VictorJuiz/thesis huggingface dataset:
Unique and Interdependent Roles of Lck and Fyn in TcR Signalling
Keywords: Immunology

It is not known whether or how the functions of Lck and Fyn are coordinated during TcR-medicated T cell activation. Our laboratory has previously demonstrated that lipid rafts (LR) function to segregate Lck and Fyn and are responsible for temporal and spatial regulation of their enzymatic activities. Specifically, Fyn localizes to LR, and the majority of Lck partitions to soluble membrane fractions. Co-aggregation of TcR and CD4 results in Lck activation outside LR, followed by its translocation into LR and the activation of LR-resident Fyn. This study, firstly, illustrates that ectopic expression of Lck variants in fibroblasts co-infected with wild type Fyn results in the formation of Lck-Fyn complexes and activation of LR-resident Fyn. Mutational analyses identified two domains of Lck critical for Lck-Fyn complex formation: (i) the active kinase domain of Lck, and (ii) the C-terminal QPQP sequence of Lck which functions as a cis-acting structural element required for partitioning of Lck to LR in fibroblasts and T cell clones. Secondly, the study shows that Fyn-/- mice succumb to influenza infections due to the lack of T cell expansion and homing to the lung. Moreover, using a preclinical model of colitis, the impaired expansion of inducer Fyn-/- T cells and the onset of disease is due to impaired IL-2 production in the absence of Fyn. Next, by means of an adenovirus-based vector system in combination with mice transgenic for the human coxsackie/adenoviral receptor (CAR), the study highlights that, both the impaired IL-2 production in vitro, and the onset of disease in vivo are rescued upon reintroduction of Fyn into Fyn-/- T cells. Lastly, the study demonstrates, using Lck-/- primary T cells, that both Fyn activation and the ensuing IL-2 production are Lck dependent. The results reconcile the obligatory and interconnected roles of both Lck and Fyn in T cell signalling.
Informing Physician Communication with Children Regarding Weight: Family Perceptions and Motivational Interviewing Tools
Keywords: childhood obesity
physician education

The goal of this research was to understand perceptions of children with obesity (study 1), their parents (study 2), and physicians (study 3) regarding weight-related communication in primary care through qualitative methods. These perceptions informed a randomized clinical trial (Motivational Interviewing (MI) vs. education) (study 4) addressing physician identification and communication about weight in primary care. Studies 1, 2, and 3: Separate focus groups and individual qualitative interviews with 35 children with obesity (5-17 years of age), their 42 parents and 12 primary care physicians were completed. The aims were to understand how the three participants of weight-related discussions in primary care perceived communication and obesity management. Data analysis was completed using the fundamental descriptive method for content analysis. Children identified factors perceived to hinder and promote positive attitudes towards weight-related behaviour change. Parents identified familial factors and feelings, perceived physician practices (parent-physician interactions and child-physician interactions), and recommendations from parents. Physicians identified barriers to weight management, how they cope and their needs for addressing weight with children. Study 4: The aim of this randomized controlled trial of MI vs. education-based training for primary care physicians was to improve the identification of obesity and communication with children with obesity, and to determine the efficacy of the MI training on MI skill retention. Outcomes included changes in rates of BMI calculating, tracking and identification of obesity, change and retention of MI scores in those randomized to the MI group. Factors associated with primary outcomes were also identified. This study indicated that primary care physicians are a difficult group to engage as subjects for training interventions. Collective physician training in management of obesity is effective at improving BMI calculation and obesity identification rates. The MI training curriculum can be applied in a brief session and group format and results indicate adoption and maintenance of MI scores on empathy, collaboration and autonomy support. The studies in this thesis identify areas where communication about weight in primary care can be targeted. They highlight a potential for MI training and adoption of technique as means of improving counseling confidence. It also identifies challenges in physician enrollment and participation in trainings.
Measurement Properties of the Whiplash Disability Questionnaire in Acute Whiplash-associated Disorders
Keywords: Measurement
Disability
Whiplash Injuries
Clinimetrics
Psychometrics
Reliability
Validity
Self-report Instrument

