• Reducing SARS-CoV-2 Vaccination Hesitancy in a Primary Care Setting

      Allison, Theresa; DeMello, Blythe; Pacheco, Christy; Locke, Sarah (The University of Arizona., 2022)
      Purpose: The purpose of this quality improvement project was to increase SARS-CoV-2 vaccination confidence and knowledge in adults who display reluctance or hesitancy through a brief educational discussion and a written pamphlet. Background: In recent history, the world was faced with an unprecedented challenge as a pandemic quickly encompassed the globe. In early 2020, this became commonly known and referred to as the COVID-19 pandemic. The severe health implications of this respiratory virus quickly overfilled hospitals and placed the health of communities at risk. To get ahead of further spread of COVID-19, it was pertinent to quickly develop an effective vaccine. Following rigorous clinical trials, two mRNA vaccines were approved by the United States (US) Food and Drug Administration (FDA). What seemed like a solution became a challenge within the US. The population of the US showed reluctance to participate in COVID-19 vaccination programs. Vaccine hesitancy related to COVID-19 mRNA vaccines prolonged communities achieving adequate herd immunity. Understanding why individuals were displaying vaccine hesitancy was pertinent for implementing strategies that would lead to increased mRNA COVID-19 vaccine compliance. Methods: Participants were recruited from Peak Family Practice in Colorado Springs, CO. A pre-survey was administered followed by a short one-on-one educational session reviewing a written pamphlet about mRNA vaccines and common misinformation related to COVID-19 vaccines. A post-survey was administered after the educational intervention. Each survey had the same five questions and assessed participant knowledge and confidence related to mRNA COVID-19 vaccines. Results: A total of 20 participants completed the pre- and post-survey responses, along with participating in the short educational session. No statistically significant differences were found, however, participants who changed their answers on post-survey showed an increase in confidence of mRNA vaccines as well as indicating they would be more likely to receive a COVID-19 vaccine. Conclusion: This educational intervention reviewing a written pamphlet of mRNA vaccine information was effective in increasing the confidence of mRNA COVID-19 vaccines in some participants. Participants who changed their post-survey answers indicated an increase in likeliness to receive COVID-19 vaccination and showed improvement in knowledge related to mRNA vaccines. Although there was evidence of clinical significance a larger sample size would be necessary to indicate true statistical significance.
    • Testing the Effects of an Affectionate Communication Intervention to Bolster Mental Health During the COVID-19 Pandemic

      Floyd, Kory; Woo, Nathan; Rains, Stephen A.; Pitts, Margaret J.; Hamann, Heidi A. (The University of Arizona., 2022)
      This study tested the efficacy of an affectionate communication intervention to help adults living in the United States bolster their mental health during the height of the COVID-19 pandemic. Ninety-eight married and cohabitating adults were randomly assigned to one of three groups: increased affectionate communication (treatment), increased thankfulness (comparison), or no change in behavior (control). The final sample contained 73 adults (ntreatment = 26, ncomparison = 24, ncontrol = 23) who completed the four-week intervention that started in September and concluded in October 2020. Although post-hoc analyses revealed that participants in the treatment group were, on average, less affection deprived, less depressed, less lonely, and less stressed than those in the comparison and the control groups halfway through the intervention and at the end of the intervention, these findings should be interpreted with caution due to a successful comparison manipulation, but a statistically nonsignificant treatment manipulation. Speculation as to why the intervention failed to reject the null hypotheses is presented in the discussion before providing methodological recommendations for future interventions in this area of research.
    • From Sexual Objects to Sexual Survivors: Exploring the Cognitive Inconsistencies Within a Media Counter-Sexualization Script

      Stevens Aubrey, Jennifer; Terán, Larissa; Harwood, Jake; Rains, Stephen A. (The University of Arizona., 2022)
      Since the #MeToo movement of 2017, the modern media landscape reflects a set of two contradicting scripts in the media. The first is the dominant script where women are sexualized and encouraged to focus on their sexual appeal for men’s pleasure whereas men are encouraged to be sexual aggressors. The second is what I refer to as the Counter-Sexualization Script, wherein men are held accountable and punished for this same sexualization of women and women are valued outside of their sexualizing roles. Across three empirical studies, this dissertation investigated these cognitively inconsistent media messages. In Study 1, focus groups (n = 19) were conducted to conceptualize and develop items of the Counter-Sexualization Script. Three themes emerged in the focus groups: (1) Giving Women the Microphone, (2) Holding Predators Accountable, and (3) Consciousness Raising. These three themes served as the factors for the Counter-Sexualization Script measure. The identified themes informed 38 items for the Counter-Sexualization Script measure. In Study 2, I conducted factor analyses to examine if the Counter-Sexualization Script fit a three-factor structure with a separate sample of emerging adults (n = 605). Results indicated that the Counter-Sexualization Script fit a three-factor structure; 18 items were removed from the measure to improve model fit. The final Counter-Sexualization Script measure included 20 items and the three factors. Study 2 also established the convergent, predictive, and concurrent validity of the Counter-Sexualization Script measure. Results suggested that the Counter-Sexualization Script measure was uniquely distinct, yet negatively associated with similar concepts (e.g., self-objectification, sexism), demonstrated predictive ability with related concepts (e.g., heterosexual script endorsement, rape myth acceptance), and was positively associated with empathy towards rape victims; the Counter-Sexualization Script was not statistically associated with enjoyment of sexualization. Finally, individuals who had personal experience with sexual assault, sexual harassment, and were supporters of the #MeToo movement were the most likely to endorse the Counter-Sexualization Script. In Study 3, a 2 X 2 pre/post factorial experimental design (counter-sexualizing article and sexualizing article, sexualizing and neutral article, counter-sexualizing and neutral article, two neutral articles) was employed to investigate the effects of cognitively inconsistent media messages. Participants were recruited from Cloud Research and a large southwestern university (n = 308). Results exhibit that there are no significant direct effects from the message conditions on sexual aggression outcomes with one exception: There was a statistically significant interaction between media exposure to counter-sexualizing messages, endorsement in the Counter-Sexualization Script (pre-test score), and bystander intervention intentions. At low levels of endorsement in the Counter-Sexualization Script, participants who were exposed to a counter-sexualizing media message reported lower bystander intervention intentions. For the cognitive dissonance outcomes, there were no significant direct effects from the message conditions on psychological discomfort, counterarguing, or neglectful feelings towards the self with one exception: participants who were exposed to a sexualizing message versus those who were not reported greater psychological discomfort. Finally, mediation analyses exhibit that psychological discomfort mediated the relationships between the message conditions, neglectful feelings towards the self, and counterarguing. Results across the three studies have theoretical implications with sexual counter scripts and contradicting media messages. Also, results have implications for practitioners, media executives/producers, and parents regarding the affective and uncomfortable state produced by cognitively inconsistent media messages regarding sexualization.
    • Much to Do about Non-Things: Exploring Agency and Responsibility Through Omissions

