ABSTRACT
Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2-4 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.
Subject(s)
COVID-19 , Critical Illness , Genome, Human , Host-Pathogen Interactions , Whole Genome Sequencing , ATP-Binding Cassette Transporters , COVID-19/genetics , COVID-19/mortality , COVID-19/pathology , COVID-19/virology , Cell Adhesion Molecules , Critical Care , Critical Illness/mortality , E-Selectin , Factor VIII , Fucosyltransferases , Genome, Human/genetics , Genome-Wide Association Study , Host-Pathogen Interactions/genetics , Humans , Interleukin-10 Receptor beta Subunit , Lectins, C-Type , Mucin-1 , Nerve Tissue Proteins , Phospholipid Transfer Proteins , Receptors, Cell Surface , Repressor Proteins , SARS-CoV-2/pathogenicity , Galactoside 2-alpha-L-fucosyltransferaseABSTRACT
All available data on asbestos consumption in Australia were collated in order to determine the most common asbestos-containing materials remaining in the built environment. The proportion of asbestos contained within each material and the types of products these materials are most commonly found in was also determined. The lifetime of these asbestos containing products was estimated in order to develop a model that projects stocks and flows of asbestos products in Australia through to the year 2100. The model is based on a Weibull distribution and was built in an excel spreadsheet to make it user-friendly and accessible. The nature of the products under consideration means both their asbestos content and lifetime parameters are highly variable, and so for each of these a high and low estimate is presented along with the estimate used in the model. The user is able to vary the parameters in the model as better data become available.
Subject(s)
Asbestos , Construction Materials/statistics & numerical data , Refuse Disposal/statistics & numerical data , Australia , Housing , Models, Theoretical , Refuse Disposal/methodsABSTRACT
The aim of this research was to predict the effect that the biodegradable municipal waste (BMW) diversion targets in the European Union landfill directive (99/31/EC) would have on landfill gas emissions. This is important for continued mitigation of these emissions. Work was undertaken in three stages using the GasSim model (v1.03) developed by the Environment Agency (England and Wales). The first stage considered the contribution to gas emissions made by each biodegradable component of the waste stream. The second stage considered how gas emissions from a landfill accepting biodegradable wastes with reduced biodegradable content would be affected. The third stage looked at the contribution to gas emissions from real samples of biologically pretreated BMW. For the first two stages, data on the waste components were available in the model. For the third stage samples were obtained from four different biological treatment facilities and the required parameters determined experimentally. The results of stage 1 indicated that in the first 15 years of the landfill the putrescible fraction makes the most significant contribution, after which paper/card becomes the most significant. The second stage found that biodegradability must be reduced by at least 60% to achieve a reduction in overall methane generation. The third stage found that emissions from samples of biologically pretreated BMW would result in a significant reduction in gas emissions over untreated waste, particularly in the early stage of the landfill lifetime; however, low level emissions would continue to occur for the long term.
Subject(s)
Gases/analysis , Methane/analysis , Models, Biological , Refuse Disposal , Waste Management , Air Pollutants/analysis , Biodegradation, Environmental , United Kingdom , Waste Products/analysisABSTRACT
Throughout the world, most municipal solid waste consists of biodegradable components. The most abundant biological component is cellulose, followed by hemicellulose and lignin. Recycling of these components is important for the carbon cycle. In an attempt to reduce the environmental impacts of biodegradable wastes, mechanical biological treatments (MBTs) are being used as a waste management process in many countries. MBT plants attempt to mechanically separate the biodegradable and nonbiodegradable components. The nonbiodegradable components are then sent for reprocessing or landfilled, whereas the biodegradable components are reduced in biological content through composting or anaerobic digestion, leaving a compost-like output (CLO). The further use of these partially degraded residues is uncertain, and in many cases it is likely that they will be landfilled. The implications of this for the future of landfill management are causing some concern because there is little evidence that the long-term emissions tail will be reduced. In this study, the CLOs from four different biological treatment processes were characterized for physical contamination through visual inspection and for biological content using a sequential digestion analysis. The results indicate that the composition of the incoming waste, dependent on the way the waste was collected/segregated, was the factor that influenced biological content most, with length of treatment process the second most important.
Subject(s)
Soil/analysis , Waste Management , Lignin/analysis , Polysaccharides/analysis , Water/analysisABSTRACT
We report on the evaluation of a novel grass hybrid that provides efficient forage production and could help mitigate flooding. Perennial ryegrass (Lolium perenne) is the grass species of choice for most farmers, but lacks resilience against extremes of climate. We hybridised L. perenne onto a closely related and more stress-resistant grass species, meadow fescue Festuca pratensis. We demonstrate that the L. perenne × F. pratensis cultivar can reduce runoff during the events by 51% compared to a leading UK nationally recommended L. perenne cultivar and by 43% compared to F. pratensis over a two year field experiment. We present evidence that the reduced runoff from this Festulolium cultivar was due to intense initial root growth followed by rapid senescence, especially at depth. Hybrid grasses of this type show potential for reducing the likelihood of flooding, whilst providing food production under conditions of changing climate.