Whiplash-associated disorders (WAD) include physical and psychological symptoms that may lead to disability. However, measuring disability following whiplash injuries is challenging because we lack valid and reliable measurement tools. The assessment of WAD-related disability relies on self-reported instruments that are specific to neck pain and do not comprehensively target the constructs associated with WAD-related disability. Designing new tools and evaluating their measurement properties is challenging because of the apparent inconsistencies in the theoretical frameworks (psychometrics and clinimetrics) used in instrument development and in reliability, validity and responsiveness evaluation. A scoping review design was used to develop a conceptual theory on the difference between clinimetrics and psychometrics in order to provide recommendations for future application. The scoping review of psychometric and clinimetric methods suggested that the two frameworks are not as divergent as reflected in the current protracted debates. Content analysis revealed that differences only exist in the scope of what is measured and in instrument development methods with no operational differences in the testing phases. Based on content analysis, I developed a new framework that bridges the two measurement schools with an overlapping informed zone between them. I designed a cohort study of 130 participants with acute WAD to assess the measurement properties of the Whiplash Disability Questionnaire (WDQ). The WDQ is a recently developed instrument designed to capture the broad construct of WAD-related disability. The WDQ measurement properties were determined in adults with WAD recruited within 21 days of their collision. My study indicates that the WDQ and its subscales are reliable and valid for clinical and research use. The WDQ can demonstrate change over time as a single scale or as the daily activities subscale. However, WDQ users should be aware of its measurement error when demonstrating change over time. Furthermore, the emotional subscale should not be used alone to demonstrate change over six weeks because it was not responsive. My thesis proposes a unified framework for studying the measurement properties of assessment tools used in clinical practice. I also demonstrated that the WDQ possesses the necessary properties to be used in patients with acute WAD.
Continuous Monitoring of Intraocular Pressure from the Sclera
Keywords: Glaucoma
Intraocular Pressure
Monitoring
Strain Gauge
Sclera
Conjunctiva

Glaucoma is an optic neuropathy often associated with increased intraocular pressure (IOP) that can lead to impaired vision and blindness. Frequently asymptomatic, this eye disease may be undetectable until vision is severely compromised. The primary goal of glaucoma management is to prevent progressive nerve damage by maintaining a reduced IOP in order to preserve vision and maintain a patient&rsquo;s quality of life. IOP is a major risk factor for glaucoma, however, studies have shown that throughout a 24-hour period IOP is not constant and fluctuates throughout the day. This results in the clinical dilemma that diurnal changes in IOP, particularly during sleep, in patients with glaucoma may not be accurately evaluated during the regular practitioners&rsquo; office hours when diagnosis and management are provided. Since lowering and stabilizing IOP remains the only proven way to reduce disease progression, the development of a continuous IOP monitoring device, for human use, is critical. To date, there remains no commercially available non-invasive human device that can reliably and accurately measure IOP throughout the 24-hour period. There is an experimental contact lens device available in Europe, but there are significant disadvantages using a silicon contact lens on the cornea. The objective of this thesis was to demonstrate the efficacy of a noninvasive strain gauge sensor, placed on the sclera, to detect changes in IOP. The specific aims are to provide proof-of-principle for a novel, scleral mounted device for measuring IOP by: (1) establishing whether IOP can be recorded from the conjunctival and scleral surface using enucleated porcine eyes; (2) establishing whether IOP can be recorded from the conjunctival surface in a live pig model; and (3) to examine the inflammatory response of a hydrogel contact lens placed overnight on the scleral, bulbar conjunctiva as a plausible carrier for the strain gauge sensor. Changes in IOP can be accurately assessed by measuring changes in the radius of curvature of the sclera in enucleated tissue as well as in a live porcine model. Analysis of silicone hydrogel contact lenses, approved for overnight wear on the cornea, showed that they may be safely mounted on the upper bulbar conjunctiva and present a promising carrier material for a 24-hour IOP monitoring device. These proof-of-principle experiments are an essential step to the realization of a safe, scleral mounted, 24-hour IOP recording device that has the potential to significantly impact the way glaucoma is diagnosed and managed.
William of Pagula's Speculum Religiosorum and its Background: Law, Pastoral Care and Religious Formation for Monks, c. 1215-c. 1350
Keywords: Monasticism
Canon Law
Preaching

This dissertation examines the intersection of law and monastic literature in the Speculum religiosorum (c.1322), a guide to the monastic life, written by the English parish priest and doctor of canon law William of Pagula (c.1285-1332). William&rsquo;s Speculum is unique among monastic treatises in that it incorporates a long compendium of monastic law. The introduction provides context for the Speculum through an overview of the history of monastic reform from the mid-eleventh century to the fourteenth. In chapter one, I examine the manuscripts of the Speculum religiosorum, its relationship to William&rsquo;s other works, and its sources. The non-legal contents of the Speculum come mostly from the Bible, the Fathers, and Cistercian writers, but I show that William&rsquo;s sources for this material were often more recent compilations, such as Thomas of Ireland&rsquo;s Manipulus florum. In chapter two I argue that the Speculum belongs to a genre that I call &ldquo;encyclopedic manuals of monastic formation,&rdquo; but that the work also has an important relationship with sermons and preaching aids. Chapters three and four cover the legal contents of the Speculum. Chapter three is an overview of monastic law from Gratian&rsquo;s Decretum to the Clementines (1311), with an emphasis on the English context. Chapter four surveys compendia of monastic law in fourteenth-century England. I argue that William&rsquo;s legal methodology is more sophisticated than that of similar works. In Chapter five, I demonstrate that wisdom is the governing theme for the Speculum as a whole. I argue that William encourages his audience to treat law as a form of wisdom, and to internalize it through meditative reading. I provide parallel examples from other monastic contexts. William&rsquo;s conception of wisdom combines elements from Augustine and from monastic exegesis of biblical wisdom literature. I conclude by observing that the Speculum does not allow for a neat division between pastoral, legal, and monastic literature.
Preventing Linear Growth Faltering and Reversal of Stunting Among Low Birth Weight Infants in Bangladesh: A Community-based Cluster Randomized Controlled Trial
Keywords: Low birth weight
Linear growth
Stunting
Infants
Infection
Hand hygiene
Bangladesh

