Cone-Opponent Ganglion Cells in the Primate Fovea Tuned to Noncardinal Color Directions.

A long-standing question in vision science is how the three cone photoreceptor types-long (L), medium (M), and short (S) wavelength sensitive-combine to generate our perception of color. Hue perception can be described along two opponent axes: red-green and blue-yellow. Psychophysical measurements of color appearance indicate that the cone inputs to the red-green and blue-yellow opponent axes are M vs. L + S and L vs. M + S, respectively. However, the "cardinal directions of color space" revealed by psychophysical measurements of color detection thresholds following adaptation are L vs. M and S vs. L + M. These cardinal directions match the most common cone-opponent retinal ganglion cells (RGCs) in the primate retina. Accordingly, the cone opponency necessary for color appearance is thought to be established in the cortex. While neurons with the appropriate M vs. L + S and L vs. M + S opponency have been reported in the retina and lateral geniculate nucleus, their existence continues to be debated. Resolving this long-standing debate is necessary because a complete account of the cone opponency in the retinal output is critical for understanding how downstream neural circuits process color. Here, we performed adaptive optics calcium imaging to noninvasively measure foveal RGC light responses in the living Macaca fascicularis eye. We confirm the presence of L vs. M + S and M vs. L + S neurons with noncardinal cone opponency and demonstrate that cone-opponent signals in the retinal output are more diverse than classically thought.

Addressing Structural Racism Through Public Policy Advocacy: A Policy Statement From the American Heart Association.

During the COVID-19 pandemic, the American Heart Association created a new 2024 Impact Goal with health equity at its core, in recognition of the increasing health disparities in our country and the overwhelming evidence of the damaging effect of structural racism on cardiovascular and stroke health. Concurrent with the announcement of the new Impact Goal was the release of an American Heart Association presidential advisory on structural racism, recognizing racism as a fundamental driver of health disparities and directing the American Heart Association to advance antiracist strategies regarding science, business operations, leadership, quality improvement, and advocacy. This policy statement builds on the call to action put forth in our presidential advisory, discussing specific opportunities to leverage public policy in promoting overall well-being and rectifying those long-standing structural barriers that impede the progress that we need and seek for the health of all communities. Although this policy statement discusses difficult aspects of our past, it is meant to provide a forward-looking blueprint that can be embraced by a broad spectrum of stakeholders who share the association's commitment to addressing structural racism and realizing true health equity.

Global protected areas seem insufficient to safeguard half of the world's mammals from human-induced extinction.

Protected areas (PAs) are a cornerstone of global conservation and central to international plans to minimize global extinctions. During the coming century, global ecosystem destruction and fragmentation associated with increased human population and economic activity could make the long-term survival of most terrestrial vertebrates even more dependent on PAs. However, the capacity of the current global PA network to sustain species for the long term is unknown. Here, we explore this question for all nonvolant terrestrial mammals for which we found sufficient data, ∼4,000 species. We first estimate the potential population size of each such mammal species in each PA and then use three different criteria to estimate if solely the current global network of PAs might be sufficient for their long-term survival. Our analyses suggest that current PAs may fail to provide robust protection for about half the species analyzed, including most species currently listed as threatened with extinction and a third of species not currently listed as threatened. Hundreds of mammal species appear to have no viable protected populations. Underprotected species were found across all body sizes, taxonomic groups, and geographic regions. Large-bodied mammals, endemic species, and those in high-biodiversity tropical regions were particularly poorly protected by existing PAs. As new international biodiversity targets are formulated, our results suggest that the global network of PAs must be greatly expanded and most importantly that PAs must be located in diverse regions that encompass species not currently protected and must be large enough to ensure that protected species can persist for the long term.

The cost of doubt: assessing the association between attributional ambiguity and mental health.

OBJECTIVE: To quantify the association between attributional ambiguity-the uncertainty of whether an experience is discrimination-and mental health. METHODS: Using a nationally representative sample of U.S. adults recruited through an online survey by Ipsos (April 23 and May 3, 2021), attributional ambiguity was quantified by asking participants if they experienced anything in the past 6 months that they were unsure was discrimination. The survey also assessed the degree to which these experiences caused participants to feel bothered and to ruminate on them. Multiple linear regression models were used to analyze associations between attributional ambiguity and depressive symptoms and mental health status. RESULTS: Black and Hispanic participants reported higher rates of attributional ambiguity than White participants. Experiencing attributional ambiguity was associated with higher levels of depressive symptoms and poorer self-reported mental health status. Among those who reported attributional ambiguity, increases in bother and rumination scores were positively associated with depressive symptoms. CONCLUSION: Attributional ambiguity is an important yet overlooked social determinant of mental health. More research is needed to fully understand the impact of this stressor on population health, particularly among minoritized populations.