      Sartorio, Ana C.; Metz, Joseph William; McKenna, Michael; Turner, Jason; Horgan, Terence (The University of Arizona., 2022)
      This dissertation centers on agency and moral responsibility concerning actions and omissions, developing a unified account of responsibility for actions and omissions while still respecting the differences and asymmetries between them. This account is unified in that responsibility both for actions and omissions is based on the same type of ability – in particular a very weak type of ability. However, the relevant scope of the abilities required for responsibility differs for omissions and actions. Roughly, responsibility for omissions requires the ability to perform the omitted act, which therefore also requires the ability to do otherwise. Responsibility for actions does not require the ability to do otherwise. Much work has been done on actions, and some recent work has been done on omissions, but very little has been done that accommodates both, as well as their differences, into a single account. Particularly central to my project is accommodating and exploring the implications of the various asymmetries that arise between actions and omissions, which are relevant to causation, agency, responsibility, and luck. I discuss several practical applications of these asymmetries concerning how we should judge ourselves and others in virtue of our positive and negative agency, and concerning moral – and likely legal – responsibility as well.
    • Evaluating the Effect of Adenine Nucleotide Translocase-1 Acetylation on Mitochondrial Bioenergetics and Metabolic Inflexibility

      Mandarino, Lawrence J.; Barakati, Neusha; Willis, Wayne T.; Coletta, Dawn K.; Luo, Moulun; Zapata Bustos, Rocio (The University of Arizona., 2022)
      ANT1 in human mitochondria was previously identified as an acetylated protein and lysines 10, 23, and 92 of human ANT1 were noted to be acetylated in most of preparations of mitochondria isolated from human skeletal muscle biopsies. Lysine 23 contributes to a net overall positive charge in the nucleotide binding pocket of ANT1, molecular dynamics modeling showed that acetylation of lysine 23 reduced the positive charge and lowered the affinity of hANT1 from about 3 to 80 M [ADP]. Further computational modeling studies showed that if about 25% or higher of total ANT1 were acetylated, the apparent Km ADP for oxidative phosphorylation would be increased sufficiently to affect ANT1 function, with consequences for glycolysis and fuel selection.Based on previous findings, we decided to evaluate the involvement of altered acetylation of ANT 1 at lysine 23 in regulation of fuel selection and mitochondrial bioenergetics. This thesis consists of three chapters that describe the involvement of altered acetylation of ANT 1 at lysine 23 in regulation of fuel selection. The first chapter describes a luciferase-based assay to evaluate the ADP kinetic parameters of mitochondrial ATP production and the extent of control that ANT has in this pathway. The high sensitivity, reproducibility of this assay enabled to assess ADP kinetic parameters and ANT flux control in isolated mitochondria from skeletal muscle. It is confirmed that under the conditions used to study isolated mitochondria, the majority of flux control over oxidative phosphorylation resides at ANT. The second chapter deals with the question of relationship between acetylation of ANT1 and ANT1 content with metabolic flexibility during insulin stimulation or mild exercise. The findings from human skeletal muscle do not provide evidence that the extent of lysine 23 acetylation of ANT1 is a predictor of fuel selection at low [ADP]. Acetylation of lysine 23 of ANT1 is abundant and variable but perhaps too low to discernibly affect the sensitivity of mitochondria to the respiratory signal provided by [ADP] during conditions of insulin stimulation or mild muscle contraction. However, greater ANT1 content, either as a marker of greater mitochondrial abundance or higher specific abundance of ANT1 per mitochondrial mass, could result in changes in fuel selection by lowering the apparent K0.5ADP, driving skeletal muscle toward higher lipid oxidation during mild exercise. The participants in this study had normal or moderately abnormal glucose metabolism. It is conceivable that patients with more poorly controlled type 2 diabetes and more severe impairments in muscle fuel selection could have higher ANT acetylation. Consequently, it would be helpful to evaluate the extent and effect of ANT1 acetylation in this group. Finally, the last chapter provides actual experimental evidence whether loss of the positive charge at lysine 23 has any effect on the affinity of ANT for ADP. The cellular modeling experiments indicate that removing the positive charge of ANT1 at lysine 23 decreases the ability of ANT1 to bind ADP and result in a higher apparent KmADP for ATP production without changing the Vmax. Although it seems clear from modeling and simulation experiments that acetylation of lysine 23 of human ANT1 affects function, direct biochemical evidence is lacking regarding the extent of this effect. Experiments using ANT incorporated into artificial liposomes may help to answer this question.
    • Chemical and Isotopic Characteristics of Sedimentary Basin Formation Waters for Evaluating Cross-Formational Mixing, Tracers of Contamination, and Li Resources

