Building CapaCITY/É for sustainable transportation: protocol for an implementation science research program in healthy cities.

INTRODUCTION: Improving sustainable transportation options will help cities tackle growing challenges related to population health, congestion, climate change and inequity. Interventions supporting active transportation face many practical and political hurdles. Implementation science aims to understand how interventions or policies arise, how they can be translated to new contexts or scales and who benefits. Sustainable transportation interventions are complex, and existing implementation science frameworks may not be suitable. To apply and adapt implementation science for healthy cities, we have launched our mixed-methods research programme, CapaCITY/É. We aim to understand how, why and for whom sustainable transportation interventions are successful and when they are not. METHODS AND ANALYSIS: Across nine Canadian municipalities and the State of Victoria (Australia), our research will focus on two types of sustainable transportation interventions: all ages and abilities bicycle networks and motor vehicle speed management interventions. We will (1) document the implementation process and outcomes of both types of sustainable transportation interventions; (2) examine equity, health and mobility impacts of these interventions; (3) advance implementation science by developing a novel sustainable transportation implementation science framework and (4) develop tools for scaling up and scaling out sustainable transportation interventions. Training activities will develop interdisciplinary scholars and practitioners able to work at the nexus of academia and sustainable cities. ETHICS AND DISSEMINATION: This study received approval from the Simon Fraser University Office of Ethics Research (H22-03469). A Knowledge Mobilization Hub will coordinate dissemination of findings via a website; presentations to academic, community organisations and practitioner audiences; and through peer-reviewed articles.

Promoting children's health through community-led street interventions: analyzing sustained voluntarism in Canadian School Streets.

BACKGROUND: Active School Travel (AST) initiatives align with the Ottawa Charter for Health Promotion, which calls for 'creating supportive environments' and 'strengthening community action.' However, their reliance on volunteers poses sustainability challenges. The main objectives of this study were to document the motivations, satisfaction, and experiences of volunteers involved in sustaining two AST initiatives in Ontario for an entire school year. METHODS: Two volunteer-led School Street initiatives in Kingston, Ontario successfully operated during pick-up and drop-off times of each school day. The first initiative operated for the entire 2021-2022 school year, and the second operated for the entire 2022-2023 school year. These initiatives were the first of their kind in the province of Ontario, Canada. Volunteers from both sites (n = 56) participated in online surveys and their motivations, satisfaction, and experiences of their role were compared using the 2-sided Fisher's Exact Test. RESULTS: Over 80% of volunteers were highly motivated to promote safety and over 70% of volunteers were highly motivated to disrupt the status quo of unsupportive, car-centric urban environments by reimagining how streets can be used. By taking collective action to re-shape the environment around these public schools to support healthy, active living, our findings reveal that over 90% of volunteers were highly satisfied. Of the volunteers, 87% felt they contributed to child safety and 85% felt they had developed stronger community connections. They appreciated the short (i.e., 40 minute) time commitment of each shift, weekly email communications by the community organization leading the initiative, and the volunteer schedule. They also appreciated the positive social interactions during volunteer shifts, which they felt outweighed the minimal resistance they experienced. CONCLUSIONS: This research demonstrates the importance of logistical, motivational, and social factors in recruiting and retaining volunteers for community-led School Streets. Our findings support appealing to prospective volunteers' influence in achieving School Street objectives (e.g., improved safety) in recruitment efforts, as well as highlighting School Streets' innovative approach. Communicating with volunteers throughout School Street planning and implementation processes and limiting traffic in the closed street zone (i.e., by excluding the school staff parking lot and private driveways from the scope) are additional recommendations based on the findings of this study.

Investigating social inequalities in children's independent mobility, active transportation and outdoor free play in two Canadian cities.