Multiple chronic diseases and psychological distress among adults in the United States: the intersectionality of chronic diseases, race/ethnicity, immigration, sex, and insurance coverage.

PURPOSE: Psychological distress significantly contributes to the burdens of morbidity and mortality in the United States (U.S.), but our understanding is limited with regards to the risk factors associated with psychological distress. We used nationally representative data to examine (1) the comorbidities of chronic diseases and their risks for psychological distress and (2) the ways in which chronic diseases combine with demographic factors such as sex, race/ethnicity, immigration status, and health insurance coverage to affect the patterning of psychological distress. METHODS: We analyzed the 2005-2018 National Health Survey Interview cross-sectional data on U.S. adults aged ≥ 18 years (n = 351,457). We fitted sequential multivariable logistic regression models. RESULTS: There was a dose-response relationship between the number of chronic diseases and psychological distress, with increased number of chronic diseases associated with increased psychological distress risk. Females (vs. males) and those without health insurance (vs. insured) were more likely to experience psychological distress. Immigrants (vs. non-immigrants) and racial/ethnic minorities (vs. White individuals) were less likely to experience psychological distress. There were significant interactions between chronic diseases and insurance coverage, immigration status, and race/ethnicity, but the three-way interactions were not statistically significant with psychological distress: chronic disease status vs. immigration status vs. health insurance coverage, and chronic disease vs. race/ethnicity vs. immigration status. CONCLUSION: The findings suggest a critical need to consider the complex ways in which chronic diseases and psychosocial factors combine to affect psychological distress and their implications for tailoring mental health screening, initiatives to reduce distress, and prevention strategies for effectively addressing health-related disparities in the general population.

Discrimination and anxiety: Using multiple polygenic scores to control for genetic liability.

An established body of research indicates that discrimination is associated with increased symptoms of anxiety and negative affect. However, the association cannot be interpreted unambiguously as an exposure effect because a common set of genetic factors can simultaneously contribute to increased liability for symptoms of anxiety, negative affect, and the perception of discrimination. The present study elucidates the association between discrimination and anxiety/negative affect by implementing strict genetic controls in a large sample of adults. We used data from the biomarker project of the Study of Midlife Development in the United States (MIDUS), a national probability sample of noninstitutionalized, English-speaking respondents aged 25 to 74 y. Participants who consented to provide genetic data were biologically unrelated and of European ancestry as determined by genotype principal components analysis (n = 1,146). A single structural regression model was fit to the data with three measures of discrimination specified to load onto a latent factor and six measures of anxiety and negative affect specified to load onto a second latent factor. After accounting for potential genetic confounds-polygenic scores for anxiety, depression, and neuroticism and the first five genetic principal components-greater discrimination was associated with greater anxiety/negative affect (ß = 0.53, SE = 0.04, P < 0.001). Findings suggest that measures of perceived discrimination should be considered environmental risk factors for anxiety/negative affect rather than indices of genetic liability for anxiety, depression, or neuroticism. Clinical interventions and prevention measures should focus on ways to mitigate the impact of discrimination to improve mental health at the population level.

Instrumental Variable Analysis of Racial Discrimination and Blood Pressure in a Sample of Young Adults.

Racial inequities in blood pressure levels have been extensively documented. Experiences of racial discrimination could explain some of this disparity, although findings from previous studies have been inconsistent. To address limitations of prior literature, including measurement error, we implemented instrumental variable analysis to assess the relationship between racial discrimination in institutional settings and blood pressure. Using data from 3,876 Black and White adults with an average age of 32 years from examination 4 (1992-1993) of the Coronary Artery Risk Development in Young Adults Study, our primary analysis examined the relationship between self-reported experiences of racial discrimination in institutional settings and blood pressure using reflectance meter measurement of skin color as an instrument. Findings suggested that an increase in experiences of racial discrimination was associated with higher systolic and diastolic blood pressure (ß = 2.23 mm Hg (95% confidence interval: 1.85, 2.61) and ß = 1.31 (95% confidence interval: 1.00, 1.62), respectively). Our instrumental variable estimates suggest that experiences of racial discrimination within institutional settings contribute to racial inequities in elevated blood pressure and cardiovascular disease outcomes in a relatively young cohort of adults and may yield clinically relevant differences in cardiovascular health over the life course.

