39339 research outputs found
Sort by
What factors influence sexual and reproductive health care among adolescent and young adult cancer patients?: a novel serial focus group study
No full textAbstract Background Disparities in sexual and reproductive health care at diagnosis and during treatment for adolescent and young adult (AYA, ages 15–39) cancer patients may be linked to various factors, including those at the patient- and system-level. We conducted serial focus groups to explore how AYA cancer patients’ experiences with sexual and reproductive health and its care are influenced by their identities (patient factors) and contextual enablers (healthcare factors). Methods We recruited individuals aged ≥ 18 years, diagnosed with cancer as an AYA, and residing in Canada. Participants were grouped into cohorts based on identity factors (e.g., gender, cancer stage) with each cohort taking in three serial focus groups mimicking support groups (e.g., sharing information, fostering community). Patient research partners contributed to topic guide development and co-facilitated focus groups. We used framework analysis guided by the PROGRESS-Plus (Place of residence, Race/ethnicity/culture/language, Occupation, Gender, Religion, Education, Social capital, Socioeconomic status, and Plus) framework on health inequity factors and Andersen’s model of access to medical care. Results Altogether, 48 participants (age 33 (21–48)) were assigned into eight cohorts. Each cohort took part in three serial focus groups, resulting in a total of 24 focus groups. Among participants, there was representation based on gender (e.g., nonbinary and gender fluid, n = 4), non-heterosexual sexual orientation (n = 14), and race (n = 12). Themes indicate AYA cancer patients’ experiences with lack of sexual and reproductive health information and support, and lack of consideration of experiences and beliefs when providing sexual and reproductive health care. Findings reveal eight identity (patient-level) factors (place of residence, self-advocacy (occupation, education, and plus), socioeconomic status, social capital (plus), gender and sex, age (plus), relationship status (plus), sexual orientation (plus)) and two contextual enablers (health care system-level factors) (inefficiencies and interactions) that influence access to appropriate and available sexual and reproductive health care. Conclusion AYA cancer patients experiences with sexual and reproductive health care are influenced by their identity factors and contextual enablers. Treatment plans, research studies, and care programs should account for these to ensure that care is both inclusive and responsive to their unique needs
Design and Pilot Testing of a Resource to Assess Risk of Bias in Observational Studies Estimating Vaccine Effectiveness
No full textThis master’s thesis addressed three interrelated research objectives aimed at identifying gaps in the assessment of risk-of-bias (RoB) in observational studies of vaccine effectiveness (VE) and proposing a draft framework for evaluation in the next phases of an ongoing research project. First, I mapped existing RoB tools used in systematic reviews of VE studies (Chapter II). The findings revealed that although RoB assessments are routinely conducted, there is considerable variation in the choice of tools used and their application, many of which were not specifically designed to address VE-related biases. Second, I identified and synthesized key bias concepts relevant to VE estimation and created a framework (Chapter III). I found that most bias concepts fell under three broad categories: confounding bias, selection bias, and information bias, though several cross-cutting biases also emerged. Third, I piloted a consensus-based survey designed to evaluate the framework and its components with the goal to assess its readiness, feasibility and appropriateness for international application (Chapter IV). Collectively, this thesis contributed to the early stages of a larger, ongoing research project focused on developing a new RoB resource for assessing biases in observational studies of VE
Associations between parent and child 24-hour movement behaviours across the COVID-19 pandemic in Canada
No full textAbstract Background Parents influence and support children’s healthy movement behaviours (physical activity, sedentary time, sleep). During the COVID-19 pandemic, families spent even more time together. Thus, parents likely had greater influence on their child’s movement behaviours than usual. This study assessed the associations between parent and child movement behaviours and compliance with movement behaviour guidelines at two time points during the COVID-19 pandemic. Methods National samples of parents of children and adolescents (5–17 years) living in Canada completed online surveys about their own and their child’s movement behaviours in October 2020 (n = 1,568, 58% women) and April 2021 (n = 1,600, 60% women). Associations between parent and child movement behaviours and compliance with 24-hour movement behaviour guidelines were examined. Results We observed mostly positive, significant correlations between parent and child movement behaviours in October 2020 (r = 0.12–0.26, p < 0.05) and April 2021 (r = 0.12–0.20, p < 0.05). A parent meeting an individual movement behaviour guideline (e.g., physical activity) was associated with an overall higher incidence of their child meeting the same guideline in October 2020 (Incidence Rate Ratio (IRR):=1.10–3.06) and April 2021 (IRR: 1.19–2.26). The incidence of children meeting the 24-hour movement guidelines in October 2020 (IRR = 3.06, 95% CI: 1.55, 6.04) and in April 2021 (IRR = 2.26, 95% CI: 1.34, 3.83) was higher when parents met the 24-hour movement guidelines. Conclusions Parent and child movement behaviours were associated with one another during the COVID-19 pandemic, particularly for children (compared with adolescents). In times of severe public health restrictions, health promotion efforts should target family units to promote healthy movement of families collectively
Identifying Neural and Performance Markers of Subjective Cognitive Decline During Fine Motor Dual Tasks
No full textSubjective cognitive decline (SCD) refers to older adults who self-report persistent cognitive deficits in the absence of objective cognitive impairment. By clinical standards, older adults with SCD are considered healthy but may be at a greater risk of progressing to dementia than older adults without SCD (i.e., non-SCD). Despite this, neuropsychological tests are not sensitive enough to detect individuals at risk of future cognitive impairment since SCD relies on self-reported symptoms. This emphasizes a need for the early identification of markers that may be used to track or detect future cognitive impairment.
