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Active upper-limb prosthesis for swimming
No full textSwimming presents unique challenges for individuals with upper-limb absence, as it requires complex coordination, symmetric propulsion, and control of body balance. Despite these demands, swimming also offers significant rehabilitative benefits, promoting muscle engagement, joint mobility, and cardiovascular health. However, current upper-limb prostheses rarely address the specific requirements of swimming, and most available devices remain passive or non-functional in aquatic environments.
This thesis proposes a novel design for a swimming-specific forearm prosthesis that actively adjusts wrist orientation in response to the swimmer's forearm motion. By segmenting the freestyle stroke into distinct phases—entry, catch, pull, push, and recovery—the control system simplifies the dynamic task into manageable sub-problems. Each phase is associated with a predefined wrist rotation, which simplifies control by reducing the continuous motion into a set of discrete, easily manageable movements. The phase recognition is performed using an inertial measurement unit (IMU), which monitors arm motion and triggers appropriate commands to the servo motor embedded in the prosthesis.
A prototype was developed to demonstrate this concept. The device includes a custom 3D-printed forearm structure that houses all electronic components—IMU, servo motor, controller, and battery—and uses a belt-pulley mechanism to transmit motion. Although the prototype is not yet suitable for use in water, it effectively demonstrates the feasibility of phase-based control for dynamic tasks such as swimming. The design emphasizes modularity, simplicity, and the potential for future development into a fully water-resistant system suitable for rehabilitation, recreational use, or part of training for competitive para-swimmers
In silico and In vitro Discovery of Plant-Based Pro-Inflammatory Cytokine Inhibitors
No full textPurpose: Dry eye disease (DED) is a prevalent condition range between 44.2% to 62.9% of the population, with female sex and aging being the greatest risk factors. The pathogenesis of DED is based on the dysregulation of tear film homeostasis, resulting in a vicious circle of desiccating stress, inflammation, and tissue damage. Mild DED is managed with artificial tears and warm compresses, whereas moderate-to-severe DED require additional anti-inflammatory therapies to break the vicious circle. Anti-inflammatory drugs such as corticosteroids are effective treatments but are associated with adverse side effects including increased risk of cataracts and glaucoma. Discovering novel anti-inflammatory therapeutics with minimal adverse side effects would greatly benefit DED patients who depend on anti-inflammatory treatment to mitigate symptoms. Flavonoids are a class of chemicals found in all vegetation; some are known for their anti-inflammatory effects. The numerous members of the flavonoid class could be leveraged to discover novel inhibitors against inflammatory DED targets. The purpose of this thesis was to discover a novel flavonoid that could act as an anti-inflammatory agent to treat DED.
Methods: This thesis employed a hybrid approach using network analysis, computational modelling, and in vitro validation. Network analysis was employed to select DED-associated protein targets and candidate flavonoids. “Dry Eye Syndrome” proteins were extracted from the STRING-DISEASE database and were cross-referenced with drug databanks using the functional enrichment analysis tool, ToppFun, for flavonoids. A network analysis tool, Cytoscape (v 3.9.1.), was utilized to visualize and rank DED-associated proteins and flavonoids by number of edge interactions. Two proteins were selected for their distinct roles in the immune response, and two flavonoids were selected for their association with multiple pro-inflammatory DED-associated proteins. Molecular docking and molecular dynamic (MD) simulations modelled and simulated the protein-ligand complex of both protein targets with each flavonoid molecule. Four protein-ligand complexes were assessed for stability and specific residue-ligand interactions. The inhibitory effects of both flavonoids were assessed in vitro with ELISAs against both protein targets. The biocompatibility of the most effective flavonoid inhibitor was assessed with human corneal epithelial cells (HCEC) using an Alamar Blue metabolic activity assay; viability was assessed by evaluating the proportion of live, apoptotic, and dead cells.
Results: The network analysis generated a protein-protein interaction network of 64 DED-associated proteins and a drug-protein network of 108 flavonoids. Tumour necrosis factor (TNF) interactions and interleukin (IL) 17A (14 interactions) were amongst the 5 highly ranked proteins and selected for their roles in the innate and adaptive immune response, respectively. Luteolin (19 interactions) and rutin (17 interactions) were the highest ranked flavonoids associated with DED-associated proteins. Molecular docking and MD simulations predicted that both flavonoids could bind directly to the receptor binding sites of both cytokines. However, ELISAs showed that neither luteolin nor rutin could inhibit TNF- and TNF receptor interaction (all p≥0.07). On the other hand, both luteolin (IC50 = 16.54 mM) and rutin (IC50 = 8.73 mM) had inhibitory effects against IL-17A and IL-17A receptor interaction (all p0.06).
