Game-Theoretically Allocating Resources to Catch Evaders and Payments to Stabilize Teams

Allocating resources optimally is a nontrivial task, especially when multiple

self-interested agents with conflicting goals are involved. This dissertation

uses techniques from game theory to study two classes of such problems:

allocating resources to catch agents that attempt to evade them, and allocating

payments to agents in a team in order to stabilize it. Besides discussing what

allocations are optimal from various game-theoretic perspectives, we also study

how to efficiently compute them, and if no such algorithms are found, what

computational hardness results can be proved.

The first class of problems is inspired by real-world applications such as the

TOEFL iBT test, course final exams, driver's license tests, and airport security

patrols. We call them test games and security games. This dissertation first

studies test games separately, and then proposes a framework of Catcher-Evader

games (CE games) that generalizes both test games and security games. We show

that the optimal test strategy can be efficiently computed for scored test

games, but it is hard to compute for many binary test games. Optimal Stackelberg

strategies are hard to compute for CE games, but we give an empirically

efficient algorithm for computing their Nash equilibria. We also prove that the

Nash equilibria of a CE game are interchangeable.

The second class of problems involves how to split a reward that is collectively

obtained by a team. For example, how should a startup distribute its shares, and

what salary should an enterprise pay to its employees. Several stability-based

solution concepts in cooperative game theory, such as the core, the least core,

and the nucleolus, are well suited to this purpose when the goal is to avoid

coalitions of agents breaking off. We show that some of these solution concepts

can be justified as the most stable payments under noise. Moreover, by adjusting

the noise models (to be arguably more realistic), we obtain new solution

concepts including the partial nucleolus, the multiplicative least core, and the

multiplicative nucleolus. We then study the computational complexity of those

solution concepts under the constraint of superadditivity. Our result is based

on what we call Small-Issues-Large-Team games and it applies to popular

representation schemes such as MC-nets.

Standardizing clinical trials workflow representation in UML for international site comparison.

BACKGROUND: With the globalization of clinical trials, a growing emphasis has been placed on the standardization of the workflow in order to ensure the reproducibility and reliability of the overall trial. Despite the importance of workflow evaluation, to our knowledge no previous studies have attempted to adapt existing modeling languages to standardize the representation of clinical trials. Unified Modeling Language (UML) is a computational language that can be used to model operational workflow, and a UML profile can be developed to standardize UML models within a given domain. This paper's objective is to develop a UML profile to extend the UML Activity Diagram schema into the clinical trials domain, defining a standard representation for clinical trial workflow diagrams in UML. METHODS: Two Brazilian clinical trial sites in rheumatology and oncology were examined to model their workflow and collect time-motion data. UML modeling was conducted in Eclipse, and a UML profile was developed to incorporate information used in discrete event simulation software. RESULTS: Ethnographic observation revealed bottlenecks in workflow: these included tasks requiring full commitment of CRCs, transferring notes from paper to computers, deviations from standard operating procedures, and conflicts between different IT systems. Time-motion analysis revealed that nurses' activities took up the most time in the workflow and contained a high frequency of shorter duration activities. Administrative assistants performed more activities near the beginning and end of the workflow. Overall, clinical trial tasks had a greater frequency than clinic routines or other general activities. CONCLUSIONS: This paper describes a method for modeling clinical trial workflow in UML and standardizing these workflow diagrams through a UML profile. In the increasingly global environment of clinical trials, the standardization of workflow modeling is a necessary precursor to conducting a comparative analysis of international clinical trials workflows.

The impact of structured support groups for pregnant South African women recently diagnosed HIV positive.

The authors of this study evaluated a structured 10-session psychosocial support group intervention for newly HIV-diagnosed pregnant South African women. Participants were expected to display increases in HIV disclosure, self-esteem, active coping and positive social support, and decreases in depression, avoidant coping, and negative social support. Three hundred sixty-one pregnant HIV-infected women were recruited from four antenatal clinics in Tshwane townships from April 2005 to September 2006. Using a quasi-experimental design, assessments were conducted at baseline and two and eight months post-intervention. A series of random effects regression analyses were conducted, with the three assessment points treated as a random effect of time. At both follow-ups, the rate of disclosure in the intervention group was significantly higher than that of the comparison group (p<0.001). Compared to the comparison group at the first follow-up, the intervention group displayed higher levels of active coping (t=2.68, p<0.05) and lower levels of avoidant coping (t=-2.02, p<0.05), and those who attended at least half of the intervention sessions exhibited improved self-esteem (t=2.11, p<0.05). Group interventions tailored for newly HIV positive pregnant women, implemented in resource-limited settings, may accelerate the process of adjusting to one's HIV status, but may not have sustainable benefits over time.