The dual-task paradigm has been previously used to identify differences in cognitive and motor performance in healthy older adults but its use in SCD has been limited. Based on the capacity model of attention, performing a cognitive and a motor task simultaneously can exceed an individual's processing capacity, leading to performance decrements on one or both tasks. The dual-task paradigm is thus a useful tool for detecting subtle cognitive deficits that may not be evident during single tasks.
Further, evidence suggests that changes in brain activity may precede observable changes in cognitive performance, including increased recruitment of neural resources (i.e., compensation), to support task performance. Neuroimaging techniques such as functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG) may, therefore, offer insights into the neural mechanisms underlying SCD. This highlights the potential use of neuroimaging to identify markers that distinguish between older adults with and without SCD during dual tasks.
To address this knowledge gap, this dissertation includes four studies aimed at identifying whether neural markers and cognitive and motor dual-task performance may be used to differentiate between older adults with and without SCD.
The first study (Chapter 2) included a systematic review and meta-analysis to quantitatively synthesize the dual-task literature on cognitive, motor, and neural outcomes in older adults with SCD compared to healthy controls, older adults with motoric cognitive risk syndrome (MCR), and objective cognitive impairment, including mild cognitive impairment (MCI) and dementia. The findings revealed decrements in gait performance between MCI and SCD but no differences between healthy older adults with and without SCD. In addition, few studies used neuroimaging to examine the underlying neural mechanisms of SCD, indicating a need for further research on markers associated with SCD during dual-task performance.
The second study (Chapter 3) used the knowledge gained from Chapter 2 by designing a dual-task paradigm consisting of walking or finger tapping with a cognitive task. In line with the literature, fNIRS findings revealed greater changes in cerebral oxygenation in the SCD compared to non-SCD group. This was observed during the finger tapping dual task, suggesting that it may be more sensitive to detecting differences in cerebral oxygenation than dual task walking. Taken together with performance findings, older adults with SCD may be demonstrating compensatory mechanisms to maintain cognitive performance, whereas the non-SCD group may prioritize walking over the cognitive task to maintain motor performance.
The third study (Chapter 4) expanded on Chapters 2-3 by investigating the effects of combining finger tapping with an n-back or double number sequence working memory task on cerebral oxygenation. The findings revealed that cognitive and motor outcomes declined with increasing cognitive load. In addition, greater changes in cerebral oxygenation were only observed in the SCD group compared to the non-SCD group during the double number sequence task. Taken together with performance findings, older adults with SCD may demonstrate compensation and neural inefficiency, in which increased brain activation may support task performance during the n-back task but not during the double number sequence task. The hemodynamic response may be sensitive to detect subtle differences in cognitive processing within the cognitive domain of working memory.
The fourth study (Chapter 5) used EEG, which has not been previously used to examine dual-task outcomes in SCD, to investigate P2 and P3 mean amplitude in the time-domain as well as power density in the delta, theta, alpha, beta, and gamma bands in the frequency domain. Findings revealed a larger P2 and P3 mean amplitude during the single task compared to the dual task, reflecting a greater availability of cognitive resources. In the frequency domain, theta and alpha power were higher in the SCD compared to non-SCD group, suggesting compensatory activation. In addition, the frequency domain may be more sensitive for detecting group differences in working memory processes compared to mean amplitude.
