• Audiologic Rehabilitation Needs of Adults with Hearing Loss

      Robbins, Chloe (The University of Arizona., 2018)
      The Living Well with Hearing Loss Audiologic Rehabilitation Program for Adults at the University of Arizona has been in existence since 2010. Over 600 adults with hearing loss and their frequent communication partners have participated in the group audiologic rehabilitation (AR) program at various stages of their journey as a person with hearing loss. This study aims to identify barriers to participation in group AR for University of Arizona Hearing Clinic patients through in-person interview. Patients who receive hearing healthcare services at the UA Hearing Clinic are classified into one of the following billing groups: Medicare, Vocational Rehabilitation (VR), Self-Pay, EPIC provider group, and Sertoma Arizona Hearing Aid Bank (HAB). A purposeful oversampling of HAB patients was performed due to an observed low attendance rate for group AR for this population. Audio-recorded interviews were conducted prospectively with a sample of 30 hearing aid patients between May-October 2016. Content analysis methods were used to gain insight into perspectives of those with hearing loss. Interview response data were coded using the Capability, Opportunity, Motivation and Behavior (COM-B) model (Michie, Atkins, & West, 2014). Results provide insight into current barriers to participation in group AR and specific modifications that may make the program more accessible for adults with hearing loss and their families in Southern Arizona.
    • The Well of the Past: How Experience with Problems While Using Prior Technologies Affects the Adoption of New Technologies

      Paik, Eugene Taeha (The University of Arizona., 2018)
      This dissertation questions how organizations’ experience with problems while using prior technologies affects the adoption of new technologies. It develops and tests a model of technology adoption that takes into account three factors – characteristics of organizations, technologies, and the environment. Drawing on organizational learning theory, this dissertation makes four general predictions. First, focal organizations’ direct experience with problems while using prior technologies increases the likelihood of adopting new technologies. Second, focal organizations’ indirect experience with problems through their production network partners increases their likelihood of adopting new technologies and strengthens the relationship between direct experience and technology adoption. Third, the relationship between learning from direct and indirect experiences and technology adoption is stronger for a new technology developed inside the industry than for that developed outside the industry. Lastly, organizations’ social relationships with production network partners, which are influenced by both types of learning, affect the likelihood of adopting new technologies. I test these predictions in the context of the music recording industry, using a longitudinal dataset of records released in the U.S. music recording industry between 1962 and 2005. Five on-line metadata servers provide detailed information on records, record labels, artists, and other participants in record production. I discuss the implications of my findings for organizational learning theory, social network perspective, and the literature on technological change.
    • Employing the Acoustic Change Complex for Vowel Discrimination

      Cheek, Diane Elizabeth (The University of Arizona., 2018)
      A change occurring within an acoustic stream evokes the cortical potential known as the acoustic change complex (ACC). The present study addressed the effects of level and vowel contrast type on ACC amplitudes and latencies. Nineteen normally hearing adults were tested with vowel tokens, /a/, /i/, /o/, and /u/, of 500 ms duration presented at 2/s, in an oddball paradigm at 40 and 70 dBA in the sound field. The ACC was present for all vowel contrasts. The ACC for vowel contrasts are robust even at low levels (40 dBA), i.e., 25-30 dB HL, as evidenced by the high prevalence of responses in the contrast (vowel change) conditions that were significantly greater in amplitude than in the control (no vowel change) conditions. ACC absolute amplitudes were significantly larger at 70 dBA and amplitudes for control conditions were 4-6 times smaller than contrast conditions, but latencies were not sensitive to level or vowel type. ACC amplitude ratios were then calculated as: amplitude of contrast responses ÷ amplitude of control responses. The ACC amplitude ratios varied with vowel pair and by level. The distribution of amplitude ratios obtained indicated that over 90% of ratios are greater than 1.0, and over 84% are greater than 2.0, suggesting that this metric is a sensitive measure of cortical speech feature discrimination. These data set a baseline for a larger study of the ACC in infants, children, and adults with hearing loss.
    • Exploration of Preconception Education Using Social Media

