Sexually transmitted diseases affect millions of lives every year. In order to most effectively use prevention resources epidemiologists deploy models to understand how the disease spreads through the population and which intervention methods will be most effective at reducing disease perpetuation. Increasingly agent-based models are being used to simulate population heterogeneity and fine-grain sociological effects that are difficult to capture with traditional compartmental and statistical models. A key challenge is using a sufficiently large number of agents to produce robust and reliable results while also running in a reasonable amount of time. In this thesis we show the effectiveness of agent-based modeling in planning coordinated responses to a sexually transmitted disease epidemic and present efficient algorithms for running these models in parallel and in a distributed setting. The model is able to account for population heterogeneity like age preference, concurrent partnership, and coital dilution, and the implementation scales well to large population sizes to produce robust results in a reasonable amount of time. The work helps epidemiologists and public health officials plan a targeted and well-informed response to a variety of epidemic scenarios.

Transdisciplinary food systems research aims to merge insights from multiple fields, often revealing confounding, complex interactions. Computational modeling offers a means to discover patterns and formulate novel solutions to such systems-level problems. The best models serve as hubs—or boundary objects—which ground and unify a collaborative, iterative, and transdisciplinary process of stakeholder engagement. This dissertation demonstrates the application of agent-based modeling, network analytics, and evolutionary computational optimization to the pressing food systems problem areas of livestock epidemiology and global food security. It is comprised of a methodological introduction, an executive summary, three journal-article formatted chapters, and an overarching discussion section. Chapter One employs an agent-based computer model (RUSH-PNBM v.1.1) developed to study the potential impact of the trend toward increased producer specialization on resilience to catastrophic epidemics within livestock production chains. In each run, an infection is introduced and may spread according to probabilities associated with the various modes of contact between hog producer, feed mill, and slaughter plant agents. Experimental data reveal that more-specialized systems are vulnerable to outbreaks at lower spatial densities, have more abrupt percolation transitions, and are characterized by less-predictable outcomes; suggesting that reworking network structures may represent a viable means to increase biosecurity. Chapter Two uses a calibrated, spatially-explicit version of RUSH-PNBM (v.1.2) to model the hog production chains within three U.S. states. Key metrics are calculated after each run, some of which pertain to overall network structures, while others describe each actor’s positionality within the network. A genetic programming algorithm is then employed to search for mathematical relationships between multiple individual indicators that effectively predict each node’s vulnerability. This “meta-metric” approach could be applied to aid livestock epidemiologists in the targeting of biosecurity interventions and may also be useful to study a wide range of complex network phenomena. Chapter Three focuses on food insecurity resulting from the projected gap between global food supply and demand over the coming decades. While no single solution has been identified, scholars suggest that investments into multiple interventions may stack together to solve the problem. However, formulating an effective plan of action requires knowledge about the level of change resulting from a given investment into each wedge, the time before that effect unfolds, the expected baseline change, and the maximum possible level of change. This chapter details an evolutionary-computational algorithm to optimize investment schedules according to the twin goals of maximizing global food security and minimizing cost. Future work will involve parameterizing the model through an expert informant advisory process to develop the existing framework into a practicable food policy decision-support tool.

Healthcare associated infections are a considerable burden to the health care system. The affected patients have their prognosis worsened and demand more resources from hospitals. Furthermore, the bacteria causing these infections are becoming increasingly resistant to antibiotics while also becoming more deadly and contagious. Contributing with knowledge for stopping these infections is, therefore, important. This thesis reports on two projects centered on data collected at the University of Iowa Hospital and Clinics. The first project consisted in analyzing data collected by sensors that reported the location and hand washing behavior of health care workers. After extracting meaning from these radio signals, I studied two socially and epidemiologically relevant tasks: the inference of contact networks, which can be used to study the spread of infections in the hospital, and the study of associations between social pressure and hand washing, learning that effectively workers in proximity to others wash their hands more, but also that not all workers are as influential. In the second project, I developed a data mining method for analyzing medical records aimed at tackling the problems of class imbalance and high dimensionality, and applied it to predicting Clostridium Difficile infection. The learnt models performed better than the state of the art and even improved prediction as the onset of symptoms approached. The main contribution, however, was in the information discovered: certain events in certain orders increased the risk of developing the infection, suggesting that reversing these orders could improve prognosis.

