African American Health Disparities Research Articles

Choosing to End African American Health Disparities in Patients With Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is three times more common and its manifestations are more severe in African American women compared to women of other races. It is not clear whether this is due to genetic differences or factors related to the physical or social environments, differences in health care, or a combination of these factors. Health disparities in patients with SLE between African American patients and persons of other races have been reported since the 1960s and are correlated with measures of lower socioeconomic status. Risk factors for these disparities have been demonstrated, but whether their mitigation improves outcomes for African American patients has not been tested except in self-efficacy. In 2002, the first true US population-based study of patients with SLE with death certificate records was conducted, which demonstrated a wide disparity between the number of African American women and White women dying from SLE. Five years ago, another study showed that SLE mortality rates in the United States had improved but that the African American patient mortality disparity persisted. Between 2014 and 2021, one study demonstrated racism's deleterious effects in patients with SLE. Racism may have been the unmeasured confounder, the proverbial "elephant in the room"-unnamed and unstudied. The etymology of "risk factor" has evolved from environmental risk factors to social determinants to now include structural injustice/structural racism. Racism in the United States has a centuries-long existence and is deeply ingrained in US society, making its detection and resolution difficult. However, racism being man made means Man can choose to change the it. Health disparities in patients with SLE should be addressed by viewing health care as a basic human right. We offer a conceptual framework and goals for both individual and national actions.

Abstract C043: SHIP-1: Therapeutic target to reduce health disparities in African Americans with pancreatic cancer

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers and African Americans (AA) have higher mortality rates compared to European Americans (EA) due to heighten inflammation which is known to be regulated by Src-homology inositol phosphatase-1 (SHIP-1). SHIP-1 is a master regulator of macrophage development and function which impacts tumor immunity and thus can be a therapeutic target that may explain treatment failure, which contributes to health disparity associated with AA vs. EA with PDAC. We reported that SHIP-1 expression is vital for the expansion of tumoricidal M1 macrophages, which in turn corresponds to an increase in anti-tumor responses in PDAC models. Our preliminary clinical data shows a significant increase in PDAC biomarker microRNA (miR-155) gene expression and a corresponding decrease in SHIP-1 gene and protein expression in the blood of healthy AA vs. EA individuals, significant increases in the percentages of inflammatory M2 macrophages with a reduction of tumoricidal M1 macrophages. Also, AA PDAC patients have significantly higher levels of inflammatory cytokines IL-6 and IL-8 in their serum, that correspond with the expansion of M2 Macrophages compared to EA PDAC patients. Our preliminary data suggests that SHIP-1 enhancers can reprogram M2 into M1 macrophages in the presence of serum from AA but not EA PDAC patients. Therefore, we hypothesize that AA PDAC patients compared to EA PDAC patients have reduced SHIP-1 expression which in turn leads to the expansion of M2 Macrophages that corresponds with dampened anti-tumor immune responses that are associated with treatment failure, and that this process can be reversed using SHIP-1 enhancers. We propose the following Specific Aims: Aim 1. To identify the cellular mechanism(s) by which SHIP-1 controls the development of monocytes into tumoricidal macrophages. Aim 2. To evaluate SHIP-1 molecular signatures required for tumoricidal macrophages and its impact on anti-tumor responses in tumor microenvironment (TME) of 3D patient-specific PDAC cultures and Aim 3. To evaluate the sensitivity of SHIP-1 stratified 3D patient-derived PDAC cultures response to checkpoint immunotherapy. We will use AA and EA PDAC clinical specimens and state-of-the-art technologies to address the aims of this study. We expect to validate SHIP-1 as a therapeutic target to treat all PDAC patients and reduce the health disparity gap for African Americans. Citation Format: Krystal Villalobos-Ayala, Valentina Laverde, Jennifer Permuth, William Kerr, Mokenge Malafa, Clayton Yates, Tomar Ghansah. SHIP-1: Therapeutic target to reduce health disparities in African Americans with pancreatic cancer [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C043.

Association of Preventive Care Attitudes and Beliefs with Colorectal Cancer Screening History among African American Patients of Community Health Centers.

