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In 2010, the American Heart Association published a statement concluding that the existing scientific evidence was consistent with a causal relationship between exposure to fine particulate matter and cardiovascular morbidity and mortality, and that fine particulate matter exposure is a modifiable cardiovascular risk factor. Since the publication of that statement, evidence linking air pollution exposure to cardiovascular health has continued to accumulate and the biological processes underlying these effects have become better understood. This increasingly persuasive evidence necessitates policies to reduce harmful exposures and the need to act even as the scientific evidence base continues to evolve. Policy options to mitigate the adverse health impacts of air pollutants must include the reduction of emissions through action on air quality, vehicle emissions, and renewable portfolio standards, taking into account racial, ethnic, and economic inequality in air pollutant exposure. Policy interventions to improve air quality can also be in alignment with policies that benefit community and transportation infrastructure, sustainable food systems, reduction in climate forcing agents, and reduction in wildfires. The health care sector has a leadership role in adopting policies to contribute to improved environmental air quality as well. There is also potentially significant private sector leadership and industry innovation occurring in the absence of and in addition to public policy action, demonstrating the important role of public-private partnerships. In addition to supporting education and research in this area, the American Heart Association has an important leadership role to encourage and support public policies, private sector innovation, and public-private partnerships to reduce the adverse impact of air pollution on current and future cardiovascular health in the United States.

Background Our objective was to determine associations of occupational exposures with cardiac structure and function in Hispanic/Latino adults. Methods and Results Employed participants were included (n=782; 52% women, mean age 52.9 years). Occupational exposures to burning wood, vehicle exhaust, solvents, pesticides, and metals at the current and longest‐held job were assessed by questionnaire. Survey multivariable linear regression analyses were used to model the relationship of each self‐reported exposure with echocardiographic measures of cardiac structure and function. Exposure to burning wood at the current job was associated with decreased left ventricular (LV) ejection fraction (−3.1%; standard error [SE], 1.0 [ P =0.002]). When the analysis was restricted to exposure at the longest‐held job, occupational exposure to burning wood was associated with increased LV diastolic volume (6.7 mL; SE, 1.6 [ P P P =0.0009]), and decreased right ventricular fractional area change (−0.02; SE, 0.004 [ P P P =0.04]), increased stroke volume (3.6 mL; SE, 1.6 [ P =0.03]), and increased LV mass indexed to BSA (9.2 g/m 2 ; SE, 3.8 [ P =0.01]) or height (4.4 g/m 2.7 ; SE, 1.9 [ P =0.02]). Conclusions Occupational exposures to burning wood, vehicle exhaust, pesticides, and metals were associated with abnormal parameters of LV and right ventricular systolic function. Reducing exposures to toxic chemicals and particulates in the workplace is a potential opportunity to prevent cardiovascular disease in populations at risk.

