Using problem-based exploratory training to improve pilot understanding of autopilot functions

Previous research indicated a need to improve pilot training with regard to understanding of autopilot logic and behavior, especially in non-routine situations. Therefore, we tested the effect of problem-based exploratory training on pilots’ understanding of autopilot functions. Using a moving-base flight simulator, general aviation pilots (n = 45) were trained to diagnose failures either without foreknowledge and guidance (exploratory group), without foreknowledge but with some guidance (exploratory-guidance group) or with foreknowledge and full guidance (control group). They subsequently performed six test scenarios in which their understanding of the effects of failures was tested by requiring them to deduce the failures and select autopilot modes that were still functioning. Those who received exploratory training with guidance were significantly more likely than the other groups to diagnose failures correctly. The exploratory training group also selected the most appropriate functioning autopilot modes significantly faster than the control group. The results suggest that exploratory training with an appropriate level of guidance is useful for gaining a practical understanding of autopilot logic and behavior. Exploratory training may help to improve transfer of training to operational practice, and prevent automation surprises and accidents

Germline variant affecting p53β isoforms predisposes to familial cancer

Germline and somatic TP53 variants play a crucial role during tumorigenesis. However, genetic variations that solely affect the alternatively spliced p53 isoforms, p53β and p53γ, are not fully considered in the molecular diagnosis of Li-Fraumeni syndrome and cancer. In our search for additional cancer predisposing variants, we identify a heterozygous stop-lost variant affecting the p53β isoforms (p.*342Serext*17) in four families suspected of an autosomal dominant cancer syndrome with colorectal, breast and papillary thyroid cancers. The stop-lost variant leads to the 17 amino-acid extension of the p53β isoforms, which increases oligomerization to canonical p53α and dysregulates the expression of p53’s transcriptional targets. Our study reveals the capacity of p53β mutants to influence p53 signalling and contribute to the susceptibility of different cancer types. These findings underscore the significance of p53 isoforms and the necessity of comprehensive investigation into the entire TP53 gene in understanding cancer predisposition

Germline variant affecting p53β isoforms predisposes to familial cancer

Germline and somatic TP53 variants play a crucial role during tumorigenesis. However, genetic variations that solely affect the alternatively spliced p53 isoforms, p53β and p53γ, are not fully considered in the molecular diagnosis of Li-Fraumeni syndrome and cancer. In our search for additional cancer predisposing variants, we identify a heterozygous stop-lost variant affecting the p53β isoforms (p.*342Serext*17) in four families suspected of an autosomal dominant cancer syndrome with colorectal, breast and papillary thyroid cancers. The stop-lost variant leads to the 17 amino-acid extension of the p53β isoforms, which increases oligomerization to canonical p53α and dysregulates the expression of p53’s transcriptional targets. Our study reveals the capacity of p53β mutants to influence p53 signalling and contribute to the susceptibility of different cancer types. These findings underscore the significance of p53 isoforms and the necessity of comprehensive investigation into the entire TP53 gene in understanding cancer predisposition