Doctor of Philosophy / Department of Sociology, Anthropology, and Social Work / Robert Schaeffer / World-system theorist Immanuel Wallerstein made two theoretical assertions in Historical Capitalism that (a) significant inequalities in the “margin of safety against…endemic dangers and erratic violence” for people in different zones of the world economy persisted over long periods of time and (b) that the “margin of safety” for people in the periphery has actually deteriorated. This study set out to test this theory by examining mortality data for countries in different zones of the world-economy. It identified a set of health-related proxies for “endemic dangers and erratic violence”, infectious diseases (malaria, polio, tuberculosis, and influenza), chronic diseases (cancer, diabetes, and cardiovascular), erratic violence (homicide, suicide, and motor vehicle accidents), and also infant mortality and life expectancy for women and men. It gathered data from the United Nations Statistical Division’s Demographic Yearbook for a select sample of countries in different zones of the world-economy (core, semiperiphery, and periphery) from 1950 to 2010, and examined how mortality from these dangers changed during this period. This study found that mortality data for infectious diseases did not provide much support for Wallerstein’s theoretical assertions. But the mortality data for chronic disease and erratic violence provided strong support for Wallerstein’s assertions. The data on life span provided some support for Wallerstein’s first assertion, but not for his second. Overall, the findings generally support Wallerstein’s theories and suggest ways that health-related inequalities might be addressed.

Master of Science / Department of Anatomy & Physiology / Deryl L. Troyer / Breast cancer ranks second as a cause of cancer death in women in the USA. Detection of early tumors and tumor-targeted treatments could decrease the problems associated with breast cancer management. Photodynamic therapy (PDT) is a cancer treatment that uses a photosensitizer and a specific wavelength of light and is currently in clinical trials for breast cancer. When tumor cells which have absorbed photosensitizer are exposed to the correct wavelength of light, reactive oxygen species are generated, resulting in tumor cell death. Poor tissue penetration of light is a major limitation in PDT, restricting its use to treatment of localized tumors. Light generation at the tumor area might increase the effectiveness of PDT. Polymorphonuclear neutrophils (PMNs) are known to often infiltrate breast adenocarcinoma, and their activatation in tumor stroma produces luminescence in the presence of luminol. Here, we hypothesized that luminol can be used as a theranostic agent for luminescence-based early tumor detection (diagnosis) and in situ PDT (treatment). BALB/c mice were transplanted with 4T1 mammary adenocarcinoma cells to establish a breast adenocarcinoma model. The early tumor detection objective was tested by daily intraperitoneal injection of luminol and in vivo luminescence imaging. To test the PDT treatment objective,the photosensitizer 5-aminolevulinic acid (ALA) and luminol were administered to mice through intraperitoneal and intravenous routes, respectively. This treatment regimen was repeated six times and ALA alone/luminol alone/saline treated tumor-bearing mice were used as controls. Results demonstrated that luminol allowed detection of activated PMNs only two days after 4T1 cell transplantation, even though tumors were not yet palpable. Relative differences in the increase of tumor volume and final tumor weights were analyzed to test the in situ PDT. Analysis of the data showed luminol treatments resulted in breast adenocarcinoma tumor growth attenuation. In conclusion this study provides evidence that luminol can be a theranostic agent for breast adenocarcinoma.

Master of Science / Department of Kinesiology / Timothy I. Musch / Chronic heart failure (CHF) reduces nitric oxide (NO) bioavailability and impairs skeletal muscle vascular control during exercise. Reduction of nitrite (NO[subscript]2-) to NO may impact exercise-induced hyperemia particularly in muscles with pathologically-reduced O[subscript]2 delivery. We tested the hypothesis that NO[subscript]2- infusion would increase exercising skeletal muscle blood flow (BF) and vascular conductance (VC) in CHF rats with a preferential effect in muscles composed primarily of type IIb+IId/x fibers. CHF (coronary artery ligation) was induced in adult male, Sprague-Dawley rats. Following a >21 day recovery, mean arterial pressure (MAP, carotid artery catheter) and skeletal muscle BF (radiolabelled microspheres) were measured during treadmill exercise (20 m•min[superscript]-1, 5% incline) with and without NO[subscript]2- infusion. The myocardial infarct size (35 ± 3%) indicated moderate CHF. NO[subscript]2- infusion increased total hindlimb skeletal muscle VC (CHF: 0.85 ± 0.09, CHF+NO[subscript]2-: 0.93 ± 0.09 ml•min[superscript]-1•100g[superscript]-1•mmHg[superscript]-1, p<0.05) without changing MAP (CHF: 123 ± 4 mmHg, CHF+NO[subscript]2-: 120 ± 4 mmHg, p=0.17). Total hindlimb skeletal muscle BF was not significantly different (CHF: 102 ± 7, CHF+NO[subscript]2-: 109 ± 7 ml•min[superscript]-1•100g[superscript]-1, p>0.05). BF increased in 6 (~21%) and VC in 8 (~29%) of the 28 individual muscles and muscle parts. Muscles and muscle portions exhibiting greater BF and VC following NO[subscript]2- infusion were comprised of ≥63% type IIb+IId/x muscle fibers. These data demonstrate that NO[subscript]2- infusion can augment skeletal muscle vascular control during exercise in CHF rats. Given the targeted effects shown herein, a NO[subscript]2[superscript]--based therapy may provide an attractive “needs-based” approach for treatment of the vascular dysfunction in CHF.

