Treatable traits in the European U-BIOPRED adult asthma cohorts

No abstract availabl

Initial results of secukinumab drug survival in patients with psoriasis: A multicentre daily practice cohort study

Interleukin 17-antagonist secukinumab demonstrated high efficacy for treatment of psoriasis in randomized controlled trials. However, performance in daily practice may differ from trials. Drug survival is a comprehensive outcome covering effectiveness and safety, suitable for analyses of daily practice. The aim of this study was to evaluate drug survival of secukinumab in a daily practice psoriasis cohort. Data were collected from 13 hospitals. Drug survival was analysed using Kaplan–Meier survival curves, split for reason of discontinuation. In total, 196 patients were included (83% biologic experienced). Overall, 12 and 18 months drug survival of secukinumab was 76% and 67%, respectively, and was mostly determined by ineffectiveness. There was a trend towards shorter drug survival in women and in biologic experienced patients. Thirteen percent of patients experienced at least one episode of fungal infection. This is one of the first studies of drug survival of secukinumab in patients with psoriasis treated in daily practice

Regulation of steroidogenesis in a primary pigmented nodular adrenocortical disease-associated adenoma leading to virilization and subclinical Cushing's syndrome

Context: Primary pigmented nodular adrenocortical disease (PPNAD) can lead to steroid hormone overproduction. Mutations in the cAMP protein kinase A regulatory subunit type 1A (PRKAR1A) are causative of PPNAD. Steroidogenesis in PPNAD can be modified through a local glucocorticoid feed-forward loop. Objective: Investigation of regulation of steroidogenesis in a case of PPNAD with virilization. Materials and methods : A 33-year-old woman presented with primary infertility due to hyperandrogenism. Elevated levels of testosterone and subclinical ACTH-independent Cushing's syndrome led to the discovery of an adrenal tumor, which was diagnosed as PPNAD. In vivo evaluation of aberrantly expressed hormone receptors showed no steroid response to known stimuli. Genetic analysis revealed a PRKAR1A protein-truncating Q28X mutation. After adrenalectomy, steroid levels normalized. Tumor cells were cultured and steroid

Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

A Pre-Landing Assessment of Regolith Properties at the InSight Landing Site

This article discusses relevant physical properties of the regolith at the Mars InSight landing site as understood prior to landing of the spacecraft. InSight will land in the northern lowland plains of Mars, close to the equator, where the regolith is estimated to be ≥3--5 m thick. These investigations of physical properties have relied on data collected from Mars orbital measurements, previously collected lander and rover data, results of studies of data and samples from Apollo lunar missions, laboratory measurements on regolith simulants, and theoretical studies. The investigations include changes in properties with depth and temperature. Mechanical properties investigated include density, grain-size distribution, cohesion, and angle of internal friction. Thermophysical properties include thermal inertia, surface emissivity and albedo, thermal conductivity and diffusivity, and specific heat. Regolith elastic properties not only include parameters that control seismic wave velocities in the immediate vicinity of the Insight lander but also coupling of the lander and other potential noise sources to the InSight broadband seismometer. The related properties include Poisson’s ratio, P- and S-wave velocities, Young’s modulus, and seismic attenuation. Finally, mass diffusivity was investigated to estimate gas movements in the regolith driven by atmospheric pressure changes. Physical properties presented here are all to some degree speculative. However, they form a basis for interpretation of the early data to be returned from the InSight mission.Additional co-authors: Nick Teanby and Sharon Keda

Measurement of the azimuthal anisotropy of Y(1S) and Y(2S) mesons in PbPb collisions at √S^{S}NN = 5.02 TeV

The second-order Fourier coefficients (υ$_{2}$) characterizing the azimuthal distributions of Υ(1S) and Υ(2S) mesons produced in PbPb collisions at $\sqrt{s_{NN}}$ = 5.02 TeV are studied. The Υmesons are reconstructed in their dimuon decay channel, as measured by the CMS detector. The collected data set corresponds to an integrated luminosity of 1.7 nb$^{-1}$. The scalar product method is used to extract the υ$_{2}$ coefficients of the azimuthal distributions. Results are reported for the rapidity range |y| < 2.4, in the transverse momentum interval 0 < p$_{T}$ < 50 GeV/c, and in three centrality ranges of 10–30%, 30–50% and 50–90%. In contrast to the J/ψ mesons, the measured υ$_{2}$ values for the Υ mesons are found to be consistent with zero