Introduction The BMT-CTN 1204 study for Hemophagocytic Syndromes or Selected Primary Immune Deficiencies (NCT01998633) (RICHI) was a single arm study testing safety and efficacy of reduced intensity conditioning (RIC) with alemtuzumab (1mg/kg), fludarabine (150 mg/m2) and melphalan (140 mg/m2). Survival was favorable compared to historical studies, but patients experienced high rates of mixed chimerism (MC) and ultimate secondary graft failure (GF). Mechanisms for GF are not known. Expansion of recipient T cells and interferon-gamma pathway activation have been proposed as drivers for GF. However, high peri-transplant alemtuzumab levels have been associated with higher risk of MC and eventual secondary GF, suggesting an inverse relationship between GF and immune activation in the context of RIC. In order to elucidate mechanisms of GF for patients on the RICHI study, we systematically evaluated cytokine patterns and alemtuzumab levels and their association with durable engraftment. Methods Serial blood samples were collected, processed, and stored for consenting patients at day -14 (window: day -28 to -14), day -7 (+/- 1 day), day -1 (+/- 1), day +1 (+1 to +3), day +14 (+/- 2), day +28 (+/- 2), day +42 (+/- 3), day +70 (+/- 10), and day +100 (+/- 10). Alemtuzumab levels were measured using a flow cytometric assay as previously described. Comprehensive cytokine analysis was performed for over 100 analytes using the MagPix platform. Primary GF was defined as donor chimerism Results Thirty-three patients were included in this study with HLH (n=25), CAEBV (n=3), CGD (n=2), HIGM (n=2), and IPEX (n=1). All patients received bone marrow grafts and 27 (82%) patients had unrelated donors. Twenty-one grafts were 8/8 or 6/6 HLA-matched (64%) and 12 grafts were 7/8 HLA-matched (36%). Among all patients, 1 patient (3%) developed primary GF, 22 (67%) developed mixed chimerism (MC), and 11 patients (33%) developed secondary GF. Survival with sustained engraftment without DLI or second HCT was 40.0%. We first evaluated peripheral blood levels of 100+ cytokines. Analysis revealed significant differences between patients with and without GF as shown in Figure 1A. Notably, on day +14 and +28, patients with secondary GF had significantly lower CXCL9 levels than those without GF. We then estimated the cumulative incidence (CI) of secondary GF among patients with CXCL9 levels above and below the day +14 median level of 2394pg/mL. The CI of secondary GF in patients with a day +14 CXCL9 level ≤2394pg/mL was 73.6% vs 0% in patients with a level >2394pg/mL (p=0.002). The CI of secondary GF in patients with a day +28 CXCL9 level ≤2867pg/mL (day +28 median) was 64.3%, vs 0% in patients with levels >2867pg/mL (p=0.004). We then sought to correlate CXCL9 levels with alemtuzumab exposure, as high alemtuzumab levels would result in more efficient T cell depletion of donor grafts that could lead to lower CXCL9 levels. Indeed, CXCL9 levels inversely correlated with day 0 alemtuzumab levels. Patients with day 0 alemtuzumab levels >0.32µg/mL had lower CXCL9 levels compared to patients with levels ≤0.32µg/mL (Figure 1B). Finally, we examined the impact of alemtuzumab levels on MC and secondary GF. Patients with day 0 alemtuzumab levels ≤0.32µg/mL had a lower CI of MC compared to patients with levels >0.32µg/mL, 14.3% vs 90.9%, respectively (p=0.03). The CI of secondary GF was 0% in patients with day 0 alemtuzumab levels ≤0.32µg/mL compared to 54.3% in patients with levels >0.32µg/mL (p=0.08). Conclusions This study demonstrates a strong relationship between alemtuzumab levels and durable engraftment. Further, interferon gamma activity, as reflected by CXCL9, inversely correlates with peri-transplant alemtuzumab levels in this prospective cohort treated with RIC. Our findings support the paradigm that higher alemtuzumab levels drive efficient T cell depletion of the stem cell product which increases the risk of MC and secondary GF, suggesting that donor T cells promote engraftment via a graft versus hematopoiesis function. Precision alemtuzumab dosing strategies may offer an opportunity to improve outcomes for patients who undergo RIC HCT. Figure 1 Figure 1. Disclosures Pulsipher: Adaptive: Research Funding; Equillium: Membership on an entity's Board of Directors or advisory committees; Jasper Therapeutics: Honoraria. Bollard: Neximmune: Current equity holder in publicly-traded company; Catamaran Bio: Membership on an entity's Board of Directors or advisory committees; Cabaletta Bio: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Mana Therapeutics: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Cellectis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Repertoire Immune Medicines: Current equity holder in publicly-traded company; ROCHE: Consultancy, Honoraria; SOBI: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kean: Regeneron: Research Funding; Bristol Myers Squibb: Patents & Royalties: From clinical trial data, Research Funding; Bluebird Bio: Research Funding; Gilead: Research Funding; Vertex: Consultancy; Novartis: Consultancy; EMD Serono: Consultancy. Jordan: Sobi: Consultancy. Allen: Sobi: Consultancy. OffLabel Disclosure: Alemtuzumab, humanized monoclonal antibody against CD52, used as part of allogeneic HCT conditioning

Environmental exposures in low- and middle-income countries lie at the intersection of increased economic development and the rising public health burden of cardiovascular disease. Increasing evidence suggests an association of exposure to ambient air pollution, household air pollution from biomass fuel, lead, arsenic, and cadmium with multiple cardiovascular disease outcomes, including hypertension, coronary heart disease, stroke, and cardiovascular mortality. Although populations in low- and middle-income countries are disproportionately exposed to environmental pollution, evidence linking these exposures to cardiovascular disease is derived from populations in high-income countries. More research is needed to further characterize the extent of environmental exposures.

We developed a haploidentical transplantation protocol with post-transplant cyclophosphamide (CY) for in vivo T-cell depletion using a novel adapted-dosing schedule (25 mg/kg on days +3 and +4) for Fanconi Anemia. With median follow-up of 3 years (range, 37 days to 6.2 years), all six patients engrafted. Two patients with multiple co-morbidities and late referrals to transplant died from sepsis (n=2) and chronic graft-versus-host disease (GVHD) (n=1). Four patients without pre-existing co-morbidities and early transplant referrals are alive with 100% donor chimerism and excellent performance status. We conclude that modulated-dosing post-transplant CY is effective in vivo T-cell depletion to promote full donor engraftment in patients with Fanconi anemia.