Master of Science / Department of Psychology / Gary L. Brase / In 2006, the Center for Disease Control and Prevention recommended the revision of state HIV testing laws. With these recommendations, more low-risk individuals are tested regardless of their risk group. However, there is a greater chance of a false positive test result for low-risk individuals than for high-risk individuals. Additionally, previous research found that doctors and HIV counselors in Germany did not accurately communicate the relationship between risk factors and false positive tests (Gigerenzer, Hoffrage, & Ebert, 1998). This study aimed to (1) compare the findings of the 1998 German sample to HIV hotline counselors in the United States in 2011; and (2) to investigate the ability of students to calculate the conditional probability of HIV for a low-risk individual after receiving a positive test, based on idealized transcripts of conversations with HIV hotline counselors. The first study found that HIV hotline counselors use both verbal expressions of risk and percentages to communicate HIV testing statistics. Additionally, 2011 American counselors were more aware of the chance of false positives and false negatives than compared to the 1998 German sample. However, no 2011 American counselors were able to provide an accurate positive predictive value for a low-risk woman. The second study found low performance among students in the calculation of the positive predictive value. Performance was facilitated by a natural frequency format for high numerate individuals. There were different patterns of results for the General Numeracy Scale and the Subjective Numeracy Scale. This would suggest that these two scales might be measuring different constructs. These findings are consistent with the two theories supporting the Frequency Effect, namely the Frequentist Hypothesis and the Nested Sets Hypothesis. Additionally, this research suggests computation of the conditional risk of HIV is facilitated by a natural frequency format. Teaching techniques have been developed and demonstrate long lasting improvement in health related computations. If a few hours of training is all that it takes to communicate these life and death statistics in a manner that is consistent with reasoning, health practitioners and students should be required to have more education in communicating and computing probabilities.

Master of Science / School of Journalism and Mass Communications / Nancy Muturi / This study was an examination of the determinants of disordered eating development among female collegiate distance runners. More specifically, the study examined the impact of thinness-emphasizing and thinness-promoting messages disseminated by mass media and running-specific media, and how those messages affected disordered eating among a sample of female collegiate distance runners. It also examines current female collegiate distance runners’ attitudes toward disordered eating, subjective norms from referent individuals close to female collegiate distance runners regarding disordered eating, and female collegiate distance runners’ perceived behavioral control regarding disordered eating—which was divided into various internal and external control factors either inhibiting or facilitating disordered eating among them. The study was qualitative in nature and assumed a multi-method approach. It included an online, anonymous, self-administered questionnaire among 166 current NCAA Division I female distance runners; four small, confidential focus groups with current NCAA Division I female distance runners from four different teams; and 16 in-depth interviews with professional distance runners, dietitians, coaches, physicians, and sports psychologists. The study sought to answer four research questions—each based on an element of the study’s guiding theory, the theory of planned behavior (Ajzen, 1991). Overall, the study found media messages, attitudes, subjective norms, and various internal and external control factors all facilitated disordered eating among NCAA Division I female distance runners. Based upon these findings, the study offers recommendations for practitioners in the field of health communication, coaches, academic institutions with cross country and track teams, and female collegiate distance runners.

Master of Science / Department of Computing and Information Sciences / John Hatcliff / Medical devices are safety-critical systems whose failure may put human life in danger. They are becoming more advanced and thus more complex. This leads to bigger and more complicated code-bases that are hard to maintain and verify. Model-driven development provides high-level and abstract description of the system in the form of models that omit details, which are not relevant during the design phase. This allows for certain types of verification and hazard analysis to be performed on the models. These models can then be translated into code. However, errors that do not exist in the models may be introduced during the implementation phase. Automated translation from verified models to code may prevent to some extent. This thesis proposes approach for model-driven development and verification of medical devices. Models are created in AADL (Architecture Analysis & Design Language), a language for software and hardware architecture modeling. AADL models are translated to SPARK Ada, contract-based programming language, which is suitable for software verification. Generated code base is further extended by developers to implement internals of specific devices. Created programs can be verified using SPARK tools. A PCA (Patient Controlled Analgesia) pump medical device is used to illustrate the primary artifacts and process steps. The foundation for this work is "Integrated Clinical Environment Patient-Controlled Analgesia Infusion Pump System Requirements" document and AADL Models created by Brian Larson. In addition to proposed model-driven development approach, a PCA pump prototype was created using the BeagleBoard-xM device as a platform. Some components of PCA pump prototype were verified by SPARK tools and Bakar Kiasan.

