Duration-sensitive association between air pollution exposure and changes in cardiometabolic biomarkers: Evidence from a predominantly African American cohort.

BACKGROUND: Ambient fine particulate matter (PM2.5) exposure has been related to cardiometabolic diseases, but the underlying biological pathways remain unclear at the population level. OBJECTIVE: To investigate the effect of PM2.5 exposure on changes in multiple cardiometabolic biomarkers across different exposure durations. METHOD: Data from a prospective cohort study were analyzed. Ten cardiometabolic biomarkers were measured, including ghrelin, resistin, leptin, C-peptide, creatine kinase myocardial band (CK-MB), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNF-alpha), N-terminal pro B-type natriuretic peptide (NT-proBNP), troponin, and interleukin-6 (IL-6). PM2.5 levels across exposure durations from 1 to 36 months were assessed. Mixed effect model was used to estimate changes in biomarker levels against 1 µg/m3 increase in PM2.5 level across different exposure durations. RESULTS: Totally, 641 participants were included. The average PM2.5 exposure level was 9 µg/m3. PM2.5 exposure was inversely associated with ghrelin, and positively associated with all other biomarkers. The magnitudes of these associations were duration-sensitive and exhibited a U-shaped or inverted-U-shaped trend. For example, the association of resistin were ß = 0.05 (95% CI: 0.00, 0.09) for 1-month duration, strengthened to ß = 0.27 (95% CI: 0.14, 0.41) for 13-month duration, and weakened to ß = 0.12 (95% CI: -0.03, 0.26) for 24-month duration. Similar patterns were observed for other biomarkers except for CK-MB, of which the association direction switched from negative to positive as the duration increased. Resistin, leptin, MCP-1, TNF-alpha, and troponin had a sensitive exposure duration of nearly 12 months. Ghrelin and C-peptide were more sensitive to longer-term exposure (>18 months), while NT-proBNP and IL-6 were more sensitive to shorter-term exposure (<6 months). CONCLUSION: PM2.5 exposure was associated with elevated levels in cardiometabolic biomarkers related to insulin resistance, inflammation, and heart injury. The magnitudes of these associations depended on the exposure duration. The most sensitive exposure durations of different biomarkers varied.

The Impact of Neighborhood Disadvantage on Asthma Prevalence in a Predominantly African-American, Chicago-Based Cohort.

This study aimed to investigate the joint effect of neighborhood disadvantages on asthma prevalence and evaluate whether individual-level variables protect residents against neighborhood disadvantages. Data from the Chicago Multiethnic Prevention and Surveillance Study (from 2013-2020) were analyzed. Eight neighborhood characteristics were measured using the Chicago Health Atlas, including neighborhood unsafety, limited access to healthy food, neighborhood alienation, severe rent burden, vacant housing, single-parent household, neighborhood poverty, and unemployment. A structured questionnaire measured asthma diagnosis (childhood or adulthood) and individual-level variables including sex, age, income, education, and race. Weighted quantile sum (WQS) regression was used to evaluate the impact of neighborhood disadvantages. Stratified analysis was performed by income and education. A total of 6,592 participants (mean age = 53.5 (standard deviation, 11.1) years) were included. Most of the study population were non-Hispanic Black (82.5%) and reported an annual household income less than $15,000 (53%). Asthma prevalence was 23.6%. The WQS index, which represents the overall neighborhood disadvantages, was associated with asthma prevalence (odds ratio = 1.14, 95% confidence interval: 1.07, 1.22) when adjusted for individual-level confounders. Neighborhood poverty contributed 40.8% to the overall impact, followed by vacant housing (23.1%) and neighborhood alienation (22.9%). When stratified by individual-level income or education, no difference was observed for the association between WQS index and asthma prevalence.

Household air pollution, ultrasound measurement, fetal biometric parameters and intrauterine growth restriction.