The Representation of Emotion in Autonomic and Central Nervous System Activity

Phenomenologically, humans effectively label and report feeling distinct emotions, yet the extent to which emotions are represented categorically in nervous system activity is controversial. Theoretical accounts differ in this regard, some positing distinct emotional experiences emerge from a dimensional representation (e.g., along axes of valence and arousal) whereas others propose emotions are natural categories, with dedicated neural bases and associated response profiles. This dissertation aims to empirically assess these theoretical accounts by examining how emotions are represented (either as disjoint categories or as points along continuous dimensions) in autonomic and central nervous system activity by integrating psychophysiological recording and functional neuroimaging with machine-learning based analytical methods. Results demonstrate that experientially, emotional events are well-characterized both along dimensional and categorical frameworks. Measures of central and peripheral responding discriminate among emotion categories, but are largely independent of valence and arousal. These findings suggest dimensional and categorical aspects of emotional experience are driven by separable neural substrates and demonstrate that emotional states can be objectively quantified on the basis of nervous system activity.

Electrostatic Energetics of Bacillus subtilis Ribonuclease P Protein Determined by Nuclear Magnetic Resonance-Based Histidine pKa Measurements.

The pKa values of ionizable groups in proteins report the free energy of site-specific proton binding and provide a direct means of studying pH-dependent stability. We measured histidine pKa values (H3, H22, and H105) in the unfolded (U), intermediate (I), and sulfate-bound folded (F) states of RNase P protein, using an efficient and accurate nuclear magnetic resonance-monitored titration approach that utilizes internal reference compounds and a parametric fitting method. The three histidines in the sulfate-bound folded protein have pKa values depressed by 0.21 ± 0.01, 0.49 ± 0.01, and 1.00 ± 0.01 units, respectively, relative to that of the model compound N-acetyl-l-histidine methylamide. In the unliganded and unfolded protein, the pKa values are depressed relative to that of the model compound by 0.73 ± 0.02, 0.45 ± 0.02, and 0.68 ± 0.02 units, respectively. Above pH 5.5, H22 displays a separate resonance, which we have assigned to I, whose apparent pKa value is depressed by 1.03 ± 0.25 units, which is ∼0.5 units more than in either U or F. The depressed pKa values we observe are consistent with repulsive interactions between protonated histidine side chains and the net positive charge of the protein. However, the pKa differences between F and U are small for all three histidines, and they have little ionic strength dependence in F. Taken together, these observations suggest that unfavorable electrostatics alone do not account for the fact that RNase P protein is intrinsically unfolded in the absence of ligand. Multiple factors encoded in the P protein sequence account for its IUP property, which may play an important role in its function.

Evaluating the Impact of the Positive Choices Intervention on Substance Use, Psychological, and Care Engagement Outcomes Relevant to Current National HIV Prevention Goals

The HIV epidemic in the United States continues to be a significant public health problem, with approximately 50,000 new infections occurring each year. National public health priorities have shifted in recent years towards targeted HIV prevention efforts among people living with HIV/AIDS (PLWHA) that include: increasing engagement in and retention in care, improving HIV treatment adherence, and increasing screening for and treatment of substance use and psychological difficulties. This study evaluated the efficacy of Positive Choices (PC), a brief, care-based, theory-driven, 3-session counseling intervention for newly HIV-diagnosed men who have sex with men (MSM), in the context of current national HIV prevention priorities. The study involved secondary analysis of data from a preliminary efficacy trial of the PC intervention (n=102). Descriptive statistics examined baseline substance use, psychological characteristics and strategies, and care engagement and HIV-related biological outcomes. Generalized Estimating Equations (GEE) examined longitudinal changes in these variables by study condition. Results indicated that PC improved adherence to HIV treatment, but increased use of illicit drugs, specifically amyl nitrates and other stimulant drugs; additionally, moderation analyses indicated differences in patterns of change over time in viral load by baseline depression status. Implications of the findings and suggestions for future research are discussed.

Role of Hydrological Process Representation on Erosion, Deposition, and Sediment Yield Estimate

Soil erosion by water is a major driven force causing land degradation. Laboratory experiments, on-site field study, and suspended sediments measurements were major fundamental approaches to study the mechanisms of soil water erosion and to quantify the erosive losses during rain events. The experimental research faces the challenge to extent the result to a wider spatial scale. Soil water erosion modeling provides possible solutions for scaling problems in erosion research, and is of principal importance to better understanding the governing processes of water erosion. However, soil water erosion models were considered to have limited value in practice. Uncertainties in hydrological simulations are among the reasons that hindering the development of water erosion model. Hydrological models gained substantial improvement recently and several water erosion models took advantages of the improvement of hydrological models. It is crucial to know the impact of changes in hydrological processes modeling on soil erosion simulation.

