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Abstract Background Transportation policies can impact health outcomes while simultaneously promoting social equity and environmental sustainability. We developed an agent-based model (ABM) to simulate the impacts of fare subsidies and congestion taxes on commuter decision-making and travel patterns. We report effects on mode share, travel time and transport-related physical activity (PA), including the variability of effects by socioeconomic strata (SES), and the trade-offs that may need to be considered in the implementation of these policies in a context with high levels of necessity-based physical activity. Methods The ABM design was informed by local stakeholder engagement. The demographic and spatial characteristics of the in-silico city, and its residents, were informed by local surveys and empirical studies. We used ridership and travel time data from the 2019 Bogotá Household Travel Survey to calibrate and validate the model by SES. We then explored the impacts of fare subsidy and congestion tax policy scenarios. Results Our model reproduced commuting patterns observed in Bogotá, including substantial necessity-based walking for transportation. At the city-level, congestion taxes fractionally reduced car use, including among mid-to-high SES groups but not among low SES commuters. Neither travel times nor physical activity levels were impacted at the city level or by SES. Comparatively, fare subsidies promoted city-level public transportation (PT) ridership, particularly under a ‘free-fare’ scenario, largely through reductions in walking trips. ‘Free fare’ policies also led to a large reduction in very long walking times and an overall reduction in the commuting-based attainment of physical activity guidelines. Differential effects were observed by SES, with free fares promoting PT ridership primarily among low-and-middle SES groups. These shifts to PT reduced median walking times among all SES groups, particularly low-SES groups. Moreover, the proportion of low-to-mid SES commuters meeting weekly physical activity recommendations decreased under the 'freefare' policy, with no change observed among high-SES groups. Conclusions Transport policies can differentially impact SES-level disparities in necessity-based walking and travel times. Understanding these impacts is critical in shaping transportation policies that balance the dual aims of reducing SES-level disparities in travel time (and time poverty) and the promotion of choice-based physical activity.

Purpose: To conduct a genome-wide association study (GWAS) of individuals with neuropathic ocular pain (NOP) symptoms to identify genomic variants that may predispose to NOP development. Design: Prospective study of individuals with NOP. Participants: Three hundred twenty-nine patients recruited from the Miami Veterans Affairs eye clinic. Methods: The Neuropathic Pain Symptom Inventory modified for the eye (NPSI-Eye) was completed to calculate a NPSI-Eye-Sub-Score (summed ratings of burning and wind sensitivity) as an indicator of NOP severity. A GWAS was performed for the NPSI-Eye-Sub-Score with a significance threshold of P 0.8) within ENSG00000279046 coding for transcript ENST00000624288.1. The most significant genes from gene-based tests were matrix metalloproteinase-19 (MMP19) (P = 1.12 × 10−5), zinc finger RNA-binding motif and serine/arginine rich-1 (ZRSR1) (P = 1.48 × 10−4), CTC-487M23.8 (P = 1.79 × 10−4), receptor expression-enhancing protein-5 (REEP5) (P = 2.36 × 10−4), and signal recognition particle-19 (SRP19) (P = 2.56 × 10−4). From gene set enrichment analysis, the sensory perception (false discovery rate = 6.57 × 10−3) and olfactory signaling (false discovery rate = 1.63 × 10−2) pathways were enriched with the most significant genes. Conclusions: Our GWAS revealed genes with protein products that may impact sensory perception, lending biological plausibility to a role for SNPs identified by our GWAS in the development of NOP. A better understanding of the biological relevance of these genes and pathways in the pathophysiology associated with NOP may facilitate future novel mechanism-based treatments. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Green vegetation may protect against heat-related death by improving thermal comfort. Few studies have investigated associations of green vegetation with heat-related mortality in Latin America or whether associations are modified by the spatial configuration of green vegetation. We used data from 323 Latin American cities and meta-regression models to estimate associations between city-level greenness, quantified using population-weighted normalized difference vegetation index values and modeled as three-level categorical terms, and excess deaths from heat (heat excess death fractions [heat EDFs]). Models were adjusted for city-level fine particulate matter concentration (PM2.5), social environment, and country group. In addition to estimating overall associations, we derived estimates of association stratified by green space clustering by including an interaction term between a green space clustering measure (dichotomized at the median of the distribution) and the three-level greenness variable. We stratified analyses by climate zone (arid vs. temperate and tropical combined). Among the 79 arid climate zone cities, those with moderate and high greenness levels had modestly lower heat EDFs compared to cities with the lowest greenness, although protective associations were more substantial in cities with moderate versus high greenness levels and confidence intervals (CI) crossed the null (Beta: −0.41, 95% CI: −1.06, 0.25; Beta −0.23, 95% CI: −0.95, 0.49, respectively). In 244 non-arid climate zone cities, associations were approximately null. We did not observe evidence of effect modification by green space clustering. Our results suggest that greenness may offer modest protection against heat-related mortality in arid climate zone Latin American cities.

