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

Multi-Indicator harvest strategies for Data-Limited fisheries: A practitioner guide to learning and design

As the world population grows, fisheries practitioners will be under increased pressure to address global challenges in data-limited fisheries management. With a focus on addressing localized and case-specific management needs, we provide a practical guide to the design and development of multi-indicator frameworks for fishery management. In a data-limited context, indicators are observations or estimates of the state of the fishery resource that are typically proxies for variables of interest, rather than quantities such as stock biomass estimated from data-rich stock assessments. Indicator frameworks structure the integration and interpretation of indicators to guide tactical fishery decision-making, often when the application of more formal analytical assessments is not feasible, yet where indicators in combination provide insight into stock status. With a focus on multi-indicator frameworks, we describe a pragmatic approach for their development via a set of organizational steps, considering a wide spectrum of types and severity of information limitations. We highlight where multi-indicator frameworks can be insightful and informative in relation to single indicator approaches but also point to potential pitfalls, with emphasis on critical evaluation and detection of performance flaws during the design phase using methods such as management strategy evaluation

Pollution abatement with limited enforcement power and citizen suits

Federal environmental laws in the U.S. can be enforced by government agencies or by private parties through citizen suits against polluters. Here, I extend the standard enforcement model to examine the role played by citizen suits. The main results from the paper suggest that in a model with limited enforcement power and citizen suits the regulator fully exercises his enforcement power when the expected penalty from a citizen suit is low, but increases his reliance on citizen suits as the expected penalty rises. Whether an enforcement regime that allows private enforcement is efficient depends not only on the relative costs of private and agency enforcement, but also on the changes in inspection costs that may be caused by private enforcement and the expected penalty from losing a citizen suit. These results suggest that in practice private enforcement may lower social costs as long as relatively inexpensive agency enforcement options, such as administrative proceedings, do not preclude citizen suits. Copyright Springer Science+Business Media, LLC 2007Pollution control, Environmental regulation, Compliance, Self-reporting, Enforcement, Citizen suits, D62, L51, K32, K42, Q25,

On the Use of Targeting to Reduce Moral Hazard in Agri-environmental Schemes

This paper applies the economic theory of targeting an agent's policy compliance to deal with asymmetric information in agri-environmental policies. The paper has had a major policy impact, with the author commissioned to write and present an associated paper on asymmetric information in agri-environmental policies to the OECD in 2005

A decomposition of trends in U.S. consumer expenditures on communications and travel: 1984–2002

Consumer expenditures, Structural change, Taste changes, Technological change, Trend analysis,