VictorJuiz/thesis huggingface dataset:
Selective Neuro-oncological Therapies Using Focused Ultrasound to Disrupt the Blood-brain Barrier
Keywords: Blood-brain barrier disruption
Brain tumour therapy
HIFU
Image-guided therapy
MRI-guided focused ultrasound
Therapeutic ultrasound

Ultrasound in clinical medicine is most commonly associated with imaging, but can be harnessed to yield an array of bioeffects. Of particular interest in neuro-oncology is the interaction of ultrasound with pre-formed ultrasound contrast agents, the combination of which can be used to increase the permeability of the cerebrovasculature in a reversible manner [blood-brain barrier (BBB) disruption]. Many promising therapeutic agents have in vitro efficacy but fail in vivo due to their inability to accumulate to any significant degree in the central nervous system (CNS). While primary brain tumours alone do not impose an enormous healthcare burden compared with many other cancers, as many as 40% of all cancer patients will eventually develop brain metastasis, making the potential impact of drug delivery with ultrasound significantly larger. We focused particularly on therapeutic agents that, once in the brain, selectively targeted malignant cells, as existing therapies cause much morbidity in their wake secondary to collateral neuronal injury. We investigated the effects of BBB disruption on boron neutron capture therapy with the delivery agent boronophenylalanine. BBB disruption increased the absolute boron concentration, important for tumour killing, by almost 150%, and improved the ratio between normal brain and tumour, minimizing radiation to healthy cells. It also increased the uptake in infiltrating cells, particularly important for tumours like glioblastoma. We then demonstrated that an even more selective agent - engineered, targeted immune cells - could be delivered to a brain tumour in a viable state. Furthermore, we demonstrated improved survival in a brain metastasis model of HER2 amplified breast cancer. Both of these targeted therapies have been investigated in early clinical trials, and with the mounting evidence for the safety of BBB disruption with ultrasound, there exists real potential to translate these promising therapies into the clinical realm and offer new treatments to patients with little hope for a cure.
Exploring Maternal Personal and Interpersonal Functioning to Explain the Relation between Maternal Childhood Maltreatment History and Child Behaviour Problems
Keywords: Child behaviour
Maltreatment
Maternal depression
Maternal functioning
Parenting
Parenting stress

I investigated the association between maternal childhood maltreatment history and child behaviour problems in the next generation, and what maternal personal and interpersonal variables mediate this relation. I hypothesized that previously studied maternal variables (maternal depression, social support, and parenting) which have largely been tested in high-risk samples, would emerge as significant mediators in this study's low-risk sample. The inclusion of two untested but theoretically important maternal constructs (adult attachment and parenting stress) were also examined. Examining these five maternal constructs in the same study using simple and parallel mediator models allowed for the opportunity to identify the unique variance contributed by these mediators. Ninety-six mother-child dyads were assessed at two time points. When children were 16 months, mothers were given measures to assess childhood maltreatment history, adult attachment, depressive symptoms, parenting stress, and social support. Mothers were also observed with their children to assess maternal sensitivity. When children were 5-years old, an observational measure of compliance was completed and maternal reports of child behaviour were collected. Simple and parallel mediation models were constructed. Results included a positive association between maternal childhood trauma and mother-reported child behaviour problems. Observed child compliance was excluded from the main analyses, as it was not significantly related to maternal study variables. In regards to child internalizing behaviour problems, maternal depressive symptoms and parenting stress emerged as significant mediators when assessed separately. When both simple mediators were examined in parallel, maternal depressive symptoms was the only significant mediator. Maternal sensitivity was found to have a significant suppressor effect. In regards to mother-reported child externalizing behaviour problems, adult avoidant attachment, maternal depressive symptoms, parenting stress, and social support, were all significant simple mediators when assessed individually. When these four mediators were examined in parallel, parenting stress emerged as the only significant mediator. These findings provide additional evidence that childhood trauma has far-reaching impact on functioning into adulthood and that adult personal and interpersonal dysfunction impact child behaviour in the next generation. Further, depending on the child outcome (i.e., internalizing or externalizing behaviour), different mediators explain unique variance in the relation between maternal childhood maltreatment history and child behaviour problems.
Constructing Biology Curriculum for a Diverse Student Population: Opportunities for the Integration of STSE Education and Issues of Social Justice
Keywords: action research
curriculum
inclusive
science education
social justice
STSE