Latin America is the world’s most urbanized region and its heterogeneous urban development may impact chronic diseases. In this study, the authors evaluate the association of built environment characteristics with body mass index, obesity, and type 2 diabetes.

IntroductionThis study provides an evaluation of the impacts of classroom-based adult bicycle education on bicycling activity, confidence and competency self-perceptions while bicycling, knowledge of the bicycling rules of the road, and mode choice in a sample of residents of the San Francisco Bay Area in the US.MethodsChanges were measured with self-administered surveys completed before and six weeks after the course intervention. Self-reported data were validated using objective data collected using the Ride Report app. We used multivariable regression analyses to examine changes in self-reported data over time.ResultsParticipants reported statistically significant increases in confidence while bicycling in both traffic and car-free areas, feelings of safety while bicycling in car-free areas, and knowledge of the rules of the road. While there were significant changes in the proportion of trips by foot, transit and TNC, there was no change in the count of trips made by bicycle.DiscussionAlthough overall changes in bicycling activity did not change, participants with initial low confidence increased bicycling activity and feelings of safety in traffic, compared to participants overall. Classroom-based bicycle education courses can improve bicycling confidence self-perception and increase knowledge of the bicycling rules of the road.

Abstract Background Transport walking has drawn growing interest due to its potential to increase levels of physical activities and reduce reliance on vehicles. While existing studies have compared built environment-health associations between Euclidean buffers and network buffers, no studies have systematically quantified the extent of bias in health effect estimates when exposures are measured in different buffers. Further, prior studies have done the comparisons focusing on only one or two geographic regions, limiting generalizability and restricting ability to test whether direction or magnitude of bias are different by context. This study aimed to quantify the degree of bias in associations between built environment exposures and transport walking when exposures were operationalized using Euclidean buffers rather than network buffers in diverse contexts. Methods We performed a simulations study to systematically evaluate the degree of bias in associations between built environment exposures in Euclidean buffers and network buffers and transport walking, assuming network buffers more accurately captured true exposures. Additionally, we used empirical data from a multi-ethnic, multi-site cohort to compare associations between built environment amenities and walking for transport where built environment exposures were derived using Euclidean buffers versus network buffers. Results Simulation results found that the bias induced by using Euclidean buffer models was consistently negative across the six study sites (ranging from -80% to -20%), suggesting built environment exposures measured using Euclidean buffers underestimate health effects on transport walking. Percent bias was uniformly smaller for the larger 5 km scale than the 1 km and 0.25 km spatial scales, independent of site or built environment categories. Empirical findings aligned with the simulation results: built environment-health associations were stronger for built environment exposures operationalized using network buffers than using Euclidean buffers. Conclusion This study is the first to quantify the extent of bias in the magnitude of the associations between built environment exposures and transport walking when the former are measured in Euclidean buffers vs. network buffers, informing future research to carefully conceptualize appropriate distance-based buffer metrics in order to better approximate real geographic contexts. It also helps contextualize existing research in the field that used Euclidean buffers when that were the only option. Further, this study provides an example of the uncertain geographic context problem.

