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Extraordinary medical advances have led to significant reductions in the burden of infectious diseases in humans. However, infectious diseases still account for more than 13 million annual deaths. This large burden is partly due to some pathogens having found suitable conditions to emerge and spread in denser and more connected

Extraordinary medical advances have led to significant reductions in the burden of infectious diseases in humans. However, infectious diseases still account for more than 13 million annual deaths. This large burden is partly due to some pathogens having found suitable conditions to emerge and spread in denser and more connected host populations, and others having evolved to escape the pressures imposed by the rampant use of antimicrobials. It is then critical to improve our understanding of how diseases spread in these modern landscapes, characterized by new host population structures and socio-economic environments, as well as containment measures such as the deployment of drugs. Thus, the motivation of this dissertation is two-fold. First, we study, using both data-driven and modeling approaches, the the spread of infectious diseases in urban areas. As a case study, we use confirmed-cases data on sexually transmitted diseases (STDs) in the United States to assess the conduciveness of population size of urban areas and their socio-economic characteristics as predictors of STD incidence. We find that the scaling of STD incidence in cities is superlinear, and that the percent of African-Americans residing in cities largely determines these statistical patterns. Since disparities in access to health care are often exacerbated in urban areas, within this project we also develop two modeling frameworks to study the effect of health care disparities on epidemic outcomes. Discrepant results between the two approaches indicate that knowledge of the shape of the recovery period distribution, not just its mean and variance, is key for assessing the epidemiological impact of inequalities. The second project proposes to study, from a modeling perspective, the spread of drug resistance in human populations featuring vital dynamics, stochasticity and contact structure. We derive effective treatment regimes that minimize both the overall disease burden and the spread of resistance. Additionally, targeted treatment in structured host populations may lead to higher levels of drug resistance, and if drug-resistant strains are compensated, they can spread widely even when the wild-type strain is below its epidemic threshold.
ContributorsPatterson-Lomba, Oscar (Author) / Castillo-Chavez, Carlos (Thesis advisor) / Towers, Sherry (Thesis advisor) / Chowell-Puente, Gerardo (Committee member) / Arizona State University (Publisher)
Created2014
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Description
Public mass shootings occur at a rate in the U.S. that is higher than any other developed country. These event initiate wide spread media attention. The media attention these events achieve have shown to impact the public behavior (e.g., increased firearm sales). However, the impact public mass shootings have on

Public mass shootings occur at a rate in the U.S. that is higher than any other developed country. These event initiate wide spread media attention. The media attention these events achieve have shown to impact the public behavior (e.g., increased firearm sales). However, the impact public mass shootings have on firearm storage and carry habits of the public is not well understood. Using data collected from the Transportation Security Administration, this study examines how mass shootings have led to moral panics occurring within the U.S. through the examination of the firearm carrying habits among the population immediately following mass shootings. The results indicate that loaded firearms with rounds in the chamber detected by the TSA have significantly increased since 2012. Further, firearms detected immediately following a public mass shooting had a higher proportion of firearms loaded with a round in the chamber relative to 7 days prior to the shooting. Moreover, the increase in proportions of firearms found loaded with a round in the chamber exponentially decays as days past the initial shooting, these events occur at a higher rate than the decay rate can normalize these occurrences. I conclude that in the wake of these shootings a moral panic ensues that is partially responsible for the change in the general public’s arming configuration habits. Further research is needed in to determine the impact on crime, and public health related issues due to this change in the public’s firearm carrying habits.
ContributorsCordova, Richard Donald (Author) / Reisig, Michael (Thesis advisor) / Towers, Sherry (Committee member) / Wang, Xia (Committee member) / Holtfreter, Kristy (Committee member) / Arizona State University (Publisher)
Created2018
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Description
According to the Centers for Disease Control and Prevention (CDC), type 2 diabetes accounts for 90-95% of diabetes (29.1 million) cases and manifests in 15-30% of prediabetes (86 million) cases, where 9 out of 10 individuals do not know they have prediabetes. Obesity, observed in 56.9% of diabetes cases, arises