Four main outcomes emerged from this dissertation: 1) Research on dual-task outcomes in SCD is still emerging, with most studies focusing on dual-task walking and few studies examining the neural mechanisms underlying SCD. 2) Overall, older adults with and without SCD demonstrate similar levels of cognitive and motor dual-task performance. 3) The hemodynamic and electrophysiological response may be useful in detecting subtle differences in cognitive processing during dual tasks in older adults with and without SCD. 4) Longitudinal evidence is needed to better understand the trajectory of cognitive decline following SCD and whether early neural markers or performance outcomes can be used to predict the progression of cognitive impairment over time
Lung lobe segmentation: performance of open-source MOOSE, TotalSegmentator, and LungMask models compared to a local in-house model
No full textAbstract Background Lung lobe segmentation is required to assess lobar function with nuclear imaging before surgical interventions. We evaluated the performance of open-source deep learning-based lung lobe segmentation tools, compared to a similar nnU-Net model trained on a smaller but more representative clinical dataset. Materials and methods We collated and semi-automatically segmented an internal dataset of 164 computed tomography scans and classified them for task difficulty as easy, moderate, or hard. The performance of three open-source models—multi-organ objective segmentation (MOOSE), TotalSegmentator, and LungMask—was assessed using Dice similarity coefficient (DSC), robust Hausdorff distance (rHd95), and normalized surface distance (NSD). Additionally, we trained, validated, and tested an nnU-Net model using our local dataset and compared its performance with that of the other software on the test subset. All models were evaluated for generalizability using an external competition (LOLA11, n = 55). Results TotalSegmentator outperformed MOOSE in DSC and NSD across all difficulty levels (p < 0.001), but not in rHd95 (p = 1.000). MOOSE and TotalSegmentator surpassed LungMask across metrics and difficulty classes (p < 0.001). Our model exceeded all other models on the internal dataset (n = 33) in all metrics, across all difficulty classes (p < 0.001), and on the external dataset. Missing lobes were correctly identified only by our model and LungMask in 3 and 1 of 7 cases, respectively. Conclusion Open-source segmentation tools perform well in straightforward cases but struggle in unfamiliar, complex cases. Training on diverse, specialized datasets can improve generalizability, emphasizing representative data over sheer quantity. Relevance statement Training lung lobe segmentation models on a local variety of cases improves accuracy, thus enhancing presurgical planning, ventilation-perfusion analysis, and disease localization, potentially impacting treatment decisions and patient outcomes in respiratory and thoracic care. Key Points Deep learning models trained on non-specialized datasets struggle with complex lung anomalies, yet their real-world limitations are insufficiently assessed. Training an identical model on a smaller yet clinically diverse and representative cohort improved performance in challenging cases. Data diversity outweighs the quantity in deep learning-based segmentation models. Accurate lung lobe segmentation may enhance presurgical assessment of lung lobar ventilation and perfusion function, optimizing clinical decision-making and patient outcomes. Graphical Abstrac
Local Translation in Sustained Autophagy
No full textAutophagy is an evolutionarily conserved catabolic process. It involves a cascade of over 35 autophagy-related genes. During this process, a cupped phagophore membrane expands to surround cytoplasmic material, and eventually seals itself to form an autophagosome, which then fuses with lysosomes. Large numbers of autophagosomes form during stress responses, while simultaneously cells drastically reduce translation to conserve energy. Here, using proximity-labeling and Fluorescence in situ Hybridization we demonstrate that multiple mRNAs encoding proteins required for autophagy preferentially localize in proximity to forming autophagosomes. Polysome fractionation and proteomics of nascent proteins in proximity to forming autophagosomes further reveal that these mRNAs are preferentially actively translated there.
The ribosome-binding protein RACK1 and eIF5A were essential to the localization of these autophagy-related mRNAs to forming autophagosomes and their local translation. Depletion of RACK1 or eIF5A disrupts the synthesis of essential autophagy proteins, leading to a reduction in autophagosome formation. This suggests that local translation provides an energy-efficient mechanism for rapidly supplying autophagy-related proteins, ensuring cells to massively induce autophagy while conserving energy during cell stress. Our findings highlight the critical role of local translation in autophagy regulation and demonstrate that inhibiting this process compromises cellular homeostasis, potentially exacerbating defects in autophagy and contributing to cellular dysfunction
Understanding the Effects of Ciliopathy Gene Mutation in LRRC56 on Model Species Danio rerio
No full textÀ la demande de l'auteur, le résumé a été retiré en raison de la nature confidentielle de la thèse. Il sera ajouté une fois la période d'embargo terminée.
At the author’s request, the abstract has been removed due to the confidential nature of the thesis. It will be added once the embargo period has passed
Towards New Linchpin Reagents for the Direct Preparation of NCO-Containing Molecules
No full textThe development and application of reagents that serve as building blocks for the construction of molecules have resulted in significant advances to the scientific community. Among these, linchpins are small, strategically designed molecules that can be chemoselectively functionalized by sequential reactions, enabling the coupling of two or more reagents through a single, central scaffold. While there is literature precedent for olefin, ketone, and polyene-forming linchpins, no such linchpin exists for amide synthesis despite the ubiquitous nature of these and other NCO-containing subunits in pharmaceuticals and agrochemicals. This thesis focuses on the development of new linchpin reagents for NCO-containing products through the formation of C-N and C-X bonds.
