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    • Development of Bioanalytical Assays Using Scintillant Polymer-Core Silica-Shell Nanoparticles

      Mokhtari, Zeinab (The University of Arizona., 2018)
      Ideal nanosensors of biomolecules are sensitive, selective, stable, minimally invasive, amenable to mass production with low-cost, and applicable for reproducible in vitro and in vivo analyses. The nano scintillation proximity assay (nanoSPA) presented here is based on a composite architecture of polystyrene-core and silica-shell nanoparticles, with a high surface area to volume ratio (ca. 2×107 m-1) and density of approximately 1.6 g/cm3. nanoSPA obviates the need for separation of bound from free radiolabeled molecules prior to measurements, with minimized complexity and maximized versatility. Selected β-emitter radioisotopes were utilized for the development of radioassays for analysis of biological processes using nanoSPA. 35S was employed for thiol/disulfide ratio analysis for the first time. Thiolresponsive nanoSPA was used for quantification of 33S-cysteine and 33S-cystine as models of 35S-thiol and 35S-disulfide. Synthetic samples of 33S-cysteine and 33S-cystine and human embryonic kidney (HEK293) cell lysates were analyzed using thiolresponsive nanoSPA for evaluation of thiol/disulfide ratio as a measure of redox status of the sample. Limit of detection for 35S-thiol analysis was <1.1 pM (<1.1 nCi) with a signal to background ratio over 10-fold. 33P-labeled adenosine triphosphate (ATPγ33P) was utilized for the development of kinase activity assays. Three nanoSPA platforms were developed for kinase activity analysis including adsorption, binding, and immuno-nanoSPA that respond based on electrostatic non-specific adsorption, covalent binding, and antibody-antigen binding, respectively. Signal to background ratio up to 24 was observed using separation-free analyses with nanoSPA, compared to approximately 11.5 using liquid scintillation analysis after many washing steps. 3H emits the lowest energy β-particles and it was utilized with nanoSPA for development of saccharide sensors. Dynamic binding of 3H-D-glucose to nanoSPA functionalized with several monoboronic acids (monoBAs) and diboronic acids (diBAs) was evaluated. The signal to background ratio was up to 2.2-fold that must be improved. Further platforms may be developed based on phospholipid-nanoSPA with minimal nonspecific adsorption and more specificity.
    • Impact of Geographic Variation, Disability, Socioeconomic Status and Risk Adjustment on High-Risk Medication Use among Elderly Medicare Beneficiaries