Many human papilloma virus (HPV) types are sexually transmitted and HPV DNA types 16, 18, 31, and 45 account for more than 75% if all cervical dysplasia. Candidate vaccines are successfully completing US Federal Drug Agency (FDA) phase III testing and several drug companies are in licensing arbitration. Once this vaccine become available it is unlikely that 100% vaccination coverage will be probable; hence, the need for vaccination strategies that will have the greatest reduction on the endemic prevalence of HPV. This thesis introduces two discrete-time models for evaluating the effect of demographic-biased vaccination strategies: one model incorporates temporal demographics (i.e., age) in population compartments; the other non-temporal demographics (i.e., race, ethnicity). Also presented is an intuitive Web-based interface that was developed to allow the user to evaluate the effects on prevalence of a demographic-biased intervention by tailoring the model parameters to specific demographics and geographical region.

Epidemiologists engage in the study of the distribution and determinants of health-related states or events in human populations. Eventually, they will apply that study to prevent and control problems and contingencies associated with the health of the population. Due to the spread of new pathogens and the emergence of new bio-terrorism threats, it has become imperative to develop new and expand existing techniques to equip public health providers with robust tools to predict and control health-related crises. In this dissertation, I explore the effects caused in the disease dynamics by the differences in individuals’ physiology and social/behavioral characteristics. Multiple computational and mathematical models were developed to quantify the effect of those factors on spatial and temporal variations of the disease epidemics. I developed statistical methods to measure the effects caused in the outbreak dynamics by the incorporation of heterogeneous demographics and social interactions to the individuals of the population. Specifically, I studied the relationship between demographics and the physiological characteristics of an individual when preparing for an infectious disease epidemic.

Agent-based epidemic simulation (ABES) is a powerful and realistic approach for studying the impacts of disease dynamics and complex interventions on the spread of an infection in the population. Among many ABES systems, EpiSimdemics comes closest to the popular agent-based epidemic simulation systems developed by Eubank, Longini, Ferguson, and Parker. EpiSimdemics is a general framework that can model many reaction-diffusion processes besides the Susceptible-Exposed-Infectious-Recovered (SEIR) models. This model allows the study of complex systems as they interact, thus enabling researchers to model and observe the socio-technical trends and forces. Pandemic planning at the world level requires simulation of over 6 billion agents, where each agent has a unique set of demographics, daily activities, and behaviors. Moreover, the stochastic nature of epidemic models, the uncertainty in the initial conditions, and the variability of reactions require the computation of several replicates of a simulation for a meaningful study. Given the hard timelines to respond, running many replicates (15-25) of several configurations (10-100) (of these compute-heavy simulations) can only be possible on high-performance clusters (HPC). These agent-based epidemic simulations are irregular and show poor execution performance on high-performance clusters due to the evolutionary nature of their workload, large irregular communication and load imbalance. For increased utilization of HPC clusters, the simulation needs to be scalable. Many challenges arise when improving the performance of agent-based epidemic simulations on high-performance clusters. Firstly, large-scale graph-structured computation is central to the processing of these simulations, where the star-motif quality nodes (natural graphs) create large computational imbalances and communication hotspots. Secondly, the computation is performed by classes of tasks that are separated by global synchronization. The non-overlapping computations cause idle times, which introduce the load balancing and cost estimation challenges. Thirdly, the computation is overlapped with communication, which is difficult to measure using simple methods, thus making the cost estimation very challenging. Finally, the simulations are iterative and the workload (computation and communication) may change through iterations, as a result introducing load imbalances. This dissertation focuses on developing a cost estimation model and load balancing schemes to increase the runtime efficiency of agent-based epidemic simulations on high-performance clusters. While developing the cost model and load balancing schemes, we perform the static and dynamic load analysis of such simulations. We also statically quantified the computational and communication workloads in EpiSimdemics. We designed, developed and evaluated a cost model for estimating the execution cost of large-scale parallel agent-based epidemic simulations (and more generally for all constrained producer-consumer parallel algorithms). This cost model uses computational imbalances and communication latencies, and enables the cost estimation of those applications where the computation is performed by classes of tasks, separated by synchronization. It enables the performance analysis of parallel applications by computing its execution times on a number of partitions. Our evaluations show that the model is helpful in performance prediction, resource allocation and evaluation of load balancing schemes. As part of load balancing algorithms, we adopted the Metis library for partitioning bipartite graphs. We have also developed lower-overhead custom schemes called Colocation and MetColoc. We performed an evaluation of Metis, Colocation, and MetColoc. Our analysis showed that the MetColoc schemes gives a performance similar to Metis, but with half the partitioning overhead (runtime and memory). On the other hand, the Colocation scheme achieves a similar performance to Metis on a larger number of partitions, but at extremely lower partitioning overhead. Moreover, the memory requirements of Colocation scheme does not increase as we create more partitions. We have also performed the dynamic load analysis of agent-based epidemic simulations. For this, we studied the individual and joint effects of three disease parameter (transmissiblity, infection period and incubation period). We quantified the effects using an analytical equation with separate constants for SIS, SIR and SI disease models. The metric that we have developed in this work is useful for cost estimation of constrained producer-consumer algorithms, however, it has some limitations. The applicability of the metric is application, machine and data-specific. In the future, we plan to extend the metric to increase its applicability to a larger set of machine architectures, applications, and datasets. / Ph. D.

