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

The role of picture books in young children’s mathematics learning

In this chapter we address the role of picture books in kindergartners’ learning of mathematics. The chapter is based on various studies we carried out on this topic from different perspectives. All studies sought to provide insight into the power of picture books to contribute to the development of mathematical understanding by young children. We start the chapter with some background information about picture books as a didactical tool in mathematics education. Then, we discuss a framework of picture book characteristics that support young children’s learning of mathematics. In the next section, we give a short impression of children’s spontaneous mathematics-related utterances that occur during the reading of a picture book. This section is followed by a deeper look at the influence of the pictures in a picture book. Hereafter, the reading itself is the focus. Three book reading techniques are discussed and illustrated by classroom vignettes. Finally, based on an intervention program in which kindergartners were read a series of picture books, we report what we learned about the effectiveness of picture book reading on kindergartners’ performance in mathematics

High efficiency removal of dissolved As(III) using iron nanoparticle-embedded macroporous polymer composites

Novel nanocomposite materials where iron nanoparticles are embedded into the walls of a macroporous polymer were produced and their efficiency for the removal of As(III) from aqueous media was studied. Nanocomposite gels containing ?-Fe2O3 and Fe3O4 nanoparticles were prepared by cryopolymerisation resulting in a monolithic structure with large interconnected pores up to 100 ?m in diameter and possessing a high permeability (ca. 3 × 10?3 m s?1). The nanocomposite devices showed excellent capability for the removal of trace concentrations of As(III) from solution, with a total capacity of up to 3 mg As/g of nanoparticles. The leaching of iron was minimal and the device could operate in a pH range 3–9 without diminishing removal efficiency. The effect of competing ions such as SO42? and PO43? was negligible. The macroporous composites can be easily configured into a variety of shapes and structures and the polymer matrix can be selected from a variety of monomers, offering high potential as flexible metal cation remediation devices