Background: Active transportation (AT) and free play (FP) are the primary ways in which children engage in unstructured physical activity in cities, with independent mobility (IM) gaining increased attention as a potential precursor of AT and FP. However, current trends show that children are engaging in less FP and AT, and have less IM, than previous generations and it is not well understood how these practices, and their interrelatedness, differ by neighbourhood-level socio-economic stats (SES) and municipal contexts. Objectives: This study aims to address the gaps in knowledge by quantifying, comparing, and correlating IM, AT, and FP practices in high and low-SES neighbourhoods within and across the cities of Montreal and Kingston, Canada. Methods: 584 questionnaires were distributed among children in grades 1 to 5, living in low- and high-SES neighbourhoods of these two citiesResultsEngagement in the three practices was low in every study neighbourhood, though all three practices were higher in high-SES compared to low-SES neighbourhoods in both cities. Levels of FP were higher in Kingston compared to Montreal, while AT was higher in Montreal than in Kingston. Conclusion: This study revealed social inequalities in all three of these practices based on socioeconomic status and city. Since IM is likely a precursor to both independent FP and AT, more research is warranted into how our cities can become more conducive to IM in children, particularly in low SES neighbourhoods where children have less freedom of movement independently and otherwise.

Children's right to the city and their independent mobility: why it matters for public health.

Automobile-centric community design, or 'motornormativity', severely restricts opportunities for children to engage in active transportation (AT) and outdoor free play (OFP). As these activities are critical to children's health and well-being, their decline has become a major public health concern. Meanwhile, independent mobility (IM) has emerged as a critical determinant of child development and well-being. Defined as 'the freedom for children to move about their neighbourhood without adult supervision', children's IM is in direct conflict with motornormativity. And yet, very few studies explore these three practices together, and very few public health interventions actively confront motornormativity to support children's IM. We hypothesise that IM is foundational to AT and OFP, and that efforts to increase AT and OFP are doomed to fail without a deep understanding of the barriers to children's IM. We conclude with ideas to study and support children's IM in public health research and practice.

How to Recognize and Correct Artifacts on Contrast-Enhanced Mammography.

Contrast-enhanced mammography (CEM) has emerged as an important new technology in breast imaging. It can demonstrate a number of imaging artifacts that have the potential to limit interpretation by either obscuring or potentially mimicking disease. Commonly encountered artifacts on CEM include patient motion artifacts (ripple and misregistration), pectoral highlighting artifact, breast implant artifact, halo artifact, corrugation artifact, cloudy fat artifact, contrast artifacts (retention and contamination), skin artifacts (skin line enhancement and skin overexposure), and skin lesions. Skin lesions may demonstrate a variety of imaging appearances and have both benign and malignant etiologies. It is important that the technologist, radiologist, and physicist be aware of potential artifacts and skin enhancement on CEM that may affect interpretation and understand their causes and potential solutions.

A Tale of Two Cities: Unpacking the Success and Failure of School Street Interventions in Two Canadian Cities.

One innovative strategy to support child-friendly cities is street-based interventions that provide safe, vehicle-free spaces for children to play and move about freely. School streets are one such innovation involving closing streets around elementary schools to vehicular traffic to improve children's safety as they come and go from school while providing opportunities for children to play and socialize on the street. Launching these initiatives in communities dominated by automobiles is enormously challenging and little is known about why these interventions are successfully launched in some places but not others. As part of a larger research project called Levelling the Playing Fields, two School Street initiatives were planned for the 2021-2022 school year; one initiative was successfully launched in Kingston, ON, while the second initiative failed to launch in Montreal, QC. Using a critical realist evaluation methodology, this paper documents the contextual elements and key mechanisms that enabled and constrained the launch of these School Streets in these cities, through document analysis and key informant interviews. Our results suggest that municipal and school support for the initiative are both imperative to establishing legitimacy and collaborative governance, both of which were necessary for a successful launch.

Automated phantom analysis for gamma cameras and SPECT: A methodology for use in a clinical setting.