BACKGROUND: Low birthweight, intrauterine growth restriction (IUGR) and perinatal mortality have been associated with air pollution. However, intervention studies that use ultrasound measurements to assess the effects of household air pollution (HAP) on fetal biometric parameters (FBP) are rare. We investigated the effect of a cookstove intervention on FBP and IUGR in a randomized controlled trial (RCT) cohort of HAP-exposed pregnant Nigerian women. METHODS: We recruited 324 women early in the second trimester of pregnancy. Between 16 and 18 weeks, we randomized them to either continue cooking with firewood/kerosene (control group) or receive a CleanCook stove and ethanol fuel (intervention group). We measured fetal biparietal diameter (BPD), head circumference (HC), femur length (FL), abdominal circumference (AC) and ultrasound-estimated fetal weight (U-EFW) in the second and third trimesters. The women were clinically followed up at six regular time points during their pregnancies. Once during the women's second trimester and once during the third, we made 72-h continuous measurements of their personal exposures to particulate matter having aerodynamic diameter < 2.5 µm (PM2.5). We adopted a modified intent-to-treat approach for the analysis. Differences between the intervention and control groups on impact of HAP on fetal growth trajectories were analyzed using mixed effects regression models. RESULTS: There were no significant differences in fetal growth trajectories between the intervention and control groups. CONCLUSIONS: Larger studies in a setting of low ambient air pollution are required to further investigate the effect of transitioning to a cleaner fuel such as ethanol on intrauterine growth. TRIAL REGISTRATION: ClinicalTrials.gov NCT02394574 ; September 2012.

Implementing oncology clinical trials in Nigeria: a model for capacity building.

BACKGROUND: There is both higher mortality and morbidity from cancer in low and medium income countries (LMICs) compared with high income countries (HICs). Clinical trial activities and development of more effective and less toxic therapies have led to significant improvements in morbidity and mortality from cancer in HICs. Unfortunately, clinical trials remain low in LMICs due to poor infrastructure and paucity of experienced personnel to execute clinical trials. There is an urgent need to build local capacity for evidence-based treatment for cancer patients in LMICs. METHODS: We conducted a survey at facilities in four Teaching Hospitals in South West Nigeria using a checklist of information on various aspects of clinical trial activities. The gaps identified were addressed using resources sourced in partnership with investigators at HIC institutions. RESULTS: Deficits in infrastructure were in areas of patient care such as availability of oncology pharmacists, standard laboratories and diagnostic facilities, clinical equipment maintenance and regular calibrations, trained personnel for clinical trial activities, investigational products handling and disposals and lack of standard operating procedures for clinical activities. There were two GCP trained personnel, two study coordinators and one research pharmacist across the four sites. Interventions were instituted to address the observed deficits in all four sites which are now well positioned to undertake clinical trials in oncology. Training on all aspects of clinical trial was also provided. CONCLUSIONS: Partnerships with institutions in HICs can successfully identify, address, and improve deficits in infrastructure for clinical trial in LMICs. The HICs should lead in providing funds, mentorship, and training for LMIC institutions to improve and expand clinical trials in LMIC countries.

Randomized Controlled Ethanol Cookstove Intervention and Blood Pressure in Pregnant Nigerian Women.

RATIONALE: Hypertension during pregnancy is a leading cause of maternal mortality. Exposure to household air pollution elevates blood pressure (BP). OBJECTIVES: To investigate the ability of a clean cookstove intervention to lower BP during pregnancy. METHODS: We conducted a randomized controlled trial in Nigeria. Pregnant women cooking with kerosene or firewood were randomly assigned to an ethanol arm (n = 162) or a control arm (n = 162). BP measurements were taken during six antenatal visits. In the primary analysis, we compared ethanol users with control subjects. In subgroup analyses, we compared baseline kerosene users assigned to the intervention with kerosene control subjects and compared baseline firewood users assigned to ethanol with firewood control subjects. MEASUREMENTS AND MAIN RESULTS: The change in diastolic blood pressure (DBP) over time was significantly different between ethanol users and control subjects (P = 0.040); systolic blood pressure (SBP) did not differ (P = 0.86). In subgroup analyses, there was no significant intervention effect for SBP; a significant difference for DBP (P = 0.031) existed among preintervention kerosene users. At the last visit, mean DBP was 2.8 mm Hg higher in control subjects than in ethanol users (3.6 mm Hg greater in control subjects than in ethanol users among preintervention kerosene users), and 6.4% of control subjects were hypertensive (SBP ≥140 and/or DBP ≥90 mm Hg) versus 1.9% of ethanol users (P = 0.051). Among preintervention kerosene users, 8.8% of control subjects were hypertensive compared with 1.8% of ethanol users (P = 0.029). CONCLUSIONS: To our knowledge, this is the first cookstove randomized controlled trial examining prenatal BP. Ethanol cookstoves have potential to reduce DBP and hypertension during pregnancy. Accordingly, clean cooking fuels may reduce adverse health impacts associated with household air pollution. Clinical trial registered with www.clinicaltrials.gov (NCT02394574).