      McIntosh, Jennifer; Marza, Mohammad; Ferguson, Grant; Meixner, Thomas; Guo, Bo (The University of Arizona., 2022)
      Understanding the origin, diagenetic history, chemical composition, and migration pathways of saline fluids in sedimentary basins is important for extraction of subsurface resources (e.g., critical elements, such as Li), storage of alternative energy (e.g., H2) and saline produced waters, and long-term sequestration of anthropogenic CO2 and spent nuclear fuel. The presence of confining units, such as evaporites and shale, may impede basinal-scale fluid flow and can be a source of highly saline fluids to adjacent formations. Upward migration of saline fluids may contaminate surface waters or shallow aquifers. Identifying the source of saline fluids (e.g., fluids sourced from specific oil/gas reservoirs) through unique fluid isotopic signatures may help to remediate contamination. This issue is complicated by the fact that many subsurface reservoirs have been altered by extensive fluid injection activities (e.g., water flooding or disposal of produced, saline waters), which may modify original formation water chemistry. This dissertation aims to evaluate Sr isotopes as an adequate tracer for fingerprinting distinct sources of produced waters from overlapping oil/gas fields, influence of fluid surface storage and subsurface injection activities, and cross-formational fluid migration through evaporite confining units, combined with major ion, Br, and water stable isotope chemistry. Furthermore, this dissertation aims to explore the potential of Li production from sedimentary basin brines.To test the utility of Sr isotopes as a tracer of subsurface, saline fluid sources, Sr isotopes (87Sr/86Sr) of formation waters were evaluated from hydrocarbon reservoirs within three major oil/gas producing regions: the Williston, Appalachian, and Permian basins in North America. Based on a non-parametric statistical test, Sr isotope ratios of formation waters from multiple stacked oil and gas reservoirs within each basin have overlapping (i.e., non-unique) values. In regions where Sr isotope ratios of formation waters overlaps, Sr isotopes alone may not be a sensitive tracer of saline, produced water contamination in near surface environments, as previously proposed. Sr isotopes, along with major ion chemistry, Br, and water stable isotopes, were further applied to investigate the potential of fluid migration across a thick evaporite confining unit (Gotnia Formation) within the Kuwait Basin, as proposed by previous studies. Results indicate that the Pre-Gotnia (below the evaporites) and Post-Gotnia (above the evaporites) sections have distinct Sr isotopes signatures suggesting the Gotnia Formation impedes vertical fluid migration. These results are supported by major ion chemistry, Br, and water stable isotopes. The upward migration or downward leakage of saline water can deteriorate the quality of drinking water and modifies the formation waters chemical and isotopic signature. Interestingly, several of the subsurface reservoirs show extensive mixing with seawater, likely from water flooding activities for enhanced oil recovery. Replacement of formation waters by injection of different fluids may cause difficulties in fingerprinting sources of potential contamination, deteriorate the reservoir quality, lead to borehole scaling, and alter subsurface microbial activity. Li (and other critical elements) extraction from oil-field brines has been proposed, yet relatively little is known about the concentration of Li in various sedimentary basin fluids and potential extraction rates based on fluid fluxes. To address this issue, I investigated Li concentrations and potential Li extraction rates of formation waters from stacked oil/gas reservoirs in sedimentary basins across North America. Six of the basins contained [Li] above 65 mg/L, with the highest Li contents in the Smackover Formation in the Gulf Coast, E. Texas and Arkla basins (up to 1700 mg/L), which has been the focus of previous studies. The Paradox, Appalachian, Williston, Gulf Coast, East Texas, and Arkla basins also contained [Li] above 65 mg/L. In general, the highest Li concentrations are found in basinal brines sourced from highly evaporated seawater (halite to potash salt precipitation stage) from the geologic past. Li was then enriched by interaction with Li-rich rocks and minerals in the subsurface (e.g., detrital sediments, shales, and volcanic ash). Lithium concentrations and potential production rates are most promising in the Paradox Formation in the Paradox Basin, Clinton/Medina Groups in the Appalachian Basin, and Devonian section and Charles Formation in the Williston Basin. Results of this study show that basinal brines may be a competitive resource compared to more traditional continental brines for Li (and possibly other critical elements) production, worthy of further investigation.
    • Partner Support as a Buffer between Parental Depressive Symptoms and Parental Engagement

      Barnett, Melissa A.; Vasquez, Maria Belinda; Curran, Melissa A.; Speirs, Katherine (The University of Arizona., 2022)
      The risks and economic pressures experienced by low-income families can lead to psychological distress such as depressive symptoms (Masarik & Conger, 2017), which can impact parenting behaviors. The present study addressed how parental depressive symptoms might be a risk associated to parent-child relationships, especially positive parental engagement. Using a risk and resilience framework, the current study is the first to explore three forms of partner support (emotional support, financial support, and emergency child-care support) as potential protective factors that buffer the association between depressive symptoms and parental engagement among N = 3,165 mothers and fathers of three-year-olds. Participants were predominantly unmarried and from diverse minority ethnic backgrounds (Hispanic= 24%, Black Non-Hispanic=57%, White Non-Hispanic=17%, and other race=2%). Results indicated that parental depressive symptoms are negatively associated with positive parental engagement. The more depressive symptoms a parent is experiencing, the less likely they are to participate in positive parental engagement activities (e.g., singing, playing). Findings also suggested that emergency child-care partner support was a protective factor only for fathers. Emotional partner support and financial partner support were not a significant buffer for mothers or fathers. Findings highlight the need to address mental health needs in low-income families and explore complex associations between parenting practices and potential protective factors that promote resilience.
    • Renal Cell Carcinoma: American Indians, Metabolism, Metastasis, and Treatment

      Badger, Terry; Cordova-Marks, Felina; Lybarger, Lonnie; Briehl, Margaret (The University of Arizona., 2022)
      Renal cell cancer disproportionately affects American Indians/Alaskan Natives. This same population is also not included in published clinical trials and not reported on in published renal cancer clinical trials. Renal cancer treatment is needed that not only implements targeting new pathways or combinations of pathways that have not been targeted prior and integrating with traditional health. Almost 2/3 of American Indian’s report utilizing traditional medicine and cancer patients from this population report seeking traditional healers. New potential interventions should be created that combine traditional health with western medicine focused on metabolic pathways. Blocking in one treatment HIF1 and SIRT2; a separate treatment blocking VEGF and production of interleukins 6 and 8; and increasing BPTES to decrease glutamine; as well as adding in traditional aspects of health such as sweat ceremonies and usage of sage for example. Combining both western medicine and traditional health could increase the quality of life and outcomes for this population.
    • Microcircuit Electrophysiological Functional Relationships in the Cortico-Basal Ganglia Network with Deep Brain Stimulation in Parkinson's Disease

