VictorJuiz/thesis huggingface dataset:
Balancing Tensions in Regulatory Reform: Changes to Regulation of Health Professions in Australia, the United Kingdom, and Ontario, Canada
Keywords: case study
health law
health professions
legislation
policy
regulation

Regulation of health professions is a dynamic field that continues to cause strife among policy, government, and regulatory actors. At the heart of these debates is the question of how to balance the potentially conflicting policy tensions in the regulatory agenda: professional versus public interests, transparency versus privacy, and accountability versus autonomy. In recent years, the balance of these tensions has shifted in many jurisdictions through legislative reform, impacting the relationship between governments and health profession regulators. This changing balance and the factors and forces behind it were examined using a qualitative multiple case study research design of Australia, the United Kingdom, and Ontario, Canada. In Australia, the struggle between striving for national uniformity while still achieving adequate accountability was dominant after the enactment of a nationally coordinated regulatory scheme and subsequent state-based deviations. In the United Kingdom, the balance between autonomy for regulators and legislated consistency was contentious following the creation of a powerful meta-regulator and the elimination of elected professional majorities on regulatory bodies. Reform in Ontario was more incremental, with continued adherence to elements of traditional self-regulation, including professional majorities on governing councils of regulators and considerable delegated power for these professional regulators. Despite this, the nature of health profession self-regulation in Ontario has been altered through enhanced government oversight powers, heightened accountability and transparency requirements, and constrained discretion for regulatory bodies. The level of autonomy and freedom from state intrusion that self-regulated health professions previously enjoyed are unlikely to be seen in Ontario again. It is clear there is no panacea for perceived problems in regulation of the health professions. Reform agendas were coloured by the modern political, legal, and social context of each jurisdiction. These findings help elucidate the different policy tensions that have informed the reform. Certain values are gaining greater traction in each regulatory framework, including the importance of transparency and collaboration, the need to balance regulatory force to ensure economic viability, the utility of articulating regulatory principles, and the necessity of sustaining governmental and societal confidence in the ability to do what regulation of health professions is supposed to: protect the public.
The Influence of Attachment Phenomena on Alcohol and Tobacco Use
Keywords: alcohol
attachment security
child abuse
tobacco

Alcohol and tobacco use are leading causes of preventable death. Studying novel determinants of substance use may inform prevention and cessation. Attachment insecurity (attachment avoidance and attachment anxiety) describes interactions between adults and their attachment figures, which may influence substance use. This thesis assessed how attachment may be relevant in understanding and addressing substance use. Study 1, a cross-sectional survey study of 348 adult primary care patients, tested hypothesized associations between childhood adversity, attachment insecurity and substance use; if attachment insecurity could mediate between childhood adversity and substance use; and hypothesized sex differences in these associations. In Study 2, 38 smokers participated in experiments designed to assess the influence of cigarette cues and an attachment figure photo on craving and affect. In Study 1, 61% of participants reported childhood adversity, 11% reported harmful drinking and 20% reported current smoking. Attachment anxiety was associated with harmful drinking in women and men. Attachment anxiety was a statistical mediator between childhood adversity and harmful drinking (95% CI 0.09 to 0.30). Sex did not moderate the relationship between attachment anxiety and hazardous drinking in this mediation model. In women, attachment anxiety was associated with both childhood adversity (p=.002) and current smoking (p=.04), and was a statistical mediator between childhood adversity and smoking (95% CI 0.003 to 0.236). In Study 2, 56% of participants reported decreased craving after seeing an attachment figure photo (Neutral photo = 50.9 (SD 29.8), Attachment figure photo = 38.2 (SD 31.6), t(35)= -2.661, p=0.01). Cigarette cues (d=.50) and the attachment figure photo (d=.42) had similar effect sizes. Cigarette cue reactivity and attachment figure smoking status did not influence responses to photo exposures. Attachment anxiety was associated with alcohol and tobacco use, and may mediate between childhood adversity and substance use. Viewing an attachment figure photo decreased craving in smokers, with an effect that is comparable to the increase caused by cigarette cues. These studies indicate that attachment phenomena may play a role in substance use. Childhood adversity, attachment anxiety, and the presence of an attachment figure are factors to consider in the design of prevention and cessation strategies.
Functional Divergence of Glioblastoma Stem Cells
Keywords: Cancer Heterogeneity
Cancer Stem Cell
Glioblastoma