Biomass fuel exposure and asthma symptoms among rural school children in Nigeria.

BACKGROUND: Approximately 70% of rural Nigerian households rely on biomass fuels for cooking. The International Study of Asthma and Allergies in Childhood (ISAAC) estimates the prevalence of current wheeze among children in Nigeria to have risen from 10.7% in 1999 to approximately 20% in 2014. OBJECTIVE: To examine the effects of biomass smoke exposure on asthma symptom prevalence in rural children in Nigeria. METHODS: We conducted a cross-sectional survey in rural communities in Nigeria. Asthma symptoms were defined according to ISAAC definitions. Biomass smoke exposure was determined by the types of fuel used for cooking. Logistic regression was used to explore associations between biomass smoke and asthma symptoms. RESULTS: The study population comprised 1,690 school children, of which 865 lived in households cooking with biomass and 825 lived in households not using biomass. Asthma symptoms were reported in 481 (28.5%) children. Biomass fuel was associated with increased odds of asthma symptoms. Adjusted odds ratios (aORs) were 1.38 (95% CI: 1.05-1.80) for nocturnal cough, 1.26 (95% CI: 1.00-1.61) for current wheeze, and 1.33 (95% CI: 1.05-1.69) for report of any asthma-related symptoms. Sex modified the associations between asthma symptoms with biomass fuel: aORs were stronger and significant for males (nocturnal cough = 1.85, 95% CI: 1.24-2.76; current wheeze = 1.48, 95% CI: 1.03-2.13; report of any asthma-related symptoms = 1.60, 95% CI: 1.12-2.28), but weaker and non-significant for females. CONCLUSION: The risk of asthma symptoms related to biomass smoke exposure appears to differ by sex.

Household biomass fuel use, asthma symptoms severity, and asthma underdiagnosis in rural schoolchildren in Nigeria: a cross-sectional observational study.

BACKGROUND: In 2014, the International Study of Asthma and Allergies in Childhood (ISAAC) reported that the highest prevalence of symptoms of severe asthma was found in the low- and middle-income countries (LMICs), including Nigeria. While exposure to biomass fuel use may be an important risk factor in the development of asthma, its association with asthma symptoms severity has not been well-established. The aim of this study is to extend the spectrum of environmental risk factors that may be contributing towards increasing asthma morbidity, especially asthma symptoms severity in rural schoolchildren in Nigeria and to examine possible asthma underdiagnosis among this population. METHODS: Authors conducted a cross-sectional survey in three rural communities in Nigeria. Asthma symptoms were defined according to the ISAAC criteria. Information on the types of household fuel used for cooking was used to determine household cooking fuel status. Asthma symptoms severity was defined based on frequencies of wheeze, day- and night-time symptoms, and speech limitations. Logistic regression analyses were used to explore associations. RESULTS: A total of 1,690 Nigerian schoolchildren participated in the study. Overall, 37 (2.2%) had diagnosed asthma and 413 (24.4%) had possible asthma (asthma-related symptoms but not diagnosed asthma). Children from biomass fuel households had higher proportion of possible asthma (27.7 vs. 22.2%; p < 0.05) and symptoms of severe asthma (18.2 vs. 7.6%; p = 0.048). In adjusted analyses, biomass fuel use was associated with increased odds of severe symptoms of asthma [odds ratios (OR) = 2.37; 95% CI: 1.16-4.84], but not with possible asthma (OR = 1.22; 95% CI: 0.95-1.56). CONCLUSION: In rural Nigerian children with asthma symptoms, the use of biomass fuel for cooking is associated with an increased risk of severe asthma symptoms. There is additional evidence that rural children might be underdiagnosed for asthma.

