Incommensurability and Multi-paradigm Grounding in Design Science Research: Implications for Creating Knowledge

International audienceThe problem identification-design-build-evaluate-theorize structure of design science research has been proposed as an approach to creating knowledge in information systems and in broader organizational and social domains. Although the approach has merit, the philosophical foundations of two specific components warrant attention. First, the grounding of design theory on potentially incommensurate kernel theories may produce incoherent design theory. In addition, design theory has no strong logical connection to kernel theories, and so cannot be used to test or validate the contributing kernel theories. Second, the philosophical grounding of evaluation may inadvertently shift from functionally based measures of utility and efficiency, to evaluation based on the pragmatic fulfillment of multidimensional human actions as people encounter information systems, resulting in evaluation errors. Although design and evaluation from a single paradigm is not desirable, sufficient, or representative of design science research, multi-paradigm grounding of design and evaluation must be realized and used consciously by the research community if the design science approach is to remain a legitimate approach to knowledge creation

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

Medical Ontology and Virtual Staff for a Health Network

International audienc