This dissertation explores the impact of environmental dependent risk on disease dynamics within a Lagrangian modeling perspective; where the identity (defined by place of residency) of individuals is preserved throughout the epidemic process. In Chapter Three, the impact of individuals who refuse to be vaccinated is explored. MMR vaccination and birth rate data from the State of California are used to determine the impact of the anti-vaccine movement on the dynamics of growth of the anti-vaccine sub-population. Dissertation results suggest that under realistic California social dynamics scenarios, it is not possible to revert the influence of anti-vaccine

contagion. In Chapter Four, the dynamics of Zika virus are explored in two highly distinct idealized environments defined by a parameter that models highly distinctive levels of risk, the result of vector and host density and vector control measures. The underlying assumption is that these two communities are intimately connected due to economics with the impact of various patterns of mobility being incorporated via

the use of residency times. In short, a highly heterogeneous community is defined by its risk of acquiring a Zika infection within one of two "spaces," one lacking access to health services or effective vector control policies (lack of resources or ignored due to high levels of crime, or poverty, or both). Low risk regions are defined as those with access to solid health facilities and where vector control measures are implemented routinely. It was found that the better connected these communities are, the existence of communities where mobility between risk regions is not hampered, lower the overall, two patch Zika prevalence. Chapter Five focuses on the dynamics of tuberculosis (TB), a communicable disease, also on an idealized high-low risk set up. The impact of mobility within these two highly distinct TB-risk environments on the dynamics and control of this disease is systematically explored. It is found that collaboration and mobility, under some circumstances, can reduce the overall TB burden.

Soil-transmitted helminthiasis (STH), a neglected tropical disease (NTD) remains a major health problem all over the world especially in developing countries such as, Cameroon with a prevalence of 30.8%, Nigeria and Ghana with a prevalence of 25.4% (Pullan et. al, 2014). This study touches on transmission patterns and investigates the effectiveness of policies on mass drug administration as a means to control STH in Ghana. The government of Ghana currently focuses mass drug administration efforts on school aged children (SAC) that are children between the ages of 5-14 years. This paper develops and evaluates a different mass drug administration strategy by hypothesizing that it would be more cost-effective to target some percentage of vulnerable adults in MDA efforts as opposed to only targeting SAC between ages 5-14 years in Ghana. This we hypothesize would lead to a faster reduction in prevalence over time, would be cost-effective and would hopefully lead to an eventual reduction in morbidity caused by this disease to a level of no public health significance in Ghana. We conduct three cost-effectiveness analyses based on three different case setups. Given the parameter values from literature, our results suggest that it is most cost-effective to cover 20% of adults while covering at least 24% of children in mass drug administration assuming that the number of individuals covered is equal to 80% a figure which is the current total coverage of school-aged children.

Background
Several past studies have found that media reports of suicides and homicides appear to subsequently increase the incidence of similar events in the community, apparently due to the coverage planting the seeds of ideation in at-risk individuals to commit similar acts.
Methods
Here we explore whether or not contagion is evident in more high-profile incidents, such as school shootings and mass killings (incidents with four or more people killed). We fit a contagion model to recent data sets related to such incidents in the US, with terms that take into account the fact that a school shooting or mass murder may temporarily increase the probability of a similar event in the immediate future, by assuming an exponential decay in contagiousness after an event.
Conclusions
We find significant evidence that mass killings involving firearms are incented by similar events in the immediate past. On average, this temporary increase in probability lasts 13 days, and each incident incites at least 0.30 new incidents (p = 0.0015). We also find significant evidence of contagion in school shootings, for which an incident is contagious for an average of 13 days, and incites an average of at least 0.22 new incidents (p = 0.0001). All p-values are assessed based on a likelihood ratio test comparing the likelihood of a contagion model to that of a null model with no contagion. On average, mass killings involving firearms occur approximately every two weeks in the US, while school shootings occur on average monthly. We find that state prevalence of firearm ownership is significantly associated with the state incidence of mass killings with firearms, school shootings, and mass shootings.

Background
The transmission dynamics of Tuberculosis (TB) involve complex epidemiological and socio-economical interactions between individuals living in highly distinct regional conditions. The level of exogenous reinfection and first time infection rates within high-incidence settings may influence the impact of control programs on TB prevalence. The impact that effective population size and the distribution of individuals’ residence times in different patches have on TB transmission and control are studied using selected scenarios where risk is defined by the estimated or perceive first time infection and/or exogenous re-infection rates.
Methods
This study aims at enhancing the understanding of TB dynamics, within simplified, two patch, risk-defined environments, in the presence of short term mobility and variations in reinfection and infection rates via a mathematical model. The modeling framework captures the role of individuals’ ‘daily’ dynamics within and between places of residency, work or business via the average proportion of time spent in residence and as visitors to TB-risk environments (patches). As a result, the effective population size of Patch i (home of i-residents) at time t must account for visitors and residents of Patch i, at time t.
Results
The study identifies critical social behaviors mechanisms that can facilitate or eliminate TB infection in vulnerable populations. The results suggest that short-term mobility between heterogeneous patches contributes to significant overall increases in TB prevalence when risk is considered only in terms of direct new infection transmission, compared to the effect of exogenous reinfection. Although, the role of exogenous reinfection increases the risk that come from large movement of individuals, due to catastrophes or conflict, to TB-free areas.
Conclusions
The study highlights that allowing infected individuals to move from high to low TB prevalence areas (for example via the sharing of treatment and isolation facilities) may lead to a reduction in the total TB prevalence in the overall population. The higher the population size heterogeneity between distinct risk patches, the larger the benefit (low overall prevalence) under the same “traveling” patterns. Policies need to account for population specific factors (such as risks that are inherent with high levels of migration, local and regional mobility patterns, and first time infection rates) in order to be long lasting, effective and results in low number of drug resistant cases.

