8 research outputs found
Using hypermedia to develop an intelligent tutorial/diagnostic system for the Space Shuttle Main Engine Controller Lab
This is a tutorial/diagnostic system for training personnel in the use of the Space Shuttle Main Engine Controller (SSMEC) Simulation Lab. It also provides a diagnostic capable of isolating lab failures at least to the major lab component. The system was implemented using Hypercard, which is an program of hypermedia running on Apple Macintosh computers. Hypercard proved to be a viable platform for the development and use of sophisticated tutorial systems and moderately capable diagnostic systems. This tutorial/diagnostic system uses the basic Hypercard tools to provide the tutorial. The diagnostic part of the system uses a simple interpreter written in the Hypercard language (Hypertalk) to implement the backward chaining rule based logic commonly found in diagnostic systems using Prolog. Some of the advantages of Hypercard in developing this type of system include sophisticated graphics, animation, sound and voice capabilities, its ability as a hypermedia tool, and its ability to include digitized pictures. The major disadvantage is the slow execution time for evaluation of rules (due to the interpretive processing of the language). Other disadvantages include the limitation on the size of the cards, that color is not supported, that it does not support grey scale graphics, and its lack of selectable fonts for text fields
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The Value of Rare Genetic Variation in the Prediction of Common Obesity in European Ancestry Populations.
Polygenic risk scores (PRSs) aggregate the effects of genetic variants across the genome and are used to predict risk of complex diseases, such as obesity. Current PRSs only include common variants (minor allele frequency (MAF) ≥1%), whereas the contribution of rare variants in PRSs to predict disease remains unknown. Here, we examine whether augmenting the standard common variant PRS (PRScommon) with a rare variant PRS (PRSrare) improves prediction of obesity. We used genome-wide genotyped and imputed data on 451,145 European-ancestry participants of the UK Biobank, as well as whole exome sequencing (WES) data on 184,385 participants. We performed single variant analyses (for both common and rare variants) and gene-based analyses (for rare variants) for association with BMI (kg/m2), obesity (BMI ≥ 30 kg/m2), and extreme obesity (BMI ≥ 40 kg/m2). We built PRSscommon and PRSsrare using a range of methods (Clumping+Thresholding [C+T], PRS-CS, lassosum, gene-burden test). We selected the best-performing PRSs and assessed their performance in 36,757 European-ancestry unrelated participants with whole genome sequencing (WGS) data from the Trans-Omics for Precision Medicine (TOPMed) program. The best-performing PRScommon explained 10.1% of variation in BMI, and 18.3% and 22.5% of the susceptibility to obesity and extreme obesity, respectively, whereas the best-performing PRSrare explained 1.49%, and 2.97% and 3.68%, respectively. The PRSrare was associated with an increased risk of obesity and extreme obesity (ORobesity = 1.37 per SDPRS, Pobesity = 1.7x10-85; ORextremeobesity = 1.55 per SDPRS, Pextremeobesity = 3.8x10-40), which was attenuated, after adjusting for PRScommon (ORobesity = 1.08 per SDPRS, Pobesity = 9.8x10-6; ORextremeobesity= 1.09 per SDPRS, Pextremeobesity = 0.02). When PRSrare and PRScommon are combined, the increase in explained variance attributed to PRSrare was small (incremental Nagelkerke R2 = 0.24% for obesity and 0.51% for extreme obesity). Consistently, combining PRSrare to PRScommon provided little improvement to the prediction of obesity (PRSrare AUC = 0.591; PRScommon AUC = 0.708; PRScombined AUC = 0.710). In summary, while rare variants show convincing association with BMI, obesity and extreme obesity, the PRSrare provides limited improvement over PRScommon in the prediction of obesity risk, based on these large populations