      Chinthammit, Chanadda (The University of Arizona., 2018)
      BACKGROUND Inappropriate medication use is common and represents a substantial clinical and economic burden in the United States (US). The Center for Medicare and Medicaid Services (CMS) has adopted one of the Pharmacy Quality Alliance (PQA)’s quality measures to assess percentages of older adult beneficiaries receiving high-risk medications (HRM) in Medicare Advantage Prescription Drug plan and stand-alone Prescription Drug plan. Understanding geographic patterns of HRM use may help CMS and their partners develop and tailor prevention strategies (such as prior authorization) to be implemented in the areas of need. Furthermore, The HRM use measure was used to assess Medicare Advantage Prescription drug plan (MA-PD) and stand-alone Prescription Drug plan (PDP) performance and to provide guidance for practitioners to reduce the use of such medications. Limited evidence exists on how HRM use is associated with patient characteristics and whether risk adjustment is necessary to accurately evaluate health plan performance on the HRM measure. OBJECTIVES The overall objectives of this research were to understand regional and patient characteristics associated with HRM use measure to develop a risk adjustment model for the HRM measure to accurately evaluated health plan performance. The first specific aims were to examined HRM use patterns among Medicare beneficiaries enrolled in: (1) Medicare Advantage prescription drug plans (MA-PDs); and (2) stand-alone prescription drug plans (PDPs) across geographic areas over time in the United States. The second specific aims were to: (a) measure HRM use in MA-PD and PDP beneficiaries with disadvantaged characteristics, including low income and disability; and (b) examine the relationship between disadvantaged characteristics and HRM use given constant effect of health plans. The third specific aims were to examine the relations between patient risk factors and the HRM measure and develop risk adjustment tool for the HRM measure in older adults enrolled in MA-PDs and PDPs. METHODS This cross-sectional study used a 5% national Medicare sample (2011–2013 for the first aims and 2013 for the second and third aims). Among beneficiaries aged ³65 years who were continuously enrolled in MA-PDs or PDPs (~1.3 million each year), we identified those with ≥2 prescriptions for the same HRM (e.g., amitriptyline) during the year based on the HRM list provided by CMS and Pharmacy Quality Alliance. For the first specific aims, multivariable logistic regression was used to estimate adjusted annual HRM use rates across 306 Dartmouth Atlas of Health Care hospital referral regions (HRRs), adjusting for sociodemographic, health-status, and access-to-care factors. For the second aims, Multivariable generalized linear mixed models were used to assess the association of HRM use and disadvantage factors such as low-income subsidy (LIS)/dual eligibility status (DE) and disability after adjusting for health plan effect and patient-level confounding characteristics (i.e., sociodemographic, geographic, clinical complexity). For the third aims, multivariable generalized linear mixed models were used to assess the association of HRM use and patient risk factors (e.g., age, gender) and identify risk factors after adjusting for health plan effect. The identified risk factors were used as variables for regression-based risk adjustment for the HRM measure. Unadjusted and adjusted quality rankings among health plans were compared. RESULTS First, a total of 1,161,076, 1,237,653, and 1,402,861 beneficiaries satisfied the study criteria and were included in 2011, 2012, and 2013, respectively. Among our study sample, nearly 40% (39%, 39% and 37% in 2011, 2012 and 2013 respectively) were enrolled in MA-PD plans, whereas remaining 60% (61%, 61%, and 63% in 2011, 2012 and 2013 respectively) were enrolled in PDP plans. HRM use significantly decreased over time among Medicare beneficiaries enrolled in MA-PD (13.1% to 8.4%, p<0.001) and PDP (16.2% to 12.2%, p<0.001) plans. Among MA-PD beneficiaries, HRM users more frequently: female (70.4% vs. 59.9%, p<0.001); White (84.6% vs. 81.4%, p < 0.001); eligible for the Part D Low Income Subsidy or Medicaid benefits (22.3% vs. 16.6%, p<0.001); and disabled (15.6% vs 8.7%, p<0.001) compared to non-HRM users in 2013. Among PDP beneficiaries, HRM users had higher proportions of: females (72.8% vs. 62.5%, p < 0.001); Whites (86.6% vs. 85.3%, p<0.001); LIS/DEs (29.2% vs. 23.3%, p<0.001); and disabled people (15.4% vs 8.5%, p<0.001) compared to non-HRM users. In 2013, the ratios of 75th-to-25th percentile HRM use rates across HRRs were 1.42 (MAPDs) and 1.31 (PDPs). HRRs with the highest HRM use rates were: Casper, WY (20.4%), Waco, TX (16.7%), Lubbock, TX (15.7%), Santa Barbara, CA (15.2%), and Temple, TX (15.1%) (MA-PDs); and Lawton, OK (18.8%), Alexandria, LA (18.8%), Lake Charles, LA (18.6%), Oklahoma City, OK (18.0%), and Slidell, LA (18.0%) (PDPs). Second, there were a total of 520,019 MA-PD and 881,264 PDP beneficiaries who met the study criteria. Of the MA-PD beneficiaries, 88,693 (17.1%) were LIS/DE and 48,997 (9.4%) were disabled. Of PDP beneficiaries, 213,096 (24.2%) were LIS/DE, and 83,593(9.5%) were disabled. LIS/DE beneficiaries had a higher percent of HRM users compared to non-LIS/DE MA-PD (17.0% vs. 9.6%, p < 0.001) and PDP (17.1% vs. 13.2%, p < 0.001) beneficiaries. Disabled beneficiaries had a higher percent of HRM users compared to non-LIS/DE MA-PD (17.0% vs. 9.6%, p < 0.001)) and PDP (17.0% vs. 9.6%, p < 0.001) beneficiaries. Multivariable analyses showed LIS/DE (OR = 1.07; 95% CI: 1.04, 1.10) and disability (OR =1.38; 95% CI: 1.34, 1.42) were associated with HRM among the MA-PD population as well as in the PDP population (LIS/DE OR = 1.14; 95% CI: 1.12, 1.16 and disability OR = 1.37; 955 CI: 1.34, 1.40). Third, the HRM users were more likely to be younger (OR = 0.981, 95% CI, 0.980-0.983 for MA-PD and OR=0.982, 95% CI, 0.981-0.983 for PDP); women (OR = 1.545; 95% CI,1.514-1.576 for MA-PD and OR=1.606, 95% CI, 1.584-1.628); eligible to receive low-income subsidy (OR = 1.086, 95%CI, 1.057-1.115 for MA-PD and 1.170, 95% CI, 1.150–1.190 for PDP); disabled (OR = 1.380, 95%CI, 1.342 –1.420 for MA-PD and 1.378, 95%CI, 1.352–1.405 for PDP); seeing multiple prescibers (OR =1.076, 95%CI, 1.072, 1.081 for MA-PD and 1.072, 95%CI, 1.069-1.075); filling prescriptions at multiple pharmacies (OR = 1.092, 95%CI, 1.083-1.102 for MA-PD and OR = 1.092, 95%CI, 1.086, 1.099 for PDP); and had higher average modified RxRisk-V (OR = 1.176, 95%CI ,1.171 – 1.181 for MA-PD and OR = 1.173, 95%CI, 1.170-1.176 for PDP). Being older and white were protective against receipt of HRMs. These variables were recommended for the risk adjustment model. Unadjusted scores showed low levels of agreement (Cohen’s kappa < 0.7) with risk-adjusted scores in identifying statistical outliers suggesting risk adjustment is necessary. CONCLUSION Geographic variation in HRM use exists among older adults in Medicare, regardless of prescription drug plans. Areas with high HRM rates may benefit from targeted interventions to prevent potential adverse consequences. LIS/DE; disability; demographic such as age, gender, race; and clinical complexity were associated with higher HRM use in both the MA-PD and PDP populations even when controlling for health plan effects. Failure to adjust for beneficiaries case mix might penalize some truly high-quality MA-PD and PDP providers that serve sick beneficiaries or beneficiaries with poor socioeconomic conditions.
    • Examining Three Levels of Social Integration and Health in Minorities: A Bioecological Perspective

