• Molecular Strategies to Distinguish Key Subphenotypes in Sarcoidosis

      Garcia, Joe G. N.; Casanova, Nancy Gonzalez; Gomez, Jorge; Culver, Melanie; Bime, Christian; Sun, Xiaoguang (The University of Arizona., 2020)
      Sarcoidosis is a multisystemic disease of unknown etiology and unpredictable course, characterized by histopathological conglomerates of inflammatory cells defined as granulomas. These lesions however are non-pathognomonic, and in the absence of an identifiable etiologic agent, there are not specific diagnostic test for sarcoidosis. Despite the variable course of sarcoidosis, the lungs are affected in 90 percent of the cases. Approximately 25-30% of sarcoidosis patients progress to a complicated phenotype with progressive disease, leading to pulmonary fibrosis and organ dysfunction with increased mortality. These cases are in desperate need for biomarkers, conventional sarcoidosis biomarkers have proven to be insufficiently sensitive for implementation in routine clinical care. In this dissertation, I focused on the use of alternate strategies for biomarkers development utilizing genomic base approaches based on high-throughput molecular assays to characterize genotype, gene expression, and epigenetics that define sarcoidosis subphenotypes. Our results demonstrated that the integration of expression quantitative loci (eQTL) studies increase the power of Genome-wide association studies (GWAS). We identified SNPs that were associated to complicated sarcoidosis in African Americans (AA) and in European Americans (EA), and then we validated these SNPs by Massarray. Furthermore, at the transcript level, we identified the Peripheral Mononuclear Cells (PBMCs) responses to TNF-α exposure, a cytokine involved in the initiation of granulomas and progression of fibrosis in sarcoidosis and identified a differential dysregulation in pathways unique to complicated sarcoidosis. At the transcriptome level, we profiled microdisected granulomas from lung and lymph nodes, and identified a hub of genes that were dysregulated only in sarcoidosis in both compartments. Additionally, we compared the genomic profile of these granulomas in Sarcoidosis vs Tuberculosis (TB) and Coccidioidomycosis. We corroborated that some genes previously suggested as potential sarcoidosis markers were also present in fungal or mycobacterium granulomas, pointing to a common mechanistic origin. We also demonstrated a strong similarity at the transcriptional level between Sarcoidosis and TB. The contribution of the epigenetic mechanisms to the clinical presentation of sarcoidosis was assessed through DNA methylation analysis, complicated sarcoidosis reveled a hypo-methylated pattern in genes within HLA complex while the miRNA analysis derived a molecular signature consisting of 17 protein-coding genes, potentially regulated by 8 miRNAs dysregulated in complicated sarcoidosis.
    • Geographic and Racial Disparities in Mortality of Dialysis Patients

      Calhoun, Elizabeth A.; Mohan, Prashanthinie; Roy-Chaudhury, Prabir; Barraza, Leila Fs; Gilliland, Stephen (The University of Arizona., 2020)
      BACKGROUND: The incidence rate and hospitalization rate for patients with End Stage Renal Disease (ESRD) vary across different counties in the U.S. Little information is available on how geography can impact patient mortality through county health status and gaps in supply and demand for hemodialysis services. METHODS: This is a retrospective cohort study where adult patients who initiated in-center hemodialysis between 2007 and 2016 and recorded in the United States Renal Data System (USRDS) were assessed for survival time and mortality rate. The primary exposure variable in Aim 1 was the overall county health status (Most Healthy vs Least Healthy) based on the health factor ranks published by County Health Rankings & Roadmap (CHR&R). The primary exposure variable for Aim 2 was the supply-demand gap for hemodialysis services as measured by the patient-station ratio for each county. The primary exposure variable for Aim 3 was the change in the number of dialysis stations between 2011 and 2016 for each county. Kaplan-Meier estimate used to compute the median survival time and Cox regression analysis was used to compute the hazard rate (HR) for mortality after adjusting for various confounders. RESULTS: Most Healthy counties in the U.S. are likely to be larger urban counties with predominantly white and older patients. On the contrary, Least Healthy counties are comparatively more rural and smaller counties with a higher percentage of African American population, more unemployed and Medicaid patients. Patients residing in Most Healthy counties (HR = 0.899, 95% CI 0.825,0.979) had a lower hazard rate (HR) for mortality compared to patients living in Least Healthy Counties (p value = 0.0143). In Aim 2, counties in Category 1 (counties with no hemodialysis stations), Category 2.1 (underutilized HD stations with population <50,000) and Category 2.2 (underutilized HD stations with population 50,000) had higher HR compared to the reference Category 3. However, when stratified by age and race, the HR was statistically significant for Blacks only for Category 2.2 for all age groups (HR = 1.11, 95% CI 1.06,1.16) and for Whites for Category 1 (aged 40 – 79; HR=1.1) and Category 2.2 (aged 65 – 79; HR=1.11). In Aim 3, counties with No Change had a marginally higher hazard rate (HR=1.04, 95% CI 1.02, 1.07) compared to counties with an increase in dialysis stations. Race was a significant confounder but not an effect modifier to this association (p-value 0.2942). CONCLUSION: County health status and lack of hemodialysis facilities affects survival of ESRD patients. Additionally, patients residing in some suburban counties or smaller metros had a higher hazard rate for mortality despite excess supply of dialysis stations. It is important for care providers and local health officials to understand the health factor profile and spatial distribution of dialysis stations in their county to help ESRD patients navigate barriers to care, reduce rates of dialysis withdrawal, and improve mortality outcomes.
    • Cancer Capacity and Resources in Rural Arizona

