VictorJuiz/thesis huggingface dataset:
Characterization and Development of a Novel Cytomegalovirus for Evaluation as an HIV Vaccine Viral Vector in a Non-Human Primate Model
Keywords: HIV
Vaccine Viral Vector
Cytomegalovirus
Non-Human Primate
Herpesvirus
Cynomolgus Macaque

Within the field of HIV vaccine design, it has been recognized that there is a real need to diversify the pool of vectors undergoing testing and to utilize vectors that can induce durable immunity. Herpesviruses, such as cytomegalovirus (CMV), show much promise as viral vectors, as they establish lifelong latency with periodic reactivation, enabling persistent expression of vaccine antigens. We propose that using CMV as a lifelong reactivating HIV viral vector will generate a robust and persistent effector memory T cell response at the mucosa and thus, may impair HIV replication at its earliest stage. In an effort to evaluate CMV-based HIV/SIV vectors in a non-human primate (NHP) model, I isolated CMV from cynomolgus macaques (CyCMV), and performed preliminary phenotypic and genomic classification of the novel virus. To characterize the CyCMV genome, facilitate targeted recombination for vaccine construction, and inform possible attenuation strategies, I sequenced and annotated the complete viral genome using next-generation sequencing. Furthermore, I compared and contrasted the structural and functional genes of CyCMV to human and rhesus macaque CMV with respect to genes involved in pathogenesis, immune evasion, species-specificity, and more. In order to maximize the ability to manipulate the virus for vaccine purposes, I cloned CyCMV as a Bacterial Artificial Chromosome (BAC). The cloning of CyCMV-BAC enabled the virus to be transformed into a bacterial system for downstream insertion of vaccine antigens, as well as future viral manipulations, including attenuations. This newly characterized CMV provides a novel model in which to study HIV/SIV CMV-based vaccines in hopes of informing forthcoming human clinical trials. Additionally, CyCMV-BAC will provide an invaluable resource for CMV biologists allowing for virus manipulation studies, functional characterization of CMV genes, as well as HCMV pathogenesis and vaccine development research.
Health Systems Integration: Competing or Shared Mental Models?
Keywords: integrated care
shared mental models
health systems integration
large-scale change

For over two decades, health services researchers and managers have focused on improving integration between organizations and levels of care. Yet, healthcare systems capable of delivering integrated care have not developed widely. This dissertation argues that structural and process strategies for integration need to be supplemented by attention to the social cognitions that characterize the behaviours of actors within healthcare systems. The aim of this dissertation is to explore how Shared Mental Model Theory might advance our understanding and measurement of integration processes and performance. The first paper in this dissertation examines the evolution of healthcare integration strategies over twenty-five years as reported in the academic literature. Six major, inter-related shifts were identified in strategy content. This evolution in conceptualization and practice highlights the importance of attention to meanings and perceptions. The second paper draws from Shared Mental Model Theory, and an exploratory, theory-driven literature review, to identify mental model content specific to system-level integration efforts, and to develop a theoretical framework of the antecedents, moderators and outcomes of shared mental models of integration. The final paper validates and improves the proposed content framework using a two-round, web-based modified Delphi process with a diverse, pan-Canadian group of integration experts, including policymakers, planners, managers, care providers, educators, researchers and patient advocates. The proposed “Integration Mindsets Framework” may be used to facilitate the planning, implementation, management and evaluation of integration initiatives. A shared mental models lens complements and fills the gaps of current approaches to the study of integration in the healthcare sector by focusing attention on the evolution and interplay of meanings, interpretations and knowledge about integration – and their potential impact on practice. Together, these studies provide theory-based, expert-validated constructs and frameworks that enable researchers and practitioners to describe, conceptualize and analyze health systems integration from a socio-cognitive perspective.
“A Dream of the Future”: Race, Empire, and Modernity at the Atlanta and Nashville International Expositions, 1895-1897
Keywords: World's Fairs
International Expositions
Southern Expositions
U.S. South
Atlanta
Nashville
Negro Buildings
Jim Crow
Modernity
Race
Empire
Cotton States Exposition
Cotton States and International Exposition
Tennessee Centennial Exposition
Progress
New South
Civil War Reunion
African Americans
Booker T. Washington
Atlanta Compromise
Modernization
Industrialization
Southerners

