Learning RNA Viral Disease Dynamics from Molecular Sequence Data

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Description
The severity of the health and economic devastation resulting from outbreaks of viruses such as Zika, Ebola, SARS-CoV-1 and, most recently, SARS-CoV-2 underscores the need for tools which aim to delineate critical disease dynamical features underlying observed patterns of infectious

The severity of the health and economic devastation resulting from outbreaks of viruses such as Zika, Ebola, SARS-CoV-1 and, most recently, SARS-CoV-2 underscores the need for tools which aim to delineate critical disease dynamical features underlying observed patterns of infectious disease spread. The growing emphasis placed on genome sequencing to support pathogen outbreak response highlights the need to adapt traditional epidemiological metrics to leverage this increasingly rich data stream. Further, the rapidity with which pathogen molecular sequence data is now generated, coupled with advent of sophisticated, Bayesian statistical techniques for pathogen molecular sequence analysis, creates an unprecedented opportunity to disrupt and innovate public health surveillance using 21st century tools. Bayesian phylogeography is a modeling framework which assumes discrete traits -- such as age, location of sampling, or species -- evolve according to a continuous-time Markov chain process along a phylogenetic tree topology which is inferred from molecular sequence data.

While myriad studies exist which reconstruct patterns of discrete trait evolution along an inferred phylogeny, attempts to translate the results of phyloegographic analyses into actionable metrics that can be used by public health agencies to direct the development of interventions aimed at reducing pathogen spread are conspicuously absent from the literature. In this dissertation, I focus on developing an intuitive metric, the phylogenetic risk ratio (PRR), which I use to translate the results of Bayesian phylogeographic modeling studies into a form actionable by public health agencies. I apply the PRR to two case studies: i) age-associated diffusion of influenza A/H3N2 during the 2016-17 US epidemic and ii) host associated diffusion of West Nile virus in the US. I discuss the limitations of this (and Bayesian phylogeographic) approaches when studying non-geographic traits for which limited metadata is available in public molecular sequence databases and statistically principled solutions to the missing metadata problem in the phylogenetic context. Then, I perform a simulation study to evaluate the statistical performance of the missing metadata solution. Finally, I provide a solution for researchers whom are interested in using the PRR and phylogenetic UTMs in their own genomic epidemiological studies yet are deterred by the idiosyncratic, error-prone processes required to implement these methods using popular Bayesian phylogenetic inference software packages. My solution, Build-A-BEAST, is a publicly available, object-oriented system written in python which aims to reduce the complexity and idiosyncrasy of creating XML files necessary to perform the aforementioned analyses. This dissertation extends the conceptual framework of Bayesian phylogeographic methods, develops a method to translates the output of phylogenetic models into an actionable form, evaluates the use of priors for missing metadata, and, finally, provides a solution which eases the implementation of these methods. In doing so, I lay the foundation for future work in disseminating and implementing Bayesian phylogeographic methods for routine public health surveillance.
Date Created
2020
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Mathematical Modeling of Systematic Treatment Implementation and Dynamics of Neglected Tropical Diseases: Case Studies of Visceral Leishmaniasis & Soil-Transmitted Helminths

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Description
Neglected tropical diseases (NTDs) comprise of diverse communicable diseases that affect mostly the developing economies of the world, the “neglected” populations. The NTDs Visceral Leishmaniasis (VL) and Soil-transmitted Helminthiasis (STH) are among the top contributors of global mortality and/or morbidity.

Neglected tropical diseases (NTDs) comprise of diverse communicable diseases that affect mostly the developing economies of the world, the “neglected” populations. The NTDs Visceral Leishmaniasis (VL) and Soil-transmitted Helminthiasis (STH) are among the top contributors of global mortality and/or morbidity. They affect resource-limited regions (poor health-care literacy, infrastructure, etc.) and patients’ treatment behavior is irregular due to the social constraints. Through two case studies, VL in India and STH in Ghana, this work aims to: (i) identify the additional and potential hidden high-risk population and its behaviors critical for improving interventions and surveillance; (ii) develop models with those behaviors to study the role of improved control programs on diseases’ dynamics; (iii) optimize resources for treatment-related interventions.

Treatment non-adherence is a less focused (so far) but crucial factor for the hindrance in WHO’s past VL elimination goals. Moreover, treatment non-adherers, hidden from surveillance, lead to high case-underreporting. Dynamical models are developed capturing the role of treatment-related human behaviors (patients’ infectivity, treatment access and non-adherence) on VL dynamics. The results suggest that the average duration of treatment adherence must be increased from currently 10 days to 17 days for a 28-day Miltefosine treatment to eliminate VL.