      Luckart, Julie Kathleen (The University of Arizona., 2018)
      Women that experience unintended pregnancies have significantly poorer maternal, neonatal and fetal outcomes. Nearly half of all pregnancies are unintended, underscoring the need to find more effective strategies to educate women about preconception care. The body of evidence for using social media to disseminate and gain health information is rapidly growing, as one in four Americans now uses social media to seek health information. This pilot project is constructed around the elements of preconception care, the internet, and social media and is designed to explore if and how young women in Clark County, Washington, are using social media to gain knowledge about preconception care. Qualitative description was the design for this study. Twelve non-pregnant, English speaking female residents of Clark County, between the ages of 18 to 24, were recruited via Facebook and snowballing, and took an online survey, using Qualtrics. Results revealed that to learn about health care topics, 75% of respondents use the Internet, 58% use their healthcare provider, and 25% use social media, but to get information that they trust, 58% prefer a health database and 42% prefer a healthcare provider. Respondents also indicated that 81% were not taking folic acid supplementation and 78% were overweight or obese. It appears that the Internet and apps are used and trusted more than social media, and online platforms are preferred for receiving health information. Respondents expressed a high level of trust in health care providers, but used online platforms first to save time, prepare for appointments, and compare information to achieve consensus. Recommendations include collaborative educational interventions with the March of Dimes, the public health department, and local health care delivery entities to share how to protect online privacy, where to look for credible information online, designing an online intervention to promote folic acid supplementation, and suggestions for further research.
    • On Congruence Modules Related To Hilbert Eisenstein Series

      Shih, Sheng-Chi (The University of Arizona., 2018)
      We generalize the work of Ohta on the congruence modules attached to elliptic Eisenstein series to the setting of Hilbert modular forms. Our work involves three parts. In the rst part, we construct Eisenstein series adelically and compute their constant terms by computing local integrals. In the second part, we prove a control theorem for one-variable ordinary \Lambda-adic modular forms following Hida's work on the space of multivariable ordinary \Lambda-adic cusp forms. In part three, we compute congruence modules related to Hilbert Eisenstein series through an analog of Ohta's methods.
    • Flashy, Patchy, and Coupled: Using Spectral and Gas Exchange Approaches to Refine Dryland Carbon Uptake Predictions Across Spatial and Temporal Scales

      Barnes, Mallory Liebl (The University of Arizona., 2018)
      Carbon dioxide, a greenhouse gas, traps heat in the atmosphere, causing the planet to warm. The rate at which plants take up atmospheric carbon dioxide depends on climatic and biophysical factors, including soil moisture, atmospheric demand, and drought. Climate models disagree on the magnitude and trend in the terrestrial carbon sink. Accurate assessment of the role of terrestrial plants in the carbon cycle is essential to predicting the degree of future climate change. Drought impacts on the carbon cycle are driven by the cascading impacts of leaf-level physiological responses to limit water loss. Dryland ecosystems like those in the Southwest (southwest United States and northwest Mexico) are an exemplary location to study drought impacts on the carbon cycle due to persistent water limitation and associated tight coupling between hydrologic and carbon cycles. Furthermore, future climate projections suggest more frequent and intense drought in the world’s water-limited regions. My dissertation research improves understanding of coupled carbon and water cycles in dryland ecosystems, and informs predictions of vegetation response to future climate conditions. Using a combination of remotely sensed and gas exchange data, I explore drought impacts on plant productivity and carbon uptake in water-limited systems across spatial and temporal scales. The studies contained in this dissertation address three key knowledge gaps: 1) the effects of drought timing on vegetation and ecosystem processes, 2) relationships between leaf-level spectral and physiological properties, and 3) impacts of climate variability on coupled carbon and hydrologic cycles and associated predictions of regional and global carbon dynamics. First, I investigate how the intra-annual timing of drought in the Southwest influences the productivity of grasslands, shrublands, and forests. This study underscores the importance of sub-annual droughts in dryland carbon uptake dynamics and identifies the critical climate period for Southwest forests, shrublands and grasslands during which climate conditions disproportionately impact annual carbon uptake. Second, I establish a link between spectral measures of productivity and photosynthetic capacity at the leaf level in the context of a field experiment. This experiment compared hyperspectral imagery with photosynthetic capacity estimated from leaf gas exchange measurements. Performed during a mid-summer period with low rainfall and associated reductions in photosynthetic capacity, the results of this experiment suggest that spectrally-derived estimates of photosynthetic capacity are robust to within-season temporal variation. Thirdly, I upscale ecosystem-level eddy covariance observations to the Southwest region to assess drought impacts on regional carbon uptake using machine learning techniques. The results of this study highlight the crucial importance of accounting for water balance and drought dynamics in studies of carbon uptake in water-limited ecosystems. The application of the derived algorithm to the global scale suggests that the inclusion of intra- and inter- annual drought metrics can improve modeled interannual variability in global carbon uptake. Soil moisture is a key control on vegetation productivity and carbon uptake in dryland ecosystems, and I use drought indices and meteorological variables as proxies for soil moisture dynamics in this research. Collectively, my work is showing how the timing and intensity of drought impacts carbon uptake and vegetation productivity in dryland ecosystems. This cross-scale approach provides new insights into drought impacts on vegetation productivity and biosphere-atmosphere interactions in drylands. Overall, improved representation of the spatial and temporal dynamics of interactions between drought and carbon in drylands will lead to better projections of future water and carbon cycling and the magnitude and speed of global climate change.
    • Multimodal Biliteracies in the Arizona-Sonora Borderland