For a region often viewed as outside the processes of modernization, the United States South’s international expositions were symbolic opportunities to demonstrate its embrace of a narrative of industrial, cultural, and racial progress. Taking the 1895 Atlanta Cotton States and International Exposition and the 1897 Nashville Tennessee Centennial Exposition as an analytical basis, this dissertation investigates how southerners transformed modernity by making it “Jim Crow.” It explores the ways white and African American southerners performed a variety of racialized and classed identities that embraced and critiqued modern progress. Responding to the dissolution of old certainties, southerners turned to science and technology as a stable site of truth and meaning. At the same time, their response to modernity was rooted in the South and its developing “New South” cities. In these cities southerners formulated a distinctive modernity that was compatible with the region’s racial dynamics and was adopted by the North as the nation expanded and encountered non-white colonial subjects. This dissertation makes clear the ways in which southerners, often considered on the periphery of change, responded to dislocating events by rooting their responses in the local. The specific economic, social, racial, and political realities of the South all shaped southerners reactions to and articulations of modernity and empire. By narrowing the question of southern modernity to a specific time and space this dissertation redefines a key moment in southern and American history, showing how responses to the dislocating effects of modernity were grounded in the specific temporal and spatial contexts of the South and were exported as American empire.
Revisiting the Power-duration Relationship and Developing Alternative Protocols to Estimate Critical Power Parameters
Keywords: critical power
exercise
modeling
performance
testing

Critical Power concept is used extensively in sport to characterize an individual's fitness by estimating the anaerobic and the aerobic component of the energy system, anaerobic work capacity (W') and Critical Power (CP). The model makes an assumption that all types of athlete have the same pattern of responses when it comes to power and time to exhaustion, however recent study showed different observation. Therefore, a more generalized model was proposed with a relationship constant, n, that can freely describe the relationship and the model demonstrated no difference between types of athlete across swimming (n=0.29) and cycling (n=0.48), but the relationship is significantly different from traditional assumption (p
Benefits of a Mindfulness-based Program in Early Childhood Classrooms
Keywords: mindfulness
prosocial behaviour
self-regulation

The effects of a 6-week mindfulness-based intervention program on children's social and emotional functioning in kindergarten classrooms were examined in two related studies. Eight Ontario full-day kindergarten (FDK) classrooms were randomly assigned to either the Mindfulness Group or to a Control Group. The first study examined the effects of the intervention on a direct performance-based measure of self-regulation and a behavioral screening questionnaire completed by teachers. The analyses revealed that the Mindfulness Group showed stronger self-regulation skills, more prosocial behaviors and less hyperactive behaviors relative to the Control Group after receiving the mindfulness-based program. The Control Group showed limited change in the dependent variables over the course of this study. Thus, the results offer preliminary support of implementation of a mindfulness-based program in kindergarten classrooms. The second study examined children's sharing behavior. The analyses of the results from a task designed to examine children's sharing behavior showed no significant differences in general sharing behavior between the Mindfulness Group and the Control Group. However a general pattern of differences in sharing behavior emerged, offering some support for the hypothesis that children participating in the mindfulness-based program would share more than children who did not participate in the program. Further, in part of the task involving sharing behavior with a "sick stranger" (one of the recipients included in the task), analyses revealed that more children from the Mindfulness Group shared with the sick stranger than children from the Control Group. This finding suggested that the mindfulness-based program increased children's empathy. Furthermore, children's reasons for sharing were recorded, coded and analyzed. Two distinct reasons for sharing emerged: reasons related to (1) Characteristics of the Recipient and reasons related to (2) Wanting to Behave Prosocially. However no significant between-group differences were found in children's reasons for sharing. As such, both groups were collapsed and reasons for sharing for all children participating in the study were reported both quantitatively and qualitatively. Implications of this study and directions for future research on mindfulness-based programs in early childhood classrooms are discussed.
Sleep in Adults with Attention-deficit/Hyperactivity Disorder of the Predominantly Inattentive and Combined Subtypes
Keywords: ADHD
sleep
subtypes