Genetic heterogeneity in cancer is well-established using genomic sequencing, while functional assays of prospectively isolated cancer subsets have demonstrated the existence of developmental programs in many hematological and solid malignancies. CD133 expressing cells have a unique propensity for initiating and sustaining hierarchical growth in human glioblastoma, a property analogous to that of neural stem cells. However, it remains unclear whether putative cancer stem cells exhibit further intratumoral variations in functional properties as a consequence of genetic or epigenetic heterogeneity. Here, we describe two complementary approaches to characterize functional intratumoral heterogeneity of human glioblastoma within the glioma stem cell (GSC) compartment at single cell resolution. In the first approach, we generated cohorts of single-cell derived stem cell cultures from primary glioblastoma and subjected them to in depth functional analyses. We demonstrate that multiple clones derived from the same GBM are capable of tumour initiation, yet differ in key functional properties such as proliferation, differentiation, and response to temozolomide chemotherapy. Genetic mutations unique to each clone could also be applied to reconstruct tumour phylogeny, indicating that the self-renewing compartment is reflective of complex tumour evolutionary histories. In the second approach, we labelled primary GBM cells with permanent genetic barcodes for the characterization of their functional properties in vivo. Using this approach, we demonstrated that self-renewal is restricted to a subset of GBM xenograft forming cells thereby confirming the maintenance of a stable developmental hierarchy within human GBMs at initial presentation. We also show that functional divergence of GBM clones emerges over time as a small subset of clones become more proliferative, and that intrinsically chemotherapy resistant clones may be selected for by frontline therapies. Furthermore, we show differential targeting of proliferative and relatively non-proliferative clones within the same tumour using epigenetic compounds. Our findings demonstrate the relevance of clonal heterogeneity in GBM pathogenesis, and suggest that complete elimination of all GSCs is possible using a combination of epigenetic compounds.
On-Chip Jitter Measurement and Mitigation Techniques for Clock and Data Recovery Circuits
Keywords: adaptive cdr
cdr
clock and data recovery
jitter
jitter measurement
wireline

This thesis describes three contributions in the area of on-chip jitter measurement and characterization, which can be used to help optimize the performance of wireline transceivers. Two on-chip jitter measurement techniques are developed and demonstrated, along with an adaptive loop gain CDR, which characterizes jitter on-chip to optimize its jitter tolerance. In the first measurement technique, the absolute jitter of random data is measured on-chip by correlating the phase detector outputs of two 10Gb/s CDRs locked to the same data. This technique allows the jitter's autocorrelation function to be estimated, from which the jitter's RMS value and power spectral density are extracted without using any external reference clock. Correlating the phase detectors in the CDRs with a third phase detector, which measures the phase difference between the clocks recovered by the two CDRs, allows measurement of the absolute recovered clock jitter. A test chip fabricated in 65nm CMOS demonstrates that this scheme can measure RMS jitter with sub-picosecond accuracy. To demonstrate the usefulness of on-chip jitter characterization in improving CDR performance, a loop gain adaptation strategy is proposed, which optimizes the jitter tolerance of a 28Gb/s PI-based CDR. The technique increases the CDR's loop gain to suppress the most jitter while monitoring the autocorrelation function of the bang-bang PD output to prevent the CDR from becoming too underdamped. The proposed technique requires no prior knowledge of the CDR's latency or jitter characteristics and can also be extended to operate in the presence of sinusoidal jitter. The concept is demonstrated in a test chip fabricated in 28nm CMOS. Lastly, a second jitter measurement technique is proposed, which estimates the relative jitter between the input data and recovered clock of a 28Gb/s half-rate digital PI-based CDR without using an eye monitor. Square wave jitter with a known amplitude is injected into the CDR, by adding a corresponding signal to the CDR's PI code. By measuring the effect of the injected jitter on the autocorrelation function of the CDR's bang-bang PD output, the RMS relative jitter is estimated with sub-picosecond accuracy. The scheme is demonstrated in the same 28nm test chip described above.
Hypoxia Promotes Stem Cell Phenotypes, Resistance to Therapy and Poor Prognosis through Epigenetic Regulation of DICER
Keywords: DICER
EMT/stemness
epigenetics
hypoxia
miRNA
tumor microenvironment