Colorectal cancer (CRC) is the third most common cancer and third leading cause of cancer-related death among African Americans in the United States. However, when detected early, CRC is treatable and survival rates are high. CRC health disparities for African Americans compared with other groups may be due in part to lower screening adherence and later stage diagnosis. The objective of this research phase was to test predictors of ever having received CRC screening (i.e., self-report of lifetime receipt of CRC screening) using survey measures in the domains of healthcare communication, trust in doctors, CRC perceived susceptibility, CRC worry, negative cancer beliefs, CRC screening self-efficacy, and cultural constructs for CRC screening in a sample of African American community health center patients. The study recruited 115 African American patients between the ages of 45 to 64years old from community health centers in north Florida to complete the baseline survey. Our results show significant differences in CRC screening history by age, marital status, level of mistrust of healthcare providers, and level of empowerment toward cancer screening. To increase CRC screening in this population, the study findings suggest development of intervention programs that focus on priority populations of younger, unmarried African Americans, especially given the current trend of early onset CRC. Moreover, survival rates are lower for unmarried and younger African Americans relative to older and married individuals. Such interventions should also aim to increase trust in healthcare providers and increase empowerment for CRC screening decision making to increase screening participation.

THE INTERACTIVE EFFECTS OF EDUCATION AND SOCIAL SUPPORT ON COGNITION IN AFRICAN AMERICANS

Abstract This study examines whether the effects of receiving or providing social support on cognition differ by education. Data from 602 African American adults (48-95 years) enrolled in the Baltimore Study of Black Aging—Patterns of Cognitive Aging were analyzed using multiple linear regression. We found no main effects of receiving or providing social support on global cognition. However, a significant moderation effect was observed for memory, such that received social support was more strongly associated with higher working memory among less-educated individuals than those with high levels of education, adjusting for age, sex, marital status, chronic health conditions, and depressive symptoms. Study findings demonstrate that social support and education have joint effects on memory outcomes, highlighting the importance of considering psychosocial protective factors that might alleviate, reduce, or even eliminate cognitive health disparities in African Americans.

The Interactive Effects of Education and Social Support on Cognition in African Americans.

Objectives: This study examines whether the effects of receiving and providing social support on cognition differ by education. Methods: Data from 602 African American adults (48-95years) enrolled in the Baltimore Study of Black Aging-Patterns of Cognitive Aging were analyzed using multiple linear regression. Results: We found no main effects of receiving or providing social support on global cognition. Main effects for receiving or providing social support on memory were detected. Further, a significant moderation effect was observed for memory, such that received social support was more strongly associated with higher working memory among less-educated individuals than those with high levels of education, adjusting for age, sex, marital status, chronic conditions, and depressive symptoms. Discussion: Study findings demonstrate that social support and education have joint effects on memory outcomes, highlighting the importance of considering psychosocial protective factors that might alleviate, reduce, or even eliminate cognitive health disparities in African Americans.

The impact of SBF2 on taxane-induced peripheral neuropathy.

Taxane-induced peripheral neuropathy (TIPN) is a devastating survivorship issue for many cancer patients. In addition to its impact on quality of life, this toxicity may lead to dose reductions or treatment discontinuation, adversely impacting survival outcomes and leading to health disparities in African Americans (AA). Our lab has previously identified deleterious mutations in SET-Binding Factor 2 (SBF2) that significantly associated with severe TIPN in AA patients. Here, we demonstrate the impact of SBF2 on taxane-induced neuronal damage using an ex vivo model of SBF2 knockdown of induced pluripotent stem cell-derived sensory neurons. Knockdown of SBF2 exacerbated paclitaxel changes to cell viability and neurite outgrowth while attenuating paclitaxel-induced sodium current inhibition. Our studies identified paclitaxel-induced expression changes specific to mature sensory neurons and revealed candidate genes involved in the exacerbation of paclitaxel-induced phenotypes accompanying SBF2 knockdown. Overall, these findings provide ex vivo support for the impact of SBF2 on the development of TIPN and shed light on the potential pathways involved.

