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Rank-Based Analyses and Designs with Clustered Data
No full textClustered data are common in biomedical research. It is often of interest to evaluate the correlations within clusters and between variables with clustered data. Conventional approaches, including intraclass correlation coefficients (ICCs) and Pearson correlations, are commonly used in analyses with clustered data. However, these conventional approaches are sensitive to extreme values and skewness. They also depend on the scale of the data and are not applicable to ordered categorical data. In this dissertation, we define population parameters for the rank ICC and between- and within-cluster Spearman rank correlations. These definitions are natural extensions of the conventional correlations to the rank scale. We show that the total Spearman rank correlation approximates a weighted sum of between- and within-cluster Spearman rank correlations, with weights determined by the rank ICCs of the two random variables. We also describe estimation and inference for these four rank-based correlations, conduct simulations to evaluate the performance of our estimators, and illustrate their use with real data examples. Furthermore, we apply the rank ICC in the design of clustered randomized controlled trials (RCTs), proposing unified and simple sample size calculations for cluster RCTs with skewed or ordinal outcomes. Our calculation involves inflating the sample size for an adequately powered individual RCT for an ordinal outcome with a design effect that incorporates the rank ICC. For continuous outcomes, our calculation sets the number of distinct ordinal levels to the sample size. We show that with continuous data, our calculations closely approximate more complicated sample size calculations based on clustered Wilcoxon rank-sum tests. We conduct simulations to evaluate our calculations' performance and illustrate their use in the design of two cluster RCTs, one with a skewed continuous outcome and a non-inferiority trial with an irregularly distributed count outcome
Putting the self in context: An integrative analysis of interoception in autism
No full textIn this dissertation, we used multiple complementary approaches to understand how the sense of interoception develops from childhood to adulthood and how this relates to the types of interoceptive challenges commonly experienced by autistic individuals. These approaches were designed to account for the often subconscious, situational ways that we process these stimuli. First, we examined the properties of interoceptive brain systems, which informs how we process information beyond our conscious awareness. In Chapter 2, we examined the structural properties of interoceptive brain regions in autistic and non-autistic individuals and in Chapter 3, we analyzed communication between primary interoceptive regions with the rest of the brain. Then in Chapter 4, to link these findings back to behavior and perceptual experiences, we analyzed interoception using a new generation of interoceptive perceptual tasks that links the study of interoception with the multisensory literature. Using these approaches, we built a deeper understanding of how interoception is developed and refined along a gradient of complexity. We found only a few areas in which interoceptive-exteroceptive integration, or its neural correlates, differed in autism as a whole. However, our findings suggests that interactions between autism and individual characteristics including age, the degree of autism-related behaviors, physiology, and anxiety levels may explain more about interoceptive profiles than diagnosis alone. These findings provide ideas for how to personalize a new generation of interoceptive supports for individuals who experience these challenges
Cultivating the Capacity to Lead Culture and Character in Charter School Networks
No full textLeadership and Learning in Organizations capstone projectThe Charter School Growth Fund (CSGF) aims to foster character and culture development in its portfolio of charter schools. The Thick Practice Cohort was established to support schools in implementing a comprehensive approach to character development. This study investigates the implementation of thick cultural practices within the cohort and assesses its impact on human flourishing and character development. Through interviews with network leaders and surveys of teachers and school-based leaders, this study identifies challenges and opportunities for improvement. Key findings include the positive impact of the cohort on leadership development and peer learning, as well as challenges related to organizational growth and the alignment of values and practices. Recommendations include developing measurement tools, creating a logic model, requiring strategic planning, providing tailored support, and leveraging the cohort structure to enhance accountability and community building. By addressing these recommendations, CSGF can further strengthen the impact of the Thick Practice Cohort and promote the development of thriving school cultures
Middle-School Students’ Mathematical Sensemaking in Videogame Play
