Modeling the Dynamics of Heroin and Illicit Opioid Use Disorder, Treatment, and Recovery

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Description
A leading crisis in the United States is the opioid use disorder (OUD) epidemic. Opioid overdose deaths have been increasing, with over 100,000 deaths due to overdose from April 2020 to April 2021. This dissertation presents two mathematical models to

A leading crisis in the United States is the opioid use disorder (OUD) epidemic. Opioid overdose deaths have been increasing, with over 100,000 deaths due to overdose from April 2020 to April 2021. This dissertation presents two mathematical models to address illicit OUD (IOUD), treatment, and recovery within an epidemiological framework. In the first model, individuals remain in the recovery class unless they relapse. Due to the limited availability of specialty treatment facilities for individuals with OUD, a saturation treat- ment function was incorporated. The second model is an extension of the first, where a casual user class and its corresponding specialty treatment class were added. Using U.S. population data, the data was scaled to a population of 200,000 to find parameter estimates. While the first model used the heroin-only dataset, the second model used both the heroin and all-illicit opioids datasets. Backward bifurcation was found in the first IOUD model for realistic parameter values. Additionally, bistability was observed in the second IOUD model with the heroin-only dataset. This result implies that it would be beneficial to increase the availability of treatment. An alarming effect was discovered about the high overdose death rate: by 2038, the disease-free equilibrium would be the only stable equilibrium. This consequence is concerning because although the goal is for the epidemic to end, it would be preferable to end it through treatment rather than overdose. The IOUD model with a casual user class, its sensitivity results, and the comparison of parameters for both datasets, showed the importance of not overlooking the influence that casual users have in driving the all-illicit opioid epidemic. Casual users stay in the casual user class longer and are not going to treatment as quickly as the users of the heroin epidemic. Another result was that the users of the all-illicit opioids were going to the recovered class by means other than specialty treatment. However, the relapse rates for those individuals were much more significant than in the heroin-only epidemic. The results above from analyzing these models may inform health and policy officials, leading to more effective treatment options and prevention efforts.
Date Created
2022
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Mathematically Modeling the Impact of RdCVFL in Photoreceptors

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Description
Recent experimental and mathematical work has shown the interdependence of the rod and cone photoreceptors with the retinal pigment epithelium in maintaining sight. Accelerated intake of glucose into the cones via the theoredoxin-like rod-derived cone viability factor (RdCVF) is

Recent experimental and mathematical work has shown the interdependence of the rod and cone photoreceptors with the retinal pigment epithelium in maintaining sight. Accelerated intake of glucose into the cones via the theoredoxin-like rod-derived cone viability factor (RdCVF) is needed as aerobic glycolysis is the primary source of energy production. Reactive oxidative species (ROS) result from the rod and cone metabolism and recent experimental work has shown that the long form of RdCVF (RdCVFL) helps mitigate the negative effects of ROS. In this work I investigate the role of RdCVFL in maintaining the health of the photoreceptors. The results of this mathematical model show the necessity of RdCVFL and also demonstrate additional stable modes that are present in this system. The sensitivity analysis shows the importance of glucose uptake, nutrient levels, and ROS mitigation in maintaining rod and cone health in light-damaged mouse models. Together, these suggest areas on which to focus treatment in order to prolong the photoreceptors, especially in situations where ROS is a contributing factor to their death such as retinitis pigmentosa (RP). A potential treatment with RdCVFL and its effects has never been studied in mathematical models. In this work, I examine an optimal control with the treatment of RdCVFL and mathematically illustrate the potential that this treatment might have for treating degenerative retinal diseases such as RP. Further, I examine optimal controls with the treatment of both RdCVF and RdCVFL in order to mathematically understand the potential that a dual treatment might have for treating degenerative retinal diseases such as RP. The RdCVFL control terms are nonlinear for biological accuracy but this results in the standard general theorems for existence of optimal controls failing to apply. I then linearize these models to have proof of existence of an optimal control. Both nonlinear and linearized control results are compared and reveal similarly substantial savings rates for rods and cones.
Date Created
2022
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Mathematical Models of Opinion Dynamics

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Description
This dissertation consists of three papers about opinion dynamics. The first paper is in collaboration with Prof. Lanchier while the other two papers are individual works. Two models are introduced and studied analytically: the Deffuant model and the Hegselmann-Krause~(HK) model.