Most epidemiological systems described in the literature are built for evaluation and analysis of specific diseases, such as Influenza-like-illness. The modeling environments that support these systems are implemented for specific diseases and epidemiological models. Hence they are not reusable or extendable. This thesis focuses on the design and development of an integrated analytical environment with flexible data integration methodologies and multi-level web services for evaluation and forecasting of various epidemics in different regions of the world. The environment supports analysis of epidemics based on any combination of disease, surveillance sources, epidemiological models, geographic regions and demographic factors. The environment also supports evaluation and forecasting of epidemics when various policy-level and behavioral interventions are applied, that may inhibit the spread of an epidemic. First, we describe data integration methodologies and schema design, for flexible experiment design, storage and query retrieval mechanisms related to large scale epidemic data. We describe novel techniques for data transformation, optimization, pre-computation and automation that enable flexibility, extendibility and efficiency required in different categories of query processing. Second, we describe the design and engineering of adaptable middleware platforms based on service-oriented paradigms for interactive workflow, communication, and decoupled integration. This supports large-scale multi-user applications with provision for online analysis of interventions as well as analytical processing of forecast computations. Using a service-oriented architecture, we have provided a platform-as-a-service representation for evaluation and forecasting of epidemics. We demonstrate the applicability of our integrated environment through development of the applications, DISIMS and EpiCaster. DISIMS is an interactive web-based system for evaluating the effects of dynamic intervention strategies on epidemic propagation. EpiCaster is a situation assessment and forecasting tool for projecting the state of evolving epidemics such as flu and Ebola in different regions of the world. We discuss how our platform uses existing technologies to solve a novel problem in epidemiology, and provides a unique solution on which different applications can be built for analyzing epidemic containment strategies. / Ph. D.