Population-level contribution of interpersonal discrimination to psychological distress among Australian Aboriginal and Torres Strait Islander adults, and to Indigenous-non-Indigenous inequities: cross-sectional analysis of a community-controlled First Nations cohort study.

BACKGROUND: International and population-specific evidence identifies elevated psychological distress prevalence among those experiencing interpersonal discrimination. We aim to quantify the potential whole-of-population contribution of interpersonal discrimination to psychological distress prevalence and Indigenous-non-Indigenous gaps in Australia. METHODS: We did a cross-sectional analysis of data from Mayi Kuwayu: the National Study of Aboriginal and Torres Strait Islander Wellbeing. Baseline surveys were completed between June 8, 2018, and Sept 28, 2022. We analysed responses from participants who were aged 18 years or older at survey completion, whose surveys were processed between Oct 1, 2018, and May 1, 2021. Sample weights were developed on the basis of national population benchmarks. We measured everyday discrimination using an eight-item measure modified from the Everyday Discrimination Scale and classified experiences as racial discrimination if participants attributed these experiences to their Indigeneity. Psychological distress was measured using a validated, modified Kessler-5 scale. Applying logistic regression, we calculated unadjusted odds ratios (ORs), to approximate incident rate ratios (IRRs), for high or very high psychological distress in relation to everyday discrimination and everyday racial discrimination across age-gender strata. Population attributable fractions (PAFs), under the hypothetical assumption that ORs represent causal relationships, were calculated using these ORs and population-level exposure prevalence. These PAFs were used to quantify the contribution of everyday racial discrimination to psychological distress gaps between Indigenous and non-Indigenous adults. FINDINGS: 9963 survey responses were eligible for inclusion in our study, of which we analysed 9951 (99·9%); 12 were excluded due to responders identifying as a gender other than man or woman (there were too few responses from this demographic to be included as a category in stratified tables or adjusted analyses). The overall prevalence of psychological distress was 48·3% (95% CI 47·0-49·6) in those experiencing everyday discrimination compared with 25·2% (23·8-26·6) in those experiencing no everyday discrimination (OR 2·77 [95% CI 2·52-3·04]) and psychological distress prevalence was 49·0% (95% CI 47·3-50·6) in those experiencing everyday racial discrimination and 31·8% (30·6-33·1) in those experiencing no everyday racial discrimination (OR 2·06 [95% CI 1·88-2·25]. Overall, 49·3% of the total psychological distress burden among Aboriginal and Torres Strait Islander adults could be attributable to everyday discrimination (39·4-58·8% across strata) and 27·1% to everyday racial discrimination. Everyday racial discrimination could explain 47·4% of the overall gap in psychological distress between Indigenous and non-Indigenous people (40·0-60·3% across strata). INTERPRETATION: Our findings show that interpersonal discrimination might contribute substantially to psychological distress among Aboriginal and Torres Strait Islander adults, and to inequities compared with non-Indigenous adults. Estimated PAFs include contributions from social and health disadvantage, reflecting contributions from structural racism. Although not providing strictly conclusive evidence of causality, this evidence is sufficient to indicate the psychological harm of interpersonal discrimination. Findings add weight to imperatives to combat discrimination and structural racism at its core. Urgent individual and policy action is required of non-Indigenous people and colonial structures, directed by Aboriginal and Torres Strait Islander peoples. FUNDING: National Health and Medical Research Council of Australia, Ian Potter Foundation, Australian Research Council, US National Institutes of Health, and Sierra Foundation.

Linking specific biological signatures to different childhood adversities: findings from the HERO project.