      Calhoun, Elizabeth A.; Lent, Adrienne; Jacobs, Elizabeth T.; Barraza, Leila (The University of Arizona., 2020)
      Background: Cancer is the second leading cause of death in the U.S. Rural urban cancer disparities exist nationally and in Arizona. Previous studies on the availability of rural cancer services are cancer-specific, limited to specific points along the cancer care continuum (e.g., screening, diagnosis, or treatment), or require updating to capture the current landscape as it relates to rural health. This study explored the following three aims: 1) Describe the availability of cancer capacity and services for breast, cervical, colorectal and lung cancer across the cancer care continuum in low populous counties in Arizona; 2) Evaluate the association between breast cancer capacity and resources with breast cancer incidence and mortality; and 3) Provide policy recommendations focused on increasing capacity and resources in low populous, rural counties in Arizona. Methods: For Aim 1, a cancer capacity and resources survey was developed and distributed to healthcare organizations operating outside of Arizona’s largest population centered counties, Maricopa and Pima. Numbers of healthcare providers were pulled from the Center for Medicare and Medicaid Services. Numbers of clinical sites and healthcare providers were converted to county-level per capita rates. Rural Urban Continuum (RUC) codes were used to designate county metropolitan status. County demographic information from the U.S. Census Bureau, income data from the US Bureau of Economic Analysis, and unemployment rates from the US Department of Labor were included. Descriptive statistics were used to summarize the results. A student’s t-test was used to evaluate differences between rural and urban counties. For Aim 2, the Arizona Department of Health Services Cancer Registry provided county level cancer incidence and death rates from 2010 through 2016. Linear regression was used to evaluate the association between rural status and breast cancer capacity and services with breast cancer incidence and mortality rates. For Aim 3, current US federal and state level policies focused on increasing the rural workforce were reviewed. Results: Out of Arizona’s 15 counties, 13 were represented. Six were urban (RUC codes 1 – 3) and seven were rural (RUC codes 4 – 7). Urban counties had a larger average population (216,773) than rural counties (49,507) (p-value = 0.01). Rural counties had more per capita clinical sites (20.4) than urban counties (8.9) (p-value = 0.02). Rural counties had more per capita cervical cancer screening sites (18.9) than urban counties (7) (p-value = 0.02) and rural counties had more per capita colorectal cancer screening sites (15.7) than urban counties (2.5) (p-value = 0.02). Urban counties had more per capita gastroenterologists (2.2) than rural counties (0) (p-value = 0.02) and urban counties had more per capita pathologists (1.0) than rural counties (0) (p-value = <0.01). Rural counties had zero medical oncologists. Per capita, rural counties with RUC codes 4 and 6 had hematology and oncology physicians (0.3, 2.5) and radiologists (2.8, 6.0) but those with RUC code 7 had zero. Although not significantly different, rural counties with RUC code 6 had three times as many per capita registered nurses (306.7) than urban counties (90.8). Rural county status was associated with a decrease in breast cancer incidence (β = -20.1, 95% CI: -37.2, 3.1). There was no association between breast cancer incidence and county per capita sites providing breast cancer screening (β = -8.8, 95% CI: -23.9, 6.9), diagnosis (β = -5.2, 95% CI: -22.2, 11.7), treatment (β = -6.5, 95% CI: -23.2, 10.2), and all three services (β = -8.0, 95% CI: -23.9, 7.9) or county per capita primary care physicians (β = 0.0, 95% CI: -0.54, 0.48), hematology oncology physicians (β = -0.9, 95% CI: -15.7, 13.8), medical oncology physicians (β = 35.2, 95% CI: -22.7, 93.0), OBGYN physicians (β = -0.5, 95% CI: -4.2, 3.2), radiologists (β = -0.2, 95% CI: -6.8, 6.4), and surgeons (β = 1.6, 95% CI: -3.1, 6.3). In the unadjusted model, rural RUC codes four (β = -24.1, 95% CI: -41.8, -6.4) and six (β = -32.6, 95% CI: -53.0, -12.2) were associated with breast cancer incidence. There was no association between breast cancer incidence and RUC code 7 (β = -1.8, 95% CI: -22.3, 18.6). In the model adjusted for race (percent of the county population that’s Hispanic) and Ethnicity (percent of the county population that’s American Indian and Alaska Native), RUC codes four (β = -19.0, 95% CI: -37.7, -0.4) and six (β = -32.6, 95% CI: -56.0, -7.9) were associated with breast cancer incidence. There was no association between breast cancer mortality and rural county status (β = -1.1, 95% CI: -7.7, 5.6), county per capita sites providing breast cancer screening (β = -0.2, 95% CI: -4.2, 3.8), diagnosis (β = 0.4, 95% CI: -3.8, 4.6), treatment (β = 0.4, 95% CI: -3.9, 4.6), all three services (0.2, -3.9, 4.3) or county per capita primary care physicians (β = 0.0, 95% CI: -0.1, 0.0), hematology oncology physicians (β = -1.6, 95% CI: -5.3, 2.1), medical oncology physicians (β = -0.9, 95% CI: -17.2, 15.3), OBGYN physicians (β = -0.6, 95% CI: -1.5, 0.3), radiologists (β = -0.7, 95% CI: -2.4, 1.0), and surgeons (β = -0.1, 95% CI: -1.4, 1.2). Conclusions: While rural counties may have more physical infrastructure, they lack specialists integral to providing cancer services. Non-physician clinical providers may be more prevalent in rural areas and represent opportunities for improving cancer care. Compared to urban counties, rural county status was associated with lower breast cancer incidence rates but not associated with breast cancer death. The number of sites delivering breast cancer services and physicians were not associated with breast cancer incidence or mortality at the county level. Other factors may contribute to rural urban differences in breast cancer incidence. Federal and state level policies have been effective in increasing the rural healthcare workforce. However, opportunities for improving rural cancer care through policies and programs exist. Improved data collection and availability from state level workforce data and the FDA mammography database can help improve cancer capacity research. Increased exposure to rural locations during residency, transformation of GME payment, and expansion of loan repayment and scholarship programs may help increase the number of specialists delivering cancer care in rural Arizona and nationally. Increased training opportunities and the scope of work expansions for non-physician clinicians and advanced practice providers may help improve the delivery of cancer prevention and treatment services in rural areas that lack specialist physicians. Future research should explore these factors as well as the association between cancer capacity and resources at a more local level since Arizona counties can be a heterogeneous unit of observation.
    • When Land Becomes Property: Promises and Pitfalls of Land Titling for Indigenous Guarani and Campesinos in Northern Paraguay