Air Pollution and Racial Disparities in Pregnancy Outcomes in the United States: A Systematic Review.

BACKGROUND: Exposure to air pollutants and other environmental factors increases the risk of adverse pregnancy outcomes. There is growing evidence that adverse outcomes related to air pollution disproportionately affect racial and ethnic minorities. The objective of this paper is to explore the importance of race as a risk factor for air pollution-related poor pregnancy outcomes. METHODS: Studies investigating the effects of exposure to air pollution on pregnancy outcomes by race were reviewed. A manual search was conducted to identify missing studies. Studies that did not compare pregnancy outcomes among two or more racial groups were excluded. Pregnancy outcomes included preterm births, small for gestational age, low birth weight, and stillbirths. RESULTS: A total of 124 articles explored race and air pollution as risk factors for poor pregnancy outcome. Thirteen percent of these (n=16) specifically compared pregnancy outcomes among two or more racial groups. Findings across all reviewed articles showed more adverse pregnancy outcomes (preterm birth, small for gestational age, low birth weight, and stillbirths) related to exposure to air pollution among Blacks and Hispanics than among non-Hispanic Whites. CONCLUSION: Evidence support our general understanding of the impact of air pollution on birth outcomes and, specifically, of disparities in exposure to air pollution and birth outcomes for infants born to Black and Hispanic mothers. The factors driving these disparities are multifactorial, mostly social, and economic factors. Reducing or eliminating these disparities require interventions at individual, community, state, and national level.

Multi-omics in nasal epithelium reveals three axes of dysregulation for asthma risk in the African Diaspora populations.

Asthma has striking disparities across ancestral groups, but the molecular underpinning of these differences is poorly understood and minimally studied. A goal of the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to understand multi-omic signatures of asthma focusing on populations of African ancestry. RNASeq and DNA methylation data are generated from nasal epithelium including cases (current asthma, N = 253) and controls (never-asthma, N = 283) from 7 different geographic sites to identify differentially expressed genes (DEGs) and gene networks. We identify 389 DEGs; the top DEG, FN1, was downregulated in cases (q = 3.26 × 10-9) and encodes fibronectin which plays a role in wound healing. The top three gene expression modules implicate networks related to immune response (CEACAM5; p = 9.62 × 10-16 and CPA3; p = 2.39 × 10-14) and wound healing (FN1; p = 7.63 × 10-9). Multi-omic analysis identifies FKBP5, a co-chaperone of glucocorticoid receptor signaling known to be involved in drug response in asthma, where the association between nasal epithelium gene expression is likely regulated by methylation and is associated with increased use of inhaled corticosteroids. This work reveals molecular dysregulation on three axes - increased Th2 inflammation, decreased capacity for wound healing, and impaired drug response - that may play a critical role in asthma within the African Diaspora.

Fine mapping of breast cancer genome-wide association studies loci in women of African ancestry identifies novel susceptibility markers.

Numerous single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility have been identified by genome-wide association studies (GWAS). However, these SNPs were primarily discovered and validated in women of European and Asian ancestry. Because linkage disequilibrium is ancestry-dependent and heterogeneous among racial/ethnic populations, we evaluated common genetic variants at 22 GWAS-identified breast cancer susceptibility loci in a pooled sample of 1502 breast cancer cases and 1378 controls of African ancestry. None of the 22 GWAS index SNPs could be validated, challenging the direct generalizability of breast cancer risk variants identified in Caucasians or Asians to other populations. Novel breast cancer risk variants for women of African ancestry were identified in regions including 5p12 (odds ratio [OR] = 1.40, 95% confidence interval [CI] = 1.11-1.76; P = 0.004), 5q11.2 (OR = 1.22, 95% CI = 1.09-1.36; P = 0.00053) and 10p15.1 (OR = 1.22, 95% CI = 1.08-1.38; P = 0.0015). We also found positive association signals in three regions (6q25.1, 10q26.13 and 16q12.1-q12.2) previously confirmed by fine mapping in women of African ancestry. In addition, polygenic model indicated that eight best markers in this study, compared with 22 GWAS-identified SNPs, could better predict breast cancer risk in women of African ancestry (per-allele OR = 1.21, 95% CI = 1.16-1.27; P = 9.7 × 10(-16)). Our results demonstrate that fine mapping is a powerful approach to better characterize the breast cancer risk alleles in diverse populations. Future studies and new GWAS in women of African ancestry hold promise to discover additional variants for breast cancer susceptibility with clinical implications throughout the African diaspora.