BACKGROUND: Although investigations have begun to differentiate biological and neurobiological responses to a variety of adversities, studies considering both endocrine and immune function in the same datasets are limited. METHODS: Associations between proximal (family functioning, caregiver depression, and anxiety) and distal (SES-D; socioeconomic disadvantage) early-life adversities with salivary inflammatory biomarkers (IL-1ß, IL-6, IL-8, and TNF-α) and hair HPA markers (cortisol, cortisone, and dehydroepiandrosterone) were examined in two samples of young U.S. children (N = 142; N = 145). RESULTS: Children exposed to higher SES-D had higher levels of TNF-α (B = 0.13, p = 0.011), IL-1ß (B = 0.10, p = 0.033), and DHEA (B = 0.16, p = 0.011). Higher family dysfunction was associated with higher cortisol (B = 0.08, p = 0.033) and cortisone (B = 0.05, p = 0.003). An interaction between SES-D and family dysfunction was observed for cortisol levels (p = 0.020) whereby children exposed to lower/average levels of SES-D exhibited a positive association between family dysfunction and cortisol levels, whereas children exposed to high levels of SES-D did not. These findings were partially replicated in the second sample. CONCLUSIONS: Our results indicate that these biological response systems may react differently to different forms of early-life adversity. IMPACT: Different forms of early-life adversity have varied stress signatures, and investigations of early-life adversities with inflammation and HPA markers are lacking. Children with higher socioeconomic disadvantage had higher TNF-α, IL-1ß, and DHEA. Higher family dysfunction was associated with higher hair cortisol and cortisone levels, and the association between family dysfunction and cortisol was moderated by socioeconomic disadvantage. Biological response systems (immune and endocrine) were differentially associated with distinct forms of early-life adversities.

In Search of the Promised Land: County-Level Disadvantage and Low Birth Weight among Black Mothers of the Great Migration.

The Great Migration was a movement of roughly eight million Black Southerners relocating to the North and West from 1910 to 1980. Despite being one of the most significant mass internal migrations during the twentieth century, little is known about the health outcomes resulting from migration and whether migrators' destination choices were potential mechanisms. This study measured the association between destination county disadvantage and odds of low birth weight during the last decade of the Great Migration. We used the US Census from 1970 as well as the birth records of first-time Black mothers who migrated from the South collected through the National Center of Health Statistics from 1973 to 1980 (n = 154,145). We examined three measures of area-based opportunity: Black male high school graduation rate, Black poverty rate, and racialized economic residential segregation. We used multilevel logistic regression, where mothers were nested within US counties, to quantify the relationship between county disadvantage and low birth weight. After adjusting for individual risk and protective factors for infant health, there was no relationship between county opportunity measures and low birth weight among migrators. Although high socioeconomic opportunity is typically associated with protection of low birth weight, we did not see these outcomes in this study. These results may support that persistent racial discrimination encountered in the North inhibited infant health even as migrators experienced higher economic opportunity relative to the South.

Future threats to biodiversity and pathways to their prevention.

Tens of thousands of species are threatened with extinction as a result of human activities. Here we explore how the extinction risks of terrestrial mammals and birds might change in the next 50 years. Future population growth and economic development are forecasted to impose unprecedented levels of extinction risk on many more species worldwide, especially the large mammals of tropical Africa, Asia and South America. Yet these threats are not inevitable. Proactive international efforts to increase crop yields, minimize land clearing and habitat fragmentation, and protect natural lands could increase food security in developing nations and preserve much of Earth's remaining biodiversity.

Optogenetic therapy restores retinal activity in primate for at least a year following photoreceptor ablation.

All retina-based vision restoration approaches rely on the assumption that photoreceptor loss does not preclude reactivation of the remaining retinal architecture. Whether extended periods of vision loss limit the efficacy of restorative therapies at the retinal level is unknown. We examined long-term changes in optogenetic responsivity of foveal retinal ganglion cells (RGCs) in non-human primates following localized photoreceptor ablation by high-intensity laser exposure. By performing fluorescence adaptive optics scanning light ophthalmoscopy (AOSLO) of RGCs expressing both the calcium indicator GCaMP6s and the optogenetic actuator ChrimsonR, it was possible to track optogenetic-mediated calcium responses in deafferented RGCs over time. Fluorescence fundus photography revealed a 40% reduction in ChrimsonR fluorescence from RGCs lacking photoreceptor input over the 3 weeks following photoreceptor ablation. Despite this, in vivo imaging revealed good cellular preservation of RGCs 3 months after the loss of photoreceptor input, and histology confirmed good structural preservation at 2 years. Optogenetic responses of RGCs in primate persisted for at least 1 year after the loss of photoreceptor input, with a sensitivity index similar to optogenetic responses recorded in intact retina. These results are promising for all potential therapeutic approaches to vision restoration that rely on preservation and reactivation of RGCs.