Implementing community-based participatory research among African Americans with serious and persistent mental illness: A qualitative study

Community-based participatory research (CBPR) is an approach that involves community members in research, not as research participants, but as partners. However, few studies have examined CBPR projects conducted among African Americans with serious and persistent mental illness (SPMI). This article focuses specifically on the Inspiring Change (IC) model, which includes a leadership trio comprised of an academic researcher, health service provider and an African American with lived experience of SPMI. Our purpose is to investigate how the IC model shapes not only how research is conducted but how research is understood and experienced by the community. We achieve this purpose by (1) describing an innovative CBPR model and pilot projects that involved African Americans with SPMI in all stages of the research project; and (2) presenting findings from qualitative interviews conducted with CBPR team members about strengths, challenges and leadership particular to this model of CBPR, an area rarely explored in CBPR literature.
 With the guidance of an advisory board and the manualised IC curriculum, two CBPR teams initiated and conducted nine-month long research projects focusing on health disparities for African Americans with SPMI. Members of the two CBPR teams (n = 13), which included individuals with lived experience, service providers and researchers, completed qualitative interviews. Benefits of CBPR projects included opportunities to learn, a sense of purpose in helping others and increased trust of research participants. Challenges pertained to disorganisation of leadership, lack of transparency with compensation, time pressures and interpersonal conflicts. These challenges highlight the importance of preparing and supporting those from both academic and lived experience backgrounds in skills necessary to thrive in leadership roles for CBPR projects.

Disentangling the Coronavirus Disease 2019 Health Disparities in African Americans: Biological, Environmental, and Social Factors.

The stark racial disparities related to the coronavirus disease 2019 (COVID-19) pandemic in the United States, wherein minority populations are disproportionately getting infected and succumbing to the disease, is of grave concern. It is critical to understand and address the underlying causes of these disparities that are complex and driven by interacting environmental, social and biological factors. In this article we focus on the African American community and examine how social and environmental determinants of health intersect with biological factors (comorbidities, underlying genetics, host immunity, vitamin D levels, epigenetics) to exacerbate risk for morbidity and mortality.

Resident-Led Neighborhood Development to Support Health: Identifying Strategies Using CBPR.

Evidence suggests that where people live, learn, work, and play affects a range of health outcomes for children and adults. Differential access to social, economic, and environmental supports puts some community members at greater risk, leading to disparities in health and well-being. The 2014 release of the For the Sake of All report highlighted persistent health disparities for African Americans in St. Louis, Missouri, and their social and economic impacts on the St. Louis region. This study extends this work by developing partnerships with community organizations and neighborhood residents to address health disparities. Community-based participatory research (CBPR) methods were utilized to engage partners in a 10-month research process to address community concerns that impact health. Seven community residents, neighborhood researchers, engaged in workshops to learn about the research process and used techniques to gather information to implement action strategies. Neighborhood researchers selected 14 vacant lots to implement their action plan, which included visions for repurposing the land into a community park, produced a report for dissemination, and organized a community action forum to communicate their findings. This study highlights a promising approach to promote healthy communities and health equity by empowering neighborhood residents using participatory methodologies.

Abstract A112: Integrative epigenomic and transcriptomic analyses of kidney cancers from African Americans and European Americans

