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

Performance outcomes and success factors of vendor managed inventory (VMI)

Purpose – The purpose of this paper is to seek to investigate performance outcomes of vendor managed inventory (VMI) from a buyer's perspective and enablers for its successful application. Design/methodology/approach – Structural equation modelling through Partial Least Squares (PLS) is used to identify relationships between four enablers (information systems, information sharing, information quality, and relationship quality), perceived VMI success, and three outcomes (cost reductions, customer service, and supply chain control). Findings – Buyer-perceived VMI success is impacted by the quality of the buyer-supplier relationship, the quality of the IT-system and the intensity of information sharing, but not by the actual quality of the information shared. Furthermore, VMI leads to three performance outcomes: higher customer service levels, improved supply chain control and, to a lesser extent, cost reduction. Research limitations/implications – Although theory stipulates a positive impact of high quality information on the success of VMI, this study shows that the effect of information quality is limited in practice. Practical implications – The results of the survey show that purchasing managers who invest in the relationship with their suppliers and a good IT infrastructure are more likely to get better results from a VMI implementation. Furthermore, this paper shows that while most managers expect major cost reductions when implementing VMI, benefits primarily come from improved service levels. Originality/value – The study provides empirical evidence of why VMI in practice does not achieve all the benefits claimed in theory