Measurement of prompt D0^{0} and D‾\overline{D}0^{0} meson azimuthal anisotropy and search for strong electric fields in PbPb collisions at root SNN\sqrt{S_{NN}} = 5.02 TeV

The strong Coulomb field created in ultrarelativistic heavy ion collisions is expected to produce a rapiditydependent difference (Av2) in the second Fourier coefficient of the azimuthal distribution (elliptic flow, v2) between D0 (uc) and D0 (uc) mesons. Motivated by the search for evidence of this field, the CMS detector at the LHC is used to perform the first measurement of Av2. The rapidity-averaged value is found to be (Av2) = 0.001 ? 0.001 (stat)? 0.003 (syst) in PbPb collisions at ?sNN = 5.02 TeV. In addition, the influence of the collision geometry is explored by measuring the D0 and D0mesons v2 and triangular flow coefficient (v3) as functions of rapidity, transverse momentum (pT), and event centrality (a measure of the overlap of the two Pb nuclei). A clear centrality dependence of prompt D0 meson v2 values is observed, while the v3 is largely independent of centrality. These trends are consistent with expectations of flow driven by the initial-state geometry. ? 2021 The Author. Published by Elsevier B.V. This is an open access article under the CC BY licens

Performance of reconstruction and identification of τ leptons decaying to hadrons and vτ in pp collisions at √s=13 TeV

The algorithm developed by the CMS Collaboration to reconstruct and identify τ leptons produced in proton-proton collisions at √s=7 and 8 TeV, via their decays to hadrons and a neutrino, has been significantly improved. The changes include a revised reconstruction of π⁰ candidates, and improvements in multivariate discriminants to separate τ leptons from jets and electrons. The algorithm is extended to reconstruct τ leptons in highly Lorentz-boosted pair production, and in the high-level trigger. The performance of the algorithm is studied using proton-proton collisions recorded during 2016 at √s=13 TeV, corresponding to an integrated luminosity of 35.9 fb¯¹. The performance is evaluated in terms of the efficiency for a genuine τ lepton to pass the identification criteria and of the probabilities for jets, electrons, and muons to be misidentified as τ leptons. The results are found to be very close to those expected from Monte Carlo simulation

Performance of the CMS Level-1 trigger in proton-proton collisions at √s = 13 TeV

At the start of Run 2 in 2015, the LHC delivered proton-proton collisions at a center-of-mass energy of 13\TeV. During Run 2 (years 2015–2018) the LHC eventually reached a luminosity of 2.1× 10$^{34}$ cm$^{-2}$s$^{-1}$, almost three times that reached during Run 1 (2009–2013) and a factor of two larger than the LHC design value, leading to events with up to a mean of about 50 simultaneous inelastic proton-proton collisions per bunch crossing (pileup). The CMS Level-1 trigger was upgraded prior to 2016 to improve the selection of physics events in the challenging conditions posed by the second run of the LHC. This paper describes the performance of the CMS Level-1 trigger upgrade during the data taking period of 2016–2018. The upgraded trigger implements pattern recognition and boosted decision tree regression techniques for muon reconstruction, includes pileup subtraction for jets and energy sums, and incorporates pileup-dependent isolation requirements for electrons and tau leptons. In addition, the new trigger calculates high-level quantities such as the invariant mass of pairs of reconstructed particles. The upgrade reduces the trigger rate from background processes and improves the trigger efficiency for a wide variety of physics signals

Observation of a new Xi(b) baryon

The first observation of a new b baryon via its strong decay into Xi(b)^- pi^+ (plus charge conjugates) is reported. The measurement uses a data sample of pp collisions at sqrt(s) = 7 TeV collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 5.3 inverse femtobarns. The known Xi(b)^- baryon is reconstructed via the decay chain Xi(b)^- to J/psi Xi^- to mu^+ mu^- Lambda^0 pi^-, with Lambda^0 to p pi^-. A peak is observed in the distribution of the difference between the mass of the Xi(b)^- pi^+ system and the sum of the masses of the Xi(b)^- and pi^+, with a significance exceeding five standard deviations. The mass difference of the peak is 14.84 +/- 0.74 (stat.) +/- 0.28 (syst.) MeV. The new state most likely corresponds to the J^P=3/2^+ companion of the Xi(b).Comment: Submitted to Physical Review Letter