BackgroundModeling of the transmission dynamics of typhoid allows for an evaluation of the potential direct and indirect effects of vaccination; however, relevant typhoid models rooted in data have rarely been deployed.Methodology/Principal FindingsWe developed a parsimonious age-structured model describing the natural history and immunity to typhoid infection. The model was fit to data on culture-confirmed cases of typhoid fever presenting to Christian Medical College hospital in Vellore, India from 2000–2012. The model was then used to evaluate the potential impact of school-based vaccination strategies using live oral, Vi-polysaccharide, and Vi-conjugate vaccines. The model was able to reproduce the incidence and age distribution of typhoid cases in Vellore. The basic reproductive number (R 0) of typhoid was estimated to be 2.8 in this setting. Vaccination was predicted to confer substantial indirect protection leading to a decrease in the incidence of typhoid in the short term, but (intuitively) typhoid incidence was predicted to rebound 5–15 years following a one-time campaign.Conclusions/SignificanceWe found that model predictions for the overall and indirect effects of vaccination depend strongly on the role of chronic carriers in transmission. Carrier transmissibility was tentatively estimated to be low, consistent with recent studies, but was identified as a pivotal area for future research. It is unlikely that typhoid can be eliminated from endemic settings through vaccination alone.

Despite progressive improvements over the decades, the rich temporally resolved data in an echocardiogram remain underutilized. Human assessments reduce the complex patterns of cardiac wall motion, to a small list of measurements of heart function. All modern echocardiography artificial intelligence (AI) systems are similarly limited by design – automating measurements of the same reductionist metrics rather than utilizing the embedded wealth of data. This underutilization is most evident where clinical decision making is guided by subjective assessments of disease acuity. Predicting the likelihood of developing post-operative right ventricular failure (RV failure) in the setting of mechanical circulatory support is one such example. Here we describe a video AI system trained to predict post-operative RV failure using the full spatiotemporal density of information in pre-operative echocardiography. We achieve an AUC of 0.729, and show that this ML system significantly outperforms a team of human experts at the same task on independent evaluation.

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A computational tool is developed for simulating the dynamic response of the human cardiovascular system to various stressors and injuries. The tool couples 0-dimensional models of the heart, pulmonary vasculature, and peripheral vasculature to 1-dimensional models of the major systemic arteries. To simulate autonomic response, this multiscale circulatory model is integrated with a feedback model of the baroreflex, allowing control of heart rate, cardiac contractility, and peripheral impedance. The performance of the tool is demonstrated in 2 scenarios: neurogenic hypertension by sustained stimulation of the sympathetic nervous system and an acute 10% hemorrhage from the left femoral artery.