Conclusion: This thesis identified rutin as a novel flavonoid inhibitor of IL-17A. These findings suggest that rutin may play a role in anti-inflammatory therapeutics for DED
DeTAILS: Deep Thematic Analysis with Iterative LLM Support
No full textReflexive thematic analysis (TA) yields rich insights but is challenging to scale to large datasets due to the intensive, iterative interpretation it requires. We present DeTAILS: Deep Thematic Analysis with Iterative LLM Support, a researcher-centered toolkit that integrates large language model (LLM) assistance into each phase of Braun \& Clarke’s six-phase reflexive TA process through iterative human-in-the-loop workflows. DeTAILS introduces key features such as “memory snapshots” to incorporate the analyst’s insights, “redo-with-feedback” loops for iterative refinement of LLM suggestions, and editable LLM-generated codes and themes, enabling analysts to accelerate coding and theme development while preserving researcher control and interpretive depth. In a user study with 18 qualitative researchers (novice to expert) analyzing a large, heterogeneous dataset, DeTAILS demonstrated high usability. The study also showed that chaining LLM assistance across analytic phases enabled scalable yet robust qualitative analysis. This work advances Human-LLM collaboration in qualitative research by demonstrating how LLMs can augment reflexive thematic analysis without compromising researcher agency or trust
Toward Scalable and Sustainable Perovskite Solar Cells: Optimizing Atmospheric-Pressure Spatial Atomic Layer Deposition SnOX for Enhanced Perovskite Crystallization and Performance
No full textPerovskite solar cells (PSCs) have rapidly achieved power conversion efficiencies (PCEs) comparable to crystalline silicon over the past decade, offering a promising low-cost alternative. However, commercialization remains hindered by the reliance on lab-scale fabrication methods and the use of toxic solvents, which pose environmental and health concerns. Atmospheric-pressure spatial atomic layer deposition (AP-SALD) represents a scalable, solvent-free approach for fabricating charge transport layers, and when combined with green-solvent-processed perovskites, offers a sustainable pathway for large-scale PSC production.
Despite this potential, tin oxide (SnOX) electron transport layers deposited via AP-SALD (SALD SnOX) have historically underperformed compared to their nanoparticle-based counterparts (NP SnOX). This study investigates the root causes of this performance gap by analyzing the energetic, chemical, and morphological properties of SALD SnOX layers and their interfaces with perovskite light absorbers. Furthermore, the work explores and optimizes PSCs fabricated entirely using green-solvent and solvent-free techniques.
Our findings show that post-annealing SALD SnOX at 180 ˚C significantly enhances conductivity, thereby improving key photovoltaic parameters. Additionally, we demonstrate that the conformal-coating nature of AP-SALD can amplify substrate roughness, negatively affecting perovskite crystallization—unlike spin-coating, which inherently smooths the surface. By optimizing the SALD SnOX thickness and utilizing smoother fluorine-doped tin oxide (FTO) substrates, SALD SnOX-based n-i-p PSCs achieve a PCE exceeding 20%, matching the performance of NP SnOX-based reference cells for the first time.
Introducing a green-solvent-processed perovskite layer into the PSC stack initially results in reduced performance. To address this, polystyrene (PS) is incorporated into the perovskite precursor to form a cross-linked polymer–perovskite network, which improves grain nucleation and growth, leading to enhanced device performance. Notably, the SALD SnOX ETL demonstrates a positive influence on the crystallinity of the green-solvent perovskite, supporting earlier findings.
Overall, this work delivers critical insights into interfacial engineering strategies for achieving scalable, environmentally friendly, and high-performance PSCs, reinforcing the viability of AP-SALD for industrial application
A CRISPR-Cas9 and next-generation sequencing approach for late/very late AcMNPV gene disruption and comprehensive mutation analysis
No full textThe recent global pandemic COVID-19 has taught us the importance of an efficient biologics manufacturing platform that is cost-effective, reliable, and has high product yield and quality. The baculovirus expression vector system (BEVS) has proven to be a promising platform for the production of recombinant proteins, vaccines, virus-like particles (VLPs), viral vectors, and/or other biologics. In the last two decades, many vaccines and therapeutics manufactured using BEVS have received licenses for animal and human use. The majority of the commercially available BEVS transfer plasmids have foreign genes under the viral polyhedrin (polh) or p10 promoters. Although high gene expression can be achieved with the endogenous baculovirus promoters p10 and polh, they are only active very late in the infection cycle when most of the host cellular machinery is turned off. Significant work has been done to identify native promoters and other regulatory elements with expression profiles higher than polh, as well as promoters weaker than polh to express secretory proteins that require extensive post-translational modifications (PTMs).
