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Background Sustaining health promotion programs (HPP) is critical to maintain their intended health benefits, community capacity, and to optimize resources and investment. However, not all programs are sustained beyond their initial implementation period. This is partly due to uncertainty regarding sustainability: lack of a clear definition; infrequent use of a sustainability framework; and lack of understanding of the factors that influence sustainability. The aim of this systematic review is to identify barriers and facilitators that promote or inhibit the sustainability of HPP, particularly those that can be considered in program planning. Methods Two search strategies were used: 1) electronic database searching; and 2) grey literature searching. Inclusion criteria included papers published since 1998, in English, focusing on the sustainability of HPP that explicitly used a sustainability framework and specifically reported on facilitators and barriers to sustainability. Exclusion criteria included papers that addressed environmental, system or sector sustainability. Quality assessment was conducted on all included papers and a quality assessment tool was developed for grey literature. Data analysis included a thematic analysis, using an a priori framework to initially code barriers and facilitators, which were then grouped into factors for HPP sustainability. Factors were then analyzed for frequency, importance, and relevance, and categorized into one of three tiers. Results Sixteen papers were included in this review. Eleven definitions of sustainability and 13 sustainability frameworks were used. A total of 83 barriers and 191 facilitators were identified and categorized into 14 factors: nine from the a priori framework, and five additional ones based on the results of our analysis. Tier 1 factors were the most important for sustainability with organizational capacity scoring the highest; tier 3, the least important. Conclusion This review provides clarity regarding existing definitions of sustainability and sustainability frameworks. It identifies fourteen factors that influence program sustainability, which practitioners can consider when planning, developing and implementing HPP. In addition, it is important for practitioners to clearly articulate program elements that should be sustained, define sustainability as it relates to the context of their program, select a sustainability framework to guide their work, and consider these factors for sustainability.

Background Due to the myriad of benefits of children’s outdoor play and time, there is increasing concern over its decline. This systematic review synthesized evidence on the correlates of outdoor play and outdoor time among children aged 3-12 years. Methods A total of 12 electronic databases in five different languages (Chinese, English, Korean, Spanish, Portuguese) were searched between October 28, 2019 and July 27, 2020. Covidence software was used for screening and Microsoft Excel with a predesigned coding form was used for data extraction. Evidence was synthesized and correlates were categorized using the socioecological model framework. Results Based on 107 studies representing 188,498 participants and 422 childcare centers from 29 countries, 85 studies examined potential correlates of outdoor play while 23 studies examined that of outdoor time (one examined both). The duration of outdoor play and outdoor time ranged between 60 and 165 min/d and 42-240 min/d, respectively. Out of 287 (outdoor play) and 61 (outdoor time) potential correlates examined, 111 correlates for outdoor play and 33 correlates for outdoor time were identified as significant correlates. Thirty-three variables were identified as key/common correlates of outdoor play/time, including eight correlates at the individual level (e.g., sex/gender, race/ethnicity, physical activity), 10 correlates at the parental level (e.g., parental attitude/support/behavior, parenting practice), nine at the microsystem level (e.g., proximal home/social environment such as residence type, peer influence), three at the macrosystem/community level (e.g., availability of space children can play), and three at the physical ecology/pressure for macrosystem change level (e.g., seasonality, rurality). No key correlates were found at the institutional level. Conclusions Individual, parental, and proximal physical (home) and social environments appear to play a role in children’s outdoor play and time. Ecological factors (i.e., seasonality, rurality) also appear to be related to outdoor play/time. Evidence was either inconsistent or lacking at institutional and macrosystem/community levels. Standardizing terminology and measures of outdoor play/time is warranted. Future work should investigate the interactions and processes of multiple variables across different levels of socioecological modelling to better understand the mechanisms through which outdoor play/time opportunities can be optimized for children while paying special attention to varying conditions in which children are born, live, and play.