Background: Vertebral fractures, frequently resulting from high-impact trauma to the spine, are an increasingly relevant public health concern. Little is known about the long-term economic and demographic trends affecting patients undergoing surgery for such fractures. This study examines national economic and demographic trends in vertebral fracture surgery in the United States to improve value-based care and health care utilization. Methods: The National Inpatient Sample (NIS) was queried for patients who underwent surgical treatment of a vertebral fracture (ICD-9-CM-3.53) (excluding kyphoplasty and vertebroplasty) between 1993 and 2015. Demographic data included patient age, sex, income, insurance type, hospital size, and location. Economic data including aggregate charge, aggregate cost, hospital cost, and hospital charge were analyzed. Results: The number of vertebral fracture surgeries, excluding kyphoplasty and vertebroplasty, increased 461% from 3,331 in 1993 to 18,675 in 2014, while inpatient mortality increased from 1.9% to 2.5%.The mean age of patients undergoing vertebral fracture surgeries increased from 42 in 1993 to 53 in 2015. The aggregate cost of surgery increased from $189,164,625 in 2001 to $1,060,866,580 in 2014, a 461% increase. Conclusions: The significant increase in vertebral fracture surgeries between 1993 and 2014 may reflect an increased rate of fractures, more surgeons electing to treat fractures surgically, or a combination of both. The increasing rate of vertebral fracture surgery, coupled with increasing hospital costs and mortality, signifies that the treatment of vertebral fractures remains a challenging issue in healthcare. Further research is necessary to determine the underlying cause of both the increase in surgeries and the increasing mortality rate.

Abstract Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and leads to deadly metastases for which there is no approved treatment. Genetic events driving early tumor development are well-described, but those occurring later during metastatic progression remain poorly understood. We performed multiregional genomic sequencing on 22 tumors collected from two patients with widely metastatic UM who underwent rapid autopsy. We observed multiple seeding events from the primary tumors, metastasis-to-metastasis seeding, polyclonal seeding, and late driver variants in ATM, KRAS, and other genes previously unreported in UM. These findings reveal previously unrecognized temporal and anatomic complexity in the genetic evolution of metastatic uveal melanoma, and they highlight the distinction between early and late phases of UM genetic evolution with implications for novel therapeutic approaches.

Despite the worldwide popularity of bus rapid transit (BRT), empirical evidence of its effects on land uses and development remains limited. This paper examines BRT’s impacts on land use and development in Bogotá and Quito, by using a parcel-level difference-in-differences research design. We estimate a propensity score-weighted regression model of parcel development characteristics in treatment and control areas. In Bogotá, although parcels in close proximity to the BRT are subject to fewer changes in terms of development intensity (changes in built-up area) in relation to parcels in the control area, they are more likely to change uses, shifting toward commercial activities. In Quito, the results are mixed; parcels in one BRT corridor are more likely to be subject to redevelopment, but the parcels in a more recent BRT corridor are less likely to be subject to development activity in relation to parcels in the control corridor. Taken together, our results suggest that changes in land use are important but frequently overlooked impacts produced by BRT implementation. Attempts to capture value from mass transit investments should also consider the ancillary planning decisions required to allow changes in land use.

Abstract Background Although neighborhood-level access to food differs by sociodemographic factors, a majority of research on neighborhoods and food access has used a single construct of neighborhood context, such as income or race. Therefore, the many interrelated built environment and sociodemographic characteristics of neighborhoods obscure relationships between neighborhood factors and food access. Methods The objective of this study was to account for the many interrelated characteristics of food-related neighborhood environments and examine the association between neighborhood type and relative availability of sit-down restaurants and supermarkets. Using cluster analyses with multiple measures of neighborhood characteristics (e.g., population density, mix of land use, and sociodemographic factors) we identified six neighborhood types in 1993 in the Twin Cities Region, Minnesota. We then used mixed effects regression models to estimate differences in the relative availability of sit-down restaurants and supermarkets in 1993, 2001, and 2011 across the six neighborhood types. Results We defined six types of neighborhoods that existed in 1993, namely, urban core, inner city, urban, aging suburb, high-income suburb, and suburban edge. Between 1993 and 2011, inner city neighborhoods experienced a greater increase in the percent of sit-down restaurants compared with urban core, urban, and aging suburbs. Differences in the percent of sit-down restaurants between inner city and aging suburbs, high-income suburbs and suburban edge neighborhoods increased between 1993 and 2011. Similarly, aging suburb neighborhoods had a greater percent of supermarkets compared with urban and high-income suburb neighborhoods in 2001 and 2011, but not in 1993, suggesting a more varied distribution of food stores across neighborhoods over time. Thus, the classification of neighborhood type based on sociodemographic and built environment characteristics resulted in a complex and increasingly varied distribution of restaurants and food stores. Conclusions The temporal increase in the relative availability of sit-down restaurants in inner cities after accounting for all restaurants might be partly related to a higher proportion of residents who eat-away-from-home, which is associated with higher calorie and fat intake.

