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The impact of frailty on clinical outcomes among individuals with COPD: a systematic review and meta-analysis
No full textAbstract Background Frailty is a prevalent and robust predictor of poor outcomes for older adults and those with chronic disease. We performed a systematic review and meta-analysis of the literature to understand the association between frailty and clinical outcomes for people with COPD. Methods We searched MEDLINE, EMBASE, Cochrane Central, CINAHL, and Web of Science from inception to February 2022, for observational studies evaluating the association between frailty and clinical outcomes among individuals with COPD. Included studies defined COPD by spirometry, used a validated frailty assessment tool, and compared dyspnea, symptom burden, health related quality of life, exacerbations, hospitalization, or mortality between frail and non-frail individuals. Risk of bias was assessed using the Newcastle Ottawa Scale. Mean differences or hazard ratios were calculated using inverse variance (IV) methods, odds ratios were calculated using Mantel–Haenszel methods, and homogeneity was assessed using I 2 statistics. Results were pooled using a random effects model. Results Of 1385 identified studies, 16 studies were included with 7 studies included in the meta-analyses, representing 5903 individuals. The Fried Frailty Phenotype instrument was used in 50% of included studies. When comparing frail vs. non-frail people with COPD, pooled estimates revealed frail people with COPD had higher dyspnea scores [modified Medical Research Council (mMRC) score standardized mean difference (95% CI): 1.67 (1.40–1.92), I 2 = 24%]; higher symptom burden [COPD Assessment Test (CAT) score mean difference (95% CI): 10.24 (8.30–12.17), I 2 = 31%]; more COPD exacerbations in the prior year [mean difference (95% CI): 1.09 (0.62–1.56), I 2 = 0%), and increased odds of being hospitalized in the previous year [OR (95% CI): 2.94 (1.57–5.50); I 2 = 0%]. The largest study with longest follow up period showed increased mortality risk among frail vs. non-frail individuals with COPD, [HR (95% CI): 1.83 (1.24–2.68)]. Conclusions People with COPD and frailty experience increased dyspnea, symptom burden, exacerbation history, and hospitalizations compared to non-frail patients with COPD. Frailty is a robust predictor of outcomes among people with COPD and should be considered a treatable trait. Additional work is needed to standardize screening methods for frailty, and to understand the optimal timing of non-pharmacologic interventions to treat frailty among people with COPD. Prospero Registry ID CRD4202232989
Wrong-site, wrong-procedure, and retained foreign object events in out-of-hospital settings: analysis of closed medico-legal complaints in Canada (2012–2021)
No full textAbstract Background Surgical sentinel events (SSEs) are serious safety incidents associated with significant patient harm and medico-legal consequences for healthcare teams and institutions. SSEs include wrong-site surgeries, wrong procedures, and unintentional retention of foreign objects. SSEs occur in hospitals and out-of-hospital operating spaces (physician offices or ambulatory surgical centres). It is unclear how the resource constraints and workflow differences of an out-of-hospital setting contribute to SSEs. Methods We conducted a retrospective review and descriptive content analysis of all out-of-hospital SSEs reported to the Canadian Medical Protective Association (CMPA) between 2012 and 2021. Medico-legal files, medical records, and peer expert opinions were analyzed to identify the contributing factors to out-of-hospital wrong-site, wrong-procedure, and retained-object SSEs. Results A total of 276 medico-legal complaints involved a wrong-site, wrong-procedure or retained-object SSE, of which 24 (24/276; 9%) occurred out of hospital. Only twenty of these out-of-hospital complaints were included in the qualitative content analysis. We identified five main contributing factor categories to out-of-hospital SSEs. These categories included (1) incomplete preoperative verification, (2) inadequate intraoperative surgical counts, (3) insufficient review of patient medical records, (4) surgery performed without the necessary resources, and (5) administrative errors or office disorganization. Half of the complaints were assigned more than one contributing factor. The majority of out-of-hospital SSEs (19/20; 95%) resulted in an unfavourable outcome for the operating physician and most (18/20; 90%) required additional healthcare resources to resolve or mitigate the consequences of the SSE. Conclusions Recognizing the contributing factors to an out-of-hospital SSE enables targeted improvements in facility protocols to support patient safety. Some factors identified in this dataset overlap with hospital-based contributing factors previously identified in literature (incomplete preoperative verification and inadequate surgical counts), whereas other novel factors are associated with the practice environment of an out-of-hospital setting (resource constraints, office disorganization). Addressing the identified contributing factors may mitigate the risk of SSEs in all facilities
Cross-Domain Latent Conditioning for Coherent Generative Synthesis
No full textGenerative models have revolutionized synthesis research, enabling machines to produce images and text that rival human-created content. However, challenges in controllability, diversity, and coherence limit their application. This thesis investigates generative models with applications to multiple domains: texture synthesis, texture concept blending using vision-language model latent spaces, and language generation for procedural dialogue in computer role-playing games.