      Green, Linda B.; Tusing, Cari; Vásquez León, Marcela; Sheridan, Thomas E. (The University of Arizona., 2020)
      This dissertation examines how rural people in Northern Paraguay manage land and navigate land titling in order to stake claims to land and property, particularly under continuing processes of settler colonialism. Land title in Paraguay is touted as the key to securing land and livelihoods for campesinos and indigenous people. Through a multi-sited ethnography, I challenge this assumption by showing that the title implementation is irregular and slow; title itself does not guarantee possession nor guard against dispossession; and title requires a certain ideal-type community in order to be achieved. Titling reorders rural people’s relationships to land as collective or individual lots are granted or held in suspension, and reorders rural people’s relationships to each other as they contest or cooperate on claims. I investigate the grinding precarity of rural livelihoods that both campesinos and indigenous people confront in ethnographic detail, focusing on the intersection of rural landowners including Paraguayan and Brasiguayo elites, campesinos, and indigenous peoples’ concepts of land rights and property. I find that despite legal mechanisms to title land, lasting settler colonial categorizations reproduce unequal material differences in land access and livelihoods. At the same time, communities are able to assert certain forms of autonomy by leveraging legal concepts of property and ownership. I argue that land title is a fraught opportunity, with both promises and pitfalls for marginalized communities.
    • Basin-Scale Aquifer Characterization: Theory and Application

      Yeh, Tian-Chyi Jim; Wang, Yu-Li; Ferre, Paul A.; Guo, Bo (The University of Arizona., 2020)
      Groundwater is one of important water resources for the socio-economic development of a community. Its reserve, distribution, and movement are mainly controlled by the subsurface hydraulic characteristics. For management of the groundwater resources, mathematical models of groundwater dynamics have been used for estimation, prediction, and scenario analysis. The accuracy of these analyses relies on the detailed knowledge of the subsurface hydraulic characteristic distributions. However, a reliable evaluation of groundwater resources remains intractable due to multi-scale variability of the subsurface characteristics and our limited ability to characterize it over a large groundwater basin. This difficulty thus hinders adequate assessments of water sustainability, and in turn, impedes the development of community. In order to overcome this difficulty, a new generation of basin-scale aquifer characterization method must be developed. My dissertation is to explore and develop the new generation of basin-scale aquifer characterization approach. The dissertation is composed of three parts. In, the first part, we investigate the feasibility of utilizing river stage fluctuation as spatial and temporal varying excitation sources to characterize the basin-scale aquifers. The wavelet analysis is first conducted to investigate the temporal characteristics of groundwater level, precipitation, and stream stage. The results of the analysis show that variations of groundwater level and stream stage are highly correlated over seasonal and annual periods while that between precipitation is less significant. Subsequently, spatial cross-correlation between seasonal variations of groundwater level and river stage data is analyzed. It is found that the correlation contour map reflects the pattern of sediment distribution of the fan. This finding is further substantiated by the cross-correlation analysis using both noisy and noise-free groundwater and river stage data of a synthetic aquifer, where aquifer heterogeneity is known exactly. The ability of river stage tomography is then tested with these synthetic data sets to estimate hydraulic diffusivity (D) distribution. Finally, the river stage tomography is applied to the alluvial fan. The results of the application reveal that the apex and southeast of the alluvial fan are regions with relatively high D and the D values gradually decrease toward the shoreline of the fan. In addition, D at northern alluvial fan is slightly larger than that at southern. These findings are consistent with the geologic evolution of this alluvial fan. In the second part of the dissertation, we investigate the effects of different types of river stage variation and the monitoring network design on the large-scale aquifer characterization. It evaluates the spatiotemporal cross-correlation between the observed head and D parameters in heterogeneous aquifers under static and migrating periodic excitations with different frequencies and other factors, and a moving single excitation along a river boundary. Results of the cross-correlation analysis are verified by estimating the parameters in a synthetic heterogeneous aquifer under these excitations. For assuring the statistical significance of the results based on a single realization, Monte Carlo experiments of estimating the parameters with these excitations are conducted. The experiments also explore the relationship between the resolution of the estimated parameters and the distance from the excitation to the observation wells, the frequency, and amplitude of the excitation, and the mean diffusivity of the aquifer. In addition, the relationship between the resolution of the estimates and monitoring network spatial density is investigated. Finally, the usefulness of moving single excitations, effects of frequencies of the periodic excitations under different situations, the density of monitoring network in term of correlation scale, and the ergodicity issue corresponding to the number of observation and size of simulation domain are discussed. In the third part, we evaluate the capability of periodic excitations with different frequencies and multi-frequency to estimate hydraulic transmissivity and storage coefficient fields in heterogeneous aquifers. The residual flux and residual storage presented in the stochastic groundwater flow model are examined by the unconditional and conditional effective approaches. Afterward, the first order approximation and the singular value decomposition are substantiated to quantify the similarity and dissimilarity of amplitude and phase shift of unconditional flux and storage under different pumping frequencies. The result of the cross-correlation analysis is verified by estimating the parameters in a set of synthetic heterogeneous aquifers. The Monte Carlo experiment is required for assuring the statistical significance of the results. These resulting data and the reanalyzing data from previous studies lead us to a conclusion that the heads induced by pumping with different frequencies or multi-frequency carry the same information about the heterogeneity. Finally, the parameter (e.g., hydraulic conductivity and specific storage) and state variable (e.g., water level and flow fields) ergodicities emphasize the importance of dense monitoring network and cost-effective data collection procedure on the resolution of delineating heterogeneity.
    • Innovative Methods for Outcome-Based Pricing of Treatments from the US Payer Perspective (The Six Delta Platform)

      Abraham, Ivo; Alkhatib, Nimer; Ramos, Kenneth; Erstad, Brian; McBride, Ali; Slack, Marion; Bhattacharjee, Sandipan (The University of Arizona., 2020)
      An independent group of researchers from the Center for Health Outcomes and PharmacoEconomic Research (HOPE), University of Arizona, has committed to designing, validating, and disseminating a platform of transparent methodologies for pricing of treatments that could potentially be used for outcome-based contracting from the US payer perspective. In brief, the suggested pricing methodology uses a multidimensional price assessment in which six dimensions (also termed δ) are used to provide price variations. Two-time horizons for assessing these 6 δs are considered, comprising two δs based on long-term assessments and four δs based on short-term assessments (Figure 1). Individually, each of these six δs is designed to use different scenarios for creating price variations (also termed dispersions) at the dimensional level. The price variations in each δ are simulated by Monte Carlo Simulation (MCS) methods to generate a price at the dimensional level (i.e., the dimension-specific price, DSP), and a price when all dimensions are integrated (i.e., the average of all dimensional prices, ADP). A proof-of-concept for the six pricing δs is provided for osimertinib in the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation.
    • Robust Model Predictive Control of Cyber-Physical Systems

