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

The institutionalisation of political risk assessment (IPRA) in Jordanian international firms

This paper investigates the determinants of the institutionalisation of political risk assessment (IPRA) within publicly traded international firms in Jordan. The aim is to contribute to the development of IPRA theory by identifying indicators of institutionalisation; by describing and explaining their determinants; and by investigating their relative importance. The paper also represents one of the first studies of political risk assessment of firms in a Middle East context. The study focuses on firm-specific characteristics and extends previous research by investigating firms’ size and degree of internationalisation. A survey strategy was adopted and self-administered questionnaires were distributed to the entire target population of Jordanian international firms. 44 usable responses were obtained (54.9%). Non-parametric statistics were used to test the research hypotheses. The main findings are that the level of institutionalisation of political risk assessment (PRA) within firms is significantly and positively correlated with a firm's total assets, international revenue and number of operating countries. Of the three significant determinants of institutionalisation, the number of operating countries is found to be the most important. The more countries in which a firm operates, the more likely it is to face significant risks, and so to institutionalise political risk assessment

Managerial perceptions of political risk in international projects

This paper examines the vulnerability of international projects to political risks. A brief review of the literature on general risks – natural, financial, cultural and political – is undertaken and then a more detailed review of the literature on political risk is presented. It was found that relatively few studies of political risk, particularly in the context of international projects, have been carried out. More particularly the focus has been almost exclusively on developed, rather than developing, countries. Questionnaires were distributed therefore to the entire target population of Jordanian international projects. The findings suggest that the political risk associated with international projects poses a threat to the majority of respondents and that the vulnerability to political risk is related to a firm’s degree of internationalisation. International projects are more concerned about host-society and interstate related risks than host-government related risks

The use of political risk assessment techniques in Jordanian international firms

The aim of this research was to describe and explain the use of techniques of political risk assessment (PRA) in Jordanian international firms. The research identified the extensive use of qualitative PRA techniques due to their flexibility, simplicity and low cost. Quantitative techniques, on the other hand, were used by only a minority of respondents. In any event, Jordanian international firms believe that official data is subject to censorship and is therefore not reliable. This undermines the efficiency of using highly sophisticated quantitative techniques

Effect of spacing of reinforcement on the behaviour of partially grouted masonry shear walls

Partially Grouted Reinforced Masonry (PGRM) shear walls perform well in places where the cyclonic wind pressure dominates the design. Their out-of-plane flexural performance is better understood than their inplane shear behaviour; in particular, it is not clear whether the PGRM shear walls act as unreinforced masonry (URM) walls embedded with discrete reinforced grouted cores or as integral systems of reinforced masonry (RM) with wider spacing of reinforcement. With a view to understanding the inplane response of PGRM shear walls, ten full scale single leaf, clay block walls were constructed and tested under monotonic and cyclic inplane loading cases. It has been shown that where the spacing of the vertical reinforcement is less than 2000mm, the walls behave as an integral system of RM; for spacing greater than 2000mm, the walls behave similar to URM with no significant benefit from the reinforced cores based on the displacement ductility and stiffness degradation factors derived from the complete lateral load – lateral displacement curves