      Flores, Melissa Ann (The University of Arizona., 2018)
      Background. Understanding and dismantling health disparities remain one of the most essential imperatives for our nation. The complexity of interacting sociodemographic and structural factors affecting health is difficult to quantify. Thus, sophisticated approaches which take into account not only an individual but their dynamic, social environments are necessary for understanding resiliency and strengths in these populations (Thornton et al., 2016). In this dissertation, I adopted a developmental perspective (e.g. Bioecological Theory) that may guide scientists when considering several interacting, sociocultural environmental factors at once. Social integration is a powerful force in an individual's life. Although 'social integration' may have many names (perceived social support, closeness of social ties, diverse social networks, etc.), broadly, it is accepted that one's social life has a profound impact on their corresponding health and mortality through various behavioral and physiological pathways (Holt-Lunstad, Smith, & Layton, 2010; Robles & Kiecolt-Glaser, 2003; Symister & Friend, 2003). Thus, any comprehensive study on health should include a broader investigation of socio-environmental variables including measures of social integration and broader community culture and resources. Historically, however, investigations focused on social integration, physical health, and the association between the two have traditionally underrepresented minority individuals (Heiat, Gross, & Krumholz, 2002; Hussain-Gambles, Atkin, & Leese, 2004; Murthy, Krumholz, & Gross, 2004). Research Aim and Questions. Adopting a social-ecological systems approach, the focus of my dissertation is to examine social integration at three levels (the spousal/partner relationship, immediate family-level dynamics, and neighborhood and community level factors) and the association of these levels of social integration with the health of minority individuals (Bronfenbrenner & Evans, 2000; Bronfenbrenner & Morris, 1998, 2007). I addressed this aim through three, separate research questions (RQ)/Chapters: RQ1/Chapter II) The individual and spousal/partner relationship, What are the associations between marital status and social support with health quality of life (HQoL), and mortality in post-menopausal, Hispanic women? RQ2/ Chapter III) Immediate family-level dynamics, Does synchrony of emotional arousal in diverse families facing breast cancer predict depressive mood and coping style in breast cancer patients? RQ3/ Chapter IV) Neighborhood and community level factors, Do social ties or social support mediate the ethnic density effect for Hispanics and other racial-ethnic groups? Methods and Data Sources. Three distinct data sources were examined within this body of work. In Chapter II, I utilized data from the Women's Health Initiative, Observational Study (Anderson, et al., 1998). In this analysis, I examined the relation between marital status and two outcomes: mortality and health quality of life. I also assessed whether the relations between marital status and these outcomes were attenuated or moderated by social support and language acculturation. In Chapter III, I utilized data collected for The Family Coping and Breast Cancer Project which recruited patients during the years of 1991 – 1993 (Weihs et al., 2005). In this analysis, I examined emotion arousal synchrony among family members (patient and spouse, and patient and child) using cross recurrence quantification analysis. I then examined whether the relations between emotion arousal synchrony and two breast cancer patient outcomes (coping style and depressive mood) are moderated by patient perceived family environment ratings or race. Lastly, in Chapter IV, I analyzed data from Wave 2 of the National Social Life, Health, and Aging Project (O’Muircheartaigh, English, Pedlow, & Kwok, 2014). In this analysis, I examined whether the Hispanic ethnic density effect was mediated by either social network variables (size, closeness of ties, and diversity) or social support and whether these associations were moderated by Hispanic ethnicity. Results. In the first study (Chapter II) I found that marital status was a significant predictor of mortality for older Hispanic women. Specifically, widowed women had significantly higher mortality risk when compared to their married counterparts. This relation, however, was not present after controlling for social support and language acculturation. In regard to health quality of life, marital status was associated with physical functioning, with widowed women reporting significantly worse physical functioning three years after baseline when compared with their married counterparts. This study suggests that widowed, Hispanic women may be at risk for poor health and this may be facilitated through social support and language acculturation. In the second study (Chapter III) I found that the relation between emotional arousal synchrony and patients' depressive mood in families facing breast cancer was moderated by family environment, specifically conflictual environments. I also found that the relation between emotional arousal synchrony and coping style was moderated by family environment, specifically for cohesiveness ratings. Moderation by race was not found. These results suggest that emotion arousal synchrony are family dynamics that may have differing implications depending on the family environment. In the third study (Chapter IV) I found two Hispanic ethnic density effects, but they were not mediated by social network variables. However, they were mediated by social support, but not in the direction I hypothesized. Social support was an inconsistent mediator of the relation between ethnic density and depressive symptoms and a suppressor of the relation between ethnic density and morbidity. These results suggest that for all racial/ethnic groups, ethnically dense neighborhoods do not beget higher social ties and social support. Conclusions. Overall, findings in this dissertation suggest that varying levels of the social-ecological environment are associated with health in minorities in various ways. A common phenomenon that arose in all three analyses were questions about how covariates or mediators influenced the association of the main variable of interest and its relation to different health outcomes. Broadly, this may be a common issue for social scientists interested in utilizing social variables from different social-ecological levels (micro-system, exosystem, etc.), which corroborates my previous statement regarding the complexity of social environments.
    • Effects of Stress, Sleep Hygiene, and Exercise on Academic Engagement in Undergraduate Students