Soft errors are considered as a key reliability challenge for sub-nano scale transistors. An ideal solution for such a challenge should ultimately eliminate the effect of soft errors from the microprocessor. While forward recovery techniques achieve fast recovery from errors by simply voting out the wrong values, they incur the overhead of three copies execution. Backward recovery techniques only need two copies of execution, but suffer from check-pointing overhead.

In this work I explored the efficiency of integrating check-pointing into the application and the effectiveness of recovery that can be performed upon it. After evaluating the available fine-grained approaches to perform recovery, I am introducing InCheck, an in-application recovery scheme that can be integrated into instruction-duplication based techniques, thus providing a fast error recovery. The proposed technique makes light-weight checkpoints at the basic-block granularity, and uses them for recovery purposes.

To evaluate the effectiveness of the proposed technique, 10,000 fault injection experiments were performed on different hardware components of a modern ARM in-order simulated processor. InCheck was able to recover from all detected errors by replaying about 20 instructions, however, the state of the art recovery scheme failed more than 200 times.

Combination therapy has shown to improve success for cancer treatment. Oncolytic virotherapy is cancer treatment that uses engineered viruses to specifically infect and kill cancer cells, without harming healthy cells. Immunotherapy boosts the body's natural defenses towards cancer. The combination of oncolytic virotherapy and immunotherapy is explored through deterministic systems of nonlinear differential equations, constructed to match experimental data for murine melanoma. Mathematical analysis was done in order to gain insight on the relationship between cancer, viruses and immune response. One extension of the model focuses on clinical needs, with the underlying goal to seek optimal treatment regimens; for both frequency and dose quantity. The models in this work were first used to estimate parameters from preclinical experimental data, to identify biologically realistic parameter values. Insight gained from the mathematical analysis in the first model, allowed for numerical analysis to explore optimal treatment regimens of combination oncolytic virotherapy and dendritic vaccinations. Permutations accounting for treatment scheduled were done to find regimens that reduce tumor size. Observations from the produced data lead to in silico exploration of immune-viral interactions. Results suggest under optimal settings, combination treatment works better than monotherapy of either type. The most optimal result suggests treatment over a longer period of time, with fractioned doses, while reducing the total dendritic vaccination quantity, and maintaining the maximum virotherapy used in the experimental work.

The Visceral Leishmaniasis (VL) is primarily endemic in five countries, with India and Sudan having the highest burden. The risk factors associated with VL are either unknown in some regions or vary drastically among empirical studies. Here, a dynamical model, motivated and informed by field data from the literature, is analyzed and employed to identify and quantify the impact of region dependent risks on the VL transmission dynamics. Parameter estimation procedures were developed using model-derived quantities and empirical data from multiple resources. The dynamics of VL depend on the estimates of the control reproductive number, RC, interpreted as the average number of secondary infections generated by a single infectious individual during the infectious period. The distribution of RC was estimated for both India (with mean 2.1 ± 1.1) and Sudan (with mean 1.45 ± 0.57). This suggests that VL can be established in naive regions of India more easily than in naive regions of Sudan. The parameter sensitivity analysis on RC suggests that the average biting rate and transmission probabilities between host and vector are among the most sensitive parameters for both countries. The comparative assessment of VL transmission dynamics in both India and Sudan was carried out by parameter sensitivity analysis on VL-related prevalences (such as prevalences of asymptomatic hosts, symptomatic hosts, and infected vectors). The results identify that the treatment and symptoms’ developmental rates are parameters that are highly sensitive to VL symptomatic and asymptomatic host prevalence, respectively, for both countries. It is found that the estimates of transmission probability are significantly different between India (from human to sandflies with mean of 0.39 ± 0.12; from sandflies to human with mean 0.0005 ± 0.0002) and Sudan (from human to sandflies with mean 0.26 ± 0.07; from sandflies to human with mean 0.0002 ± 0.0001). The results have significant implications for elimination. An increasing focus on elimination requires a review of priorities within the VL control agenda. The development of systematic implementation of con­trol programs based on identified risk factors (such as monitoring of asymptomatically infected individuals) has a high transmission-blocking potential.

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.