Uveal melanoma is highly metastatic and unresponsive to checkpoint immunotherapy. Here, the authors present single-cell transcriptomics of 59,915 cells in 8 primary and 3 metastatic samples, highlighting the diversity of the tumour microenvironment.

The goal of the study was to examine whether a genetic polymorphism in tumor necrosis factor receptor 1 (TNFR1) gene impacted the dry eye disease (DED) phenotype and response to anti-inflammatory therapy. The prospective study included 328 individuals with various dry eye (DE) symptoms and signs recruited from the Miami Veterans Hospital eye clinic between October 2013 and October 2017. The population underwent genetic profiling for a polymorphism within the TNFR1 gene (rs1800693 [TT, TC, CC]). The study examined the genotype distribution and relationships between the genotype, phenotype, and response to anti-inflammatory therapy. The mean age of the population was 61.7 ± 9.8 years. Here, 92% self-identified as male, 44% as White, and 21% as Hispanic; 13% (n = 42) of individuals had a CC genotype. DED symptoms and signs were similar across the three genotype groups. Thirty individuals (four with CC) were subsequently treated with an anti-inflammatory agent. There was a non-significant trend for individuals with CC genotype to have a partial or complete symptomatic response to treatment compared with the other two groups (100% for CC vs. 40% for TT and 36.4% for TC, p = 0.22). In conclusion, the presence of homozygosity of minor allele C (CC genotype) in a single nucleotide polymorphism (SNP) within TNFR1 was noted in a minority of individuals with various aspects of DED, but did not impact the DED phenotype. Our findings suggest that the current phenotyping strategies for DED are insufficient to identify underlying disease contributors, including potential genetic contributors.

Abstract Background Recent advances in single cell sequencing technologies allow for greater resolution in assessing tumor clonality using chromosome copy number variations (CNVs). While single cell DNA sequencing technologies are ideal to identify tumor sub-clones, they remain expensive and in contrast to single cell RNA-seq (scRNA-seq) methods are more limited in the data they generate. However, CNV data can be inferred from scRNA-seq and bulk RNA-seq, for which several tools have been developed, including inferCNV, CaSpER, and HoneyBADGER. Inferences regarding tumor clonality from CNV data (and other sources) are frequently visualized using phylogenetic plots, which previously required time-consuming and error-prone, manual analysis. Results Here, we present Uphyloplot2, a python script that generates phylogenetic plots directly from inferred RNA-seq data, or any Newick formatted dendrogram file. The tool is publicly available at https://github.com/harbourlab/UPhyloplot2/ . Conclusions Uphyloplot2 is an easy-to-use tool to generate phylogenetic plots to depict tumor clonality from scRNA-seq data and other sources.

Brazil is a powerhouse in terms of water resources, which are instrumental to the country’s transition to sustainability. However, to realize this potential, substantial management and conservation hurdles must first be overcome. We propose a novel strategy for the use, management, and conservation of Brazilian water resources. Our approach recognizes the spatial heterogeneity of water abundance and is based on a multisectoral perspective, including energy, food, sanitation, and environmental conservation. The main recommendations are to adopt low-cost local and subnational solutions and to design policy mixes, both based on the logic of the nexus water-food-energy-ecosystem. We offer as examples programs that 1) increase cistern infrastructure in drylands, 2) use constructed wetlands to improve sewage treatment in small cities and vulnerable areas, 3) turn the focus of conservation to aquatic ecosystems, 4) stimulate the adoption of small hydrokinetic turbines for energy generation in sparsely populated river-abundant regions, such as the Amazon Region, 5) diversify the matrix of renewable energy sources by combining hydropower with biomass and wind energy generation, and 6) mixes policies by integrating multiple sectors to improve regulation, use and management of water resources, such as the Brazilian “Water for All” Program. By following these recommendations, Brazil would align itself with the goals established in international agreements and would turn its abundance of water resources into development opportunities.