Certain regions, such as polh, chiA, and v-cath, in the baculovirus genome are not essential for their in vitro replication or foreign protein production in cell culture. Thus, it is possible that if there is an expression of genes not required for progeny virus and/or exogenous protein production in insect cell culture, the resources that are being used for their expression could be ‘an additional burden’, resulting in unnecessary depletion of cellular resources. Identifying and removing these genes would probably divert resources towards the production of foreign proteins and progeny viruses, which could improve the BEVS production platform. Moreover, it was previously demonstrated that there is a ‘competition effect’ among protein-coding genes for cellular resources when Sf9 cells are either coinfected with two monocistronic recombinant baculovirus expression vectors (rBEVs) or infected with a dual-protein producing polycistronic rBEV. This work could point to a direction where competition can arise among baculovirus genes for the use of cellular resources, and the knockout of unnecessary genes could presumably lead to appropriate usage of the resources by the essential genes. Separately, the co-production of rBEVs and recombinant protein products in the supernatant complicates the downstream purification process. Disruption of genes essential for virion formation or production could prevent baculovirus contamination in the culture supernatant, thus reducing the burden on purification processes.
In the past, gene disruption or downregulation has been a fruitful strategy to improve the expression of foreign genes in the BEVS. However, the traditional methods used for mutant baculovirus genome generation are time-consuming, labor-intensive, and sometimes also produce wild-type viruses, hence requiring additional purification steps. Not until recently has CRISPR-Cas9 gene editing technology been adapted to the Sf9 insect cells and the baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV). It is believed to be an effective tool to scrutinize baculovirus genes by targeted gene disruption and transcription repression. A systematic study of the late and very late AcMNPV genes using a CRISPR-Cas9-based transfection-infection assay (T-I assay), disrupting the unnecessary sequences, and expressing exogenous gene(s) under a late promoter instead of very late promoters could extend the production time and improve biologics production. Moreover, in the final production stage, targeting AcMNPV genes that are required for progeny virus assembly or release but do not affect foreign protein production could minimize rBEV co-production. In this study, the T-I assay was used to probe late and very late AcMNPV genes for their essentiality. Based on the effect of individual gene disruptions on foreign protein (green fluorescent protein (GFP)) and budded virus (BV) production, 38 targeted AcMNPV genes were categorized as essential (reduced both GFP and BV production) and of special interest (reduced GFP production but did not lower BV production). While we identified 19 AcMNPV genes that are essential for BV production and GFP expression from the late p6.9 promoter, 19 other genes were identified as of special interest whose disruption only reduced GFP expression from the late p6.9 promoter.
While phenotypic changes were assessed using the CRISPR-Cas9-based T-I assay, investigating the genomes using whole-genome next-generation sequencing (NGS) revealed further information. First of all, shotgun sequencing was used to generate a consensus sequence of the p6.9GFP rBEV stock used in T-I assays, and this is the first report on whole-genome rBEV sequences to the best of our knowledge. This shotgun-sequenced rBEV served as the reference genome to identify mutations upon CRISPR-Cas9-mediated gene disruptions. We also provided a set of tiled-amplicon primers based on the reference genome and adapted a high-throughput tiled-amplicon sequencing assay to control and targeted rBEV genomes. This sequencing assay, combined with a bioinformatics pipeline for major species, was able to successfully detect mutations within the gp64 gene when gp64 targeting sgRNA was delivered to Sf9-Cas9 cells via a plasmid or rBEV. We further demonstrated that gp64 disruption lowered BV levels without decreasing GFP production, thus reducing BV contamination in cell culture supernatant.
To probe the gp64 gene further, we targeted it at six different locations using the T-I assay. Plasmids carrying one or two sgRNA targets were used to evaluate the impact of single and multiple targeting sites on virion and foreign protein production. gp64 disruption with each of these sgRNA targets resulted in decreased infectious and total viral titers, whereas GFP production from the late p6.9 promoter was enhanced or remained similar to the control. Low-frequency genomic changes upon CRISPR-Cas9-mediated gp64 disruptions were successfully assessed by the tiled-amplicon sequencing assay and a variant calling pipeline based on the computational tool iVar. While the iVar tool was originally developed to investigate variants in wild-type virus populations, we adapted it to detect variants in a process system. We also demonstrated that variants can be preserved over viral propagation in cell culture, that is, variants present in the virus stock were also observed in the rBEV genomes recovered from the T-I assay, thus indicating that they are not detrimental to viral fitness
Food Policy in Recreation and Sport Facilities in Canada: Lessons Learned from Eat, Play, Live
No full textBACKGROUND
The advent of voluntary nutrition guidelines for municipally funded recreation and sport facilities in three Canadian provinces presented the opportunity to evaluate both policy impact and implementation support approaches. The current research extended the Eat, Play, Live (EPL) trial which examined food environments within recreation and sport facilities in the three nutrition guideline provinces (British Columbia, Alberta, Nova Scotia), with and without a capacity-building intervention (CBI), and a non-guideline control province (Ontario).
RESEARCH OBJECTIVES
1. Describe recreation and sport facility food environments in the absence of provincial nutrition guidelines.
a. Assess the healthfulness of food and beverages offered for sale and vending sales within a convenience sample of recreation and sport facilities in Ontario, Canada and compare between the cohort with a municipal policy banning the sale of water in single-serve plastic water bottles in municipally funded facilities versus the cohort without such a policy.