      Sprinkle, Jonathan; Risso Sepulveda, Maria Nathalie; Sanfelice, Ricardo G.; Tharp, Hal; Ditzler, Gregory; Momayez, Moe (The University of Arizona., 2020)
      Cyber-physical systems (CPS) are integrations of computation, communications and physical processes. These systems inherently require an effective interaction between the physical and digital elements. Design of CPS involves both capturing the integrated dynamics with models that can provide accurate predictions, and effective controllers which can guarantee performance, particularly when dealing with safety critical applications. Model Predictive Control (MPC) is frequently used for the control of CPS since it can provide online decision making, thanks to its ability to handle dynamic and static constraints. Since MPC is a model-based technique, the presence of uncertainty when generating predictions could result in trajectories with significant variations. This becomes particularly challenging when generating methods for CPS controller design, since CPS model approximations are hard to synthesize, and often lead to non-negligible modeling errors. This motivates the study of methods that can provide guaranteed performance under the effects of uncertainty and dynamic system constraints. In this work, we consider systems evolving in discrete-time (which could come from the discretization of a CPS model), where the state variable is set-valued. The solutions to these systems are given by sequences of sets that are explicitly generated by a set-valued map and a constraint set. This representation is beneficial since it can easily encode constraints, uncertainty and system dynamics that exhibit non-determinism. Under this approach, we can also analyze the effects of inputs generated from anytime optimization routines, where, for instance, input variability can be represented as a set and propagated to analyze reachability, in order to guarantee safety. For these systems, to which we refer as set dynamical systems, we provide several results which can be used to synthesize controllers which achieve robust performance, embedded in the set-based formulation. First, we develop tools to locate omega limit sets by using Lyapunov-like conditions and an invariance principle for set dynamical systems. The latter uses non-strict Lyapunov functions to determine convergence properties of set-valued solutions and, conveniently, is similar in spirit to the invariance principles available for continuous and discrete-time systems. Next, we provide tools to certify asymptotic stability of sets for set dynamical systems. We develop such tools by following a similar path to the development of the continuous and discrete-time counterpart for classical dynamical systems. In this way, we exploit the invariance principle for set dynamical systems, and generate sufficient conditions for asymptotic stability that resemble those by Krasovskii and Lyapunov. These results are then used to provide - though not constructive - sufficient conditions for the design of stabilizing state-feedback controllers for such systems, which, unlike the classical approach, allow for feedback laws that involve sets rather than points. Finally, we use this set-valued state representation to generate prediction models used in a robust MPC formulation. In our proposed setting, since the state trajectory is set-valued, the cost functional uses set-to-points maps to characterize the cost associated to each set-valued trajectory. For this formulation, we propose conditions that, analogous to the classical MPC formulation, lead to feasible set-valued predictive controller formulations.
    • Encouraging Dialogue around Social Issues with Latinx Students Through Literature Discussion and Culturally Relevant Literature

      Short, Kathy; Serrano, Angelica; Brochin, Carol; Durán, Leah; Yaden, David (The University of Arizona., 2020)
      This teacher research study examines literature discussions with fourth and fifth grade Latinx students about books that reflect Latinx experiences. For this study, the following questions are explored (1) What social issues do students discuss in literature groups? (2) How do literary response strategies influence student dialogue? And (3) How does my theoretical frame influence my decision making as a teacher? Theories that informed the construction of the literature discussions and the decision making occurring throughout the study are examined closely. The theories intertwine and bridge education and students’ experiences as a resource in learning more about the educational setting. In this study, the discussions of students and the literature response strategies are explored as the data is analyzed to examine the student discussions around issues of immigration, family separation, borders, and so much more. The findings in this study indicate that the experiences of Latinx students are integral to the educational setting and an education that invites who they are enhances their learning experiences. Latinx students are eager for learning opportunities that invite their voices and stories. It is through the construction and assessment of the educational setting that educators can promote culturally responsive, relevant, and sustaining teaching experiences that go beyond the classroom setting. Latinx students build relationships with each other and their teachers as they engage in discussions that allow them to share and learn with each other. This study is a reminder of the crucial role teachers play in creating such powerful spaces and the value that Latinx students bring into the classroom when invited to discuss, engage, and create powerful learning experiences.
    • Three Idiomatic Compositional Techniques of Stephen Hatfield

      Chamberlain, Bruce; Hayashi, Brad; Schauer, Elizabeth; Brobeck, John (The University of Arizona., 2020)
      Stephen Hatfield is a recognized pioneer in multiculturally influenced choral works and has been in demand internationally as a clinician and conductor. Hatfield has been commissioned to write new pieces for choral groups more than two hundred times in his career. His music is held in esteem by choral conductors throughout the world. This analysis of nine choral works by Stephen Hatfield will reveal three of his idiomatic compositional techniques: 1) combining traditional folk materials with original material or text—or both (the “Hatfield Hybrid”); 2) creating chant and ostinato inspired and influenced by specific music from an ethnocultural style to compose an entirely original work (the “Deep Hatfield Hybrid”); and 3) combining different cultural styles into an original work (the “Cultural Mashup”). Over the course of nine years I have exchanged nearly 700 emails with Stephen Hatfield. In his emails Hatfield explicated his philosophy and approach to composing, as well as describing specific compositional techniques. These emails thus offer a great deal of insight into his compositional approach, and the analysis in this document frequently refers to them.
    • Diet Quality and Disease Activity in Rheumatoid Arthritis