Subjective and objective data on correlates of sleep were collected from adults with Attention-Deficit/Hyperactivity Disorder (ADHD) to determine whether ADHD of the Predominantly Inattentive (ADHD-I) and Combined (ADHD-C) subtypes differ with respect to the nature, prevalence, and impact of sleep disturbances on the core symptoms of ADHD. Subjective data were collected from 45 ADHD-I (mean 40 ± 11 years, 24% female) and 81 ADHD-C (mean 37 ± 10 years, 27% female) adults. A high proportion of ADHD subjects had complaints of excessive daytime sleepiness, poor sleep quality and fatigue. Sleep quality and fatigue were worse for ADHD-I than for ADHD-C subjects. The interrelationships between daytime sleepiness, sleep quality, and fatigue also differed between ADHD subtypes, suggesting differences in the interplay of sleep and wakefulness in ADHD-I and ADHD-C. The idea that the interplay of sleep and wakefulness differs in ADHD subtypes was further supported by findings associated with objective measures of sleep in 27 ADHD-I (mean 39 ± 12 years, 33% females) and 41 ADHD-C (mean 37 ± 9 years, 20% females) adults. Specifically, dim light melatonin onset (DLMO) time was found to be associated with inattention in ADHD-I, and with hyperactivity/impulsivity in ADHD-C. Regarding polysomnography (PSG) measures of sleep, symptoms of inattention were found to be associated with respiratory-event related arousals (RERA) in ADHD-I, and symptoms of hyperactivity/impulsivity were found to be associated with correlates of REM sleep in ADHD-C. These findings suggest a differential role of circadian cycles and sleep in the neuromodulation of the core symptoms of ADHD in ADHD subtypes.Taken together, the findings suggest that ADHD subtype differences extend to the realm of sleep. Importantly, subtype differences lie, not in measures of sleep per se, but rather in the interrelationships between measures of sleep and the core symptoms of ADHD, suggesting ADHD-subtype differences in the interplay of sleep and wakefulness.
Practical Virtues: An Evidence-based Ethical Framework for Approaching End-of-Life Care in the Neonatal Intensive Care Unit
Keywords: End of life
Ethical framework
Interprofessional
Newborn
Parents
Virtue ethics

The challenges surrounding end-of-life care in newborns, including the moral weight of decisions, best interest standards, and parental involvement in decision-making, require an interprofessional approach in order to minimize moral distress and moral residue. The objectives of this project were to describe professional perspectives on end-of-life care in the neonatal intensive care unit, to compare and contrast these perspectives with the identified needs and perspectives of parents, and to construct a framework based on these to aid health care professionals in the approach to neonatal end-of-life care. First, using qualitative interviews, the attitudes and experiences of 43 health care professionals were explored. Participants identified the roles, challenges, and quality indicators related to meeting parents' and infants' needs at end-of-life. Broad categories included: clinical expertise and moral sensitivity; communication; guidance, support, and relationships; shared decision-making; and end-of-life planning and care. Health care professionals identified challenges to team function and quality of care related to consistency of caregivers, communication, and consensus on the interprofessional team. Next, using ethical analysis based in virtue theory, the experiences of 11 parents of infants who died following withholding/withdrawal of life-sustaining treatment were compared to those of the 43 health care professionals and used to inform a framework for approaching neonatal end-of-life care. Both individual virtues of character and virtues ascribed to the interprofessional team were important to providing good quality communication, shared decision-making, and care at end-of-life. The resulting ethical framework involves five steps: i) identifying the components of moral event(s); ii) defining the virtues important in meeting parents' and baby's needs; iii) applying combinations of these virtues in clinical context in order to iv) practice moral action; and iv) reflect on the process. Next steps include the application and evaluation of this virtue-based ethical framework to end-of-life care in the neonatal intensive care unit.
Computational Methods for Learning and Predicting the DNA binding Specificities of Transcription Factors
Keywords: Data Mining
DNA Binding Site
Gene Regulation
Machine Learning
Sequence Analysis
Transcription Factor

The protein-DNA interactions between Transcription Factors (TFs) and Transcription Factor Binding Sites (TFBSs) are the key activities in gene regulation. Considerable efforts have been spent on elucidating their binding mechanisms in the past twenty years. In this thesis, I propose and describe three methods to learn and predict the DNA binding specificities of TFs.The first method named kmerHMM is a sequence pattern recognition method to discover the sequence patterns of TFBSs from protein binding microarray (PBM) data. The novelty of kmerHMM lies in two aspects. First, it has a competitive edge over the existing methods in using Hidden Markov Models (HMMs) to derive an HMM model to represent PBM data. Secondly, kmerHMM incorporates N-Max-Product algorithm and can derive multiple motif matrix models to represent PBM data. The second method named SNPdryad is a classification method to predict the deleterious effect of amino acid substitutions on proteins (including TFs). Comprehensive performance comparisons are conducted on benchmark datasets, reflecting that SNPdryad has the performance comparable to the best of the other methods. SNPdryad has been run on the complete human proteome, generating prediction scores for all the possible amino acid substitutions. In particular, case studies are conducted to show that SNPdryad can help identify the deleterious effect on TFs if a DNA-binding residue is mutated to others.The third method is a computational framework to learn specificity-determining pair-wise residue and nucleotide interactions between TFs and TFBSs. Its novelty lies in the fact that the existing methods usually focus on learning DNA-binding residues on the protein side (TF) only, ignoring the DNA side (TFBS). In contrast, our novel framework aims at learning the interactions between both sides. The proposed method is compared to state-of-the-art methods comprehensively, demonstrating its competitive performance. We also describe case studies showing how our method can be applied to reveal meaningful biological insights into protein-DNA interactions across different DNA-binding families.
Disruption of Lymphatic Function following Lymph Node Excision and Irradiation: Integrating Natural Compensatory Responses with Potential Therapeutic Approaches to Facilitate Lymph Flow Restoration
Keywords: Lymphedema
Breast Cancer
Lymphatics
Radiation Therapy
Lymph node