      Nelson, Audrey (The University of Arizona., 2018)
      Academic engagement is important for the scholastic outcomes of college students, including degree completion. The current study examined the relations between stress and the intrinsic aspects of academic engagement (e.g. effort, attention, note-taking, attendance, asking for help, etc.), including the four factors of undergraduate engagement as outlined by Handelsman, Briggs, Sullivan, & Towler (2005): Factor 1 – “skills engagement,” Factor 2 – “emotional engagement,” Factor 3 – “participation/interaction engagement,” and Factor 4 – “performance engagement,” in addition to the mediating/moderating properties of the self-care practices of sleep hygiene and physical activity. Intrinsic versus extrinsic engagement was evaluated in this study as it is believed this approach affords more opportunities for subsequent interventions since they can be implemented in an individual or small group setting, and not be constrained by the challenges of making large institutional changes. The sample consisted of 203 undergraduate students from a large southeastern university. Results indicated that stress was negatively correlated with the factor of academic engagement most related to executive functioning (i.e. skills engagement). Of the independent variables evaluated, sleep hygiene showed the strongest correlations with academic engagement, most specifically for the skills engagement and performance engagement factors. Sleep hygiene also functioned as a mediator in the relationship between stress and the skills factor of engagement, resulting in a 47% reduction in the effect of stress. Exercise did not show correlations with any areas of engagement, but did show a small interaction effect on the relationship between stress and the academic engagement factor of participation/interaction. Stress was seen to have a positive impact on participation/interaction engagement. A moderating effect of physical activity was identified, leading to lower participation/interaction engagement when both stress and exercise were high. Exercise, ethnicity, age, class rank, and gender did not add predictive ability to any of the models for academic engagement/factors of engagement. These results highlight the potential benefits of improving sleep habits and promoting programs aimed at minimizing and addressing stress (e.g. meditation, mental health supports) in order to promote success and positive academic outcomes in undergraduate students. Directions for future research were also discussed.
    • Machine Reading for Scientific Discovery

      Hahn-Powell, Gus (The University of Arizona., 2018)
      The aim of this work is to accelerate scientific discovery by advancing machine reading approaches designed to extract claims and assertions made in the literature, assemble these statements into cohesive models, and generate novel hypotheses that synthesize findings from isolated research communities. Over 1 million new publications are added to the biomedical literature each year. This poses a serious challenge to researchers needing to understand the state of the field. It is effectively impossible for an individual to summarize the larger body of work or even remain abreast of research findings directly relevant to a subtopic. As the boundaries between disciplines continue to blur, the question of what to read grows more complicated. Researchers must inevitably turn to machine reading techniques to summarize findings, detect contradictions, and illuminate the inner workings of complex systems. Machine reading is a research program in artificial intelligence centered on teaching computers to read and comprehend natural language text. Through large-scale machine reading of the scientific literature, we can greatly advance our understanding of the natural world. Despite remarkable progress (Gunning et al., 2010; Berant et al., 2014; Cohen, 2015a), current machine reading systems face two major obstacles which impede wider adoption: <i>Assembly</i> The majority of machine reading systems extract disconnected findings from the literature (Berant et al., 2014). In areas of study such as biology, which involve large mechanistic systems with many interdependent components, it is essential that the insights scattered across the literature be contextualized and carefully integrated. The single greatest challenge facing machine reading is in learning to piece together this intricate puzzle to form coherent models and mitigate information overload. In this work, I will demonstrate how disparate biomolecular statements mined from text can be causally ordered into chains of reactions (Hahn-Powell et al., 2016b) that extend our understanding of mechanistic biology. Then, moving beyond a single domain, we will see how machine-read fragments (influence relations) drawn from a multitude of disciplines can be assembled into models of children’s heath. <i>Hypothesis generation and “undiscovered public knowledge”</i> (Swanson, 1986a) Without a notion of research communities and their interaction, machine reading systems struggle to identify knowledge gaps and key ideas capable of bridging disciplines and fostering the kind of collaboration that accelerates scientific progress. With this aim in mind, I introduce a procedure for detecting research communities using a large citation network and derive semantic representations that encode a measure of the flow of information between these groups. Finally, I leverage these representations to uncover influence relation pathways which connect otherwise isolated communities.
    • Supporting Parents as College Advisors: A Qualitative Study of First Generation College Students' Parents

      Valencia, Marylyn (The University of Arizona., 2018)
      This study identified first-generation college student’s parents’ needs and support systems during their child’s college admissions process. Literature supports the benefits of improving college knowledge among high school parents of first-generation college students. Parent college knowledge includes information about the college admissions requirements, college admissions processes, parental involvement, and access to social support. Research on these populations is more commonly done through quantitative studies that do not always include parents’ voice or qualitative research that tends to highlight students’ experiences. Regardless of the type of research, parents’ ability to provide guidance has a significant impact on first-generation college students’ enrollment and retention rates (Auerbach, 2007; Duggan, 2001). Social capital informed the design of this study to examine the access of college knowledge resources used by first-generation college students’ parents. The qualitative study was supported in a constructivist epistemology. Data were collected through semi-structured focus groups and individual interviews, which included 28 high school parents and/or guardians. Results categorized into three factors: college admissions requirements, the navigation of the college admissions process, and access to social support for guidance. The study concludes with findings that allow educators to better understand the needs of first-generation college students’ parents as well as steps that can be taken to provide parents with the tools needed to better guide their children through the college admissions process. Keywords: parent college knowledge, educational equity, college admission, high school
    • The Nature of the Vertical Distribution of Seismic Responses in Multi-Story Structures

