Faculty Bibliography

BACKGROUND: In older adults (aged 70-74 years), African-Americans have 4-fold higher risk of developing hypertension-attributed end-stage renal disease (ESRD) than European-Americans. A hypothesized mechanism linking hypertension and progressive chronic kidney disease (CKD) is the innate immune response and inflammation. Persons with CKD are also more susceptible to infection. Gene expression in peripheral blood can provide a view of the innate immune activation profile. We aimed to identify differentially expressed genes, microRNAs, and pathways in peripheral blood between cases with CKD and high blood pressure under hypertension treatment versus controls without CKD and with controlled blood pressure in African Americans. METHODS: Case and control pairs (N = 15x2) were selected from those without diabetes and were matched for age, sex, body mass index, APOL1 risk allele count, and hypertension medication use. High blood pressure under hypertension treatment was defined as hypertension medication use and systolic blood pressure (SBP) >/= 145 mmHg. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2. Cases were selected from those with CKD and high blood pressure under hypertension treatment, and controls were selected from those without CKD (eGFR: 75-120 mL/min/1.73m2 and urine albumin-to-creatinine ratio < 30mg/g) and with blood pressure controlled by hypertension medication use (SBP < 135 mmHg and D(diastolic)BP < 90 mm Hg). We perform RNA sequencing of mRNA and microRNA and conducted differential expression and co-expression network analysis. RESULTS: Of 347 miRNAs included in the analysis, 14 were significantly associated with case status (Benjamini-Hochberg adjusted p-value [BH p] < 0.05). Of these, ten were downregulated in cases: three of each belong to the miR-17 and miR-15 families. In co-expression network analysis of miRNA, one module, which included 13 of the 14 significant miRNAs, had significant association with case status. Of the 14,488 genes and 41,739 transcripts included in the analysis, none had significant association with case status. Gene co-expression network analyses did not yield any significant associations for mRNA. CONCLUSION: We have identified 14 differentially expressed miRNAs in the peripheral blood of CKD cases with high blood pressure under hypertension treatment as compared to appropriate controls. Most of the significant miRNAs were downregulated and have critical roles in immune cell functions. Future studies are needed to replicate our findings and determine whether the downregulation of these miRNAs in immune cells may influence CKD progression or complications.

INTRODUCTION/BACKGROUND:The objective of this study was to investigate whether 10 phospholipids/metabolites previously identified as prospectively predictive of mild cognitive impairment (MCI) or dementia in whites would also be predictive in a mostly African-American cohort. METHODS:We repeatedly measured 188 phospholipids/metabolites in plasma samples of 221 participants of the Atherosclerosis Risk in Communities study, 97% African American, who were followed between 2004-2006 and 2011-2013. RESULTS:After a mean follow-up of 7.3 years, 77 were classified as having MCI and 18 as having dementia. Our study failed to replicate previous findings in this mostly African American cohort, in that the 10 phospholipids/metabolites only achieved a C statistic/AUC of 0.609 in predicting development of MCI or dementia (compared to 0.96) and 0.607 in distinguishing normal from MCI or dementia at the follow-up visit. CONCLUSION/CONCLUSIONS:A panel of 10 phospholipids/metabolites previously associated with incident dementia was not predictive of MCI or dementia in an independent cohort.

BACKGROUND:It is uncertain whether being overweight, but not obese, is associated with advanced chronic kidney disease (CKD) and how the size and shape of associations between body-mass index (BMI) and advanced CKD differs among different types of people. METHODS:We used Clinical Practice Research Datalink records (2000-2014) with linkage to English secondary care and mortality data to identify a prospective cohort with at least one BMI measure. Cox models adjusted for age, sex, smoking and social deprivation and subgroup analyses by diabetes, hypertension and prior cardiovascular disease assessed relationships between BMI and CKD stages 4-5 and end-stage renal disease (ESRD). FINDINGS/RESULTS:1,405,016 adults aged 20-79 with mean BMI 27.4kg/m2 (SD 5.6) were followed for 7.5 years. Compared to a BMI of 20 to <25kg/m2, higher BMI was associated with a progressively increased risk of CKD stages 4-5 (hazard ratio 1.34, 95% CI 1.30-1.38 for BMI 25 to <30kg/m2; 1.94, 1.87-2.01 for BMI 30 to <35kg/m2; and 3.10, 2.95-3.25 for BMI ≥35kg/m2). The association between BMI and ESRD was shallower and reversed at low BMI. Current smoking, prior diabetes, hypertension or cardiovascular disease all increased risk of CKD, but the relative strength and shape of BMI-CKD associations, which were generally log-linear above a BMI of 25kg/m2, were similar among those with and without these risk factors. There was direct evidence that being overweight was associated with increased risk of CKD stages 4-5 in these subgroups. Assuming causality, since 2000 an estimated 39% (36-42%) of advanced CKD in women and 26% (22-30%) in men aged 40-79 resulted from being overweight or obese. CONCLUSIONS:This study provides direct evidence that being overweight increases risk of advanced CKD, that being obese substantially increases such risk, and that this remains true for those with and without diabetes, hypertension or cardiovascular disease. Strategies to reduce weight among those who are overweight, as well as those who are obese may reduce CKD risk, with each unit reduction in BMI yielding similar relative reductions in risk.