      Fierro, Ana Victoria (The University of Arizona., 2018)
      This qualitative study explored multimodal biliteracy found in the Arizona-Sonora borderland, a region thriving with linguistic and cultural diversity despite having an English-only policy. According to Reyes (2012) biliteracy is to think, speak, read, and write in two or more languages, and there are various modes for reading and writing in the 21st century (Reyes, Acosta, Fierro, Fu, & Zapien, 2017). This dissertation focused on Spanish and English bilinguals. First, I present a literature review (Appendix A) informed by a sociocultural framework (Vygotsky, 1978) for understanding biliteracy as a social practice and valuing language as a resource (Ruiz, 1987). Funds of knowledge (González, Moll, Amanti, 2005; Moll, González, Amanti, & Neff, 1994) is an important component in framing this qualitative study and applying methods informing an inclusive pedagogy for bilinguals. Subsequently, I go over the photographs and multimodal composition presented in two case studies of Spanish and English bilinguals. The first case study (Appendix B) documents biliteracy in the household and local community of bilinguals through photography. It contributes to previous research by Reyes, DaSilva Iddings, and Feller (2016) and the two themes from their analysis: 1) Expanding definitions of language and literacy and 2) Deepening the understanding of funds of knowledge. The second case study (Appendix C) examines how bilinguals critically and creatively expressed their Spanish and English in a multimodal composition. Thinking critically about literacy meant reflecting on their everyday reading and writing practices as bilinguals, while being creative meant thinking about the various modes of reading and writing in two languages. This moves literacy beyond a monolingual and monomodal practice into one that cultivates diversity for equity in education for bilinguals. I seek an empowering pedagogy for bilinguals by valuing and making space for linguistic and cultural diversity in the classroom. Biliteracy is a valuable contribution to class and the learning process of students with more than one language. The primary purpose of this dissertation, like funds of knowledge, was to develop critical innovations in teaching (Moll, Amanti, Neff, & González, 1992) biliteracy for the 21st century. Findings from the photographs, multimodal compositions, written reflections, and retrospective interviews demonstrate how Spanish and English biliteracy is practiced in various modes (e.g. music, dancing, singing, traditional family recipes, and religious/spiritual altars) in the Arizona-Sonora borderland.
    • Demography and Population Dynamics of Amphibians in Desert Mountain Canyons

      Zylstra, Erin (The University of Arizona., 2018)
      Changes in the distribution and abundance of species reflect variation in underlying demographic rates, including survival, reproduction, growth, and dispersal. Understanding how natural and anthropogenic processes affect demography and dynamics of species with patchy distributions can be challenging, but it is critical for developing reliable conservation strategies for landscapes that are changing at unprecedented rates. We studied amphibians that inhabit isolated, intermittent streams in mountain canyons of the desert southwest, a region where drought conditions have prevailed over the last 30 years and where the availability of surface water is likely to decrease further in response to changes in climate. Specifically, we used detection-nondetection data from 22 years of biannual visual encounter surveys with recent capture-recapture data to better understand survival, growth, and metapopulation dynamics of lowland leopard frogs (Lithobates yavapaiensis) and canyon treefrogs (Hyla arenicolor). We used a spatially-explicit metapopulation model to describe the distributional dynamics of leopard frogs in eight canyons in southern Arizona, and found that local frog populations were more likely to go extinct during periods of drought, particularly at sites that lacked deep or spring-fed pools that held water reliably. Leopard frogs were also less likely to colonize unoccupied sites when larval or dispersal periods were drier than normal or when sediment levels in pools increased following high-elevation wildfires. In one of the two watersheds we surveyed, occupancy by leopard frogs declined markedly in the latter half of the study, and we observed no frogs in this watershed after 2015. We used frequent capture-recapture surveys (≥1 survey every two weeks) based on in-situ photographs to demonstrate that the apparent extirpation was due, at least in part, to drought-mediated decreases in post-metamorphic survival. Seasonal and spatial variation in survival were governed largely by surface-water availability, and survival was particularly low at sites where water levels were lowest. Finally, seasonal variation in demographic rates was not limited to survival, as we found strong evidence of temporal variation in somatic growth of post-metamorphic canyon treefrogs. Growth rates were highest during the summer monsoon season, when both ambient temperatures and water levels in pools were typically high. Given the effects of climate and surface-water availability on demography of leopard frogs and treefrogs, distribution and abundance of these species may decline if future changes in climate reduce the quantity or quality of aquatic resources available in mountain canyons. Moreover, because leopard frog populations tend to be small and geographically isolated, they are unlikely to persist at a regional scale if increased drought frequency or severity limits the ability of individuals to disperse among populations through an increasingly arid landscape.
    • The Teacher-Text Interaction in Mathematics Instruction: Elementary and Middle School Teachers Redesign Mathematics Exercises to Increase Cognitive Demand