No full textResearch demonstrates that the dominant but narrow definitions of mathematical activity in school limit students’ opportunity to make sense of mathematics and to use mathematics to make sense of the world. Video games have the potential to disrupt these narrow definitions, because in video games players are positioned as empowered learners who solve problems with understanding. Yet, this potential can be circumscribed by the inertia of inherited pedagogical forms, such as school worksheets and textbook word problems. This dissertation draws on the notion of frames of activity to examine the tensions between the potential of videogame media and the inertia of enduring pedagogical forms in broadening and constraining children’s mathematical sensemaking in educational videogame play. The first paper examines children’s mathematical sensemaking with and without the in-game problem-solving scaffold that resembled a school worksheet. This paper demonstrates that the familiar form of worksheet invited the frame for rote participation that shifted students away from the frame of mathematical sensemaking. The second paper examines two students who framed their videogame play differently, demonstrating how children’s mathematical sensemaking was recognizable and supported when their sensemaking aligned with the frame for school mathematics, but was invisible and unsupported when their sensemaking better aligned with the frame for videogame play. The third paper examines the limitations of using textbook word problems as initial prototypes in videogame designs for mathematics learning and proposes a potential redesign that centers and extends children’s mathematizing play
“Finding a community that can open our mind”: Countering Pain Narratives among LGBTQ+ Youth in High Stigma Contexts
No full textThis study investigates the multifaceted experiences and resilience strategies of LGBTQ+ youth in Tennessee, a region marked by heightened stigma. Through focus group interviews and semi-structured individual interviews conducted via Zoom, a total of 16 LGBTQ+ youth aged 14-24 residing in Tennessee participated in the study. The research explores the challenges faced by LGBTQ+ youth in navigating a high-stigma environment while seeking support and engaging in resilience strategies. Despite encountering systemic barriers and discrimination, LGBTQ+ youth demonstrate remarkable resilience through engagement in collective activism and advocacy endeavors. Supportive family members, LGBTQ+ friends and peers, affirming mental healthcare providers, and affirming social media encounters emerge as crucial spheres of resilience, buffering against the detrimental effects of minority stressors. These findings underscore the importance of adopting a more nuanced approach to understanding mental health disparities among marginalized populations and highlight the critical need for interventions that promote well-being and resilience within high-stigma contexts. By amplifying the voices of LGBTQ+ youth, centering their experiences, and developing interventions grounded in a desire-centered research approach, this study contributes to creating more inclusive and affirming environments for all members of the LGBTQ+ communit
Dehydroalanine and Dehydrobutyrine: Post-Translational Modifications Implicated in Aging Lenses and Age-Related Nuclear Cataracts
No full textThe molecular mechanisms associated with aging and age-related diseases are still being discovered. Spontaneous degradation of proteins can lead to the formation of post-translational modifications (PTMs). Among the PTMs found among long-lived proteins, have been those that lead to irreversible protein-protein crosslinks, such as those seen in the ocular lens. Two PTMs that have been implicated in crosslink formation in age-related nuclear cataracts (ARNC) are dehydroalanine (DHA) and dehydrobutyrine (DHB). DHA is formed from cysteine/serine and DHB is formed from threonine residues. Even though DHA and DHB-mediated crosslinks have been found in ARNC, a study of DHA and DHB and how it may contribute to aging and age-related diseases has been the focus of few studies. In this dissertation work, the prevalence of DHA and DHB were studied in aging human lenses with and without ARNC. DHA-containing peptides were classified into three groups based on abundance changes with age and cataract: those that (1) increased only in ARNC, (2) increased in aged and cataractous lenses, and (3) decreased in aged lenses and ARNC. In most donor groups, proteins with DHA and DHB were more likely to be found among urea-insoluble proteins rather than among water- or urea-soluble proteins. To further study whether DHA may induce structural changes, the prevalence of DHA from cysteine loss and similarly DHA-mediated glutathione crosslinks were studied in an established ARNC animal model. DHA abundance in control guinea pig lens proteins was compared to guinea pig lens proteins exposed to a hyperbaric oxygen treatment. The results showed that DHA was more likely to be in the water-insoluble fraction while DHA-GSH crosslinks were more likely to be in the water-soluble fraction. An alanine mutant was used to measure the potential structural differences that may be caused by DHA formation in β B1-crystallin, a lens protein that was found to have DHA from previous results. These results showed that DHA may have a small but measurable impact on protein solubility
