Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine immunogenicity varies between individuals, and immune responses correlate with vaccine efficacy. Using data from 1,076 participants enrolled in ChAdOx1 nCov-19 vaccine efficacy trials in the United Kingdom, we found that inter-individual variation in normalized antibody responses against SARS-CoV-2 spike and its receptor-binding domain (RBD) at 28 days after first vaccination shows genome-wide significant association with major histocompatibility complex (MHC) class II alleles. The most statistically significant association with higher levels of anti-RBD antibody was HLA-DQB1*06 (P = 3.2 × 10−9), which we replicated in 1,677 additional vaccinees. Individuals carrying HLA-DQB1*06 alleles were less likely to experience PCR-confirmed breakthrough infection during the ancestral SARS-CoV-2 virus and subsequent Alpha variant waves compared to non-carriers (hazard ratio = 0.63, 0.42–0.93, P = 0.02). We identified a distinct spike-derived peptide that is predicted to bind differentially to HLA-DQB1*06 compared to other similar alleles, and we found evidence of increased spike-specific memory B cell responses in HLA-DQB1*06 carriers at 84 days after first vaccination. Our results demonstrate association of HLA type with Coronavirus Disease 2019 (COVID-19) vaccine antibody response and risk of breakthrough infection, with implications for future vaccine design and implementation

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Search for long-lived neutral particles in pp collisions at s√=13 TeV that decay into displaced hadronic jets in the ATLAS calorimeter

This paper describes a search for pairs of neutral, long-lived particles decaying in the ATLAS calorimeter. Long-lived particles occur in many extensions to the Standard Model and may elude searches for new promptly decaying particles. The analysis considers neutral, long-lived scalars with masses between 5 and 400 GeV, produced from decays of heavy bosons with masses between 125 and 1000 GeV, where the long-lived scalars decay into Standard Model fermions. The analysis uses either 10.8 fb−1 or 33.0 fb−1 of data (depending on the trigger) recorded in 2016 at the LHC with the ATLAS detector in proton–proton collisions at a centre-of-mass energy of 13 TeV. No significant excess is observed, and limits are reported on the production cross section times branching ratio as a function of the proper decay length of the long-lived particles

Search for single vector-like B quark production and decay via B → bH(b¯b) in pp collisions at √s = 13 TeV with the ATLAS detector

A search is presented for single production of a vector-like B quark decaying into a Standard Model b-quark and a Standard Model Higgs boson, which decays into a b¯b pair. The search is carried out in 139 fb−1 of √s = 13 TeV proton-proton collision data collected by the ATLAS detector at the LHC between 2015 and 2018. No significant deviation from the Standard Model background prediction is observed, and mass-dependent exclusion limits at the 95% confidence level are set on the resonance production cross-section in several theoretical scenarios determined by the couplings cW, cZ and cH between the B quark and the Standard Model W, Z and Higgs bosons, respectively. For a vector-like B occurring as an isospin singlet, the search excludes values of cW greater than 0.45 for a B resonance mass (mB) between 1.0 and 1.2 TeV. For 1.2 TeV < mB < 2.0 TeV, cW values larger than 0.50–0.65 are excluded. If the B occurs as part of a (B, Y) doublet, the smallest excluded cZ coupling values range between 0.3 and 0.5 across the investigated resonance mass range 1.0 TeV < mB < 2.0 TeV

Measurement of the top-quark mass using a leptonic invariant mass in pp collisions at s√ = 13 TeV with the ATLAS detector

A measurement of the top-quark mass (mt) in the tt¯ → lepton + jets channel is presented, with an experimental technique which exploits semileptonic decays of b-hadrons produced in the top-quark decay chain. The distribution of the invariant mass mℓμ of the lepton, ℓ (with ℓ = e, μ), from the W-boson decay and the muon, μ, originating from the b-hadron decay is reconstructed, and a binned-template profile likelihood fit is performed to extract mt. The measurement is based on data corresponding to an integrated luminosity of 36.1 fb−1 of s√ = 13 TeV pp collisions provided by the Large Hadron Collider and recorded by the ATLAS detector. The measured value of the top-quark mass is mt = 174.41 ± 0.39 (stat.) ± 0.66 (syst.) ± 0.25 (recoil) GeV, where the third uncertainty arises from changing the PYTHIA8 parton shower gluon-recoil scheme, used in top-quark decays, to a recently developed setup

