Neutron Capture Enhances Dose and Reduces Cancer Cell Viability in and out of Beam During Helium and Carbon Ion Therapy.

PURPOSE: Neutron capture enhanced particle therapy (NCEPT) is a proposed augmentation of charged particle therapy that exploits thermal neutrons generated internally, within the treatment volume via nuclear fragmentation, to deliver a biochemically targeted radiation dose to cancer cells. This work is the first experimental demonstration of NCEPT, performed using both carbon and helium ion beams with 2 different targeted neutron capture agents (NCAs). METHODS AND MATERIALS: Human glioblastoma cells (T98G) were irradiated by carbon and helium ion beams in the presence of NCAs [10B]-BPA and [157Gd]-DOTA-TPP. Cells were positioned within a polymethyl methacrylate phantom either laterally adjacent to or within a 100 × 100 × 60 mm spread out Bragg peak (SOBP). The effect of NCAs and location relative to the SOBP on the cells was measured by cell growth and survival assays in 6 independent experiments. Neutron fluence within the phantom was characterized by quantifying the neutron activation of gold foil. RESULTS: Cells placed inside the treatment volume reached 10% survival by 2 Gy of carbon or 2 to 3 Gy of helium in the presence of NCAs compared with 5 Gy of carbon and 7 Gy of helium with no NCA. Cells placed adjacent to the treatment volume showed a dose-dependent decrease in cell growth when treated with NCAs, reaching 10% survival by 6 Gy of carbon or helium (to the treatment volume), compared with no detectable effect on cells without NCA. The mean thermal neutron fluence at the center of the SOBP was approximately 2.2 × 109 n/cm2/Gy (relative biological effectiveness) for the carbon beam and 5.8 × 109 n/cm2/Gy (relative biological effectiveness) for the helium beam and gradually decreased in all directions. CONCLUSIONS: The addition of NCAs to cancer cells during carbon and helium beam irradiation has a measurable effect on cell survival and growth in vitro. Through the capture of internally generated neutrons, NCEPT introduces the concept of a biochemically targeted radiation dose to charged particle therapy. NCEPT enables the established pharmaceuticals and concepts of neutron capture therapy to be applied to a wider range of deeply situated and diffuse tumors, by targeting this dose to microinfiltrates and cells outside of defined treatment regions. These results also demonstrate the potential for NCEPT to provide an increased dose to tumor tissue within the treatment volume, with a reduction in radiation doses to off-target tissue.

Naturally occurring radioactive materials in offshore infrastructure: Understanding formation and characteristics of baryte scale during decommissioning planning.

Contaminants, including naturally occurring radioactive material (NORM) of the 238-uranium and 232-thorium decay series, have been recognized as a global research priority to inform offshore petroleum infrastructure decommissioning decisions. This study aimed to characterize pipeline scale retrieved from a decommissioned subsea well tubular pipe through high-resolution elemental mapping and isotopic analysis. This was achieved by utilizing transmission electron microscopy, Synchrotron x-ray fluorescence, photostimulated luminescence autoradiography and Isotope Ratio Mass Spectrometry. The scale was identified as baryte (BaSO4) forming a dense crystalline matrix, with heterogenous texture and elongated crystals. The changing chemical and physical microenvironment within the pipe influenced the gradual growth rate of baryte over the production life of this infrastructure. A distinct compositional banding of baryte and celestine (SrSO4) bands was observed. Radioactivity attributed by the presence of radionuclides (226Ra, 228Ra) throughout the scale was strongly correlated with baryte. From the detailed scale characterization, we can infer the baryte scale gradually formed within the internals of the tubular well pipe along the duration of production (i.e., 17 years). This new knowledge and insight into the characteristics and formation of petroleum waste products will assist with decommissioning planning to mitigate potential radiological risks to marine ecosystems.

Higher Neighborhood Drivability Is Associated With a Higher Diabetes Risk in Younger Adults: A Population-Based Cohort Study in Toronto, Canada.