      Rishor, Donna Marie (The University of Arizona., 2018)
      Mathematics teachers modify problems for use in their classrooms but we know little about what exercises they choose to modify, in what ways they typically modify them, and what role teaching experience plays. Additionally, the modification of pre-written tasks can impact the mathematics students have the opportunity to learn, so it is important to learn more about this phenomenon. This qualitative, empirical study explored the ways that K-8 teachers interacted with mathematics curriculum materials with the goal of redesigning exercises into more cognitively demanding tasks. Seventy early career and experienced teachers participated in the study, which took place over the course of a school year. Data were collected in two stages, first from early career teachers and then with more experienced teachers. The collected data consisted of the original and redesigned tasks, teachers’ written reflections on the work that they did, audio-recorded work sessions of third and sixth-grade teacher groups, and the researcher’s reflective journal. Analysis occurred within and between grade bands and teacher experience levels. Findings indicate that teachers tended to choose simple exercises to modify and typically redesigned them by making structural changes to the task, or by opening them up to become student explorations. Results of this study indicate that teachers may benefit from frameworks that detail a hierarchy of how children best develop the mathematical understanding of concepts beyond basic number operations.
    • Improving the Specificity of Lung Cancer Diagnosis with acidoCEST MRI

      Lindeman, Leila Renee (The University of Arizona., 2018)
      Acido-Chemical Exchange Saturation Transfer (acidoCEST) Magnetic Resonance Imaging (MRI) is a non-invasive method for creating spatial maps of the extracellular pH (pHe) in solid tissues in vivo. Cancer cells are known to export increased quantities of lactic acid into the extracellular space as a result of glycolytic metabolic processes. Localized tissue acidosis can therefore function as a cancer biomarker, and acidoCEST MRI may be an impactful tool for increasing the specificity of imaging results. My work has focused on applying acidoCEST MRI to the diagnosis of lung cancer, where low-dose CT screening tests have a false positive rate of 95%. Chapter 1 discusses recent advances in MRI for the diagnosis, prognosis and management of pulmonary disease. Chapter 2 refers to a published manuscript reprinted in Appendix A which describes a method comparison study wherein I determined that the exchange rate (kex) of amide protons quantified by endogenous CEST MRI could not serve as a proxy measurement for pHe quantified by acidoCEST MRI. Chapter 3 describes a study in which I determined that lung tumors and valley fever granulomas in preclinical murine models have significantly different pHe. Chapter 4 discusses future directions of inquiry towards diagnostic CEST MRI methods for lung cancer including: application of endogenous CEST MRI, further development of the BSL-2 compatible murine valley fever model, and potential improvements to acidoCEST MRI image acquisition and analysis methods to aid in future clinical translation.
    • Conceptualizing and Measuring Drivers of Policy Change in Urban Water Governance

      Bell, Emily Virginia (The University of Arizona., 2018)
      This dissertation conceptualizes and measures key drivers of policy change articulated in the Advocacy Coalition Framework (ACF). The ACF is a widely-used framework that has guided researchers worldwide in their efforts to find answers to leading policy puzzles. Analysts have continued to improve the framework over the past three decades, but there is still room for theoretical and methodological development. With better clarification of concepts and measurement, scholars can gain better traction in offering theoretical contributions in the ACF’s research program. This work presents three studies that contribute to the objective of advancing the ACF. The first study investigates how narratives in gray literature highlight important actors in the policy network, and how well this aligns with centrality measures in the network structure. The second discusses ways to conceptualize environmental shocks, and examines how these affect change in the structure of a policy coordination network over time. Finally, the third study assesses the validity of gray literature data used for the first two studies by correlating coordination networks of policy actors detected through analysis of gray literature and survey methods. These efforts collectively offer novel ways to improve the clarity of concepts in the ACF, as well as the framework’s utility for empirical studies across a variety of policy domains and geographic settings.
    • Creation of a Universal Pediatric Pain Education Program for Third World Healthcare Workers Using the CIPP Model for Improvement