      Insel, Kathleen I.; Crane, Tracy E.; McGarrity-Yoder, Maureen Elizabeth; Pace, Thaddeus W.W. (The University of Arizona., 2020)
      Background: Rheumatoid arthritis (RA) is a common autoimmune disease that affects the health-related quality of life (HRQOL) of over 1.3 million Americans. RA significantly affects HRQOL through joint deformity, disability, and an increased risk for significant sequela, often regardless of pharmacological therapy. Diet has been considered a factor in exacerbation of RA for decades, and diet quality has been associated with RA risk, associated disability, and disease progression. Unfortunately, research is limited, and findings are unclear. Dietary recommendations continue to be excluded from clinical practice guidelines in RA treatment, and communication is often lacking between providers and patients. Up to 25% of those diagnosed with RA believe their dietary intake affects disease activity and many people change their diet in an attempt to improve their HRQOL. Purpose: The purpose of this study is to examine the association between diet quality and disease activity in adults with RA. Methods: This cross-sectional, descriptive study examined the association between diet quality and disease activity of 50 adults diagnosed with RA. Participants completed the Arizona Food Frequency Questionnaire to measure dietary intake, which was scored with the Healthy Eating Index (HEI)-2015 to determine diet quality. Disease activity was measured via the self-reported Health Assessment Questionnaire-Disability Index and Pain Scale(HAQ-DI and pain scale), hematology analyses for erythrocyte sedimentation rate (ESR) and high-sensitivity C-reactive protein (hs-CRP), and a Disease Activity Score Including 28 Joints (DAS28). The DAS28 was calculated by examining 28 joints, participant self-report, and, in this study, ESR results. Perceived stress was measured with the Perceived Stress Scale. Results: Higher diet quality was not associated with any measures of disease activity (HAQ-DI, pain, DAS28, ESR, or CRP). The mean diet quality score was 56 (SD ± 12), which is lower than the national mean of 59. Higher quality diets were more common in older individuals (p=.015) and women (p=.003). In total, 44% (n=22) participants reported they believe diet affects RA disease activity, and those who believe their diet affects RA were significantly more likely to report dietary changes (p<.0001). Participants with higher educational level (some college or more) were more likely to report the belief that diet affects disease activity (B=-1.535, p=.023). Women with lower diet quality were more likely to have higher HAQ-DI scores (B=.570, p=.001). An increased BMI was associated with decreased DAS28 scores in those with a poor-quality diet (p = .018), but with lower diet quality in those with fair-good diet quality (p =.023). A decreased BMI was significantly correlated with current tobacco use in adults with fair/good quality diet (p= .013). Perceived stress was significantly associated with HAQ-DI and pain scores (B= .445, p=.001 and B= .289, p=.042, respectively). Conclusion: Many individuals with RA should improve their diet as poor diet quality was associated with increased pain and may be related to inflammation. Keywords: Rheumatoid Arthritis, Diet Quality, Disease Activity, Biopsychosocial, Psychoneuroimmunology.
    • Cotton Agriculture and the Function of Gravel Mulch in the Northern Rio Grande

      Towner, Ronald H.; Kessler, Nicholas Victor; Holliday, Vance T.; Mills, Barbara J.; Kuhn, Steven L.; Dean, Jeffrey S. (The University of Arizona., 2020)
      The site of Poshu’Owingeh was one of several ancestral Tewa villages to experience rapid growth in the 14th and 15th centuries A.D. in northern New Mexico. Recent research has proposed that this growth was one aspect of a trend characterized by nonlinear socioeconomic change produced by increasing population size and connectivity. Agriculture, commodity production, and exchange are fundamental to this model, but direct evidence for intensification is limited and no empirical data exists for the function and mechanics of the technologies which are supposed to have supported surplus production. This research addresses the problem by examining paleobotanical and soil evidence for the function of gravel mulch, a unique agricultural technology hypothesized to have supported cotton agriculture in portions of the Northern Rio Grande. Physical soil properties and base cation ratios are used to reconstruct the irrigation effect of gravel mulch, and soil nutrient levels are measured to assess change in soil quality associated with cultivation. Fossil pollen assemblages recovered from agricultural soil layers are used to determine the mix of crops grown in gravel mulch fields. A spatial database of archaeological sites is used to reconstruct Puebloan population dynamics in the Tewa Basin. This is compared to published estimates of population growth, the timing of socioeconomic developments in the region, and climate reconstructions. Fossil pollen concentrations indicate that cotton was the main crop grown at Poshu’Owingeh. The substantial increase in the ratio of cotton to maize and a decrease in the diversity of economic wild plant taxa at Poshu’Owingeh suggest cotton cultivation was more intensive here than other documented sites in the region. Soil analysis revealed no evidence for degradation associated with gravel mulch. Cation ratios and particle size distribution in the A horizon suggest that gravel mulch continues to enhance subsurface water flux. I estimate that the runoff required to produce the sodium leaching observed in mulched profiles is generated by relatively intense precipitation generated by monsoon storms. Peak rates for the spatial expansion of farming populations responsible for the construction of the gravel mulch-cotton fields follows rapid population growth in the great Tewa Basin, is coincident with the intensification of regional exchange networks, and strengthening of the North American Monsoon. Given the mechanics of agricultural technology documented in this study, and hypotheses for the importance of cotton in the regional economy; it is concluded that population dynamics, climate change, and human niche construction interacted played a significant role in social change and economic expansion in the late precontact Northern Rio Grande.
    • A Framework for Automatic Dynamic Constraint Verification in Cyber Physical System Modeling Languages

      Sprinkle, Jonathan M.; Bunting, Matt Robert; Tharp, Hal S.; Lysecky, Roman (The University of Arizona., 2020)
      Design of Cyber-Physical Systems (CPSs) involves overlapping the domains of control theory, network communication, and computational algorithms. Involving multiple domains within the same design greatly increases the system complexity. Furthermore, the physical nature of CPSs generally involves important safety constraints where constraint violations can be catastrophic. The design of CPSs benefits from focusing on the construction of abstracted, high-level models in a DomainSpecific Modeling Language (DSML). A Domain-Specific Modeling Environment (DSME) may aid in the design of such complex systems by enforcing structural design constraints during the construction of models. Models built using a DSME may also use compilers or interpreters to produce real working, low-level artifacts that represent the high-level design. Though each model in a DSME may abide by a formal specification, the behavior of a design may violate dynamic constraints if deployed. Engineers are tasked to ensure that models behave safely by implementing their expert knowledge after using appropriate verification tools. Constraint violations may be eliminated by a modification of the model based on verification feedback, known as Dynamic Constraint Feedback (DCF). Mending such constraint violations is a task generally performed by the model designer. Such a process could potentially be automated through the capture of well-known design practices. The challenging task when automating model correction then becomes in the design of a DSML. A designer of a DSML may have a clear understanding of how to design the syntax and semantics for their domain, but there are no formal methods for implementing verification tools for automatic model correction. Such a framework could greatly aid in the selection of available verification tools, implement well-established design methods, and model dynamic constraints. Presented is the Dynamic Constraint Feedback Metamodeling Language (DCFML), a new metamodel to implement DCF upfront in DSML design. This particular solution provides a concrete solution to the abstraction of the various components of DCF, and then appends them to the DSML design process provided by a DSME.
    • Independent Component Analysis for Group Comparison of Functional MRI Images in Individuals with Parkinson's Disease