Parental mental health may be a critical component in understanding the overlapping health burdens of mental health symptomatology and drug use in young men who have sex with men (YMSM), yet studies of YMSM have not fully examined these associations. To understand these relationships, data drawn from a study of gay, bisexual, and other YMSM were used examine associations between perceived parental psychopathology and the mental health symptomatology and drug use of YMSM. Findings suggest that YMSM reporting at least one parent with perceived depression, manic depression, schizophrenia, or antisocial behavior anytime during their childhoods were more likely to report higher levels of both depressive symptomatology and post-traumatic stress disorder (PTSD) than those reporting no perception of any of these psychopathologies in their parents. Number of different drugs uses in one's were higher among participants who perceived at least one parent as depressed. Mediation analyses indicated that the relationship between perceived parental depression and lifetime drug use of YMSM was mediated both by YMSM depression and YMSM PTSD. These results suggest that parental psychopathology plays an important role in the health of sexual minority men, a population with elevated levels of mental health burden and drug use across the lifespan.

BACKGROUND:Arteriovenous accesses (AVA) in patients performing hemodialysis (HD) are labeled "permanent" for AV fistulas (AVF) or grafts (AVG) and "temporary" for tunneled central venous catheters (TCVC). Durability and outcomes of permanent vascular accesses based on the sequence in which they were placed or used receives little attention. This study analyzed longitudinal transitions between TCVC-based and AVA-based HD outcomes according to the order of placement. METHODS:All 391 patients initiating chronic HD via a TCVC between 2012 and 2013 at 12 outpatient academic dialysis units were included in this study. Chronological distributions of HD vascular accesses were recorded over a mean (SD) of 2.8 (0.9) years and sequentially grouped into periods for TCVC-delivered and AVA-delivered (AVF or AVG) HD. Primary AVA failure and cumulative access survival were evaluated based on access placement sequence and type, adjusting for age. RESULTS:In total, 92.3% (361/391) of patients underwent 497 AVA placement surgeries. Analyzing the initial 3 surgeries, primary AVF failure rates increased with each successive fistula placement (p = 0.008). Among the 82.9% (324/391) of TCVC patients successfully converted to an AVA, 30.9% returned to a TCVC, followed by a 58.0% conversion rate to another AVA. Annual per-patient vascular access transition rates were 2.02 (0.09) HD periods using a TCVC and 0.54 (0.03) HD periods using an AVA. Comparing the first AVA used with the second, cumulative access survivals were 701.0 (370.0) vs. 426.5 (275.0) days, respectively. Excluding those never converting to an AVF or AVG, 169 (52.2%) subsequently converted from a TCVC to a permanent access and received HD via AVA for ≥80% of treatments. CONCLUSIONS:HD vascular access outcomes differ based on the sequence of placement. In spite of frequent AVA placements, only half of patients effectively achieved a "permanent" vascular access and used an AVA for the majority of HD treatments.

A growing literature has demonstrated that early math skills are associated with later outcomes for children. This research has generated interest in improving children's early math competencies as a pathway to improved outcomes for children in elementary school. The Making Pre-K Count study was designed to test the effects of an early math intervention for preschoolers. Its design was unique in that, in addition to causally testing the effects of early math skills, it also allowed for the examination of a number of additional questions about scale-up, the influence of contextual factors and the counterfactual environment, the mechanism of long-term fade-out, and the role of measurement in early childhood intervention findings. This chapter outlines some of the design considerations and decisions put in place to create a rigorous test of the causal effects of early math skills that is also able to answer these questions in early childhood mathematics and intervention. The study serves as a potential model for how to advance science in the fields of preschool intervention and early mathematics.