OBJECTIVE: Car dependency contributes to physical inactivity and, consequently, may increase the likelihood of diabetes. We investigated whether neighborhoods that are highly conducive to driving confer a greater risk of developing diabetes and, if so, whether this differs by age. RESEARCH DESIGN AND METHODS: We used administrative health care data to identify all working-age Canadian adults (20-64 years) who were living in Toronto on 1 April 2011 without diabetes (type 1 or 2). Neighborhood drivability scores were assigned using a novel, validated index that predicts driving patterns based on built environment features divided into quintiles. Cox regression was used to examine the association between neighborhood drivability and 7-year risk of diabetes onset, overall and by age-group, adjusting for baseline characteristics and comorbidities. RESULTS: Overall, there were 1,473,994 adults in the cohort (mean age 40.9 ± 12.2 years), among whom 77,835 developed diabetes during follow-up. Those living in the most drivable neighborhoods (quintile 5) had a 41% higher risk of developing diabetes compared with those in the least drivable neighborhoods (adjusted hazard ratio 1.41, 95% CI 1.37-1.44), with the strongest associations in younger adults aged 20-34 years (1.57, 95% CI 1.47-1.68, P < 0.001 for interaction). The same comparison in older adults (55-64 years) yielded smaller differences (1.31, 95% CI 1.26-1.36). Associations appeared to be strongest in middle-income neighborhoods for younger residents (middle income 1.96, 95% CI 1.64-2.33) and older residents (1.46, 95% CI 1.32-1.62). CONCLUSIONS: High neighborhood drivability is a risk factor for diabetes, particularly in younger adults. This finding has important implications for future urban design policies.

Complete Genome Sequence of the Gordonia Bacteriophage BiggityBass.

Here, we characterized the complete genome of the Siphoviridae BiggityBass, a lytic subcluster DR bacteriophage infecting Gordonia terrae CAG3. Its 63.2-kb genome contains 84 protein-coding genes, of which 40 could be assigned a putative function. BiggityBass is related most closely to AnClar and Yago84 with 90.61% and 90.52% nucleotide identity, respectively.

Comparative Genomics of Closely-Related Gordonia Cluster DR Bacteriophages.

Bacteriophages infecting bacteria of the genus Gordonia have increasingly gained interest in the scientific community for their diverse applications in agriculture, biotechnology, and medicine, ranging from biocontrol agents in wastewater management to the treatment of opportunistic pathogens in pulmonary disease patients. However, due to the time and costs associated with experimental isolation and cultivation, host ranges for many bacteriophages remain poorly characterized, hindering a more efficient usage of bacteriophages in these areas. Here, we perform a series of computational genomic inferences to predict the putative host ranges of all Gordonia cluster DR bacteriophages known to date. Our analyses suggest that BiggityBass (as well as several of its close relatives) is likely able to infect host bacteria from a wide range of genera-from Gordonia to Nocardia to Rhodococcus, making it a suitable candidate for future phage therapy and wastewater treatment strategies.

Guillain-Barré syndrome as an early manifestation of angioimmunoblastic T-cell lymphoma.

Guillain-Barré syndrome (GBS) is a rare condition caused by autoimmune damage of peripheral nerves. We describe a case where a man in his 80s presented with subacute, progressive fatigue and weakness. He had received an outpatient work-up for possible haematological malignancy, but eventually presented to the emergency department for worsening weakness. A physical exam and cerebrospinal fluid analysis suggested a diagnosis of GBS. Subsequently, a pathological diagnosis of angioimmunoblastic T-cell lymphoma was made. The patient underwent intravenous immunoglobulin treatment for GBS and was started on cyclophosphamide, doxorubicin, vincristine and prednisone therapy. Prior research has suggested that incident malignancy may be associated with GBS, which may be caused by a paraneoplastic-type phenomenon, malignancy-associated immune dysregulation or an autoimmune reaction triggered by a common exposure. Clinicians should be aware of the possible association between these two conditions and should remain open minded to the possibility of non-infectious triggers for GBS.