      Greger, Bradley; Qiu, Shenfeng; Guest, Ashley Cerise; Mirzadeh, Zaman; Kruer, Michael; Anderson, Trent (The University of Arizona., 2022)
      Objective: This dissertation aims to learn about the neural networks involved with using deep brain stimulation (DBS) to treat Parkinson’s disease (PD) and increase our understanding of the mechanism of DBS. The particular focus is on examining network dynamics in the cortico-basal ganglia (BG) circuit and how DBS modulates functional connectivity in the cortico-BG circuit. The overarching hypothesis of this work is that DBS changes electrophysiological environments to alter the brain’s activity on a network level, examined here in the cortico-BG network in PD. Background: Deep brain stimulation (DBS) is the therapeutic use of chronic electrical stimulation of the brain via an implanted electrode and is a treatment for a variety of neurological disorders. The brain is an electrically active organ, containing neurons that communicate in circuits using action potentials (APs) and local field potentials (LFPs). We can infer information about how neurons communicate by studying these signals, how they behave in PD, and how they respond to DBS. PD is a neurodegenerative disease that manifests motor symptoms of bradykinesia, tremor, and rigidity, as well as a host of non-motor symptoms including cognitive impairment. It is characterized by a loss of dopamine (DA) neurons in the substantia nigra (SN), which has downstream effects on the function of the cortico-BG network. The cortico-BG network is an intricate web of connections between anatomical areas that regulates movement. DBS is used to treat the motor symptoms of PD with widespread success and has long-lasting efficacy. The DBS electrodes are placed into subcortical structures in the cortico-BG network, most commonly the subthalamic nucleus (STN) and the globus pallidus internus (GPi). There are many theories concerning how DBS works, and this project sought to provide increased mechanistic understanding. Empirical evidence attests to the effectiveness of DBS as a treatment for PD and how it must change some pathological activity to restore motor function. I hypothesized that rather than changing individual neuron properties, DBS acts on neuronal microcircuits embedded in the greater cortico-BG network as part of its neuromodulatory mechanism. Methods: Data was recorded during surgery for DBS electrode implantation from 2 sources: a microelectrode placed in the surgical target (STN or GPi) and a µ-electrocorticography (ECoG) grid placed on the motor association cortex. In one group of subjects, as the microelectrode was lowered along the surgical trajectory, we stopped at multiple sites with neuronal activity for periods of approximately 0.5-5 minutes. In another subset of subjects, DBS was applied across subtherapeutic, thereapeutic and supratherapeutic frequencies. The electrophysiological functional relationships between the STN or GPi and the cortex were studied using through examining APs and LFPs and their temporal and spatial connectivity. Additionally, I examined the DBS waveform and the relationship between the electromotive force (EMF) generated by DBS and distance to the recording electrode. Results: A subset of individual neurons in the STN has an electrophysiological functional relationship to the local electrical environment, and another subset of STN neurons has functional connectivity with the cortex as measured with the AP aligned average LFP. These electrophysiological connections have a high degree of spatial specificity, differing between neighboring neurons and within a few millimeters on the cortex. The effect of DBS on these microcircuits was an increase in LFP power in the alpha band (8-12 Hz) during 140 Hz stimulation. DBS modulated activity in the cortico-BG network at a therapeutically relevant frequency of 140 Hz, but not at subtherapeutic and supratherapeutic frequencies. The DBS waveform is attenuated as distance from the source of stimulation (the DBS lead) increases. Conclusions: The STN and the motor association cortex had an intricate and complex functional connectivity with a high degree of spatial specificity. The topographies of these functional connections varied across neurons and on a sub-centimeter scale on the cortex. When DBS was applied changes in these functional connections were seen with stimulation delivered at 140 Hz. These microcircuits are embedded within in the larger cortico-BG network and are affected by a therapeutically relevant frequency of DBS. The pathological activity in the cortico-BG network is modulated on fine temporal and spatial scales, which explains some of the short-latency effect of DBS on motor symptoms. Significance: We expect the outcomes of this project to be a better understanding of the electrophysiological mechanisms underlying the therapeutic effects of DBS. The broader implications of this research include improving DBS as an intervention and expanding its application to other neurological disorders. Examining the cortico-BG circuit is important in the effort to understand both normal and abnormal motor information processing and to improve neuromodulation therapies.
    • TVET (Technical Vocational Education Training) Contributions toward Education Policy, Economic Sustainability, Development, and Poverty Abatement in a Globalized Economy: A Wicked Problem

      Koyama, Jill; Frick, Sumaya; Bosworth, Kris; Lee, Jenny (The University of Arizona., 2022)
      This dissertation is a study of policy stakeholders (N=24) in four countries within the regional Caribbean Community and Common Market (CARICOM) policy environment. The scope was to identify how they navigated and interpreted conceptualizations of TVET and general education, which have been explicitly tied to national and regional sustainability, development, poverty abatement and skilled labor migration initiatives. Despite variable levels of codified TVET policy, academic centric institutional frameworks, and political will, education policy stakeholders recognized the substantive impact of TVET on their nations and the region. Supported by networked regional knowledge exchanges that are informed by shared tenets central to the Ideal Caribbean Person, they strategically implemented nationally adapted blended TVET and academic education policy. As such, this policy environment has operationalized a rarely seen collaborative governance institutional design and learning system, quadruple-loop learning. At the national level, quadruple-learning principals conditioned calculated risk-taking and innovation, which productively informed regional knowledge exchanges and policy. As an effective tool to recognize, identify, and manage wicked problems, the outcome of this research is a new quadruple-loop learning policy model useful across different regions, national contexts, and connected institutional systems. Data was collected from interviews, policy documents, environmental scans, and public records. Analysis methods employed triangulating coded data, and network and policy analyses to produce modified comparative multi-site case studies and a comparative analysis of case study findings. Keywords: Caribbean, CARICOM, development, education policy, Ideal Caribbean Person, poverty abatement, networks, regional policy, skilled labor migration, social networks, sustainability, TVET, quadruple-loop learning, wicked problems
    • The Gale Transform

      Izosimov, Anton; Dirdak, Abigayle Lynn; Pickrell, Doug; Ercolani, Nick (The University of Arizona., 2021)
      The Gale transform is a map between collections of points in projective spaces. Historically the Gale transform has been defined in several different ways. In this paper I compile three of these definitions to show that they are well defined and that they are equivalent as maps.
    • Sowing the Seeds of Resistance: The Mexican American Struggle for Political Power, the Rise of the Young Barrio Intellectuals, and Police-State Violence in Los Angeles, 1939-1972

      Rodríguez, Roberto; Cid, David; Téllez, Michelle; Otero, Lydia; Magaña, Maurice R. (The University of Arizona., 2022)
      This dissertation explores Mexican American political struggle in Los Angeles from 1939 to 1972. The dissertation begins with an examination of Carta Editorial, an alternative Mexican American periodical, which emerged as a counternarrative response to the bias reporting of the Los Angeles Times, the Los Angeles Herald-Examiner, La Opinion, and other establishment newspapers, which did not portray the Mexican-origin community objectively or fairly. Carta Editorial was a voice for equality, a voice for empowerment, a voice for representation and ultimately a voice for Mexican American liberation. The dissertation then assesses the first six Mexican American Youth Leadership Conferences from 1963 to 1968, emphasizing the themes, dialogues, central figures, and their implications for Chicana and Chicano youth identity, cultural awareness, political consciousness, and community mobilization prior to the historic East Los Angeles High School Walkouts in March 1968. The Mexican American Youth Leadership Conferences were paramount to bringing about the sociopolitical conditions conducive to an emergent generation of young barrio intellectuals. The youth organization that epitomized the ascent of young barrio intellectuals were the Young Citizens for Community Action (YCCA). Despite its short existence, the dissertation argues that YCCA were a pivotal organization in leading and influencing the consciousness raising efforts amongst Mexican-origin youths to organize against a century of educational neglect and police brutality. YCCA aggregated Mexican-origin political heritage of community organizing by cultivating a new framework for youth empowerment and civil rights. During the 1960s and 1970s, Chicana and Chicano activists confronted racial oppression, economic inequality, and sexism on the home front and U.S. imperialistic policies abroad. Amid the Mexican-origin urban rebellions of the 1960s and 1970s, Chicana and Chicano barrio 8 intellectuals self-determined to control their histories, identities, and experiences. As a result of the heightened political activism among young Chicanas and Chicanos, Los Angeles civic leaders, including the Los Angeles Times, elected officials, and police agencies, identified politicized Mexican Americans as a threat to the status quo. The dissertation provides an overview of state-sanctioned police violence against the Los Angeles Mexican-origin community. In accentuating the genealogy of police-community conflict in Los Angeles, the dissertation describes the convergence of the Los Angeles Times and Los Angeles police agencies in criminalizing Mexican-origin youths first as juvenile delinquents in the 1940s and then as subversives in the 1960s. To understand why state-sanctioned police brutality persists, the dissertation appraises the Los Angeles Times’ archives revealing that the influential and powerful daily did not hesitate to absolve the police of charges of brutality and misconduct by editorializing and reporting that holding the police accountable for their misdeeds would lead to low morale conditions among police officers. The dissertation ends with an inquiry of the four known police infiltrators and informants who disrupted Chicano Movement activities between 1967 and 1972. I also appraise the Grand Jury Inquest into the East Los Angeles High School Walkouts in 1968 and the Carlos Montes Trial in 1979. Notably, the dissertation probes how the Los Angeles Police Department, the Los Angeles Sheriff’s Department, the Federal Bureau of Investigation targeted Chicano Movement activists through surveillance, infiltration, intimidation, threats of violence, harassment, and disruption of constitutionally protected rights. Police forces sought to destroy the Chicano Movement in Los Angeles to maintain white supremacy.
    • Mosquitoes in Paradise: An Interdisciplinary Approach To Explore the Adoption of Community-Based Mosquito Control Strategies for Aedes aegypti in Peñuelas, Puerto Rico