A decline in response rates in traditional household surveys, combined with increased internet coverage and decreased research budgets, has resulted in increased attractiveness of web survey research designs based on purposive and voluntary opt-in sampling strategies. In the study of hidden or stigmatised behaviours, such as cannabis use, web survey methods are increasingly common. However, opt-in web surveys are often heavily criticised due to their lack of sampling frame and unknown representativeness. In this article, we outline the current state of the debate about the relevance of pursuing representativeness, the state of probability sampling methods, and the utility of non-probability, web survey methods especially for accessing hidden or minority populations. Our article has two aims: (1) to present a comprehensive description of the methodology we use at Global Drug Survey (GDS), an annual cross-sectional web survey and (2) to compare the age and sex distributions of cannabis users who voluntarily completed (a) a household survey or (b) a large web-based purposive survey (GDS), across three countries: Australia, the United States, and Switzerland. We find that within each set of country comparisons, the demographic distributions among recent cannabis users are broadly similar, demonstrating that the age and sex distributions of those who volunteer to be surveyed are not vastly different between these non-probability and probability methods. We conclude that opt-in web surveys of hard-to-reach populations are an efficient way of gaining in-depth understanding of stigmatised behaviours and are appropriate, as long as they are not used to estimate drug use prevalence of the general population.

Purpose: To date, no studies utilizing global positioning system (GPS) technologies to measure mobility and environmental exposures have been conducted among a sample of transgender women despite the potential salient role neighborhood contexts may play in the health of this population. As such, the purpose of this study was to assess the acceptability and feasibility of a weeklong GPS protocol among a sample of transgender women in New York City. Methods: A sample of 14 transgender women residing in the New York City metropolitan area were recruited through community based methods to wear and charge a GPS device for 7 days to measure daily mobility. The acceptability of these methods was assessed using a pre- and postprotocol survey and their feasibility was measured using objective data derived from the GPS device. Pre- and postprotocol survey measures were compared using McNemar's test. Results: Participants reported high ratings of preprotocol acceptability, as well as few concerns regarding safety, appearance, and losing the device, all of which were maintained after completing the protocol. All 14 devices that were distributed were returned. In addition, all 14 participants had GPS data for at least 1 h on 1 day, and nine participants (64.3%) had at least 8 h of GPS data on all days. Conclusion: The findings of this pilot study demonstrate that the GPS methods are both acceptable and feasible among this sample of transgender women. GPS devices may be used in research among transgender women to understand neighborhood determinants of HIV and other STIs.

The study evaluated the acceptability of text message- and voice-based ecological momentary assessment (EMA) methods among a sample (n=74) of young men who have sex with men (MSM). We assessed the acceptability of text message- and voice-based EMA methods. Almost all participants (96%) reported that they would be willing to accept texts on their smartphone to answer questions about their current mood, surroundings, or feelings. A large majority (89%) also reported being willing to accept phone calls to answer these questions. This work suggests that different EMA methods are acceptable for use among young MSM.

OBJECTIVE: Atherosclerosis is exaggerated in African American (AA) systemic lupus erythematosus (SLE) patients, with doubled cardiovascular disease (CVD) risk compared to White patients. The extent to which common Apolipoprotein L1 (APOL1) risk alleles (RA) contribute to this trend is unknown. This retrospective cohort study assessed prevalent atherosclerotic disease across APOL1 genotypes in AA SLE patients. METHODS: One hundred thirteen AA SLE subjects were APOL1-genotyped and stratified as having: zero risk alleles, one risk allele, or two risk alleles. Chart review assessed CVD manifestations including abdominal aortic aneurysm, angina, carotid artery disease, coronary artery disease, myocardial infarction, peripheral vascular disease, stroke, and vascular calcifications. Associations between the genotypes and a composite endpoint defined as one or more CVD manifestations were calculated using logistic regression. Symptomatic atherosclerotic disease, excluding incidental vascular calcifications, was also assessed. RESULTS: The 0-risk-allele, 1-risk-allele and 2-risk-allele groups, respectively, comprised 34%, 53%, and 13% of the cohort. Respectively, 13.2%, 41.7%, and 60.0% of the 0-risk allele, 1-risk-allele, and 2-risk-allele groups met the composite endpoint of atherosclerotic CVD (p = 0.001). Adjusting for risk factors-including smoking, ESRD, BMI >25 and hypertension-we observed an association between carrying one or more RA and atherosclerotic CVD (OR = 7.1; p = 0.002). For symptomatic disease, the OR was 3.5 (p = 0.02). In a time-to-event analysis, the proportion of subjects free from the composite primary endpoint, symptomatic atherosclerotic CVD, was higher in the 0-risk-allele group compared to the 1-risk-allele and 2-risk-allele groups (chi2 = 6.5; p = 0.04). CONCLUSIONS: Taken together, the APOL1 RAs associate with prevalent atherosclerotic CVD in this cohort of AA SLE patients, perhaps reflecting a potentiating effect of SLE on APOL1-related cardiovascular phenotypes.