The Weight of Place: Built Environment Correlates of Obesity and Diabetes.

In recent decades, the prevalence of obesity and diabetes has risen substantially in North America and worldwide. To address these dual epidemics, researchers and policymakers alike have been searching for effective means to promote healthy lifestyles at a population level. As a consequence, there has been a proliferation of research examining how the "built" environment in which we live influences physical activity levels, by promoting active forms of transportation, such as walking and cycling, over passive ones, such as car use. Shifting the transportation choices of local residents may mean that more members of the population can participate in physical activity during their daily routine without structured exercise programs. Increasingly, this line of research has considered the downstream metabolic consequences of the environment in which we live, raising the possibility that "healthier" community designs could help mitigate the rise in obesity and diabetes prevalence. This review discusses the evidence examining the relationship between the built environment, physical activity, and obesity-related diseases. We also consider how other environmental factors may interact with the built environment to influence metabolic health, highlighting challenges in understanding causal relationships in this area of research.

Microgravity × Radiation: A Space Mechanobiology Approach Toward Cardiovascular Function and Disease.

In recent years, there has been an increasing interest in space exploration, supported by the accelerated technological advancements in the field. This has led to a new potential environment that humans could be exposed to in the very near future, and therefore an increasing request to evaluate the impact this may have on our body, including health risks associated with this endeavor. A critical component in regulating the human pathophysiology is represented by the cardiovascular system, which may be heavily affected in these extreme environments of microgravity and radiation. This mini review aims to identify the impact of microgravity and radiation on the cardiovascular system. Being able to understand the effect that comes with deep space explorations, including that of microgravity and space radiation, may also allow us to get a deeper understanding of the heart and ultimately our own basic physiological processes. This information may unlock new factors to consider with space exploration whilst simultaneously increasing our knowledge of the cardiovascular system and potentially associated diseases.

Mitochondrial Translocator Protein (TSPO) Expression in the Brain After Whole Body Gamma Irradiation.

The brain's early response to low dose ionizing radiation, as may be encountered during diagnostic procedures and space exploration, is not yet fully characterized. In the brain parenchyma, the mitochondrial translocator protein (TSPO) is constitutively expressed at low levels by endothelial cells, and can therefore be used to assess the integrity of the brain's vasculature. At the same time, the inducible expression of TSPO in activated microglia, the brain's intrinsic immune cells, is a regularly observed early indicator of subtle or incipient brain pathology. Here, we explored the use of TSPO as a biomarker of brain tissue injury following whole body irradiation. Post-radiation responses were measured in C57BL/6 wild type (Tspo +/+) and TSPO knockout (Tspo -/-) mice 48 h after single whole body gamma irradiations with low doses 0, 0.01, and 0.1 Gy and a high dose of 2 Gy. Additionally, post-radiation responses of primary microglial cell cultures were measured at 1, 4, 24, and 48 h at an irradiation dose range of 0 Gy-2 Gy. TSPO mRNA and protein expression in the brain showed a decreased trend after 0.01 Gy relative to sham-irradiated controls, but remained unchanged after higher doses. Immunohistochemistry confirmed subtle decreases in TSPO expression after 0.01 Gy in vascular endothelial cells of the hippocampal region and in ependymal cells, with no detectable changes following higher doses. Cytokine concentrations in plasma after whole body irradiation showed differential changes in IL-6 and IL-10 with some variations between Tspo-/- and Tspo +/+ animals. The in vitro measurements of TSPO in primary microglial cell cultures showed a significant reduction 1 h after low dose irradiation (0.01 Gy). In summary, acute low and high doses of gamma irradiation up to 2 Gy reduced TSPO expression in the brain's vascular compartment without de novo induction of TSPO expression in parenchymal microglia, while TSPO expression in directly irradiated, isolated, and thus highly activated microglia, too, was reduced after low dose irradiation. The potential link between TSPO, its role in mitochondrial energy metabolism and the selective radiation sensitivity, notably of cells with constitutive TSPO expression such as vascular endothelial cells, merits further exploration.