In texture synthesis, the thesis introduces a novel method for generating diverse, high-quality non-homogeneous textures from a single exemplar. The approach combines a Generative Adversarial Network (GAN) and a Variational Autoencoder within a unified architecture, that uses custom layers to share information during training. This method also presents a similarity loss term that promotes output diversity while enhancing quality. The architecture enables rapid training, producing superior results in less time when compared to state-of-the-art techniques.
The challenges of texture synthesis extend into the text domain, where describing complex textures is often difficult. This inspired the hypothesis that vision-language models, such as Contrastive Language-Image Pretraining (CLIP), might encode spatial information that could enable latent exploration, akin to GAN latent space traversal. To explore this, the thesis introduces a novel pipeline for constructing latent manifolds from a texture dataset that uses the CLIP model. This pipeline enables spatially optimized interpolation between user-selected inputs, for the generation of coherent and novel blends of visual concepts that are challenging to describe with text prompts.
Finally, using text synthesis for procedural dialogue generation, the thesis presents a structured framework that overcomes the limitations of traditional parser-based systems by integrating Large Language Models (LLMs) with a graph-based state tracking approach for use in computer role playing games. This approach frames interactions as puzzles with goal-based milestones to enforce narrative progression. The method empowers designers to craft abstract rules that enable players to invent solutions rather than adhere to predefined paths. A proof-of-concept game demonstrates how this system realistically enhances player freedom, validated through both qualitative and quantitative analysis. This method represents a move towards the long-standing goal of improving player agency in games
Intelligent Inside Threat Detection Framework Based on Digital Twin, Transformer Variant Models, and Transfer Learning
No full textWith the rise of networked systems and modern hacker techniques, insider threats have become a greater concern than external hackers, as they often cause more significant damage and are harder to detect due to authorized access, complex behaviors, data imbalances, and a lack of explainability. To address these challenges, we proposed DTITD, a centralized learning framework that combines Digital Twin (DT) technology and transformer models. DTITD tackles data imbalance by utilizing contextual embeddings from pre-trained Large Language Models (LLMs), and it provides insights into user behavior through Digital Twin analysis, enhancing detection explainability. Extensive experiments on CERT r4.2 (dense) and CERT r6.2 (sparse) datasets show that DistilledTrans, a customized transformer model, outperforms baseline models in accuracy, precision, recall, F1-score, and AUC, while being computationally efficient. To overcome challenges like data privacy and resource costs, we introduced FedITD, a Federated Parameter-Efficient Tuning (PETuning) framework with Federated Learning (FL) and Transfer Learning. This framework allows for decentralized model learning without data transmission, safeguarding privacy and reducing resource costs. Combining DTITD and FedITD provides a highly accurate, efficient, and privacy-preserving solution for insider threat detection at an enterprise level
Investigating a Protective Role for Parkin Downstream of Dopamine Stress in In-Vitro Cell Models
No full textParkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the Substantia nigra pars compacta (SNc), a region particularly vulnerable to dopamine (DA) metabolite toxicity and oxidative stress. Mutations in the PRKN gene, which encodes parkin, an E3 ubiquitin ligase thought to be important for mitophagy, underlie what is known as autosomal recessive, early-onset PD (EOPD). In parkin-linked PD, the loss of DA-producing neurons is relatively selective for SNc and Locus coeruleus (LC) neurons, highlighting parkin's crucial role in protecting them. Recent studies from our lab have shown that parkin also plays an antioxidant role, protecting DA-producing neurons from oxidative damage by reducing reactive oxygen species (ROS) and sequestering DA-derived radicals. This protective action leads to parkin's own oxidation and subsequent insolubility. Notably, this shift to an insoluble state has been shown to impair parkin's E3 ligase function, suggesting that parkin's protective role under oxidative stress conditions may be independent of its role in mitophagy. Furthermore, in normal human brain, parkin has been found to associate with neuromelanin (NM), a pigment formed in catecholaminergic neurons via the sequestration of toxic DA radicals, as well as with CD63-positive lysosomal vesicles, suggesting a role for parkin in lysosomal pathways that mitigate cellular damage.