      Galligan, Erin (The University of Arizona., 2018)
      Background: The World Health Organization, the American Medical Association, and the International Association for the Study of Pain indicate pediatric pain is a significant global health issue, especially in the third world. Pain is the leading cause of patients seeking medical attention in the third world. Undertreated pain can lead to a lifetime of severe disability. Therefore, proper pain management is of great worldwide interest. Many studies have identified a lack of education as a barrier to pain management. Objective: The purpose of this project is to ameliorate the dearth of pain education amongst third world healthcare workers. With expert input, this project aimed to create a universal and comprehensive pediatric pain teaching program that any Western-trained healthcare worker can utilize in a third world healthcare setting to help the local staff learn about pain. This program was shared for dissemination with Health Volunteers Overseas. Design: This is a program evaluation employing the Context, Input, Process, Product (CIPP) design used to determine useful updates to a comprehensive educational tool created by the primary investigator. Participants: Western-trained healthcare professionals with backgrounds in third world healthcare, and educational experts. Measurements: Educational and third world healthcare setting experts were surveyed. They were asked four open-ended questions, two binary questions and two demographical questions. Common themes from the open-ended answers were identified and illustrated with Mind Maps. Results: All experts surveyed responded with a combined 79 years of multidisciplinary experience guiding feedback. Common themes on the project's accuracy, successful attributes and areas for improvement were identified, and the teaching program was updated accordingly. The experts all felt the teaching program contains accurate information and has the potential to improve pediatric pain treatment in the third world. Conclusion: The purpose of this program evaluation was to create a clinical teaching tool that was refined according to expert commentary. Areas for future research include gathering feedback from a more varied group of experts, and also utilization of the teaching program in the third world and assessing its effectiveness with the tools provided.
    • Dane Rudhyar's Transmutation of 1976: Transformative Use of the Descending and Ascending Harmonic Series as a Compositional Device

      Suescun Valencia, Katherine (The University of Arizona., 2018)
      The French-American composer Dane Rudhyar (1895-1985) uses the harmonic series in a unique manner to create dissonant harmonies. His method incorporates the principles of order, interaction, and interpenetration whereby the fundamental pitches and shared partials of two interrelated harmonic series are made explicit. He uses both the ascending and the descending versions of the harmonic series as a unifying factor that substantiates his metaphysical conception of the harmonic series and his notion of the piano as a collection of gongs capable of powerful resonance. Rudhyar’s mature piece, Transmutation: Tone-Sequence in Seven Movements for the Piano (1976) exhibits the use of such interpenetrated harmonies particularly in Movements 3, 6, and 7. The scrutiny and analysis of these movements in this document reveal compelling implementations of interpenetrated dissonant harmonies as generators of the melodic and harmonic framework, gong-like textures, climaxes, and endings.
    • Novel Techniques and Instrumentation for Material Characterization from Microwave to THz Frequencies

      Tuo, Mingguang (The University of Arizona., 2018)
      This dissertation focuses on the investigation of microwave and terahertz (THz) nanomaterials, devices, components and systems. The work done in this dissertation is categorized into three main parts: theoretical modeling and experimental characterization of THz photoconductive antennas (PCAs) in the far-field time-domain spectroscopy (TDS) configuration, demonstration and performance study of an emitter array based THz near-field imaging system, and the intrinsic property characterization of carbon-based nanomaterials. First, the important applications of THz technology and the critical elements involved in the generation of THz pulsed signal, including femtosecond (fs) laser, photoconductive material and PCA structure itself, are introduced. The theoretical modeling approaches of THz PCA used in the literature are compared and the 3D full-wave model is chosen and implemented using the finite-difference time-domain (FDTD) algorithm. Two exemplary PCAs, stripline and dipole, are simulated using this full-wave model and compared. Second, the effects of the photoconductive materials (with different carrier lifetime and mobility) and the antenna structures on the far-field THz radiation properties are systematically examined in terms of pump laser power dependence and DC bias voltage dependence via an in-house built THz-TDS system. The polarization and cancellation effects are additionally investigated experimentally to better understand the PCA radiation mechanism. The THz bandwidth improvement with regard to the dispersion of the critical optical component is illustrated and the refractive indices of several dielectric materials are coherently characterized afterwards with this new TDS setup. Third, a PCA array based THz near-field imaging system in emission mode is proposed incorporating the Hadamard multiplexing method to achieve system signal-to-noise ratio (SNR) improvement. The system performance is represented in terms of spatial resolution. Simulation estimations based on the HFSS time-domain solver combined with the FDTD algorithm show reasonable agreement with the experiments. Furthermore, intrinsic microwave properties of single-walled carbon nanotube (SWCNT) and graphene are measured with the aid of two different coplanar waveguide (CPW) transmission-line test fixtures, extracted with de-embedding algorithms and expressed by lumped-element equivalent circuit models. In addition, the nonlinearity (power dependence) of graphene material in terms of its second- and third-order harmonics is reported. The third-order harmonic is specially considered to estimate the intermodulation distortion (IMD) towards graphene antenna applications.
    • Indo-Pacific Sea Level as an Indicator of Climate Variability and Change

