School Attendance Among Pediatric Oncology Patients During the COVID-19 Pandemic in Ontario, Canada.

Supporting schooling for current and past pediatric oncology patients is vital to their quality of life and psychosocial recovery. However, no study has examined the perspectives toward in-person schooling among pediatric oncology families during the COVID-19 pandemic. In this online survey study, we determined the rate of and attitudes toward in-person school attendance among current and past pediatric oncology patients living in Ontario, Canada during the 2020-2021 school year. Of our 31-family cohort, 23 children (74%) did attend and 8 (26%) did not attend any in-person school during this time. Fewer children within 2 years of treatment completion attended in-person school (5/8; 62%) than those more than 2 years from treatment completion (13/15; 87%). Notably, 22 of 29 parents (76%) felt that speaking to their care team had the greatest impact compared to other potential information sources when deciding about school participation, yet 13 (45%) were unaware of their physician's specific recommendation regarding whether their child should attend. This study highlights the range in parental comfort regarding permitting in-person schooling during the COVID-19 pandemic. Pediatric oncologists should continue to address parental concerns around in-person school during times of high transmission of COVID-19 and potentially other communicable diseases in the future.

Neighborhood walkability, neighborhood social health, and self-selection among U.S. adults.

OBJECTIVES: Neighborhood walkability is favorably related to multiple physical health outcomes, but associations with social health are less clear. Present analyses examined how neighborhood walkability was related to neighborhood social health and explored the potential confounding role of neighborhood self-selection. METHODS: Cross-sectional data were analyzed for 1745 adults, ages 20-66, recruited from two US regions. We created a walkability index around each participant's home (1 km street network buffer) based on residential density, street intersection density, mixed land use, and retail floor area ratio. Neighborhood social health outcomes included reported social interactions with neighbors and sense of community. Two mixed model regressions were conducted for each outcome, with and without adjusting for walkability-related reasons for moving to the neighborhood (self-selection). Covariates included sex, age, socioeconomic status, white/nonwhite race/ethnicity, marital status, and time living in the neighborhood. RESULTS: Neighborhood walkability was positively related to social interactions with neighbors, both without (b = 0.13, p < .001) and with adjustment for self-selection (b = 0.09, p = .008). Neighborhood walkability was positively associated with sense of community, but only before adjusting for self-selection (b = 0.02, p = .009). CONCLUSION: Neighborhood walkability may promote specific aspects of neighborhood social health, which together are beneficial for physical and mental health. These findings provide additional impetus for enhancing walkability of US communities.

A qualitative study of what motivates and enables climate-engaged physicians in Canada to engage in health-care sustainability, advocacy, and action.

Increasing numbers of health-care professionals are aware of the need to deliver low-carbon sustainable health systems. We aimed to explore how physicians can be motivated and supported to pursue this ambition by conducting an exploratory qualitative descriptive study that involved individual in-depth interviews with climate-engaged Canadian physicians participating in health-care sustainability advocacy and action. Interview transcripts were analysed to identify themes related to the actions that physicians can take to promote sustainable health care, and the motivators and enablers of physician engagement in sustainable health care. Participants (n=19) engaged in a spectrum of health-care sustainability initiatives ranging from reducing health-care waste to lobbying and political action. They were motivated to advance health-care sustainability by their concern about the health implications of climate change, frustration with health-care waste, and recognition of their locus of influence as physicians. Participants articulated that policy and system, organisational and team, and knowledge generation and translation supports are required to strengthen their capacity to advance health-care sustainability. These findings can provide inspiration for engagement opportunities in health-care sustainability, guide service delivery and educational innovations to promote health-care professionals' interest in becoming sustainability champions, and extend the capacity of health-care professionals to reduce the climate impact of health care.

City planning policies to support health and sustainability: an international comparison of policy indicators for 25 cities.

City planning policies influence urban lifestyles, health, and sustainability. We assessed policy frameworks for city planning for 25 cities across 19 lower-middle-income countries, upper-middle-income countries, and high-income countries to identify whether these policies supported the creation of healthy and sustainable cities. We systematically collected policy data for evidence-informed indicators related to integrated city planning, air pollution, destination accessibility, distribution of employment, demand management, design, density, distance to public transport, and transport infrastructure investment. Content analysis identified strengths, limitations, and gaps in policies, allowing us to draw comparisons between cities. We found that despite common policy rhetoric endorsing healthy and sustainable cities, there was a paucity of measurable policy targets in place to achieve these aspirations. Some policies were inconsistent with public health evidence, which sets up barriers to achieving healthy and sustainable urban environments. There is an urgent need to build capacity for health-enhancing city planning policy and governance, particularly in low-income and middle-income countries.

Development and initial clinical correlation of a DNA methylation-based blood test for prostate cancer.

BACKGROUND: One of the principle limitations for more precise management of advanced prostate cancer is the lack of accurate biomarkers allowing estimation of tumor burden, ongoing assessment of progression, and response to treatment. Although prostate-specific antigen (PSA) performs modestly, nonsecreting cancers including those with early castrate-resistance warrant investigation of other predictive biomarkers. The objectives of these studies were to develop and perform initial validation of a circulating tumor DNA (ctDNA) methylation assay. METHODS: Methylation DETection of Circulating Tumor DNA (mDETECT) is a highly multiplexed targeted sequencing DNA methylation-based ctDNA blood test that captures the vast majority of prostate cancer phenotypes due to a careful development process that ensures that each probe region is methylated in at least 50% of all methylation-based subtypes and is not methylated in normal tissues. Next-generation sequencing of targeted polymerase chain reaction (PCR) products whose amplification is biased towards methylated DNA ensures the specificity of the assay by identifying multiple tumor-specific methylated CpG residues in each read. RESULTS: The final test is comprised of 46 PCR probes to 40 regions. It is relatively resistant to contaminating normal DNA and as a result functions in both serum and plasma samples. The assay was initially validated in a variety of prostate cancer cell lines to ensure specificity. Using a small number of longitudinal samples from prostate cancer patients initiating androgen deprivation therapy, the ability of mDETECT to track tumor burden was assessed compared with PSA. The mDETECT test signal generally paralleled that of PSA increasing and decreasing commensurate with tumor evolution in these patients. In two cases it appeared to anticipate clinical progression by a number of months compared to PSA and in a PSA nonproducing case, it was able to track tumor progression. CONCLUSIONS: mDETECT offers a promising tool for the assessment of prostate cancer burden based on the sensitive detection of prostate-specific ctDNA and requires further validation.

Structural Basis of Enhanced Crystallizability Induced by a Molecular Chaperone for Antibody Antigen-Binding Fragments.

Monoclonal antibodies constitute one of the largest groups of drugs to treat cancers and immune disorders, and are guiding the design of vaccines against infectious diseases. Fragments antigen-binding (Fabs) have been preferred over monoclonal antibodies for the structural characterization of antibody-antigen complexes due to their relatively low flexibility. Nonetheless, Fabs often remain challenging to crystallize because of the surface characteristics of complementary determining regions and the residual flexibility in the hinge region between the variable and constant domains. Here, we used a variable heavy-chain (VHH) domain specific for the human kappa light chain to assist in the structure determination of three therapeutic Fabs that were recalcitrant to crystallization on their own. We show that this ligand alters the surface properties of the antibody-ligand complex and lowers its aggregation temperature to favor crystallization. The VHH crystallization chaperone also restricts the flexible hinge of Fabs to a narrow range of angles, and so independently of the variable region. Our findings contribute a valuable approach to antibody structure determination and provide biophysical insight into the principles that govern the crystallization of macromolecules.