      Ernst, Kacey C.; Madera Garcia, Valerie; Jacobs, Elizabeth; Ellingson, Katherine; Walker, Kathleen R. (The University of Arizona., 2022)
      Background: Aedes (Ae.) aegypti, predominantly found in urban environments, oviposit in human-made containers in and around households, and is the primary vector of dengue, Zika, and chikungunya viruses in tropical and subtropical areas of the world. While the continental United States has had only sporadic outbreaks, dengue transmission has been intractable in Puerto Rico, where seasonal outbreaks have been recorded since 1915. Recent emergence of chikungunya and Zika further worsened health outcomes from mosquito-borne diseases in Puerto Rico. Prevention and reduction of arboviral diseases continue to depend on controlling mosquito populations. Vector control efforts have shown a minimal degree of success over the last 50 years in Puerto Rico. Evidence suggests that community mobilization is an essential component of successful and sustainable mosquito control efforts. Before implementing these interventions, it is imperative to obtain community-level information and input. The objectives of this interdisciplinary dissertation were to characterize the human and environmental factors associated with immature Ae. aegypti habitats in Peñuelas, Puerto Rico, explore the application of stated preferences methodologies in vector control research, and measure preferences for an Ae. aegypti mosquito control program in Peñuelas, Puerto Rico using a best-worst choice (BWC) approach. Methods: Outdoor house inspections were performed in the 69 selected houses from 10 neighborhoods of Peñuelas, and all containers were searched and inspected for water and mosquito immatures. Descriptive statistics were used to summarize demographics and human factors (i.e., knowledge about mosquito breeding sites) among the surveyed sample and to characterize containers, water-holding containers, and containers producing immature mosquitoes. Principal container analyses were used to quantify immature mosquito abundance in proportion to water-holding containers. Multiple regression models were used to examine the relationship between demographic and human factors (i.e., age, education) and containers, water-holding containers, and mosquito immature abundance. A PRISMA-guided scoping literature review was performed in August 2021 to synthesize and summarize the current use of stated preferences tools and vector control and provide recommendations to improve the application of these tools in the development and evaluation of vector control programming. A total of three databases (PubMed, Embase, PsycInfo) were searched for eligible studies, and data were extracted from studies meeting the eligibility criteria. Recommendations for improving the application of stated preferences tools to vector control programming were made. Finally, a total of 175 participants from Peñuelas were selected and surveyed face-to-face in July 2021 using a two-stage cluster design. Stated preferences toward various components of mosquito control programs were identified by implementing BWC in the participants from Peñuelas. Furthermore, willingness/unwillingness to participate in and willingness to pay for a mosquito control program was explored. A conditional logit analysis was used to estimate preferences and random effects logit was used to measure willingness to participate and willingness to pay. Results: A total of 4090 containers were identified and inspected during the outdoor inspections of 69 homes, from which 7.0% held water, 1.5% were larvae-positive, and 0.5% pupae-positive. Bromeliads were the most common water-holding container and were found to be responsible for 37.8% of the production of mosquito immatures in the surveyed houses. Higher education level was significantly negatively associated with container abundance and with lower odds of having mosquito immatures in their houses. Also, knowing at least one specific container that serves a breeding site was significantly associated with higher odds of mosquito immature infestation. In the scoping review, only 17 studies were included from the 686 articles screened. Most of the studies were conducted in sub-Saharan African countries (72.2%), focused on insecticide-treated nets (ITNs) for malaria prevention (52.9%), and used contingent valuation methods (82.4%). Studies were classified into reducing human-vector contact (64.7%), reducing mosquito abundance (29.4%), or both (5.9%). While demand exists for vector control programs, there were no consistent associations between demand and explanatory factors (i.e., demographics, etc.) in either human-vector studies or mosquito abundance studies. The BWC assessment indicates that the most important features of a mosquito control program were that it was applied at the neighborhood level, implemented by the local government, and focused specifically on reducing disease transmission instead of mosquito abundance (i.e., dengue). Programs targeting the reduction of disease transmission had a positive effect on willingness to participate in the program. Education was positively correlated with expressing willingness to participate in a mosquito control program. Our study results revealed that participants were willing to pay up to $72.00 to have a program targeting the reduction of diseases, such as dengue. Conclusion: The results of this dissertation provide evidence that bromeliads, the most common water-holding container and disproportionately productive, must be targeted in future mosquito control efforts. Conversely, having mosquito control strategies targeting large water storage containers might not be efficient at reducing mosquito indices in Peñuelas. The current literature on stated preferences and vector control is limited in the scope of vector control methods being investigated, the countries being studied, and the determinants of demand measured. Future research is needed to expand the application of stated preferences to measure demand and preferences for various vector control strategies, including newly developed and community-based methods. This dissertation demonstrated that reducing disease transmission is the highest priority and influences the likelihood of participation for the residents in Peñuelas. Individuals were willing to pay a considerable amount of money for a program with this focus. This finding suggests that a mosquito control program can specifically target Ae. aegypti mosquitoes, which transmit dengue, chikungunya, and Zika in the study area. The results of this dissertation can improve stakeholders’ decisions regarding mosquito control strategies implemented in Peñuelas, Puerto Rico. There is strong potential to incorporate community-based efforts with government-led efforts to decrease Ae. aegypti mosquito abundance and reduce the transmission of dengue in Peñuelas, Puerto Rico.
    • Conservation Genomic Analyses of the Endangered Masked Bobwhite Quail (Colinus Virginianus Ridgewayi)