Science, technology, society, and the environment (STSE) education is both a part of the mandated science curriculum in Ontario schools and also a philosophical and theoretical positioning for a science teacher. The study seeks to understand how biology curriculum can be developed that is inclusive of a diverse student body with special attention to STSE education as a vehicle for integration with issues of social justice. Participants were provided with opportunities to explore their understanding of STSE education, their role and identification as teachers, and how they meet student needs, in relation to the curriculum development process. The research then is a confluence of three areas: inclusive curriculum, STSE/social justice, and teacher identification. This qualitative study uses individual interviews, group meetings, and participant action research to explore, how teachers, develop and implement inclusive science curriculum for a diverse student population, how science teachers understand themselves and their role, and, how teachers understand STSE/social justice perspectives and practices. Findings showed that this is difficult work. Teachers are faced with pressures such as assessment challenges inherent in STSE education, student attitudes related to what science teaching is, and personal and contextual barriers that influence curriculum development and implementation, teaching content and issues, as well as the action research cycle in general. Teacher development of a personal critical theory of teaching and understanding of the political, historical, and sociological context of teacher work is an ongoing question from this research. Findings may have impact on how teachers see themselves and understand their role, how they approach issues in their teaching, how they understand teaching as a political act, and how they use social justice issues as one part of an STSE-informed approach to more inclusive science teaching.
Emotional intelligence and the socialization of new graduate nurses during a preceptorship program
Keywords: Socialization
emotional intelligence
preceptorship
new graduate nurses

The literature on new graduate nurses is reflecting concern with turnover rates within the first two years of practice ranging from 13% to 61.5% (Kovner et al., 2007; Lavoie- Tremblay et al., 2008). The under preparation of and lack of support for new graduate nurses during their early work experiences are often reported reasons for these high turnover rates. Preceptorship programs, as a method of organizational socialization, have been implemented to specifically address the challenges faced by new nurses. Research suggests that the social elements of socialization, such as working closely with a more senior colleague, has a great impact on new employee outcomes. Although the literature identifies that preceptors, who are acting as socialization agents, are important to the process of new employee socialization, little is known about this relationship, particularly the individual differences of the preceptor. One such individual difference is emotional intelligence (EI). The literature on EI suggests that it may play a role in the work environment and in predicting work-related outcomes. Preceptors are aptly situated to have a direct impact on new nurses. Thus, the focus of this study was to explore the impact of preceptors’ EI on new graduate nurses’ socialization during a preceptorship program and was guided by Van Maanen and Schein’s Theory of Organizational Socialization (1979). A multi-site cross-sectional design was used to examine the proposed relationships between a preceptor’s EI and new graduate nurses’ socialization outcomes. A sample of 51 dyads of new graduate nurses and their primary preceptor participated in this study. New graduate nurses in this study experienced low role ambiguity, role conflict and turnover intent and high job satisfaction. New nurses’ job satisfaction was associated with their role conflict and ambiguity. The proposed hypotheses about the relationships between preceptors’ EI and new nurses’ transition outcomes were not supported in this sample. The results provide some insight into how these new graduate nurses are adjusting to their role at the end of a preceptorship program. Additionally, the results provide a greater understanding of three preceptor characteristics that have not yet been studied: EI, personality and cognitive intelligence.
Introducing the 'Third Phase' of Priority Setting: Advancing Methods for Priority Setting Practice through the Contribution of Systems Theory. Lessons from a Case Study of District Health Planning and Priority Setting in Ethiopia
Keywords: Developing Countries
Ethiopia
Health Planning
Priority Setting
Resource Allocation
Systems Theory

