Coordinated Cellular Neighborhoods Orchestrate Antitumoral Immunity at the Colorectal Cancer Invasive Front.

Antitumoral immunity requires organized, spatially nuanced interactions between components of the immune tumor microenvironment (iTME). Understanding this coordinated behavior in effective versus ineffective tumor control will advance immunotherapies. We re-engineered co-detection by indexing (CODEX) for paraffin-embedded tissue microarrays, enabling simultaneous profiling of 140 tissue regions from 35 advanced-stage colorectal cancer (CRC) patients with 56 protein markers. We identified nine conserved, distinct cellular neighborhoods (CNs)-a collection of components characteristic of the CRC iTME. Enrichment of PD-1+CD4+ T cells only within a granulocyte CN positively correlated with survival in a high-risk patient subset. Coupling of tumor and immune CNs, fragmentation of T cell and macrophage CNs, and disruption of inter-CN communication was associated with inferior outcomes. This study provides a framework for interrogating how complex biological processes, such as antitumoral immunity, occur through concerted actions of cells and spatial domains.

Transcription Factor-Directed Re-wiring of Chromatin Architecture for Somatic Cell Nuclear Reprogramming toward trans-Differentiation.

MYOD-directed fibroblast trans-differentiation into skeletal muscle provides a unique model to investigate how one transcription factor (TF) reconfigures the three-dimensional chromatin architecture to control gene expression, which is otherwise achieved by the combinatorial activities of multiple TFs. Integrative analysis of genome-wide high-resolution chromatin interactions, MYOD and CTCF DNA-binding profile, and gene expression, revealed that MYOD directs extensive re-wiring of interactions involving cis-regulatory and structural genomic elements, including promoters, enhancers, and insulated neighborhoods (INs). Re-configured INs were hot-spots of differential interactions, whereby MYOD binding to highly constrained sequences at IN boundaries and/or inside INs led to alterations of promoter-enhancer interactions to repress cell-of-origin genes and to activate muscle-specific genes. Functional evidence shows that MYOD-directed re-configuration of chromatin interactions temporally preceded the effect on gene expression and was mediated by direct MYOD-DNA binding. These data illustrate a model whereby a single TF alters multi-loop hubs to drive somatic cell trans-differentiation.

AnnoView enables large-scale analysis, comparison, and visualization of microbial gene neighborhoods.

The analysis and comparison of gene neighborhoods is a powerful approach for exploring microbial genome structure, function, and evolution. Although numerous tools exist for genome visualization and comparison, genome exploration across large genomic databases or user-generated datasets remains a challenge. Here, we introduce AnnoView, a web server designed for interactive exploration of gene neighborhoods across the bacterial and archaeal tree of life. Our server offers users the ability to identify, compare, and visualize gene neighborhoods of interest from 30 238 bacterial genomes and 1672 archaeal genomes, through integration with the comprehensive Genome Taxonomy Database and AnnoTree databases. Identified gene neighborhoods can be visualized using pre-computed functional annotations from different sources such as KEGG, Pfam and TIGRFAM, or clustered based on similarity. Alternatively, users can upload and explore their own custom genomic datasets in GBK, GFF or CSV format, or use AnnoView as a genome browser for relatively small genomes (e.g. viruses and plasmids). Ultimately, we anticipate that AnnoView will catalyze biological discovery by enabling user-friendly search, comparison, and visualization of genomic data. AnnoView is available at http://annoview.uwaterloo.ca.

The health implications of cumulative exposure to contextual (dis)advantage: Methodological and substantive advances from a unique data linkage.