      Culver, Melanie; Vargas, Karla Leonor; Gallery, Rachel; Badyaev, Alexander; Faircloth, Brant (The University of Arizona., 2022)
      The unparalleled rate at which biodiversity is disappearing around the globe has made conservation of imperiled populations an urgent but difficult task. Critical resources are increasingly limited, constraining effective conservation practices. Genetic distinctiveness is an important metric used to prioritize conservation efforts. The masked bobwhite (Colinus virginianus ridgwayi) is a peripheral population and genetically differentiated subspecies of the northern bobwhite. To generate data beneficial to conservation efforts for the endangered masked bobwhite, I used genomic sequencing methods to resolve fine scale evolutionary relationships among the masked bobwhite, Texas bobwhite, and Mexican subspecies of northern bobwhite. I analyzed thousands of single nucleotide polymorphisms (SNPs) to elucidate genetic diversity patterns and population structure among subspecies, and I applied a maximum entropy approach to generate species distribution models (SDMs) to assess climate variables that affect the geographic distributions, to examine similarity among key subspecies’ habitats, and to project potential habitat suitability of key subspecies under present-day and future climate change scenarios. The results from this study suggest that C. v. ridgwayi, C. v texanus, and C. v. graysoni are more closely related to each other than to other Mexican subspecies and support the genetic distinctiveness of C. v. ridgwayi. SNP analyses suggest some genetic distinction between contemporary and historical samples of the masked bobwhite, which should be further explored since results rely on only one successful historical sample. SDM analyses to estimate climatic variables most important to current and future habitat quality for northern bobwhite showed that specific climate variables that contribute to current and future potential distribution of the northern bobwhite differ when modeling distribution at the species- versus subspecies-level. Also, the distribution of C. v. ridgwayi and C. v. graysoni seemed to be determined by variables other than climate. SDM results suggest possible changes in habitat suitability over time, but the choice of variables and climate models could alter predictions, therefore, the SDM results should be used as a preliminary baseline to direct and build future model development for northern bobwhite. The results from this work could be used by managers for conservation planning and decision making and to aid the recovery efforts for the highly endangered masked bobwhite.
    • Utilizing Environmental Analytical Chemistry to Establish Culturally Appropriate Community Partnerships

      Briehl, Margaret; Ingram, Jani C.; Credo, Jonathan; Gachupin, Francine; Warneke, James (The University of Arizona., 2022)
      In the United States, minority communities are disproportionately exposed to environmental contaminants due to a combination of historically discriminatory based racial policies and a lack of social political capital. Within this demographic, American Indian/Alaskan Native (AI/AN) communities have additional factors that increase the likelihood of contaminant exposure. Some of these factors include the disparity of social, cultural, and political representation, differences in cultural understandings between AI/AN communities and western populations, and the unique history of tribal sovereignty in the US. Research from both private and federal organizations starting in the 1990s led to a change in research agendas that emphasized a push to conduct research with AI/AN communities. However, although many research pursuits may be rooted in beneficence, the rift in cultural upbringing can lead to negative outcomes as well as further isolation and misrepresentation of AI/AN communities. Arguably the most significant example of this breakdown is the Havasupai v Arizona Board of Regents case surrounding the misuse of Havasupai blood samples. The outcome of this case led to many Tribal Nations around the United States increasing their distrust of outsiders, regardless of their organizational affiliation. Despite this sobering example, collaborations with AI/AN communities need not be difficult or tempestuous. However, it does require a change in the existing western scientific approach to both community collaborations as well as how science is viewed. Simply put, researchers must work to overcome the initial distrust many Tribal Nations have towards outsiders, and this attitude must be maintained throughout the duration of the partnership. Some obstacles to collaboration include the amount of time and resource allocation as well as identifying the most culturally appropriate methodology while maintaining scientific rigor. Instead of viewing these hurdles as nuisances, western scientists should view them as challenges and the opportunity to adapt their approaches while still maintaining rigorous and reproducible science. An achievable change in heuristics is to approach these type of collaborations as if one is forging a healthy friendship with another individual. This dissertation exemplifies the benefits of adopting these approaches and outlines four years of effort to secure enough trust with two Tribal Nations, the Cocopah and the Colorado River Indian Tribes, to be allowed to conduct a pilot study within their Tribal lands in full collaboration with their governing body. As part of that four years, in addition to numerous in-person and virtual meetings, preliminary data was gathered to demonstrate the potential harm of environmental contaminants to the Tribal population. It should be noted, although there are similarities in the approved methodologies for the pilot grants with the Tribes, they are distinctly different but still address the underlying concerns of the Tribes. This versatility is one of the hallmark benefits of utilizing environmental analytical chemistry in this capacity. Specifically, it allows researchers numerous modalities to investigate the root causes of the environmental concerns a Tribal Nation may have and can be modified to be unique for each community.
    • Reciprocity Across Communities: An Infrastructure of Accountability in Community Engagement

      Robbins, Stephanie T.; Iglesias, Charisse Hope Sayo; Shivers-McNair, Ann; Mapes, Aimee; Bose, Dev (The University of Arizona., 2022)
      My research and practice into reciprocal community engagement developed from my Peace Corps experience in Indonesia from 2014-2016. Although my Peace Corps experience was educational and fruitful, I observed many instances of Peace Corps volunteers—myself included—who exhibited traits of a savior complex and who failed to conduct equitable and reciprocal community engagement with our local constituents. A large part of my doctoral research has been composing comics as reflection, which can be an indirect strategy of dealing with difficult feelings because the process redirects the focus on the artwork, rather than on myself. By doing so, I have been able to step back, see the whole picture, and make connections between what was experienced at the moment and the lessons that came from it. The Peace Corps and my reflection of those experiences propelled this dissertation project into developing systemic changes in how we work with diverse communities.Since continuing my community engagement projects and reflective practices after the Peace Corps and throughout my doctoral studies at the University of Arizona, I have often wondered: What can we do to help community-engaged practitioners avoid the mistakes I made leading up to experiences that were not practiced reciprocally? This question connects to questions that many community-engaged practitioners and organizations are asking: What systemic changes can we make to improve how people engage diverse communities? How can we better connect with historically marginalized people and prioritize their needs while avoiding the savior complex? My dissertation addresses these questions about community engagement through a systemic, critically feminist lens that confronts the common missteps of working with diverse communities. Reciprocity Across Communities is a capacity-building framework establishing an infrastructure of accountability in community engagement through qualitative and quantitative data collected from: National volunteer program (administration) Regional community writing program (training) Course on technical and professional communication (TPC) for culturally and linguistically diverse audiences (teaching). The foundational concept of reciprocity can disrupt power imbalances in community engagement. As a critical feminist intervention, reciprocity creates space for negotiating difference and co-constructed meaning making as well as repositions traditional framing of communities as recipients of knowledge and service. Through the case studies in my dissertation, I show how different conceptualizations of reciprocity can add to existing conversations around service learning, community-university partnerships, community outreach projects, etc. to launch a Reciprocity Across Communities model that foregrounds the interconnectedness of administration, training, and teaching through accountability. Developing reciprocal community-engaged partnerships is full of gray areas and flexible expectations, interpersonal conflicts may prevent meaningful engagement, and saying or behaving in unwelcome ways could invite all kinds of miscommunication. My hope with Reciprocity Across Communities is to share a model that triangulates how we engage with diverse communities, encourages strategies that meet the (un)spoken needs of our constituents, and holds us accountable to how we create meaning with each other.
    • New Approaches to Population Genetics in the Light of Load at Many Loci