Introduction Congenital dyserythropoietic anemias (CDA) are a rare group of hereditary disorders characterized by anemia, ineffective erythropoiesis, and secondary hemochromatosis. While some CDA patients respond to interferon α therapy (type I CDA) or splenectomy (type II CDA), others are dependent on chronic red cell transfusions lifelong. Hematopoietic cell transplant (HCT), remains the only curative option for this disease. In 39 patients reviewed by the European Society for Blood and Marrow Transplant (EBMT), graft rejection (GR) was 12% (1-23%), the 3-year overall survival (OS) and event free survival (EFS) were 71% (55-87%) and 45% (45-63%) respectively1. A trend towards higher incidence of GR and severe (Grade III-IV) acute graft versus host disease (GvHD) was observed in patients with iron overload and unrelated donor HCT but these risk factors were not statistically significant1. We report the outcomes in 17 children with CDA who underwent HCT at participating Pediatric Transplantation and Cellular Therapy Consortium (PTCTC) centers. Methods Clinical information on transplant and associated outcomes were collected retrospectively after IRB approval using a common questionnaire. Data were analyzed using descriptive statistics. Comparisons between groups were made using Fisher's exact tests. Survival estimates and corresponding 95% confidence intervals were performed using the Kaplan-Meier method. Results Seventeen patients (11 males) with CDA were eligible by diagnosis and underwent HCT from 2002-2019. The median age at diagnosis was 0.7 (range: 0.2 - 14) years. A majority (n=12) of patients had CDA type II while the remainder either had CDA type I (n=2) or were unknown (n=3). Twelve (71%) patients had evidence of iron overload by biopsy or imaging and 11 received pre-HCT chelation. Three of the 12 patients had liver fibrosis confirmed by biopsy. Thirteen patients had splenomegaly and four underwent splenectomy prior to HCT. Three patients received pre-HCT immunosuppressive therapy (PTIS). Median age at the time of HCT was 5.5 (range: 0.7 - 15) years. The median interval between diagnosis and HCT was 3.8 (range 0 - 12.3) years. Most patients received myeloablative busulfan-based conditioning (n=12); however, 5 patients received nonmyeloablative (n=1) or reduced intensity (n=4) fludarabine-based conditioning regimens. Donor sources included HLA matched sibling (n=3), matched unrelated (n=9), haploidentical (n=1) and mismatched unrelated (n=4) donors. Graft source was bone marrow in all but 2 patients who received umbilical cord blood. The median total nucleated cell (TNC) dose for bone marrow grafts was 6.0 (range: 3.4- 20.6) x 108/kg. Cord blood recipients received a TNC dose of 3.8 x 107 and 4.8 x 107/kg. Five (29%) patients developed acute GvHD grade II-IV, with one patient with grade III-IV acute GvHD (5.8%). Post-HCT complications included veno-occlusive disease (n=3), acute kidney injury (n=1), congestive cardiac failure (n=1), thrombotic microangiopathy (n=1), CMV viremia requiring therapy (n=2), mucormycosis (n=1), streptococcal pneumonia (n=1), recurrent clostridium difficle colitis (n=1), and parvovirus infection (n=1). Four patients developed chronic GvHD (23.5%; 2 limited and 2 extensive). Characteristics and outcomes of the four patients (23.5%) who developed GR are shown in Table 1. With a median follow-up of 3.4 (range: 0.08 - 14) years; fourteen patients are alive. Three patients died from respiratory failure due to adenovirus, congestive cardiac failure and extensive chronic GvHD post 2nd HCT. The 2-year OS, EFS and GvHD-free-rejection-free survival of the entire cohort (95% confidence interval) were 87% (72-100%), 64% (44 -92%), and 58% (39- 88%), respectively (Figure 1). Due to limited sample size, we did not find any patient or HCT-related factors that were associated with GR, OS or GvHD. Conclusion HCT can be curative for patients with CDA. The incidence of GR and GvHD in our CDA cohort was comparable to the recent EBMT report1. Strategies such as aggressive chelation, use of PTIS and perhaps early HCT in the presence of a suitable donor before co-morbidities occur are needed to improve engraftment without increasing risk for toxicities and mortality. Not unexpectedly we observed considerable morbidities in patients who had GR and required a 2nd HCT. Disclosures Pulsipher: Novartis: Honoraria; Bellicum: Honoraria; Jasper: Honoraria; Mesoblast: Honoraria; Miltenyi: Honoraria, Research Funding; Adaptive: Research Funding.