Modeling and predicting multivariate time series data has been of prime interest to researchers for many decades. Traditionally, time series prediction models have focused on finding attributes that have consistent correlations with target variable(s). However, diverse surrogate signals, such as News data and Twitter chatter, are increasingly available which can provide real-time information albeit with inconsistent correlations. Intelligent use of such sources can lead to early and real-time warning systems such as Google Flu Trends. Furthermore, the target variables of interest, such as public heath surveillance, can be noisy. Thus models built for such data sources should be flexible as well as adaptable to changing correlation patterns. In this thesis we explore various methods of using surrogates to generate more reliable and timely forecasts for noisy target signals. We primarily investigate three key components of the forecasting problem viz. (i) short-term forecasting where surrogates can be employed in a now-casting framework, (ii) long-term forecasting problem where surrogates acts as forcing parameters to model system dynamics and, (iii) robust drift models that detect and exploit 'changepoints' in surrogate-target relationship to produce robust models. We explore various 'physical' and 'social' surrogate sources to study these sub-problems, primarily to generate real-time forecasts for endemic diseases. On modeling side, we employed matrix factorization and generalized linear models to detect short-term trends and explored various Bayesian sequential analysis methods to model long-term effects. Our research indicates that, in general, a combination of surrogates can lead to more robust models. Interestingly, our findings indicate that under specific scenarios, particular surrogates can decrease overall forecasting accuracy - thus providing an argument towards the use of 'Good data' against 'Big data'. / Ph. D.

Publicly available datasets in health science are often large and observational, in contrast to experimental datasets where a small number of data are collected in controlled experiments. Variables' causal relationships in the observational dataset are yet to be determined. However, there is a significant interest in health science to discover and analyze causal relationships from health data since identified causal relationships will greatly facilitate medical professionals to prevent diseases or to mitigate the negative effects of the disease. Recent advances in Computer Science, particularly in Bayesian networks, has initiated a renewed interest for causality research. Causal relationships can be possibly discovered through learning the network structures from data. However, the number of candidate graphs grows in a more than exponential rate with the increase of variables. Exact learning for obtaining the optimal structure is thus computationally infeasible in practice. As a result, heuristic approaches are imperative to alleviate the difficulty of computations. This research provides effective and efficient learning tools for local causal discoveries and novel methods of learning causal structures with a combination of background knowledge. Specifically in the direction of constraint based structural learning, polynomial-time algorithms for constructing causal structures are designed with first-order conditional independence. Algorithms of efficiently discovering non-causal factors are developed and proved. In addition, when the background knowledge is partially known, methods of graph decomposition are provided so as to reduce the number of conditioned variables. Experiments on both synthetic data and real epidemiological data indicate the provided methods are applicable to large-scale datasets and scalable for causal analysis in health data. Followed by the research methods and experiments, this dissertation gives thoughtful discussions on the reliability of causal discoveries computational health science research, complexity, and implications in health science research.

Abstract Probabilistic reasoning under uncertainty suits well to analysis of disease dynamics. The stochastic nature of disease progression is modeled by applying the principles of Bayesian learning. Bayesian learning predicts the disease progression, including prevalence and incidence, for a geographic region and demographic composition. Public health resources, prioritized by the order of risk levels of the population, will efficiently minimize the disease spread and curtail the epidemic at the earliest. A Bayesian network representing the outbreak of influenza and pneumonia in a geographic region is ported to a newer region with different demographic composition. Upon analysis for the newer region, the corresponding prevalence of influenza and pneumonia among the different demographic subgroups is inferred for the newer region. Bayesian reasoning coupled with disease timeline is used to reverse engineer an influenza outbreak for a given geographic and demographic setting. The temporal flow of the epidemic among the different sections of the population is analyzed to identify the corresponding risk levels. In comparison to spread vaccination, prioritizing the limited vaccination resources to the higher risk groups results in relatively lower influenza prevalence. HIV incidence in Texas from 1989-2002 is analyzed using demographic based epidemic curves. Dynamic Bayesian networks are integrated with probability distributions of HIV surveillance data coupled with the census population data to estimate the proportion of HIV incidence among the different demographic subgroups. Demographic based risk analysis lends to observation of varied spectrum of HIV risk among the different demographic subgroups. A methodology using hidden Markov models is introduced that enables to investigate the impact of social behavioral interactions in the incidence and prevalence of infectious diseases. The methodology is presented in the context of simulated disease outbreak data for influenza. Probabilistic reasoning analysis enhances the understanding of disease progression in order to identify the critical points of surveillance, control and prevention. Public health resources, prioritized by the order of risk levels of the population, will efficiently minimize the disease spread and curtail the epidemic at the earliest.