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.

Perturbational phenotyping of human blood cells reveals genetically determined latent traits associated with subsets of common diseases.

Although genome-wide association studies (GWAS) have successfully linked genetic risk loci to various disorders, identifying underlying cellular biological mechanisms remains challenging due to the complex nature of common diseases. We established a framework using human peripheral blood cells, physical, chemical and pharmacological perturbations, and flow cytometry-based functional readouts to reveal latent cellular processes and performed GWAS based on these evoked traits in up to 2,600 individuals. We identified 119 genomic loci implicating 96 genes associated with these cellular responses and discovered associations between evoked blood phenotypes and subsets of common diseases. We found a population of pro-inflammatory anti-apoptotic neutrophils prevalent in individuals with specific subsets of cardiometabolic disease. Multigenic models based on this trait predicted the risk of developing chronic kidney disease in type 2 diabetes patients. By expanding the phenotypic space for human genetic studies, we could identify variants associated with large effect response differences, stratify patients and efficiently characterize the underlying biology.