Hypoxia is a common characteristic of solid tumors, associated with aggressive disease and poor prognosis in multiple sites, including breast and cervix cancer. These properties are attributed to the influence of hypoxia on treatment resistance to both radiotherapy and chemotherapy as well as biological responses that promote altered tumor biology. Extensive research has led to a good understanding of the mechanisms of cellular adaptation to hypoxia, and regulation of metabolic and angiogenic phenotypes. However, considerably less is known regarding mechanisms responsible for the influence of hypoxia on metastasis and stemness. In a search to identify novel genes that contribute to the cellular response during hypoxia, we discovered that hypoxia represses DICER, a key enzyme required for generation of mature miRNA. DICER is a known haplo-insufficient tumor suppressor that can stimulate cancer development through a reduction in miRNA generation. We demonstrate that tumor hypoxia is a major regulator of DICER expression in large cohorts of breast cancer patients and that DICER expression is suppressed by hypoxia to levels similar to that in tumors with monoallelic DICER loss. We also demonstrate that DICER repression occurs through a novel epigenetic mechanism requiring inhibition of the oxygen-dependent H3K27me3 demethylases KDM6A/B. Hypoxic suppression of DICER creates a miRNA processing defect and results in selective reduction of mature levels of the miR-200 family. Consequently, hypoxia leads to derepression of the miR-200 target ZEB1, stimulates the epithelial to mesenchymal transition and results in acquisition of stem cell phenotypes in human mammary epithelial cells. Finally, we demonstrate the importance of reduced DICER in mediating therapeutic response to fractionated radiation treatment in vivo. Our work suggests that in breast cancer the acquisition of EMT and stem cell properties, through epigenetic repression of DICER and loss of miR-200, may drive the known association of hypoxia and poor clinical outcome.
Surface Modification of Commonly used Polymer Plastics for Increased Hemocompatibility in Medical Equipment
Keywords: Biomedical
Blood
Coating
Plastics
Polymer
Surface Chemistry

Exposure of synthetic materials to body fluids may result in undesirable protein−material interactions, this can potentially trigger deleterious biological processes such as thrombosis. The result is increased chances of heart attack, stroke or other cardiovascular complication after extravascular blood procedure. For our experiment, we have chosen a wide variety of materials used in making perfusion equipment components: polyethylene terephthalate (PET), polycarbonate (PC), polyvinyl chloride (PVC), polypropylene (PP), poly (methyl methacrylate) (PMMA), polyurethane (PU), polysulfone (PS). All materials had MEG-OH adlayer formed and characterized with x-ray photoelectron spectroscopy, attenuated total internal reflection and contact angle goniometry. Several of the materials (PVC, PC, and PS) were tested directly for their compatibility with whole human blood. Antithrombogenicity was assessed after 2,5,10 and 60 min, 3 hours, 6 hours, and 3 days exposure to whole human blood dispensed at a shear rate of 1, 300, 900, 1000 and 1500 s−1. Most MEG-OH covered plastics had >90% less platelet adhesion than bare plastics, the result was repeated on all exposure times and shear rates. Surface protein composition was analyzed by SDS–PAGE. First trails using MEG-OH on PVC as an implant material for cranial windows on rats decreased the amount of fouling comparable to bare PVC. Overall the MEG-OH proved to be robust on a wide variety of materials with very high potential in blood compatibility.
The Role of C-Type Natriuretic Peptide Signaling in Aortic Valve Disease
Keywords: aortic valve disease
C-type natriuretic peptide
echocardiographic particle image velocimetry
heart valve
natriuretic peptide receptor 2
proteoglycan

