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Description
High-dimensional systems are difficult to model and predict. The underlying mechanisms of such systems are too complex to be fully understood with limited theoretical knowledge and/or physical measurements. Nevertheless, redcued-order models have been widely used to study high-dimensional systems, because they are practical and efficient to develop and implement. Although

High-dimensional systems are difficult to model and predict. The underlying mechanisms of such systems are too complex to be fully understood with limited theoretical knowledge and/or physical measurements. Nevertheless, redcued-order models have been widely used to study high-dimensional systems, because they are practical and efficient to develop and implement. Although model errors (biases) are inevitable for reduced-order models, these models can still be proven useful to develop real-world applications. Evaluation and validation for idealized models are indispensable to serve the mission of developing useful applications. Data assimilation and uncertainty quantification can provide a way to assess the performance of a reduced-order model. Real data and a dynamical model are combined together in a data assimilation framework to generate corrected model forecasts of a system. Uncertainties in model forecasts and observations are also quantified in a data assimilation cycle to provide optimal updates that are representative of the real dynamics. In this research, data assimilation is applied to assess the performance of two reduced-order models. The first model is developed for predicting prostate cancer treatment response under intermittent androgen suppression therapy. A sequential data assimilation scheme, the ensemble Kalman filter (EnKF), is used to quantify uncertainties in model predictions using clinical data of individual patients provided by Vancouver Prostate Center. The second model is developed to study what causes the changes of the state of stratospheric polar vortex. Two data assimilation schemes: EnKF and ES-MDA (ensemble smoother with multiple data assimilation), are used to validate the qualitative properties of the model using ECMWF (European Center for Medium-Range Weather Forecasts) reanalysis data. In both studies, the reduced-order model is able to reproduce the data patterns and provide insights to understand the underlying mechanism. However, significant model errors are also diagnosed for both models from the results of data assimilation schemes, which suggests specific improvements of the reduced-order models.
ContributorsWu, Zhimin (Author) / Kostelich, Eric (Thesis advisor) / Moustaoui, Mohamed (Thesis advisor) / Jones, Chris (Committee member) / Espanol, Malena (Committee member) / Platte, Rodrigo (Committee member) / Arizona State University (Publisher)
Created2021
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Description
The representation of a patient’s characteristics as the parameters of a model is a key component in many studies of personalized medicine, where the underlying mathematical models are used to describe, explain, and forecast the course of treatment. In this context, clinical observations form the bridge between the mathematical frameworks

The representation of a patient’s characteristics as the parameters of a model is a key component in many studies of personalized medicine, where the underlying mathematical models are used to describe, explain, and forecast the course of treatment. In this context, clinical observations form the bridge between the mathematical frameworks and applications. However, the formulation and theoretical studies of the models and the clinical studies are often not completely compatible, which is one of the main obstacles in the application of mathematical models in practice. The goal of my study is to extend a mathematical framework to model prostate cancer based mainly on the concept of cell-quota within an evolutionary framework and to study the relevant aspects for the model to gain useful insights in practice. Specifically, the first aim is to construct a mathematical model that can explain and predict the observed clinical data under various treatment combinations. The second aim is to find a fundamental model structure that can capture the dynamics of cancer progression within a realistic set of data. Finally, relevant clinical aspects such as how the patient's parameters change over the course of treatment and how to incorporate treatment optimization within a framework of uncertainty quantification, will be examined to construct a useful framework in practice.
ContributorsPhan, Tin (Author) / Kuang, Yang (Thesis advisor) / Kostelich, Eric J (Committee member) / Crook, Sharon (Committee member) / Maley, Carlo (Committee member) / Bryce, Alan (Committee member) / Arizona State University (Publisher)
Created2021