Background The complex interaction between pulmonary function, cardiac function and adverse cardiovascular events has only been partially described. We sought to describe the association between pulmonary function with left heart structure and function, all-cause mortality and incident cardiovascular hospitalization. Methods This study is a retrospective analysis of patients evaluated in a single tertiary care medical center. We used multivariable linear regression analyses to examine the relationship between FVC and FEV1 with left ventricular ejection fraction (LVEF), left ventricular internal dimension in systole and diastole (LVIDS, LVIDD) and left atrial diameter, adjusting for baseline characteristics, right ventricular function and lung hyperinflation. We also used Cox proportional hazards models to examine the relationship between FVC and FEV1 with all-cause mortality and cardiac hospitalization. Results A total of 1807 patients were included in this analysis with a median age of 61 years and 50% were female. Decreased FVC and FEV1 were both associated with decreased LVEF. In individuals with FVC less than 2.75 L, decreased FVC was associated with increased all-cause mortality after adjusting for left and right heart echocardiographic variables (hazard ratio [HR] 0.49, 95% CI 0.29, 0.82, respectively). Decreased FVC was associated with increased cardiac hospitalization after adjusting for left heart size (HR 0.80, 95% CI 0.67, 0.96), even in patients with normal LVEF (HR 0.75, 95% CI 0.57, 0.97). Conclusion In a tertiary care center reduced pulmonary function was associated with adverse cardiovascular events, a relationship that is not fully explained by left heart remodeling or right heart dysfunction.

Background: Research implicates acute and chronic stressors in racial/ethnic health disparities, but the joint impact of multiple stressors on racial/ethnic disparities in cardiovascular health is unknown. Methods: In 25 062 women (24 053 white; 256 Hispanic; 440 black; 313 Asian) articipating in the Women’s Health Study follow-up cohort, we examined the relationship between cumulative psychosocial stress (CPS) and ideal cardiovascular health (ICH), as defined by the American Heart Association’s 2020 strategic Impact Goals. This health metric includes smoking, body mass index, physical activity, diet, blood pressure, total cholesterol, and glucose, with higher levels indicating more ICH and less cardiovascular risk (score range, 0–7). We created a CPS score that summarized acute stressors (eg, negative life events) and chronic stressors (eg, work, work-family spillover, financial, discrimination, relationship, and neighborhood) and traumatic life event stress reported on a stress questionnaire administered in 2012 to 2013 (score range, 16–385, with higher scores indicating higher levels of stress). Results: White women had the lowest mean CPS scores (white: 161.7±50.4; Hispanic: 171.2±51.7; black: 172.5±54.9; Asian: 170.8±50.6; P overall P P Conclusions: Both CPS and ICH varied by race/ethnicity. ICH remained worse in blacks and better in Asians compared with whites, despite taking into account socioeconomic factors and CPS.

Background Financial strain is a prevalent form of psychosocial stress in the United States; however, information about the relationship between financial strain and cardiovascular health remains sparse, particularly in older women. Methods The cross-sectional association between financial strain and ideal cardiovascular health were examined in the Women's Health Study follow-up cohort (N = 22,048; mean age = 72± 6.0 years).Six self-reported measures of financial strain were summed together to create a financial strain index and categorized into 4 groups: No financial strain, 1 stressor, 2 stressors, and 3+ stressors. Ideal cardiovascular health was based on the American Heart Association strategic 2020 goals metric, including tobacco use, body mass index, physical activity, diet, blood pressure, total cholesterol and diabetes mellitus. Cardiovascular health was examined as continuous and a categorical outcome (ideal, intermediate, and poor). Statistical analyses adjusted for age, race/ethnicity, education and income. Results At least one indicator of financial strain was reported by 16% of participants. Number of financial stressors was associated with lower ideal cardiovascular health, and this association persisted after adjustment for potential confounders (1 financial stressor (FS): B = −0.10, 95% Confidence Intervals (CI) = −0.13, −0.07; 2 FS: B = −0.20, 95% CI = −0.26, −0.15; 3+ FS: B = −0.44, 95% CI = −0.50, −0.38). Conclusion Financial strain was associated with lower ideal cardiovascular health in middle aged and older female health professional women. The results of this study have implications for the potential cardiovascular health benefit of financial protections for older individuals.