The built environment of cities is complex and influences social and environmental determinants of health. In this study we, 1) identified city profiles based on the built landscape and street design characteristics of cities in Latin America and 2) evaluated the associations of city profiles with social determinants of health and air pollution. Landscape and street design profiles of 370 cities were identified using finite mixture modeling. For landscape, we measured fragmentation, isolation, and shape. For street design, we measured street connectivity, street length, and directness. We fitted a two-level linear mixed model to assess the association of social and environmental determinants of health with the profiles. We identified four profiles for landscape and four for the street design domain. The most common landscape profile was the “proximate stones” characterized by moderate fragmentation, isolation and patch size, and irregular shape. The most common street design profile was the “semi-hyperbolic grid” characterized by moderate connectivity, street length, and directness. The “semi-hyperbolic grid”, “spiderweb” and “hyperbolic grid” profiles were positively associated with higher access to piped water and less overcrowding. The “semi-hyperbolic grid” and “spiderweb” profiles were associated with higher air pollution. The “proximate stones” and “proximate inkblots” profiles were associated with higher congestion. In conclusion, there is substantial heterogeneity in the urban landscape and street design profiles of Latin American cities. While we did not find a specific built environment profile that was consistently associated with lower air pollution and better social conditions, the different configurations of the built environments of cities should be considered when planning healthy and sustainable cities in Latin America.

Abstract This article describes the origins and characteristics of an interdisciplinary multinational collaboration aimed at promoting and disseminating actionable evidence on the drivers of health in cities in Latin America and the Caribbean: The Network for Urban Health in Latin America and the Caribbean and the Wellcome Trust funded SALURBAL (Salud Urbana en América Latina, or Urban Health in Latin America) Project. Both initiatives have the goals of supporting urban policies that promote health and health equity in cities of the region while at the same time generating generalizable knowledge for urban areas across the globe. The processes, challenges, as well as the lessons learned to date in launching and implementing these collaborations, are described. By leveraging the unique features of the Latin American region (one of the most urbanized areas of the world with some of the most innovative urban policies), the aim is to produce generalizable knowledge about the links between urbanization, health, and environments and to identify effective ways to organize, design, and govern cities to improve health, reduce health inequalities, and maximize environmental sustainability in cities all over the world.

In this paper we employ Mecklenburg County, North Carolina, a polycentric city with 10 employment subcenters, as a case study to explore the role of employment subcenters in determining residential location decisions. We estimate discrete choice models of residential location decisions: conditional logit models and heteroscedastic logit models with both the full choice set and sampled choices. We find that access to certain employment subcenters, measured in terms of generalized cost, is an important determinant of households' residential location decisions. The proximity to specific employment subcenters varies across households with different income levels. These patterns can be explained by existing land use and transportation patterns, as well as by subcenters' economic specialization.

Este artigo apresenta uma perspectiva geral dos impactos observados por mudanças no uso e cobertura da terra em bacias hidrográficas, com ênfase em regiões tropicais. Primeiramente, são abordadas as primeiras asserções sobre os impactos das mudanças no uso e cobertura da terra, os primeiros debates e os artigos científicos pioneiros em relação ao tema. Então, se expõe, em termos gerais, os impactos diretos e indiretos das mudanças no uso e cobertura da terra e o papel das florestas nesse contexto. Em seguida, apresenta-se um levantamento não detalhado de estudos em nível mundial e explora-se as regiões tropicais, com estudos na América do Sul, Ásia e África. Adicionalmente, discute-se o efeito de escala, tanto nos estudos em geral quanto na fragmentação dos habitats e considerações finais, identificando algumas tendências e propostas para o futuro de estudos no tema.

