VictorJuiz/thesis huggingface dataset:
Neural Correlates of Pain and its Associated Clinical and Psychological Correlates in the Dynamic Pain Connectome in Patients with Ankylosing Spondylitis

Chronic pain is a major public health issue. Despite its prevalence, the brain and behavioural mechanisms underlying chronic pain are not well understood, hampering effective treatment. Both individual factors (such as how we adapt in response to stressors), and brain function contribute to variability in pain perception. Abnormalities in brain and behaviour may indicate (mal)adaptive response or functioning in chronic pain patients. The overall goal of this thesis is to elucidate brain and behavioral mechanisms involved in pain. I first explore brain communication within and between networks of the dynamic pain connectome (default mode network; DMN, salience network; SN, sensorimotor network; SMN) that reflect chronic pain symptoms. Second, I examine how resilience – an individual’s ability to adapt well in response to stress – contributes to individual differences in pain perception. Finally, I investigate the intersection of brain communication and resilience and how this relationship is altered in chronic pain. My participants included healthy controls and patients with ankylosing spondylitis (AS) experiencing chronic pain. Participants underwent a resting state fMRI scan and psychophysical testing, and completed questionnaires probing resilience and other factors. I found that 1) AS patients exhibit abnormal, heightened DMN-SN cross-network functional connectivity, 2) cross-network connectivity between the DMN, SN, SMN, and descending pain system tracks AS pain-related outcomes, 3) resilience, anxiety, and their interaction predict pain-related affect in response to experimental pain stimuli, 4) AS patients reporting high pain intensity and disease activity are less resilient, 5) Chronic pain intensity is related to (heightened) DMN – SMN cross network connectivity, and 6) within-DMN connectivity tracks resilience in healthy individuals and patients reporting minimal pain. This thesis demonstrates that AS patients have chronic pain-related abnormalities between brain networks of the dynamic pain connectome, and that resilience plays a role in the pain experience and its representation in the brain.

Keywords: brain
fMRI
MRI
neuroscience
pain
Advisor: Davis, Karen D
Flexible Shape-memory Scaffold for Minimally Invasive Delivery of Functional Tissues

Despite great progress in engineering functional tissues for organ repair, including the heart, an invasive surgical approach is still required for their implantation. Here, we designed an elastic and microfabricated scaffold using a biodegradable polymer (poly(octamethylene maleate (anhydride) citrate)) for functional tissue delivery via injection. The scaffold’s shape memory was due to the microfabricated lattice design. Scaffolds and cardiac patches (1 cm × 1 cm) were delivered through an orifice as small as 1 mm, recovering their initial shape following injection without affecting cardiomyocyte viability and function. In a subcutaneous syngeneic rat model, injection of cardiac patches was equivalent to open surgery when comparing vascularization, macrophage recruitment and cell survival. The patches significantly improved cardiac function following myocardial infarction in a rat, compared with the untreated controls. Successful minimally invasive delivery of human cell-derived patches to the epicardium, aorta and liver in a large-animal (porcine) model was achieved. Engineering mature tissues requires a guided assembly of cells into organized three-dimensional (3D) structures with multiple cell types. The assembly of individual units into functional 3D tissues is often time-consuming, relying on cell ingrowth and matrix remodeling, whereas disassembly requires an invasive method that includes either matrix dissolution or mechanical cutting. We invented Tissue-Velcro, a bio-scaffold with a microfabricated hook and loop system. The assembly of Tissue-Velcro preserved the guided cell iii alignment realized by the topographical features in the 2D scaffold mesh and allowed for the instant establishment of coculture conditions by spatially defined stacking of cardiac cell layers or through endothelial cell coating. The assembled cardiac 3D tissue constructs were immediately functional as measured by their ability to contract in response to electrical field stimulation. Facile, on-demand tissue disassembly was demonstrated while preserving the structure, physical integrity, and beating function of individual layers.