Background: Low birth weight (LBW) infants in low income countries are vulnerable to frequent infections and suboptimal breastfeeding and complementary feeding practices, which together may result in postnatal linear growth faltering and poor neurodevelopment. Objectives: To measure the relative effect of directed use of benzalkonium chloride-containing, water-based hand sanitizers (HS) and broad-range multiple micronutrient powder (MNP) along with nutrition, health and hygiene education (NHHE) to prevent infections and linear growth faltering among LBW infants. Methods: A prospective 2X2 factorial, cluster-randomized controlled trial was conducted among 467 full-term LBW infants from 0-12 months, using 48 clusters randomly assigned as follows: A. From 0 to 6 months, i) NHHE alone or ii) NHHE plus HS; B. From 6-12 months i) NHHE alone; ii) NHHE plus HS; iii) NHHE plus MNP (to be provided with complementary foods); and iv) NHHE plus both HS and MNP. Results: Combined intervention of ‘directed hand-sanitizer use’ and ‘micronutrient powder’ along with ‘NHHE’ significantly improved linear growth of low birth weight infants compared to ‘NHHE’ alone. At the end of 12-month intervention, the ‘NHHE+HS+MNP’ and ‘NHHE+MNP’ groups had significantly lower prevalence of moderate and severe stunting (length-for-age <−2 Z-score) compared to the ‘NHHE only’ group, (P<0.01, for both). A marked increase in linear growth was found only during the second half of infancy (from 6-12 months) through provision of MNP with complementary foods. Mean duration of diarrhea episodes during infancy (0-6 mo) was significantly lower in the ‘HS plus NHHE’ group compared to the ‘NHHE alone’ group (3.1±1.2 vs. 5.8±1.6 days, P<0.01). Upper respiratory tract infections (URTI) and cough were also significantly lower in the ‘HS plus NHHE’ group compared to the ‘NHHE alone’ group (22.5% vs. 27.1% and 8.1% vs. 11.2%, P<0.05, for both). Although HS independently reduced infections, no impact of HS on linear growth was found in the first six months. Conclusions: The use of hand sanitizer in combination with MNP reduced infections and impacted on rates of stunting among term LBW infants in the first year of life. Implications: Further evidence is needed to confirm the beneficial effects of hand sanitizers and MNPs among other populations of infants. Trial registration: http://www.clinicaltrials.gov (identifier NCT01455636)
CMOS Universal Real-time Label-free DNA Analysis System-on-Chip
Keywords: CMOS
DNA

Amperometric electrochemical DNA sensors have emerged as a low-cost, highthroughput and real-time alternative to the conventional optical sensory methods. This thesis presents the design, implementation, and validation of a fully integrated, mixedsignal CMOS thermally controlled amperometric electrochemical DNA-sensing systemon- chip (SoC). The microsystem includes 54 current-to-digital channels, 600 on-chip nanostructured DNA sensors and 54 on-chip pH sensors. It reuses key circuits to perform three key functions: 1) cyclic voltammetry and pH sensing, 2) impedance spectroscopy, and 3) temperature regulation. Cyclic voltammetry DNA analysis and pH sensing is implemented by utilizing the current-to-digital channel and an on-chip programmable waveform generator. The current-to-digital channel is multiplexed between a bank of DNA sensors and a pH sensor. The on-chip programmable waveform generator provides a wide range of usercontrolled rate, shape, and amplitude parameters of the sensor interrogation waveform, with a maximum scan range of 1.2V and a scan rate ranging from 0.1mV/sec to 300V/sec. Impedance spectroscopy DNA analysis is implemented by utilizing frequency response analysis (FRA) to extract the impedance components of the biosensor. The most computationally intensive operations, the multiplication and integration, required by the FRA algorithm are performed by the in-channel dual-slope multiplying ADC in the mixed-signal domain resulting in small integration area and power consumption. The on-chip heating and temperature-sensing elements are implemented without any post-CMOS processing. Temperature is regulated to within 0.5C using PID feedback control. This enables precise thermal control of on-chip DNA hybridization. The two computationally intensive operations, multiplication and subtraction, required by the PID algorithm are also efficiently performed by the same in-channel dual-slope multiplying ADC in the mixed-signal domain. A digital ultra-wideband transmitter based on a delay line architecture provides wireless data communication capabilities. The 3mm&times;3mm prototype fabricated in a 0.13&mu;m standard CMOS technology has been experimentally validated in the context of prostate cancer synthesized DNA marker detection. Each recording channel occupies an area of only 0.06mm2 and consumes 42&mu;W of power from a 1.2V supply. The digital ultra-wideband transmitter provides wireless data communication capabilities with data rates of up to 50 Mb/s while consuming 400&mu;W.
A Systematic Study of Solubility of Physical Blowing Agents and their Blends in Polymers and their Nanocomposites
Keywords: foam, solubility, BA