For STH, children are considered as a high-risk group due to their hygiene behaviors leading to higher exposure to contamination. Hence, Ghana, a resource-limited country, currently implements a school-based Mass Drug Administration (sMDA) program only among children. School staff (adults), equally exposed to this high environmental contamination of STH, are largely ignored under the current MDA program. Cost-effective MDA policies were modeled and compared using alternative definitions of “high-risk population”. This work optimized and evaluated how MDA along with the treatment for high-risk adults makes a significant improvement in STH control under the same budget. The criticality of risk-structured modeling depends on the infectivity coefficient being substantially different for the two adult risk groups.

This dissertation pioneers in highlighting the cruciality of treatment-related risk groups for NTD-control. It provides novel approaches to quantify relevant metrics and impact of population factors. Compliance with the principles and strategies from this study would require a change in political thinking in the neglected regions in order to achieve persistent NTD-control.
Date Created
2020
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Impact of Teaching an Interdisciplinary Course Introduction of Applied Mathematics for the Life and Social Sciences on High School Students' Skills and Attitudes Towards Mathematics in a JBMSHP Summer Program

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Description

Research shows that the subject of mathematics, although revered, remains a source of trepidation for many individuals, as they find it difficult to form a connection between the work they do on paper and their work's practical applications. This research

Research shows that the subject of mathematics, although revered, remains a source of trepidation for many individuals, as they find it difficult to form a connection between the work they do on paper and their work's practical applications. This research study describes the impact of teaching a challenging introductive applied mathematics course on high school students' skills and attitudes towards mathematics in a college Summer Program. In the analysis of my research data, I identified several emerging changes in skills and attitudes towards mathematics, skills that high-school students needed or developed when taking the mathematical modeling course. Results indicated that the applied mathematics course had a positive impact on several students' attitudes, in general, such as, self-confidence, meanings of what mathematics is, and their perceptions of what solutions are. It also had a positive impact on several skills, such as translating real-life situations to mathematics via flow diagrams, translating the models' solutions back from mathematics to the real world, and interpreting graphs. Students showed positive results when the context of their problems was applied or graphical, and fewer improvement on problems that were not. Research also indicated some negatives outcomes, a decrease in confidence for certain students, and persistent negative ways of thinking about graphs. Based on these findings, I make recommendations for teaching similar mathematical modeling at the pre-university level, to encourage the development of young students through educational, research and similar mentorship activities, to increase their inspiration and interest in mathematics, and possibly consider a variety of sciences, technology, engineering and mathematics-related (STEM) fields and careers.

Date Created
2020
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The Influence of Class Nonlinear Dynamics and Education on Socio-Economic Mobility

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Description
The dissertation addresses questions tied in to the challenges posed by the impact of environmental factors on the nonlinear dynamics of social upward mobility. The proportion of educated individuals from various socio-economic backgrounds is used as a proxy for

The dissertation addresses questions tied in to the challenges posed by the impact of environmental factors on the nonlinear dynamics of social upward mobility. The proportion of educated individuals from various socio-economic backgrounds is used as a proxy for the environmental impact on the status quo state.

Chapter 1 carries out a review of the mobility models found in the literature and sets the economic context of this dissertation. Chapter 2 explores a simple model that considers poor and rich classes and the impact that educational success may have on altering mobility patterns. The role of the environment is modeled through the use of a modified version of the invasion/extinction model of Richard Levins. Chapter 3 expands the socio-economic classes to include a large middle class to study the role of social mobility in the presence of higher heterogeneity. Chapter 4 includes demographic growth and explores what would be the time scales needed to accelerate mobility. The dissertation asked how long it will take to increase by 22% the proportion of educated from the poor classes under demographic versus non-demographic growth conditions. Chapter 5 summarizes results and includes a discussion of results. It also explores ways of modeling the influence of nonlinear dynamics of mobility, via exogenous factors. Finally, Chapter 6 presents economic perspectives about the role of environmental influence on college success. The framework can be used to incorporate the impact of economic factors and social changes, such as unemployment, or gap between the haves and have nots. The dissertation shows that peer influence (poor influencing the poor) has a larger effect than class influence (rich influencing the poor). Additionally, more heterogeneity may ease mobility of groups but results depend on initial conditions. Finally, average well-being of the community and income disparities may improve over time. Finally, population growth may extend time scales needed to achieve a specific goal of educated poor.
Date Created
2020
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Alternative Medicine Perspectives Among 1.5 Generation Indian American Immigrants