2. Explore components of the CBI that had the greatest impact on the healthfulness of food environments within recreation and sport facilities in nutrition guideline provinces randomized to receive the EPL CBI.
a. Examine the relationships among the implementation factors: guideline mobilization, facility context, and facility-level policy, and changes to the healthfulness of the food environment in facilities within nutrition guideline provinces randomized to receive the CBI; and
b. Describe and frame relationships between and among CBI components and changes to the healthfulness of recreation and sport facility food environments using the updated Consolidated Framework for Implementation Research (CFIR) [1].
METHODS
Study 1: Ontario Recreation and Sport Facility Food Environment
Cross-sectional descriptive data on the food environments in municipal recreation and sport facilities in Ontario were collected on two occasions; time 1 (T1) and time 2 (T2), marking the start and end of the 18-month CBI. Differences in the healthfulness of food and beverages between facilities with and without a bottled water ban were measured using:
a) Vending and concession packaged product profiles assessed by classifying healthfulness of each according to established British Columbia Ministry of Health Guidelines as Sell Most, Sell Sometimes, and Do Not Sell [2];
b) Concession food environments scoring as measured using the Nutrition Environment Measures Survey-Restaurant reduced item audit (rNEMS-R) Fast Casual and Fast Food Summary [3]; and
c) Itemized sales data for vending products targeting a two-week period around facility audits.
Descriptive statistics were calculated and differences between the two groups compared using Student’s two-sided t-test.
Study 2: Guideline Implementation Factors and Changes in Facility Food Environment
In facilities across three voluntary nutrition guideline provinces (British Columbia, Alberta, Nova Scotia) that had been randomized to the EPL 18-month CBI, a qualitative comparative analysis (QCA) examined relationships between implementation factors: guideline mobilization (Mobilization), facility context (Context), and facility-level policy (Policy), and positive (healthier) food environment changes. Regression analysis was also used to examine the strength of relationships between the implementation factors and changes to healthfulness.
Implementation factor ratings (low [1], low-moderate [2], moderate [3], moderate-high [4], high [5]) from a cross-case analysis, with each facility acting as an independent case, were used to conduct both the QCA and regression analyses. Facility healthfulness was assessed as described for Study 1. For the QCA positive change was defined as a decrease in the proportion of Do Not Sell products for vending and concession packaged beverages and snacks and as an increase in score for rNEMS-R Fast Summary scores. The ratings for the implementation factors were based on indicators for guideline mobilization, (the number and intensity of CBI activities implemented, access and use CBI of resources), facility context (training/expertise, priorities, structural characteristics, partnerships, champion and staff changes) and facility-level policy (quality, status and breadth) that were extracted from a range of data sources:
a) An implementation summary for each facility was created by EPL provincial coordinators which included the following documentation:
a. Implementation plans documenting goals, tasks, responsibility, and timeline according to operational area (e.g., vending);
b. Mobilization summaries documenting activities, intensity of activities and access and use of EPL resources;
c. Context summaries documenting relevant context changes (e.g., food service contractor changes);
d. Technical support provided;
e. Regional teleconference minutes;
f. Interview transcripts of intervention mid-point and end-point interview with facility representatives (CBI facility Leads);
g. Provincial coordinator documentation around role and engagement of CBI facility Leads, buy-in, and major challenges and facilitators;
h. A facility level policy assessment using purpose-built questions integrated in a self-assessment audit tool adapted to the recreation and sport facility context and available documents on facility-level policy or policies.
Study 3: EPL CBI Multiple-case Evaluation Framed by CFIR
A multi-case study approach was used to examine the impact and strategy variation of the CBI across different facility contexts. Two facilities who achieved greater success at increasing the healthfulness of the recreation and sport facility food environment (as a proxy for provincial nutrition guideline uptake/implementation) were compared and contrasted with two facilities that were less successful at effecting change. The updated CFIR [1] was used to frame the analysis. The selection of case facilities from the 17 receiving the CBI was based on facility rankings for nine food environment outcomes assessed through facility audits (as outlined for Study 1) at baseline (T1) and end-of-study (T2).
RESULTS
Study 1: Ontario Recreation and Sport Facility Food Environment
Packaged snack and beverage offerings available in vending machines and at concessions were predominantly Do Not Sell and rNEMS-R scores were well below ideal across the 16 participating facilities. Packaged snacks ranged from 94-96% Do Not Sell in facilities that allowed the sale of bottled water (n=8) and similarly from 87-94% in facilities banning bottled water (n=8). Beverages ranged from 74-77% Do Not Sell in facilities that allowed the sale of bottled water and differed significantly (p<0.05) from the 87-88% Do Not Sell in facilities banning bottled water. rNEMS-R Fast Casual scores were similar at 6.1 and 7.1 for facilities allowing bottled water versus those banning its sale, compared to an ideal score of 48.
