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

Developing Industry 4.0 applications

The design and development of Industry 4.0 applications requires focused research work and close collaboration with the industry. Such an approach requires a balance between technical work and social interactions with industry partners: a social construction of technology (SCOT) perspective providing a lens for understanding how joint optimisation of the technical with the social dimension may be achieved. This chapter explores work conducted on the BIM risk library project: a successful three-year research collaboration to develop and launch a new BIM digital tool to assist designers with their health and safety work. Describing the activities undertaken, including ontology creation, industry workshops, software development and piloting of a digital tool, the technical and social interrelatedness is noted as critical to success. Application of concepts from the social construction of technology – technological frames, social groups, problems/solutions, closure/stabilisation – and wider context further clarify the evolution of the digital tool from conceptual idea to prize-winning application. The aim is to reinforce the importance of a social constructivist approach to technology development for the construction industry; the insights and reflections of the chapter, including the identification of SCOT optimisation triggers, are useful for Industry 4.0 technology developers and researchers active in the field