UMD Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/3
New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a given thesis/dissertation in DRUM.
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Item A FRAMEWORK FOR CREDIBILITY ASSESSMENT OF SUBJECT-SPECIFIC PHYSIOLOGICAL MODELS(2022) Parvinian, Bahram; Hahn, Jin-Oh; Mechanical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Physiological closed-loop controllers and decision support systems are medical devices that enable some degree of automation to meet the needs of patients in resource-limited environments such as critical care and surgical units. Traditional methods of safety and effectiveness evidence generation such as pre-clinical animal and human clinical studies are cost prohibitive and may not fully capture different performance attributes of such complex safety-criticalsystems primarily due to subject variability. In silico studies using subject-specific physiological models (SSPMs) may provide a versatile platform to generate pre-clinical and clinical safety evidence for medical devices and help reduce the size and scope of animal studies and/or clinical trials. To achieve such a goal, the credibility of the SSPMs must be established for the purpose it is intended to serve. While in the past decades significant research has been dedicated towards development oftools and methods for development and evaluation of SSPMs, adoption of such models remains limited, partly due to lack of trust in SSPMs for safety-critical applications. This may be due to a lack of a cohesive and disciplined credibility assessment framework for SSPMs. In this dissertation a novel framework is proposed for credibility assessment of SSPMs. The framework combines various credibility activities in a unified manner to avoid or reduce resource intensive steps, effectively identify model or data limitations, provide direction as to how to address potential model weaknesses, and provide much needed transparency in the model evaluation process to the decision-makers. To identify various credibility activities, the framework is informed by an extensive literature review of more mature modeling spaces focusing on non- SSPMs as well as a literature review identifying gaps in the published work related to SSPMs. The utility of the proposed framework is successfully demonstrated by its application towards credibility assessment of a CO2 ventilatory gas exchange model intended to predict physiological parameters, and a blood volume kinetic model intended to predict changes in blood volume inresponse to fluid resuscitation and hemorrhage. The proposed framework facilitates development of more reliable SSPMs and will result in increased adoption of such models to be used for evaluation of safety-critical medical devices such as Clinical Decision Support (CDS) and Physiological Closed-Loop Controlled (PCLC) systems.Item HARMFUL ALGAE IN CHESAPEAKE BAY: A STUDY FOCUSED ON KARLODINIUM VENEFICUM APPLYING TIME SERIES, PHYSIOLOGICAL, AND MODELING APPROACHES(2018) Lin, Chih-Hsien; Glibert, Patricia M.; Marine-Estuarine-Environmental Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Harmful algal blooms (HABs) are expanding worldwide. The harmful dinoflagellate Karlodinium veneficum is of concern because its toxigenic properties cause fish kills. Despite considerable study on nutrient-HAB relationships, there is a lack of data on HAB nutrient physiology because of the complexity of HAB nutrition. Many bloom-forming harmful algae consume particulate prey when nutrients are not available in the dissolved form. The goal of this dissertation was to apply statistical time series analysis, together with a series of laboratory experiments, and multi-nutrient quota models to improve our understanding and predictive capability of this important HAB species. Statistical time series analysis of K. veneficum abundance in Chesapeake Bay showed the predictive power of multiplicative factors (i.e., physical factors, nutrients, and prey) and the importance of temporal lags in some of these factors in bloom promotion. In laboratory experiments, feeding rates were determined for K. veneficum on prey when both were in varying nutritional conditions. Highest feeding rates were found for K. veneficum initially under low nitrogen:phosphorus condition and fed nitrogen-rich prey. Based on these data, a conceptual model was developed of mid-Bay summer K. veneficum blooms that incorporates the role of prey with a high nitrogen:phosphorus ratio originating from river inputs and a source inocula of K. veneficum from southern Bay waters with a lower nitrogen:phosphorus content. Further laboratory experiments were conducted using multi-wavelength fluorometry to measure growth, grazing and photo-physiology of K. veneficum with single and multiple prey species. Growth of K. veneficum increased with increasing prey concentrations of the cryptophyte Rhodomonas salina, but declined with Synechococcus as the prey. Subsequent multi-nutrient mechanistic modeling was undertaken, simulating the growth of dinoflagellate K. veneficum and its common prey, Rhodomonas. The model was run varying nutrient ratios (molar nitrogen:phosphorus of 4, 16 and 32) and temperatures. The modeled biomass of K. veneficum was highest when they consumed prey under high nitrogen:phosphorus conditions. When nutrients were in balanced proportions, lower biomass of the dinoflagellate was attained at all temperatures in the model. This study underscores the importance of considering prey and their nutritional quality, as well as dissolved nutrients, in modeling HAB dynamics.