The solubility of a blowing agent (BA) in polymer melts is a critically important parameter affecting the plastic foams fabrication. Theoretically, cell nucleation occurs when the pressure of the polymer/gas mixture drops below the solubility pressure. For effective process design, accurate solubility data for blowing agents in polymers is necessary. However, getting more accurate solubility data is a big scarce. Through this research, it was possible to generate more accurate solubility and pressure-volume-temperature (PVT) data and to verify various equations of states (EOS). During the last two decades, due to ozone-depleting-potential (ODP) and global warming issues of BAs, the plastic foam industry has experienced serious regulatory, environmental, and economical pressures. In response to this, researchers and industry have been exploring the uses of blowing agent blends. Nevertheless, very limited fundamental research on the foaming mechanism using blowing agent mixtures has been conducted. The end results of this research is expected to provide guidance to choose the optimal composition of environmental-friendly blowing agent blends and offer insights to develop sustainable foaming technology. This thesis also highlights a comprehensive research for the PVT and solubility behavior of polymer nanocomposites (PNCs). By using the magnetic suspension balance (MSB) and PVT apparatus, it was possible to determine the solubility behavior of PNC more accurately. Fully experimental results indicated that infusion of nanoparticles decreases the volume swelling as well as solubility and diffusivity. It was hypothesized that infusion of organoclay nanoparticles generates a significant amount of solidified (solid-like) polymer near its surface and consequently reduces total absorption capacity of the system. However, it is believed that the solubility behavior of polymeric composites fully depends on the interaction or affinity between fillers (micro or nano) and gas. In other words, if the nanoparticles (such as CaCO3, aluminum oxide, tin oxide) or fillers (such as carbon black, zeolites, silica gel) are highly polar and/or porous, overall sorption (absorption + adsorption) might increase due to adsorption phenomenon. Through the solubility, PVT and modeling of nanocomposites, this research has advanced the understanding of the effect of nanoparticles on solubility that governs different physical phenomena (such as cell nucleation and, cell growth) during plastic foaming.
Rupture, Defragmentation and Reconciliation: Re-visioning the Health of Urban Indigenous Women in Toronto
Keywords: Indigenous women's health
Indigenous health and well-being
urban Indigenous women
Indigenous approaches to research
defragmentation

This doctoral research seeks to advance understanding about what impacts the health and well-being of urban Indigenous women in Toronto, Ontario, Canada. It is grounded in the goal of centering Indigenous women’s knowledge and revitalizing recognition of Indigenous women as leaders in the care of health knowledge, who continue to carry roles and responsibilities as knowledge and vision keepers, healers, helpers and caregivers despite the mass devastation caused by colonization. Utilizing an Indigenous research method, research circles and interviews were used to gather knowledge with twenty-three Indigenous women asking the following questions: 1) What helps you to be healthy and well here in the city? 2) What gets in the way of your health and well-being? and 3) What do you envision as needed to support your health and well-being and that of Indigenous women generally here in Toronto? The findings of the research highlight the ways in which women seek wholeness and (w)holistic health care and services in attending to their health and well-being. The stories shared speak to the rupture and fragmentation caused by colonization as experienced by the participants, specifically the disconnection and dislocation that they faced due to child welfare apprehension, adoption or violence, while emphasizing the ways in which they have or are presently navigating these challenges in relation to their health and well-being – a process of defragmentation. This thesis is also, in part, the story of how I am learning my role as a caretaker of knowledge (as I would describe the role of researcher), learning how to gather it, care for it and share it back in a good way. It is the story of what I know now, a knowledge that will continue to grow over time, with more experience to better understand the full beauty and depth of what has been shared. This thesis is a knowledge bundle of stories gathered with urban Indigenous women in the city of Toronto to help better understand what impacts their health and well-being, and what they see as needed moving forward. It is woven together with my own story of who I am, where I come from and why I came looking for this knowledge.