Over the last 20 years, there has been considerable scholarly attention paid to developing priority setting methods with an emphasis on improving the evidence base of priority setting decisions, the use of explicit decision criteria, and the fairness of decision-making processes. Case studies of priority setting in health institutions and systems internationally have identified a variety of factors in practice that influence the effectiveness of these methods. There is a paucity of research, however, that empirically examines how these factors operate and to what extent they comprise enablers or barriers to fair priority setting. The purpose of this dissertation is to advance priority-setting methods by examining how systems theory may inform our understanding of priority setting through a case study of district health planning in Ethiopia. To fulfill this purpose, three objectives were undertaken. The first objective sought to describe the district health planning and priority setting process in Ethiopia. A qualitative case study of Ethiopian district health planning was undertaken in 2010 and 2011. Methods included 57 in-depth key informant interviews with decision makers, participant observation, and document analysis. The second objective sought to analyze this description through the theoretical lens of Accountability for Reasonableness (A4R) and the Transformative Systems Change Framework (TSCF). The third objective sought to conceptually synthesize these findings by situating priority setting practice and procedural fairness within a robust understanding of the system. The study findings reaffirm priority setting is a highly complex process that is value laden and influenced by a multiplicity of system-level factors. Through the application of the TSCF, a nuanced understanding of priority setting practice is understood that situates this process within a system of influencing components that include: norms, operations, regulations, and resources. Analysis reveals a number of system barriers and facilitators that impact not only the implementation of district health planning, but also the degree to which elements of procedural fairness are upheld. In light of these findings, I propose the introduction of a third phase in the priority setting discourse that emphasizes the need for methods and approaches inclusive of system-level considerations. I conclude with the development of a series of practical questions to guide practitioners in the design and implementation of their priority setting methods.
The Experiences of Parents Seeking Integrated Placements in Ontario Schools for their Children with Disabilities
Keywords: accommodation disability
critical disability studies
Education Act in Ontario
legislative inadequacies
parental activism
social construction of disability in education

A series of ethnographic interviews were conducted to explore the experiences of parents seeking integrated placements for their children in Ontario schools. The scope of the study was dual in nature. Firstly, it set out to examine parental activism as a response to the historical exclusion of disability in the educational system. Secondly, the study sought to examine whether the intent and letter of the special education practice was operative in respondent experiences which included nine parents, who reported on 8 children; 6 students had Down Syndrome, while the other 2 students also had visible disabilities. The parental responses were recorded, transcribed, and evaluated utilizing the constant comparison method defined by Glaser. Following the transcription of these narratives, thematic comparisons were drawn between respondents. The experiences of the respondents were then compared to the legislative framework established by Ontario's Education Act (Education Act, R.S.O., 1990 ) associated regulations, and the onus for service provision in the Human Rights Code (Human Rights Code, R.S.O., 1990) in Ontario. Findings indicated that while the letter and intent of the legislation appeared specific, it was rarely occurring in practice. Flaws inherent within the legislation served as a barrier to integrated classroom placements. The study demonstrated that the presence of negative attitudes combined with legislative inadequacies impeded advocacy efforts for integration, while the presence of positive attitudes, support integrated placements. This research study suggests that legislative reforms are required to meet the intent of the letter of the law to ensure the provision of integrated placements for students with disabilities in Ontario.
Assessment of Iron Chelation Therapy in an Atherosclerotic Animal Model of Intraplaque Red Blood Cell Deposition
Keywords: Animal model
Atherosclerosis
Histopathology
Intraplaque hemorrhage
Iron chelation
Magnetic resonance imaging

Atherosclerosis, the pathological thickening of the arterial wall, is the underlying disease process leading to heart attack and stroke. Atherosclerotic plaques cause narrowing of important blood vessels and unstable plaques can develop blood clots which can fully occlude vessels and deprive downstream tissues of oxygen and nutrients. Bleeding within a plaque, termed intraplaque hemorrhage, is an important plaque feature associated with cardiovascular events such as heart attack and stroke. Hemorrhage deposits red blood cells rich in hemoglobin within the plaque. Hemoglobin-derived iron is thought to catalyze oxidation of lipids and drive atherosclerosis. Current treatment relies on bypass grafting, angioplasty, and stenting to open significantly narrowed vessels and medical therapy to address modifiable risk factors such as high cholesterol. However, there are no therapeutics targeted towards intraplaque hemorrhage. This thesis aims to test the effectiveness of iron chelation therapy in removing plaque iron and reducing intraplaque hemorrhage-driven atherosclerotic plaque progression. An atherosclerotic rabbit model of intraplaque hemorrhage was established using a needle-tipped catheter to deliver red blood cells to aortic plaques with delivery confirmed by noninvasive imaging. A semi-automated image analysis approach for measuring plaque progression on magnetic resonance images was developed, validated against histology, and tested for reliability. Using these newly developed tools, iron chelation therapy was shown to reduce plaque progression following intraplaque red blood cell delivery in the rabbit model.
Fronthaul-constrained Uplink Cloud Radio-access Networks: Capacity Analysis and Algorithm Design
Keywords: Cloud Radio-Access Networks
Compress-and-forward
Fronthaul Compression
Joint Beamforming and Compression
network MIMO
Successive Decoding and Joint Decoding

