Machine learning approaches to identifying social determinants of health in electronic health record clinical notes

Social determinants of health (SDH) represent the complex set of circumstances in which individuals are born, or with which they live, that impact health. Relatively little attention has been given to processes needed to extract SDH data from electronic health records. Despite their importance, SDH data in the EHR remains sparse, typically collected only in clinical notes and thus largely unavailable for clinical decision making. I focus on developing and validating more efficient information extraction approaches to identifying and classifying SDH in clinical notes. In this dissertation, I have three goals: First, I develop a word embedding model to expand SDH terminology in the context of identifying SDH clinical text. Second, I examine the effectiveness of different machine learning algorithms and a neural network model to classify the SDH characteristics financial resource strain and poor social support. Third, I compare the highest performing approaches to simpler text mining techniques and evaluate the models based on performance, cost, and generalizability in the task of classifying SDH in two distinct data sources.Doctor of Philosoph

Neuropilin-1 Modulates p53/Caspases Axis to Promote Endothelial Cell Survival

Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF), one of the crucial pro-angiogenic factors, functions as a potent inhibitor of endothelial cell (EC) apoptosis. Previous progress has been made towards delineating the VPF/VEGF survival signaling downstream of the activation of VEGFR-2. Here, we seek to define the function of NRP-1 in VPF/VEGF-induced survival signaling in EC and to elucidate the concomitant molecular signaling events that are pivotal for our understanding of the signaling of VPF/VEGF. Utilizing two different in vitro cell culture systems and an in vivo zebrafish model, we demonstrate that NRP-1 mediates VPF/VEGF-induced EC survival independent of VEGFR-2. Furthermore, we show here a novel mechanism for NRP-1-specific control of the anti-apoptotic pathway in EC through involvement of the NRP-1-interacting protein (NIP/GIPC) in the activation of PI-3K/Akt and subsequent inactivation of p53 pathways and FoxOs, as well as activation of p21. This study, by elucidating the mechanisms that govern VPF/VEGF-induced EC survival signaling via NRP-1, contributes to a better understanding of molecular mechanisms of cardiovascular development and disease and widens the possibilities for better therapeutic targets

Effects of moderate hypercholesterolemia on rabbit endothelium.

We investigated the effects of moderate hypercholesterolemia and endothelial regrowth on the function of vascular endothelium. Groups of rabbits were fed either a high or low cholesterol diet and subjected to removal of the aortic endothelium or sham-operated. Endothelial removal caused diffuse thickening of the myointima. The high cholesterol diet did not affect the extent of endothelial regeneration. To test endothelial function, 1 minute before sacrifice each animal was infused with horseradish peroxidase, which will penetrate the intima in areas of increased permeability. After sacrifice, the aorta was removed en bloc and exposed to diaminobenzidine and H2O2, which produce a brown stain on reaction with horseradish peroxidase. The luminal surface of the aorta was examined, and brown-stained areas, indicating increased permeability, were quantitated by stereology. Rabbits fed the cholesterol-rich diet had a greater percentage of brown-stained areas than did rabbits fed the low cholesterol diet; this was true for both intact and regenerated endothelium. The differences were significant at the p less than 0.01 level. Scanning electron microscopy of brown areas showed that, although the surface characteristics of the endothelium were altered, endothelial sloughing did not occur. Therefore, it appears that hypercholesterolemia can be associated with a functional endothelial defect in the absence of endothelial loss.</jats:p