Knowledge Management in the Context of an Ageing Workforce: Organizational Memory and Mentoring

Organizational memory has significant potential for companies’ competitive advantage, with mentoring considered a particularly effective method of transferring this knowledge. Older workers are often considered ideal mentors because of their experience and alleged willingness to pass on their knowledge. There is an associated assumption that these workers anticipate and experience positive outcomes from mentoring others. This thesis tested if these assumptions hold up in 21st century workplaces - some discriminatory practices towards older workers and a career contract that no longer guarantees employment, may discourage knowledge sharing. An organizational memory scale was constructed to help test the assumptions and an exploratory factor analysis involving 143 employees from eight companies resulted in 21 items and five correlated factors including socio-political knowledge, job knowledge, external network, history, and industry knowledge. Two confirmatory factor analyses, the first involving 287 employees and the second 115 retirees, found support for five correlated first-order factors and a second order factor, organizational memory. In a third study involving 134 employees, support was found for a model of organizational memory and empowerment. Age was found to relate to organizational memory but this relationship was mediated by organizational tenure. In turn, organizational memory was found to relate to psychological empowerment and the frequency with which participants were requested to share knowledge at work. Organizational memory, empowerment and request to train and mentor others also positively related to organization-based self-esteem. In the fourth study, an organizational case study involving 78 employees, support was found for a model of organizational memory and the intention to mentor within the context of an aging workforce. Generativity and the expected cost of the time and effort involved in mentoring mediated the relationship between organizational memory (specifically, socio- political knowledge) and the intention to mentor. Furthermore those participants with high scores on both organizational memory and occupational self-efficacy anticipated more cost in time and effort, and indicated less intention to mentor, than those with high organizational memory but low occupational self-efficacy. These findings challenge the assumption that experienced workers are, as a matter of course, willing to mentor others. In a final study involving 96 retired individuals, there were no significant differences found between retirees with and those without experience as a mentor, in career satisfaction and unwelcome work ruminations. However notably, the study showed that participants did experience unwelcome work ruminations even (as in the case of some) well into retirement. The thesis concludes with a summary of findings as they relate to the assumptions under examination, an outline of the overall implications of the findings for future research and for organizational practice, and closing remarks about the overall research contribution of the thesis

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease

Knowledge Management in the Context of an Ageing Workforce: Organizational Memory and Mentoring

Organizational memory has significant potential for companies’ competitive advantage, with mentoring considered a particularly effective method of transferring this knowledge. Older workers are often considered ideal mentors because of their experience and alleged willingness to pass on their knowledge. There is an associated assumption that these workers anticipate and experience positive outcomes from mentoring others. This thesis tested if these assumptions hold up in 21st century workplaces - some discriminatory practices towards older workers and a career contract that no longer guarantees employment, may discourage knowledge sharing. An organizational memory scale was constructed to help test the assumptions and an exploratory factor analysis involving 143 employees from eight companies resulted in 21 items and five correlated factors including socio-political knowledge, job knowledge, external network, history, and industry knowledge. Two confirmatory factor analyses, the first involving 287 employees and the second 115 retirees, found support for five correlated first-order factors and a second order factor, organizational memory. In a third study involving 134 employees, support was found for a model of organizational memory and empowerment. Age was found to relate to organizational memory but this relationship was mediated by organizational tenure. In turn, organizational memory was found to relate to psychological empowerment and the frequency with which participants were requested to share knowledge at work. Organizational memory, empowerment and request to train and mentor others also positively related to organization-based self-esteem. In the fourth study, an organizational case study involving 78 employees, support was found for a model of organizational memory and the intention to mentor within the context of an aging workforce. Generativity and the expected cost of the time and effort involved in mentoring mediated the relationship between organizational memory (specifically, socio- political knowledge) and the intention to mentor. Furthermore those participants with high scores on both organizational memory and occupational self-efficacy anticipated more cost in time and effort, and indicated less intention to mentor, than those with high organizational memory but low occupational self-efficacy. These findings challenge the assumption that experienced workers are, as a matter of course, willing to mentor others. In a final study involving 96 retired individuals, there were no significant differences found between retirees with and those without experience as a mentor, in career satisfaction and unwelcome work ruminations. However notably, the study showed that participants did experience unwelcome work ruminations even (as in the case of some) well into retirement. The thesis concludes with a summary of findings as they relate to the assumptions under examination, an outline of the overall implications of the findings for future research and for organizational practice, and closing remarks about the overall research contribution of the thesis

The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection

Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity

Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as describedw previously. Nominally significant associations were found for rare functional variants in BBS1, BBS9, GNAS, MKKS, CLOCK and ANGPTL6. The p.S284X variant in ANGPTL6 drives the association signal (rs201622589, MAF∼0.1%, odds ratio = 10.13, p-value = 0.042) and results in complete loss of secretion in cells. Further analysis including additional case-control studies and population controls (N = 260,642) did not support association of this variant with obesity (odds ratio = 2.34, p-value = 2.59 × 10-3), highlighting the challenges of testing rare variant associations and the need for very large sample sizes. Further validation in cohorts with severe obesity and engineering the variants in model organisms will be needed to explore whether human variants in ANGPTL6 and other genes that lead to obesity when deleted in mice, do contribute to obesity. Such studies may yield druggable targets for weight loss therapies

Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits

High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future