Sociopolitical stress and acute cardiovascular disease hospitalizations around the 2016 presidential election.

Previous research suggests that stressors may trigger the onset of acute cardiovascular disease (CVD) events within hours to days, but there has been limited research around sociopolitical events such as presidential elections. Among adults ≥18 y of age in Kaiser Permanente Southern California, hospitalization rates for acute CVD were compared in the time period immediately prior to and following the 2016 presidential election date. Hospitalization for CVD was defined as an inpatient or emergency department discharge diagnosis of acute myocardial infarction (AMI) or stroke using International Classification of Diseases, 10th revision codes. Rate ratios (RR) and 95% confidence intervals (CIs) were calculated comparing CVD rates in the 2 d following the 2016 election to rates in the same 2 d of the prior week. In a secondary analysis, AMI and stroke were analyzed separately. The rate of CVD events in the 2 d after the 2016 presidential election (573.14 per 100,000 person-years [PY]) compared to the rate in the window prior to the 2016 election (353.75 per 100,000 PY) was 1.62 times higher (95% CI 1.17, 2.25). Results were similar across sex, age, and race/ethnicity groups. The RRs were similar for AMI (RR 1.67, 95% CI 1.00, 2.76) and stroke (RR 1.59, 95% CI 1.03, 2.44) separately. Transiently heightened cardiovascular risk around the 2016 election may be attributable to sociopolitical stress. Further research is needed to understand the intersection between major sociopolitical events, perceived stress, and acute CVD events.

Structural Racism and Inequities in Incidence, Course of Illness, and Treatment of Psychotic Disorders Among Black Americans.

Psychotic disorders (e.g., schizophrenia, schizoaffective disorder) are a leading cause of morbidity and premature mortality and an overlooked health inequity in the United States. European data indicate inequities in incidence, severity, and treatment of psychotic disorders, particularly for Black communities, that appear to be primarily attributable to social adversities. The dominant US narrative is that any observed differences are primarily a result of clinician bias and misdiagnosis. We propose that employing the framework of structural racism will prompt European and US research to converge and consider the multifaceted drivers of inequities in psychotic disorders among Black Americans. In particular, we describe how historical and contemporary practices of (1) racialized policing and incarceration, and (2) economic exploitation and disinvestment, which are already linked to other psychiatric disorders, likely contribute to risks and experiences of psychotic disorders among Black Americans. This framework can inform new strategies to (1) document the role of racism in the incidence, severity, and treatment of psychotic disorders; and (2) dismantle how racism operates in the United States, including defunding the police, abolishing carceral systems, and redirecting funds to invest in neighborhoods, housing, and community-based crisis response and mental health care. (Am J Public Health. 2022;112(4):624-632. https://doi.org/10.2105/AJPH.2021.306631).

Purpose in life and 8-year mortality by gender and race/ethnicity among older adults in the U.S.

We examined the associations between a sense of purpose and all-cause mortality by gender and race/ethnicity groups. Data were from the Health and Retirement Study, a nationally representative cohort study of U.S. adults aged >50 (n = 13,159). Sense of purpose was self-reported at baseline (2006/2008), and risk of all-cause mortality was assessed over an 8-year follow-up period. We also formally tested for potential effect modification by gender and race/ethnicity. We observed the associations between higher purpose and lower all-cause mortality risk across all gender and race/ethnicity groups. There was modest evidence that the highest level of purpose (versus lowest quartile) was associated with even lower risk of all-cause mortality among women (risk ratio = 0.66, 95% confidence interval: 0.56, 0.77) compared to men (risk ratio = 0.80, 95% confidence interval: 0.69, 0.93; p-value for multiplicative effect modification =0.07). However, we observed no evidence of effect modification by race/ethnicity. Having a higher sense of purpose appears protective against all-cause mortality regardless of gender and race/ethnicity. Purpose, a potentially modifiable factor, might be a health asset across diverse populations.

Racial disparities in psychological distress in post-apartheid South Africa: results from the SANHANES-1 survey.