In this study, I aimed to investigate how DA-induced cellular stress affects parkin's oxidation, solubility, and localization within the cell, with a particular interest in its interaction with NM and CD63. To explore this, I used two models of DA-linked stress. The first model involved the direct addition of DA to the culture medium to simulate oxidative stress from DA auto-oxidation. The second model utilized tyrosinase cDNA transfection in M17 neuroblastoma cells to drive intracellular melanin synthesis, creating a controlled system for examining parkin's interactions with melanin. There, melanin synthesis arises from the formation of DA oxidation products via tyrosinase activity. My results showed that DA treatment led to partial oxidation and insolubilization of parkin, particularly when the antioxidant glutathione was depleted by using buthionine sulfoximine (BSO), which exacerbates oxidative stress. These modifications were not associated with any visible co-localization by wild-type (WT) parkin with CD63 in M17 cells or microscopically visible aggregate formation. Unexpectedly, parkin remained dispersed throughout the cell post DA-treatment. In the tyrosinase model, parkin did not undergo any significant changes in oxidation or solubility with increasing melanin accumulation, nor did parkin visibly co-localize with melanin granules. However, cells expressing parkin showed accelerated melanin formation compared to those without.
Overall, this study explored the behavior of parkin under DA-induced stress conditions in an undifferentiated, human M17 neuroblastoma cell culture system. While parkin does undergo oxidative changes, these results suggested that the extent of these changes - along with parkin's solubility and localization - are highly dependent on the chosen cell model and experimental conditions employed. The cellular environment, as determined by factors, such as the capacity to neutralize endogenous as well as exogenously added DA metabolites, likely plays a role in shaping parkin's response to stress. These findings emphasize the need for further investigation into how parkin behaves in different neural models to better understand its role in protecting dopaminergic neurons, particularly in the context of brain ageing, which will likely inform the pathogenesis of EOPD, and possibly of sporadic PD
Le parrainage collectif des personnes réfugiées au Québec : Entre solidarité et (re)production des inégalités
No full textCette thèse explore la complexité des expériences vécues dans le cadre du parrainage collectif de personnes réfugiées, en s’attardant particulièrement aux relations entre les parrainants et les personnes parrainées dans le contexte du Programme de parrainage collectif des personnes réfugiées au Québec (PPCR). Celle-ci propose de s’éloigner des cadres traditionnels qui évaluent la réussite du parrainage à travers le prisme de l’autonomie des personnes parrainées et mobilise des perspectives féministes et postcoloniales pour interroger les structures formelles et informelles qui sous-tendent l’asymétrie des relations parrainants-parrainé-e-s. Le concept de cointégration est développé pour comprendre ces déséquilibres de pouvoir et redéfinir les critères de réussite du parrainage en mettant l’accent sur l’atteinte de relations équilibrées entre les parrainants et les parrainé-e-s. À partir de données qualitatives issues de 35 entretiens individuels et d’un groupe de discussion avec des parrainé-e-s, les résultats montrent que, selon les paramètres actuels du PPCR, les relations entre parrainants et parrainé-e-s sont plus susceptibles de rester inégalitaires que de s’équilibrer au cours du parrainage. Ces dynamiques sont particulièrement exacerbées dans les parrainages réalisés entre inconnu-e-s, où les hiérarchies sociales et raciales préexistantes sont reproduites et peuvent mener à des dynamiques oppressives.