Deleterious neighborhood conditions are associated with poor health, yet the health impact of cumulative lifetime exposure to neighborhood disadvantage is understudied. Using up to five decades of residential histories for 4,177 adult participants in the Survey of Health of Wisconsin (SHOW) and spatio-temporally linked neighborhood conditions, we develop four operational approaches to characterizing cumulative neighborhood (dis)advantage over the life course. We estimated their associations with self-reported general health and compared to estimates using neighborhood (dis)advantage at time of study enrollment. When cumulative exposures were assessed with the most granular temporal scale (Approach 4), neighborhood transport constraints (OR = 1.21, 95% CI: 1.08, 1.36), residential turnover (OR = 1.20, 95% CI: 1.07, 1.34), education deficit (OR = 1.17, 95% CI: 1.04, 1.32), racial segregation (OR = 1.20, 95% CI: 1.04, 1.38) and median household income (OR = 0.85, 95% CI: 0.75, 0.97) were significantly associated with risk of fair or poor health. For composite neighborhood disadvantage, cumulative exposures had a stronger association (OR = 1.05, 95% CI: 1.02, 1.08) than the cross-sectional exposure (OR = 1.03, 95% CI: 1.01, 1.06). Single point-in-time neighborhood measures underestimate the neighborhood and health relationship, underscoring the importance of a life course approach to cumulative exposure measurement.

Constructing Residential Histories in a General Population-Based Representative Sample.

Research on neighborhoods and health typically measures neighborhood context at a single point in time. However, neighborhood exposures accumulate over the life course, influenced by both residential mobility and neighborhood change, with potential implications for estimating the impact of neighborhoods on health. Commercial databases offer fine-grained longitudinal residential address data that can enrich life-course spatial epidemiology research, and validated methods for reconstructing residential histories from these databases are needed. Our study draws on unique data from a geographically diverse, population-based representative sample of adult Wisconsin residents and the LexisNexis (New York, New York) Accurint, a commercial personal profile database, to develop a systematic and reliable methodology for constructing individual residential histories. Our analysis demonstrated that creating residential histories across diverse geographical contexts is feasible, and it highlights differences in the information obtained from available residential histories by age, education, race/ethnicity, and rural/urban/suburban residency. Researchers should consider potential address data availability and information biases favoring socioeconomically advantaged individuals and their implications for studying health inequalities. Despite these limitations, LexisNexis data can generate varied residential exposure metrics and be linked to contextual data to enrich research into the contextual determinants of health at varied geographic scales.

Association between Neighborhood Stressors and Allostatic Load in Breast Cancer Survivors: The Pathways Study.

Allostatic load (AL) is an intermediary outcome through which neighborhood drivers of health may impact cancer survivorship outcomes. We examined associations of neighborhood stressors and AL in 2,553 women with breast cancer recruited into the Pathways Study in 2006-2013. AL score was derived from biomarkers in the cardiovascular, metabolic, and immune domains of physiological stress measured within 3 years after baseline. Neighborhood data were appended to participants' geocoded baseline addresses. Odds ratios (OR) and 95% confidence intervals (CI) were used to estimate associations between neighborhood stressors and risk of higher AL score. Adjusting for age and stage, high AL was positively associated with low versus high neighborhood socioeconomic status (nSES; OR=2.24, 95% CI=1.61-3.12) and green space (OR=1.55, 95% CI=1.18-2.03); high versus low traffic (OR=1.32, 95% CI=1.01-1.72), crime (OR=1.32, 95% CI=1.05-1.67), and household crowding (OR=1.57, 95% CI=1.22-2.01); and more versus no fast-food restaurants (OR=1.50, 95% CI=1.21-1.84). Associations remained for nSES and fast-food restaurants after co-adjustment with other neighborhood stressors, and for fast-food restaurants after additional adjustment with individual sociodemographic and lifestyle factors. Our preliminary findings can inform further studies of the physiological effects of neighborhood stressors, which collectively may help improve survivorship outcomes for the growing population of breast cancer survivors.

Racial and Economic Segregation Over the Life Course and Incident Hypertensive Disorders of Pregnancy Among Black Women in California.

Black women in the United States have the highest incidence of hypertensive disorders of pregnancy (HDP) and are disproportionately burdened by its adverse sequalae, compared with women of all racial and ethnic groups. Segregation, a key driver of structural racism for Black families, can provide information critical to understanding these disparities. We examined the association between racial and economic segregation at 2 points and incident HDP using intergenerationally linked birth records of 45,204 Black California-born primiparous mothers (born 1982-1997) and their infants (born 1997-2011), with HDP ascertained from hospital discharge records. Women's early childhood and adulthood neighborhoods were categorized as deprived, mixed, or privileged based on the Index of Concentration at the Extremes (a measure of concentrated racial and economic segregation), yielding 9 life-course trajectories. Women living in deprived neighborhoods at both time points experienced the highest odds of HDP (from mixed effect logistic regression, unadjusted odds ratio = 1.26, 95% confidence interval: 1.13, 1.40) compared with women living in privileged neighborhoods at both time points. All trajectories involving residence in a deprived neighborhood in early childhood or adulthood were associated with increased odds of HDP, whereas mixed-privileged and privileged-mixed trajectories were not. Future studies should assess the causal nature of these associations.