This dissertation consists of three papers about opinion dynamics. The first paper is in collaboration with Prof. Lanchier while the other two papers are individual works. Two models are introduced and studied analytically: the Deffuant model and the Hegselmann-Krause~(HK) model. The main difference between the two models is that the Deffuant dynamics consists of pairwise interactions whereas the HK dynamics consists of group interactions. Translated into graph, each vertex stands for an agent in both models. In the Deffuant model, two graphs are combined: the social graph and the opinion graph. The social graph is assumed to be a general finite connected graph where each edge is interpreted as a social link, such as a friendship relationship, between two agents. At each time step, two social neighbors are randomly selected and interact if and only if their opinion distance does not exceed some confidence threshold, which results in the neighbors' opinions getting closer to each other. The main result about the Deffuant model is the derivation of a positive lower bound for the probability of consensus that is independent of the size and topology of the social graph but depends on the confidence threshold, the choice of the opinion space and the initial distribution. For the HK model, agent~$i$ updates its opinion~$x_i$ by taking the average opinion of its neighbors, defined as the set of agents with opinion at most~$\epsilon$ apart from~$x_i$. Here,~$\epsilon > 0$ is a confidence threshold. There are two types of HK models: the synchronous and the asynchronous HK models. In the former, all the agents update their opinion simultaneously at each time step, whereas in the latter, only one agent is selected uniformly at random to update its opinion at each time step. The mixed model is a variant of the HK model in which each agent can choose its degree of stubbornness and mix its opinion with the average opinion of its neighbors. The main results of this dissertation about HK models show conditions under which the asymptotic stability holds or a consensus can be achieved, and give a positive lower bound for the probability of consensus and, in the one-dimensional case, an upper bound for the probability of consensus. I demonstrate the bounds for the probability of consensus on a unit cube and a unit interval.
Date Created
2021
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Modeling and Analyzing the Progression of Retinitis Pigmentosa

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Description
Patients suffering from Retinitis Pigmentosa (RP), the most common type of inherited retinal degeneration, experience irreversible vision loss due to photoreceptor degeneration. The preservation of cone photoreceptors has been deemed medically relevant as a therapy aimed at preventing blindness in

Patients suffering from Retinitis Pigmentosa (RP), the most common type of inherited retinal degeneration, experience irreversible vision loss due to photoreceptor degeneration. The preservation of cone photoreceptors has been deemed medically relevant as a therapy aimed at preventing blindness in patients with RP. Cones rely on aerobic glycolysis to supply the metabolites necessary for outer segment (OS) renewal and maintenance. The rod-derived cone viability factor (RdCVF), a protein secreted by the rod photoreceptors that preserves the cones, accelerates the flow of glucose into the cone cell stimulating aerobic glycolysis. This dissertation presents and analyzes ordinary differential equation (ODE) models of cellular and molecular level photoreceptor interactions in health and disease to examine mechanisms leading to blindness in patients with RP.

First, a mathematical model composed of four ODEs is formulated to investigate the progression of RP, accounting for the new understanding of RdCVF’s role in enhancing cone survival. A mathematical analysis is performed, and stability and bifurcation analyses are used to explore various pathways to blindness. Experimental data are used for parameter estimation and model validation. The numerical results are framed in terms of four stages in the progression of RP. Sensitivity analysis is used to determine mechanisms that have a significant affect on the cones at each stage of RP. Utilizing a non-dimensional form of the RP model, a numerical bifurcation analysis via MATCONT revealed the existence of stable limit cycles at two stages of RP.