      Kuzucu, Ismail Bahadir (The University of Arizona., 2018)
      This Ph.D. research investigates the vertical distribution of seismic responses and controlling seismic response patterns in multi-story reinforced concrete and steel structures. Seismic responses of buildings designed by conventional force-based or displacement-based approaches result in significant force demands compared to nominal design as observed in both experimental studies and earthquake simulations. Furthermore, force patterns suggest that the floor forces are predominantly controlled by higher modes especially when modal properties of buildings alter due to inelastic deformations. Therefore, actual force patterns experienced by buildings may not comply with the design code assumptions such as equivalent lateral force or response spectrum analysis. The main assumption in those methods, that the response of a building is dominated by the first mode excitation, may not be valid under strong earthquakes when inelastic deformations contribute significantly to the total response. Design code assumptions imply inelasticity to have same effects in all modes of response, though it may have significant effects on the demands associated with the first mode, higher modes may not be affected the same way. Further the distribution of seismic responses may differ for different types of lateral force resisting systems since each system possesses different response mechanisms such as formation of inelastic deformations. To better understand the distribution of seismic demands, response intensity measures obtained through nonlinear time history analysis are examined closely in terms of magnitude and shape along the height of buildings for different types of lateral force resisting systems in this study. This dissertation examines various types of buildings to address and shade light on those issues and observations mentioned above.
    • Planetary Granular Topography: Slope Angles & Crater Concentric Ridges

      Atwood-Stone, Corwin (The University of Arizona., 2018)
      In the first portion of this dissertation I examine the effect of gravitational acceleration on the angle of repose of granular features. To do this I have used HiRISE DTMs to compare the slipface angles of Martian sand dunes with those measured on Earth. In doing this I have found that the slopes of active dunes on Mars do not differ from their terrestrial counterparts, and as such I have concluded that gravitational acceleration does not effect the angle of repose. In the second, larger portion of this dissertation I examine the morphology and formation of Crater Concentric Ridges (CCRs). These features, formerly known as 'Lunar Concentric Dunes', are ridges oriented concentrically to fresh craters a few kilometers in diameter. Using LROC NAC data I have created a catalog of 77 craters that have these features in their ejecta blankets. Further, I have used this data to map and measure the CCRs around eight craters of varying diameters in order to analyze their distributions. I have also been able to characterize the morphology of these ridges and how that morphology changes with distance from the host crater. Using DTMs made from NAC images I have studied the three-dimensional topography of CCRs in order to fully describe the morphology of these features. This morphological analysis has allowed me to refute several hypotheses for the formation of these features, including the previously accepted ballistic impact sedimentation and erosion hypothesis. In order to formulate a new theory for the formation of these features I have created simulations of crater ejecta flowing over regolith using discrete element modeling. In these simulations I found that Kelvin-Helmholtz instabilities form at the interface between the ejecta and regolith. I posit that these instabilities are responsible for the formation of Crater Concentric Ridges. This hypothesis is supported by the observation that the topography produced in my simulations strongly resembles that which I have measured and described around real lunar craters.
    • Socially Constructed Narratives for Exploring the Impacts of Air Pollutant Infiltration in Built Environments

      Bernal, Sandra Maria (The University of Arizona., 2018)
      This dissertation is an autoethnographic (self-guided) interdisciplinary process done by an empathetic entity (me) who noted a problem sorting out the effects of outdoor air pollutants that infiltrate indoors from those of other indoor pollutants. This problem is the lack of understanding by architects, planners, and other experts of relevant implications of their lack of attention to the infiltration of airborne dust indoors in the arid regions of Arizona. This systematic process of informed reflections is written in a continuous narrative, and breakouts or Vignettes. Each Vignette corresponds to a topic directly relevant to the research and contains the evidence that answers an inquiry followed by a reflection based on my experience and observations. In the study of arid lands, autoethnographic Vignettes provide an alternative approach for taking a scientific point of view to reveal complex interactions between the natural and built environments for arid regions and other regions that may experience drier and warmer climatic conditions in the future.
    • Statistical Methods for Next Generation Sequencing Data

      Zhang, Miao (The University of Arizona., 2018)
      Statistical genetics is a scientific field concerned with the development of statistical methods for drawing inferences from genetic data. Research in statistical genetics generally involves developing theory or methodology to support research in one of three related areas: population genetics, genetic epidemiology and quantitative genetics. This dissertation is an ensemble of my research work in statistical genetics, including three projects with varying focuses. The first project applies a rare variant region-based test to identify sets of common or rare variants aggregated in and around genes associated with Dravet Syndrome. The second project proposes a score-based test to investigate the association for a set of rare variants and ordinal traits. The third project describes an implement of dimensionality reduction method in genotype data for population inference.
    • The European Yankee: A Study and Performance Guide of George Chadwick’s A Flower Cycle

      McNiff, Brian (The University of Arizona., 2018)
      This document examines the solo vocal music of American composer, George Whitefield Chadwick (1854-1931), and focuses on his 1892 collection, A Flower Cycle, with poetry written by Arlo Bates (1850-1918). It highlights the European influence in Chadwick’s writing style that created a Euro-American hybridized style in the United States. Though his instrumental works have been widely performed and analyzed, his art songs have not received the same amount of attention. Excerpts of the songs in A Flower Cycle will be analyzed and compared to various German lied and French mélodie to show the similarities in style and Chadwick’s penchant for being influenced by these European composers. The second intent of this document is to provide a guide with which to perform any or all of the pieces therein with proper understanding of the text and how it is set musically. The poetry is believed to have been written specifically to be set to the music for this collection with the exception of The Jacqueminot Rose, which was the inspiration for the construction of A Flower Cycle
    • L1 Biases in Learning Root-And-Pattern Morphology