Evaluating the impact of sickle cell disease on COVID-19 susceptibility and severity: a retrospective cohort study based on electronic health record.

Background: Sickle cell trait/disease (SCT/SCD) are enriched among Black people and associated with various comorbidities. The overrepresentation of these characteristics prevents traditional regression approach obtaining convincing evidence for the independent effect of SCT/SCD on other health outcomes. This study aims to investigate the association between SCT/SCD and COVID-19-related outcomes using causal inference approaches that balance the covariate. Methods: We leveraged electronic health record (EHR) data from the University of Chicago Medicine between March 2020 and December 2021. Demographic characteristics were retrieved. Medical conditions were identified using ICD-10 codes. Five approaches, including two traditional regression approaches (unadjusted and adjusted) and three causal inference approaches [covariate balancing propensity score (CBPS) matching, CBPS weighting, and CBPS adjustment], were employed. Results: A total of 112,334 patients were included in the study, among which 504 had SCT and 388 SCD. Patients with SCT/SCD were more likely to be non-Hispanic Black people, younger, female, non-smokers, and had a diagnosis of diabetes, heart failure, asthma, and cerebral infarction. Causal inference approaches achieved a balanced distribution of these covariates while traditional approaches failed. Across these approaches, SCD was consistently associated with COVID-19-related pneumonia (odds ratios (OR) estimates, 3.23 (95% CI: 2.13-4.89) to 2.57 (95% CI: 1.10-6.00)) and pain (OR estimates, 6.51 (95% CI: 4.68-9.06) to 2.47 (95% CI: 1.35-4.49)). While CBPS matching suggested an association between SCD and COVID-19-related acute respiratory distress syndrome (OR = 2.01, 95% CI: 0.97-4.17), this association was significant in other approaches (OR estimates, 2.96 (95% CI: 1.69-5.18) to 2.50 (95% CI: 1.43-4.37)). No association was observed between SCT and COVID-19-related outcomes in causal inference approaches. Conclusion: Using causal inference approaches, we provide comprehensive evidence for the link between SCT/SCD and COVID-19-related outcomes.

Impact of prenatal maternal psychological distress on fetal biometric parameters in household air pollution-exposed Nigerian women.

RATIONALE: Studies identify prenatal household air pollution (HAP) exposure and maternal psychological distress (PMPD) as independent factors contributing to gestational ill-health and adverse birth outcomes. OBJECTIVE: We investigated the impact of PMPD on fetal biometric parameters (FBP) in HAP-exposed pregnant Nigerian women. METHODS: The randomized controlled trial (RCT; ClinicalTrials.gov NCT02394574) investigated effects of HAP exposure in pregnant Nigerian women (n = 324), who customarily cooked with polluting fuels (firewood or kerosene). Half of the women (intervention group) were given CleanCook ethanol stoves to use for 156 days during the study. Once a month, all women were administered an abridged version of the SF-12v2TM health-related quality of life questionnaire to assess psychological distress. Using mixed effects linear regression models, adjusted for relevant covariates, we analyzed associations between the women's exposure to PM2·5 (particulate matter with an aerodynamic diameter<2·5 microns) from HAP, their PMPD scores, and FBP (ultrasound estimated fetal weight [UEFW], head circumference [HC], abdominal circumference [AC], femur length [FL], biparietal diameter [BPD], estimated gestational age [GA] and intrauterine growth restriction [IUGR]), and birth anthropometric measures (birth weight [BW] and birth length [BL]). RESULTS: PMPD negatively impacted UEFW, HC, FL, BPD and BL (p<0·05). Controls (kerosene/firewood users) experienced significantly higher PMPD compared with ethanol-stove users (p<0·05). The mediation analysis revealed that the proportion of the outcome (fetal biometrics, birth anthropometrics, IUGR and GA), which can be explained via PMPD by groups (intervention vs. control) after adjusting for confounding variables was 6·2% (0·062). No significant correlation was observed between levels of PM2.5 exposure and PMPD scores. CONCLUSIONS: PMPD was an independent mediator of adverse fetal biometric parameters in pregnant women, who were exposed to HAP from burning of firewood/kerosene. Formulating preventative measures to alleviate maternal distress during pregnancy and reducing exposure to HAP is important from public health perspectives.