      Bedrick, Edward J.; Hu, Chengcheng; Yaffe, Kirsten; Chou, Ying-hui; Hsu, Chiu-Hsieh (The University of Arizona., 2020)
      Parkinson's Disease (PD) is an age-related disorder that affects cognitive and motor abilities and lowers quality of life. As there is currently no cure, it is an area of interest for many research efforts. Parkinson's disease has a substantial effect on structures in the basal ganglia, which may be used to indicate signs of Parkinson's disease progression. Functional MRI (fMRI) is a means of measuring metabolic functioning in the brain. Brain imaging studies are not used to diagnose Parkinson's disease because it is unclear how it manifests in neuroimages. However, Parkinson's disease has a preclinical phase during which structures within the brain are affected, but external symptoms have not yet manifested. In this study, we sought to identify effects of Parkinson's disease that may be seen in functional imaging scans to allow earlier detection. We used independent component analysis (ICA) to identify functional brain networks followed by dual regression to estimate subject-level components for making comparisons of the functional images between the two groups: a group of subjects with Parkinson's disease and a group of healthy control subjects. We were able to generate subject-level components; however, identifying one component at the group level that included the basal ganglia proved problematic. Methods of identifying neural structures within the application we used provided conflicting evidence. Therefore, we were unable to determine if differences between the study groups existed that could be seen in functional imaging scans. Testing our primary endpoint using a voxel-wise linear regression with each of the components was not successful because most of the p values on the coefficient of interest were non-significant. In addition, there was a poor model fit seen in the regression models. We were unable to provide scientific evidence of differences that might be seen in functional MRI studies between subjects with Parkinson's disease and healthy control subjects.
    • Comparative Study of Transfer Matrix Formalism vs Single-Mode Model for Semiconductor Microcavities

      Binder, Rolf; Carcamo, Mario; Wright, Ewan; Kieu, Khanh (The University of Arizona., 2020)
      An optical semiconductor micrcavity consisting of two distributed bragg reflectors (DBRs) and a quantum well between, can be modeled using a transfer matrix approach, which solves the propagation through the DBR mirrors and the cavity segment in between the mirrors. Such an approach is easy to use if the interband polarization of the quantum well PQW is a given function of time or frequency, which includes the case of linear optical response, where PQW is given in terms of the linear susceptibility and the electric field at the position of the quantum well, EQW. In many cases of practical interest, the quantum well response is a nonlinear function of EQW, in which case the transfer matrix approach becomes impractical. In such cases, a time differential equation for PQW, which is of the form i¯ h dPQW(t) dt= F[PQW(t),EQW(t)] where F is a nonlinear function of PQW, is solved via time-stepping from earlier to later times. To obtain the electric field EQW needed as input to the PQW solution, a commonly used phenomenological approach utilizes the single-mode equation i¯ h dEQW(t) dt= hωcEQW(t)−ΩPQW(t) + S(t) with the source term S(t) being defined by S(t) = ¯ htcE+ inp(t) and corresponding constants that are defined in section 5 of this thesis. However, apart from containing phenomenological parameters, the simple source term entering the single-mode equation does not account for propagation, retardation, and pulse filtering effects of the incident light field traversing the DBR mirror. In this thesis, an alternate approach is presented along with evidence of its validity using a bounded convolution integral instead. The integral is used to determine the electric field as a function of time and therefore can be used to determine the time derivative of the polarization. The integral being EQW(t) =Z t −∞ [A(t−t0)E+ inp(t0) + B(t−t0)PQW(t0)]dt0. We show in the final sections that it is adequate to use this bounded integral to resolve pulses in the time domain. Evidence of that is done using a gaussian pulse and linear response. This method could then be used in conjunction with a time stepping algorithm to resolve nonlinear responses.
    • The CCAP: A New Physical Unclonable Function (PUF) for Protecting Internet of Things (IoT) and Other FPGA-Based Embedded Systems

      Hariri, Salim; Josiah, Jeff G.; Akoglu, Ali; Bruyere, Donald; Li, Ming (The University of Arizona., 2020)
      The importance of cybersecurity has grown exponentially over the years due to our highly interconnected world and the evolution of computer threats. These threats – once as simple as annoying computer viruses – are now destructive malware, ransomware, and advanced persistent threats (APT) sponsored by nation states used to steal military secrets, wage industrial espionage, and weaponize the Cyberspace into the 5th domain of future military conflict right behind Land, Sea, Air, and Space. Every device that interfaces with the Internet is a potential target. For instance, the attack surface for Internet of Things (IoT) is expected to expand with an estimated 14.2 billion connected “things” projected to be in use this year alone. These “things” are diverse and include rugged-industrial sensors, personal wearables, in-home appliances, and even some of the vehicles on the road today. Many IoT devices are beginning to utilize Field Programmable Gate Arrays (FPGAs) for their processing subsystem due to design flexibility and because FPGAs, as a design element, enable product lifecycle support through aftermarket upgradability of both the computer software (CSCI) and firmware/hardware (FWCI) configuration items. This allows manufacturers to enhance product functionality through over-the-Internet (OTI) or over-the-air (OTA) upgrades. Unfortunately, the increasing use of FPGAs has also brought a major concern of intellectual property (IP) theft and product counterfeiting. To help thwart IP theft, FPGA vendors such as Xilinx and Intel PSG (formerly Altera) provide end-users with the ability to encrypt design bitstreams at rest with a cryptographic key. This encryption key is typically stored in EEPROM, Battery-Backed RAM, or within dedicated Anti-Fuses within the device; however, numerous non-invasive, semi-invasive, and invasive attacks exist that can retrieve the encryption key and compromise the design bitstream. Physical (sometimes referred to as physically) unclonable functions (PUFs) have been proposed as a countermeasure to eliminate the need for cryptographic key storage. PUFs have been widely researched for nearly two decades. An efficient implementation for FPGAs has remained elusive and is an area of much needed research focus. The goal of this research was to deliver a new, innovative PUF design targeted specifically for FPGA implementation. We propose the CCAP which is an efficient, scalable hardware security primitive supporting today’s most advanced FPGAs. It requires no hard macros or interactive design floorplanning and is portable to any UltraScale+-based FPGA. Experimental results on several Avnet Ultra96 boards have shown excellent PUF performance in terms of PUF inter-device uniqueness, acceptable performance for PUF intra-device uniqueness, and good overall PUF output stability at the targeted operating temperatures. Additionally, the randomness of several CCAP “raw” signatures at various FPGA die locations have been tested and deemed random according to the NIST Randomness Test Suite, and chi-square “Goodness of Fit” test calculations. In the un-redacted portions of this dissertation, we discuss the motivation for this work, cover several of the prior PUF architectures in open literature and their shortcomings for FPGA implementation, examine our testing methodologies, provide some test results and analyses, propose a few real-world applications for the CCAP primitive, before ending with conclusion and possible future work. NOTE: The CCAP architecture and details pertaining to it are not publicly disclosed at this time.
    • Demystifying the Infrared Emission of Type-1 AGNs from z~0 to z~6