ObjectiveWe assessed the hypothesis that metabolic syndrome is associated with adverse changes in cardiac structure and function in participants of the Echocardiographic Study of Latinos (Echo-SOL).MethodsNon-diabetic Echo-SOL participants were included in this cross-sectional analysis. Metabolic syndrome was defined according to the American Heart Association/National Heart, Lung, and Blood Institute 2009 Joint Scientific Statement. Survey multivariable linear regression analyses using sampling weights were used adjusting for multiple potential confounding variables. Additional analysis was stratified according to the presence/absence of obesity (body mass index (BMI) ≥25 kg/m2) and the presence/absence of metabolic syndrome.ResultsWithin Echo-SOL, 1260 individuals met inclusion criteria (59% female; mean age 55.2 years). Compared with individuals without metabolic syndrome, those with metabolic syndrome had lower medial and lateral E′ velocities (−0.4 cm/s, (SE 0.1), p=0.0002; −0.5 cm/s (0.2), p=0.02, respectively), greater E/E′ (0.5(0.2), p=0.01) and worse two-chamber left ventricular longitudinal strain (0.9%(0.3), p=0.009), after adjusting for potential confounding variables. Increased left ventricular mass index (9.8 g/m2 (1.9), p2 (1.7), p2) and metabolic syndrome had worse left ventricular global longitudinal strain (2.1%(0.7), p=0.002) and reduced left ventricular ejection fraction (−3.5%(1.4), p=0.007) compared with normal-weight individuals without metabolic syndrome.ConclusionsIn a sample of US Hispanics/Latinos metabolic syndrome was associated with worse left ventricular systolic and diastolic function. Adverse changes in left ventricular size and function were observed in obese individuals with and without metabolic syndrome but decreased left ventricular function was also present in normal-weight individuals with metabolic syndrome.

ObjectiveTo describe the relationship of household secondhand smoke (SHS) exposure and cardiac structure and function.MethodsParticipants (n=1069; 68 % female; age 45–74 years) without history of tobacco use, coronary artery disease or severe valvular disease were included. Past childhood (starting at age ResultsSHS exposure in childhood only was associated with reduced E/A velocity ratio (β=−0.06 (SE 0.02), p=0.008). SHS exposure in adolescence/adult only was associated with increased left ventricular ejection fraction (LVEF) (1.2 (0.6), p=0.04), left atrial volume index (1.7 (0.8), p=0.04) and decreased isovolumic relaxation time (−0.003 (0.002), p=0.03). SHS exposure in childhood and adolescence/adult was associated with worse left ventricular global longitudinal strain (LVGLS) (two-chamber) (0.8 (0.4), p= 0.049). Compared with individuals who do not live with a tobacco smoker, individuals who currently live with at least one tobacco smoker had reduced LVEF (−1.4 (0.6), p=0.02), LVGLS (average) (0.9 (0.40), p=0.03), medial E′ velocity (−0.5 (0.2), p=0.01), E/A ratio (−0.09 (0.03), p=0.003) and right ventricular fractional area change (−0.02 (0.01), p=0.01) with increased isovolumic relaxation time (0.006 (0.003), p=0.04).ConclusionsPast and current household exposure to SHS was associated with abnormalities in cardiac systolic and diastolic function. Reducing household SHS exposure may be an opportunity for cardiac dysfunction prevention to reduce the risk of future clinical heart failure.

Prokineticins are involved in many physiological processes including circadian rhythms, neurogenesis, angiogenesis, and cancer. Recently, they have been found to play a role in regulating food intake. Historically, proteins that increase feeding behavior in mammals decrease reproductive behavior to prevent pregnancy and lactation when food is scarce. In the current study, prokineticin-2 (PK2) had pronounced effects on reproductive and ingestive behaviors when given to female Syrian hamsters. Administration of PK2 prevented ingestive behaviors induced by food restriction, such as the amount of time spent with food and eating. Hamsters given PK2 preferred to engage in reproductive behaviors, including spending time with a male and lordosis. Furthermore, analysis of blood plasma revealed that changes to behavior persisted despite similar levels of des-acyl ghrelin (DAG) and reduced glucose concentrations in the blood. Additionally, administering 10 mg/kg of acyl ghrelin (AG) to a different cohort of animals significantly decreased the amount of time females spent with a potential mating partner, increased the amount of time females spent with food, decreased the duration of lordosis, and increased the duration of eating. Results from the current study support the need for further research investigating the reproductive and ingestive roles of PK2 and ghrelin.