Keywords: biomaterials
cardiac tissue engineering
shape-memory
soft-lithography
Advisor: Radisic, Milica
Student Debt and the University-to-Workforce Transition: The Role of Risk and Socio-Economic Background

Post-secondary education has increased in importance for economic prosperity and in cost, which has led to rising student debt in many nations. Researchers have lagged in determining how student debt affects new post-secondary graduates and, in particular, how it affects the labour market transitions of new university graduates? This dissertation explore this topic using nationally representative data on 2010 Canadian graduates. The effects of student debt on labour market transitions and outcomes are tested in three empirical studies. In Chapter 2, high levels of student debt are found to be associated with graduates reporting that they could not wait for the job they wanted, that they were actively looking for a different job despite currently being employed, and, for first-generation students only, that they were willing to move cities if it improved their job prospects. In Chapter 3, I find that highly indebted graduates are more likely to take a temporary first job and to have had more employers since graduation. I also find that highly indebted first-generation graduates have fewer job benefits and lower estimated incomes both two and three years after graduation. Not surprisingly given the aforementioned adverse effects of high student debt found for first-generation graduates, in Chapter 4 I also find that they report lower satisfaction levels. Specifically, compared to all other graduates, highly indebted first-generation graduates report lower job and life satisfaction, and are significantly less likely to say they would do the same education if they could choose again. Taken together, these findings have implications for higher education policy and the ability of university to function as a great equalizer. The findings are alarming given that upwards of 60% of students rely primarily on debt to fund their higher education. They suggest that student debt creates desperation in the job searches of new university graduates, which leads to greater job precarity, reduced job quality, and lower job and life satisfaction. Overall, this research casts doubt on the effectiveness of using student loans as s primary means of providing access to higher education.

Keywords: Student Debt
Advisor: Andersen, Robert
Investigating the Roles of Parvalbumin and Cholecystokinin Interneurons of the Ventral Hippocampus and Medial Prefrontal Cortex in Schizophrenia-Related Behaviours

Schizophrenia is characterized by neuropathological changes in inhibitory GABA interneurons in the hippocampus (HPC) and medial prefrontal cortex (mPFC) (Benes and Berretta, 2001; Lisman et al., 2008; Lewis et al., 2012). A diverse population of GABA interneurons participates in organizing network activity underlying behaviours mediated by the HPC and mPFC (Klausberger and Somogyi, 2008; Tremblay et al., 2016). Two major classes of perisomatic interneurons disrupted in schizophrenia, express parvalbumin (PV) or cholecystokinin (CCK) and differ in their electrophysiological properties, molecular expression, anatomical distribution, and connectivity (Armstrong and Soltesz, 2012). This raises the important question of whether PV and CCK interneurons play distinct roles in the sensorimotor and mnemonic functions of the HPC and mPFC (Freund and Katona, 2007). Using intersectional genetic labeling in combination with chemogenetics and optogenetics, we evaluated how PV and CCK interneuron dysfunction in the ventral HPC and mPFC contribute to behavioural abnormalities associated with schizophrenia. In the ventral HPC, PV and GAD65 interneurons were both involved in working memory while contributing to different forms of sensorimotor processing. Furthermore, the CCK-expressing subset of GAD65 interneurons in the vCA1/Sub specifically contributed to learning context-reward associations, potentially through their interaction with NAc-projecting neurons. In the mPFC, PV and CCK interneurons played important roles during working memory depending on task phase. Functional differences in the mPFC were mirrored by anatomical differences in their laminar distribution, and prominent monosynaptic connections from CCK interneurons onto PV interneurons. These findings reveal the unique behavioural functions of PV and CCK interneurons, and elucidate the contribution of their impairment to specific deficits in schizophrenia.