To date, there is a lack of information about the optimal conditions of the warm-up to lead to a better performance in elite tennis players. The aim of this study was to compare the effects of two different warm-up protocols (dynamic vs. self-myofascial release with foam rolling) on neuromuscular variables associated with physical determinants of tennis performance. Using a crossover randomised experimental design, eleven professional men tennis players (20.6 ± 3.5 years) performed either a dynamic warm-up (DWU) or a selfmyofascial release with foam rolling (SMFR) protocol. DWU consisted of 8 min of dynamic exercises at increasing intensity and SMFR consisted of 8 min of rolling on each lower extremity unilaterally. Just before (baseline) and after completing warm-up protocols, players performed a countermovement jump (CMJ), the 5-0-5 agility test, a 10-m sprint test and the Straight Leg Raise and Thomas tests to assess range of motion. Compared to baseline, the DWU was more effective to reduce the time in the 5-0-5 test than SMFR (-2.23 vs. 0.44%, respectively, p = 0.042, ηp2 = 0.19). However, both warm-up protocols similarly affected CMJ (2.32 vs. 0.61%, p = 0.373, ηp2 = 0.04) and 10-m sprint time changes (-1.26 vs. 1.03%, p = 0.124, ηp2 = 0.11). Changes in range of motion tests were also similar with both protocols (p = 0.448–1.000, ηp2 = 0.00–0.02). Overall, both DWU and SMFR were effective to prepare well-trained tennis players for highly demanding neuromuscular actions. However, DWU offered a better preparation for performing change of direction and sprint actions, and hence, in high-performance tennis players, the warm-up should include dynamic exercises.

Chagas disease, a worldwide public health concern, is a chronic infection caused by Trypanosoma cruzi. Considering T. cruzi chronic persistence correlates with CD4+ and CD8+ T cell dysfunction and the safety and efficacy profiles of Benznidazol and Nifurtimox, the two drugs currently used for its etiological treatment, are far from ideal, the search of new trypanocidal treatment options is a highly relevant issue. Therefore, the objective of this work was to evaluate the trypanocidal effect and cytokine production induction of three extracts (hexane, dichloromethane and hydroalcoholic) obtained from Clethra fimbriata, a plant traditionally used as a febrifuge in Colombia. Additionally, the extracts’ major components with the highest trypanocidal activity were determined. It was evidenced C. fimbriata hexane extract exhibited the highest activity capable of inhibiting the three parasite developmental stages with an IC50/EC50 of 153.9 ± 29.5 (epimastigotes), 39.3 ± 7.2 (trypomastigotes), and 45.6 ± 10.5 (amastigotes) μg/mL, presenting a low cytotoxicity in VERO cells with a selectivity index ranging from 6.49 to 25.4. Moreover, this extract induced trypomastigote apoptotic death and inhibited parasite cell infection. The extract also induced IFN-γ and TNF production in CD4+ and CD8+ T cells, as well as de novo production of the cytotoxic molecules granzyme B and perforin in CD8+ T cells from healthy donors. Fatty acids and terpenes represented C. fimbriata key compounds. Thus, the trypanocidal activity and cytokine production induction of the hexane extract may be associated with terpene presence, particularly, triterpenes.

In post-industrial settings, apolipoprotein E4 (APOE4) is associated with increased cardiovascular and neurological disease risk. However, the majority of human evolutionary history occurred in environments with higher pathogenic diversity and low cardiovascular risk. We hypothesize that in high-pathogen and energy-limited contexts, the APOE4 allele confers benefits by reducing innate inflammation when uninfected, while maintaining higher lipid levels that buffer costs of immune activation during infection. Among Tsimane forager-farmers of Bolivia (N = 1266, 50% female), APOE4 is associated with 30% lower C-reactive protein, and higher total cholesterol and oxidized LDL. Blood lipids were either not associated, or negatively associated with inflammatory biomarkers, except for associations of oxidized LDL and inflammation which were limited to obese adults. Further, APOE4 carriers maintain higher levels of total and LDL cholesterol at low body mass indices (BMIs). These results suggest that the relationship between APOE4 and lipids may be beneficial for pathogen-driven immune responses and unlikely to increase cardiovascular risk in an active subsistence population.