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Background Garadacimab, a fully human IgG4 monoclonal antibody, inhibits the kallikrein-kinin pathway at a key initiator, activated coagulation factor XII (FXIIa), and may play a protective role in preventing the progression of COVID-19. This phase 2 study evaluated the efficacy and safety of garadacimab plus standard of care (SOC) versus placebo plus SOC in patients with severe COVID-19. Methods Patients hospitalised with COVID-19 were randomised (1:1) to a single intravenous dose of garadacimab (700 mg) plus SOC or placebo plus SOC. Co-primary endpoint was incidence of endotracheal intubation or death between randomisation and Day 28. All-cause mortality, safety and pharmacokinetic/pharmacodynamic parameters were assessed. Results No difference in incidence of tracheal intubation or death (p = 0.274) or all-cause mortality was observed (p = 0.382). Garadacimab was associated with a lower incidence of treatment-emergent adverse events (60.3% vs 67.8%) and fewer serious adverse events (34 vs 45 events) versus placebo. No garadacimab-related deaths or bleeding events were reported, including in the 45.9% (n = 28/61) of patients who received concomitant heparin. Prolonged activated partial thromboplastin time (aPTT), and increased coagulation factor XII (FXII) levels were observed with garadacimab versus placebo to Day 14, whilst FXIIa-mediated kallikrein activity (FXIIa-mKA) was suppressed to Day 28. Conclusion In patients with severe COVID-19, garadacimab did not confer a clinical benefit over placebo. Transient aPTT prolongation and suppressed FXIIa-mKA showed target engagement of garadacimab that was not associated with bleeding events even with concomitant anticoagulant use. The safety profile of garadacimab was consistent with previous studies in patients with hereditary angioedema. ClinicalTrials. gov Identifier NCT04409509. Date of registration: 28 May, 2020., Author(s): Alberto Papi [sup.1], Renee D. Stapleton [sup.2], Paul M. Shore [sup.3], Mihai Alexandru Bica [sup.4], Younan Chen [sup.5], Michael Larbig [sup.6], Tobias Welte [sup.7] Author Affiliations: (1) grid.8484.0, 0000 [...]

Purpose: This paper aims to demonstrate how science and engineering graduates can be recruited and trained to Masters level in precision engineering as an aid to reducing the skills shortage of mechanical engineers in UK industry. Design/methodology/approach: The paper describes a partnership between three UK academic institutions and industry, creating an Integrated Knowledge Centre (IKC) in Ultra Precision Structured Surfaces. Within this project sits a Knowledge Transfer activity that seeks to channel graduate scientists and engineers through an MSc in "Ultra Precision Technologies" into the UK engineering industry. The creation and implementation of this pipeline, its systems and its processes, is the subject of this paper and its case study. Findings: In order to retain competitive advantage, the UK precision engineering industry requires a regular supply of technically proficient and organizationally prepared graduates. This paper has explained the approach taken at Cranfield University to increase the size of the pool of postgraduate precision engineers. The approach involves the design of a multi-level system, which draws on increased connectivity between the University, UK engineering companies, and the student. Academic institutions need to exhibit the appropriate flexibility to meet the demands of industry and the aspirations of the student. Research limitations/implications: The paper describes only the early stages of implementation, and further work is necessary. Practical implications: The systems model and case studies provide a framework and detail that is of immediate benefit to manufacturing industries and higher education establishments. Originality/value: The originality of the approach lies in the level of integration between the sub-systems that comprise the Open system, within which students and skills are forged together in a programme to produce employable engineering postgraduates. (Contains 1 table and 5 figures.)

Throughout the world there has been concern that persons with disabilities are being perceived as "other" than us and that differences imparted by disability result in more dissimilarity than actually exists. A summary of this concept of "otherness" and disability in the United States, Eastern Europe, and India is presented.