      Drake, Shiloh N. (The University of Arizona., 2018)
      This dissertation addresses the question of whether non-adjacent morphological dependencies are as difficult to learn as non-adjacent phonological dependencies. Non-adjacent dependencies have been investigated in the past, and have proven to be at best difficult to learn (Bonatti, Peña, Nespor, & Mehler, 2005; Gómez, 2002; LaCross, 2011, 2015; Newport & Aslin, 2004), and at worst, completely unlearnable (Newport & Aslin, 2004: experiment 1). LaCross (2011, 2015) showed that speakers of a language employing non-adjacent dependencies were able to learn an artificial grammar employing analogous non-adjacent dependencies easily, suggesting there may be a linguistic bias that makes speakers more aware or capable of unconsciously parsing non-adjacent dependencies so long as they speak a language that employs vowel harmony. The research in this dissertation studies three subject populations with two tasks and two grammars to discover whether speakers of a language utilizing root-and-pattern morphology also have the ability to unconsciously parse non-adjacent dependencies pred- icated on morphological structure. Chapter 2 uses a segmentation or statistical learning task similar to the experiments mentioned above, while Chapter 3 uses a word elicitation task to establish a more fine-grained representation of what experiment participants learn after a very short exposure. The experiments show that there may be a cognitive bias toward concatenative morphology even among Arabic and Maltese speakers, but also that Arabic and Maltese speakers are willing to adjust CV skeleta and syllabic structure when deriving plural forms from singular forms. The methods that they use when producing novel plural forms are similar to those found in their L1, showing that this type of bias is predicated on morphophonological structure in the participants’ L1. The results together support a root-based lexicon for Arabic and Maltese and aggressive morphological decomposition (Boudelaa & Marslen-Wilson, 2001, 2004a, 2004b, 2015; Deutsch, Frost, & Forster, 1998; Frost, Deutsch, & Forster, 2000; Frost, Forster, & Deutsch, 1997; Ussishkin, Dawson, Wedel, & Schluter, 2015) even in novel words. Additionally, this work supports the notion of morphological abstraction, abstract grammatical features (such as past or plural) may be expressed by multiple allomorphs, particularly in the context of learning a new language. I extend this work to suggest that a processing model of Distributed Morphology (Halle & Marantz, 1993; Harley & Noyer, 1999; inter alia) would be appropriate both to model the results here and to better explain morphological processing disorders. Although Distributed Morphology has not been extensively tested as a processing model, recent research shows compatibility with existing psycholinguistic models (Gwilliams & Marantz, 2015; Stockall & Marantz, 2006) and has better explanatory power for deficits in morphological processing (Tat, 2013).
    • Residential Flood Risk and Knowledge Assessment in the Tucson Metropolitan Area

      Jordan, Erin Theresa (The University of Arizona., 2018)
      This research explores the challenges of reducing arid land flood risk among a diverse and growing community, plus reveals how population demographics can play a role in determining vulnerability to flooding. Communities make an effort to become more resilient when natural disasters occur. Ideally, these efforts will lessen the physical and economic impacts during and after subsequent events. For the Tucson Metropolitan Area (TMA), a major push to build resilience was initiated after a 1983 flood event. Those efforts proved successful, reducing damage and recovery time when other major floods hit the area. However, homes remain in high risk flood areas and data show Hispanic homeowners may be the most vulnerable to flooding in the TMA. But, data also indicate all homeowners, no matter their race or cultural heritage, in high risk areas may be able to better afford flood insurance, which is a policy supplemental to home insurance. Plus, survey results show homeowners may be more likely to accept personal responsibility for the financial impacts of floods as compared to an earlier study also completed in the TMA. Tailored education efforts addressing why a homeowner would choose or not choose a flood insurance policy could increase the number of policies in force, which potentially builds personal resilience, while also strengthening the community’s ability to withstand the impacts of the next big event.
    • The Transit Light Source Effect

      Rackham, Benjamin Vern (The University of Arizona., 2018)
      Transmission spectroscopy provides a powerful probe of exoplanet atmospheres, enabling constraints on their compositions and structures. Recent advances in instrumentation and observational techniques have enabled detections of molecules in the atmospheres of exoplanets as small as Neptune as well as provided constraints on cloud properties for Earth-sized and super-Earth exoplanets. However, these precise observations have also revealed that the heterogeneous nature of stellar photospheres presents a significant challenge to high-precision transit depth determinations. This owes to a fundamental limitation of the transmission spectroscopy technique, which is that transiting exoplanet atmospheres are illuminated by a spatially resolved region of the stellar photosphere, the spectrum of which we cannot directly measure. Any difference between the out-of-transit disk-averaged emergent spectrum of the star—our necessary reference by which we measure transit depths—and the average emergent spectrum of the transit chord—the true light source for the transmission measurement—will imprint on the observed transmission spectrum. This phenomenon is what I term the transit light source effect. In this thesis, I present my work to understand the transit light source effect in F to M dwarf systems and constrain stellar contamination signals in transmission spectra from two M dwarf systems. I first describe a modeling effort to constrain spot and faculae covering fractions and the concomitant stellar contamination spectra on M dwarfs. I find that large covering fractions of active regions are possible for typically active M dwarfs, and therefore stellar contamination signals can be likewise large and even overwhelm planetary atmospheric features produced by small transiting planets. This is indeed what I find in two observational studies of transiting M dwarf systems: the M4.5V GJ 1214 system and the M8V TRAPPIST-1 system. I then expand the analysis to F5V to K9V spectral types, investigating stellar contamination signals with a model similar to that presented for M dwarfs. I find that stellar contamination signals are much weaker for typical F to K dwarfs than for M dwarfs, though signals are detectable in high-precision transmission spectra, and active G and K dwarfs, in particular, can impart relatively large transit depth changes. Finally, I summarize the findings of this thesis and conclude with a look toward future prospects for disentangling stellar and planetary signals in exoplanet transmission spectra.
    • Characterization, Setting, and Drama: Rhetorical Practice in Schütz’s Weihnachtshistorie, SWV 435