PURPOSE: We introduce an automated, quantitative image analysis package for gamma camera and single photon emission computed tomography quality control. Our focus was to produce consistent methods that are feasible in clinical settings and use standard phantoms. METHODS: Four gamma cameras were used to acquire planar images of four-quadrant bar phantoms and projection views of an American College of Radiology (ACR) phantom as part of a standard gamma camera quality control program. Images were sent to QC-Track® (Atirix Medical Systems, Inc., Minneapolis, MN, USA), which automatically placed predetermined regions of interest (ROIs) and performed analysis. For the bar phantom, a standard deviation (SD)-based modulation transfer function was calculated for a circular ROI in each quadrant. The bar widths at various MTF values were reported using linear interpolation as applicable. For the ACR phantom, the contrast-to-noise ratio (CNR) for each sphere, a modulation for each rods section, and a percent deviation for uniformity ROIs was calculated. Spheres corresponding to a CNR of 3, and the rod size at various modulations were also reported using linear interpolation. Visual analysis was performed by three medical physicists to evaluate interobserver variability and correlation to quantitative values. RESULTS: Analysis of the bar phantom showed predictable differences with changes in matrix size and bar width and showed consistency over similar acquisitions over the course of the study. Analysis of the ACR Phantom showed increasing CNR and modulation with increasing sphere and rod diameter, as expected. For both phantoms, quantitative values from linear interpolation correlated well with visual analysis. CONCLUSION: Our automated method for quantitative image analysis is consistent and shows increased precision and sensitivity when compared to standard visual methods. Thresholds correspond well with visual analysis and previous guidelines for observer visibility (e.g., Rose criterion), making our framework suitable for routine use in a nuclear medicine department.

The IκB-protein BCL-3 controls Toll-like receptor-induced MAPK activity by promoting TPL-2 degradation in the nucleus.

Proinflammatory responses induced by Toll-like receptors (TLRs) are dependent on the activation of the NF-ĸB and mitogen-activated protein kinase (MAPK) pathways, which coordinate the transcription and synthesis of proinflammatory cytokines. We demonstrate that BCL-3, a nuclear IĸB protein that regulates NF-ĸB, also controls TLR-induced MAPK activity by regulating the stability of the TPL-2 kinase. TPL-2 is essential for MAPK activation by TLR ligands, and the rapid proteasomal degradation of active TPL-2 is a critical mechanism limiting TLR-induced MAPK activity. We reveal that TPL-2 is a nucleocytoplasmic shuttling protein and identify the nucleus as the primary site for TPL-2 degradation. BCL-3 interacts with TPL-2 and promotes its degradation by promoting its nuclear localization. As a consequence, Bcl3-/- macrophages have increased TPL-2 stability following TLR stimulation, leading to increased MAPK activity and MAPK-dependent responses. Moreover, BCL-3-mediated regulation of TPL-2 stability sets the MAPK activation threshold and determines the amount of TLR ligand required to initiate the production of inflammatory cytokines. Thus, the nucleus is a key site in the regulation of TLR-induced MAPK activity. BCL-3 links control of the MAPK and NF-ĸB pathways in the nucleus, and BCL-3-mediated TPL-2 regulation impacts on the cellular decision to initiate proinflammatory cytokine production in response to TLR activation.

Signal and contrast to noise ratio evaluation of fluoroscopic loops for interventional fluoroscope quality control.

Modern fluoroscopes pose a challenge for the clinical physicist for annual testing and continued upkeep. These fluoroscopes are critical to providing care to patients for complex interventions, and continue to evolve in automated image quality adjustments. Few tools in software or hardware currently exist to assist the physicist or technologist in gauging fluoroscope constancy or readiness for procedures. Many modalities such as mammography, computed tomography or even magnetic resonance imaging are much more evolved with respect to testing or quality control. In this work we sought to provide simple reproducible tools and methods for spot evaluating or continued quality testing of interventional fluoroscopes.

"It's not a food issue; it's an income issue": using Nutritious Food Basket costing for health equity advocacy.