      Masel, Joanna; Matheson, Joseph Daniel; Enard, David; Figueredo, Aurelio; Walsh, Bruce (The University of Arizona., 2022)
      Hermann Muller first used the term ‘genetic load’ in 1950 to refer to the burden imposed on populations by deleterious genetic variants, but fears about heritable deleterious traits proliferating have haunted the newborn field of population genetics from the beginning. Classical population genetic theory seemed to suggest that load could build up to dangerous levels in a variety of situations: rapid adaptation, high mutation rates, or sufficiently weak natural selection. Different formulations of load problems have been proposed and then apparently solved, but the solutions have not all stood the test of time. In this dissertation, I will highlight some places where established population genetic theory fails to sufficiently capture the effects of load, especially mildly deleterious load dispersed across many linked loci.I first investigate Haldane’s Dilemma, an implausibly strict speed limit on adaptation proposed by Haldane based on his analysis of the load that builds up during the process of substituting one allele for another. This dilemma was apparently solved by noting that Haldane’s calculations used the wrong type of load, but substantial confusion in the literature on the topic has left a more accurate formulation of the dilemma still unsolved. I apply this formulation to an Arabidopsis dataset tracking seed production, seed survival, and juvenile plant survival across eight different environments. In this dataset, the dilemma poses no real threat because a much higher fraction of deaths contribute to adaptation than had been anticipated by previous estimates. I then investigate the effects of removing deleterious load on neutral variation, a phenomenon known as background selection. The prevailing analytical approach assumes no linkage between deleterious mutations as a simplification. There are theoretical reasons to expect that this assumption will be wrong, and given the sheer quantity of deleterious mutations entering populations, violations of this assumption are likely not trivial. I find that when simulating a genome with realistic degrees of mutation and recombination, background selection has much stronger effects on neutral diversity than the prevailing theory predicts. I last investigate accumulation of small-effect deleterious load, a load problem which Kondrashov (1995) suggests should have killed us ‘one hundred times over’. One standard answer to this problem — synergistic epistasis between deleterious mutations — has been contradicted by empirical evidence. The second answer — beneficial mutations counteracting deleterious load — is promising, but previous theoretical descriptions again ignored the effects of linkage. I built a novel simulation model to investigate accumulating load in the presence of rare beneficial mutations. I find that rare large-effect beneficial mutations can asymmetrically counteract deleterious load. However, whether there are enough beneficial mutations left over for populations to adapt depends on the value of beneficial parameters for which we still lack good empirical estimates. I show in a variety of cases that new approaches which account for the effects of deleterious load across many linked loci are able to contribute new answers to foundational questions in population genetics.
    • Implementing and Testing Exterior Calculus Discretization Techniques for PDEs

      Gillette, Andrew; Levine, Joshua; Crum, Justin Robert; Brio, Moysey; Imbert-Gerard, Lise Marie (The University of Arizona., 2022)
      Finite element exterior calculus and discrete exterior calculus have been actively used and developed in the last two decades. In this dissertation we first work in the context of finite element exterior calculus, studying the “trimmed serendipity” finite element family by building an implementation of them that allows for analyzing their properties in practice. Then, we apply the trimmed serendipity elements to the monodomain equation, an application problem of interest in cardiac modeling. Finally, we swap to the discrete exterior calculus context where we define and apply a fractional discrete exterior derivative. By using a Python package called Firedrake, we illustrate how to implement the trimmed serendipity finite elements. Using that code, we then give a rigorous analysis of how the trimmed serendipity finite elements compare against the tensor product finite elements on a variety of toy problems. These include a projection problem, a primal formulation of the Poisson problem, a mixed formulation of the Poisson problem, and the Maxwell cavity eigenvalue problem. After testing the elements on these toy problems, we move to applying the elements to approximating the solution of the mondomain equation. This particular equation can be changed in different ways to model how electricity flows through the heart. Depending on the exact choice of model used, it can range from a simple model that shows only the macro-scale dynamics all the way to a complicated model that incorporates micro-scale dynamics of different ionic compounds. Using this model, we test the trimmed serendipity elements in conjunction with a recent implementation of Runge-Kutta methods in Firedrake. Finally, we end with studying how fractional derivatives can be discretized in the setting of discrete exterior calculus. While the discrete exterior derivative and many other operators are well defined and commonly used in discrete exterior calculus, the fractional derivative operator is a little more difficult. The nonlocal nature of a fractional operator leads to issues of how to define distances between non-adjacent simplices in a mesh, which discrete exterior calculus does not normally do. After giving a definition for a fractional discrete exterior derivative, we analyze its properties and give a discussion on some of these difficulties.
    • Glyoxalase 1 as a Novel Molecular Marker of High-Grade Prostatic Intraepithelial Neoplasia and Causative Effector in the Progression of Prostate Cancer