Master of Public Health / Human Nutrition / Richard R. Rosenkranz / Background: Type 2 diabetes mellitus (T2DM) is a costly and burdensome lifelong disease, and without proper glycemic control, severe life-threatening complications result. In Southeast Asia, the prevalence of T2DM is forecast to increase markedly from 2000 to 2030. Although literature reviews on lifestyle modification for glycemic control are available, these are mainly for the Western context, and there is a dearth of evidence for Southeast Asians who are at greater risk of T2DM and have differing patterns of diet, physical activity and body composition than Western populations. Objective: To systematically review literature on the effectiveness of lifestyle modification interventions for glycemic control in T2DM patients from Southeast Asia. Methods: Randomized controlled trials (RCT) with interventions ≥ 8 weeks that compared HbA1c or blood glucose for intervention (lifestyle modification) versus control groups were identified from searches in Cochrane Library, CINAHL, PubMed, ProQuest, Science Direct, SPORTDiscus, Scopus and Web of Science. Results: Seven RCTs (679 participants) meeting inclusion and exclusion criteria were identified. There was a significant reduction in HbA1c% (MD = -0.56%; 95% CI = -0.95,-0.16%; p = 0.006; n = 5 studies) and in blood glucose mg/dl (MD = -16.76 mg/dl; 95% CI = -31.36, -2.17 mg/dl; p = 0.02; n = 4 studies) over 3 months for lifestyle modification intervention groups. Lifestyle interventions included diet (n = 2), exercise (n = 2), and general lifestyle interventions (n = 3). Duration of interventions ranged from 12 weeks to 6 months. Studies included populations from Thailand (n = 5) and Malaysia (n = 2). Conclusion: Overall, lifestyle modification interventions are effective for the glycemic control of T2DM patients in countries of Southeast Asia.

Doctor of Philosophy / Department of Anatomy and Physiology / Deryl L. Troyer / Many cell types were known to have migratory properties towards tumors and different research groups have shown reliable results regarding cells as delivery vehicles of therapeutics for targeted cancer treatment. Present report discusses proof of concept for 1. Cell mediated delivery of Magnetic nanoparticles (MNPs) and targeted Magnetic hyperthermia (MHT) as a cancer treatment by using in vivo mouse cancer models, 2. Cells surface engineering with chimeric proteins for targeted cancer treatment by using in vitro models. 1. Tumor homing cells can carry MNPs specifically to the tumor site and tumor burden will decrease after alternating magnetic field (AMF) exposure. To test this hypothesis, first we loaded Fe/Fe3O4 bi-magnetic NPs into neural progenitor cells (NPCs), which were previously shown to migrate towards melanoma tumors. We observed that NPCs loaded with MNPs travel to subcutaneous melanoma tumors. After alternating magnetic field (AMF) exposure, the targeted delivery of MNPs by the NPCs resulted in a mild decrease in tumor size (Chapter-2). Monocytes/macrophages (Mo/Ma) are known to infiltrate tumor sites, and also have phagocytic activity which can increase their uptake of MNPs. To test Mo/Ma-mediated MHT we transplanted Mo/Ma loaded with MNPs into a mouse model of pancreatic peritoneal carcinomatosis. We observed that MNP-loaded Mo/Ma infiltrated pancreatic tumors and, after AMF treatment, significantly prolonged the lives of mice bearing disseminated intraperitoneal pancreatic tumors (Chapter-3). 2. Targeted cancer treatment could be achieved by engineering tumor homing cell surfaces with tumor proteases cleavable, cancer cell specific recombinant therapeutic proteins. To test this, Urokinase and Calpain (tumor specific proteases) cleavable; prostate cancer cell (CaP) specific (CaP1 targeting peptide); apoptosis inducible (Caspase3 V266ED3)- rCasp3V266ED3 chimeric protein was designed in silico. Hypothesized membrane anchored chimeric protein (rCasp3V266ED3, rMcherry red) plasmids were constructed. Membrane anchoring and activity of designed proteins were analyzed in RAW264.7 Mo/Ma and HEK293 cells in vitro. Further, Urokinase (uPA) mediated cleavage and release of rCasp3V266ED3 from engineered cells was tested (Chapter-4). Animal models for cancer therapy are invaluable for preclinical testing of potential cancer treatments. Final chapter of present report shows evidence for immune-deficient line of pigs as a model for human cancers (Chapter-5)