Advisor: Kim, Junchul
A LATENT GROWTH MODELLING APPROACH TO INVESTIGATING GENDER DIFFERENCES IN THE DEVELOPMENT OF BEHAVIOURAL SELF-REGULATION AND ACADEMIC OUTCOMES FROM KINDERGARTEN TO GRADE 2

A growing body of literature indicates the behavioural aspect of self-regulation, including paying attention, remembering instructions, controlling impulses and directing one’s action, amidst environmental distractions, is a critical component of successful school functioning. Some studies have identified differences between male and female students’ behavioural self-regulation abilities; however, it is unclear whether improvements in this ability are influenced by gender and whether they parallel growth in the development of reading and math abilities. The present study explored gender differences in the development of children’s behavioural self-regulation from kindergarten to Grade 2, using a direct assessment. Longitudinal associations between behavioural self-regulation and early reading and math skills were also examined. A latent growth modelling approach was utilized for the analyses across three waves of data collection. The study participants included 197 children (106 males and 91 females). On average, children were approximately five years old at the start of the study (M =5.39, SD=0.593). The study results revealed gender similarities in behavioural self-regulation growth, positive correlated initial skill levels and rates of growth between behavioural self-regulation and reading, and positive correlated initial skill levels between behavioural self-regulation and math. Implications for future research, as well as educational policies and instructional practices, are discussed.

Keywords: behavioural self-regulation
kindergarten
latent growth model
math
reading
Advisor: Pelletier, Janette
A Qualitative Study of Embodiment among Women with Physical Disabilities during the Perinatal Period and Early Motherhood

Although there are over 500,000 mothers with disabilities in Canada, little is known about how women with disabilities experience becoming and being mothers. This dissertation qualitatively explores how thirteen women with physical disabilities in Ontario experienced their embodiment during the perinatal period and early motherhood. Informed by feminist disability scholarship, embodiment here is understood as relational; that is, the intertwining of the body and the mind and the interplay between the material body and the social world. Findings are presented according to three “stages”: pregnancy, breastfeeding, and mothering. I found that participants’ embodied experiences across these interrelated “stages” were shaped by dominant discourses of pregnancy, breastfeeding, and motherhood, as well as dominant discourses of disability, often enacted through social interaction. Participants desired to be perceived of as “good mothers,” seemingly to avoid being perceived of as “unfit” and in turn affirming stigmatizing discourses of disability. Meeting the expectations of the “good mother” proved to be challenging, however, as disability limited what participants could physically do. Consequently, some experienced ambivalent and negative feelings about disability. Importantly, I also found that disability was experienced as valuable in the context of becoming and being a mother. The embodied experience of disability provided opportunity to subvert the sometimes-unrealistic expectations associated with pregnancy, breastfeeding, and mothering, as well as discourses of disability as defective and undesirable. Regarding pregnancy, the embodied experience of disability was appreciated, offering a reimagination of the “unruly” pregnant body. Disability in the context of breastfeeding and mothering called attention to the need for self-care and challenged understandings of accessibility and independence. In sum, participants’ embodied experiences of the perinatal period and early motherhood both aligned with and subverted dominant discourses. In documenting how these discourses shaped embodied experience, I discuss their potential implications for health research and practice. Notably, I argue that the ways in which participants’ embodied experiences subvert dominant discourses evoke new ways to think about the body, disability, and parenting. These new ways of thinking add to feminist disability and perinatal embodiment scholarship, as well as present opportunities for more inclusive and equitable health research and practice.

Keywords: breastfeeding
embodiment
feminist disability studies
motherhood
physical disability
pregnancy
Advisor: Ross, Lori E
Strike, Carol J
Peptide-based studies of hydrophobicity in membrane environments