Calcific aortic valve disease (CAVD) is a cell-mediated pathology without effective pharmacotherapy whose early pathogenesis is drastically understudied. C-type natriuretic peptide (CNP) is expressed 3x more on the disease-protected ventricular side than the disease-prone aortic side of the valve, and inhibits valvular interstitial cell myofibrogenesis and osteogenesis in vitro. Importantly, CNPâ s functional significance to CAVD in vivo has not been studied. In this thesis, a mildly atherogenic dietary mouse model of CAVD was characterized. Diet-induced proteoglycan synthesis identified in these mouse valves was versican-rich, occurred along with increased SOX9 expression, and developed before myofibrogenesis, calcification, or deficits in valvular function. Subsequently, mice with a loss-of-function mutation of the CNP receptor Npr2 were employed to test whether CNP/NPR2 were protective against CAVD in vivo. Npr2+/- mice developed cardiac dysfunction, hypertrophy, and fibrosis. Npr2 deficiency produced impaired valve function, which was exacerbated by long-term hypercholesterolemia. A portion of Npr2+/- mice had bicuspid aortic valves (BAVs, ~10%) with the most severe deficits in valvular function, and worst cusp thickening, fibrosis, and calcification. Lastly, NPR2-deficient mice developed ascending aortic dilatations characterized by elastin fragmentation and loss of medial collagen and smooth muscle cells; dilatation was accelerated in those mutants with BAVs. Abnormal hemodynamics likely contribute to aggravated CAVD and aortic dilatation in BAVs. However, there is a lack of tools to quantify complex hemodynamics in small animals where genetic/metabolic contributions to disease can be controlled. Echocardiographic particle image velocimetry (echoPIV) without exogenous contrast particles was employed with high-framerate ECG-gated Kilohertz Visualization (EKV) to track erythrocyte movement in the mouse ventricle and aortic root. EKV+echoPIV identified strong ventricular vortices during diastolic filling that transitioned to high-velocity systolic outflow. In the aortic root, that systolic aortic jet with recirculatory flow in the sinuses was apparent; oscillatory flow occurred once valve leaflets apposed. In summary, this thesis sheds light on the early pathogenesis of CAVD, identifies a novel therapeutic signaling axis in vivo, and presents a novel imaging technique for quantifying hemodynamics in small animal models of cardiovascular disease.
Modelling Air Bubble Entrapment and Transport in Sprayed Liquid Films
Keywords: Bubble Entrapment
Bubble Impact
Droplet Coalescence
Marangoni Flow
Spray Paint Film
VOF Numerical Modelling

A parallel, three-dimensional multiphase fluid flow solver was employed to model the physics of droplet coalescence, bubble entrapment, bubble impact, and Marangoni convection in a sprayed liquid layer. The results are relevant to understanding the formation of common defects in paint films such as non-uniform thickness, bubble entrapment and surface patterns. Coalescence of unequal sized droplets eventually results in the smaller droplet being drawn into the larger droplet. Droplets sprayed on a solid surface do not form a uniform film but agglomerate in large liquid masses. Air bubbles are entrapped under impacting droplets because of increased pressure in the air film between the droplets and the solid surface. The substrate orientation and liquid-solid contact angle influence the number of bubbles remaining in a liquid film. Once liquid motion stops, buoyancy forces drive the bubbles towards the substrate for a downward facing substrate. Depending on the bubble approach velocity and substrate properties the bubbles may either attach to the surface or bounce off. In evaporating liquid films, surface tension gradients create Marangoni flows that transport bubbles along with them and may force them to the free liquid surface where they break through and escape. Marangoni convection flows can also deform the surface of paint films and create orange peel defects.
A Variable Gain Direct Digital Readout System for Capacitive Inertial Sensors
Keywords: accelerometers
charge balanced
flexible
interface circuits
ratiometric
readout circuits