L’analyse des données est structurée en quatre chapitres. Le premier, explore les facteurs contextuels propres au Canada et au Québec et démontre que le programme de parrainage ne se contente pas de s’inscrire dans un cadre déjà structuré par des hiérarchies sociales et raciales, mais qu’il participe également à leur (re)production et à leur légitimation. Ces hiérarchies sont inscrites dans des schèmes de pensée qui influencent structurellement les perceptions et les rôles des participant-e-s et qui limitent l’émergence de contre-discours susceptibles de remettre en question les dynamiques de pouvoir dominantes. Le deuxième chapitre analyse l’architecture institutionnelle du programme de parrainage collectif, révélant comment celle-ci peut renforcer les asymétries de pouvoir. Les pouvoirs et les responsabilités accordés aux parrainants par l’État leur confèrent une position de contrôle et cantonne les personnes parrainées dans un rôle de bénéficiaires passifs. De plus, le manque de soutien et de formation adaptées laisse les personnes impliquées mal préparées à naviguer les tensions inhérentes aux expériences de parrainage qui demeurent des initiatives d’aide profondément complexes. Le troisième chapitre mobilise un cadre analytique inspiré des quatre phases de l’éthique du care selon Berenice Fisher et Joan Tronto (1990) pour analyser en profondeur les dynamiques documentées. Ce cadre met en lumière comment les interprétations des besoins des parrainé-e-s par les parrainants reflètent souvent des normes culturelles hégémoniques, marginalisant ainsi les besoins sociaux et renforçant une relation de dépendance. L’étude met également en évidence une participation limitée des parrainé-e-s aux décisions les concernant, ce qui constitue un déni de leur agentivité et peut s’expliquer par le paternalisme et la posture de sauveur qu’adoptent certains parrainants. L'analyse met en évidence un contraste dans la réceptivité entre les personnes parrainées par des inconnu-e-s et celles parrainées par des proches : les premières déclarent généralement une satisfaction moindre quant au soutien reçu, comparativement aux secondes. Cette différence peut être influencée par les attentes préalables concernant le type de soutien qui sera fourni, ainsi que par la racialisation différenciée des parrainants et des parrainé-e-s, qui affecte davantage le degré de réceptivité. Par ailleurs, les attentes implicites de gratitude de la part des personnes parrainées perpétuent une forme de domination symbolique profondément ancrée dans ces relations. Le dernier chapitre examine le parrainage à titre d’initiative se situant au croisement de la solidarité et de la charité. Il est démontré que lorsque l’expérience de parrainage s’apparente à un acte de charité, elle tend à perpétuer des relations inégalitaires, limitant ainsi son potentiel transformateur. À l’inverse, une approche fondée sur la solidarité met l’accent sur la réciprocité, les bénéfices mutuels et la responsabilité partagée, essentiels pour atteindre une véritable cointégration. Cependant, les parrainages qui s’apparentent à une solidarité exempte de relations de pouvoir sont rares dans la pratique en raison de barrières normatives et institutionnelles. En conclusion, la thèse propose des recommandations pour réorienter le PPCR afin que celui-ci puisse devenir un levier de la cointégration entre les parrainants et les parrainé-e-s favorisant des relations intergroupes véritablement solidaires
Equity, Diversity, and Inclusion in Canadian National Sport Organizations
No full textThe purpose of this thesis was to assess the Canadian National Sport Organization (NSO) landscape through developing a graph that measures equity, diversity, and inclusion (EDI) engagement and consistency and to further understand how EDI could be embedded within an organization's culture through a Management by Values (MBV) approach. To achieve this purpose, a phased exploratory sequential mixed-methods approach was used. In study one, website and supporting document information from 16 NSOs were gathered and analyzed. NSOs were strategically chosen to ensure a diverse sample. The information was used to graph EDI engagement (e.g., providing an EDI policy and statement) and consistency (e.g., NSOs' presence of EDI engagement on the website and downloadable as supporting documentation). The information was also used to understand how the terms EDI were being used by leaders of NSOs. Results uncovered that the terms EDI were being used to develop human resources management and organizational culture, to create opportunities for diverse participation in sport, and to eliminate barriers. From the graphed EDI engagement and consistency and developed themes, it appeared that NSOs are espousing EDI. However, inconsistencies were found between NSOs' websites and their supporting documentation when EDI engagement and consistency was graphed.
