Association of candidate pharmacogenetic markers with platinum-induced ototoxicity: PanCareLIFE dataset

Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase (TPMT) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in a pharmacogenetic guideline. The PanCareLIFE cross-sectional cohort study evaluated the genetic associations in a large pan-European population and assessed the diagnostic accuracy of the genetic markers. 1,112 pediatric cancer survivors who had provided biomaterial for genotyping were screened for participation in the pharmacogenetic association study. 900 participants qualified for inclusion. Based on the assessment of original audiograms, patients were assigned to three phenotype categories: no, minor, and clinically relevant hearing loss. Fourteen variants in eleven candidate genes (ABCC3, OTOS, TPMT, SLC22A2, NFE2L2, SLC16A5, LRP2, GSTP1, SOD2, WFS1, and ACYP2) were genotyped. The genotype and phenotype data represent a resource for conducting meta-analyses to derive a more precise pooled estimate of the effects of genes on the risk of hearing loss due to platinum treatment

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

Learning, Development, and Change in a Community-Based Enterprise in Myanmar

The purpose of this qualitative case study was to understand the process of learning and organization development and change (ODC) in a community-based enterprise in Myanmar as impacted by a certificate program in organizational development. Decades of military rule, civil war, and limited access to high-quality health and education services led to the creation of over 200,000 community-based organizations and enterprises in Myanmar. One initiative to support development and change in these organizations was the Payap University-International Rescue Committee Certificate Program in Organizational Development that was offered to members of over 100 organizations in Southeast Myanmar and along the Thai-Myanmar border from 2014-2017. One exemplary organization that had four members participate in the certificate program was selected for this study, and data were collected over a four-week period through interviews, observations, documents, and a focus group. The primary research question framing this study addressed how the process of learning and ODC occurred in this organization as impacted by the certificate program. The following three categories emerged from the data analysis: learning from the certificate program, the process of learning and change, and evidence for change. These findings led to an understanding of the essence of the process of learning and change, first through the diffusion of learning in the organization as a driver of development and change, and then through an open-systems change model including its inputs, changes processes, and outputs. In addition to the certificate program as an input to development and change processes, this study showed the importance of political and economic changes, culture, and organization characteristics as antecedents to change. This research highlighted the centrality of social learning through role modeling in the diffusion of learning and demonstrated the importance of buy-in from the organization’s members as well as their perceived alignment of the change efforts with the needs or the organization

Developing Human Resources in Southeast Asia: A Holistic Framework for the ASEAN Community

This book provides readers with a comprehensive introduction to human resource development (HRD) in Southeast Asia and offers a holistic framework for the phenomenon of Regional HRD in Southeast Asia. It argues that viewing HRD in ASEAN as a complex adaptive system is the most effective way to understand the expansive and multifarious processes and activities involved in Regional HRD. As a region, Southeast Asia continues to emerge as one of the most dynamic and compelling in the world with a need to develop its human resources to further its independence, economic prosperity, and sovereignty. By focusing on a regional perspective of HRD, this book establishes the missing link in the transition from the national HRD to the global HRD perspective. Offering a framework for understanding how HRD policy and practice function within a dynamic ecosystem, this book appeals to scholars, practitioners, and policymakers alike, particularly those interested in ASEAN.https://repository.lsu.edu/facultybooks/1285/thumbnail.jp