Abstract Background: Kidney cancer ranks as a top ten leading site of new cancer cases (~64,000) in the United States each year. Renal cell carcinoma (RCC) is the most common type of kidney cancer (90% cases), with clear cell RCC (ccRCC) being the most prevalent histology (70% RCC cases). RCC risk factors include nonmodifiable, modifiable, environmental, and occupational causes. RCC subtypes each have a different histology, clinical course, and response to therapy, in addition to distinctive genetic and molecular alterations. African Americans (AA) have higher incidence rates of ccRCC than European Americans (EA) for reasons that are unclear. Biologic determinants of this cancer health disparity have been largely understudied. Recent work has identified population-specific genomic drivers in ccRCC tumors from AA compared with EA. To date, no study has explored epigenomic or transcriptomic determinants of kidney cancer health disparities in AA. Hypothesis: We hypothesized population-specific changes in DNA methylation, between AA and EA, drive differences in ccRCC biology through regulation of the transcriptome. Methods: Comparative integrative genomic and transcriptomic analyses were performed using clinical demographic and ccRCC data (Illumina 450K methylation array and mRNA-seq) from TCGA (n=50 AA, 266 EA) and Partek Genomics Suite. Results: Differential methylation analysis discovered 2,048 genes varied significantly by race (P value + FDR = ≤0.01). Gene Ontology Enrichment Score (ES) analysis revealed these genes were involved with various molecular functions (nucleic acid binding ES 38.52, protein binding ES 38.03), biologic processes (cellular metabolic process ES 78.60), and cellular component localization (intracellular organelles ES 87.24). Differential gene expression analysis revealed 3,296 genes were altered in AA compared with EA race (P value + FDR = ≤0.01). GSEA analysis revealed distinct biologic pathways were enriched. Conclusion and Future Directions: Collectively, our data suggest that DNA methylation and mRNA expression drive differences in tumor biology amongst AA and EA kidney cancer patients. Future studies include integrating miRNA expression data, validating these findings in a separate cohort, profiling other RCC histologies for population-specific signatures, and using kidney cancer cell lines from AA and EA to explore novel biologic mechanisms for therapeutic purposes. Citation Format: Heinric Williams, Khadijah A. Mitchell. Integrative epigenomic and transcriptomic analyses of kidney cancers from African Americans and European Americans [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A112.

‘Walk a mile in my shoes:’ African American caregiver perceptions of caregiving and self-care

ABSTRACT African American Alzheimer’s disease and related dementia (ADRD) family caregivers are understudied in intervention research with discrepant evidence existing on their mental and physical health outcomes. The stress toll of ADRD caregiving, coupled with the well-documented health disparities for African Americans, place these caregivers at higher risk for morbidity and mortality. Objectives: The purpose of this study was to explore African American ADRD family caregivers’ perceptions of caregiving and self-care. Design: Qualitative descriptive study based on individual, one-time, semi-structured interviews from a purposeful sample of current/former African American ADRD community-dwelling family caregivers. Participants agreed to either face-to-face or telephonic interviews between 60 and 90 minutes in length. Results: Twenty-one caregiver interviews were conducted with primarily adult children (mean age = 62.61 (SD = 12.88); 81% completed college; 57% women). Content analysis yielded three major themes: Stressors, Resources, and Coping. The results demonstrate a complex interaction of sociocultural and environmental stressors and perceptions of resources that influence the coping strategies adopted by caregivers to navigate their caregiving experience. Conclusions: These findings suggest a broadened perspective to further inform the development and testing of interventions to address the health outcomes and caregiving needs of African American ADRD caregivers.

RACIAL DISPARITIES IN ELIGIBILITY FOR LOW-DOSE COMPUTED TOMOGRAPHY LUNG CANCER SCREENING AMONG OLDER ADULTS WITH A HISTORY OF SMOKING

Lung cancer early detection screening has been demonstrated to decrease lung cancer mortality among high-risk smokers. This study aimed to examine whether current screening guidelines may disproportionately exclude African American smokers who are at higher overall risk for lung cancer. Data from the 2014 Health and Retirement Study were analyzed. Older African Americans and Whites with a history of smoking were included in the analyses (n = 7,348). Eligibility criteria established by the U.S. Preventive Services Task Force (USPSTF) for LDCT lung cancer screening were used. Multivariate logistic regression analyses were conducted to examine racial differences in eligibility for LDCT lung cancer screening. Overall, 21.1% of current and 10.5% of former smokers met USPSTF’s eligibility criteria for LDCT screening. In multivariate logistic regression analyses, African American smokers were less likely to be eligible for LDCT lung cancer screening compared to Whites (odds ratio = 0.5; p < 0.001). African American smokers were less likely to meet established lung cancer screening eligibility criteria compared to Whites. Current lung cancer screening criteria may not adequately capture African Americans at risk and may widen the health disparities in African Americans. Further longitudinal studies are needed to evaluate the efficacy of current lung cancer screening guideline.

Racial disparities in eligibility for low-dose computed tomography lung cancer screening among older adults with a history of smoking.