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Description
This study evaluates medical pluralism among 1.5 generation Indian American immigrants. 1.5 generation Indian Americans (N=16) were surveyed regarding their engagement in complementary and alternative medical systems (CAM), how immigration affected that, and reasons for and for not continuing the

This study evaluates medical pluralism among 1.5 generation Indian American immigrants. 1.5 generation Indian Americans (N=16) were surveyed regarding their engagement in complementary and alternative medical systems (CAM), how immigration affected that, and reasons for and for not continuing the use of CAM. Results indicated most 1.5 Indian immigrants currently engage in CAM, given that their parents also engage in CAM. The top reasons respondents indicated continued engagement in CAM was that it has no side effects and is preventative. Reasons for not practicing CAM included feeling out of place, not living with parents or not believing in CAM. After immigration, most participants decreased or stopped their engagement in CAM. More women than men continued to practice CAM after immigration. From the results, it was concluded that CAM is still important to 1.5 generation Indian immigrants.
Date Created
2020-05
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Identifying and Evaluating the Impact of Ecological Factors on the Patterns of Health Risk Behaviors Among Arizona State University Students

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Description
Ecological modeling can be used to analyze health risk behaviors and their relationship to ecological factors, which is useful in determining how social environmental factors influence an individual’s decisions. Environmental interactions shape the way that humans behave throughout the day,

Ecological modeling can be used to analyze health risk behaviors and their relationship to ecological factors, which is useful in determining how social environmental factors influence an individual’s decisions. Environmental interactions shape the way that humans behave throughout the day, either through observation, action, or consequences. Specifically, health risk behaviors can be analyzed in relation to ecological factors. Alcohol drinking among college students has been a long concern and there are many risks associated with these behaviors in this population. Consistent engagement in health risk behaviors as a college student, such as drinking and smoking, can pose a much larger issues later in life and can lead to many different health problems. A research study was conducted in the form of a 27 question survey to determine and evaluate the impact of ecological factors on drinking and smoking behaviors among Arizona State University students. Ecological factors such as demographics, living conditions, contexts of social interactions, and places where students spend most of their time were used to evaluate the relationship between drinking and smoking behaviors and the ecological factors, both on- and off- campus.
Date Created
2020-05
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The Impact of Anthropologically Motivated Human Social Networks on the Transmission Dynamics of Infectious Disease

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Description
Understanding the consequences of changes in social networks is an important an-

thropological research goal. This dissertation looks at the role of data-driven social

networks on infectious disease transmission and evolution. The dissertation has two

projects. The first project is an examination of

Understanding the consequences of changes in social networks is an important an-

thropological research goal. This dissertation looks at the role of data-driven social

networks on infectious disease transmission and evolution. The dissertation has two

projects. The first project is an examination of the effects of the superspreading

phenomenon, wherein a relatively few individuals are responsible for a dispropor-

tionate number of secondary cases, on the patterns of an infectious disease. The

second project examines the timing of the initial introduction of tuberculosis (TB) to

the human population. The results suggest that TB has a long evolutionary history

with hunter-gatherers. Both of these projects demonstrate the consequences of social

networks for infectious disease transmission and evolution.

The introductory chapter provides a review of social network-based studies in an-

thropology and epidemiology. Particular emphasis is paid to the concept and models

of superspreading and why to consider it, as this is central to the discussion in chapter

2. The introductory chapter also reviews relevant epidemic mathematical modeling

studies.

In chapter 2, social networks are connected with superspreading events, followed

by an investigation of how social networks can provide greater understanding of in-

fectious disease transmission through mathematical models. Using the example of

SARS, the research shows how heterogeneity in transmission rate impacts super-

spreading which, in turn, can change epidemiological inference on model parameters

for an epidemic.

Chapter 3 uses a different mathematical model to investigate the evolution of TB

in hunter-gatherers. The underlying question is the timing of the introduction of TB

to the human population. Chapter 3 finds that TB’s long latent period is consistent

with the evolutionary pressure which would be exerted by transmission on a hunter-

igatherer social network. Evidence of a long coevolution with humans indicates an

early introduction of TB to the human population.

Both of the projects in this dissertation are demonstrations of the impact of var-

ious characteristics and types of social networks on infectious disease transmission

dynamics. The projects together force epidemiologists to think about networks and

their context in nontraditional ways.
Date Created
2019
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Mathematical Modeling of Honeybee Population Dynamics

Description
Honeybees are important pollinators worldwide and pollinate about one-third of the food we consume. Recently though, honeybee colonies have been under increasing stress due to changing environments, pesticides, mites, and viruses, which has increased the incidence of
colony collapse.