OBJECTIVES: Ontario's public health units (PHUs) face considerable challenges in addressing the social determinants of health, even though "reducing health inequities" is a primary population health outcome in the Ontario Public Health Standards (OPHS). Since 1998, the OPHS mandated PHUs to use the Nutritious Food Basket (NFB) protocol to document food costs, a requirement that was removed in 2018. This study examined how the NFB advanced health equity advocacy by Ontario PHUs, and why some have used this tool more strategically than others. METHODS: Semi-structured qualitative phone interviews were conducted with 18 public health dietitians (PHDs) and three key informants between May and October 2017. Interviews were audio-recorded, transcribed, inductively coded, and analyzed. RESULTS: The PHDs agreed that the NFB tool provides essential localized evidence of inadequate incomes for people living in poverty, and supports the health equity mandate of PHUs in Ontario. Factors that support NFB research and advocacy work include strong PHU leadership regarding health equity, participation in community coalitions, and engagement with Ontario Dietitians in Public Health (ODPH). Interviewees identified lack of support at the PHU level and lack of coordination of food insecurity work at the Ministry of Health as significant barriers to PHUs' use of the NFB to advance health equity mandates. CONCLUSION: This study offers compelling evidence for reinstating NFB costing in the Ontario Public Health Standards as a mandatory requirement of PHUs. Without this requirement, the already-limited capacity of PHUs to advance health equity in Ontario will be further compromised.

Residential moves, neighbourhood walkability, and physical activity: a longitudinal pilot study in Ontario Canada.

BACKGROUND: Numerous cross-sectional studies have consistently demonstrated an association between attributes of urban form or 'walkability' and individual- and population-level physical activity (PA) patterns. However, in the absence of longitudinal research, the self-selection problem undermines the claim that a walkable built form produces more physically active people. Through a longitudinal pilot study of 'imminent movers' in Ontario using a quasi-experimental approach, we sought to examine the feasibility of longitudinal methods that would produce stronger evidence for a causal relationship between the built environment and PA levels. METHODS: Participants were recruited using publicly available real estate listings. Successful recruits were sent a PA diary to track their activity for a week, and were also scheduled for a 45-min phone interview that collected demographic details, neighbourhood perceptions and self-efficacy for walking, and verified the PA diary. Following their move, participants were given the same tasks and then sorted into groups based on changes in their neighbourhood walkability (measured with Walk Score) from baseline to follow-up. RESULTS: There were challenges in recruiting a sufficient number of participants and counter-factuals to examine the relationship between changes in walkability and PA. Our limited sample showed a substantial decrease in Walk Score over the entire sample, from an average of 45.8 to 30.6, with most participants moving to less walkable areas. From baseline to follow-up, the largest declines in reported self-efficacy for walking were to grocery stores, banks, and for entertainment. For the entire sample, utilitarian PA decreased, while recreational and job-related PA increased. CONCLUSIONS: This pilot study highlighted the methodological challenges involved in collecting quasi-experimental evidence on the effect of walkable environments on PA. Additionally, the low sample size and the tendency for most participants to move to less walkable areas meant there were insufficient counter-factuals for study of the effect of walkability on PA. Despite these challenges, we saw important changes in self-efficacy for walking that were commensurate with changes to the built environment. In sum, while longitudinal research on health and the built environment is urgently needed, recruiting an adequate sample size for a quasi-experimental study such as this is extremely challenging.

Implicating municipalities in addressing household food insecurity in Canada: A pan-Canadian analysis of news print media coverage.

OBJECTIVES: Household food insecurity (HFI) affects approximately 13% of Canadian households and is especially prevalent among low-income households. Actions to address HFI have been occurring primarily at the local level, despite calls for greater income supports from senior governments to reduce poverty. News media may be reinforcing this trend, by emphasizing food-based solutions to HFI and the municipal level as the site where action needs to take place. The objective of this study was to examine the level and framing of print news media coverage of HFI action in Canada. METHODS: Using a quantitative newspaper content analysis approach, we analyzed 547 articles gathered from 2 national and 16 local/regional English-language newspapers published between January 2007 and December 2012. RESULTS: News coverage increased over time, and over half was produced from Ontario (33%) and British Columbia (22%) combined. Of the 374 articles that profiled a specific action, community gardens/urban agriculture was most commonly profiled (17%), followed by food banks/meal programs (13%); 70% of articles implicated governments to take action on HFI, and of these, 43% implicated municipal governments. Article tone was notably more negative when senior governments were profiled and more neutral and positive when municipal governments were profiled. CONCLUSION: News media reporting of this issue in Canada may be placing pressure on municipalities to engage in food-based actions to address HFI. A more systematic approach to HFI action in Canada will require more balanced media reporting that acknowledges the limitations of food-based solutions to the income-based problem of HFI.