      Peyser, Cheryl (The University of Arizona., 2018)
      The Indo-Pacific Ocean, particularly in Southeast Asia, directly affects an enormous coastal and island population, drives heat and moisture transfer across the globe, and provides a critical influence on future anthropogenic climate change. Natural variability in the climate system, acting in concert with global warming, leads to sea level changes that vary considerably across the region. Here we present three studies where sea level gradients in the Indo-Pacific are used to better understand variability and trends in global climate Satellite altimetry measurements have recently reached 25 years in length (1993 to 2017) providing a precise global sea level record to illuminate changes in ocean heat storage. The data shows that from 1993 to 2012 sea level in the western Pacific has risen up to four times faster than the global mean due to strengthening trade winds. To ensure robust results and extend the sea level record further our work includes data from state-of-the-art climate models, reanalysis products, sea level reconstructions, and ocean temperature databases. In Appendix A (published in Geophysical Research Letters), we quantify for the first time the relationship between fast sea level rise in the western Pacific and the observed slowdown of global average surface temperature from 1998-2012. In Appendix B (published in Water), we use the east-west sea level gradient in the Pacific as a metric for evaluating climate model skill in simulating variability. In Appendix C (in preparation for submission to Geophysical Research Letters), we show how the Indonesian Throughflow response to western Pacific sea level rise differs between reanalysis products and climate model simulations. In these three studies we utilize the newly available satellite altimetry record to better understand Indo-Pacific Ocean dynamics and how they are represented in the current generation of climate models.
    • Anesthesia Provider Perspectives of Preoperative Music-Listening as a Means for Anxiolysis Among Geriatric Patients

      Klein, Matthew (The University of Arizona., 2018)
      Studies have demonstrated that the majority of patients undergoing a surgical procedure experience some level of preoperative anxiety. However, outside of the administration of anxiolytic medications and the preoperative interview, the majority of certified registered nurse anesthetists (CRNA) do not utilize nonpharmacologic methods for preoperative anxiolysis among the geriatric patient population, such as music-listening. In turn, placing these patients at risk for either the consequences of untreated anxiety or receiving anxiolytic medications that may place them at increased risk for postoperative delirium (POD). The purpose of this DNP project was to assess existing CRNA perspectives and practices, at a 200-bed Phoenix. AZ teaching hospital, regarding the use of preoperative music-listening among geriatric patients as a means for anxiolysis and to assess changes in perspective after an educational presentation. Participants (N=7) included CRNAs working within this 200-bed facility. The methodology consisted of pretest/posttest individually recorded interviews with varying question styles. Results showed that this DNP project demonstrated that CRNAs are aware of music-listening as a means for preoperative anxiolysis, but knowledge gaps regarding its use and the consequences of using anxiolytic medications do exist. However, a positive educational impact was made and demonstrated via improvement in posttest scores.
    • Phylogenetic Incongruence as a Signature of Past Events: Uncovering the Genomic Watermarks of Introgression and Gene Duplication

      Forsythe, Evan Sullivan (The University of Arizona., 2018)
      Eukaryotic genomes are ever-changing mosaics of past evolutionary events. Each site in the genome provides information about the evolutionary processes that have shaped its identity. Phylogenetics has long used the nucleotide identities at genomic sites as characters with which to reconstruct the ‘tree of life’ that unites living organisms. However, it was soon recognized that different sites in the genome often evolve independently, and thus each site tells a story of its own evolution, which may conflict with the stories told by other sites in the same genome. For example, in contradiction to the tidy concept of bifurcating tree-like evolution, we recognize that genetic material can be transferred between species, causing independent branches to reunite (i.e. reticulate) to form a shape that is more web-like than tree-like, referred to as a phylogenetic network. Further, when this type of reticulation occurs, it may only affect a portion of the genome, meaning phylogenies from some sites in the genome will reflect a history of reticulation while others will reflect a history of simple speciation. Another evolutionary process that can affect portions of the genome is gene duplication, which can result in a locus in the genome sharing homology with other loci in the same genome. When such multi-copy loci are used to infer branching order of several species, it can become very difficult to distinguish orthologs from out-paralogs, thus obscuring which nodes on the gene tree correspond with speciation events and which correspond with duplication events. Both reticulation and gene duplication can result in discordance between phylogenies inferred from differing regions in the genome, a condition termed phylogenetic incongruence. In plant evolution, reticulation and gene duplication are ubiquitous and a large field of study is devoted to the phylogenetic challenges caused by these processes. However, in addition to obfuscating species tree inference, these two processes are known to have considerable effects on the functional evolution of species; both can underlie the acquisition of novel adaptive traits. Therefore, it is important to identify and characterize these processes in model and crop systems. Toward this goal, the ‘challenge’ of phylogenetic incongruence can be turned on its head and instead used as a signature that illuminates the genomic watermarks of historical reticulation and duplication. In this dissertation, I present three studies in which I used genome-wide patterns of phylogenetic incongruence to infer evolutionary processes. In Appendix A, my coauthors and I describe a reticulation event that occurred more than nine million years ago in Brassicaceae and I explore the genomic and functional consequences that are still detectable in extant genomes. In Appendix B, I develop a method for determining which species received foreign genetic material during introgression events. I explore the versatility of this method by applying it to simulated whole genome sequences, as well as empirical genome data from extant and extinct hominins as well as mosquitos. Finally, In Appendix C, I infer complex duplication histories of more than 1,000 non-coding RNAs across the Arabidopsis genome, thereby revealing a mechanism underlying diversification in plant transcriptomes.
    • “Who Breaked the Rule?”: Rethinking English Past Tense Overregularizations