This thesis considers the uplink of a cloud radio access network (C-RAN), in which base-stations (BSs) are connected to a cloud-computing based central processor (CP) via noiseless fronthaul links with finite capacities. The compress-and-forward strategy is employed, where the BSs compress the received signals and send the quantized bits to the CP. Then, the CP performs either joint decoding of both the quantization and message codewords simultaneously, or generalized successive decoding of quantization and message codewords in an arbitrary order. Under this setup, this thesis establishes several information theoretic results and proposes a number of practical algorithm designs. From a theoretical perspective, this thesis first proves that under joint decoding and Gaussian input, Gaussian quantization maximizes the achievable rate region. Second, it is shown that generalized successive decoding achieves the identical rate region as joint decoding under a sum fronthaul capacity constraint. Third, a particular successive decoding scheme, in which quantization codewords are decoded first followed by message codewords, referred to as the virtual multiple-access channel (VMAC) scheme, achieves the same maximum sum rate as joint decoding under individual fronthaul constraints. Furthermore, it is shown that under a sum fronthaul constraint, Wyner-Ziv coding, quantized at the background noise level, can achieve the sum-capacity to within a constant gap. A similar constant-gap result is shown for single-user compression under a diagonally dominant channel condition. From an optimization perspective, this thesis investigates the optimization of beamforming design and fronthaul compression for the VMAC schemes. First, under a sum fronthaul constraint, this thesis proposes a novel alternating convex optimization algorithm to maximize the weighted sum-rate for single-antenna uplink C-RAN. It is shown that setting the quantization noise levels to be proportional to the background noise levels is near optimal when the signal-to-quantization-noise-ratio is high. Second, under individual fronthaul constraints, this thesis develops a weighted minimum mean-square-error successive convex approximation algorithm to jointly optimize beamforming and fronthaul compression for multi-antenna uplink C-RAN. The performances of the proposed algorithms are verified under practical multicell and heterogeneous networks through numerical evaluation.
Study of the Yeast Vacuolar-type ATPase by Electron Cryomicroscopy
Keywords: cryo-EM
magnification anisotropy
SidK
TMaCS
V-ATPase

Vacuolar-type ATPases (V-ATPases) are rotary enzymes that use energy from hydrolysis of adenosine triphosphate (ATP) to pump protons across membranes and control the pH of many intracellular compartments. ATP hydrolysis in the soluble catalytic region of the enzyme is coupled to proton translocation through the membrane-bound region by rotation of a rotor subcomplex. Studies of ATP synthases, V-ATPases, and vacuolar/archaeal ATPases (V/A-ATPases) have suggested that flexibility is necessary for the catalytic mechanism of rotary ATPases but the structures of different rotational states have never been observed experimentally. V-ATPases also serve an important role in the immune system and are targeted by intracellular pathogens. Legionella pneumophila, the causative agent of Legionnaires' Disease, secretes a protein effector called SidK that binds and inhibits V-ATPases, preventing acidification of lysosomes and promoting survival of the bacterium inside macrophages. The mechanism of V-ATPase inhibition by SidK is not known. The structure of V-ATPases can be analyzed by single particle electron cryomicroscopy (cryo-EM), an imaging technique involving the identification of tens to hundreds of thousands of individual proteins in micrographs. A partially-automated image selection program was developed to increase particle image identification throughput. A method was also developed to correct for magnification anisotropy that was identified in our images. Cryo-EM maps were obtained for structures of three rotational states of the V-ATPase from the yeast Saccharomyces cerevisiae. The three different maps reveal the conformational changes that occur to couple rotation in the soluble catalytic region to the symmetry-mismatched membrane-bound proton-translocating region. The structures of these states provide direct evidence that deformation during rotation enables the smooth transmission of power through rotary ATPases. To investigate the molecular mechanism of V-ATPase inhibition by SidK, we determined structures of the V-ATPase:SidK complex by cryo-EM. The cryo-EM maps reveal SidK to be an elongated protein composed of a structured region that interacts with the soluble catalytic region of V-ATPase and a flexible region of unknown function. The structures suggest a novel inhibition site for V-ATPases and provides evidence that the activity of these proton pumps is linked to the flexibility of the A-subunit.