Impact Resistance of Corner Supported Concrete Panels
No full textIn modern architectural settings, the resilience of reinforced concrete cladding panels is paramount, particularly in regions where they might be subjected to projectile impacts or blast loadings. This research is centered on formulating a modeling and simulation approach for reinforced concrete cladding panels, both with and without glazed window openings. Drawing insights from an exhaustive analysis of impact and blast loadings, the research adapted the physical details of the panels in accordance with prevailing standards in Saudi Arabia, specifically focusing on panels anchored solely by comer supports, representing a structurally challenging case. Two predominant panel variants were studied: solid panels and those with glazed window openings. A novel post-construction hardening technique, using bonded polyethylene film, was introduced to enhance the panels' resistance. This study embarked on an extensive material testing phase, encapsulating concrete, steel reinforcement, glass, and polyethylene film. Consecutively, the panels were subjected to projectile impact tests using the Instron Drop Weight Impact Tester. The primary validation tool was a computer simulation, juxtaposed with actual impact test results, which provided a holistic understanding of the panels' response under various conditions. This comprehensive approach offers significant insights and potential modifications for enhancing the safety and durability of reinforced concrete panels in contemporary structures. The effectiveness of bonded polyethylene film in hardening the cladding panel was ensured by a series of simulations with higher impact velocities than was possible in the laboratory
DETERMINING THE ROLE OF ACIDIC PH SENSING AND RESISTANCE IN UROPATHOGENIC ESCHERICHIA COLI PATHOGENESIS
No full textUropathogenic Escherichia coli (UPEC) is one of the most prevalent human pathogens, causing about 80% of urinary tract infections (UTI) in the world. To establish an infection in the bladder, UPEC must survive in the gastrointestinal tract and genitourinary tract. These bodily niches present significant stresses to UPEC, including acidic pH stress. UPEC are equipped with multiple different acid resistance mechanism, however, the role these systems play during UTI has not been elucidated.In this work, I describe a new acid resistance mechanism in UPEC that utilizes serine deamination. I determine that loss of serine deamination leads to reduced survival in acidic media conditions. I show that serine is imported by UPEC under acidic media conditions. I also show that serine deamination is also important for the activation of a cross regulating two-component system, BtsS-YpdB. Through RNAseq analyses, I show that BtsS-YpdB is involved in regulating cysteine metabolism in acidic conditions, providing additional evidence of how acidic conditions impact cell metabolism. Additionally, through systematic deletion of UPEC’s acid resistance mechanism genes, I determine that lysine decarboxylation plays a key role in early bladder colonization. During bladder cell infection, the lysine decarboxylase, cadA, is upregulated in UPEC. Deletion of cadA reduces UPEC’s ability to survive within bladder cells compared to wildtype strains. Collectively, this work helps to elucidate how UPEC utilizes its acid resistance mechanisms during infection and identify lysine decarboxylation as a critical mechanism for early bladder colonization
Welcome Back, Teacher: A Quantitative Exploration of Teacher Labor Movement Out of and Returning to the Classroom and the Impact of Time Away on Teacher Quality Measures
No full textAs concern grows about teacher attrition and the resulting teacher shortages, one underexplored solution is the return of teachers who previously left. These papers provide an updated descriptive and comparative look at these teachers in the specific context of the state of Tennessee. In addition to observable characteristics, this research is the first to offer a descriptive analysis of how teachers performed prior to leaving, both in terms of test-based value-added measures (VAM) and in Principal rating scores. Teachers that returned are more likely to be younger, return within 5 years, and fully licensed. Measures of a teacher’s quality prior to exit are not as salient, but they do operate as a sorting mechanism within gender to predict returns. I also explore the relationships of returning teachers to their principals through a descriptive analysis of whether teachers return to the same school or district that they left from. Further, this study also provides a first attempt to quantify the impact of their absence on the VAM score and Principal ratings of a returning teacher compared to teachers with uninterrupted careers. Using a difference-in-differences and matching methodology, I find no statistically significant difference between returning teachers and matched teachers, though the sample of returning teachers outperforms on VAM scores six years after returning, and the sample of returning teachers receive higher principal ratings compared with teachers with equivalent experience at the time of return. Returning teachers could represent an untapped source of teacher talent that is underappreciated given their relative cost due to salary schedules