      Sletta, Travis John (The University of Arizona., 2018)
      This study demonstrates how the compositional choices Heinrich Schütz made while completing Weihnachtshistorie reflect the influence of musica poetica and musical rhetoric. The study examines how selected musical processes accomplish rhetorical or persuasive goals. Special attention is paid to the musical-rhetorical methods Schütz used to individualize, illuminate, and highlight the personal qualities of each of the mortal characters through musical means to strengthen the overall credibility of the story. The study reveals that the colorful manner in which Schütz paints his characters, while aesthetically pleasing, is a consequence of the application of rhetorical principles to musical composition meant to persuade the listener of the central theological proposition of the work.
    • In Questo Proposito: Formal Innovations in the Vespers by Chiara Margarita Cozzolani

      Nihira, Caleb (The University of Arizona., 2018)
      The focus of the current study is the use of form in the collection of Vespers music by Chiara Margarita Cozzolani (1602-c.1678), an Italian Benedictine nun living in Milan who spent her entire life cloistered within the walls of the Santa Radegonda convent. Although her life was typical of upper-class Milanese women, her compositions demonstrate that her approach to music is anything but typical. She composed in every genre of her day and published a large amount of music during her lifetime. Cozzolani’s collection of Vespers music comes from her final publication of 1650. With the exception of a few historians who have focused specifically on convent music, such as Robert L. Kendrick and Craig Monson, this music has largely been overlooked. The reasons for this are unclear given the wealth of material and the quality of musical aesthetic of this music. It is, however, heartening to see the body of research into Cozzolani’s music grow due to the renewed interest in music by female composers both past and present.
    • Challenging the Status Quo: What Arizona Principals of High Performing Urban Schools are Doing to Improve the Outcomes of Latino Students

      White, Mary M Carter (The University of Arizona., 2018)
      This qualitative comparison case study investigates the beliefs and behaviors of two Arizona principals who serve predominantly Latino students in excelling urban public high schools. It also examines the structures positioned to promote equitable educational opportunities. Although the majority of K-12 students in Arizona are Latino, the public education system is designed to accommodate the White minority with Eurocentric curricula and assessment, rigorous coursework, and access to post-secondary education. However, a purposive sampling demonstrates how two high poverty schools with majority Latino student populations are disrupting the status quo as evidenced by the outstanding graduation rates and low dropout ratio; additionally, their Latino students are entering post- secondary education at higher rates than the state and National averages of their peers. Moreover, both principals cultivate a caring and supportive climate amidst politically charged concerns that disrupt the educational environment. By applying a tripartite synthesis of Scanlan and Lopez (2012) and Khalifa, Gooden and Davis’ (2016) framework, the principals’ behaviors and beliefs are analyzed through the constructs of culturally responsive and equitable leadership. Critical consciousness, deficit thinking, high quality teaching, sociocultural integration, and other themes are explored. Through a comparative case study (CCS) approach (Bartlett & Vavrus, 2016), interviews and observations of the principals as well as field notes and artifacts are analyzed on the horizontal and vertical axes. The data are triangulated for validity to determine what beliefs, behaviors and structures are utilized by principals to promote educational success for their Latino students. Additionally, Arizona’s educational policy is analyzed on the transversal axis over time and space exposing unfair practices that historically have hindered and continue to oppress the advancement of our Latino youth. The study discovers how the principals’ critical awareness of their students’ background and lived experiences contribute to the development of a caring, inclusive, and efficacious campus environment. Also discovered, the importance of principal beliefs to empower Latino youth. Both school leaders yield high expectations for every student with the belief that each can and will be successful, and the principals assume responsibility to provide access to higher education for every graduating senior. Other findings reveal deficit thinking, segregation, and discrimination continue to plague school environments which may result from the dominant culture reigning over Arizona’s educational policy, curricula, structures and practice. An unintentional finding is the influence of politics, safety and media on the schools, the students, and their families; these themes emerge as primary concerns in contemporary public education. One interesting conclusion that implicates further research is the value of principals who have similar ethnic, social, and cultural backgrounds as their students; the connection may be significant in contributing to improved academic outcomes. In the end, the study reveals the behaviors and beliefs of school leaders that can improve or inhibit Latino student outcomes; ultimately, there is urgent need for advocacy and policy reform on the local, state, and federal level if our student majority is to learn and thrive in Arizona schools.
    • An O(n) Framework for Internal Coordinate Molecular Dynamics Applicable to Molecules with Arbitrary Constraints and Geometries