Lung cancer early detection screening has been demonstrated to decrease lung cancer mortality among high-risk smokers. This study aimed to examine whether current screening guidelines may disproportionately exclude African American smokers who are at higher overall risk for lung cancer. Data from the 2014 Health and Retirement Study were analyzed. Older African Americans and Whites with a history of smoking were included in the analyses (n = 7,348). Eligibility criteria established by the U.S. Preventive Services Task Force (USPSTF) for LDCT lung cancer screening were used. Multivariate logistic regression analyses were conducted to examine racial differences in eligibility for LDCT lung cancer screening. Overall, 21.1% of current and 10.5% of former smokers met USPSTF's eligibility criteria for LDCT screening. In multivariate logistic regression analyses, African American smokers were less likely to be eligible for LDCT lung cancer screening compared to Whites (odds ratio = 0.5; p < 0.001). African American smokers were less likely to meet established lung cancer screening eligibility criteria compared to Whites. Current lung cancer screening criteria may not adequately capture African Americans at risk and may widen the health disparities in African Americans. Further longitudinal studies are needed to evaluate the efficacy of current lung cancer screening guideline.

Identifying health conditions, priorities, and relevant multilevel health promotion intervention strategies in African American churches: A faith community health needs assessment

Identifying health conditions, priorities, and relevant multilevel health promotion intervention strategies in African American churches: A faith community health needs assessment

"As a Community, We Need to be More Health Conscious": Pastors' Perceptions on the Health Status of the Black Church and African-American Communities.

Churches are recognized for their potential capacity to provide health services and interventions to address health disparities in African-Americans (blacks). Since pastors are central community leaders, their support and involvement can influence both implementation and outcomes for church-based health programs. The purpose of this qualitative study was to explore pastors' perceptions of congregant health status within the black church. Semi-structured interviews were conducted with 11 pastors whose female congregants participated in a physical activity intervention. Thematic analysis techniques were used to analyze interview data. Three major themes emerged: (1) health risks in the African-American community, (2) health promotion in the black church, and (3) the importance of women in the black family and the church. Pastors noted numerous health disparities affecting their congregants and the African-American community at large, including obesity and infant mortality. They viewed health holistically and included faith in their perspectives. According to pastors, holistic health was promoted through health ministry programming in black churches. Women were described as the cornerstone of the black church, yet faced unique health concerns from their roles as family caretakers and congregants. Pastors shared their major concerns for congregant health status and the African-American community. Health interventions focusing on African-Americans in church settings should include pastor involvement and should incorporate holistic approaches to address health risks.

Hypothalamic-Pituitary-Adrenal Reactivity to Acute Stress: an Investigation into the Roles of Perceived Stress and Family Resources.

Rurally situated African Americans suffer from chronic exposure to stress that may have a deleterious effect on health outcomes. Unfortunately, research on potential mechanisms that underlie health disparities affecting the African American community has received limited focus in the scientific literature. This study investigated the relationship between perceived stress, family resources, and cortisol reactivity to acute stress. A rural sample of African American emerging adults (N = 60) completed a battery of assessments, the Trier Social Stress Test (TSST), and provided four samples of salivary cortisol: prior to receiving TSST instructions, prior to conducting the speech task, immediately following the TSST, and 15-20min following the TSST. As predicted, cortisol levels increased in response to a controlled laboratory inducement of acute stress. Moreover, diminished levels of family resources were associated with blunted cortisol reactivity to acute stress. Of note, higher levels of perceived stress over the past month and being male were independently associated with lower levels of cortisol at baseline. Lack of family resources had a blunting relationship on the hypothalamic-pituitary-adrenal axis reactivity. These findings provide biomarker support for the relationship between family resources-an indicator associated with social determinants of health-and stress physiology within a controlled laboratory experiment. Identifying mechanisms that work toward explanation of within-group differences in African American health disparities is both needed and informative for culturally informed prevention and intervention efforts.

Psychosocial Mechanisms Linking the Social Environment to Mental Health in African Americans.

