Faculty Bibliography

This study examines whether changes in classroom quality predict within-child changes in achievement and behavioral problems in elementary school (ages spanning approximately 6-11 years old). Drawing on data from a longitudinal study of children in predominantly low-income, nonurban communities (n = 1,078), we relied on child fixed effects modeling, which controlled for stable factors that could bias the effects of classroom quality. In general, we found that changes in classroom quality had small and statistically nonsignificant effects on achievement and behavior. However, we found that moving into a high-quality classroom, particularly those rated as high in Classroom Organization, had positive effects on achievement and behavior for children with significant exposure to poverty in early life.

Left censoring in salivary bioscience data occurs when salivary analyte determinations fall below the lower limit of an assay's measurement range. Conventional statistical approaches for addressing censored values (i.e., recoding as missing, substituting or extrapolating values) may introduce systematic bias. While specialized censored data statistical approaches (i.e., Maximum Likelihood Estimation, Regression on Ordered Statistics, Kaplan-Meier, and general Tobit regression) are available, these methods are rarely implemented in biobehavioral studies that examine salivary biomeasures, and their application to salivary data analysis may be hindered by their sensitivity to skewed data distributions, outliers, and sample size. This study compares descriptive statistics, correlation coefficients, and regression parameter estimates generated via conventional and specialized censored data approaches using salivary C-reactive protein data. We assess differences in statistical estimates across approach and across two levels of censoring (9% and 15%) and examine the sensitivity of our results to sample size. Overall, findings were similar across conventional and censored data approaches, but the implementation of specialized censored data approaches was more efficient (i.e., required little manipulations to the raw analyte data) and appropriate. Based on our review of the findings, we outline preliminary recommendations to enable investigators to more efficiently and effectively reduce statistical bias when working with left-censored salivary biomeasure data.

Restrictive immigration policies are important social determinants of health, but less is known about the health implications and health-related content of protective immigration policies, which may also represent critical determinants of health. We conducted a content analysis of types, themes, and health-related language in 328 "sanctuary" policies enacted between 2009 and 2017 in the United States. Sanctuary policies were introduced in thirty-two states and Washington, D.C., most frequently in 2014 and 2017. More than two-thirds of policies (67.6 percent) contained language related to health, including direct references to access to services. Health-related themes commonly co-occurred with language related to supporting immigrants in communities, including themes of antidiscrimination, inclusion, trust, and privacy. Our work provides foundational, nuanced data about the scope and nature of sanctuary policies that can inform future research exploring the impacts of these policies on health and health care.

The needs of persons living with Alzheimer's disease and Alzheimer's disease-related dementia (AD/ADRD) are challenged by tremendous complexity impacting both care delivery and financing. Most persons living with dementia (PLWD) also suffer from other chronic medical or mental health conditions, which further burden quality of life and function. In addition to difficult treatment choices, optimal dementia care models likely involve people and services that are not typical pieces of the health care delivery system but are all critical partners-care partners, social workers, and community services, to name a few. More than 200 models of dementia care have demonstrated some efficacy. However, these successful interventions that might address much of the care needed by PLWD are uninsured in the United States, where insurance coverage has focused on acute care needs. This poses great difficulties for both care provision and care financing. In this article, we review these 3 key challenges: dementia care for those with chronic comorbid disease; care models that require people who are not typical providers in traditional care delivery systems; and the mandate to provide high-quality care that is currently not funded by usual health care insurance. We propose promising next steps that could substantially improve the lives of PLWD and the lives of their care partners, and highlight some of the many research questions that remain.

We report the largest and most diverse genetic study of type 1 diabetes (T1D) to date (61,427 participants), yielding 78 genome-wide-significant (P < 5 × 10^-8) regions, including 36 that are new. We define credible sets of T1D-associated variants and show that they are enriched in immune-cell accessible chromatin, particularly CD4⁺ effector T cells. Using chromatin-accessibility profiling of CD4⁺ T cells from 115 individuals, we map chromatin-accessibility quantitative trait loci and identify five regions where T1D risk variants co-localize with chromatin-accessibility quantitative trait loci. We highlight rs72928038 in BACH2 as a candidate causal T1D variant leading to decreased enhancer accessibility and BACH2 expression in T cells. Finally, we prioritize potential drug targets by integrating genetic evidence, functional genomic maps and immune protein-protein interactions, identifying 12 genes implicated in T1D that have been targeted in clinical trials for autoimmune diseases. These findings provide an expanded genomic landscape for T1D.

Interpersonal violence is a major global public health problem, and the burden of nonfatal assault injuries is far greater than that of homicides. To understand trends and inform prevention priorities, we sought to describe nonfatal assault injury trends across demographic groups from 2005 to 2015 in California, USA. Comprehensive hospitalization and emergency department discharge records were used to estimate annual rates of nonfatal assault injury overall and by means and age group and age-standardized annual rates by race/ethnicity, gender, and county. The overall rate of assault injury was stable in California from 2005 to 2015 (mean = 364 per 100,000), but there was substantial heterogeneity across demographic groups, including increases among African Americans (900 to 1,194), American Indian/Alaskan Natives (423 to 572), older individuals (age 25-29 = 697 to 727; 30-39 = 495 to 557; 40-49 = 352 to 404; 50-59 = 194 to 313; 60+ = 66 to 106), and women (199 to 252). Assault injury rates increased among several demographic groups, warranting the attention of professionals involved in violence prevention efforts. Epidemiologic examination to better understand causes of increases can inform prevention efforts. Similar analyses should be applied to other settings to determine how broadly these patterns are observed.