Mirroring availability, sales from vending snacks and beverages were also predominantly Do Not Sell. Differences were found for beverage availability and sales between facilities in jurisdictions banning bottled water and those that allowed the sale of bottled water. The proportion of Do Not Sell beverages available was significantly (p<0.05) higher in the absence of bottled water (90% versus 79%) and the proportion of Sell Most (0% versus 14%) was significantly (p<0.05) lower in bottled water banned versus allowed facilities. This significant difference (p<0.05) was also reflected in the proportions of sales dollars for each category with 80% Do Not Sell and 14% Sell Most where bottled water was allowed compared to 91% Do Not Sell and 0% Sell Most in those facilities with a ban.
Study 2: Guideline Implementation Factors and Changes in Facility Food Environment
A breakdown of indicators that informed ratings for each guideline implementation factor and examples corresponding to higher ratings were provided.
QCA Results
QCA findings indicated that configurations with implementation factor ratings for each of Mobilization, Context and Policy indicated that higher levels were necessary to effect positive change in healthfulness outcomes. While high (5) ratings of each factor invariably resulted in positive change, there were various factor combinations of high (5), moderately-high (4) and moderate (3) factor ratings that were sufficient. Overall, somewhat higher ratings for Mobilization than the other two factors emerged in all successful configurations.
Regression Analysis Results
For Vending Beverages and Snacks, multiple regression analysis indicated that the three factors in the model: Mobilization, Context, and Facility-level Policy, were each significantly associated with a decrease in the proportion of Do Not Sell products. No significant associations with guideline implementation factors were found for beverage and snack proportions of Do Not Sell items within concessions nor for rNEMS-R Fast Summary scores.
Study 3: EPL CBI Multiple-case Evaluation Framed by CFIR
The facilities that emerged as ‘More’ (n=2) and ‘Less’ Successful (n=2) in improving the healthfulness of food offerings were, in each case, from British Columbia and Alberta. Each had made some positive changes across the multiple outcomes. Comparing and contrasting the More and Less Successful facilities across 49 constructs and sub-constructs of CFIR [1], 24 were distinguishing, 23 were not distinguishing and two were mixed. In particular, the More Successful facilities stood out for leveraging partnerships with local public health Registered Dietitians (Relational Connections, Implementation Facilitators), navigating resistance to nutrition guidelines and pushing for change (Tension for Change), accessing resources and utilizing EPL provincial coordinator support (Communication and Access to Knowledge & Information) and taking action toward improving healthfulness of the facility food environment (Planning, Tailoring Strategies, Engaging, Doing).
CONCLUSIONS BY STUDY
Study 1: Ontario Recreation and Sport Facility Food Environment
In the absence of provincial nutrition policy/guidelines, most food and beverage offerings in participating facilities in Ontario were energy-dense and nutrient-poor, a finding mirrored in vending sales. Moreover, the healthfulness of the food environment was found to be vulnerable to unintended consequences of municipal-level policy. In jurisdictions that banned the sale of water in single-use plastic bottles offerings and sales of Do Not Sell beverages were proportionately higher than in facilities permitting bottled water. Moving forward, newer environmentally sustainable packaging options may provide a way for both health and sustainability goals to be met. Ironically, this finding demonstrated the power of mandated policy to alter food environments. Given that the food environment in facilities participating in the EPL study remained largely unhealthy even in provinces with voluntary nutrition guidelines [4], a mandated nutrition policy approach is recommended for Ontario moving forward. This would ensure that municipally-run facilities align with public health guidance by shifting the nutrition healthfulness of foods offered for sale. Ultimately, this would support the overall health of those enjoying recreation and sport facilities in Ontario.
Study 2: Guideline Implementation Factors and Changes in Facility Food Environment
The EPL trial found that recreation and sport facilities exposed to a capacity building intervention were better able to improve the availability of healthy foods in response to voluntary provincial nutrition guidelines than those without these supports [4]. This research aimed to determine the elements of the intervention that were most helpful. Higher ratings (moderate and above) in all three implementation factors (Mobilization, Context and Facility-level Policy) were necessary to support changes in recreation and sport facility food environments indicating implementation support approaches must include attention to all three to effect change. For Mobilization, ratings of moderately-high or high were necessary, suggesting that efforts supporting the number and intensity of mobilization activities such as monitoring and enforcement of existing food service contracts and food choice architecture approaches (e.g., positionality, cueing, changing default options) could have an impact on food environment healthfulness. Yet, Mobilization activities did not happen in isolation. Context and Policy were also necessary at moderate or moderately-high levels in combination with the higher Mobilization ratings and played a pivotal role in supporting mobilization activities; thus, attention to strategies focused on context elements (e.g., training, expertise, priority issues, structural barriers, partnerships) and facility-level policy development (e.g., food service contracts with healthfulness provisions) are critical.