Zinc Accumulates in the Nodes of Wheat Following the Foliar Application of 65Zn Oxide Nano- and Microparticles.

Using zinc (Zn) foliar fertilizers to enhance the grain quality of wheat (Triticum aestivum) can be an effective alternative or supplement to Zn soil fertilizers. However, knowledge about the mechanisms of Zn absorption and translocation following foliar application is scarce. Here, autoradiography and γ-spectrometry were used to investigate the behavior of 65Zn applied to wheat leaves as soluble 65Zn chloride (65ZnCl2), chelated 65Zn (65ZnEDTA), 65Zn oxide nanoparticle (65ZnO-NP) suspensions, and 65ZnO microparticle (65ZnO-MP) suspensions. The largest amount of 65Zn absorption occurred in 65ZnCl2 treated leaves. However, this treatment (65ZnCl2) also had the lowest proportion of absorbed 65Zn translocated away from the treated leaf after 15 d due to leaf scorching (p = 0.0007). Foliar-applied 65ZnO-NPs and 65ZnO-MPs had the lowest absorption, but 65ZnO-NPs had the highest relative translocation. 65Zinc EDTA was intermediate, with higher 65Zn absorption than 65ZnO treatments but similar translocation. Regardless, the majority of the foliar-applied 65Zn remained in the treated leaf for all treatments. Furthermore, 65ZnO-NPs and 65ZnO-MPs accumulated in plant nodes, suggesting that Zn was absorbed as dissolved 65Zn and particulate 65ZnO. Overall, the form and amount of absorbed 65Zn affected translocation.

Social Cohesion and Community Resilience During COVID-19 and Pandemics: A Rapid Scoping Review to Inform the United Nations Research Roadmap for COVID-19 Recovery.

Shock events uncover deficits in social cohesion and exacerbate existing social inequalities at the household, community, local, regional, and national levels. National and regional government recovery planning requires careful stakeholder engagement that centers on marginalized people, particularly women and marginalized community leaders. The aim of this rapid scoping review was to inform the United Nations Research Roadmap for the COVID-19 Recovery, based on Pillar 5 of the United Nations Framework for the Immediate Socioeconomic Response to COVID-19: Social Cohesion and Community Resilience. We present a summary of key concepts across the literature that helped situate this review. The results include a description of the state of the science and a review of themes identified as being crucial to sustainable and equitable recovery planning by the United Nations. The role of social cohesion during a disaster, particularly its importance for upstream planning and relationship building before a disaster occurs, is not well understood and is a promising area of future research. Understanding the applicability of social cohesion measurement methodologies and outcomes across different communities and geographies, as well as the development of new and relevant instruments and techniques, is urgently needed in the context of the global COVID-19 pandemic.

The uneven impacts of avoiding public transit on riders' access to healthcare during COVID-19.