Next, a novel eleven dimensional ODE model of molecular and cellular level interactions is described. The subsequent analysis is used to uncover mechanisms that affect cone photoreceptor functionality and vitality. Preliminary simulations show the existence of oscillatory behavior which is anticipated when all processes are functioning properly. Additional simulations are carried out to explore the impact of a reduction in the concentration of RdCVF coupled with disruption in the metabolism associated with cone OS shedding, and confirms cone-on-rod reliance. The simulation results are compared with experimental data. Finally, four cases are considered, and a sensitivity analysis is performed to reveal mechanisms that significantly impact the cones in each case.
Date Created
2020
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Modeling collective motion of complex systems using agent-based models & macroscopic models

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Description
The main objective of mathematical modeling is to connect mathematics with other scientific fields. Developing predictable models help to understand the behavior of biological systems. By testing models, one can relate mathematics and real-world experiments. To validate predictions numerically, one

The main objective of mathematical modeling is to connect mathematics with other scientific fields. Developing predictable models help to understand the behavior of biological systems. By testing models, one can relate mathematics and real-world experiments. To validate predictions numerically, one has to compare them with experimental data sets. Mathematical modeling can be split into two groups: microscopic and macroscopic models. Microscopic models described the motion of so-called agents (e.g. cells, ants) that interact with their surrounding neighbors. The interactions among these agents form at a large scale some special structures such as flocking and swarming. One of the key questions is to relate the particular interactions among agents with the overall emerging structures. Macroscopic models are precisely designed to describe the evolution of such large structures. They are usually given as partial differential equations describing the time evolution of a density distribution (instead of tracking each individual agent). For instance, reaction-diffusion equations are used to model glioma cells and are being used to predict tumor growth. This dissertation aims at developing such a framework to better understand the complex behavior of foraging ants and glioma cells.
Date Created
2019
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Rigorous Proofs of Old Conjectures and New Results for Stochastic Spatial Models in Econophysics

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Description
This dissertation examines six different models in the field of econophysics using interacting particle systems as the basis of exploration. In each model examined, the underlying structure is a graph G = (V , E ), where each x ∈

This dissertation examines six different models in the field of econophysics using interacting particle systems as the basis of exploration. In each model examined, the underlying structure is a graph G = (V , E ), where each x ∈ V represents an individual who is characterized by the number of coins in her possession at time t. At each time step t, an edge (x, y) ∈ E is chosen at random, resulting in an exchange of coins between individuals x and y according to the rules of the model. Random variables ξt, and ξt(x) keep track of the current configuration and number of coins individual x has at time t respectively. Of particular interest is the distribution of coins in the long run. Considered first are the uniform reshuffling model, immediate exchange model and model with saving propensity. For each of these models, the number of coins an individual can have is nonnegative and the total number of coins in the system is conserved for all time. It is shown here that the distribution of coins converges to the exponential distribution, gamma distribution and a pseudo gamma distribution respectively. The next two models introduce debt, however, the total number of coins again remains fixed. It is shown here that when there is an individual debt limit, the number of coins per individual converges to a shifted exponential distribution. Alternatively, when a collective debt limit is imposed on the whole population, a heuristic argument is given supporting the conjecture that the distribution of coins converges to an asymmetric Laplace distribution. The final model considered focuses on the effect of cooperation on a population. Unlike the previous models discussed here, the total number of coins in the system at any given time is not bounded and the process evolves in continuous time rather than in discrete time. For this model, death of an individual will occur if they run out of coins. It is shown here that the survival probability for the population is impacted by the level of cooperation along with how productive the population is as whole.
Date Created
2019
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Application of Optimal Control for Pharmacokinetics/Pharmacodynamics

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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,

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.
Date Created
2018-05
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Latina Women in STEM: How Race and Class Shape the Experiences of Undergraduate Women in STEM Majors at Arizona State University

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Description
Women and people of color are some of the most underrepresented groups in the STEM field (science, technology, engineering, and mathematics). The purpose of this study was to uncover the barriers that undergraduate Hispanic women, as well as other women