Objective To compare all-cause and cause-specific mortality among 3 distinct groups: within-country, rural-to-urban migrants, and rural and urban dwellers in a longitudinal cohort in Peru. Methods The PERU MIGRANT Study, a longitudinal cohort study, used an age-stratified and sex-stratified random sample of urban dwellers in a shanty town community in the capital city of Peru, rural dwellers in the Andes, and migrants from the Andes to the shanty town community. Participants underwent a questionnaire and anthropomorphic measurements at a baseline evaluation in 2007–2008 and at a follow-up visit in 2012–2013. Mortality was determined by death certificate or family interview. Results Of the 989 participants evaluated at baseline, 928 (94%) were evaluated at follow-up (mean age 48 years; 53% female). The mean follow-up time was 5.1 years, totalling 4732.8 person-years. In a multivariable survival model, and relative to urban dwellers, rural participants had lower all-cause mortality (HR=0.27; 95% CI 0.07 to 0.98), and both the rural (HR=0.07; 95% CI 0.01 to 0.87) and migrant (HR=0.13; 95% CI 0.02 to 0.81) groups had lower cardiovascular mortality. Conclusions Cardiovascular mortality of migrants remains similar to that of the rural group, suggesting that rural-to-urban migrants do not appear to catch up with urban mortality in spite of having a more urban cardiovascular risk factor profile.

Household air pollution from biomass fuel use affects 3 billion people worldwide; however, few studies have examined the relationship between biomass fuel use and blood pressure. We sought to determine if daily biomass fuel use was associated with elevated blood pressure in high altitude Peru and if this relationship was affected by lung function. We analyzed baseline information from a population-based cohort study of adults aged ≥35 years in Puno, Peru. Daily biomass fuel use was self-reported. We used multivariable regression models to examine the relationship between daily exposure to biomass fuel smoke and blood pressure outcomes. Interactions with sex and quartiles of forced vital capacity were conducted to evaluate for effect modification. Data from 1004 individuals (mean age, 55.3 years; 51.7% women) were included. We found an association between biomass fuel use with both prehypertension (adjusted relative risk ratio, 5.0; 95% confidence interval, 2.6–9.9) and hypertension (adjusted relative risk ratio, 3.5; 95% confidence interval, 1.7–7.0). Biomass fuel users had a higher systolic blood pressure (7.0 mm Hg; 95% confidence interval, 4.4–9.6) and a higher diastolic blood pressure (5.9 mm Hg; 95% confidence interval, 4.2–7.6) when compared with nonusers. We did not find interaction effects between daily biomass fuel use and sex or percent predicted forced vital capacity for either systolic blood pressure or diastolic blood pressure. Biomass fuel use was associated with a higher likelihood of having hypertension and higher blood pressure in Peru. Reducing exposure to household air pollution from biomass fuel use represents an opportunity for cardiovascular prevention.

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for pediatric patients with hematologic malignancies. Historically, matched sibling donors (MSD) have been the preferred donor source given ease of availability and lower rates of graft-versus-host-disease (GVHD). However, only 30% of patients have a MSD and relapse rates are high after MSD HSCT, raising the question of best donor choice. As conditioning regimens evolve, GVHD management improves and supportive care advances, it is important to evaluate the role of donor source on short and long-term clinical outcomes to inform donor selection. We performed a single-center retrospective analysis comparing post-HSCT outcomes in a cohort of pediatric patients undergoing MSD, matched unrelated donor (MUD), and umbilical cord blood (CB) transplants from 2006 to 2018. Methods: A retrospective analysis was performed on an IRB-approved protocol through Fred Hutchinson Cancer Research Center. 232 patients were included who received MSD (n=56), MUD (n=89) or CB (n=87) transplants. Of note, 24 CB patients received expanded CB cells in addition to unmanipulated unit(s). GVHD prophylaxis in all patients consisted of a calcineurin inhibitor and MMF or methotrexate. The vast majority received a high-intensity conditioning regimen (86%, 96%, and 82% respectively for MSD, MUD and CB). Overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method. Probabilities of non-relapse mortality (NRM), relapse, and acute GVHD were evaluated using cumulative incidence (CI) estimates with appropriate competing risks. The Cox regression model was used for adjusted analysis for age, year of transplant, sex, CMV status, MRD status, disease risk, and conditioning regimen. Results: Patient/treatment/donor demographics are shown in Table 1. Median follow-up was 2.6, 3.7 and 3.1 years for MSD, MUD and CB respectively. Patient diagnosis, disease risk, gender, age, and CMV serology were balanced between groups. CI of engraftment was similar as well, with only one graft failure in the MUD group (Fig 1). Median time to platelet recovery was significantly faster in MUD and MSD groups as compared to the CB group (p Conclusions: Our data demonstrate no difference in unadjusted OS between MSD, MUD and CB recipients. Importantly, despite this equivalence, 5-year DFS was significantly better in the CB v. MSD group, reflecting the lower relapse rate observed in CB patients and seen previously by us and others. CB continues to be viewed as an "alternative" donor for HSCT due to the low stem cell dose in a CB graft resulting in delayed neutrophil recovery, primary graft failure and increased NRM. However, this was not observed herein, supporting the use of CB for pediatric HSCT perhaps especially in patients at high risk of post-transplant relapse. Disclosures Milano: ExCellThera: Research Funding; Amgen: Research Funding. Delaney:Nohla Therapeutics: Employment, Equity Ownership; Biolife Solutions: Membership on an entity's Board of Directors or advisory committees. Bleakley:HighPass Biotherapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.