Background: During the COVID-19 pandemic, many urban residents stopped riding public transit despite their reliance on it to reach essential services like healthcare. Few studies have examined the implications of public transit reliance on riders' ability to reach healthcare when transit is disrupted. To understand how shocks to transportation systems impact healthcare access, this study measures the impact of avoiding public transit on the ability of riders to access healthcare and pharmacy services during lockdowns. Methods: We deployed a cross-sectional survey of residents of Toronto and Vancouver in May 2020 through Facebook advertisements and community list-serves. Eligibility criteria included riding transit at least weekly prior to the pandemic and subsequent cessation of transit use during the pandemic. We applied multivariable modified Poisson models to identify socio-demographic, transportation, health-related, and neighborhood predictors of experiencing increased difficulty accessing healthcare and getting prescriptions while avoiding public transit. We also predicted which respondents reported deferring medical care until they felt comfortable riding transit again. Results: A total of 4367 former transit riders were included (64.2% female, 56.1% Toronto residents). Several factors were associated with deferring medical care including: being non-White (Toronto, APR, 1.14; 95% CI, 1.00-1.29; Vancouver, APR, 1.52; 95% CI, 1.26-1.84), having a physical disability (Toronto, APR, 1.20; 95% CI, 1.00-1.45; Vancouver, APR, 1.42; 95% CI, 1.08-1.87), having no vehicle access (Toronto, APR, 1.74; 95% CI, 1.51-2.00; Vancouver, APR, 2.74; 95% CI, 2.20-3.42), and having low income (Toronto, APR, 1.77; 95% CI, 1.44-2.17; Vancouver, APR, 1.51; 95% CI, 1.06-2.14). Discussion: During COVID-19 in two major Canadian cities, former transit riders from marginalized groups were more likely to defer medical care than other former riders. COVID-19 related transit disruptions may have imposed a disproportionate burden on the health access of marginalized individuals. Policymakers should consider prioritizing healthcare access for vulnerable residents during crises.

A Qualitative Study on the Barriers to Learning in a Primary Care-Behavioral Health Integration Program in an Academic Hospital: the Family Medicine Perspective.

OBJECTIVE: Integrating behavioral health services into the primary care setting is a recognized approach to improving timely access and building capacity for primary care providers. The aim of this study was to examine barriers to family medicine resident learning in a co-located primary care-behavioral health integration program with psychiatrists in an academic hospital. METHODS: The authors used a descriptive qualitative study design to collect data on participants' learning experiences from focus groups and semi-structured interviews with 5 family medicine residents, 3 psychiatry residents, 5 family physicians, 3 psychiatrists, 2 office coordinators, and 2 educational coordinators. Thematic analysis of transcripts was performed. RESULTS: Three themes were identified with respect to barriers to learning in the program from the family medicine perspective. Organizational barriers encompassed lack of clear vision, goals, roles, and responsibilities. Administrative barriers involved complex appointment bookings and scheduling. Communication and engagement barriers included insufficient communication between team members and lack of patient engagement in the program. CONCLUSIONS: The study findings highlight the importance of several factors for the successful implementation of a co-located academic primary care-behavioral health integrated model. This includes the formalization of program structure that encompasses shared vision, goals, roles, and responsibilities; coordinated processes for appointment bookings; team communication and patient engagement; and diverse educational and longitudinal care opportunities. With the growing number of integrated care programs, these results provide guidance for health care leaders involved in the design and management of primary care-behavioral health integration programs.

Association Between Neighborhood Walkability and Predicted 10-Year Cardiovascular Disease Risk: The CANHEART (Cardiovascular Health in Ambulatory Care Research Team) Cohort.

Background Individuals living in unwalkable neighborhoods appear to be less physically active and more likely to develop obesity, diabetes mellitus, and hypertension. It is unclear whether neighborhood walkability is a risk factor for future cardiovascular disease. Methods and Results We studied residents living in major urban centers in Ontario, Canada on January 1, 2008, using linked electronic medical record and administrative health data from the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) cohort. Walkability was assessed using a validated index based on population and residential density, street connectivity, and the number of walkable destinations in each neighborhood, divided into quintiles (Q). The primary outcome was a predicted 10-year cardiovascular disease risk of ≥7.5% (recommended threshold for statin use) assessed by the American College of Cardiology/American Heart Association Pooled Cohort Equation. Adjusted associations were estimated using logistic regression models. Secondary outcomes included measured systolic blood pressure, total and high-density lipoprotein cholesterol levels, prior diabetes mellitus diagnosis, and current smoking status. In total, 44 448 individuals were included in our analyses. Fully adjusted analyses found a nonlinear relationship between walkability and predicted 10-year cardiovascular disease risk (least [Q1] versus most [Q5] walkable neighborhood: odds ratio =1.09, 95% CI: 0.98, 1.22), with the greatest difference between Q3 and Q5 (odds ratio=1.33, 95% CI: 1.23, 1.45). Dose-response associations were observed for systolic blood pressure, high-density lipoprotein cholesterol, and diabetes mellitus risk, while an inverse association was observed with smoking status. Conclusions In our setting, adults living in less walkable neighborhoods had a higher predicted 10-year cardiovascular disease risk than those living in highly walkable areas.