Honeybees are important pollinators worldwide and pollinate about one-third of the food we consume. Recently though, honeybee colonies have been under increasing stress due to changing environments, pesticides, mites, and viruses, which has increased the incidence of
colony collapse. This paper aims to understand how these different factors contribute to the decline of honeybee populations by using two separate approaches: data analysis and mathematical modeling. The data analysis examines the relative impacts of mites, pollen, mites, and viruses on honeybee populations and colony collapse. From the data, low initial bee populations lead to collapse in September while mites and viruses can lead to collapse in December. Feeding bee colonies also has a mixed effect, where it increases both bee and mite populations. For the model, we focus on the population dynamics of the honeybee-mite interaction. Using a system of delay differential equations with five population components, we find that bee colonies can collapse from mites, coexist with mites, and survive without them. As long as bees produce more pupa than the death rate of pupa and mites produce enough phoretic mites compared to their death rates, bees and mites can coexist. Thus, it is possible for honeybee colonies to withstand mites, but if the parasitism is too large, the colony will collapse. Provided
this equilibrium exists, the addition of mites leads to the colony moving to the interior equilibrium. Additionally, population oscillations are persistent if they occur and are connected to the interior equilibrium. Certain parameter values destabilize bee populations, leading to large
oscillations and even collapse. From these parameters, we can develop approaches that can help us prevent honeybee colony collapse before it occurs.
Date Created
2019-05
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Identifying and Evaluating the Impact of Ecological Factors on the Patterns of Health Risk Behaviors Among Arizona State University Students: A Survey-Based Study

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Description
Ecological modeling can be used to analyze health risk behaviors and their relationship to ecological factors, which is useful in determining how social environmental factors influence an individual’s decisions. Environmental interactions shape the way that humans behave throughout the day,

Ecological modeling can be used to analyze health risk behaviors and their relationship to ecological factors, which is useful in determining how social environmental factors influence an individual’s decisions. Environmental interactions shape the way that humans behave throughout the day, either through observation, action, or consequences. Specifically, health risk behaviors can be analyzed in relation to ecological factors. Alcohol drinking among college students has been a long concern and there are many risks associated with these behaviors in this population. Consistent engagement in health risk behaviors as a college student, such as drinking and smoking, can pose a much larger issues later in life and can lead to many different health problems. A research study was conducted in the form of a 27 question survey to determine and evaluate the impact of ecological factors on drinking and smoking behaviors among Arizona State University students. Ecological factors such as demographics, living conditions, contexts of social interactions, and places where students spend most of their time were used to evaluate the relationship between drinking and smoking behaviors and the ecological factors, both on- and off- campus. The sample size of this study is 541 students. Statistical tests were conducted using Excel and RStudio to find relationships between patterns of health risk behaviors and various ecological factors. The data from the survey was analyzed to address three main questions. The first question analyzed drinking behaviors in relation to demographics, specifically gender and race. The second question assessed drinking behaviors with participation in Greek life and clubs on campus. The third question evaluated the relationship between health risk behaviors and students’ living conditions, such as living on or off campus. The results show that while gender does not have a statistically significant influence on drinking behaviors, race does. White individuals are more likely to engage in drinking behaviors and are more at risk than non-whites. Participation in Greek life was shown to be statistically significant in determining health risk behaviors, while involvement in clubs was not. Finally, on campus students are less likely to engage in health risk behaviors than off-campus students.
Date Created
2019-05

Modeling Dynamics of Methamphetamine Markets and Use: A Case Study of Arizona and California

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Description
Substance abuse has become a major problem in the USA in the past decade, with immense public health and societal consequences. Methamphetamine (meth) use has grown due to an increased number of meth production and distribution markets. Border states such

Substance abuse has become a major problem in the USA in the past decade, with immense public health and societal consequences. Methamphetamine (meth) use has grown due to an increased number of meth production and distribution markets. Border states such as Arizona and California are especially concerned with Mexico’s production and distribution of meth to their residents. A mathematical model for meth use and markets was developed and then analyzed to track multiple types of drug markets and drug-related arrests for possession or distribution. The importance of social influences as a major causal factor in the onset of illicit drug use is explicitly incorporated. The model parameters are then estimated using meth-related data from California and Arizona. A parameter sensitivity analysis on the model output was carried out. The results suggest that law enforcement policy aimed at marketers will be significantly more effective than targeting current users. Moreover, local unorganized markets have a greater role in maintaining the endemic level of meth users. Whereas, global organized markets play a role in initiating meth use outbreaks. Some implications for interventions and health promotion for the two states are also discussed.
Date Created
2019-05
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