Women and people of color are some of the most underrepresented groups in the STEM field (science, technology, engineering, and mathematics). The purpose of this study was to uncover the barriers that undergraduate Hispanic women, as well as other women of color, face while pursuing an education in a STEM-related major at Arizona State University (ASU). In-depth interviews were conducted with 13 adult participants to dig deeper into the experiences of each woman and analyze how race and class overlap in each of the women's experiences. The concept of intersectionality was used to highlight various barriers such as perceptions of working versus middle-class students, the experience of being a first-generation college student, diversity campus-wide and in the classroom, effects of stereotyping, and impacts of mentorships. All women, no matter their gender, race, or socioeconomic status, faced struggles with stereotyping, marginalization, and isolation. Women in STEM majors at ASU performed better when provided with positive mentorships and grew aspirations to become a professional in the STEM field when encouraged and guided by someone who helped them build their scientific identities. Working-class women suffered from severe stress related to finances, family support, employment, and stereotyping. Reforming the culture of STEM fields in higher education will allow women to achieve success, further build their scientific identities, and increase the rate of women graduating with STEM degrees.
Date Created
2018-05
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The Development and Interaction of Terrorist and Fanatic Groups

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Description

Through the mathematical study of two models we quantify some of the theories of co-development and co-existence of focused groups in the social sciences. This work attempts to develop the mathematical framework behind the social sciences of community formation. By

Through the mathematical study of two models we quantify some of the theories of co-development and co-existence of focused groups in the social sciences. This work attempts to develop the mathematical framework behind the social sciences of community formation. By using well developed theories and concepts from ecology and epidemiology we hope to extend the theoretical framework of organizing and self-organizing social groups and communities, including terrorist groups. The main goal of our work is to gain insight into the role of recruitment and retention in the formation and survival of social organizations. Understanding the underlining mechanisms of the spread of ideologies under competition is a fundamental component of this work. Here contacts between core and non-core individuals extend beyond its physical meaning to include indirect interaction and spread of ideas through phone conversations, emails, media sources and other similar mean.

This work focuses on the dynamics of formation of interest groups, either ideological, economical or ecological and thus we explore the questions such as, how do interest groups initiate and co-develop by interacting within a common environment and how do they sustain themselves? Our results show that building and maintaining the core group is essential for the existence and survival of an extreme ideology. Our research also indicates that in the absence of competitive ability (i.e., ability to take from the other core group or share prospective members) the social organization or group that is more committed to its group ideology and manages to strike the right balance between investment in recruitment and retention will prevail. Thus under no cross interaction between two social groups a single trade-off (of these efforts) can support only a single organization. The more efforts that an organization implements to recruit and retain its members the more effective it will be in transmitting the ideology to other vulnerable individuals and thus converting them to believers.

Date Created
2013-09-11

Theoretical studies on a two strain model of drug resistance: understand, predict and control the emergence of drug resistance

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Description
Infectious diseases are a leading cause of death worldwide. With the development of drugs, vaccines and antibiotics, it was believed that for the first time in human history diseases would no longer be a major cause of mortality. Newly emerging

Infectious diseases are a leading cause of death worldwide. With the development of drugs, vaccines and antibiotics, it was believed that for the first time in human history diseases would no longer be a major cause of mortality. Newly emerging diseases, re-emerging diseases and the emergence of microorganisms resistant to existing treatment have forced us to re-evaluate our optimistic perspective. In this study, a simple mathematical framework for super-infection is considered in order to explore the transmission dynamics of drug-resistance. Through its theoretical analysis, we identify the conditions necessary for the coexistence between sensitive strains and drug-resistant strains. Farther, in order to investigate the effectiveness of control measures, the model is extended so as to include vaccination and treatment. The impact that these preventive and control measures may have on its disease dynamics is evaluated. Theoretical results being confirmed via numerical simulations. Our theoretical results on two-strain drug-resistance models are applied in the context of Malaria, antimalarial drugs, and the administration of a possible partially effective vaccine. The objective is to develop a monitoring epidemiological framework that help evaluate the impact of antimalarial drugs and partially-effective vaccine in reducing the disease burden at the population level. Optimal control theory is applied in the context of this framework in order to assess the impact of time dependent cost-effective treatment efforts. It is shown that cost-effective combinations of treatment efforts depend on the population size, cost of implementing treatment controls, and the parameters of the model. We use these results to identify optimal control strategies for several scenarios.
Date Created
2011
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