      Rieke, George H.; Lyu, Jianwei; Fan, Xiaohui; Green, Richard; Egami, Eiichi; Behroozi, Peter (The University of Arizona., 2020)
      The accretion of supermassive black holes (SMBHs) is accompanied by large columns of dusty gas connected to the host galaxy interstellar medium, resulting in significant emission in the infrared (IR) spectral range (λ ∼1–1000 μm). IR observations of these systems provide a wealth of information to reveal the physics of active galactic nuclei (AGN) and its role in galaxy evolution. In this thesis, I present a systematic study to characterize and decipher the IR emission of Type-1 AGNs over very broad ranges of luminosity (L_{AGN,bol} ∼ 10^8 –10^14 L_⊙) and redshift (z ∼0–6) from different perspectives: (1) we have demonstrated that the intrinsic IR SEDs of type-1 quasars at z ∼0–6 have variations from hot-/warm-dust-deficient populations to the normal population and characterized the similar AGN-heated far-IR SEDs among different AGN populations; (2) By adding UV-optical obscuration and IR-reprocessed emission of an extended distribution of large dust grains to the intrinsic AGN templates, we have successfully reconciled the IR behaviors of all major populations of type-1 AGNs, including the strong polar dust emission found in several Seyfert-1 nuclei by mid-IR interferometry observations and the large SED variations among local Seyfert-1 nuclei, normal blue quasars, extremely red quasars at z ∼2–3, AGNs with mid-IR excess emission at z ∼0.7–2, hot-dust-obscured galaxies at z ∼1.5–4, and dust-free quasars at z ∼ 6, which provided critical insights on how the diverse AGN dust environment can be reflected by the different IR SED shapes; (3) With an innovative usage of the time-series data from asteroid/supernova-hunting surveys, we have developed the first mid-IR dust reverberation survey of quasars and put several important constraints on the AGN torus structures and supported the unification model; (4) Based on an accurate knowledge of galaxy and AGN IR emission, we have shown the far-IR properties of quasar host galaxies at z ∼5–6 should be similar to the low-metallicity starbursting galaxy Haro 11 and studied the quasar star formation rates and typical stellar masss when the Universe is only ∼1 Gyr old.
    • Pore-Scale Modeling of the Surface Roughness Effect on Fluid-Fluid Interfacial Area for Contaminant Transport in Vadose Zone

      Brusseau, Mark L.; Jiang, Hao; Guo, Bo; Farrell, James (The University of Arizona., 2020)
      Interaction between solid, wetting fluids and nonwetting fluids frequently occurs in natural environmental processes. An ongoing concern for researchers is the fluid-fluid interfaces on rough solid surfaces inside natural porous media. Interfacial area between the immiscible fluids could be greatly affected by grain surface roughness, in which the adsorbed wetting-fluid films serve as the critical intermediary. It has been demonstrated that the configuration of wetting films is a combination of two competitive surface forces: DLVO adsorption and capillarity, whose effects on wetting fluids can lead to significant changes in the shape of films, and thus distinctive film area under different matric potentials. Therefore, the methodology of the research is to characterize the mechanism of surface roughness involved in the configuration of wetting film, and the resultant change of film area, with an explicit quantitative model. The main body of the present modeling approach is to use a bundle-of-cylindrical-capillaries (BCC) model for pore geometry that is modified with a surface roughness factor based on the solid surface area. Film-associated interfacial area in the model is represented by an interfacial area factor normalized with solid surface roughness, which is quantified by an explicit sigmoid function (logistic function) that defines the change of film area within the range of two limiting conditions: smooth-surface and maximum roughness. For a given porous medium, its inherent solid phase properties, especially the fractal-scale microstructures of surface roughness, will generate a characteristic profile of interfacial-area vs. wetting-fluid saturation, which can be fitted from measured data from interfacial partitioning tracer tests (IPTT). Following the development of modeling approach, simulations with both pre-determined input parameters and actual experimental data were conducted. Example calculations and sensitivity analyses of critical model parameters revealed the phenomenon of “surface roughness masking” that occurred in the interfacial-area vs. saturation curves. Simulation test on experimental data sets for multiple porous media demonstrated the excellent performance of the modeling approach, in which each medium can be explicitly quantified with five critical modeling parameters—two for pore size distribution, one for the sample-scale surface roughness, and two for micro-scale roughness. Inspection of the relationship between roughness-related parameters showed that the micro-scale surface roughness of natural porous media only partially correlate to soil texture. Studies on images from scanning electron microscopy (SEM) also illustrated the complexity of surface roughness. The complicated nature of the micro-scale surface roughness highlighted the potential of the proposed methodology in various environmental applications. It would be particularly useful for systems that comprise large magnitudes of interfacial domain, with energy or mass transport between solid, fluid, and atmosphere.
    • Evaluation of Critical Care Nurses Utilization of Pain Assessment Tools in Clinical Practice