Dynamic chromosome association with nuclear organelles in living cells.

The development of progressively sophisticated tools complemented by the integration of live cell imaging enhances our understanding of the four-dimensional (4D) nucleome, revealing elaborate molecular interactions and chromatin states. Yet, the dynamics of chromosomes in relation to nuclear organelles or to each other across cell cycle in living cells are underexplored. We have developed photoconvertible GFP H3-Dendra2 stably expressing in PC3M cells. The nuclear lamina and perinucleolar associated heterochromatin or diffuse chromosome regions were photoconverted through a single-point activation using a confocal microscope. The results demonstrated a dynamic nature for both types of chromosomes in the same cell cycle and across mitosis. While some chromosome domains were heritably associated with either nuclear lamina or nucleoli, others changed alliance to different nuclear organelles postmitotically. In addition, co-photoconverted chromosome domains often do not stay together within the same cell cycle and across mitosis, suggesting a transient nature of chromosome neighborhoods. Long-range spreading and movement of chromosomes were also observed. Interestingly, when cells were treated with a low concentration of actinomycin D that inhibits Pol I transcription through intercalating GC-rich DNA, chromosome movement was significantly blocked. Treatment with another Pol I inhibitor, metarrestin, which does not impact DNA, had little effect on the movement, suggesting that the DNA structure itself plays a role in chromosome dynamics. Furthermore, inhibition of Pol II transcription with α-amanitin also reduced the chromosome movement, demonstrating that Pol II, but not Pol I transcription, is important for chromosome dynamics in the nucleus.

Latino Enclaves and Healthcare Accessibility: An Ecologic Study Across Five States.

BACKGROUND: Hispanic or Latino populations (hereafter, "Latinos") are a rapidly expanding U.S. demographic and have documented inequities in preventable diseases and conditions. Many Latinos reside in ethnic enclaves, and understanding the context and healthcare accessibility within these places is critical. OBJECTIVE: This study described the neighborhood social and built environment attributes of Latino enclaves and evaluated associations between enclaves and geographic healthcare accessibility. DESIGN: Cross-sectional ecologic analysis. SUBJECTS: Our unit of analysis was all neighborhoods (n ~ 20,000 census tracts) in California, Florida, New Jersey, New York, and Texas in years 2000 and 2010. MAIN MEASURES: The primary exposure of interest, "Latino enclaves," was defined using neighborhood-level data on the percentage of Latino residents, foreign-born Latinos, Spanish speakers with limited English proficiency, and linguistically isolated Spanish-speaking households. The primary outcome was a neighborhood-level measure of geographic healthcare accessibility of primary care physicians, which accounted for both the supply of physicians and population demand for healthcare (i.e., population size within driving distance). RESULTS: Approximately 30% of neighborhoods were classified as Latino enclaves, 87% of which were enclaves in both 2000 and 2010. Compared with non-enclaves, Latino enclaves had more markers of structural disadvantage including having higher proportions of poverty, uninsured individuals, crowded housing, and higher crime scores. Results from multivariable models suggest that more culturally distinct neighborhoods (i.e., higher enclave score) had lower healthcare accessibility, though when stratified, this association persisted only in high (≥ 20%) poverty neighborhoods. CONCLUSION: This study highlights several neighborhood structural disadvantages within Latino enclaves, including higher poverty, uninsured individuals, and crime compared to non-enclave neighborhoods. Moreover, our findings point to the need for interventions aimed at improving healthcare accessibility particularly within socioeconomically disadvantaged Latino enclaves. Addressing these inequities demands multifaceted approaches that consider both social and structural factors to ensure equitable healthcare access for Latino populations.

Neighborhood social composition and refugee mental health - quasi-experimental evidence of associations from a Danish population register study.