According to the Centers for Disease Control and Prevention (CDC), type 2 diabetes accounts for 90-95% of diabetes (29.1 million) cases and manifests in 15-30% of prediabetes (86 million) cases, where 9 out of 10 individuals do not know they have prediabetes. Obesity, observed in 56.9% of diabetes cases, arises from the interactions among genetic, biological, environmental, and behavioral factors that are not well understood. Assessing the strength of these links in conjunction with the identification and evaluation of intervention strategies in vulnerable populations is central to the study of chronic diseases. This research addresses three issues that loosely connect three levels of organization utilizing a combination of quantitative and qualitative methods. First, the nonlinear dynamics between insulin, glucose, and free fatty acids is studied via a hypothesis-based model and validated with bariatric surgery data, demonstrating key metabolic factors for maintaining glucose homeostasis. Second, the challenges associated with the treatment or management, and prevention of diabetes is explored in the context of an individualized-based intervention study, highlighting the importance of diet and environment. Third, the importance of tailored school lunch programs and policies is studied through contagion models developed within a social ecological framework. The Ratatouille Effect, motivated by a pilot study among PreK-8th grade Arizona students, is studied and exposes the importance of institutionalizing practical methods that factor in the culture, norms, and values of the community. The outcomes of this research illustrate an integrative framework that bridges physiological, individual, and population level approaches to study type 2 diabetes and obesity from a holistic perspective. This work reveals the significance of utilizing quantitative and qualitative methods to better elucidate underlying causes of chronic diseases and for developing solutions that lead to sustainable healthy behaviors, and more importantly, the need for translatable multilevel methodologies for the study of the progression, treatment, and prevention of chronic diseases from a multidisciplinary perspective.
ContributorsLe Murillo, Anarina (Author) / Castillo-Chavez, Carlos (Thesis advisor) / Li, Jiaxu (Thesis advisor) / Phillips, Elizabeth D. (Committee member) / Towers, Sherry (Committee member) / Arizona State University (Publisher)
Created2016
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Description
Head and neck squamous cell carcinoma (HNSCC), the sixth most common cancer

type worldwide, accounts for more than 630,000 new cases and 350,000 deaths

annually. Drug-resistance and tumor recurrence are the most challenging problems

in head and neck cancer treatment. It is hypothesized that a very small fraction

of stem-like cells within HNSCC tumor,

Head and neck squamous cell carcinoma (HNSCC), the sixth most common cancer

type worldwide, accounts for more than 630,000 new cases and 350,000 deaths

annually. Drug-resistance and tumor recurrence are the most challenging problems

in head and neck cancer treatment. It is hypothesized that a very small fraction

of stem-like cells within HNSCC tumor, called cancer stem cells (CSCs), is

responsible for tumor initiation, progression, resistance and recurrence. It has also

been shown that IL-6 secreted by head and neck tumor-associated endothelial cells

(ECs) enhances the survival, self-renewal and tumorigenic potential of head and

neck CSCs. In this study we will use a mathematical multi-scale model which operates

at the intracellular, molecular, and tissue level to investigate the impacts of

EC-secreted IL-6 signaling on the crosstalk between tumor cells and ECs during

tumor growth. This model will be calibrated by using the experimental in vivo

data.

Eventually the model will be modified to explore the responses of head and neck

cancer cells to combination therapy involving Tocilizumab (an anti-IL-6R antibody)

and Cisplatin (the most frequently used chemotherapy for head and neck

cancer). The model will be able to predict the final proportion of CSCs in response

to endothelial cell-secreted IL-6 and drug therapies. The model will be validated

by directly comparing the experimental treatment data and the model predictions.

This could potentially provide a condition under which we could control enlargement

of the head and neck CSC pool and tumor recurrence. It may also suggest

the best bounds for Cisplatin and/or Tocilizumab dose and frequency to be tested

in the clinical trial.
ContributorsNazari, Fereshteh (Author) / Jackson, Trachette L. (Thesis advisor, Committee member) / Castillo-Chavez, Carlos (Committee member) / Towers, Sherry (Committee member) / Kang, Yun (Committee member) / Arizona State University (Publisher)
Created2017
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Description
The 2009-10 influenza and the 2014-15 Ebola pandemics brought once again urgency to an old question: What are the limits on prediction and what can be proposed that is useful in the face of an epidemic outbreak?

This thesis looks first at the impact that limited access to vaccine

The 2009-10 influenza and the 2014-15 Ebola pandemics brought once again urgency to an old question: What are the limits on prediction and what can be proposed that is useful in the face of an epidemic outbreak?