Resource-poor social environments predict poor health, but the mechanisms and processes linking the social environment to psychological health and well-being remain unclear. This study explored psychosocial mediators of the association between the social environment and mental health in African American adults. African American men and women (n = 1467) completed questionnaires on the social environment, psychosocial factors (stress, depressive symptoms, and racial discrimination), and mental health. Multiple-mediator models were used to assess direct and indirect effects of the social environment on mental health. Low social status in the community (p < .001) and U.S. (p < .001) and low social support (p < .001) were associated with poor mental health. Psychosocial factors significantly jointly mediated the relationship between the social environment and mental health in multiple-mediator models. Low social status and social support were associated with greater perceived stress, depressive symptoms, and perceived racial discrimination, which were associated with poor mental health. Results suggest the relationship between the social environment and mental health is mediated by psychosocial factors and revealed potential mechanisms through which social status and social support influence the mental health of African American men and women. Findings from this study provide insight into the differential effects of stress, depression and discrimination on mental health. Ecological approaches that aim to improve the social environment and psychosocial mediators may enhance health-related quality of life and reduce health disparities in African Americans.

Can L-Cysteine and Vitamin D Rescue Vitamin D and Vitamin D Binding Protein Levels in Blood Plasma of African American Type 2 Diabetic Patients?

Aims: Vitamin D (VD) deficiency has become a worldwide epidemic, particularly affecting African Americans (AA). VD deficiency has been implicated in the excessive rate of complications associated with diabetes in AA. Blood levels of VD binding protein (VDBP) and glutathione (GSH) are lower in AA compared with those in Caucasians. This study tested the hypothesis that lower GSH levels are linked to VDBP and VD deficiency in AA-type 2 diabetic (AA-T2D) patients. Blood was analyzed from T2D and nondiabetic subjects (N). Experiments examining GSH deficiency and l-cysteine (LC) supplementation were performed using THP-1 monocytes. Results: Plasma levels of LC, GSH, VDBP, and VD were significantly lower in AA-T2D compared with age-matched AA-N or Caucasian-T2D. Lower levels of LC and GSH showed a significant positive correlation with lower VDBP and VD levels in AA-T2D. GSH deficiency investigated using an antisense approach depleted VDBP/vitamin D receptor (VDR); LC supplementation caused significant upregulation of GSH and of VDBP/VDR, while supplementation with VD+LC caused a significantly greater GSH and VDBP/VDR upregulation compared with that of VD alone in monocytes. Innovation and Conclusion: The reported observations suggest that VD deficiency may be linked to GSH and LC status and lead to a novel hypothesis that supplementation with LC in combination with VD will be effective in increasing VD levels and reducing health disparities in AA. Antioxid. Redox Signal. 23, 688–693.

Talking About Race

This article is a reflection of the individual and collective experiences of university professors of color whose work addresses African American health disparities. As instructors with the responsibility of introducing undergraduate students to the concept of health disparities, we believe it is beneficial for students to examine health disparities within the historical context of race. From our collective experiences, we offer selected resources to help students (1) understand race as a social construct and (2) understand that health disparities are not a consequence of inherent race-based biological differences. This is paramount to initiating a discussion of African American health disparities. Furthermore, this challenges students to think critically about social determinants of health and the broader ecological factors associated with health disparities. In preparing future professionals in health promotion, this results in more well-rounded practitioners who are better able to engage with more diverse communities.

Finding a Voice: an Allocentric Worldview to Guide Effective Reduction of Behavioral Health Disparities in African Americans

Reduction and elimination of African American health disparities, a major challenge of our society for the past 20 years, has not been realized, although empirical studies, clinical practice and policy initiatives have made progress in their attempt to achieve this goal. Behavioral health risks are a significant component of such disparities. In this paper the authors maintain that the precise lack of understanding of how much behavioral health is influenced by worldview, and the importance of historical roots of African American people, and the challenges they face in the 21st century need to be explored and understood within the context of worldview. Specifically, the allocentric worldview should be considered an essential component in discussions surrounding behavioral health disparities. This paper argues that anything less than an historical assessment of the conditions leading up to behavioral health ills in African American urban and rural communities today will be incomplete, inaccurate and fall short of achieving the goals of reducing behavioral health disparities in this population. The purpose of this manuscript is to present the allocentric worldview and explore how its adoption is critical to behavioral health recovery among African Americans today. It is proposed that knowing and adopting a cultural and historical worldview that is indigenous to African descended peoples may significantly improve motivation and action among African Americans to adopt healthier behavioral health life styles.