BACKGROUND: Refugees are at an elevated risk of some mental disorders with studies highlighting the contributing role of post-migration factors. Studies of migrant groups show neighborhood social composition, such as ethnic density, to be important. This is the first longitudinal study to examine this question for refugees and uses a novel quasi-experimental design. METHODS: We followed a cohort of 44 033 refugees from being first assigned housing under the Danish dispersal policy, operating from 1986 to 1998, until 2019. This comprised, in effect, a natural experiment whereby the influence of assigned neighborhood could be determined independently of endogenous factors. We examined three aspects of neighborhood social composition: proportion of co-nationals, refugees, and first-generation migrants; and subsequent incidence of different mental disorders. RESULTS: Refugees assigned to neighborhoods with fewer co-nationals (lowest v. highest quartile) were more likely to receive a subsequent diagnosis of non-affective psychosis, incident rate ratio (IRR) 1.25 (95% confidence interval (CI) 1.06-1.48), and post-traumatic stress disorder (PTSD), IRR 1.21 (95% CI I.05-1.39). A comparable but smaller effect was observed for mood disorders but none observed for stress disorders overall. Neighborhood proportion of refugees was less clearly associated with subsequent mental disorders other than non-affective psychosis, IRR 1.24 (95% CI 1.03-1.50). We found no statistically significant associations with proportion of migrants. CONCLUSIONS: For refugees, living in a neighborhood with a lower proportion of co-nationals is related to subsequent increased risk of diagnosed mental disorders particularly non-affective psychosis and PTSD.

A formal goodness-of-fit test for spatial binary Markov random field models.

Binary spatial observations arise in environmental and ecological studies, where Markov random field (MRF) models are often applied. Despite the prevalence and the long history of MRF models for spatial binary data, appropriate model diagnostics have remained an unresolved issue in practice. A complicating factor is that such models involve neighborhood specifications, which are difficult to assess for binary data. To address this, we propose a formal goodness-of-fit (GOF) test for diagnosing an MRF model for spatial binary values. The test statistic involves a type of conditional Moran's I based on the fitted conditional probabilities, which can detect departures in model form, including neighborhood structure. Numerical studies show that the GOF test can perform well in detecting deviations from a null model, with a focus on neighborhoods as a difficult issue. We illustrate the spatial test with an application to Besag's historical endive data as well as the breeding pattern of grasshopper sparrows across Iowa.

Neighborhood Racial Composition and Unequal Exposure to Violent Crime in Everyday Contexts.

Exposure to violence is a critical aspect of contemporary racial inequality in the United States. While extensive research has examined variations in violent crime rates across neighborhoods, less attention has been given to understanding individuals' everyday exposure to violent crimes. This study investigates patterns of exposure to violent crimes among neighborhood residents using cell phone mobility data and violent crime reports from Chicago. The analysis reveals a positive association between the proportion of Black residents in a neighborhood and the level of exposure to violent crimes experienced by residents. Controlling for a neighborhood's level of residential disadvantage and other neighborhood characteristics did not substantially diminish the relationship between racial composition and exposure to violent crimes in everyday life. Even after controlling for violence within residents' neighborhoods, individuals residing in Black neighborhoods continue to experience significantly higher levels of violence in their day-to-day contexts compared to those living in White neighborhoods. This suggests that racial segregation in everyday exposures, rather than residential segregation, plays a central role in racial inequality in exposure to violence. Additionally, the analysis suggests that neighborhoods with more Hispanic and Asian residents are exposed to less and more violent crime, respectively, compared to neighborhoods with more White residents. However, this is only observed when not adjusting for the volume of visits points of interest receive; otherwise, the finding is reversed. This study offers valuable insights into potentially novel sources of racial disparities in exposure to violent crimes in everyday contexts, highlighting the need for further investigation.

Systematic Review of Neighborhood Factors Impacting HIV Care Continuum Participation in the United States.

