1 unit increase in total cholesterol). Results for the trait specific scores were similar; however, the trait specific scores explained much smaller phenotypic variance. Conclusions Genetic predisposition to increased blood cholesterol and triglyceride lipid levels is not associated with elevated LOAD risk. The observed epidemiological associations between abnormal lipid levels and LOAD risk could therefore be attributed to the result of biological pleiotropy or could be secondary to LOAD. Limitations of this study include the small proportion of lipid variance explained by the GRS, biases in case-control ascertainment, and the limitations implicit to Mendelian randomization studies. Future studies should focus on larger LOAD datasets with longitudinal sampled peripheral lipid measures and other markers of lipid metabolism, which have been shown to be altered in LOAD

Measurement of neutrino and antineutrino oscillations by the T2K experiment including a new additional sample of νe interactions at the far detector

The T2K experiment reports an updated analysis of neutrino and antineutrino oscillations in appearance and disappearance channels. A sample of electron neutrino candidates at Super-Kamiokande in which a pion decay has been tagged is added to the four single-ring samples used in previous T2K oscillation analyses. Through combined analyses of these five samples, simultaneous measurements of four oscillation parameters, | Δ m 2 32 | , sin 2 θ 23 , sin 2 θ 13 , and δ CP and of the mass ordering are made. A set of studies of simulated data indicates that the sensitivity to the oscillation parameters is not limited by neutrino interaction model uncertainty. Multiple oscillation analyses are performed, and frequentist and Bayesian intervals are presented for combinations of the oscillation parameters with and without the inclusion of reactor constraints on sin 2 θ 13 . When combined with reactor measurements, the hypothesis of C P conservation ( δ CP = 0 or π ) is excluded at 90% confidence level. The 90% confidence region for δ CP is [ − 2.95 , − 0.44 ] ( [ − 1.47 , − 1.27 ] ) for normal (inverted) ordering. The central values and 68% confidence intervals for the other oscillation parameters for normal (inverted) ordering are Δ m 2 32 = 2.54 ± 0.08 ( 2.51 ± 0.08 ) × 10 − 3     eV 2 / c 4 and sin 2 θ 23 = 0.5 5 + 0.05 − 0.09 ( 0.5 5 + 0.05 − 0.08 ), compatible with maximal mixing. In the Bayesian analysis, the data weakly prefer normal ordering (Bayes factor 3.7) and the upper octant for sin 2 θ 23 (Bayes factor 2.4)

Updated T2K measurements of muon neutrino and antineutrino disappearance using 1.5 × 10^21 protons on target

We report measurements by the T2K experiment of the parameters θ23 and Δm322 governing the disappearance of muon neutrinos and antineutrinos in the three-flavor neutrino oscillation model. Utilizing the ability of the experiment to run with either a mainly neutrino or a mainly antineutrino beam, the parameters are measured separately for neutrinos and antineutrinos. Using 7.482×1020 POT in neutrino running mode and 7.471×1020 POT in antineutrino mode, T2K obtained sin2(θ23)=0.51-0.07+0.08 and Δm322=2.53-0.13+0.15×10-3 eV2/c4 for neutrinos, and sin2(θ-23)=0.42-0.07+0.25 and Δm-232=2.55-0.27+0.33×10-3 eV2/c4 for antineutrinos (assuming normal mass ordering). No significant differences between the values of the parameters describing the disappearance of muon neutrinos and antineutrinos were observed

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

First measurement of time-dependent CP violation in B0s→K+K− decays

Direct and mixing-induced CP-violating asymmetries in B0s→K+K− decays are measured for the first time using a data sample of pp collisions, corresponding to an integrated luminosity of 1.0 fb−1, collected with the LHCb detector at a centre-of-mass energy of 7 TeV. The results are C KK  = 0.14 ± 0.11 ± 0.03 and S KK  = 0.30 ± 0.12 ± 0.04, where the first uncertainties are statistical and the second systematic. The corresponding quantities are also determined for B 0 → π + π − decays to be C ππ  = −0.38 ± 0.15 ± 0.02 and S ππ  = −0.71 ± 0.13 ± 0.02, in good agreement with existing measurements

Observation of J/ψφJ/ψφ structures consistent with exotic states from amplitude analysis of B+→J/ψφK+B^+\to J/ψφK^+ decays

The first full amplitude analysis of $B^+\to J/\psi \phi K^+$ with $J/\psi\to\mu^+\mu^-$, $\phi\to K^+K^-$ decays is performed with a data sample of 3 fb$^{-1}$ of $pp$ collision data collected at $\sqrt{s}=7$ and $8$ TeV with the LHCb detector. The data cannot be described by a model that contains only excited kaon states decaying into $\phi K^+$, and four $J/\psi\phi$ structures are observed, each with significance over $5$ standard deviations. The quantum numbers of these structures are determined with significance of at least $4$ standard deviations. The lightest is best described as a $D_s^{\pm}D_s^{*\mp}$ cusp, but a resonant interpretation is also possible with mass consistent with, but width much larger than, previous measurements of the claimed $X(4140)$ state

Measurement of νˉμ\barν_μ and νμν_μ charged current inclusive cross sections and their ratio with the T2K off-axis near detector

We report a measurement of cross section $\sigma(\nu_{\mu}+{\rm nucleus}\rightarrow\mu^{-}+X)$ and the first measurements of the cross section $\sigma(\bar{\nu}_{\mu}+{\rm nucleus}\rightarrow\mu^{+}+X)$ and their ratio $R(\frac{\sigma(\bar \nu)}{\sigma(\nu)})$ at (anti-)neutrino energies below 1.5 GeV. We determine the single momentum bin cross section measurements, averaged over the T2K $\bar{\nu}/\nu$-flux, for the detector target material (mainly Carbon, Oxygen, Hydrogen and Copper) with phase space restricted laboratory frame kinematics of $\theta_{\mu}$500 MeV/c. The results are $\sigma(\bar{\nu})=\left( 0.900\pm0.029{\rm (stat.)}\pm0.088{\rm (syst.)}\right)\times10^{-39}$ and $\sigma(\nu)=\left( 2.41\ \pm0.022{\rm{(stat.)}}\pm0.231{\rm (syst.)}\ \right)\times10^{-39}$ in units of cm$^{2}$/nucleon and $R\left(\frac{\sigma(\bar{\nu})}{\sigma(\nu)}\right)= 0.373\pm0.012{\rm (stat.)}\pm0.015{\rm (syst.)}$