Isocyanates are useful synthons and reactive intermediates. To control the exposure to these toxic reagents and their instability, blocked (or masked) isocyanates have been developed: an equilibrium generates the isocyanate in-situ, allowing for safer precursors and better control over the concentration of the reactive isocyanate. This strategy enables the development of new reactivity, particularly for heteroatom-substituted isocyanates. In Chapter 2, a bench-stable masked O-isocyanate with optimized leaving groups (OPh and OBz) is proven to indeed be an amide linchpin reagent, overcoming the limitations of traditional amide synthesis with a built-in N-C(=O) bond. The C(=O)-OPh and N-OBz bonds can undergo sequential reactions to functionalize the N-C=O subunit. The biselectrophilicity of the linchpin reagent imparts unique reactivity, making them attractive as linchpin molecules with high chemoselectivity. The linchpin reagent was first functionalized via rhodium-catalyzed electrophilic amination, followed by derivatization using Grignard reagents to provide hindered secondary amides and enamides. While this method was limited by its incompatibility with alkyl boronic acids, it provided a novel and effective route to amide derivatives. Tertiary amides were also accessed by trapping of the magnesium amidate intermediate with an alkylating agent. Finally, extensions toward a general NCO linchpin were explored through the synthesis of lactams and unsymmetrical ureas.
In Chapter 3, a simpler, amphoteric linchpin is developed to overcome the limitations of the linchpin developed in Chapter 2. The simpler linchpin reagent was first functionalized via reductive amination, followed by derivatization with Grignard reagents to provide secondary amides or with amines to provide unsymmetrical ureas. While this method does give access to N-alkyl amides, it does not yet extend to ureas due to competing reaction pathways.
In summary, these studies show that linchpin-based methods can simplify the synthesis of NCO-containing molecules, offering chemists new tools for assembling complex structures with importance in agrochemical and pharmaceutical industries
Swipe, Scroll, Diagnose: A Critical Look at Anxiety and Depression Discourse on TikTok
No full textAn estimated 581 million people worldwide live with anxiety or depressive disorders, with onset typically occurring between the ages of 17 and 29, an age group that aligns closely with TikTok's core user demographic. As discussions of mental health increasingly unfold on social media platforms, it is important to understand the nature and quality of these conversations. This study explored the question: How are anxiety and depression represented on TikTok, and what is the quality of the information shared? A total of 100 TikTok videos were sampled, 50 using #anxiety (or related derivatives) and 50 using #depression (or related derivatives). A multimodal thematic analysis was conducted to capture textual, visual, and auditory elements. A subset of videos mentioning specific disorders was assessed using three quality assessment tools: DISCERN, the JAMA benchmarks, and the Global Quality Score.
Key themes identified in the anxiety sample included: signs & symptoms, depictions of anxiety, diagnosis, relief strategies, and supportive messaging. For the depression sample, themes included: signs & symptoms, depictions of depression, management strategies, and supportive messaging. The findings reveal that TikTok is being used as an informal source of mental health information and peer support. However, the quality of this information varies, and it often lacks the depth and reliability required for accurate health literacy.
This study highlights the platform's dual role as both a space for community support and a potential source of misinformation. It underscores the need for public health stakeholders to engage with digital platforms and promote evidence-based mental health content to better support young users as they seek information and make sense of mental health topics online
Exploring success in sub-acute hospital-to-home transitions for palliative patients: a descriptive qualitative study
No full textAbstract Background Transitioning from a sub-acute hospital to home is highly desirable to some palliative and end-of-life individuals and their family caregivers, but the transition process itself is complex and can be logistically challenging. This formative assessment sought to better understand what constitutes a successful sub-acute hospital-to-home transition from the perspectives of health care providers connected to a sub-acute care facility in Ottawa, Canada, with reflections from a patient and a family caregiver. Methods Our descriptive qualitative study involved 13 virtual interviews and one virtual focus group between February and May 2023. Our sample included health care providers involved in the sub-acute hospital-to-home transition for palliative patients from a sub-acute facility, as well as one patient and one family caregiver who had experienced a palliative transition in this context. We used reflexive thematic analysis to code the data, and we inductively developed themes based on participants’ experiences. Results We collected data from 14 health care providers, one patient, and one family caregiver who were involved in, or had experienced, a sub-acute hospital-to-home transition. We found three themes delineating participants’ shared perceptions of the key foundations of a successful sub-acute hospital-to-home transition in the palliative context: meeting patient goals; sharing information to ensure informed decision-making; and having someone to coordinate the transition. Conclusions Our study highlighted that a successful sub-acute hospital-to-home transition should be person-centred and requires effective communication and coordination, both within and across, hospital and home environments. These insights will help inform intervention co-design to improve palliative care transitions in the next phase of this project