Social determinants have been increasingly implicated in accelerating HIV vulnerability, particularly for disenfranchised communities. Among these determinants, neighborhood factors play an important role in undermining HIV prevention. However, there has been little research comprehensively examining the impact of neighborhood factors on HIV care continuum participation in the US. To address this, we conducted a systematic review (PROSPERO registration number CRD42022359787) to determine neighborhood factors most frequently associated with diminished HIV care continuum participation. Peer-reviewed studies were included if published between 2013 - 2022, centralized in the US, and analyzed a neighborhood factor with at least one aspect of the HIV care continuum. The review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Study quality was guided by LEGEND (Let Evidence Guide Every New Decision) evaluation guidelines. Systematic review analysis was conducted using Covidence software. There were 3,192 studies identified for initial screening. Forty-four were included for review after eliminating duplicates, title/abstract screening, and eligibility assessment. Social and economic disenfranchisement of neighborhoods negatively impacts HIV care continuum participation among persons living with HIV. In particular, five key neighborhood factors (socioeconomic status, segregation, social disorder, stigma, and care access) were associated with challenged HIV care continuum participation. Race moderated relationships between neighborhood quality and HIV care continuum participation. Structural interventions addressing neighborhood social and economic challenges may have favorable downstream effects for improving HIV care continuum participation.

Lasting Legacy: The Enduring Relationship Between Racially Restrictive Housing Covenants and Health and Wellbeing.

Racially restrictive covenants in housing deeds, commonplace in Minnesota for houses built from the 1910s to the 1950s, provided a foundation for the myriad of policies that made it difficult for people of color to obtain housing. Though covenants were ruled illegal in 1968, their legacy continues to shape neighborhoods. The Mapping Prejudice Project's efforts in Hennepin County, Minnesota, produced the first systematic documentation of racially restrictive covenants. We use this novel data set to explore the relationship between historic covenants and current health and wellbeing outcomes. Using regression analysis to control for neighborhood level covariates, we compare previously covenanted neighborhoods to neighborhoods without covenants. Today, previously covenanted neighborhoods have higher life expectancy and lower rates of obesity, diabetes, coronary heart disease, and asthma than neighborhoods without racially restrictive covenants. Additionally, previously covenanted neighborhoods have less upward mobility for children from poorer households, and there are larger gaps in upward mobility between white and Black children. These findings contribute to a growing literature that shows racist policies, even decades after they are legally enforceable, leave an imprint on neighborhoods. Using the novel data from the Mapping Prejudice Project, we provide statistical analysis that confirms qualitative and anecdotal evidence on the role of racial covenants in shaping neighborhoods.

Area-Level Social Vulnerability and Severe COVID-19: A Case-Control Study Using Electronic Health Records from Multiple Health Systems in the Southeastern Pennsylvania Region.

Knowledge about neighborhood characteristics that predict disease burden can be used to guide equity-based public health interventions or targeted social services. We used a case-control design to examine the association between area-level social vulnerability and severe COVID-19 using electronic health records (EHR) from a regional health information hub in the greater Philadelphia region. Severe COVID-19 cases (n = 15,464 unique patients) were defined as those with an inpatient admission and a diagnosis of COVID-19 in 2020. Controls (n = 78,600; 5:1 control-case ratio) were a random sample of individuals who did not have a COVID-19 diagnosis from the same geographic area. Retrospective data on comorbidities and demographic variables were extracted from EHR and linked to area-level social vulnerability index (SVI) data using ZIP codes. Models adjusted for different sets of covariates showed incidence rate ratios (IRR) ranging from 1.15 (95% CI, 1.13-1.17) in the model adjusted for individual-level age, sex, and marital status to 1.09 (95% CI, 1.08-1.11) in the fully adjusted model, which included individual-level comorbidities and race/ethnicity. The fully adjusted model indicates that a 10% higher area-level SVI was associated with a 9% higher risk of severe COVID-19. Individuals in neighborhoods with high social vulnerability were more likely to have severe COVID-19 after accounting for comorbidities and demographic characteristics. Our findings support initiatives incorporating neighborhood-level social determinants of health when planning interventions and allocating resources to mitigate epidemic respiratory diseases, including other coronavirus or influenza viruses.

Neighborhood and Individual Disparities in Community-Based Naloxone Access for Opioid Overdose Prevention.