The probability of diabetes and hypertension by levels of neighborhood walkability and traffic-related air pollution across 15 municipalities in Southern Ontario, Canada: A dataset derived from 2,496,458 community dwelling-adults.

Individuals' risk for cardiovascular disease is shaped by lifestyle factors such as participation in physical activity. Some studies have suggested that rates of physical activity may be higher in walkable neighborhoods that are more supportive of engaging in physical activity in daily life. However, walkable neighborhoods may also contain increased levels of traffic-related air pollution (TRAP). Traffic-related air pollution, often measured through a surrogate marker (e.g. NO2), has been associated cardiovascular disease risk and risk factors [1], [2], [3], [4]. The higher levels of TRAP in walkable neighborhoods may in turn increase the likelihood of developing conditions like hypertension and diabetes. Our recent work assessed how walkability and TRAP jointly affect the odds of diabetes and hypertension in a sample of community-dwelling adults from Southern Ontario, Canada [5]. This article contains additional data on the probability and odds of hypertension and diabetes according to their walkability and TRAP exposures. Data on cardiovascular risk factors were collected using health administrative databases and environmental exposures were assessed using national land use regression models predicting ground level concentrations of NO2 and validated walkability indices. The included data were generated using logistic regression accounting for exposures, covariates, and neighborhood clustering. These data may be used as primary data in future health risk assessments and systematic reviews, or to aid in the design of studies examining interactions between built environment and TRAP exposures (e.g. sample size calculations).

Interaction between neighborhood walkability and traffic-related air pollution on hypertension and diabetes: The CANHEART cohort.

BACKGROUND: Living in unwalkable neighborhoods has been associated with heightened risk for diabetes and hypertension. However, highly walkable environments may have higher concentrations of traffic-related air pollution, which may contribute to increased cardiovascular disease risk. We therefore aimed to assess how walkability and traffic-related air pollution jointly affect risk for hypertension and diabetes. METHODS: We used a cross-sectional, population-based sample of individuals aged 40-74 years residing in selected large urban centres in Ontario, Canada on January 1, 2008, assembled from administrative databases. Walkability and traffic-related air pollution (NO2) were assessed using validated tools and linked to individuals based on neighborhood of residence. Logistic regression was used to estimate adjusted associations between exposures and diagnoses of hypertension or diabetes accounting for potential confounders. RESULTS: Overall, 2,496,458 individuals were included in our analyses. Low walkability was associated with higher odds of hypertension (lowest vs. highest quintile OR = 1.34, 95% CI: 1.32, 1.37) and diabetes (lowest vs. highest quintile OR = 1.25, 95% CI: 1.22, 1.29), while NO2 exhibited similar trends (hypertension: OR = 1.09 per 10 p.p.b., 95% CI: 1.08, 1.10; diabetes: OR = 1.16, 95% CI: 1.14, 1.17). Significant interactions were identified between walkability and NO2 on risk for hypertension (p < 0.0001 and diabetes (p < 0.0001). At higher levels of pollution (40 p.p.b.), differences in the probability of hypertension (lowest vs. highest walkability quintile: 0.26 vs. 0.25) or diabetes (lowest vs. highest walkability quintile: 0.15 vs. 0.15) between highly walkable and unwalkable neighborhoods were diminished, compared to differences observed at lower levels of pollution (5 p.p.b.) (hypertension, lowest vs. highest walkability quintile: 0.21 vs. 0.13; diabetes, lowest vs. highest walkability quintile: 0.09 vs. 0.06). CONCLUSIONS: Walkability and traffic-related air pollution interact to jointly predict risk for hypertension and diabetes. Although walkable neighborhoods appear to have beneficial effects, they may accentuate the harmful effects of air pollution on cardiovascular risk factors.