      Buchner, Brian; Griffin, Rebecca; Insel, Kathleen; Muzzy, Angela (The University of Arizona., 2020)
      Background: Unmanaged pain among critically ill patients is a primary stressor that leads to acute and long-term complications, increased mortality, and a decline in patient outcomes (Chookalayia et al., 2018; Gélinas, 2010). This project inquiry aims to evaluate TMC critical care nurses’ utilization of BPS and NVPS pain assessment tools used and the amount of analgesics used in clinical practice. Methods: A retrospective chart review on 16 ventilated patients requiring analgesic administration to (1) to evaluate nurses’ utilization of the BPS and NVPS pain assessment tools to guide analgesic administration and (2) determine if the pain assessment scores correlate with the current pain scale used and analgesics given for pain control, and utilization of RASS to guide sedation administration used in clinical practice. Results: Of the 16 patients evaluated approximately 25.8% of the time were critical care nurses compliant in documenting NVPS with analgesic titrations and 24.5% compliant in recording BPS with analgesic titrations. This data showed that critical care nurses used both pain scales successfully 30.5% of the time when titrating analgesia. Conclusion: The literature supports the use of NVPS or BPS as a pain assessment tool to guide titration of analgesics in the general population admitted to the ICU requiring mechanical ventilation (Bouajram et al., 2018; Rijkenberg et al., 2017). However, this DNP project showed low compliance with using validated tools NVPS or BPS, indicating that the current practice utilized at Tucson Medical Center (TMC) does not correspond to the current literature. Future studies could explore a nurse's perspective on ease of use and effectiveness of the NVPS or BPS for assessing pain to the general population admitted to the ICU requiring mechanical ventilation.
    • Evolutionary Trajectories of Cognitive Abilities and of their Putative Neuroanatomical and Allometric Correlates: Testing Novel Hypotheses of Cognitive Evolution and Cognitive Integration with Phylogenetic Comparative Methods

      Figueredo, Aurelio José; Barcellos Ferreira Fernandes, Heitor; Jacobs, William J.; Steklis, Horst D.; Davis, Melinda F. (The University of Arizona., 2020)
      The study of primate intelligence, and specifically of general intelligence, has progressed rapidly in the last two decades, however several issues remain unexplored. While neuroanatomical volume measures (NVMs) such as brain size, neocortex size, and absolute or relative size of other brain regions have been frequently framed as substrates for general intelligence, such claims are largely based on simple correlative analyses. Furthermore, while factor analytical techniques have identified a general factor among cognitive abilities when using datasets of species’ mean performances, there have been no examinations of whether the common factor is predictably more strongly present in some primate lineages than in others, and whether relations among brain regions are similarly stronger in some primate lineages than in others. Here, such issues in the comparative literature on primate intelligence are addressed in a new set of studies that present two main novel contributions to the scientific understanding of primate intelligence: First, the evolutionary patterns of the history of changes in general intelligence in primates is examined and compared to those behind the history of changes in brain size and the size of brain regions most commonly used in comparative cognition studies. Studying evolutionary patterns behind a trait permits examining how conserved it is across evolutionary time, how fast it has evolved, and the degree to which it has evolved in a particular direction (i.e., if natural selection regimes have been consistent). Phylogenetic comparative methods employed on datasets of primate species reveal that general intelligence has evolved at a faster pace than NVMs and it has evolved more consistently towards a selection optimum. In contrast to the overall emphasis given in the literature to brain size and neocortex ratio as substrates for intelligence, the NVM with results that most strongly approached the patterns identified for general intelligence is residual cerebellar size (relative to body size). Secondly, a hypothesis is advanced that species higher on general intelligence exhibit a stronger manifold (i.e., higher factor loadings) as general intelligence has previously been empirically associated with ecological generalism, rather than with specialism. As such, cognitive specialization and independence among abilities should be a hallmark of species that have not evolved strong general intelligence. The Continuous Parameter Estimation Model (CPEM) is used in a dataset of cognitive abilities in primate species, and largely confirms the hypothesis forwarded. However, when the same analytical approach is replicated using data on sizes of brain regions, it is found that brain size fails to predict or coevolve with factor loadings of brain regions. Similarly, telencephalon size (a brain structure that holds several of the regions theoretically proposed to serve as substrates for intelligence) fails to predict the strength of factor loadings of telencephalic regions. This set of studies supports the notion that the comparability between the evolution of general intelligence and the evolution of volumes of neuroanatomical structures is more limited than previously thought. Alternative substrates for general intelligence are discussed.
    • Optogenetic Manipulation of Posterior Caudatoputamen Indirect Pathway Neurons Causes Auditory Cortical Activation in Rats

      Hammer, Ronald P.; Yellowman, Zachary George; Nikulina, Ella M.; Qiu, Shenfeng (The University of Arizona., 2020)
      Auditory hallucinations are prevalent in many neuropsychiatric disorders and are also a cardinal symptom of schizophrenia. Most research on the mechanism of auditory hallucinations has focused on functional imaging of the auditory cortex. Recent research has revealed structural and functional interaction between the striatum and the neocortex. Previous studies in our laboratory have shown that dopamine infusion into the posterior caudatoputamen (CPu), the “auditory striatum,” produce activation of the rat auditory cortex. To establish the next projection site from these neurons, we virally infused an anterograde AAV-GFP into this region of the auditory striatum which resulted in expression mainly at the same rostral-caudal level of the lateral globus pallidus (LGP) as the infusion site. Since antipsychotic drugs target D2 dopamine receptors on neurons of the indirect pathway (CPu-LGP) to alleviate psychotic symptoms, we transfected terminals in the LGP with a retrograde AAV-Jaws-GFP to neuroanatomically discriminate the indirect pathway. Inactivation of the striatal indirect pathway neurons with Jaws stimulation resulted in significant activation of the auditory cortex via c-Fos expression. Conversely, activation of these same striatal indirect pathway neurons with stimulation of ChannelRhodopsin-2 (ChR2) showed no significant change in auditory cortex activation. The results of these studies will elucidate a potential alternative neural circuit mechanism underlying the pathophysiology of auditory hallucinations in neuropsychiatric disorders.