      Xu, Xiankun (The University of Arizona., 2018)
      Molecular Dynamics (MD) is a numerical simulation technique which is used to obtain the time evolution trajectory of a system of interacting particles. Consideration of the molecular movement in the space of generalized internal coordinate rather than in Cartesian coordinate is an efficient way to deal with the constraints such as fixed angles and lengths. This type of molecular dynamics is called Internal Coordinate Molecular Dynamics (ICMD). To integrate the equation we need to invert the dense mass matrix. Since the direct calculation of mass matrix inversion is cubically scaled with the number of atoms in a molecule, a more efficient method is required for macro-molecules simulation. Fixman's work in 1974 and the follow-up studies have developed a method that can factorize the inverse of mass matrix into an arithmetic combination of three sparse matrices—one of them is positive definite and need to be further factorized by using the Cholesky decomposition or similar methods. When the molecule subjected to study is of serial chain structure, this method can achieve $\mathcal{O}(n)$ computational scaling, where $n$ is the number of atoms within a specific molecule. However, for molecules with long branches and loops, the nonzero structure of this positive definite matrix makes its decomposition in scaling of $\mathcal{O}(n^3)$. We have presented a new method which can guarantee for no fill-in in doing the Cholesky decomposition. As a result, the inverting of mass matrix will remain the $\mathcal{O}(n)$ scaling, no matter the molecule structure has long branches or not. Based on the above $\mathcal{O}(n)$ method in inverting mass matrix, an $\mathcal{O}(n)$ framework for internal coordinated molecular dynamics has been built. It has the following properties: has $\mathcal{O}(n)$ time complexity; constraints such as constant bond lengths and angles can be arbitrarily applied\added{ on tree structures}; suitable to complex geometries such as branches, \added{flexible }loops, dummy atoms/sites; and is singularity free in inverting mass matrix. When compared to traditional MD methods, the new method is especially powerful in macromolecule simulations. The ICMD utilizes the bond angle $\theta_i$, torsional angle $\phi_i$, and bond length $b_i$ as the basic types of internal coordinate parameters. However, there is a serious problem of using $\theta_i$ and $\phi_i$ as the internal coordinates. When $\theta_i$ is very close to $0$ or $\pi$, the mass matrix becomes singular and its inverse does not exist, so that the numerical integration of the equations of motion is unstable in this situation. In this work, we will introduce a convention switch method which can prevent the singularity by adopting two alternative rotation conventions. According to our test, this method is suitable to any size of molecule. In addition, it only requires a very small amount of additional computational cost. The conservation of total energy in microcanonical (NVE) ensemble simulation is extremely important because the NVE ensemble simulation is a statistical sampling over the constant energy surface in the hyperdimensional phase space. A symplectic numerical scheme can make the error of the total energy be bounded even for exponentially large simulation time. On the other hand, non-symplect time integrators such as 4th order Runge-Kutta (RK4) would give monotonic increasing or decreasing total energy. In internal coordinate molecular dynamics, the Hamiltonian is a strongly coupled equation which depends both on the momentum and position vectors, and very few explicit symplectic numerical methods existing for inseparable Hamiltonian. In this work, the influence of symplectic and non-symplectic time integrators on the energy conservation of ICMD have been studied.
    • Experimental and Theoretical Investigation of Electrochemical Water Treatment Processes

      Chen, Yingying (The University of Arizona., 2018)
      Two kinds of electrochemical methods for water treatment were investigated, namely electrocoagulation and bipolar membrane electrodialysis (BMED). Electrocoagulation with mild steel anode was investigated to remove dissolved silica from simulated high efficiency reverse osmosis (HERO) concentrate solutions, and was compared with traditional chemical coagulation with FeCl3. The recommended optimal initial pH value for electrocoagulation is 8. 76-89% silica removal was achieved with 4.0 mM iron dose in electrocoagulation, while a maximum of 64% removal was achieved by chemical coagulation with a dose of 4.0 mM FeCl3. BMED was used to produce acid and base from dilute sodium sulfate or sodium chloride salt solutions. Using single pass BMED, >75% current utilization was achieved producing acids and bases with concentrations of ~75% of the feed salt concentration. Factors affecting current utilization and limiting current density were investigated. The energy required to produce a mole of acid or based increased linearly with increasing current density. The energy costs for producing acids and bases were ~10 times lower than costs for purchasing bulk HCl and NaOH from local suppliers. A BMED stack was used in a zero-liquid-discharge (ZLD) system of water softening for regenerating ion exchange media and for promoting crystallization of hardness minerals in a fluidized bed crystallization reactor (FBCR). The overall closed-loop process eliminates the addition of extra chemicals and the creation of waste brine solutions. However, the key component in BMED – bipolar membranes (BPMs) are ill suited for water/wastewater treatments, due to low stability in alkaline solutions and high voltage drop at low current densities. The alkaline stability of the BPMs was improved by replacing the anion exchange layer with base-stable anion exchange membranes designed for alkaline fuel cells. In order to decrease the water splitting voltage, different electronically conductive materials and graphene oxide were tested as the interlayer catalyst of BPMs. Two methods of modeling were applied to study the structure of BPM and the mechanisms of water splitting in BPM. A 3-D point-charge method was used to model the 3-D interlayer of the BPM, where each functional group in both ion exchange layer (IEL) was treated as a point charge and different charge screening was applied. A one-dimensional continuum model of BPM was also applied to investigate ion concentration gradients in BPMs under reverse bias conditions.
    • Rediscovering the Unique Role of the Contralto in the Operas of Gioachino Rossini

      Pack-Smith, Piper (The University of Arizona., 2018)
      Gioachino Rossini was perhaps more prolific than any known composer in his operatic writing for the mezzo-soprano and contralto voices. While modern practice casts many of these roles as somewhat interchangeable among mezzo-sopranos, recent writings have lamented the decline in the number of contraltos. This asks the question of whether or not the composer's own distinctions indicate that contraltos should be uniquely represented in these roles. This paper is an examination of Rossini's writing for some of his favorite singers, including Marietta Marcolini, Adelaide Malanotte, and Isabella Colbran, as well as later interpretations by Giuditta Pasta, in order to discover the unique imprint that they left on these roles. In addition, this paper will outline the history of the contralto as it pertains to the development of Rossini as a composer and the facets of character, tessitura, range and ensemble writing to explore how Rossini may have heard and appreciated the central part of the female voice, and what makes his writing for these voice types historically distinct and significant.