Hydrophobicity – fear of water – drives the folding of soluble proteins into their final folded state. However, within the lipid bilayer, an environment devoid of water, the concept of hydrophobicity, and its role in protein folding, becomes more obscure. Utilizing synthetic peptides of length and hydrophobic content typical of nascent transmembrane (TM) segments, in this thesis we systematically assessed how altering amino acid sequence while maintaining composition impacts peptide-membrane interactions. We used four distinct sequence patterns: scrambled sequences, with hydrophobic character dispersed along the sequence length; clustered (or block) sequences, with a continuous stretch of hydrophobic character; amphipathic sequences, with one polar face and one hydrophobic face; and lipopathic sequences, with two hydrophobic faces where one is more hydrophobic than the other. Biophysical techniques, including circular dichroism and fluorescence spectroscopy, and HPLC retention times, were employed to measure peptide properties in a range of membrane mimetics. This versatile approach enabled us to relate specific features of sequence and environment to observed peptide-membrane interactions. We found that peptides containing a hydrophobic block or face were deemed most hydrophobic in membrane mimetics. Comparison to in vivo protein-assisted membrane insertion revealed that the translocon machinery could lower the energetic barrier to membrane integration, allowing a hydrophobic block to ‘carry’ polar residues into the bilayer. As well, local hydrophobic and helical patterning, including interchange of leucine and isoleucine residues, were found to play central roles in mediating peptide-membrane interactions. We concluded that the lack of water in the membrane does not render TM sequences any less “hydrophobic”; rather, the accessibility of a protein’s irregular surface to lipid acyl chains becomes a measure of “lipophilicity/lipopathy”, where the overall TM sequence produces the mix of protein-membrane and protein-protein interactions that fold a membrane protein into its final biologically-functional structure.

Keywords: Folding
Insertion
Lipid Bilayer
Membrane mimetics
Peptide
Transmembrane
Advisor: Deber, Charles M
ROBUSTNESS AND FLEXIBILITY IN CODING FOR DISTRIBUTED STORAGE SYSTEMS

This dissertation presents new methods for analysis and design of coding schemes for distributed storage. We introduce a generalization of the regenerating codes by simultaneously incorporating flexibility and error resiliency in the code design. For flexibility we consider bandwidth-adaptive repair, which allows selecting the number of helpers during the runtime, while achieving optimal repair bandwidth adaptively. We also consider robustness against an omniscient adversary, which can control a limited number of nodes, to ensure a desired level of error resiliency. In this extended setting, we formulate the optimum trade-off between the storage overhead and repair bandwidth. After deriving the theoretical lower bounds on storage overhead and repair bandwidth, we focus our attention to explicit code construction for the extreme points of this trade-off, achieving theminimumrepair bandwidth (theMBR code) and the minimum storage overhead (the MSR code). For each case we present novel explicit codes and show that these codes achieve the optimal trade-off for bandwidth-adaptive and error-resilient (BAER) setting. All of the code constructions in this dissertation are designed in a well-known framework called Product Matrix, which is widely accepted to be practically appealing for implementation. An important feature of all these codes is their exact repair mechanism that guarantees recovering the same content of any failed storage node. In the MBR BAER case we present two coding schemes. The first one requires the code alphabet size to be large, but adds no restrictions to the choice of other code parameters compared to non-BAER codes. In the second MBR BAER code, alphabet size can be bounded by the number of nodes in the system, which is similar to practical solutions such as the Reed-Solomon codes, at the cost of some extra restrictions on the subpacketization level. To the best of our knowledge these are the first exact-repair BAER MBR codes. We also present an explicit MSR BAER code construction, and show that it can perform optimal exact repair for a wide range of choices for the number of helpers, while realizing an exponentially smaller subpacketization level compared to the only other existing solution.

Keywords: Adaptive Systems
Big Data
Cloud Services
Distributed Storage Systems
Error Resiliency
Advisor: Khisti, Ashish
The Relationship of Ocular and Cerebrospinal Fluids to the Optic Nerve in Health and Glaucoma