Race may modify the association between blood type and COVID-19 infection.

This study aims to investigate the race/ethnicity-specific association between blood type and COVID-19 susceptibility during March, 2020 and December, 2021 using data from the electronic health record at the University of Chicago Medicine. The study population was stratified into four groups: non-Hispanic White, non-Hispanic Black, Hispanic, and other. Log-binomial generalized mixed model was used to estimate the relative risk (RR) and 95% confidence interval (CI). When compared to blood type O, type B was associated with positive COVID-19 test in Blacks (RR = 1.12, 95% CI: 1.02-1.23), Whites (RR = 1.28, 95% CI: 0.99-1.66), and Hispanic (RR = 1.36, 95% CI: 0.97-1.92).

Impact of prenatal and postnatal household air pollution exposure on lung function of 2-year old Nigerian children by oscillometry.

RATIONALE: Lung function is adversely affected by exposure to household air pollution (HAP). Studies investigating the impact of prenatal and postnatal HAP exposure on early childhood lung development are limited, especially from Sub-Saharan Africa. OBJECTIVE: We used oscillometry to investigate the impact on lung function of prenatal and postnatal HAP exposure of children born to Nigerian women who participated in a randomized controlled cookstove intervention trial. METHODS: We performed oscillometric measurements (R: airway resistance; X: airway reactance; Fres: resonant frequency; AX: reactance area) in 223 children starting at age of 2 years (ethanol stove, n = 113; firewood/kerosene, n = 110). Personal exposure monitoring assessed mothers' prenatal exposure to particulate matter less than 2.5 µm in aerodynamic diameter (PM2.5). Postnatal HAP exposure was measured by determining household PM2.5 levels. We employed linear regression analysis to examine the association of prenatal and postnatal HAP exposures with children's lung function. Models were adjusted for age, gender, weight, height, group (intervention or control), birthweight and gestational age. RESULTS: Mean age of the children was 2.9 years (standard deviation = 0.3); 120 were boys (53.8%) and 103 were girls (46.2%). Higher postnatal PM2.5 exposures were significantly associated with higher airway reactance at 5 Hz (X5 Hz; p = 0.04) in adjusted models. There were no significant associations between prenatal or postnatal PM2.5 exposure levels and other oscillometry parameters in adjusted regression analysis. CONCLUSIONS: This is the first study to use oscillometry to explore the relationship between HAP exposure and lung function in children as young as 2 years. The findings provide some evidence that increased postnatal HAP exposure may result in poorer lung function in children, although larger studies are needed to confirm observed results. This study indicates that oscillometry is a low-cost and effective method to determine lung function in early childhood.

ARETTA: Assessing Response to Neoadjuvant Taxotere and Subcutaneous Trastuzumab in Nigerian Women With HER2-Positive Breast Cancer: A Study Protocol.

