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

Improving mobile app development using transpilers with maintainable outputs

National audienceMobile application developers often target both iOS and Android in an effort to extend their target user base. There are several tools that can aid this development effort, allowing developers to maintain a single codebase for both platforms instead of two. These tools often face a few shortcomings, of which two are noteworthy: they are hard-to-replace dependencies in the codebase, and often present some type of obstacle for integrating platform-independent native code with the shared codebase. The goal of this work is to propose a new approach to creating cross-platform development tools that improves on these two aspects, and to analyze the viability of a real-world implementation of the proposed approach. An analysis of the current state of the practice indicates cross-platform compilers as a promising direction, and a study is made on the common concerns and challenges faced when developing these compilers. Based on these analyses, this work proposes the creation of a compiler that translates one platform's hand-written native code into maintainable native code for the other platform. The feasibility of implementing this approach is tested with the development of a proof-of-concept compiler from Swift to Kotlin. An analysis is made on the readability of the resulting prototype's output code, as well as other relevant metrics. The conclusion is that, while some trade-offs might be necessary, such an approach is viable if applied in an adequate ecosystem