High fidelity interface circuits for capacitive accelerometers make use of feedback for signal detection but these feedback systems are limited by the sense capacitance and sensitivity of the accelerometers. This problem is addressed by a variable gain delta sigma based interface circuit that time multiplexes the accelerometer sense capacitance between the feedforward gain stage and feedback digital to analog (DAC) stage. Interfaced with a commercial accelerometer with sensitivity of 4.5 fF/g, the circuit achieves 40.6 dB SNDR in the x-direction and 42.5 dB SNDR in the y-direction due to limitations of the available testing equipment. With proper equipment, the system has the potential to achieve 53.0 and 54.9 dB SNDR in the x and y direction respectively while significantly reducing harmonics associated with the non-linear variable sense capacitors. Other interface circuits using the same sensor at comparable power would achieve linearity below 40 dB due to the limitation of the feedback structure.
Malignant Europeanization: Schengen, Irregular Migration Governance, and Insecurity on Europe's Peripheries
Keywords: Europeanization
Migration
Refugee Regime
Regionalism
Security

This thesis examines the relationship between open borders and free mobility in Europe, the Schengen regime, and security around Europe’s peripheries. Schengen is a constitutive element of the European project. Its maintenance depends on what the EU refers to as “compensatory measures” for addressing uncontrolled migration. I ask two questions: What is the relationship between the European project and changes in irregular migration systems? How do Schengen’s compensatory measures meet the EU’s stated foreign policy goals of fostering a ring of stable democracies in its near-abroad? My causal argument is that Schengen’s compensatory measures cause changes in irregular migration systems, which result in insecurity around Europe’s peripheries. I argue these dynamics are evidence of Malignant Europeanization, which I define as insecurity and regressive practices and norms resulting from Europe’s regional integration. I situate this project in the Europeanization literature, which analyzes relationships between European integration and changes in practices, institutions, and norms. Europeanization’s main indicators are reform toward democratic governance, rule of law, rights protections, and liberal market economies: benign Europeanization. In contrast, I identify eight indicators for Malignant Europeanization: migrant insecurity; increased transnational crime; security sector corruption; emboldened militarized non-state actors; domestic political contestation; entrenched authoritarianism and democratic backsliding; burden-shifting and regional tensions; and international norm degeneration. Findings are based on comparative case studies across four irregular migration systems: the Western Mediterranean, Central Mediterranean, Western Balkans, and Central and Eastern Europe. Evidence is derived from three years of fieldwork. Variation depends on domestic characteristics in transit states and external incentive structures. In the absence of membership incentives Europe lacks leverage to foster benign Europeanization. Findings problematize the framing of Europe as a progressive global influence. They also raise significant questions about the effectiveness of European foreign policy goals of fostering a ring of stable democracies around its near abroad.
THE IMPACT OF UNIVERSITY COSTS AND STUDENT DEBT IN ONTARIO AND QUEBEC: A COMPARATIVE STUDY
Keywords: Neoliberalism
Ontario
Quebec
Survey
Tuition Fees
University

For the past three decades, Canada has adopted post-secondary education policies that have reduced per student funding for universities and increased tuition fees and student debt levels. This thesis used mixed methods to investigate the impact of this neoliberal policy matrix on university students in Canada’s two largest provinces, Ontario and Quebec. The research includes the findings of a survey of 1,982 university students and 10 follow-up interviews. Ontario and Quebec provide the basis for a natural experiment as Ontario has the lowest per-student government funding and highest student debt in Canada, whereas Quebec has among the highest government funding and lowest student debt (Canadian Association of University Business Officers, 2015; CFS, 2015; MacDonald Shaker, 2013). The survey results show that median tuition fees were double for Ontario ($8,000) versus Quebec respondents ($3,000) and that median student debt was significantly higher in Ontario ($20,000) than Quebec ($12,000). The research investigated five potential impacts of university costs and student debt that are identified in the literature and found that a significantly larger proportion of Ontario than Quebec students reported: • that cost is a barrier to accessing the program, university and career of their choice, • that their university values them for the revenue they provide rather than as individuals, • and that they have higher levels of mental distress. The third finding on mental distress is concerning. In Ontario 46.0% scored above the diagnostic cut off using the Mental Health Index-5 versus 28.7% in Quebec. The results also show that approximately one quarter of Ontario respondents and one fifth of Quebec respondents report that cost is a barrier to achieving good grades or continuing and completing their studies. The policies that have led to students paying for a large portion of their own university education through debt were proposed by the neoliberal economist, Milton Friedman, in the early 1960s. The findings of this research project indicate a need to review this neoliberal policy matrix because of the detrimental effects on students.