Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r =-0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r =-0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation

Large range sizes link fast life histories with high species richness across wet tropical tree floras

Understanding how the traits of lineages are related to diversification is key for elucidating the origin of variation in species richness. Here, we test whether traits are related to species richness among lineages of trees from all major biogeographical settings of the lowland wet tropics. We explore whether variation in mortality rate, breeding system and maximum diameter are related to species richness, either directly or via associations with range size, among 463 genera that contain wet tropical forest trees. For Amazonian genera, we also explore whether traits are related to species richness via variation among genera in mean species-level range size. Lineages with higher mortality rates—faster life-history strategies—have larger ranges in all biogeographic settings and have higher mean species-level range sizes in Amazonia. These lineages also have smaller maximum diameters and, in the Americas, contain dioecious species. In turn, lineages with greater overall range size have higher species richness. Our results show that fast life-history strategies influence species richness in all biogeographic settings because lineages with these ecological strategies have greater range sizes. These links suggest that dispersal has been a key process in the evolution of the tropical forest flora

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

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Precision measurement of the B0 meson lifetime using B0 → J/ψ K∗0 decays with the ATLAS detector

Abstract A measurement of the $$B^{0}$$ B 0 meson lifetime using $$B^{0} \rightarrow J/\psi K^{*0}$$ B 0 → J / ψ K ∗ 0 decays in data from 13  $$\text {TeV}$$ TeV proton–proton collisions with an integrated luminosity of $$140~\mathrm {fb^{-1}}$$ 140 fb - 1 recorded by the ATLAS detector at the LHC is presented. The measured effective lifetime is $$\tau = 1.5053\pm 0.0012~\mathrm {(stat.)} \pm 0.0035~\mathrm {(syst.)~ps}.$$ τ = 1.5053 ± 0.0012 ( stat . ) ± 0.0035 ( syst . ) ps . The average decay width extracted from the effective lifetime, using parameters from external sources, is $$\begin{aligned} \Gamma _d = 0.6639\pm 0.0005~\mathrm {(stat.)} \pm 0.0016~\mathrm {(syst.)}\\ \pm 0.0038~\text {(ext.)} \text {~ps}^{-1}, \end{aligned}$$ Γ d = 0.6639 ± 0.0005 ( stat . ) ± 0.0016 ( syst . ) ± 0.0038 (ext.) ps - 1 , where the uncertainties are statistical, systematic and from external sources. The earlier ATLAS measurement of $$\Gamma _s$$ Γ s in the $$B^{0}_{s} \rightarrow J/\psi \phi$$ B s 0 → J / ψ ϕ decay was used to derive a value for the ratio of the average decay widths $$\Gamma _d$$ Γ d and $$\Gamma _s$$ Γ s for $$B^{0}$$ B 0 and $$B^{0}_{s}$$ B s 0 mesons respectively, of $$\frac{\Gamma _d }{\Gamma _s } = 0.9905\pm 0.0022~\text {(stat.)} \pm 0.0036~\text {(syst.)} \pm 0.0057~\text {(ext.)}.$$ Γ d Γ s = 0.9905 ± 0.0022 (stat.) ± 0.0036 (syst.) ± 0.0057 (ext.) . The measured lifetime, average decay width and decay width ratio are in agreement with theoretical predictions and with measurements by other experiments. This measurement provides the most precise result of the effective lifetime of the $$B^{0}$$ B 0 meson to date. </jats:p

Search for charged Higgs bosons produced in top-quark decays or in association with top quarks and decaying via H±→τ±ντ in 13 TeV pp collisions with the ATLAS detector

Charged Higgs bosons produced either in top-quark decays or in association with a top quark, subsequently decaying via H±→τ±ντ, are searched for in 140  fb−1 of proton-proton collision data at s=13  TeV recorded with the ATLAS detector. Depending on whether the top quark is produced together with the H± decays hadronically or semileptonically, the search targets τ+jets or τ+lepton final states, in both cases with a τ-lepton decaying into a neutrino and hadrons. No significant excess over the Standard Model background expectation is observed. For the mass range of 80≤mH±≤3000  GeV, upper limits at 95% confidence level are set on the production cross section of the charged Higgs boson times the branching fraction B(H±→τ±ντ) in the range 4.5 pb–0.4 fb. In the mass range 80–160 GeV, assuming the Standard Model cross section for tt¯ production, this corresponds to upper limits between 0.27% and 0.02% on B(t→bH±)×B(H±→τ±ντ).</jats:p