New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

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

Virtual construction of architecture using 3D CAD and simulation

3D modelling and computer simulations provide new ways for architecture students to study the relationship between the design and construction of buildings. Digital media help to integrate and expand the content of courses in drafting, construction and design. This paper describes computer-based exercises that intensify the student's experience of construction in several courses from sophomore to senior level. The courses integrate content from drafting and design communication, construction, CAD, and design. Several techniques are used to strengthen students'awareness and ability in construction. These include: Virtual design-build projects in which students construct 3D CAD models that include all elements that are used in construction. Virtual office in which several students must collaborate under the supervision of a student acting as project architect to create a 3D CAD model and design development documents. Virtual sub-contracting in which each student builds a trade specific 3D CAD model of a building and all of the trade specific models must be combined into a single model. Construction simulations (4D CAD) in which students build 3D CAD models showing all components and then animate them to illustrate the assembly process. Cost estimating using spreadsheets. These techniques are applied and reapplied at several points in the curriculum in both technical laboratory courses and design studios. This paper compares virtual construction methods to physical design-build projects and provides our pedagogical arguments for the use of digital media for understanding construction.