The three pillars of sustainability are the economic, environmental and social pillars. To achieve sustainable construction projects, these three priorities must be balanced. Considering social aspects is of equal importance when considering the design, materials and technologies used in buildings. The increased use of naturally based materials from renewable sources using traditional techniques is common in sustainable buildings and can help balance some of the social aspects. Building with traditional technologies such as compressed earth blocks (CEBs), rammed earth, adobe, or strawbale technologies is a viable option to conventional construction methods when the structure meets modern scientific and engineering standards. High-quality, sustainable buildings are achievable using local resources and local labour. This paper presents case studies from remote Australia and Europe and shows the social and environmental impacts according to the technology used. Prior consideration of the social aspects can result in the improvement of the sustainability of the building.

Both environmental (e.g., energy use) and human sustainability (occupant wellbeing/productivity) need to be considered in building design and operation. The challenging climatic and socioeconomic conditions in remote regions of Australia mean that achieving sustainability is difficult and costly. Currently, the energy use patterns, thermal performance, and indoor atmospheric quality (IAQ) of remote health clinic buildings are unknown, meaning that there is an information gap in the design and operation of such buildings. This paper reports the results of an investigation into the environmental performance of a clinic in the remote clinic of Numbulwar. Climate variables, energy consumption, and IAQ variables were instrumentally monitored at the clinic from April 2017 to March 2018 at 10-minute intervals, with data uploaded to a cloud database now holding 3 million values. Analyzed temporal variations in the measured variables for the clinic and the relationships between them reveal the performance of the building. The results obtained provide a basis for the formulation of strategic interventions, design guidance, and further investigation, including: (i) the range of indoor atmospheric conditions needs to be narrowed to provide more consistent occupant comfort; (ii) an occupancy profile needs to be developed to determine user behaviours with respect to energy use; (iii) the heat-exhaust/aircon systems need to be reviewed for more efficient use; (iv) the cycling of air, heat, moisture, and pollutants through the building needs to be further investigated; and (v) BIM should be undertaken using the data as input to test future design solutions.

Opportunities for collaboration on global noncommunicable disease (NCD) research across international borders and scientific disciplines are increasingly available, coinciding with globalization of science and an unprecedented interest in global health among U.S. students, clinicians, and early-career investigators (1). However, challenges to developing and funding a global NCD research agenda remain. In September 2014, researchers representing 41 institutes, including universities, government agencies, private companies, journals, and foundations in the United States met to discuss the challenges and identify opportunities for moving forward on a global NCD research agenda. Four action items emerged from this conference.

Despite the Institute of Medicine report on racial and ethnic disparities in health care outcomes that was published more than 10 years ago, disparities in health outcomes including cardiovascular disease outcomes persist. The recent literature on racial and ethnic disparities in cardiovascular disease outcomes incorporates geospatial-mapping analyses in order to shed light on the ways in which disparities vary by location, highlighting variability in access to health care. In addition the problem of access to health care, the quality of the health care that is available to minority communities has also been scrutinized, underscoring the potential of quality improvement interventions to reduce existing disparities in cardiovascular outcomes. Targeted interventions to expand health education, expand access to primary and tertiary care and improve the quality of the health care received by racial and ethnic minorities could reduce disparities in cardiovascular outcomes.

While household air pollution from biomass fuel combustion has been linked to cardiovascular disease, the effects on cardiac structure and function have not been well described. We sought to determine the association between biomass fuel smoke exposure and cardiac structure and function by transthoracic echocardiography. We identified a random sample of urban and rural residents living in the high-altitude region of Puno, Peru. Daily biomass fuel use was self-reported. Participants underwent transthoracic echocardiography. Multivariable linear regression was used to examine the relationship of biomass fuel use with echocardiographic measures of cardiac structure and function, adjusting for age, sex, height, body mass index, diabetes, physical activity, and tobacco use. One hundred and eighty-seven participants (80 biomass fuel users and 107 non-users) were included in this analysis (mean age 59 years, 58% women). After adjustment, daily exposure to biomass fuel smoke was associated with increased left ventricular internal diastolic diameter (P=.004), left atrial diameter (P=.03), left atrial area (four-chamber) (P=.004) and (two-chamber) (P=.03), septal E' (P=.006), and lateral E' (P=.04). Exposure to biomass fuel smoke was also associated with worse global longitudinal strain in the two-chamber view (P=.01). Daily biomass fuel use was associated with increased left ventricular size and decreased left ventricular systolic function by global longitudinal strain.