      Figueroa, Megan Danielle (The University of Arizona., 2018)
      To learn a language, children must go beyond simply imitating speech and learn the rules of the language from their surrounding linguistic environment. One way to tell that children learn rules is that they apply rules to an overly broad set of words. For example, English-learning children produce forms like ‘breaked’ or ‘catched’ at around 3 years of age. These forms, called past tense overregularizations, show that children have implicitly discovered the past tense formation rule: namely, “add ‘–ed’ to a verb to create the past tense.” But does it take children until age 3 to discover such rules? This dissertation combines a behavioral study with 16-month-olds and a corpus analysis of longitudinal, spontaneous child speech to achieve two goals: the first is to seek evidence that the past tense rule can be found in 16-month-olds, which would be consistent with many observations that children display significant receptive abilities long before their productive abilities reach the same level. The second goal is to determine if the production of past tense overregularizations can be explained by factors other than the discovery of a grammatical rule. Results indicate that children have enough experience with English by 16 months of age to represent verb + ‘–ed’ months before they begin to overregularize in production; therefore, production does not seem to reflect when the past tense rule actually comes online. 16-month-olds were able to discriminate between overregularized verbs and 1) their correct counterparts, 2) nonce verbs + ‘–ed’, and 3) English noun stems marked with ‘–ed’. Further, overregularizations in production seem to reflect children's need to simplify their utterances as they attempt to say more and more complex sentences.
    • Assessing Substrate-Dependence and Mechanism of Ligand Interaction with the Organic Cation Transporter, OCT2