Improving access to naloxone for laypersons is a cornerstone of the US strategy to reduce opioid overdose deaths. This study evaluated change in distance to opioid overdose prevention programs (OOPPs) providing walk-in naloxone across two time points. We also explored individual and neighborhood disparities in distance to OOPPs, associations between 2020 OOPP locations and 2018 overdoses, and associations between OOPPs and neighborhood fatal overdose rates. Using fatal opioid overdose locations in 2018 (n = 1167) and 2020 (n = 2045) in New York City, we mapped OOPP locations and fatal overdose locations to visualize areas of unmet naloxone need. We used logistic regression to assess individual (age, sex, race/ethnicity) and neighborhood correlates of odds of an overdose occurring within walking distance (≤ 0.5 miles or 0.8 km) of an OOPP and negative binomial regression to assess the relationship between census tract-level OOPP counts and overdose rates. Distance to OOPPs significantly improved over time, with average distance decreasing by 1.7 miles (2.7 km) (p < 0.001). OOPPs were more likely to be located in neighborhoods with higher poverty in both years and in closer proximity to Latinos in 2020-suggesting improved access for Latinos and in higher poverty neighborhoods. OOPP locations in 2020 were significantly positively associated with overdose locations in 2018. OOPPs were not well-situated in neighborhoods with elevated overdose rates in 2018 but were better situated in 2020, controlling for other neighborhood variables. Community lay naloxone access through OOPPs improved over time and could have promising effects for improved overdose rates in the future.

Historical Structural Racism in the Built Environment and Physical Health among Residents of Allegheny County, Pennsylvania.

Historical structural racism in the built environment contributes to health inequities, yet to date, research has almost exclusively focused on racist policy of redlining. We expand upon this conceptualization of historical structural racism by examining the potential associations of probable blockbusting, urban renewal, and proximity to displacement from freeway construction, along with redlining, to multiple contemporary health measures. Analyses linked historical structural racism, measured continuously at the census-tract level using archival data sources, to present-day residents' physical health measures drawn from publicly accessible records for Allegheny County, Pennsylvania. Outcome measures included average life expectancy and the percentage of residents reporting hypertension, stroke, coronary heart disease, smoking, insufficient sleep, sedentary behavior, and no health insurance coverage. Multiple regression analyses were conducted to examine separate and additive associations between structural racism and physical health measures. Redlining, probable blockbusting, and urban renewal were associated with shorter life expectancy and a higher prevalence of cardiovascular conditions, risky health behaviors, and residents lacking health insurance coverage. Probable blockbusting and urban renewal had the most consistent correlations with all 8 health measures, while freeway displacement was not reliably associated with health. Additive models explained a greater proportion of variance in health than any individual structural racism measure alone. Moreover, probable blockbusting and urban renewal accounted for relatively more variance in health compared to redlining, suggesting that research should consider these other measures in addition to redlining. These preliminary correlational findings underscore the importance of considering multiple aspects of historical structural racism in relation to current health inequities and serve as a starting point for additional research.

Citizens' perspectives on healthy weight approaches in low SEP neighborhoods: a qualitative study from a systems perspective.

BACKGROUND: The physical and the social environment are important predictors of healthy weight, especially in low socioeconomic position (SEP) neighborhoods. Many Dutch municipalities have implemented a healthy weight approach (HWA). Yet, there is room for improvement. This system science study examined what influences the utilization of HWA facilities and activities, and what aspects can help to achieve a desired systems change (also called leverage point themes (LPTs)) in the HWA system as perceived by citizens living in low SEP neighborhoods. METHOD: All research phases were performed with four citizens co-researchers. Forty-seven citizens living in low SEP neighborhoods were semi-structurally interviewed about the neighborhood HWA facilities and municipal HWA activities. A rapid coding qualitative analysis approach was applied per topic. The topics were citizens' healthy living description, personal circumstances, and satisfaction with foot and cycle paths, sports facilities, playgrounds, green spaces, museums and theaters, community centers, churches, healthcare, school, food supplies, contact with neighborhood, unfamiliar and/or unused activities, familiar and used activities, unavailable but desired (lacking) activities, and reaching citizens. RESULTS: The utilization of HWA facilities and activities was influenced by the overarching themes of social cohesion, familiarity, reaching citizens, maintenance, safety, physical accessibility, financial accessibility, social accessibility, fit with personal context, and fit with the neighborhood's specific needs. Different overarching themes stood out across different facilities and activities. LPTs indicated the overarching themes needed in combination with one another for a specific activity or facility to increase utilization. For example, the LPT regarding foot and cycle paths was "accessible, safe, and maintained foot and cycle paths". The LPTs regarding familiar and used activities were "customized activities; information provision (e.g., about possibilities to join without paying); social contact, meeting others, and everyone feels included". CONCLUSION: Conducting inclusive qualitative research from a systems perspective among citizens living in low SEP neighborhoods has contributed valuable insights into their needs. This enables practical implementation of HWAs by providing a deeper understanding of the LPTs within the HWA system. LPTs can help HWA stakeholders to further develop current HWAs toward systems approaches. Future research could study the leverage points that may contribute to LPT implementation.