Timing of first antenatal care attendance and associated factors among pregnant women in an obstetric health facility in eThekwini district, KwaZulu-Natal Province, South Africa

The purpose of the study was to determine timing of first antenatal care attendance and associated factors among pregnant women in an obstetric health facility in eThekwini district, KwaZulu-Natal Province, South Africa. A Midwives’ Obstetric Unit forms a section of the Cato Manor Primary Health Care clinic that is responsible for providing maternal and childcare services, which include antenatal, intrapartum and postnatal care to women from socioeconomically disadvantaged community living in informal settlements. In South Africa, despite the widespread availability of free antenatal care (ANC) services, most women in underprivilleged settings present late for their first antenatal care and fail to return for ANC follow-up, potentially leading to perinatal and maternal complications. Using a crosssectional survey design, data was collected from 329 pregnant women attending ANC in a Midwives’ obstetric unit at Cato Manor Primary Health Care Clinic in eThekwini District, KwaZulu-Natal. Late booking was a challenge in the primary health care clinic. There was no evidence of association between late ANC booking and most demographic variables except one (planning of pregnancy). This highlights the importance of assisting all women to have their pregnancies planned. The number of pregnant women that initiate ANC before 12 weeks (40-50%) and the few women that still initiate ANC after 24 weeks (less than 10%) suggest an improvement in the trends of timing of ANC bookings for the rural women. There is a need to intensify community awareness programmes and social mobilisation in order to educate pregnant women about the importance of early booking at the ANC (10-12 visits) as stipulated in the guidelines of the Basic Antenatal Care approach (BANC).Keywords: Antenatal care, timing of first attendence, accessibility, primary health car

Semantic Representation Analysis: A General Framework for Individualized, Domain-Specific and Context-Sensitive Semantic Processing

Language agnostic methods for semantic extraction, encoding, and applications are an increasingly active research area in computational linguistics. This paper introduces an analytic framework for vector-based semantic representation called semantic representation analysis (SRA). The rationale for this framework is considered, as well as some successes and future challenges that must be addressed. A cloud-based implementation of SRA as a domain-specific semantic processing portal has been developed. Applications of SRA in three different areas are discussed: analysis of online text streams, analysis of the impression formation over time, and a virtual learning environment called V-CAEST that is enhanced by a conversation-based intelligent tutoring system. These use-cases show the flexibility of this approach across domains, applications, and languages. © 2014 Springer International Publishing Switzerland

Scaling functions for classical to quantum crossover in the transverse Ising model via an effective Wilsonian renormalization group approach in 4-\epsilon dimensions;

The classical to quantum crossover, which occurs in d-dimensional transverse field Ising model-like systems decreasing the temperature to zero in the influence domain of the quantum critical point (QCP), is described by employing an effective Wilsonian renormalization group approach in 4 - ε dimensions. The basic ingredient of the treatment is the static action arising from a preliminary one-loop averaging over non-zero frequency modes, which enter the original quantum one. The crossover scaling functions for susceptibility and related thermodynamic quantities are obtained to first order in ε as explicit functions of the temperature and the applied magnetic field. In our static framework, which can be easily extended to other quantum systems exhibiting a critical line which terminates in a QCP, the suitable procedure for observing this type of crossover through genuine thermodynamic measurements is clarified consistently with available experiments. Remarkably, our basic idea and results may be usefully employed to explore also the dimensional crossover which takes place in classical Ising-like systems with slab or film geometry and, possibly, in other finite-size classical systems