Next, study two was conducted to broaden upon these findings. The Diversity Engagement Survey (DES) was used to determine how engaged and included NSO full-time (FT) paid staff and members of the boards of directors (MOBs) are in their NSO's approach to being equitable diverse, and inclusive. As well, the existence of a leaky pipeline (LP; the process of leaving an organization due to structural and internal barriers, limiting advancement of a sport industry career) in NSOs was investigated. The data from participants who were at risk of the LP (0-5 years in their role) and the data of their disclosure of equity-owed intersecting identities were analyzed separately in the data analysis process. The Diversity Engagement Survey (DES) was adapted to the sport context and distributed to FT paid staff and MOBs of 64 Canadian NSOs (N = 117 surveys completed). Included in the survey were open-ended questions that were designed to provide additional context to the responses of the DES on the element of belonging being connected to understand the LP in NSOs. To ensure validity and reliability of the DES, an exploratory factor analysis (EFA) was conducted. Men and women agreed on the three factors maintained from the EFA: organization's culture operating diversity, inclusion of employees in strategic direction, and equitable organizational practices. Specifically, this pertains to the ability to work with diverse groups, alignment of the NSO's mission, vision, and values, and the NSO's commitment to equitable organizational practices. Additionally, the open-ended question responses highlighted that NSO FT paid staff and MOBs felt they belonged in their organization when they were connected to the organization, and when the organization's culture was inclusive. Furthermore, findings showed that FT paid staff and MOBs were more likely to leave their position within their NSO due to personal reasons, organizational related processes, and the culture of the organization itself. People who had equity-owed intersecting identities (i.e., participants who identified as women, women of diverse races, and women who experience a disability) also experienced additional barriers that resulted in their intention to leave.
The final study of this thesis was then conducted with the aim to further investigate what FT paid staff and MOBs felt their NSO needed to support underrepresented employees. To accomplish this, 19 interviews were conducted with nine FT paid staff and ten MOBs. Participation from women and people who identified as an underrepresented group was prioritized in this phase while also incorporating people who identified as men. Participants stated that to support underrepresented employees and develop a culture that incorporates the values of EDI, NSOs require the following: (1) an EDI resource centre, (2) assistance to strategically invest in EDI, and (3) a values-based approach. Differences between FT paid staff and MOBs were also investigated in this study. During the data analysis the only difference found was when participants discussed the NSO's cultures. MOBs did not feel they knew what the culture was like in the day-to-day activities of the NSO. NSO FT paid staff and MOBs called upon additional support and assistance from stakeholders (e.g., Sport Canada) to support underrepresented employees. In this same study, the 4-I Values Framework (4-I VF) was considered. This framework helps to determine how informed leader's practices are by their organization's values. The 4-I VF has four stages (i.e., inactive, intuitive, institutional, and inspirational) that NSOs can work through, and the use of this framework can help determine how strategically leveraged values (i.e., EDI) are in an organization. Through analyzing EDI as values in this thesis, it appears the values of EDI are leadership dependent (intuitive) and not always embedded within the organization's culture (inspirational). Although NSOs display a commitment to EDI through espousing EDI as values on their websites and in supporting documentation, the findings of this thesis suggest that to implement EDI as values within the NSO's culture, further support is needed
Repenser l’anorexie à travers un dialogue entre théories féministes critiques et savoir expérientiel des usager.e.s de soins
No full textCette thèse propose une perspective critique sur le traitement de l’anorexie, grâce à un dialogue entre personnes concernées et théories féministes critiques. Elle remet en question le paradigme biomédical, qui individualise et pathologise le trouble, ignorant les rapports de pouvoir et les violences institutionnelles qui le traversent. Fondée sur sept entretiens semidirectifs avec des femmes et personnes non-binaires au Canada et en Suisse ayant un vécu du trouble, la recherche montre comment les personnes concernées reconfigurent le soin et la « guérison ». Les analyses révèlent la stigmatisation des corps « illisibles » comme anorexiques, la violence des pratiques institutionnelles, tout en explorant des stratégies de résistance et des formes de soutien alternatives. En somme, la thèse propose une politisation de l'anorexie, l'envisageant comme un lieu de résistance et de savoirs situés