Do women living in a deprived neighborhood have higher maternity care costs and worse pregnancy outcomes? A retrospective population-based study.

BACKGROUND: Living in a deprived neighborhood is associated with poorer health, due to factors such as lower socio-economic status and an adverse lifestyle. There is little insight into whether living in deprived neighborhood is associated with adverse maternity care outcomes and maternity health care costs. We expect women in a deprived neighborhood to experience a more complicated pregnancy, with more secondary obstetric care (as opposed to primary midwifery care) and higher maternity care costs. This study aimed to answer the following research question: to what extent are moment of referral from primary to secondary care, mode of delivery, (extreme or very) preterm delivery and maternity care costs associated with neighborhood deprivation? METHODS: This retrospective cohort study used a national Dutch database with healthcare claims processed by health insurers. All pregnancies that started in 2018 were included. The moment of referral from primary to secondary care, mode of delivery, (extreme or very) preterm delivery and maternity care costs were compared between women in deprived and non-deprived neighborhoods. We reported descriptive statistics, and results of ordinal logistic, multinomial and linear regressions to assess whether differences between the two groups exist. RESULTS: Women in deprived neighborhoods had higher odds of being referred from primary to secondary care during pregnancy (adjusted OR 1.49, 95%CI 1.41-1.57) and to start their pregnancy in secondary care (adjusted OR 1.55, 95%CI 1.44-1.66). Furthermore, women in deprived neighborhoods had lower odds of assisted delivery than women in non-deprived neighborhoods (adjusted OR 0.73, 95%CI 0.66-0.80), and they had higher odds of a cesarean section (adjusted OR 1.19, 95%CI 1.13-1.25). On average, women in a deprived neighborhood had higher maternity care costs worth 156 euros (95%CI 104-208). CONCLUSION: This study showed that living in a deprived neighborhood is associated with more intensive maternal care and higher maternal care costs in the Netherlands. These findings support the needs for greater attention to socio-economic factors in maternity care in the Netherlands.

An exploration of neighborhood characteristics, psychosocial resilience resources, and cognitive functioning among midlife and older black adults.

OBJECTIVES: While existing research has shown that Black adults have worse cognitive functioning than their White counterparts, the psychosocial correlates of cognitive functioning for Black older adults are understudied. The objective of this study was to investigate the relationships among perceived neighborhood characteristics, psychosocial resilience resources, and cognitive functioning among midlife and older Black adults. METHODS: Data were from 3,191 Black adults ages 51+ in the 2008-2016 waves of the Health and Retirement Study to examine associations among neighborhood characteristics, psychosocial resilience (sense of purpose, mastery, and social support), and cognitive functioning among Black adults. Multilevel linear regression models assessed direct effects of neighborhood characteristics and psychosocial resources on cognitive functioning. We then tested whether psychosocial resources moderated the association between neighborhood characteristics and cognitive functioning. RESULTS: Mean levels of cognitive functioning, sense of purpose, social support, and mastery were significantly related to neighborhood disorder and discohesion. Regression results showed that levels of neighborhood disorder and high discohesion were significantly associated with cognitive functioning. Sense of purpose was positively associated with cognitive functioning, net of neighborhood characteristics. However, only social support moderated the association between neighborhood discohesion and cognition. CONCLUSIONS: These findings demonstrate the importance of examining psychosocial and contextual risk and resilience resources among midlife and older Black adults. This work may inform the development of cognitive behavioral interventions aimed at increasing sense of purpose to promote and enhance cognitive resiliency among Black adults. Altogether, this work may have implications for policy aimed at advancing cognitive health equity.