PURPOSE: South Africa has long endured a high prevalence of mental disorders at the national level, and its unique social and historical context could be a contributor to an increased risk of mental health problems. Our current understanding is limited regarding the relative importance of various social determinants to mental health challenges in South Africa, and how existing racial inequities may be explained by these determinants. METHODS: This study attempted to elucidate potential social determinants of mental health in South Africa using data from the nationally representative South African National Health and Nutrition Examination Survey (SANHANES-1). The main outcome of interest was psychological distress, measured with the Kessler-10 scale. Hierarchical linear regression models included covariates for demographic and socioeconomic factors, count of traumatic events, and a series of stress-related constructs. Analyses were conducted on two populations: the entire sample (n = 15,981), and the African subpopulation (n = 10,723). RESULTS: Regression models on the entire sample indicated racial disparities in psychological distress, with Africans experiencing higher distress than White and Coloured individuals. Results within the African sub-population indicated geo-spatial disparities, with Africans in formal urban settings experiencing higher psychological distress than those living in formal and informal rural locales. Across both samples, results indicated a cumulative association between count of stressors and traumatic events and distress. CONCLUSION: We found racial disparities across several mental health-related domains. Africans had greater exposure to traumatic events, social stressors, and psychological distress. This research is a necessary foundation for public health interventions and policy change to effectively reduce inequities in psychological distress.

Race, Flourishing, and All-Cause Mortality in the United States, 1995-2016.

We assessed whether race moderates the association between flourishing and all-cause mortality. We used panel data from the Midlife in the United States Study (MIDUS) (1995-2016; n = 2,851). Approximately 19% of White respondents and 23% of Black respondents in the baseline sample died over the course of the 21-year study period (n = 564). Cox proportional hazard models showed that Blacks had a higher mortality rate relative to Whites and higher levels of flourishing were associated with a lower mortality rate. Furthermore, a significant interaction between flourishing and race in predicting death was observed. Blacks with higher levels of flourishing had a mortality rate that was not significantly different from that of Whites. However, Blacks, but not Whites, with low flourishing scores had a higher mortality rate. As such, health-promotion efforts focused on enhancing flourishing among Black populations may reduce the Black-White gap in mortalityrate.

Experiences With Everyday and Major Forms of Racial/Ethnic Discrimination and Type 2 Diabetes Risk Among White, Black, and Hispanic/Latina Women: Findings From the Sister Study.

Racial/ethnic discrimination may contribute to the risk of type 2 diabetes mellitus (T2DM), but few studies have prospectively examined this relationship among racially/ethnically diverse populations. We analyzed prospective data from 33,833 eligible Sister Study participants enrolled from 2003 to 2009. In a follow-up questionnaire (2008-2012), participants reported their lifetime experiences of everyday and major forms of racial/ethnic discrimination. Self-reported physician diagnoses of T2DM were ascertained through September 2017. Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards models, overall and by race/ethnicity. Mean age at enrollment was 54.9 (standard deviation, 8.8) years; 90% of participants self-identified as non-Hispanic (NH) White, 7% as NH Black, and 3% as Hispanic/Latina. Over an average of 7 years of follow-up, there were 1,167 incident cases of T2DM. NH Black women most frequently reported everyday (75%) and major (51%) racial/ethnic discrimination (vs. 4% and 2% of NH White women, respectively, and 32% and 16% of Hispanic/Latina women, respectively). While everyday discrimination was not associated with T2DM risk, experiencing major discrimination was marginally associated with higher T2DM risk overall (hazard ratio = 1.26, 95% confidence interval: 0.99, 1.61) after adjustment for sociodemographic characteristics and body mass index. Associations were similar across racial/ethnic groups; however, racial/ethnic discrimination was more frequently reported among racial/ethnic minority women. Antidiscrimination efforts may help mitigate racial/ethnic disparities in T2DM risk.

Early Childhood Adversity, Toxic Stress, and the Impacts of Racism on the Foundations of Health.

Inequalities in health outcomes impose substantial human and economic costs on all societies-and the relation between early adversity and lifelong well-being presents a rich scientific framework for fresh thinking about health promotion and disease prevention broadly, augmented by a deeper focus on how racism influences disparities more specifically. This review begins with an overview of advances in the biology of adversity and resilience through an early childhood lens, followed by an overview of the unique effects of racism on health and a selective review of findings from related intervention research. This article presents a framework for addressing multiple dimensions of the public health challenge-including institutional/structural racism, cultural racism, and interpersonal discrimination-and concludes with the compelling need to protect the developing brain and other biological systems from the physiological disruptions of toxic stress that can undermine the building blocks of optimal health and development in the early childhood period.