OBJECTIVE: To compare the usefulness for surveillance of the peer-reviewed literature on the prevalence of hypertension in Latin America and the Caribbean published from 2001 to 2010 with a previous study of the published literature from 1962 to 2000. METHODS: A bibliographic search was conducted of publications from 2001 to 2010 that examined the prevalence of hypertension using MEDLINE and LILACS databases. The methodology of each paper was evaluated with the same critical appraisal tool used in the previous study. RESULTS: A total of 81 papers were published from 2001 to 2010 on the prevalence of hypertension in Latin America and the Caribbean. Only 24 of these studies met the minimum methodologic criteria for evaluation. While the total number of studies published in the past 10 years exceeds the number published from 1962 to 2000, the percentage of studies that met the minimum methodologic criteria has not substantially increased. In addition to major methodologic shortcomings, less than 46% of the published studies reported rates of awareness, treatment, and control of hypertension. The hypertension prevalence estimates from the peer-reviewed literature range from 7% to 49%. These studies were primarily done in urban centers and are not evenly distributed throughout the region. CONCLUSIONS: The quality and geographic distribution of the published literature on the prevalence of hypertension in Latin America and the Caribbean are inadequate. Research resources and efforts should be directed in the future toward closing this gap.OBJETIVO: Comparar la utilidad para la vigilancia epidemiológica de los artículos sobre prevalencia de hipertensión en América Latina y el Caribe publicados en revistas con arbitraje científico del 2001 al 2010, con un estudio anterior de la bibliografía publicada en el período 1962-2000. MÉTODOS: En las bases de datos MEDLINE y LILACS se efectuó una búsqueda bibliográfica de los artículos que examinaron la prevalencia de hipertensión publicados del 2001 al 2010. La metodología empleada en cada artículo se valoró con la misma herramienta de evaluación usada en el estudio anterior. RESULTADOS: Del 2001 al 2010 se publicaron 81 artículos sobre la prevalencia de la hipertensión en América Latina y el Caribe. Solo 24 de estos estudios cumplieron los criterios metodológicos mínimos para la evaluación. Aunque en los 10 últimos años se publicaron más estudios que en el período 1962-2000, el porcentaje de estudios que cumplieron los criterios metodológicos mínimos no aumentó sustancialmente. Además de presentar deficiencias metodológicas importantes, menos de 46% de los estudios publicados incluyeron información sobre la concientización, el tratamiento y el control de la hipertensión. Las estimaciones sobre la prevalencia de hipertensión en los artículos estudiados varían entre 7% y 49%. Estos estudios se realizaron principalmente en centros urbanos y no se distribuyeron de manera uniforme en toda la región. CONCLUSIONES: La bibliografía publicada sobre la prevalencia de la hipertensión en América Latina y el Caribe es insuficiente para ser útil con fines de vigilancia, y su calidad y la distribución geográfica son inadecuadas. En el futuro, los recursos y los esfuerzos de investigación deben enfocarse en reducir esta diferencia.

OBJECTIVE: To compare the usefulness for surveillance of the peer-reviewed literature on the prevalence of hypertension in Latin America and the Caribbean published from 2001 to 2010 with a previous study of the published literature from 1962 to 2000. METHODS: A bibliographic search was conducted of publications from 2001 to 2010 that examined the prevalence of hypertension using MEDLINE and LILACS databases. The methodology of each paper was evaluated with the same critical appraisal tool used in the previous study. RESULTS: A total of 81 papers were published from 2001 to 2010 on the prevalence of hypertension in Latin America and the Caribbean. Only 24 of these studies met the minimum methodologic criteria for evaluation. While the total number of studies published in the past 10 years exceeds the number published from 1962 to 2000, the percentage of studies that met the minimum methodologic criteria has not substantially increased. In addition to major methodologic shortcomings, less than 46% of the published studies reported rates of awareness, treatment, and control of hypertension. The hypertension prevalence estimates from the peer-reviewed literature range from 7% to 49%. These studies were primarily done in urban centers and are not evenly distributed throughout the region. CONCLUSIONS: The quality and geographic distribution of the published literature on the prevalence of hypertension in Latin America and the Caribbean are inadequate. Research resources and efforts should be directed in the future toward closing this gap.(AU)