Study 3: EPL CBI Multiple-case Evaluation Framed by CFIR
Use of the CFIR [1] to evaluate the CBI allowed identification of areas to direct future implementation support action to optimize nutrition guideline uptake in the municipally funded recreation and sport facility setting. The CBI training, support and resources of EPL enhanced capacity for nutrition guideline implementation and facilitated positive change in the healthfulness of foods offered. Change is difficult and some barriers were outside the control of facilities, yet all study facilities benefited to some degree from the suite of supports available and made some positive changes in enhancing the healthfulness of food environments. The More Successful facilities benefited particularly from partnerships and relationships. EPL provincial coordinators, public health dietitians, and support communities were among the relationships that facilitated their greater success. Effective engagement and ongoing communications were fundamental to those relationships.
In order to foster meaningful change to the healthfulness of recreation and sport facility food environments, the current research points to the following recommendations for provinces or other jurisdictions instituting nutrition guidelines/policy: invest in dedicated and on-going expert implementation support; establish mechanisms for an on-going community of practice among those implementing guidelines; define clear steps in the progression towards full implementation of nutrition targets; develop comprehensive tools and resources to support revenue concerns and financial viability of the transition to healthier options for food service providers and facilities; create public messaging and setting-specific education campaigns to emphasize the value of healthy eating; and mandate provincial nutrition policy and assign accountability for implementation and monitoring within the regulatory framework.
THESIS CONCLUSIONS AND CONTRIBUTIONS
The research in this thesis has direct applicability to jurisdictions looking to implement recreation and sport facility food and nutrition guidelines/policy. Findings from the province of Ontario with Study 1 clearly identified that in the absence of policy the recreation and sport facility food environment is unhealthy. Moreover, findings also indicated that a lack of policy could make facilities vulnerable to local policies that do not consider public health impact, as was the case with the plastic bottled water ban. The EPL trial demonstrated that in the absence of capacity building supports, voluntary nutrition guidelines did little to change the healthfulness of recreation and sport facility food environments [4]. Studies 2 and 3 of this thesis research took advantage of the capacity building intervention of EPL in identifying and evaluating implementation supports that could make the most difference to nutrition guideline uptake. Study 2 demonstrated that a combination of factors were required at high to moderate levels; importantly, Mobilization required even higher levels than the factors Context or Facility-level Policy. This suggests that prioritizing such guideline mobilization strategies could improve implementation outcomes. In comparing most and least successful intervention facilities using the CFIR implementation framework, Study 3 identified points of action for implementation support. The structure provided with the use of CFIR increases transferability of the research to other settings. Jurisdictions increasingly recognize the paradox of recreation and sport facilities supporting active living yet providing unhealthy food and beverages. The lessons learned from this research can support meaningful change in recreation environments. There are many, including CBI facility leads involved in the current research, that feel that nutrition policy for recreation and sport facilities should be mandated and not limited to voluntary guidelines. Certainly, the findings of this thesis research indicate that strong supports for the process of policy of guideline implementation are needed for meaningful change. Ultimately, these changes could make recreation and sport facilities healthier food environments.
Contribution
This research contributes to current understanding of population-level policy implementation in community settings and can support policy planning, development, the implementation process and evaluation. The novel use of QCA analysis allowed a better understanding of the complexity and inter-relationship among factors influencing nutrition guideline implementation. The updated CFIR allowed identification of key factors influencing nutrition guideline implementation and extends our understanding of the application of implementation science in public health
Bayesian Integral-based Methods for Differential Equation Models
No full textOrdinary differential equations (ODEs) are widely considered for modeling the dynamics of complex systems across various scientific areas. When inferring the parameters of ODEs from noisy observations, most existing parameter estimation methods that bypass numerical integration tend to rely on basis functions or Gaussian processes to approximate the ODE solution and its derivatives. Due to the sensitivity of the ODE solution to its derivatives, these methods can be hindered by estimation error, especially when only sparse time-course observations are available. Furthermore, in high-dimensional sparse ODE systems, existing methods for structure identification are predominantly frequentist, and uncertainty quantification for trajectory estimation remains a significant challenge.
In this thesis, we present a Bayesian collocation framework that operates on the integrated form of the ODEs and also avoids the expensive use of numerical solvers. In contrast to frequentist methods, the Bayesian framework provides better quantification of uncertainty. Specifically, we propose three methods to recover ODE systems with both known and unknown functional forms, as well as for model validation in systems with known functions. First, for ODEs with known functional forms, our methodology can handle general nonlinear systems to infer parameters from noisy observations. We then extend the approach to ODEs with unknown functional forms to identify system structure. Under the additive ODE model assumption, we develop a unified framework that combines the likelihood, integrated ODE constraints, and a group-wise sparse penalty, enabling simultaneous system identification and trajectory estimation. Finally, for cases involving several competing functional forms that exhibit similar dynamics, we incorporate model inadequacy as a function into the measurement model, allowing simultaneous model validation and parameter estimation. We demonstrate the favourable performance of our proposed methods, compared to existing ones, in terms of estimation accuracy and model validation. We also illustrate the methods with real data analyses
Theory and phenomenology of area-metric gravity
No full textArea metrics are generalised geometric structures to describe spacetime. They feature additional non-metric degrees of freedom beyond the metric degrees of freedom of classical gravity at low energies. As such, area-metric gravity is a candidate effective field theory for the continuum limit of loop quantum gravity and spin foams which accounts for the extended gravitational configuration space of these approaches in their semiclassical regime.
