VictorJuiz/thesis huggingface dataset:
Clinical Outcomes of Pediatric Intestinal Failure Management after Implementation of a Multidisciplinary Intestinal Rehabilitation Program

The objective of this thesis was to evaluate the effect of implementation of a multidisciplinary intestinal rehabilitation program (IRP) on clinical outcomes of pediatric intestinal failure (IF). This was attained by two comprehensive reviews and three related research projects that contribute both clinical and methodological knowledge. Pediatric IF is a complex medical condition. Advances have been made clinically in recent years, but research in the field has suffered from methodological challenges and poor quality. Many of these were outlined and solutions suggested in this thesis. The first project compared clinical outcomes of three eras of pediatric IF-management using univariate categorical and time-to-event analysis. While IRP-introduction led to an increased transplantation rate and improved clinical outcomes, further progress was made and the natural course of the disease changed with IRP-maturation and adoption of novel treatment strategies. The second project quantified the continuous change over time of pediatric IF over a 15-year time period and tested systematically introduced treatments using novel methods. Multivariate time series analysis was applied to assess the relationship between new treatment options and change in clinical outcomes. The study showed that IRP-introduction and omega-3 lipid emulsions independently decreased disease-specific mortality from liver failure and sepsis when adjusted for disease severity, while serial transverse enteroplasty and ethanol locks did not impact mortality significantly. With improved mortality of pediatric IF, assessment of morbidity became imperative. After having identified a severe lack in methodology to measure neonatal and infant health-related quality of life (NIHRQOL) in a systematic literature review, the conceptual meaning of NIHRQL was explored in the final project. It concluded that NIHRQOL is a multidimensional, multilayered and interconnected concept, in which the childâ s needs are fundamental factors, and the caregiverâ s and societyâ s ability to meet those needs characterize the interdependence between the child and its caregiving environment. In summary, the complexity of pediatric IF and related methodological challenges were identified. Methodological solutions were described and illustrated. Clinical advancements of pediatric IF were quantified, and IRP-introduction and omega-3 lipid emulsions recognized as strongest contributors. Finally, the meaning of NIHRQOL was explored and organized in a conceptual framework in this thesis.

Keywords: Intestinal failure
Methodology
Outcomes
Pediatrics
Quality of life
Time series analysis
Advisor: Wales, Paul W
Cancer Survival in First Nation and Métis Adults in Canada: Follow-up of the 1991 Census Mortality Cohort

Internationally, Indigenous persons tend to have poorer cancer survival than their non-Indigenous peers. Measuring cancer survival among Indigenous populations presents a particular set of challenges owing largely to their small share of the population and a lack of reliable and valid ethnic identifiers in cancer registries and vital statistics registries. The objectives of this thesis were to explore these challenges and how they are or are not overcome internationally, to produce the first Canada-wide estimates of cancer survival for First Nations and MĂŠtis, and to estimate the extent to which different methods of measuring cancer survival yield different results in this application. The systematic review conducted to achieve the first objective revealed that the majority of studies of this topic internationally use a cause-specific approach to measuring survival and that despite common threats to validity posed by information biases, rarely discussed these risks or their potential consequences. Data from the 1991 Census Mortality Cohort, a linkage of the 1991 Long Form Census to the Canadian Cancer Registry and the Canadian Mortality Database through to 2009, were used to accomplish the second and third objectives. Compared to non-Aboriginal cohort members, First Nation and MĂŠtis people had poorer survival for nearly all of the most common cancers and the disparity remained after taking differences in income and rurality into account. The differences in results yielded by common methods for survival analysis were shown to vary depending on the population, the type of cancer and whether survival itself or survival disparities were being measured. Taken together, this work advances our knowledge of cancer disparities between First Nation, MĂŠtis and non-Aboriginal people in Canada and our understanding of how the data and methods we use impact the magnitude of disparities we measure.

Keywords: Canada
Cancer
First Nation
MĂŠtis
Surveillance
Survival
Advisor: Marrett, Loraine D
Pole, Jason D
Dangerously Free: Outlaws and Nation-making in Literature of the Indian Territory

In this dissertation, I examine how literary representations of outlaws and outlawry have contributed to the shaping of national identity in the United States. I analyze a series of texts set in the former Indian Territory (now part of the state of Oklahoma) for traces of what I call “outlaw rhetorics,” that is, the political expression in literature of marginalized realities and competing visions of nationhood. Outlaw rhetorics elicit new ways to think the nation differently—to imagine the nation otherwise; as such, I demonstrate that outlaw narratives are as capable of challenging the nation’s claims to territorial or imaginative title as they are of asserting them. Borrowing from Abenaki scholar Lisa Brooks’s definition of “nation” as “the multifaceted, lived experience of families who gather in particular places,” this dissertation draws an analogous relationship between outlaws and domestic spaces wherein they are both considered simultaneously exempt from and constitutive of civic life. In the same way that the outlaw’s alternately celebrated and marginal status endows him or her with the power to support and eschew the stories a nation tells about itself, so the liminality and centrality of domestic life have proven effective as a means of consolidating and dissenting from the status quo of the nation-state. I introduce my argument with a brief reading of the Oklahoma Diamond Jubilee celebrations in 1982 before turning to the settler-colonial politics of outlawry in my first two chapters’ respective analyses of Charles Portis’s True Grit (1968) and turn-of-the-century narratives of the life of Belle Starr, the so-called “Bandit Queen.” The two remaining chapters take up the invocation of outlaw rhetorics in texts that approach the politics of outlawry from an Indigenous perspective, including Green Grow the Lilacs (1929) by Cherokee poet and playwright R. Lynn Riggs, and three fictional accounts of the life of Ned Christie, so-called “Cherokee outlaw,” by John M. Oskison (1926), Robert J. Conley (1991), and Robby McMurtry (2009). A brief Afterword extends the implications of my argument to political disputes that continue to afflict Oklahoma, and the Cherokee Nation in particular, in the twenty-first century.

Keywords: American Studies
Indian Territory
Indigenous Studies
Nationalism
Outlaws
Settler Colonial Studies
Advisor: Justice, Daniel H
Towards Context-aware Brain-computer Interfaces

Brain-computer interfaces (BCIs) allow individuals with disabilities to communicate and control their environment without the necessity for volitional speech or motor activation. However, most current BCIs are prone to significant performance fluctuations and incapable of adapting to their users. These shortcomings impair practical BCI usage. This thesis investigates the feasibility of a hybrid BCI that is capable of detecting and adapting to underlying changes in user mental state. The thesis comprises four major studies, each representing a step towards this ultimate goal. The first study formulates a novel signal processing algorithm for the frequency-domain analysis of electroencephalographic (EEG) recordings. The second study examines the ability to automatically detect fluctuations in three mental states that are important to BCI usage - fatigue, frustration, and attention - based on electrical activity recorded from the surface of the scalp using EEG. The third study explores the effects of each of these mental states on the online operation of a two-class EEG-BCI. The final study investigates the efficacy of two different methods - reliability prediction and adaptive classification - by which a BCI can adapt to changes in fatigue, frustration, and attention. In the first study, the novel algorithm, based on a clustering of spectral power features, was shown to compress EEG signals with less information loss than traditional frequency-domain analyses. In the second study, fluctuations in fatigue, frustration, and attention were detected with mean classification accuracies of 76.8%, 71.9%, and 86.1%, respectively. In the third study, a significant relationship between perceived frustration and BCI accuracy was uncovered and optimal regions for BCI performance were identified in several multi-dimensional representations of user mental state. In the final study, estimated mental state was used to predict the onset of low-accuracy BCI performance, with an 8% decrement in classification accuracy between the predicted high and low accuracy conditions. This study also demonstrated the ability to directly adapt BCI classification, leading to statistically significant increases in classification accuracy for roughly half of participants without significantly compromising performance for the remainder of the study population.

Keywords: brain-computer interface
electroencephalography
mental state
Advisor: Chau, Tom
Characterizing The Fat-Bazooka Interaction in Drosophila melanogaster Development

fat is a Drosophila tumor suppressor that encodes a large cadherin involved in regulation of growth, spindle orientation, a form of tissue organization called planar cell polarity (PCP) and mitochondrial function. Although Fat is known to act upstream of these processes, the exact mechanisms are unknown and few biochemical interactors of Fat have been identified. To better understand the biology of Fat signaling, I used a proteomic screening approach to identify novel interactors of Fat using affinity purification coupled to mass spectrometry (AP-MS). I used two cell culture systems and an in vivo approach using fly embryos to obtain several lists of potential Fat interactors. In parallel, the apicobasal polarity protein PAR3 was identified by AP-MS as a potential interactor of the human ortholog FAT4 in HEK293 cells. I found that the interaction is conserved in Drosophila, as Fat can be immunopurified with endogenous Bazooka (Baz; PAR3 homolog), and I identified two regions of Ft protein required for binding. Loss of ft in mutant clones in the wing disc lead to an expansion of the Baz domain and an increase in Baz protein staining intensity. Moreover, knockdown of Baz during wing development resulted in increased wing size which is dependent on Yki, indicating a role for Baz in regulating tissue growth.

Keywords: AP-MS
Bazooka
Fat
Wing
Advisor: McNeill, Helen
Combined Delivery of Chondroitinase ABC (ChABC) and Stromal Cell Derived Factor 1α (SDF1α) for Spinal Cord Regeneration

Spinal cord injury (SCI) is a devastating condition that affects millions of people worldwide. Successful drug therapies for SCI have been difficult to achieve due to the complex nature of the pathology. Increasingly, researchers are moving towards combination strategies using at least two therapeutics that target distinct injury pathways. Furthermore, sustained drug delivery to the spinal cord is complicated by the presence of the blood spinal cord barrier (BSCB) and cerebrospinal fluid flow. In this work, an injectable hydrogel was designed for the minimally invasive, localized, sustained delivery of two different protein therapeutics to the injured spinal cord: chondroitinase ABC (ChABC), an enzyme that degrades the glial scar, and stromal cell-derived factor 1Îą (SDF), a chemokine implicated in the migration of endogenous neural precursor cells (NPC) to the site of SCI. Design of experiment (DOE) was used to explore the relationships between composition and mechanical properties of a physically and chemically crosslinked methylcellulose hydrogel (XMC). An optimal gel formulation that was injectable, minimally swelling, long-lasting, and safe in vivo, was chosen for future studies. Active ChABC was released from XMC for at least 7 days using reversible affinity interactions. Additionally, a mathematical model was developed to provide a mechanistic understanding of affinity-based release systems and allow for rational design. Active SDF was released from XMC for at least 28 days by exploiting electrostatic interactions with negatively charged poly(lactic-co-glycolic acid) nanoparticles (PLGA np). This is the first evidence of long-term protein release using PLGA np without encapsulation. The efficacy of this combined treatment was tested in a rat model of compressive SCI. ChABC treatment resulted in decreased chondroitin sulfate proteoglycan (CSPG) levels for up to two weeks after injury and a trend towards improved behavioural recovery. Treatment with SDF did not improve behavioural nor histological outcomes and did not show any synergy with ChABC. Together these studies introduce XMC as a novel, injectable hydrogel platform for therapeutic protein delivery to the spinal cord and demonstrate two different methods of controlling protein release from this hydrogel.

Keywords: adult stem cells
chondroitinase abc
CXCL12
drug delivery
glial scar
spinal cord
Advisor: Shoichet, Molly S
Radiophonic Writing at the BBC, 1945-63

Creative radio is written and produced from an unavoidable set of material conditions, but received by its listeners as ephemeral and supposedly immaterial sound. Focusing on the writing, production and reception of literary radio broadcast by the BBC in the postwar era, this dissertation establishes a connection between the cultural significance of radio and the aesthetic significance of sound. The postwar BBC was a major participant in the era of British cultural welfare statism, but the corporation also flourished as a distributor of culture, providing challenging and even radical aesthetic experience. The reputedly “highbrow” BBC Third Programme, I argue, was neither elitist nor exclusive, nor was the radio drama it produced culturally or aesthetically “complete”; instead the aurality of radiophonic writing invited pluralistic and active listenership. In the postwar era radio was no longer new; however, Louis MacNeice, Giles Cooper and Samuel Beckett found new ways of exploiting radio’s maturity to develop a progressive radio aesthetics. MacNeice, a full-time BBC staff member, was a radio professional whose writings dramatize a conflict between his poetic instinct for sound and his impatience with the institutional pressures of planning in the increasingly bureaucratic postwar BBC. Conversely, Cooper had no fixed institutional position, and his sonically experimental works, reflecting this precariousness, oscillate between innovation and obsolescence. Beckett’s radio plays suggest a different type of precariousness, exploiting electroacoustic technology to convey a delicate ambiguity between exterior landscape and interior space. My analysis of all three writers demands an appreciation of their production as sound, and I offer my dissertation as a contribution to the growing field of literary sound studies; as such, I attend to the specifically sonic components of radio plays and features, giving a deserved critical prominence to producers and electroacoustic artists, particularly members of the BBC Radiophonic Workshop. The meaning of broadcast radio, I argue, is constructed in the resonant aural sphere, a space of collaborative interaction between author, producer and listener. For radio creators and radio listeners alike, this resonant interaction turned the medium’s coming obsolescence into a creatively significant moment of invention in the face of decay.

Keywords: BBC
Broadcasting
Electroacoustic
Radio
Radio drama
Sound
Advisor: Cuddy-Keane, Melba
A Nation's Dilemma: Party Politics and the Production of Nationhood, Belonging and Citizenship in France's Face Veil Debate

In April 2011 – following a two-year-long nationwide debate over Islamic veiling – the French government implemented a law that prohibits facial coverings in all public spaces. Prior research attributes this and other restrictive laws to France’s republican secular tradition. This dissertation takes a different approach. Building on literature that sees electoral politics as a site for generating – rather than merely reflecting – societal meanings, it argues that the 2011 ban arose in significant part out of political parties’ struggle to demarcate the boundaries of the electoral sphere in the face of an ultra-right electoral threat. Specifically, it shows that in seeking to prevent the ultra-right National Front party from monopolizing the religious signs issue, France’s major right and left parties agreed to portray republicanism as requiring the exclusion of face veiling from public space. Because it was forged in conflict, however, the agreement thus generated is highly fractured and unstable. It also conceals ongoing conflict, both within political parties and in civil society, over the precise meaning of French republicanism. The findings thus underscore the relationship between boundary drawing in the political sphere and the process of demarcating the cultural and political boundaries of nationhood, belonging and citizenship in contexts of immigrant diversity.

Keywords: France
Gender
Islam
Nationalism
Politics
Veil
Advisor: Korteweg, Anna C
The Development of MnIII-Porphyrins as T1 Contrast Agents for Biomedical Applications

Among clinical imaging modalities, magnetic resonance imaging (MRI) has several advantages including high spatial resolution, excellent soft tissue contrast and lack of ionizing radiation. To improve sensitivity and specificity for disease diagnosis, contrast agents (CAs) are administered. Clinical CAs are primarily Gd-based and are limited by a decrease of relaxivity at high magnetic fields,1 and have been associated with nephrogenic systemic fibrosis (NSF), a severe and debilitating disease.2 Therefore, this thesis explores the development of manganese porphyrins (MnPs) as novel CAs designed for high field MRI applications. MnPs were chosen because certain MnPs have been shown to exhibit anomalously high T1 relaxivity at high field,3 and are known to form highly stable metal chelates.4 The first section describes the design of a highly efficient Gd-free extracellular fluid CA based on a water-soluble MnP, manganese (III) meso-tetracarboxyl porphyrin (MnTCP), for clinical disease diagnosis (Chapter 2). To the best of our knowledge, MnTCP displays the highest r1 among all known small T1 CAs with molecular weight below 600 Dalton (Da) and was successfully used to detect tumors by dynamic contrast enhanced MRI. More recently, as the field of cell transplantation is rapidly expanding, CAs are needed to label and longitudinally track specific populations of cells in vivo. This led to the design and successful application of a cell-permeable, trappable and esterase-responsive MnP (Chapter 3). Highly efficient MRI labeling of two types of human cells was achieved with a relatively low concentration and short incubation time. The new CA is biocompatible and as far as we know, is the most efficient T1 cell labeling CA available to date. Finally, this thesis focuses on molecular imaging of enzyme activity. The progress towards the design and synthesis of an alkaline phosphatase responsive MnP for MRI and analogous ZnP for fluorescence is described in Chapter 4.

Keywords: Agent
Contrast
Imaging
MRI
Porphyrin
Synthesis
Advisor: Zhang, Xiao-an
Novel Functions of ATG16L1 in the Innate Response to Invasive Bacterial Pathogens

Crohnâ s disease (CD) is a chronic inflammatory condition of the gastrointestinal tract. Susceptibility to CD is determined by both environmental and genetic risk factors. While the etiology of CD remains unclear, several pathways have been consistently implicated in susceptibility. Indeed, multiple genes involved in the innate immune response have been strongly linked to CD. Studies examining the function of these innate immune genes have indicated that an inability to properly handle bacteria that come into contact with the intestinal mucosa, as well as defects in the regulation of the inflammatory response triggered by innate recognition of these bacteria, are primary factors in increasing CD susceptibility. Autophagy, a degradation system for cytoplasmic cargo, has been implicated in both of these functions. ATG16L1 is a central component of the autophagy machinery and is a CD susceptibility locus. Here, two novel functions of ATG16L1 in the innate immune response are described. First, we uncovered a regulatory role for ATG16L1 in the inflammatory response driven by NOD1 and NOD2, which are intracellular sensors of bacterial invasion. Secondly, we identified an interaction between complement C3, the central component of the complement cascade, and ATG16L1. This interaction allows for efficient targeting of complement C3-coated invasive pathogens to the autophagy machinery. Both of these functions were impaired in cells expressing the CD-associated variant of ATG16L1. Overall, these findings indicate that dysfunction of ATG16L1 in both regulation of inflammation and defective handling of complement-coated intracellular bacteria might contribute to the generation of a harmful inflammatory state in the gastrointestinal tract.

Keywords: ATG16L1
Autophagy
Infection
NOD1
NOD2
Advisor: Philpott, Dana J