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

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Curricula comparison of electrical and electronics engineering technology and similarly named associate degree programmes

The associate degree programmes discussed in this article are offered in the Kingdom of Saudi Arabia. In the first part of the article is presented a curriculum comparison study of the historically Accreditation Board for Engineering and Technology (ABET) accredited Electrical and Electronics Engineering Technology (EEET) associate degree programme at Applied College, Hafr Al Batin, the currently ABET-accredited Instrumentation and Control Engineering Technology (ICET) associate degree programme at Jubail Industrial College (JIC), and the currently ABET-accredited Electronics and Communication Technology (ECT) and Instrumentation and Control Technology (ICT) associate degree programmes at Yanbu Industrial College (YIC). The currently ABET-accredited ICET programme at JIC, and ECT and ICT programmes at YIC have served as a regional benchmark for the historically ABET-accredited EEET programme at Applied College. In the second part of the article, the indirect assessment process of ABET student outcomes and evaluation of ABET programme criteria of the EEET programme at Applied College is described

On the ABET accreditation of academic programs and rankings of universities in Saudi Arabia

In this article, the status of higher education in the Kingdom of Saudi Arabia is discussed in terms of ABET accreditation of academic programs and regional and world rankings of universities. The article first presents all currently ABET-accredited academic programs at various degree levels in Saudi higher educational institutions in 2021. The article then compares the world rankings of Saudi universities from 2015 to 2021, according to the four most widely observed world university ranking systems. In addition, the article also compares the regional rankings of Saudi universities in Asia and the Arab region from 2015 to 2021, according to the Times Higher Education and Quacquarelli Symonds, respectively. Finally, the article presents the Saudi universities featuring in the top 200 and top 500 lists of the four most widely observed world university ranking systems from 2015 to 2021

Assessment of student outcomes of an electrical and electronics engineering technology programme: A case study

In this article, the authors describe in detail the Accreditation Board for Engineering and Technology (ABET) student outcomes assessment process of the historically ABET-accredited Electrical and Electronics Engineering Technology (EEET) associate degree programme at Hafr Al Batin Community College (HBCC) in the Kingdom of Saudi Arabia. Challenges faced in the students' data collection and assessment during the Covid-19 pandemic are discussed as the student data is of paramount importance for the ABET student outcomes assessment process. Best practices of the EEET Department are outlined in preparation for the forthcoming ABET accreditation of the EEET programme at HBCC. The EEET associate programme at HBCC and its outcomes are presented and discussed including the percentage attainment of ABET student outcomes of the EEET programme for the academic year 2019-2020

Deformation of a long thermoelastic rod of rectangular normal cross-section under mixed boundary conditions by boundary integrals

Using a well-known solution for steady temperature distribution in a rectangle, a boundary integral method is used to obtain an approximate solution for a plane problem of uncoupled thermoelasticity with mixed mechanical boundary conditions. The unknown functions in the cross-section are obtained in the form of series in Cartesian harmonics, enriched with harmonic functions that have a singular behavior at the transition points. The results are discussed and the functions of practical interest are represented on the boundary and also inside the domain. The locations where possible debonding may take place are noted

Economic analysis of glucagon like peptide-1 receptor agonists from the Saudi Arabia payer perspective