Background Daily time spent in moderate-to-vigorous physical activity (MVPA), light-intensity physical activity (LIPA), sedentary behaviour (SB) and sleep (collectively known as ‘movement behaviours’) are compositional, co-dependent variables. However, most studies examining effects of these behaviours on depression outcomes in older adults do not account for this. Study objectives were to use compositional data analysis methods to (1) examine the relationship between movement behaviour composition (daily time spent in MVPA, LIPA, SB, sleep) and depression symptoms, (2) estimate the extent to which changing time spent in any given movement behaviour within the movement behaviour composition was associated with changes in depression symptoms. Methods 5643 older Canadian adults ≥ 65 years of age from the Canadian Longitudinal Study on Aging were studied using a quasi-longitudinal study design. Exposure was baseline daily movement behaviours; time spent in MVPA, LIPA and SB were derived from self-reported Physical Activity Scale for the Elderly responses. Night-time sleep was self-reported separately. Outcome was depression symptoms at follow-up obtained using the ten item Center for Epidemiologic Studies Depression Scale. Compositional data analysis was used to investigate associations between movement behaviours and depression symptoms. Results Movement behaviour composition was significantly associated with depression symptoms. Time spent in MVPA [exp(B) = 0.97 (95% CI: 0.94, 0.99)] and sleep [exp(B) = 0.91 (95% CI: 0.85, 0.97)] relative to the remaining movement behaviours were associated with lower depression symptoms scores. Relative time spent in SB was associated with higher depression symptoms scores [exp(B) = 1.09 (95% CI: 1.04, 1.15)]. Time displacement estimates revealed that the greatest change in depression symptoms scores occurred when time spent in MVPA was decreased and replaced with LIPA, SB, sleep or combination of these behaviours (+ 0.22 to 0.26 points increase on depression symptoms scores for 30 min/day displacements). Conclusions Daily movement behaviour composition was associated with depression symptoms in older Canadians. Replacing time in MVPA with equivalent time from any other behaviour was associated with increased depression symptoms. Preserving time spent in MVPA may play a key role in mitigating and improving mental health in this demographic.

The impacts of 24-hour movement behaviours [a term that collectively refers to physical activity (PA), sedentary behaviour (SB), and sleep] on healthy ageing in older adults is understudied. Of this limited literature, the extent of associations between movement behaviours and healthy ageing outcomes are largely hampered by flawed methodological approaches for analysing movement behaviour data. My aim with this thesis research is to use an integrated approach to more closely examine associations between daily movement behaviours and two key determinants of healthy ageing: quality of life (QOL) and depression symptoms. The objectives are to: 1) synthesise and critically examine the literature on movement behaviours and QOL; 2) employ compositional data analysis to examine associations between movement behaviours and QOL and depression symptoms, respectively to determine if associations still hold, and how effects of changing time spent between movement behaviours impact these two outcomes relative to the time spent in remaining behaviours, focussing exclusively on the Canadian older adult population ≥ 65 years of age.Manuscript one is the first to systematically review the literature on movement behaviours and QOL in older adults using an integrated movement behaviour approach. It is also the first to represent QOL by distinct domains, and to categorise and group study results accordingly. Overall, the findings indicate that movement behaviours are associated with QOL. Moderate-to-vigorous physical activity (MVPA) is favourably associated with QOL. The evidence regarding light-intensity physical activity (LIPA), SB and sleep duration is inconsistent.Subsequently, two empirical studies applied a compositional data analysis framework to data from the Canadian Longitudinal Study on Aging. Results from both analyses show that older Canadians spend most of their time across the day in SB and sleep, with limited activity and that daily movement behaviour composition is strongly associated with QOL and depression symptoms, respectively. In manuscript two, results show how reduction in time spent sedentary and increases in PA and sleep improve QOL. In manuscript three, results show how replacing time in MVPA with equivalent time from any other behaviour is associated with increase in depression symptoms. In both manuscripts, stratified analyses indicate that effects differ by sex and age group (younger old versus older old).Collectively, the findings from this thesis research demonstrate that the way older adults spend their time in movement behaviours throughout the course of a day has implications for healthy ageing. The work provides new avenues for researchers to explore how 24-hour movement behaviours are related to older adult health.

Treatment paradigms for patients with upper tract urothelial carcinoma (UTUC) are typically extrapolated from studies of bladder cancer despite their distinct clinical and molecular characteristics. The advancement of UTUC research is hampered by the lack of disease-specific models. Here, we report the establishment of patient derived xenograft (PDX) and cell line models that reflect the genomic and biological heterogeneity of the human disease. Models demonstrate high genomic concordance with the corresponding patient tumors, with invasive tumors more likely to successfully engraft. Treatment of PDX models with chemotherapy recapitulates responses observed in patients. Analysis of a HER2 S310F-mutant PDX suggests that an antibody drug conjugate targeting HER2 would have superior efficacy versus selective HER2 kinase inhibitors. In sum, the biological and phenotypic concordance between patient and PDXs suggest that these models could facilitate studies of intrinsic and acquired resistance and the development of personalized medicine strategies for UTUC patients. The advancement of upper tract urothelial carcinoma (UTUC) research is hampered by the lack of disease-specific models. Here, the authors report patient derived xenograft and cell line models of UTUC, and show that these models retain the genomic and biological heterogeneity of human disease.