On these grounds, following a bottom-up approach, we construct area-metric gravity perturbatively guided by the principle of general covariance. The most general local and diffeomorphism-invariant action quadratic in area-metric perturbations and of second order in derivatives contains four free parameters. These are the two masses of the right-handed and left-handed non-metric degrees of freedom, and the two interaction couplings between these and the metric degrees of freedom of the area metric. Linearised area-metric gravity violates parity for generic values of these parameters.
The effective metric actions obtained after integrating out the non-metric degrees of freedom are quasi-local linearised Einstein-Weyl actions. For special choices of couplings, the spin-2 propagator is ghostfree and exhibits only the pole associated with the massless graviton. The corresponding two-parameter subclass of linearised area-metric actions is characterised by a shift symmetry in the kinetic term. The physical spectrum of these theories consists of two massless transverse-traceless modes and five additional massive modes. The Hamiltonian dynamics mixes the two massless transverse-traceless modes in the linear polarisation basis as a result of parity
violation in the original area-metric Lagrangian.
Extending the analysis of area-metric actions, we show that modified Plebanski theories provide a natural framework for non-linear area-metric gravity. In these theories, a subset of the simplicity constraints on the bivector field in the original Plebanski action is replaced by a potential. This mechanism may be viewed as a continuum analogue of the weak imposition of second-class constraints in the spin-foam path integral. The Immirzi parameter γ, defined as the inverse coupling in front of the Holst action, and appearing in the commutator between second-class constraints in the quantum theory, is identified as a parity-violating coupling in area-metric gravity. Different from classical metric gravity, γ enters the dynamical equations of motion in area-metric gravity.
Based on these results, we proceed to analyse aspects concerning the phenomenological viability of area-metric gravity as a quantum and classical effective field theory.
Considering area-metric gravity as a local quantum effective field theory in a regime below the cutoff scale of a fundamental theory of quantum gravity, we evaluate its renormalisation-group flow towards the infrared regime. The non-metric degrees of freedom generically decouple as a result of their heavy masses at low energies. However, simultaneously growing interaction couplings between these and the metric degrees of freedom may leave an imprint in the low-energy effective action for the metric. In addition, parity violation at high energies is dynamically enhanced at low energies. The flow of the Immirzi parameter exhibits fixed points and zero and infinite γ.
Finally, we consider non-linear quasi-local Einstein-Weyl gravity as a classical effective field theory for the metric degrees of freedom in area-metric gravity. After localising the action and restricting to static spherical symmetry, we show that solutions in the weak-field regime are characterised by an effective mass parameter which reduces to the mass of the spin-2 ghost in local Einstein-Weyl gravity when the non-locality in the original action is taken to zero. Additionally, we derive a regular Frobenius solution family at the radial center as the first step towards a future classification of Frobenius solutions around a generic expansion point
Investigating socioeconomic inequities in diet quality among adults in Canada using an intersectional approach
No full textIt is well-acknowledged that diet quality differs across socioeconomic position (SEP). However, it is unclear how SEP dimensions intersect to shape diet quality. My dissertation uses an intersectional approach to identify differences in diet quality across SEP dimensions and contexts. The primary objectives of my dissertation research were: (1) to identify individual/household SEP intersections that best predicted lower and higher diet quality among a population-based sample of adults in Canada; (2) to assess whether four dimensions of neighbourhood deprivation were independently and/or jointly associated with diet quality among a nationally representative sample of adults in Canada; and (3) to compare associations between three SEP indicators (educational attainment, perceived income adequacy, household food insecurity) and diet quality between adults in Canada and the United States. In a conditional random forest analysis, I identify educational attainment and Indigenous identity and race/ethnicity as the most important intersectional predictor of diet quality among adults in Canada. By examining four dimensions of neighbourhood deprivation, I find significant interactions that suggest associations between living in a neighbourhood with less material resources and lower HEI-2015 scores was stronger in areas with a smaller proportion of recent immigrants/visible minorities and non-working individuals. In a cross-country comparison, I find that associations between SEP (educational attainment, perceived income adequacy, and household food insecurity) and diet quality did not differ between Canada and the United States. Overall, this dissertation demonstrates how an intersectional approach to quantitative health research can be used to draw attention to the complex and context-dependent nature of inequities in diet quality
Validating & Measuring Influenza Vaccine Effectiveness among and against Cardiovascular Hospitalization
No full textBackground: Influenza is a viral respiratory infection that causes serious health outcomes such as hospitalization and death and represents an important public health burden globally.