Analysing comfort with primary care discussions and openness to social prescribing as mediators of the associations between loneliness and wellbeing among Canadians aged 55 and older
No full textAbstract Background Addressing the complex health and wellbeing challenges of older adults is a critical public health priority as populations age. Social Prescribing (SP) represents a promising strategy, connecting patients to non-clinical, community-based resources to enhance physical, mental, and social wellbeing. Methods To develop a SP theory of change, this study used cross-sectional data from 2,450 community-dwelling older adults who participated in a population survey. Factor analyses identified four factors of comfort with primary care discussions (general, mental, physical, and social wellness) and three factors of openness to SP (effectiveness, meaningfulness, and supportiveness). Path analysis was conducted for each set of mediators separately. Results Path analyses revealed that comfort with primary care discussions about social wellness (β = 0.08**) is associated with better wellbeing. People who report social loneliness are most comfortable with primary care discussions about general wellness (β = − 0.17***) and least comfortable with primary care discussions about mental wellness (β = − 0.24***), whereas people who report emotional loneliness are more likely to have similar levels of comfort to discuss general wellness and mental wellness (β = − 0.18***; − 0.18***). In addition, social loneliness is associated with less comfort with primary care discussions about social wellness (β = − 0.19***) and mental wellness (β = − 0.19***), whereas association is not found for emotional loneliness. These suggest that addressing the SP needs of people who experience emotional loneliness requires a different strategy. Reporting emotional loneliness is associated with expressing support for SP (β = 0.14***), which may be key to improving wellbeing (β = 0.10***) among this population. Overall, social loneliness has a total effect size of βtotal = − 0.19, whereas emotional loneliness has a total effect size of βtotal = − 0.45, more than 2.3 times larger. Conclusions While SP may be acceptable to those who need it, some may experience greater difficulties accessing SP through primary care providers without interventions tailored to their loneliness status that could elicit buy-in and enrolment. Primary care providers may wish to pay closer attention to people with emotional loneliness. Other considerations, such as trust and motivational interviewing for positive self-beliefs may explain potential changes from loneliness to wellbeing
Public support of and attitudes toward decriminalization of possession of illegal drugs among the general population in British Columbia
No full textAbstract Background Decriminalization of possession of illegal drugs was implemented in British Columbia, Canada for a three-year period starting from January 31, 2023. As public sentiment played a large role in the outcome of a similar reform in Oregon, United States, it is important to examine the public’s perceptions of this policy. We examined public support of and attitudes toward decriminalization. Methods Data were from an online, non-probability, cross-sectional survey of adults who spoke English and resided in British Columbia (N = 1,202; March to April 2024). One item assessed support of decriminalization, and ten items assessed attitudes toward decriminalization. The analytical strategy involved descriptive statistics and multinomial logistic regression. Results In regards to support of decriminalization, 41% did not support decriminalization, 26% were neutral or not sure about supporting decriminalization and 33% supported decriminalization. The majority agreed that decriminalization will reduce criminalization of drugs (50%) and encourage drug use experimentation (53%). More agreed (44%) than disagreed (28%) that decriminalization made them feel less safe. The majority disagreed that decriminalization will reduce overdoses (55%) and drug-related crimes (50%). Older age was associated with an increased likelihood of not supporting decriminalization compared with being neutral or not sure about supporting decriminalization (OR [95% CI]: 1.97 [1.35 to 2.88] for 40 to 59 years old; 1.89 [1.19 to 3.02] for ≥ 60 years old), and female or another gender was associated with a decreased likelihood of supporting decriminalization compared with being neutral or not sure about supporting decriminalization (0.66 [0.47 to 0.91]). Conclusions Public support of decriminalization was not strong, which may be rooted in lack of robust confidence in decriminalization to achieve its goals and increased public safety concerns. These findings necessitate ongoing evaluations of the policy and increasing knowledge mobilization activities to keep the public abreast of the latest developments