      Wondrak, Georg T.; Rounds, Liliana; Nagle, Raymond B.; Chalasani, Pavani; Romagnolo, Donato; Roberts, Esteban; Riggs, Michael W. (The University of Arizona., 2022)
      The prostate is a male accessory sex gland that functions to produce many components of the seminal fluid including zinc and citrate, both of which are crucial to men fertility. The prostate gland has two main compartments: the stroma and the epithelium. Three cell types comprise the prostatic epithelium: secretory epithelial cells, basal/stem cells, and neuroendocrine cells. The prostatic epithelium is unique in that they are the only healthy human cells that produce energy by glycolysis rather than the Krebs cycle. Changes in the prostatic epithelium leading to malignant proliferation increase in incidence with age. Prostate carcinoma (PCa) is the leading malignancy and the second leading cause of cancer-associated deaths in the USA male population. PCa is a disease of the elderly and risk prediction becomes crucial. Most patients present low-risk, relatively indolent tumors; however, 20-30% of these men present tumor characteristics associated with high-risk PCa. High Grade Prostatic intraepithelial neoplasia (HGPIN) is the only widely accepted histological condition and precursor of invasive PCa. High glycolytic activity is an oncometabolic hallmark of cancer. Cancer cells turn to aerobic glycolysis for energy production in a process referred to as ‘the Warburg effect’ leading to accumulation of methylglyoxal (MG), a cytotoxic glycolytic byproduct responsible for the adduction of macromolecules, a process called advanced glycation end-products (AGEs) formation. Glyoxalase 1 (GLO1), also known as lactoylglutathione lyase (EC: 4.4.1.5), is part of the glyoxalase system, playing a crucial role in cellular detoxification of spontaneously formed MG. In a two-step reaction, GLO1 first catalyzes the conversion of highly reactive MG to S-D-lactoylgluthatione. The resulting thioester, in the case of MG, is then hydrolyzed by GLO2 to produce D-lactate and reformed glutathione (GSH). The cytoprotective glyoxalase system prevents formation of AGEs and promotes cell survival. GLO1 upregulation has been described in the context of metabolic and inflammatory stress in vitro and in vivo, serving as a cellular mechanism to detoxify high levels of MG, particularly in cancer, where high glycolytic rates as a result of the ‘Warburg effect’ are observed. Our laboratory has demonstrated GLO1 upregulation during tumor progression, observable in HGPIN and PCa versus normal prostatic tissue by immunohistochemistry in archival tumor samples. GLO1 upregulation was identified as a novel hallmark of HGPIN lesions. In PCa specimens, GLO1 expression correlated with intermediate–high risk Gleason grade but not with patient age, biochemical recurrence, or pathological stage. Using CRISPR/Cas9 we genetically engineered GLO1 knock-out isogenic clones from DU-145 prostate carcinoma cells to further examine the role of GLO1 in PCa. Interestingly, we showed upregulation of TXNIP (encoding the thioredoxin-interacting protein) in the DU-145-GLO1_KO as a function of GLO1 status. TXNIP is a master regulator of cellular energy metabolism and redox homeostasis, also considered a tumor suppressor. Furthermore, GLO1 elimination had a profound detrimental effect in the clonogenicity and invasiveness capacity. We also identified MMP-3 (encoding matrix metalloproteinase-3) and SPP1 (encoding secreted phosphoprotein 1) as the two genes displaying the most profound downregulation in response to GLO1 elimination. MMP-3 and SPP1 are two effectors implicated in the development of prostate cancer in the bone, tumor-associated inflammation, facilitating metastasis, and promoting drug resistance. Additionally, based on The Human Protein Atlas data, decreased survival probability correlated with high MMP-3 mRNA expression levels in tissue from prostate cancer patients suggesting that GLO1 expression status is a novel and underappreciated determinant of PCa invasiveness and patient survival. Our published GLO1 data generated some excitement in the private sector with a potential translational application for GLO1 in the clinical setting. Current studies performed at Roche Diagnostics seek to develop a methodology for the detection of malignant biochemical signatures in tissue by spectroscopic imaging. These signatures can be used as biomarkers of early prostate cancer associated with aggressive disease. GLO1 promises to be one of the targets of study. Our future goals seek to (a) have a better understanding of the molecular mechanisms underlining oncometabolic dysregulation in PCa, (b) an improved understanding of the molecular basis underlying early PCa with a focus on HGPIN lesions pursued in relevant murine models, (c) identify improved molecular therapeutics that allow early interventions targeting HGPIN and mPCa. Translationally, we seek to aid in the development of powerful prognostic and diagnostic biomarkers identifying HGPIN and PCa and the discovery and development of novel optics-based technologies for the antibody independent diagnosis and prediction of PCa grade and progression.
    • Resistive Robotic Gait Training to Restore Neuromuscular Function in Cerebral Palsy

      Lerner, Zachary F.; Kruer, Michael C.; Conner, Benjamin Charles; Schaefer, Sydney Y.; Duncan, Burris "Duke" (The University of Arizona., 2022)
      Individuals with cerebral palsy (CP) have deficits in strength and neuromuscular coordination, which contribute to a slow and inefficient gait pattern that makes walking difficult for an overwhelming majority of this population. Previous interventions seeking to address these aspects of gait dysfunction in CP have been unsuccessful to date in addressing both muscle weakness and motor control. In an effort to address this gap in clinical care, we developed and validated an adaptive control scheme in conjunction with an untethered ankle exoskeleton device to provide ankle plantar flexion resistance during walking that was responsive to user input. We found that compared to baseline, walking with adaptive plantar flexion resistance resulted in a 45 ± 35% increase in stance-phase plantar flexor activity (p = 0.02) and a 46 ± 25% reduction in stance-phase co-contraction at the ankle (p = 0.02) for children and young adults with CP. This modality was then applied in a pilot clinical trial in CP, whereby six pediatric participants completed ten, 20-minute training sessions with adaptive plantar flexion resistance over four weeks. We observed significant improvements in measures of strength (17 ± 8% increase in ankle plantar flexion strength, p = 0.02), preferred walking speed on a treadmill (39 ± 25% increase, p = 0.04), energetic efficiency (33 ± 9% reduction in metabolic cost of transport, p = 0.03), and measures of mobility (11 ± 9% improvement in timed up and go performance, p = 0.04; 13 ± 9% increase in six minute walk test distance, p = 0.04). These improvements in gross measures of performance were likely a result of observed improvements in neuromuscular control and mechanical efficiency, with training resulting in a 29 ± 11% decrease in co-contraction at the ankle (p = 0.02), a 33 ± 13% more typical soleus muscle activation profile (p = 0.01), a 7 ± 3% increase in neural control complexity (p < 0.01; measured via muscle synergy analysis), and a 58 ± 34% more mechanically efficient gait pattern (p < 0.05). Overall, this novel resistive robotic gait training paradigm demonstrated significant promise in improving strength and neuromuscular control at the ankle for improved mobility in children with CP. To further enhance the efficacy of this intervention, we developed an electrodeless audiovisual biofeedback system that utilized force sensitive resistors to display real-time plantar pressure to a user while walking. In validating this system against a soleus electromyography (EMG) biofeedback system in eight individuals with CP, which was considered the gold standard, we found comparable increases in mean soleus muscle activation relative to baseline (43 – 58%, p < 0.05), as well as mean (68 – 70%, p < 0.05) and peak (71 – 82%, p < 0.05) medial gastrocnemius activation, with strong relationships between the two systems for these outcome variables (R = 0.89 – 0.94). When this system was applied to our adaptive plantar flexion resistance scheme, it rapidly increased mean (36%, p < 0.05) and peak (46%, p < 0.05) soleus activation relative to resistance alone. The integration of this plantar pressure biofeedback system may help to improve active engagement with our resistive ankle exoskeleton scheme, reducing the necessity of constant verbal coaching or long acclimation periods. Finally, we aimed to better understand the underlying neuromuscular response to walking with our resistive ankle exoskeleton, as well as answer fundamental questions about reflex modulation in CP. We tested the effect of changes in motor task complexity, requiring varying levels of ankle stability, on soleus H-reflex excitability in this population. We found that individuals with CP displayed the typical decrease in soleus H-reflex excitability with increased standing task complexity (-26 ± 27%, p = 0.04). We also observed significant inverse relationships between soleus H-reflex amplitude and co-contraction at the ankle during both complex standing (R = -0.58, p < 0.01) and walking (R = -0.52, p < 0.01) tasks, suggesting the presence of reciprocal inhibition, which was previously thought to be absent in CP.