Human epidermal growth factor receptor 2 (HER2) subtype of breast cancer is aggressive, leading to a poor outcome. Targeted therapy with trastuzumab has been shown to be effective in the treatment of HER2-positive breast cancer. Cardiotoxicity is a specific adverse effect associated with trastuzumab. The initial formulation of trastuzumab was intravenous, but presently, a subcutaneous formulation (Herceptin SC) is available. Insufficient data on the response rate and cardiotoxic effects of trastuzumab among indigenous Black populations exist. In all studies evaluating the efficacy and toxicity of trastuzumab alone or in combination with chemotherapy, indigenous Black populations in Africa were not included, yet they are the ones most likely to benefit from highly effective cancer medicines. This is partly due to poor oncology clinical trial infrastructure in sub-Saharan Africa. The ARETTA study protocol (ClinicalTrials.gov identifier: NCT03879577) is a phase II multicenter feasibility study to evaluate the efficacy and toxicity of docetaxel given every 3 weeks for 4 cycles plus trastuzumab in 60 previously untreated women with nonmetastatic breast cancer. The primary endpoint is to assess the proportion of patients with complete pathologic response. Secondary endpoints include the number of patients who require dose delays in docetaxel and trastuzumab attributed to hematologic, GI, and cardiac toxicity. Pharmacokinetic profiles of subcutaneous trastuzumab will also be determined. The ARETTA study will provide important information on the clinical response and cardiac safety of subcutaneous trastuzumab in combination with docetaxel among indigenous African women with nonmetastatic breast cancer. It can also be used as a blueprint for conducting biomarker-driven oncology clinical trials in low-resource settings such as sub-Saharan Africa.

Adapting and Operationalizing the RE-AIM Framework for Implementation Science in Environmental Health: Clean Fuel Cooking Programs in Low Resource Countries.

Introduction: The use of models and frameworks to design and evaluate strategies to improve delivery of evidence-based interventions is a foundational element of implementation science. To date, however, evaluative implementation science frameworks such as Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) have not been widely employed to examine environmental health interventions. We take advantage of a unique opportunity to utilize and iteratively adapt the RE-AIM framework to guide NIH-funded case studies of the implementation of clean cooking fuel programs in eleven low- and middle-income countries. Methods: We used existing literature and expert consultation to translate and iteratively adapt the RE-AIM framework across several stages of the NIH Clean Cooking Implementation Science case study project. Checklists and templates to guide investigators were developed at each stage. Results: The RE-AIM framework facilitated identification of important emerging issues across this set of case studies, in particular highlighting the fact that data associated with certain important outcomes related to health and welfare are chronically lacking in clean fuel programs. Monitoring of these outcomes should be prioritized in future implementation efforts. As RE-AIM was not originally designed to evaluate household energy interventions, employing the framework required adaptation. Specific adaptations include the broadening of Effectiveness to encompass indicators of success toward any stated programmatic goal, and expansion of Adoption to include household-level uptake of technology. Conclusions: The RE-AIM implementation science framework proved to be a useful organizing schema for 11 case studies of clean fuel cooking programs, in particular highlighting areas requiring emphasis in future research and evaluation efforts. The iterative approach used here to adapt an implementation science framework to a specific programmatic goal may be of value to other multi-country program efforts, such as those led by international development agencies. The checklists and templates developed for this project are publicly available for others to use and/or further modify.

Assembly of a pan-genome from deep sequencing of 910 humans of African descent.

We used a deeply sequenced dataset of 910 individuals, all of African descent, to construct a set of DNA sequences that is present in these individuals but missing from the reference human genome. We aligned 1.19 trillion reads from the 910 individuals to the reference genome (GRCh38), collected all reads that failed to align, and assembled these reads into contiguous sequences (contigs). We then compared all contigs to one another to identify a set of unique sequences representing regions of the African pan-genome missing from the reference genome. Our analysis revealed 296,485,284 bp in 125,715 distinct contigs present in the populations of African descent, demonstrating that the African pan-genome contains ~10% more DNA than the current human reference genome. Although the functional significance of nearly all of this sequence is unknown, 387 of the novel contigs fall within 315 distinct protein-coding genes, and the rest appear to be intergenic.

Author Correction: Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features.

The original version of this Article contained an error in the author affiliations. The affiliation of Kevin P. White with Tempus Labs, Inc. Chicago, IL, USA was inadvertently omitted. This has now been corrected in both the PDF and HTML versions of the Article.

Author Correction: Assembly of a pan-genome from deep sequencing of 910 humans of African descent.

In the version of this article initially published, the statement "there are no pan-genomes for any other animal or plant species" was incorrect. The statement has been corrected to "there are no reported pan-genomes for any other animal species, to our knowledge." We thank David Edwards for bringing this error to our attention. The error has been corrected in the HTML and PDF versions of the article.