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- Creators: Brahms, Johannes, 1833-1897
- Creators: Hindemith, Paul, 1895-1963
Description
Diseases have been part of human life for generations and evolve within the population, sometimes dying out while other times becoming endemic or the cause of recurrent outbreaks. The long term influence of a disease stems from different dynamics within or between pathogen-host, that have been analyzed and studied by many researchers using mathematical models. Co-infection with different pathogens is common, yet little is known about how infection with one pathogen affects the host's immunological response to another. Moreover, no work has been found in the literature that considers the variability of the host immune health or that examines a disease at the population level and its corresponding interconnectedness with the host immune system. Knowing that the spread of the disease in the population starts at the individual level, this thesis explores how variability in immune system response within an endemic environment affects an individual's vulnerability, and how prone it is to co-infections. Immunology-based models of Malaria and Tuberculosis (TB) are constructed by extending and modifying existing mathematical models in the literature. The two are then combined to give a single nine-variable model of co-infection with Malaria and TB. Because these models are difficult to gain any insight analytically due to the large number of parameters, a phenomenological model of co-infection is proposed with subsystems corresponding to the individual immunology-based model of a single infection. Within this phenomenological model, the variability of the host immune health is also incorporated through three different pathogen response curves using nonlinear bounded Michaelis-Menten functions that describe the level or state of immune system (healthy, moderate and severely compromised). The immunology-based models of Malaria and TB give numerical results that agree with the biological observations. The Malaria--TB co-infection model gives reasonable results and these suggest that the order in which the two diseases are introduced have an impact on the behavior of both. The subsystems of the phenomenological models that correspond to a single infection (either of Malaria or TB) mimic much of the observed behavior of the immunology-based counterpart and can demonstrate different behavior depending on the chosen pathogen response curve. In addition, varying some of the parameters and initial conditions in the phenomenological model yields a range of topologically different mathematical behaviors, which suggests that this behavior may be able to be observed in the immunology-based models as well. The phenomenological models clearly replicate the qualitative behavior of primary and secondary infection as well as co-infection. The mathematical solutions of the models correspond to the fundamental states described by immunologists: virgin state, immune state and tolerance state. The phenomenological model of co-infection also demonstrates a range of parameter values and initial conditions in which the introduction of a second disease causes both diseases to grow without bound even though those same parameters and initial conditions did not yield unbounded growth in the corresponding subsystems. This results applies to all three states of the host immune system. In terms of the immunology-based system, this would suggest the following: there may be parameter values and initial conditions in which a person can clear Malaria or TB (separately) from their system but in which the presence of both can result in the person dying of one of the diseases. Finally, this thesis studies links between epidemiology (population level) and immunology in an effort to assess the impact of pathogen's spread within the population on the immune response of individuals. Models of Malaria and TB are proposed that incorporate the immune system of the host into a mathematical model of an epidemic at the population level.
ContributorsSoho, Edmé L (Author) / Wirkus, Stephen (Thesis advisor) / Castillo-Chavez, Carlos (Thesis advisor) / Chowell-Puente, Gerardo (Committee member) / Arizona State University (Publisher)
Created2011
ContributorsHindemith, Paul, 1895-1963 (Composer)
ContributorsBrahms, Johannes, 1833-1897 (Composer)
ContributorsBrahms, Johannes, 1833-1897 (Composer)
ContributorsBrahms, Johannes, 1833-1897 (Composer)
ContributorsBrahms, Johannes, 1833-1897 (Composer)
Description
Mathematical models are important tools for addressing problems that exceed experimental capabilities. In this work, I present ordinary and partial differential equation (ODE, PDE) models for two problems: Vicodin abuse and impact cratering.
The prescription opioid Vicodin is the nation's most widely prescribed pain reliever. The majority of Vicodin abusers are first introduced via prescription, distinguishing it from other drugs in which the most common path to abuse begins with experimentation. I develop and analyze two mathematical models of Vicodin use and abuse, considering only those patients with an initial Vicodin prescription. Through adjoint sensitivity analysis, I show that focusing efforts on prevention rather than treatment has greater success at reducing the total population of abusers. I prove that solutions to each model exist, are unique, and are non-negative. I also derive conditions for which these solutions are asymptotically stable.