Introduction: The removal or irradiation of one or more lymph nodes during cancer surgery appears to be a significant causative factor in lymphedema development. In the studies outlined in this thesis our first objective was to define the lymph transport deficit caused by nodal excision and/or the application of radiation to a single node. The second objective was to examine two potential methods to restore function after node removal, autologous node transplantation and the introduction of lymphangiogenic factors into the nodal excision site. Methods: In both sheep and rabbits, popliteal nodes were removed and/or subjected to radiation. Animals received one of two potential therapies at the excision site; lymph node transplantation or growth factor therapy (VEGF-C and Ang-2). Following surgery/treatment, a tracer was injected into a prenodal vessel and the system’s ability to transport this tracer to plasma was used as a measure of lymphatic functionality. Fluoroscopic and histological examination provided supporting data. Edema was quantified from the circumferential measurement or bioimpedance of the hind limbs. Results: Following insult to the popliteal node lymphatic function was reduced significantly in comparison to control limbs. Additionally, in the case of radiation, the pressure-flow relationships differed from controls in a way that indicated enhanced resistance to flow (possibly caused by fibrosis and the thickening of the nodal capsules and trabeculae). Fluoroscopy and studies with Evans blue dye revealed new lymphatic vessel growth and occasionally, these vessels had anastomosed with local veins. Left untreated, limbs undergoing insults regained some lymphatic functionality but did not reach control levels. Both treatments increased lymphatic functionality in comparison to non-treated limbs. Edema was almost completely resolved in animals with successful node transplants, and significantly reduced in those receiving growth factor therapies. Conclusions: Damage to and/or removal of the lymph node as a result of cancer treatment can significantly impair the lymph drainage in limbs. Regeneration of lymph vessels, the formation of collateral pathways and lymph-venous anastomoses act as natural compensatory mechanisms, although usually only to a limited extent. However, therapies such as autologous lymph node transplantation or growth factor therapy have the ability to restore lymphatic functionality and decrease edema.
Safety and School Travel: How Does the Built Environment Relate to Correlates of Safety, Mode of Travel and Physical Activity Levels to and from School
Keywords: School Travel
Pedestrian Safety
Physical activity

Many children do not meet the physical activity targets necessary to accrue health benefits. Declines in active school travel over the past half century are one example of how opportunities for daily physical activity for children have been lost. Adult safety concerns may partially relate to the recent decreases in active school travel. This dissertation examines the connection between safety, the built environment and school travel behaviour. A mixed methods study design explores the links between safety, the environment, physical activity and school transport. Findings from the first results chapter suggest that safety in general is a concern for both parents and children but safety concerns are not uniform. Both parents and children were worried about strangers, while children identified additional concerns such as dogs and bullies. Traffic safety concerns related to street crossings, incomplete sidewalks and traffic around the school. Further analysis determined that objective measures of the environment such as street crossings, sidewalk, traffic and parking relate to mode of travel. Perceptions regarding the presence of strangers, street crossings and living in a safe neighbourhood, were also important factors. Differences were observed across the to/from school models, with more environmental features influencing mode choice during the trip to school. Concerning children’s health, findings suggest that the environment may relate to healthier body weights along with encouraging walking and minutes of physical activity. Longer distances, mode of travel and traffic calming features along the route to school related to an increase the number of minutes of activity before school. There is evidence that safety is an important factor in determining travel behaviour and features of the built environment may influence these decisions. Current policies aimed at curbing bullying at both the school and provincial level should continue and be expanded. Further work should look at reducing the number of vehicles around the school to increase walking rates. More time walking translates into more physical activity and may assist children in achieving daily physical activity targets.