This thesis looks first at the impact that limited access to vaccine stockpiles may have on a single influenza outbreak. The purpose is to highlight the challenges faced by populations embedded in inadequate health systems and to identify and assess ways of ameliorating the impact of resource limitations on public health policy.

Age-specific per capita constraint rates play an important role on the dynamics of communicable diseases and, influenza is, of course, no exception. Yet the challenges associated with estimating age-specific contact rates have not been decisively met. And so, this thesis attempts to connect contact theory with age-specific contact data in the context of influenza outbreaks in practical ways. In mathematical epidemiology, proportionate mixing is used as the preferred theoretical mixing structure and so, the frame of discussion of this dissertation follows this specific theoretical framework. The questions that drive this dissertation, in the context of influenza dynamics, proportionate mixing, and control, are:

I. What is the role of age-aggregation on the dynamics of a single outbreak? Or simply speaking, does the number and length of the age-classes used to model a population make a significant difference on quantitative predictions?

II. What would the age-specific optimal influenza vaccination policies be? Or, what are the age-specific vaccination policies needed to control an outbreak in the presence of limited or unlimited vaccine stockpiles?

Intertwined with the above questions are issues of resilience and uncertainty including, whether or not data collected on mixing (by social scientists) can be used effectively to address both questions in the context of influenza and proportionate mixing. The objective is to provide answers to these questions by assessing the role of aggregation (number and length of age classes) and model robustness (does the aggregation scheme selected makes a difference on influenza dynamics and control) via comparisons between purely data-driven model and proportionate mixing models.
ContributorsMorales, Romarie (Author) / Castillo-Chavez, Carlos (Thesis advisor) / Mubayi, Anuj (Thesis advisor) / Towers, Sherry (Committee member) / Arizona State University (Publisher)
Created2016
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Description
This research focuses on the intricate dynamical systems of eusocial insects, particularly ants, and honey bees, known for their highly organized colonies and cooperative behaviors. Research on eusocial insects contributes to understanding of animal and social behavior and promises to help agriculture and have huge economic impacts. Collaborating closely with

This research focuses on the intricate dynamical systems of eusocial insects, particularly ants, and honey bees, known for their highly organized colonies and cooperative behaviors. Research on eusocial insects contributes to understanding of animal and social behavior and promises to help agriculture and have huge economic impacts. Collaborating closely with ecologists, I construct diverse mathematical models tailored to different environmental contexts. These models encompass individual stochastic (Agent-based model), Ordinary Differential Equation (ODE), non-autonomous, and Delay Differential Equation (DDE) models, rigorously validated with experimental data and statistical methods. Employing dynamical theory, bifurcation analysis, and numerical simulations, I gain deeper insights into the adaptive behaviors exhibited by these insects at both colony and individual levels. Our investigation addresses pivotal questions: 1) What mechanisms underlie spatial heterogeneity within social insect colonies, influencing the spread of information and pathogens through their intricate social networks?2) How can I develop accurate mathematical models incorporating age structures, particularly for species like honeybees, utilizing delayed differential equations? 3) What is the influence of seasonality on honeybee population dynamics in the presence of parasites, as explored through non-autonomous equations? 4) How do pesticides impact honeybee population dynamics, considering delayed equations and seasonality? Key findings highlight:1) The spatial distribution within colonies significantly shapes contact dynamics, thereby influencing the dissemination of information and the allocation of tasks. 2) Accurate modeling of honeybee populations necessitates the incorporation of age structure, as well as careful consideration of seasonal variations. 3) Seasonal fluctuations in egg-laying rates exert varying effects on the survival of honeybee colonies. 4) Pesticides wield a substantial influence on adult bee mortality rates and the consumption ratios of pollen. This research not only unveils the intricate interplay between intrinsic and environmental factors affecting social insects but also provides broader insights into social behavior and the potential ramifications of climate change.
ContributorsChen, Jun (Author) / Kang, Yun (Thesis advisor) / DeGrandi-Hoffman, Gloria (Committee member) / Fewell, Jeniffer (Committee member) / Harrison, Jon (Committee member) / Towers, Sherry (Committee member) / Arizona State University (Publisher)
Created2023