      Sandoval, Philip Joseph (The University of Arizona., 2018)
      Among its many functions, the kidney has a significant role in limiting the body’s exposure to potentially toxic xenobiotic compounds. One family of these compounds is designated as ‘organic cations’ (OCs); these are organic compounds that are positively charged at physiological pH. The multidrug organic cation transporter OCT2 is localized in the basolateral membrane of proximal tubules cells in the nephron of the kidney and is widely considered to mediate the entry step in the transepithelial secretion of these compounds by the proximal tubule cells. It is estimated that approximately 40% of prescribed medications can be designated as OCs with OCT2 playing a significant role in the elimination of many of these compounds from the body. An unfortunate consequence of many drugs sharing an elimination route via OCT2 is the potential for clinically significant drug-drug interactions (DDI). Competition of two or more drugs with a limited number of OCT2 transporters in the proximal tubules can result in altered pharmacokinetic profiles for one or both of them increasing the risk for toxicity. Efforts to predict and prevent DDIs at OCT2 include the development of predictive models of OCT2 selectivity and the use of assays in the form of decision trees to assess whether a new molecular entity is at risk to perpetrate DDIs. These predictive models rely on in vitro determined kinetic parameters of OCT2 mediated uptake including IC50 values, Michaelis Constants (Kt), and maximal rate of transport values (Jmax). In order for researchers to have confidence in these models and assays, we must be confidant in the accuracy of our measured kinetic parameters values. Unfortunately, the measured values of these parameters can be influenced by the choice of substrate or by unstirred water layers and the efflux of substrate. For example, IC50 values against the OCT2 mediated uptake of MPP are consistently greater than IC50s of the same set of compounds against the OCT2 mediated uptake of metformin (9-10 times greater in some cases). Additionally, other substrates of OCT2 have been demonstrated as having substrate dependent IC50 values, including NBD-MTMA, ASP, and atenolol, although, the relationship of the inhibitory profiles of these substrates to those for MPP and metformin is not well understood. In addition to substrate dependence, the influence of unstirred water layers (UWL) and the efflux of substrate from cells can complicate measured in vitro kinetic parameters. The traditional ‘two-step’ approach to kinetic analysis that involves measures of net uptake at a single time point, is vulnerable to the introduction of bias to both measured Kt (usually overestimates ) and Jmax (usually underestimates) values as a result of efflux and UWLs. Addressing the issues of substrate dependent IC50 values and the difficulties in assessing accurate kinetic values can improve our confidence in the values of measured kinetic parameters and, as a result, in our predictive models and outcomes using decision tree assays. To address the issue of substrate dependence I screened the inhibitory effectiveness of 400 plus compounds (Chapter 2) from the National Clinical Collection against the OCT2 mediated uptake of metformin, MPP, TEA, cimetidine, NBD-MTMA and ASP. I also measured the IC50s of twenty compounds against the OCT2 mediated uptake of metformin, MPP, TEA, NBD-MTMA, and ASP (Chapter 3). Results of the screening and IC50 studies confirmed other studies demonstrating that MPP is inhibited to a lesser extent than the other substrates; but additionally, the inhibitory profile of metformin proved to be comparable to the other substrates tested, suggesting that metformin is an excellent substrate for decision tree based assays of OCT2 DDIs due to its clinical relevance and the similarity of its inhibitory profile to other probe OCT2 substrates. To address the issues of the challenges of measuring accurate kinetics of OCT2 mediated uptake I assisted in developing a mathematical model (Chapter 4) that takes into account the influence of both UWL and efflux of substrate on Kt and Jmax values that complicate use of the two-step approach. I also assisted in the development of an empirical, time course-based analytical approach (used in Chapters 3 and 4) that limits the influence of both UWLs and substrate efflux on assessment of Jmax and Kt by estimating the rate of transport at time zero when these complicating . With this time course approach I assessed the kinetics of interaction between MPP and Metformin at OCT2. I showed that MPP inhibits metformin at OCT2 with a ‘mixed’ type mechanism while metformin inhibits MPP with a competitive mechanism. These results, in addition to the results from the IC50 study, suggest that MPP binds to a larger area of the OCT2 binding surface than metformin and the other tested substrates. Additionally, I assisted in studying the relationship between measured Jmax and Kt values (higher Jmax typically associated with higher Kt) for the transport of substrate by OCT2 and the potential for substrate off times at OCT2 to be the rate limiting step in transport (Chapter 5).
    • The Role of Kappa Opioid Receptor Signaling in Injury-Free Pain

      Nation, Kelsey Marie (The University of Arizona., 2018)
      Kappa opioid receptor (KOR) signaling has been shown to be involved in the production of negative affective states. We hypothesized that KOR signaling in the brain may also be important in promoting pain states in the absence of injury, such as in functional pain syndromes (FPS), which are difficult to study in rodents due to our current lack of understanding of the etiology underlying these disorders. In order to study FPS we developed an injury-free hyperalgesic priming model that utilizes a loss of diffuse noxious inhibitory controls (DNIC), an endogenous mechanism of pain modulation that is diminished in patients with FPS, as the output measure. After establishing the model we used it to study the contribution of KOR signaling to the loss of DNIC and found that blocking endogenous KOR signaling with a KOR antagonist was sufficient to restore the DNIC response when the KOR antagonist was administered either subcutaneously or directly into the right central nucleus of the amygdala (right CeA), but not when given into the left central nucleus of the amygdala (left CeA) or into the rostral ventromedial medulla (RVM). The loss of DNIC was accompanied by elevated levels of dynorphin, the endogenous KOR agonist, in the right CeA. Further experiments designed to study the contribution of signaling from KOR-expressing cells in various brain regions to the production of pain in the absence of an injury were performed using KOR-Cre mice and Cre-dependent designer receptors exclusively activated by designer drugs (DREADDs). When Gi-coupled DREADDs were activated in the KOR-expressing cells in the right CeA a loss of DNIC was observed in male and female mice and this was accompanied by decreases in static pain thresholds in female mice. Activation of Gi-coupled DREADDs in KOR-expressing cells in the anterior cingulate cortex (ACC) produced conditioned place aversion, suggesting a negative affective state that is relevant to pain conditions, and this aversion was not accompanied by changes in sensory thresholds. These results establish that lateralized KOR signaling in the CeA is sufficient to produce changes in static and dynamic sensory measures of pain and that blockade of this KOR signaling is sufficient to restore DNIC in our model of FPS. Additionally, these results establish that ACC KOR signaling contributes to the development of a negative affective state. These results suggest that KOR signaling plays a critical role in the development of pain in the absence of injury and that increased levels of endogenous KOR signaling may be a relevant piece of the biology that underlies the development of FPS.