Vaccination is one of the most effective interventions to prevent influenza and its complications. Although administrative databases such as pharmacy billing claims are used to measure influenza vaccination status, little is known of the validity of these databases in Ontario. Patients with cardiovascular disease (CVD) may have an altered immune response, despite being at a higher risk of influenza complications. It is not known if the Vaccine Effectiveness (VE) in this population is comparable to the general population. Further, there is a lack of research in Canada evaluating influenza vaccine effectiveness against cardiovascular outcomes, particularly using robust study designs such as the test-negative design. Three interrelated studies were carried out. First, a validation study was completed to examine the accuracy of the combination of Ontario’s administrative data from pharmacy and physician billing claims in identifying an individual’s vaccination status. The second study assessed the influenza VE against laboratory-confirmed influenza among older adults hospitalized with CVD conditions in Ontario and examined sex and age group as potential effect modifiers in the association between influenza vaccination and laboratory-confirmed influenza. The third study measured influenza VE against acute CVD outcomes using the Test-Negative Design (TND) for the first time among older adults in Ontario who were hospitalized within three days of their influenza testing.
Methods: In the first study, I validated the combined physician and pharmacy billing claims within administrative databases using the linked reference standard of self-report data from the Canadian Community Health Survey (CCHS). This study estimated sensitivity, specificity,
Positive Predictive Value (PPV), and Negative Predictive Value (NPV), with 95% Confidence Intervals (CI) of the estimates. In the second study, I used the TND to measure influenza VE against laboratory-confirmed influenza. The analysis included both crude and adjusted estimates accounting for potential confounders (sex, age group, neighbourhood income quintile, rurality, number of outpatient visits, beta-blocker medication use, statin medication use, receiving home care services, and influenza testing relative to the peak month of the season, and year of influenza season). In addition, I assessed effect modification of sex and age group on influenza VE by using two different methods: introducing interaction terms into the model and stratification. In the third study, I examined influenza VE against acute CVD outcomes, also using the TND. The exposure of interest was vaccination status, cases were those hospitalized for myocardial infarction, unstable angina, or stroke and testing positive for influenza, and controls were those hospitalized for a non-cardiovascular event and testing negative for influenza. Both crude and adjusted VE were estimated. Sensitivity analyses were performed to test the robustness of the findings by varying inclusion criteria, outcome definitions, and statistical adjustments.
Results: In the first study, the CCHS identified 43% as vaccinated across the two survey cycles of 2013 and 2014. The sensitivity for the combined pharmacy and physician billing codes was 60.1% (95% CI 59.3%–61.0%), specificity was 98.5% (95% CI 98.3%–98.7%), PPV was 96.7%
(95% CI 96.3%–97.1%) and NPV was 76.9% (95% CI 76.4%–77.5%). The second study
included 1,159 patients, and almost half were vaccinated. Among vaccinated patients, 14% tested positive for influenza compared to 20% of unvaccinated patients.. Crude and adjusted VE were 32% [95% CI, 8–50%] and 43% [95% CI 20%–60%], respectively. Neither inclusion of interaction terms separately in the full model, nor stratification by sex or age group, revealed any evidence of effect modification. The third study included 33,710 hospitalized individuals who tested positive for influenza and had a CVD event (cases) or tested negative and did not have a CVD event (controls). There were 18,519 vaccinated individuals (55%). Among vaccinated patients, 0.4% tested positive for influenza and were hospitalized for a cardiovascular event, compared to 0.8% of unvaccinated patients. The adjusted influenza VE against cardiovascular outcomes was 43% [95% CI 25%–58%; p-value =0.0001].
Conclusion: Compared to past studies with only physician billing claims, the validation study provided improved performance measures of sensitivity, specificity, PPV and NPV values in the combined physician and pharmacy billing claims in identifying individual vaccination status in Ontario. The second study estimated influenza VE against laboratory confirmed infection and supports that influenza VE among older adults with CVD hospitalization is comparable to the general population. Also, no significant effect modification in VE was observed by the patient’s sex, or age. These findings suggest that the protective effect of the influenza vaccine against laboratory-confirmed influenza is consistent across key demographic and clinical subgroups within this high-risk population. The third study found that the influenza vaccine provides a significant protective effect against CVD outcomes.
The global findings of this thesis emphasize the validity of administrative databases at estimating population-level vaccination rates and show the importance of influenza vaccination as an effective strategy to reduce both influenza hospitalization and CVD events. This unique research equips healthcare providers and policy makers with relevant findings to support their campaigns and recommendations on influenza VE, particularly in relation to CVD outcomes