Biofilm-enhanced adsorption of strong and weak cations onto different microplastic sample types: Use of spectroscopy, microscopy and radiotracer methods.

The adsorption of metals and other elements onto environmental plastics has been previously quantified and is known to be enhanced by surface-weathering and development of biofilms. However, further biofilm-adsorption characterisation is needed with respect to the fate of radionuclides. This study uses spectroscopy, microscopy and radiotracer methods to investigate the adsorption capacity of relatively strong and weak cations onto different microplastic sample types that were conditioned in freshwater, estuarine and marine conditions although marine data were limited. Fourier-transform infrared spectroscopy confirmed that surface oxidation chemistry changes induced by gamma irradiation were similar to those resulting from environmental exposures. Microscopy elemental mapping revealed patchy biofilm development, which contained Si, Al, and O, consistent with microbial-facilitated capture of clays. The plastics+biofilm of all sample types had measurable adsorption for Cs and Sr radiotracers, suggesting environmental plastics act broadly as a sink for the key pervasive environmental radionuclides of 137Cs and 90Sr associated with releases from nuclear activities. Adsorption onto high-density polyethylene plastic types was greater than that on polypropylene. However, in most cases, the adsorption rates of all types of plastic+biofilm were much lower than those of reference sediments and roughly consistent with their relative exchangeable surface areas.

Mediation analysis with a time-to-event outcome: a review of use and reporting in healthcare research.

BACKGROUND: Mediation analysis tests whether the relationship between two variables is explained by a third intermediate variable. We sought to describe the usage and reporting of mediation analysis with time-to-event outcomes in published healthcare research. METHODS: A systematic search of Medline, Embase, and Web of Science was executed in December 2016 to identify applications of mediation analysis to healthcare research involving a clinically relevant time-to-event outcome. We summarized usage over time and reporting of important methodological characteristics. RESULTS: We included 149 primary studies, published from 1997 to 2016. Most studies were published after 2011 (n = 110, 74%), and the annual number of studies nearly doubled in the last year (from n = 21 to n = 40). A traditional approach (causal steps or change in coefficient) was most commonly taken (n = 87, 58%), and the majority of studies (n = 114, 77%) used a Cox Proportional Hazards regression for the outcome. Few studies (n = 52, 35%) mentioned any of the assumptions or limitations fundamental to a causal interpretation of mediation analysis. CONCLUSION: There is increasing use of mediation analysis with time-to-event outcomes. Current usage is limited by reliance on traditional methods and the Cox Proportional Hazards model, as well as low rates of reporting of underlying assumptions. There is a need for formal criteria to aid authors, reviewers, and readers reporting or appraising such studies.

Association between residential self-selection and non-residential built environment exposures.

Studies employing 'activity space' measures of the built environment do not always account for how individuals self-select into different residential and non-residential environments when testing associations with physical activity. To date, no study has examined whether preferences for walkable residential neighborhoods predict exposure to other walkable neighborhoods in non-residential activity spaces. Using a sample of 9783 university students from Toronto, Canada, we assessed how self-reported preferences for a walkable neighborhood predicted their exposure to other walkable, non-residential environments, and further whether these preferences confounded observed walkability-physical activity associations. We found that residential walkability preferences and non-residential walkability were significant associated (ß = 0.42, 95% CI: (0.37, 0.47)), and further that these preferences confounded associations between non-residential walkability exposure and time spent walking (reduction in association = 10.5%). These results suggest that self-selection factors affect studies of non-residential built environment exposures.