The optic nerve is a white matter tract that conveys visual information from the eye to the brain. Inside the eye, the optic nerve head is exposed to ocular fluids, and behind the eye, the nerve is surrounded by cerebrospinal fluid (CSF). Ocular fluid and CSF are similar in composition and function, and are in close proximity at the optic nerve interface. Additionally, both fluids drain into cervical lymph nodes via the lymphatic system. Despite these common features, the relationship between these fluids and the optic nerve is poorly understood. Recent studies point to glymphatic paravascular entry of CSF into brain tissue to deliver nutrients and to clear metabolic waste. The hypothesis of this thesis is that ocular fluid and CSF enter the optic nerve via paravascular pathways and that this is relevant to glaucoma, the leading cause of irreversible blindness worldwide. My investigations reveal that ocular fluid flows into the optic nerve head by diffusion rather than via a paravascular pathway. In contrast, CSF flows into the optic nerve via paravascular spaces bordered by optic nerve capillaries and astrocytic endfeet containing aquaporin water channels. Furthermore, studies revealed size dependent entry of CSF solutes with preferential entry of smaller molecules. Additionally, CSF flowed into the optic nerve only up to the optic nerve head. Finally, in a spontaneous glaucoma model, studies revealed markedly impaired CSF flow into the optic nerve in association with nerve damage. These results are the first to show the intimate relationship of ocular fluid and CSF to the optic nerve. These novel findings will help us to understand the optic nerve in both health and in disease such as glaucoma.

Keywords: Aqueous Humour
Cerebrospinal Fluid
Glaucoma
Optic Nerve
Advisor: Yucel, Yeni H
Construction Schemes and their applications

We study capturing construction schemes, a new combinatorial tool introduced by Todorcevic to build uncountable structures. It consists of a ranked family of finite sets that provides a framework to do recursive constructions of uncountable objects by working with finite amalgamations of finite isomorphic substructures, the uncountable substructures of the final object can be further studied using capturing. In this Thesis we study the consistency of capturing construction schemes, and related definitions, we prove results of consistency, and give several applications of this tool both to infinite combinatorics and Banach space theory. For example, we show weaker forms of capturing, such as n-capturing, form a strict hierarchy which is related to the m-Knaster Hierarchy. We also show how capturing construction schemes can be used in constructing Suslin trees and Hausdorff gaps of a special kind in an intuitive manner. And give some applications to the theory of nonseparable Banach spaces.

Keywords: Banach Spaces
Construction Schemes
Destrutible gaps
Logic
Suslin Trees
Advisor: Todorcevic, Stevo
Economics of Maternal and Child Nutrition: Food Fortification with Vitamin A in Tanzania

In 2011, Tanzania mandated the fortification of edible oil with vitamin A to help address its vitamin A deficiency public health problem. By 2015, only 16 percent of edible oil met the standards for adequate fortification. The MASAVA project initiated the production and distribution of unrefined sunflower oil fortified with vitamin A by small- and medium-scale producers in the Manyara and Shinyanga regions of Tanzania. A quasi-experimental non-equivalent control group research trial and an economic evaluation were conducted to study 1) the determinants of vitamin A deficiency in children aged 6 to 59 months, 2) the effectiveness of fortification by small- and medium-scale producers and fortification standards, and 3) the cost-effectiveness of fortification in preventing vitamin A deficiency. Data collection was conducted through a household baseline survey with a sample of 568 mother and child pairs before the intervention and a follow-up survey 18 months later. This study found that the primary determinants of vitamin A deficiency in young children at the time of the baseline household survey were not being breastfed and the low retinol binding protein concentration level of mothers. This study demonstrated that fortification by small- and medium-scale producers was feasible and may have increased the mean retinol binding protein concentration levels in children but did not have a significant effect on the prevention of vitamin A deficiency due to insufficient coverage. Mandatory fortification standards and fortification by large-scale producers increased the mean retinol binding protein levels in children by 3.5 µg/ml as well as reduced the prevalence of vitamin A deficiency by 21.4 percentage points in the Shinyanga region. From a social perspective, the incremental cost of fortification could be as low as US$0.13, $0.06 and $0.02 per litre for small-, medium- and large-scale producers respectively. The estimated cost per disability-adjusted life year averted was $281 for large-scale producers and could be as low as $626 for medium-scale and $1,507 for small-scale producers under ideal conditions. According to World Health Organization thresholds, this is very cost-effective for large- and medium-scale producers, and cost-effective for small-scale producers.

Keywords: Child health
Economics
Fortification
Micronutrients
Nutrition
Vitamin A
Advisor: Laporte, Audrey