Verification and Validation (V&V) are necessary processes to ensure accuracy of computational methods. Simulations are essential for addressing impact cratering problems, because these problems often exceed experimental capabilities. I show that the Free Lagrange (FLAG) hydrocode, developed and maintained by Los Alamos National Laboratory, can be used for impact cratering simulations by verifying FLAG against two analytical models of aluminum-on-aluminum impacts at different impact velocities and validating FLAG against a glass-into-water laboratory impact experiment. My verification results show good agreement with the theoretical maximum pressures, and my mesh resolution study shows that FLAG converges at resolutions low enough to reduce the required computation time from about 28 hours to about 25 minutes.
Asteroid 16 Psyche is the largest M-type (metallic) asteroid in the Main Asteroid Belt. Radar albedo data indicate Psyche's surface is rich in metallic content, but estimates for Psyche's composition vary widely. Psyche has two large impact structures in its Southern hemisphere, with estimated diameters from 50 km to 70 km and estimated depths up to 6.4 km. I use the FLAG hydrocode to model the formation of the largest of these impact structures. My results indicate an oblique angle of impact rather than a vertical impact. These results also support previous claims that Psyche is metallic and porous.
The prescription opioid Vicodin is the nation's most widely prescribed pain reliever. The majority of Vicodin abusers are first introduced via prescription, distinguishing it from other drugs in which the most common path to abuse begins with experimentation. I develop and analyze two mathematical models of Vicodin use and abuse, considering only those patients with an initial Vicodin prescription. Through adjoint sensitivity analysis, I show that focusing efforts on prevention rather than treatment has greater success at reducing the total population of abusers. I prove that solutions to each model exist, are unique, and are non-negative. I also derive conditions for which these solutions are asymptotically stable.
Verification and Validation (V&V) are necessary processes to ensure accuracy of computational methods. Simulations are essential for addressing impact cratering problems, because these problems often exceed experimental capabilities. I show that the Free Lagrange (FLAG) hydrocode, developed and maintained by Los Alamos National Laboratory, can be used for impact cratering simulations by verifying FLAG against two analytical models of aluminum-on-aluminum impacts at different impact velocities and validating FLAG against a glass-into-water laboratory impact experiment. My verification results show good agreement with the theoretical maximum pressures, and my mesh resolution study shows that FLAG converges at resolutions low enough to reduce the required computation time from about 28 hours to about 25 minutes.
Asteroid 16 Psyche is the largest M-type (metallic) asteroid in the Main Asteroid Belt. Radar albedo data indicate Psyche's surface is rich in metallic content, but estimates for Psyche's composition vary widely. Psyche has two large impact structures in its Southern hemisphere, with estimated diameters from 50 km to 70 km and estimated depths up to 6.4 km. I use the FLAG hydrocode to model the formation of the largest of these impact structures. My results indicate an oblique angle of impact rather than a vertical impact. These results also support previous claims that Psyche is metallic and porous.
ContributorsCaldwell, Wendy K (Author) / Wirkus, Stephen (Thesis advisor) / Asphaug, Erik (Committee member) / Camacho, Erika T (Committee member) / Crook, Sharon (Committee member) / Plesko, Catherine S (Committee member) / Smith, Hal (Committee member) / Arizona State University (Publisher)
Created2019
Description
Pharmacokinetics describes the movement and processing of a drug in a body, while Pharmacodynamics describes the drug's effect on a given subject. Pharmacokinetic/Pharmacodynamic(Pk/Pd) models have become a fundamental tool when predicting bacterial behavior and drug development. In November of 2009, Katsube et al. published their paper detailing their Pk/Pd model for the drug Doripenem and the bacteria P. aeruginosa. In their paper, they determined that there is a dependent relationship between the drug's effectiveness and the dosing strategy of the drug. Therefore, this thesis has applied optimal control in order to optimize the drug's effectiveness, while not burdening the subject with the side effects of the drug. Optimal Control is a mathematical tool used to balance two competing factors. As a result, it has become a useful tool used to make decisions involving complex behavior. By using Optimal Control, the model will maximize the drug's effect on the bacterial population of P. aeruginosa, while minimizing the drug concentration of Doripenem. In doing so, our research will enable doctors and clinicians to maximize a drug's effectiveness on the body, while minimizing side effects.
ContributorsSawkins, Bryan Thomas (Author) / Camacho, Erika (Thesis director) / Wirkus, Stephen (Committee member) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
ContributorsBrahms, Johannes, 1833-1897 (Composer)