The Ubiquitination of NF-κB Subunits in the Control of Transcription.

Nuclear factor (NF)-κB has evolved as a latent, inducible family of transcription factors fundamental in the control of the inflammatory response. The transcription of hundreds of genes involved in inflammation and immune homeostasis require NF-κB, necessitating the need for its strict control. The inducible ubiquitination and proteasomal degradation of the cytoplasmic inhibitor of κB (IκB) proteins promotes the nuclear translocation and transcriptional activity of NF-κB. More recently, an additional role for ubiquitination in the regulation of NF-κB activity has been identified. In this case, the ubiquitination and degradation of the NF-κB subunits themselves plays a critical role in the termination of NF-κB activity and the associated transcriptional response. While there is still much to discover, a number of NF-κB ubiquitin ligases and deubiquitinases have now been identified which coordinate to regulate the NF-κB transcriptional response. This review will focus the regulation of NF-κB subunits by ubiquitination, the key regulatory components and their impact on NF-κB directed transcription.

Mapping the Interaction of B Cell Leukemia 3 (BCL-3) and Nuclear Factor κB (NF-κB) p50 Identifies a BCL-3-mimetic Anti-inflammatory Peptide.

The NF-κB transcriptional response is tightly regulated by a number of processes including the phosphorylation, ubiquitination, and subsequent proteasomal degradation of NF-κB subunits. The IκB family protein BCL-3 stabilizes a NF-κB p50 homodimer·DNA complex through inhibition of p50 ubiquitination. This complex inhibits the binding of the transcriptionally active NF-κB subunits p65 and c-Rel on the promoters of NF-κB target genes and functions to suppress inflammatory gene expression. We have previously shown that the direct interaction between p50 and BCL-3 is required for BCL-3-mediated inhibition of pro-inflammatory gene expression. In this study we have used immobilized peptide array technology to define regions of BCl-3 that mediate interaction with p50 homodimers. Our data show that BCL-3 makes extensive contacts with p50 homodimers and in particular with ankyrin repeats (ANK) 1, 6, and 7, and the N-terminal region of Bcl-3. Using these data we have designed a BCL-3 mimetic peptide based on a region of the ANK1 of BCL-3 that interacts with p50 and shares low sequence similarity with other IκB proteins. When fused to a cargo carrying peptide sequence this BCL-3-derived peptide, but not a mutated peptide, inhibited Toll-like receptor-induced cytokine expression in vitro. The BCL-3 mimetic peptide was also effective in preventing inflammation in vivo in the carrageenan-induced paw edema mouse model. This study demonstrates that therapeutic strategies aimed at mimicking the functional activity of BCL-3 may be effective in the treatment of inflammatory disease.

Measurement of NF-κB transcriptional activity and identification of NF-κB cis-regulatory elements using luciferase assays.

The NF-κB family of transcription factors is activated in response to numerous environmental stimuli and coordinates the transcriptional response to immunoreceptors such as the Toll-like receptors, cytokine receptors, and antigen receptors, growth factors, survival factors, and stress signals such as ultraviolet irradiation and oxidative stress. The transcriptional targets of these various pathways include approximately 500 experimentally indentified genes, and it is highly likely that many others remain to be discovered. A genome-wide analysis of NF-κB-chromatin interactions has revealed a surprisingly large number of NF-κB binding sites across the entire genome, many of which are found in intergenic regions and many more do not appear to be associated with changes in transcription of nearby genes. Assessing the consequences of NF-κB binding at genomic sites is therefore essential to determine the functional role of NF-κB in regulating the expression of specific genes. Luciferase-based reporter assays provide a robust and flexible method to test the contribution of specific NF-κB sites to the regulation of gene transcription. The methods described in this chapter may be applied to any promoter sequence and used in a variety of cell lines and conditions to provide critical information on the regulation of gene expression by NF-κB.