This dissertation work first created an erosion modeling tool (GEOtopSed) that takes advantage of the comprehensive hydrological model (GEOtop). The newly created tool was then tested and evaluated at an experimental watershed. The GEOtopSed model showed its ability to estimate multi-year soil erosion rate with varied hydrological conditions. To investigate the impact of different hydrological representations on soil erosion simulation, a 11-year simulation experiment was conducted for six models with varied configurations. The results were compared at varied temporal and spatial scales to highlight the roles of hydrological feedbacks on erosion. Models with simplified hydrological representations showed agreement with GEOtopSed model on long temporal scale (longer than annual). This result led to an investigation for erosion simulation at different rainfall regimes to check whether models with different hydrological representations have agreement on the soil water erosion responses to the changing climate. Multi-year ensemble simulations with different extreme precipitation scenarios were conducted at seven climate regions. The differences in erosion simulation results showed the influences of hydrological feedbacks which cannot be seen by purely rainfall erosivity method.

Screening for Sexual Trauma, Intimate Partner Violence and Mental Health Symptoms among HIV Positive South African Women

Background: The psychological sequelae of sexual trauma and physical intimate partner violence (IPV) exposure can lead to poor HIV care outcomes, including poor treatment adherence. This study aimed to estimate the prevalence of and factors associated with mental health symptoms and trauma among HIV positive women. Additionally, the study aimed to assess the feasibility and acceptability of screening for trauma and mental health symptoms among HIV positive South African women. Finally, the study aimed to elicit healthcare workers’ perceptions related to sexual trauma and the provision of care and services for HIV positive women with trauma histories.

Methods: The study utilized a mixed-methods approach that included a cross-sectional survey of 70 HIV positive women recruited through referral sampling and key informant interviews with seven healthcare workers (HCWs). A study-screening instrument consisting of 24 items from standard measures was used to screen women for sexual trauma, physical intimate partner violence (IPV), depression and PTSD. Sexual trauma and IPV were assessed across the lifetime, while depression and PTSD were current assessments. Logistic regression models were used to explore the relationship between trauma exposure and mental health symptoms, while controlling for age and education. Interview transcripts were coded and analyzed for emergent themes on HCWs perceptions on sexual trauma and HIV care.

Results: Among participants, 51% had sexual trauma experience and 75% had intimate partner violence (IPV) experience. Among participants, 36% met screening criteria for major depression; among those with traumatic experiences (n=57), 70% met screening criteria for post-traumatic stress disorder (PTSD). Compared to having no sexual trauma or IPV exposure, having both sexual trauma and IPV was significantly associated with higher odds of depression (OR = 8.11; 95% CI 1.48-44.34), while having either IPV or sexual trauma individually was not significantly associated with increased odds of depression. Compared to having either IPV or sexual trauma, having both sexual trauma and IPV was not significantly associated with PTSD. Responses from participants’ feedback on screening process suggest that screening was feasible and acceptable to participants. Some of the health care workers (HCWs) did not perceive dealing with trauma to be part of their duties, but instead viewed social workers or psychologists as the appropriate health cadre to provide care related to trauma and mental health.

Conclusions: High levels of sexual trauma, IPV and mental health distress were reported among HIV positive women in this setting. Screening for trauma and mental health symptoms was acceptable to the participants, but several challenges were encountered in implementing screening. Given the potential impact of trauma and mental health on HIV care engagement, interventions to address trauma and its psychological sequelae are needed.

Cervical cancer precursors and hormonal contraceptive use in HIV-positive women: application of a causal model and semi-parametric estimation methods.

OBJECTIVE: To demonstrate the application of causal inference methods to observational data in the obstetrics and gynecology field, particularly causal modeling and semi-parametric estimation. BACKGROUND: Human immunodeficiency virus (HIV)-positive women are at increased risk for cervical cancer and its treatable precursors. Determining whether potential risk factors such as hormonal contraception are true causes is critical for informing public health strategies as longevity increases among HIV-positive women in developing countries. METHODS: We developed a causal model of the factors related to combined oral contraceptive (COC) use and cervical intraepithelial neoplasia 2 or greater (CIN2+) and modified the model to fit the observed data, drawn from women in a cervical cancer screening program at HIV clinics in Kenya. Assumptions required for substantiation of a causal relationship were assessed. We estimated the population-level association using semi-parametric methods: g-computation, inverse probability of treatment weighting, and targeted maximum likelihood estimation. RESULTS: We identified 2 plausible causal paths from COC use to CIN2+: via HPV infection and via increased disease progression. Study data enabled estimation of the latter only with strong assumptions of no unmeasured confounding. Of 2,519 women under 50 screened per protocol, 219 (8.7%) were diagnosed with CIN2+. Marginal modeling suggested a 2.9% (95% confidence interval 0.1%, 6.9%) increase in prevalence of CIN2+ if all women under 50 were exposed to COC; the significance of this association was sensitive to method of estimation and exposure misclassification. CONCLUSION: Use of causal modeling enabled clear representation of the causal relationship of interest and the assumptions required to estimate that relationship from the observed data. Semi-parametric estimation methods provided flexibility and reduced reliance on correct model form. Although selected results suggest an increased prevalence of CIN2+ associated with COC, evidence is insufficient to conclude causality. Priority areas for future studies to better satisfy causal criteria are identified.