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Manning, A.,Highland, H. M.,Gasser, J.,Sim, X.,Tukiainen, T.,Fontanillas, P. AMERICAN DIABETES ASSOCIATION INC 2017 Diabetes Vol.66 No.7
<P>To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.</P>
Pearson, Stephen J.,Highlands, Brian,Jones, Rebecca,Matthews, Martyn J. Occupational Safety and Health Research Institute 2022 Safety and health at work Vol.13 No.1
Background: Firefighters may experience high environmental temperatures or carry out intensive physical tasks, or both, which leads to increased core body temperature and risk of fatalities. Hence there is a need to remotely and non-invasively monitor core body temperature. Methods: Estimated (heart rate algorithm) and actual core body temperature (ingested telemetric pill) measures were collected simultaneously for comparison during training exercises on 44 firefighter volunteers. Results: Prediction of core body temperature varied, with no specific identifiable pattern between the algorithm values and directly measured body core temperatures. Group agreement of Lin's Concordance of 0.74 (95% Upper 0.75, lower CI 0.73), was deemed poor. Conclusion: From individual agreement data Lin's Concordance was variable (Min 0.11, CI 0.13-0.01; Max 0.83, CI 0.86-0.80), indicating that the heart rate algorithm approach was not suitable for core body temperature monitoring in this population group, especially at the higher more critical core body temperatures seen.