Assessing sites of NF-κB DNA binding using chromatin immunoprecipitation.

The NF-κB transcription factor is in fact a family of related proteins which dimerize to form at least 12 distinct complexes which regulate the expression of hundred of genes of importance to a range of physiological and pathological processes. The binding of NF-κB to the regulatory regions and promoters of target genes is influenced by a number of factors including the sequence of DNA-binding sites, the posttranslational modification of NF-κB, and the interaction of cofactors and co-regulators of transcription. In addition, the binding of NF-κB to promoters is highly dynamic and the recruitment of specific subunits to specific binding sites may occur with distinct kinetics. Moreover, genome-wide analysis of NF-κB chromatin binding indicates that the majority of DNA-binding events are not associated with changes in transcriptional activity. Thus, the analysis of NF-κB recruitment and activity at specific binding sites is of critical importance in understanding the regulation of transcription. In this chapter we describe a chromatin immunoprecipitation assay to investigate the in situ binding of NF-κB to specific sites in the genome.

Control of NF-κB subunits by ubiquitination.

NF-κB is an essential regulator of inflammation and is also required for normal immune development and homeostasis. The inducible activation of NF-κB by a wide range of immuno-receptors such as the toll-like receptors (TLR), Tumour Necrosis Factor receptor (TNFR), and antigen T cell and B cell receptors requires the ubiquitin-triggered proteasomal degradation of IκBα to promote the nuclear translocation and transcriptional activity of NF-κB dimers. More recently, an additional role for ubiquitination and proteasomal degradation in the control of NF-κB activity has been uncovered. In this case, it is the ubiquitination and proteasomal degradation of the NF-κB subunits that play a critical role in the termination of the NF-κB-dependent transcriptional response induced by receptor activation. The primary trigger of NF-κB ubiquitination is DNA binding by NF-κB dimers and is further controlled by specific phosphorylation events which regulate the interaction of NF-κB with the E3 ligase complex and the deubiquitinase enzyme USP7. It is the balance between ubiquitination and deubiquitination that shapes the NF-κB-mediated transcriptional response. This chapter describes methods for the analysis of NF-κB ubiquitination.

Examining the relationship between social support availability, urban center size, and self-perceived mental health of recent immigrants to Canada: a mixed-methods analysis.

The experiences of settlement in a new country (e.g., securing housing and employment, language barriers) pose numerous challenges for recent immigrants that can impede their health and well-being. Lack of social support upon arrival and during settlement may help to explain why immigrant mental health status declines over time. While most urban centers in Canada offer some settlement services, little is known about how the availability of social supports, and the health statuses of recent immigrants, varies by city size. The objective of this mixed-methods study was to examine the relationship between self-perceived mental health (SPMH), social support availability, and urban center size, for recent immigrants to Canada. The quantitative component involved analysis of 2009-2010 Canadian Community Health Survey data, selecting for only recent immigrants and for those living in either large or small urban centers. The qualitative component involved in-depth interviews with managers of settlement service organizations located in three large and three small urban centers in Canada. The quantitative analysis revealed that social support availability is positively associated with higher SPMH status, and is higher in small urban centers. In support of these findings, our interviews revealed that settlement service organizations operating in small urban centers offer more intensive social supports; interviewees attributed this difference to personal relationships in small cities, and the ease with which they can connect to other agencies to provide clients with necessary supports. Logistic regression analysis revealed, however, that recent immigrants in small urban centers are twice as likely to report low SPMH compared to those living in large urban centers. Thus, while the scope and nature of settlements services appears to vary by city size in Canada, more research is needed to understand what effect settlement services have on the health status of recent immigrants to Canada, especially in smaller urban centers.