Objectives: To perform a cost of control analysis of glucagon like peptide-1 receptor agonists (GLP1RA) in Saudi Arabia (SA) and determine the economic impact of adopting GLP1RAs. Methods: A budget impact model that captures the cost of control model was constructed to simulate hypothetical patient on six treatment options: a current mix of 60% liraglutide and 40% dulaglutide, semaglutide, liraglutide, dulaglutide, exenatide, and lixisenatide. We estimated the relative amounts of SAR spend to achieve HbA1c targets (≤6.5% or < 7.0%). For each treatment option, annual treatment cost, proportion of patients achieving HbA1c targets, and cost to treat major adverse cardiovascular events (MACE) were aggregated to estimate the cost of control per patient per year (CCPPPY) over 5-year horizon (2021–2025). Probabilistic sensitivity analysis (PSA) was performed as a confirmatory analysis. Results: The CCPPPY to achieve HbA1c ≤ 6.5%/<7.0% using current mix, semaglutide, liraglutide, dulaglutide, exenatide, and lixisenatide were SAR 17,097/SAR 14,113, SAR 12,889/SAR 11,123, SAR 15,594/SAR 12,892, SAR 19,184/SAR 15,940, SAR 580,211/SAR 380,936, and SAR 246,570/SAR 143,759, respectively. The relative amounts of SAR spend to achieve HbA1c ≤ 6.5%/<7.0% relative to 1 SAR on semaglutide in case of adopting current mix, liraglutide, dulaglutide, exenatide, and lixisenatide were SAR 1.42/SAR 1.18, SAR 1.30/SAR 1.07, SAR 1.60/SAR 1.33, SAR 48.33/SAR 31.73, and SAR 20.54/SAR 11.97, respectively. These results were confirmed in the PSA. Conclusions: Semaglutide 1 mg once weekly was the most economically favorable GLP1RA; associated with the least CCPPPY, and amount of SAR spent to achieve HbA1c of ≤6.50%/<7.00% versus all other GLP1RAs. © 2022 The Author(s)Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Evaluation of knowledge about osteoporosis risk factors among adults above 40 years of age in Qassim region, Saudi Arabia

OBJECTIVE: Osteoporosis is a bone disease that develops when bone mineral density and bone mass decrease, or when the quality of bone changes. It is the most common bone disease, representing a major public health problem. This study aimed to assess the knowledge of risk factors for osteoporosis among adults above 40 in the Qassim region, Saudi Arabia. SUBJECTS AND METHODS: This is a cross-sectional study conducted among adults who were above 40 years of age and living in the Qassim region, Saudi Arabia. A survey questionnaire was distributed to respondents while they attended primary health care as well as online via social media. RESULTS: 390 participants responded to our survey (65.6% females vs. 34.4% males). The most common age group was 41 to 50 years (59.7%). The prevalence of participants who were having information about osteoporosis was 59%. Overall, the knowledge of participants about osteoporosis was good (63.1%), 33.3% had moderate knowledge and only 3.6% were assumed to have a poor knowledge level. Factors associated with increased knowledge was being a female and being an employee. CONCLUSIONS: Although the knowledge of the adult population aged above 40 years old seems adequate, there is still room for improvement. Female participants who were currently employed demonstrated a better understanding of osteoporosis than other adults. Further research is warranted to establish the effect of advanced age on their level of understanding regarding osteoporosis and its risk factors

Molecular and clinical spectra of FBXL4 deficiency.

F-box and leucine-rich repeat protein 4 (FBXL4) is a mitochondrial protein whose exact function is not yet known. However, cellular studies have suggested that it plays significant roles in mitochondrial bioenergetics, mitochondrial DNA (mtDNA) maintenance, and mitochondrial dynamics. Biallelic pathogenic variants in FBXL4 are associated with an encephalopathic mtDNA maintenance defect syndrome that is a multisystem disease characterized by lactic acidemia, developmental delay, and hypotonia. Other features are feeding difficulties, growth failure, microcephaly, hyperammonemia, seizures, hypertrophic cardiomyopathy, elevated liver transaminases, recurrent infections, variable distinctive facial features, white matter abnormalities and cerebral atrophy found in neuroimaging, combined deficiencies of multiple electron transport complexes, and mtDNA depletion. Since its initial description in 2013, 36 different pathogenic variants in FBXL4 were reported in 50 affected individuals. In this report, we present 37 additional affected individuals and 11 previously unreported pathogenic variants. We summarize the clinical features of all 87 individuals with FBXL4-related mtDNA maintenance defect, review FBXL4 structure and function, map the 47 pathogenic variants onto the gene structure to assess the variants distribution, and investigate the genotype&ndash;phenotype correlation. Finally, we provide future directions to understand the disease mechanism and identify treatment strategies

Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative.

Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75-10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights