VictorJuiz/thesis huggingface dataset:
Exploring the Post-Test Psychological Functioning and Cancer Prevention Decisions of Women Undergoing Multi-Gene Testing for Hereditary Breast and Ovarian Cancer Risk
Keywords: cancer risk reduction
hereditary breast and ovarian cancer
multi-gene panel testing
psychological distress

BACKGROUND: Advances in gene sequencing technologies have expanded the genetic landscape of hereditary breast and ovarian cancer (HBOC). This led to the clinical adoption of multi-gene panel testing, which screens high penetrance (e.g. BRCA1/2) and moderate penetrance genes now implicated in HBOC. Currently, there is limited evidence supporting the cancer risk estimates and management recommendations of several moderate penetrance variants. In addition, panel testing increases the likelihood of identifying a variant of uncertain significance (VUS). As a result, practitioners and patients face uncertain genetic risk and challenging medical decisions. The BRCA1/2 literature suggests that uncertain genetic risk associated with (VUS) or uninformative genetic test result can negatively influence one’s psychological response and uptake of risk reduction options. This study aimed to explore the psychological functioning and cancer prevention decisions of women who have undergone multi-gene panel testing for HBOC susceptibility. METHODS: This multi-center, cross-sectional survey study explored the psychological distress levels and uptake of cancer risk reduction options amongst women who underwent multi-gene panel testing for HBOC susceptibility within the previous 24 months. RESULTS: In the multi-variate model, women with a pathogenic variant (PV) (p<0.001) or VUS (p=0.007) had significantly higher levels of genetic testing-related distress compared to women with a negative result. Levels of cancer-related distress were not statistically different based upon variant pathogenicity (PV, VUS or negative result). Women with a PV in moderate penetrance gene had significantly higher levels of genetic testing-related distress compared to women with a PV in a high-risk gene (p=0.03). After undergoing panel genetic testing, 15 (5.1%) women underwent risk reduction surgery, including prophylactic bilateral mastectomy (PBM) and prophylactic bilateral salpingo-oophorectomy (PBSO). No women in our study reported current or prior use of chemoprevention. Conclusions: The findings from this thesis demonstrate the importance of evaluating psychological outcomes based upon both variant pathogenicity (PV, VUS and negative result) and gene penetrance, such that subgroups of women at risk of long-term psychological distress are identified and receive the appropriate informational and psychosocial support. Our findings are also clinically reassuring as uptake of risk reduction options largely aligned with current clinical recommendations.
Exploring Reminiscence in Multimodal Digital Spaces
Keywords: Domestic Technology
Human-Computer Interaction
Reminiscence

Oral storytelling is an ancient practice vital to our collective and individual well-being and a primary form of reminiscence. Modern reminiscence is often mediated by memory prompts, especially family or personal pictures. New technologies, like social networking sites, have brought picture access and interactions to a scale and scope not possible in analog settings. However, familiar activities like in-person reminiscence are being overlooked digitally for these novel options. Because of this, there is less space for casual, small-scale sharing of narrative from pictures, especially for families and across different generations. In my thesis, I reveal new understandings of digital picture interactions that outline current social and technical factors that are limiting reminiscence. I present alternatives to current digital norms that actively encourage social narrative experiences. This is supported by human-centred research that amplifies the voices of families.I further explore the novel opportunities offered by digital spaces that have the potential to expand on what is currently possible with reminiscence. I demonstrate the need for multimodal narrative experiences in order for reminiscence to be fully included in digital spaces. I present methods of supporting casual speech showing that these multimodal interactions are feasible now and necessary to experiences of reminiscence. The majority of pictures are now only available in digital settings. As the primary form of memory prompt, digital pictures must be accompanied by digital reminiscence. Access to these narrative activities fosters families’ social connections. I show how to support digitally-mediated narrative experiences based in detailed understandings of current social and technical factors and in the broad potential offered by the digital setting.
The Landscape of Eukaryotic Microbiota in the Gut Microbiome and their Impact on Bacterial Communities and Host Health
Keywords: amplicon sequencing
human health
malnutrition
microbiome
parasite
protozoa

Microbial communities in the human gut are significant modulators of health and disease. Studies based on deep sequencing of target genetic regions have profiled the dynamics of bacterial and fungal populations and established causal relationships with numerous disease states. The lack of similar methods suitable for profiling gut-dwelling protozoa, an enormously diverse group of organisms of considerable importance to global health, has meant that their prevalence and role in the human microbiome have remained for the most part a mystery. Studies of protozoa have thus far largely been limited to important diarrheagenic pathogens known to contribute to malnutrition and incur morbidity and mortality in millions worldwide. A number of commensal species, however, identified in healthy individuals have also been linked to inflammation and colitis in isolated cases. The ability of all to cause asymptomatic colonizations in the majority of people and symptoms in few raises questions about factors mediating their virulence. Evidence has shown that resident bacteria can influence the outcomes of protozoan infections, and vice versa, suggesting complex cross-kingdom interactions with potential impact on the host. This thesis describes a series of studies aimed at characterizing the contribution of intestinal protozoa to health and broadening our understanding of the microbiome. The first study established a sequencing-based approach for profiling of eukaryotic microbiota and demonstrated its utility in characterizing protozoa in the gut of malnourished populations. Applying this methodology to both healthy and malnourished children, the second study revealed a high carriage of diverse eukaryotes in the first two years of life, and associated considerable differences in protozoan populations with gut bacterial composition, nutritional interventions and geographic locality. The final study, using genomic and gene expression experiments, characterized the activities of one specific gut protozoan in a mouse model of colonization, and its ability to reshape the resident bacterial communities in healthy and immunocompromised hosts. The synthesis of these findings presents protozoa as key players of a complex microbial system, whose capacity to modulate the gut environment can have significant implications for host health and intestinal diseases.
Values and Social Transformation in the Design of the Decentralized Web
Keywords: alternatives
commoning
decentralization
decentralized web
values and design

This dissertation studies the wave of interest in “decentralization” over the last decade led by a loose group of technical subcultures and communities building new computing and networking technologies. While technical decentralization has a long history, this recent interest extends the concept with claims of its central role in radical social transformations. Its proponents often offer sophisticated assessments of the issues facing the web and internet today, yet frequently propose fundamentally different solutions than those envisioned by scholars and other activists. The purpose of this dissertation is to investigate the social worlds in which decentralization has emerged as well as the interplay between values and socio-technical imaginaries accompanying it within some decentralizing technologies. In three articles, this dissertation characterizes technical decentralization and the forces within current interest in it. It uses an autoethnographic approach and collective reflection to report on two projects using decentralized technologies to build alternatives to existing data stewardship and publishing infrastructures. This dissertation situates those projects within the “DWeb” community and growing “Web3” movement through interviews and analysis of public talks and writing from organizations advocating decentralization. This dissertation highlights how decentralization as a concept remains ambivalent. It traces how proponents draw on the concept’s historical dimensions to develop distinct values and articulate visions of the future. It examines what is being decentralized and how within the data stewardship project, reports on the decentralized publishing software modelling values and principles, and provides sensitizing concepts for technical decentralization drawn from its broader historical and political context. Decentralization remains elusive throughout. The dissertation ends looking back at these explorations and asking whether decentralization is a concept worth claiming in the fight for a better internet.
Electronic Transport in Mixed-dimensional van der Waals Heterostructures
Keywords: 2D material
CdSe
Mixed-dimensional
MoSe2
Nanowire
van der Waals heterostructure

Recently, graphene and other 2D materials have been integrated into van der Waals (vdW) heterostructures in which surfaces free of dangling bonds interact through vdWforces. Since this is not limited to interplanar interactions, mixed-dimensional vdW heterostructures have emerged in which 2D materials are combined with 0D, 1D and 3D materials. 1D/2D semiconductorheterostructures are particularly interesting due to constrained carrier transport and weak screening effects in nanowires, as well as strong quantization in 2D materials. The primary objective of this thesis was to characterize electronic transport in a 1D/2D vdW heterostructure of a cadmium selenide (CdSe) nanowire and molybdenum diselenide (MoSe2) flake. Nanowires were synthesized through vapour phase deposition, after which flakes were isolated through mechanical exfoliation. The electrical properties of each nanostructure were investigated through the fabrication of field-effect transistors via lithography. A CdSe/MoSe2 heterostructure was fabricated via dropcasting, and it is believed to be the first report of such a heterostructure created through this technique. Temperature-dependent electrical measurements of the heterostructure showed unusual behaviour. In the transfer curves, an extremely large positive shift in the threshold voltage was attributed to significant levels of electron trapping at the MoSe2/SiO2 interface of the device. The interface trap energy and density were estimated to be 73.5 meV and 1.3 x 10^13 cm^−2 eV^−1, respectively. The minority carrier lifetime at very low temperatures was found to be about 4.8 x 10^4 seconds, producing a gain on the order of 10^7. It was determined that the Schottky barrier height at the CdSe/metal contact decreased monotonically with temperature due to inhomogeneities at the junction, and that with a large gate voltage, this mechanism is responsible for currents greater at very low temperatures than at room temperature. A computational model was created to better understand the device. Simulations showed that a deviation from linearity in many of the output curves is due to the large Schottky barriers. They also show that it does not completely disappear unless both barriers decrease. Comparing these results to the low-temperature output curves suggests that the barrier height at the MoSe2/metal contact also decreases with temperature.
The Benefits and Pitfalls of Virtual Primary Care for Patients with Intellectual and Developmental Disabilities
Keywords: COVID-19
Developmental disability
Intellectual disability
Primary care
Qualitative
Virtual care

The COVID-19 pandemic led to an abrupt and unprecedented increase in the delivery of virtual primary health care. Adults with intellectual and developmental disabilities (IDD) have complex health care needs and little is known about the value and appropriateness of virtual care for this patient population. The aim of this dissertation was to learn about the impact of virtual care delivery on access and quality of primary care for patients with IDD. This dissertation included 3 studies. Study 1 was a scoping review of the prior literature on virtual health care for adults IDD. Twenty-two studies were identified that met inclusion criteria, of which 12 reported findings on access to care. Participants generally reported high acceptability of virtual care and results on effectiveness were positive, though conclusions were limited by small sample sizes. Challenges identified included internet quality and technical skill. Studies 2 and 3 used a qualitative approach to explore multiple perspectives on virtual primary care for adults with IDD in Ontario during the pandemic. Semi-structured interviews were conducted with 38 participants including: 11 adults with IDD, 13 family caregivers, 5 support staff and 9 primary care physicians. Study 2 used Levesque’s access to care framework as an organizing structure to synthesize themes related to access to care. An overarching finding was that accessibility needs are not static and vary according to patient characteristics, patient context, caregiver characteristics, the service context, and the reason for a particular primary care visit. Study 3 explored the impact of virtual care on patient-provider communication. Four elements of communication were identified that were impacted by virtual care: (1) the ability to hear other participants and have the time and space to speak; (2) use of nonverbal communication; (3) the ability to form trusting relationships; and (4) patient engagement in the virtual appointment. This dissertation supports the need for a flexible patient-driven approach to primary care that includes in-person, phone and video options. This approach must be supported by the appropriate infrastructure, resources and incentives to ensure that the potential benefits of virtual care can be fully realized for all patients.
Molecular Basis and Design of B Cell Targeting Therapeutics
Keywords: Antibody
B cells
CD22
Ferritin
Protein-based nanoparticle

Therapeutic antibodies are powerful and versatile tools across indications. Their success in the clinic, and the rapid rate at which therapeutic antibodies are entering the clinical trials highlight just the beginning of the potential that antibodies have as therapeutics. In this thesis, the molecular details of the B cell co-receptor, CD22, is investigated and how it is targeted by therapeutic antibody, epratuzumab, in a glycan-dependant fashion is elucidated. This thesis also highlights two applications of protein-based nanocages as a multimerization platform for antibody fragments. Ferritin, lumazine synthase, encapsulin, and E2p nanocages are explored for their ability to display high density, functional Fabs and Fc on their surfaces for improved valency, avidity, and potency of therapeutic antibody fragments, towards the goal of producing a next-generation multi-valent, multi-specific antibody modality. This antibody-display platform is subsequently leveraged for the co-display of HIV antigens and B cell-engaging antibodies as a novel immuno-modulatory HIV vaccine platform to modulate the immune responses elicited following immunization. The results discussed within this thesis illustrate the versatility and un-tapped potential for the molecular engineering of therapeutic antibodies as both a treatment and prevention modality.
New Prescription Opioid Use and Risks of Adverse Events in Ontario, Canada
Keywords: Observational Methods
Opioid-Related Harms
Opioids
Pharmacoepidemiology

Prescription opioids are an effective option to manage pain, but their role in clinical practice is complex due to their association with numerous potentially serious adverse events. The aim of this thesis was to assess the risk of opioid-related adverse events in three situations that cannot be easily examined using a randomized controlled trials in order to provide clinicians with additional guidance when considering this medication for their patients. This thesis included three population-based observational studies conducted using administrative data on individuals in Ontario, Canada who recently started prescription opioid therapy. Study one assessed the risk of motor vehicle collisions (MVC) among drivers starting prescription opioids compared to drivers starting prescription non-steroidal anti-inflammatory drugs (NSAIDs). There was no significant difference between exposure groups but the collision rates in both were higher than that for the general population, suggesting that pain may be a contributor to MVCs. The second study examined falls risk among older adults starting prescription opioids compared to prescription NSAIDs, at varying levels of concurrent central nervous system depressant burden. Those receiving opioids had a significantly higher risk of falling than those receiving NSAIDs regardless of the level of concurrent central nervous system depressant burden. Finally, the third study examined the risk of opioid toxicity, dose escalation, and new opioid use disorder (OUD) among adults with intellectual and developmental disabilities (IDD) compared to adults without IDD. Those with IDD had a significantly higher risk of opioid toxicity and OUD but a lower risk of dose escalation than those without in the unmatched analysis. However, these differences in risk were no longer significant once baseline differences in exposure groups were balanced through matching, suggesting that the IDD population is at a higher risk of opioid-related harms but this risk is not imposed by the IDD diagnosis. Rather, it is due to a clustering of known risk factors for opioid-related harms that are often present in the IDD population. Collectively, these results can be added to the evidence currently available to support clinicians and patients in their discussions to achieve safe and effective pain management.
The Clustered Protocadherins in the Form and Function of Cerebellar Purkinje Cells
Keywords: cerebellum
clustered Protocadherins
intrinsic firing
Kcnc3 Kv3.3 channels potassium voltage-gated channel subfamily C member 3
Purkinje neurons

The cerebellum is a brain region that regulates the control of movement. It also participates in non-motor functions, such as social and repetitive behaviours. At the heart of the cerebellar circuitry are the Purkinje cells (PCs). These neurons provide the sole exit of neural information from the cerebellar cortex. PCs possess distinguishing features: 1) their exuberant dendrites are uniformly distributed with minimal self-overlap through a process called dendrite self-avoidance; 2) they fire intrinsically at regular and high-frequency intervals even without synaptic input. PCs prominently express the clustered Protocadherins (cPCDHS), a group of cell surface recognition molecules. They are encoded by 58 genes, divided into three clusters: α-Pcdh (Pcdha), β-Pcdh (Pcdhb), and γ-Pcdh (Pcdhg). Previously, we showed that PCDHGs regulate PC dendrite self-avoidance (Lefebvre et al., 2012). However, the roles of the other clusters in PC self-avoidance and overall, the cPCDHs’ roles in PC function have not been elucidated. Here, I investigated the functional interactions between the Pcdha and Pcdhg clusters in PC dendrite self-avoidance, as well as their roles in PC firing and behavioural output. My PC self-avoidance analysis demonstrated that the loss of Pcdhas leads to defects of similar severity to loss of Pcdhgs, suggesting that both clusters are equally required. Dendrite self-crossing defects were exacerbated in Pcdha; Pcdhg double mutant PCs compared to single mutants, revealing partial redundancy. Developmental PCs lacking Pcdhgs displayed increased dendrite density and malformed filopodia, suggesting deficits in filopodia retraction lead to self-avoidance defects. The cPcdhs also influenced PC functions. Mouse mutants harboring a PC-specific deletion of Pcdhgs, with or without an additional global Pcdha heterozygous deletion, displayed motor impairments on the rotarod and in their gait. Non-motor functions were spared. Motor deficits were accompanied by dysfunctional PC firing properties. Mutant PCs exhibited lower intrinsic firing rates and excitability with elevated potassium currents, possibly resulting from Kv3.3 channel disinhibition. In CHO cells, a PCDHG isoform physically interacted with Kv3.3 channels, revealing a potential mechanism for cPCDH inhibition of Kv3.3 channels. My work is the first to show that the cPCDH clusters cooperate in PC dendrite self-avoidance, and that the cPCDHs can regulate the firing properties of a neuron, as well as PC-specific behavioural output.
Cultural Socialization Among Chinese Parents in Canada and the United States: Role of Racism, Co-ethnic Social Capital, and Regional-level Characteristics
Keywords: Chinese
Cultural socialization
Ecological
Neighbourhood
Racism
Social capital

Cultural socialization refers to the parenting practices that promote children’s ethnic pride and transmit cultural messages, customs, and traditions. It has been found to be beneficial to cultural minority children and adolescents in terms of their mental health, cognitive development, and identity development. Understanding the factors associated with parental cultural socialization can inform direct services and tailor program designs. However, there is a lack of literature about cultural socialization among Chinese parents who live in Canada and the United States, particularly the relationship between broader social factors and their behaviours. Using an ecological approach, supplemented by social dominance theory and theories of social capital, this dissertation studies the role of social factors, namely experiences with racism, co-ethnic social capital, and regional-level characteristics, in Chinese Canadian and Chinese American parents’ cultural socialization. This dissertation consists of an introduction, three distinct research papers, and a conclusion. All three papers present the findings of an online cross-sectional survey study with Chinese Canadian and Chinese American parents (n=478). Paper one explores the interconnection among parents’ experiences with acute, everyday, and internalized racism and their cultural socialization practices. Paper two examines the role of offline and online co-ethnic social capital (i.e., cultural resources from co-ethnic networks) in cultural socialization. Paper three investigates the interrelationship between three regional-level factors, including ethnic density, ethnic diversity, and regional socioeconomic status, and individual-level factors, namely internalized racism and cultural socialization. This dissertation fills the knowledge gap by providing insight into how social environments may affect cultural socialization through parents’ appraisal and sense-making of their social experiences. The significant role of internalized racism found in this study, along with the unique nature of anti-Asian racism, demonstrate the need for social workers and parenting services to address racial and cultural hierarchies, internalized social scripts, and the subtle and chronic forms of racism experienced by Chinese in Canada and the United States. The dissertation also points out the need to encourage co-ethnic bonds and the development of local ethnic communities. Implications for social work practices and future research are discussed.