RATIONALE & OBJECTIVE:Immune activation is fundamental to the pathogenesis of many kidney diseases. Innate immune molecules such as soluble urokinase-type plasminogen activator receptor (suPAR) have been linked to the incidence and progression of chronic kidney disease (CKD). Whether other biomarkers of immune activation are associated with incident kidney failure with replacement therapy (KFRT) in African Americans with nondiabetic kidney disease is unclear. STUDY DESIGN:Prospective cohort. SETTING & PARTICIPANTS:African American Study of Kidney Disease and Hypertension (AASK) participants with available baseline serum samples for biomarker measurement. PREDICTORS:Baseline serum levels of soluble tumor necrosis factor receptor 1 (sTNFR1), sTNFR2, tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ). OUTCOMES:Incident KFRT, all-cause mortality. ANALYTICAL APPROACH:Cox proportional hazards models. RESULTS:, and median urinary protein-creatinine ratio was 0.09g/g at baseline. Over a median follow up of 9.6 years, there were 161 (32%) KFRT and 113 (23%) death events. In models adjusted for demographic and clinical factors and baseline kidney function, each 2-fold higher baseline level of sTNFR1, sTNFR2, and TNF-α was associated with 3.66-fold (95% CI, 2.31-5.80), 2.29-fold (95% CI, 1.60-3.29), and 1.35-fold (95% CI, 1.07-1.71) greater risks of KFRT, respectively; in comparison, each doubling of baseline suPAR concentration was associated with 1.39-fold (95% CI, 1.04-1.86) greater risk of KFRT. sTNFR1, sTNFR2, and TNF-α were also significantly associated with death (up to 2.2-fold higher risks per 2-fold higher baseline levels; P≤0.01). IFN-γ was not associated with either outcome. None of the biomarkers modified the association of APOL1 high-risk status (genetic risk factors for kidney disease among individuals of African ancestry) with KFRT (P>0.05 for interaction). LIMITATIONS:Limited generalizability to other ethnic groups or causes of CKD. CONCLUSIONS:Among African Americans with CKD attributed to hypertension, baseline levels of sTNFR1, sTNFR2, and TNF-α but not IFN-γ were associated with KFRT and mortality.

BACKGROUND:Severe hypoxic respiratory failure from COVID-19 pneumonia carries a high mortality risk. There is uncertainty surrounding which patients benefit from corticosteroids in combination with tocilizumab and the dosage and timing of these agents. The balance of controlling inflammation without increasing the risk of secondary infection is difficult. At present, dexamethasone 6 mg is the standard of care in COVID-19 hypoxia; whether this is the ideal choice of steroid or dosage remains to be proven. OBJECTIVES/OBJECTIVE:The primary objective was to assess the impact on mortality of tocilizumab only, corticosteroids only, and combination therapy in patients with COVID-19 respiratory failure. METHODS:A multihospital, retrospective study of adult patients with severe respiratory failure from COVID-19 who received supportive therapy, corticosteroids, tocilizumab, or combination therapy were assessed for 28-day mortality, biomarker improvement, and relative risk of infection. Propensity-matched analysis was performed between corticosteroid alone and combination therapies to further assess mortality benefit. RESULTS:= 0.005] without increasing the risk of infection. CONCLUSION AND RELEVANCE/UNASSIGNED:Combination of tocilizumab and corticosteroids was associated with improved 28-day survival when compared with corticosteroids alone. Modification of steroid dosing strategy as well as steroid type may further optimize therapeutic effect of the COVID-19 treatment.

BACKGROUND:2014 hypertension guidelines raised treatment goals in older adults. The objective was to examine changes in blood pressure (BP) control (<140/90 mm Hg) from 2011-2013 to 2016-2017 among Black and white older adults with treated hypertension. METHODS:Participants were 1,600 white and 650 Black adults aged 71-90 years in the Atherosclerosis Risk in Communities (ARIC) Study with treated hypertension in 2011-2013 (baseline) who had BP measured in 2016-2017 (follow-up). Predictors of changes in BP control were examined by race. RESULTS:BP was controlled among 75.3% of white and 65.7% of Black participants at baseline and 59.0% of white and 56.5% of Black participants at follow-up. Among those with baseline BP control, risk factors for incident uncontrolled BP included age (relative risk [RR] 1.15 per 5 years, 95% confidence interval [CI] 1.07-1.25), female sex (RR 1.36, 95% CI 1.16-1.60), and chronic kidney disease (RR 1.19, 95% CI 1.01-1.40) among white participants, and hypertension duration (RR 1.14 per 5 years, 95% CI 1.03-1.27) and diabetes (RR 1.48, 95% CI 1.15-1.91) among Black participants. Among those with uncontrolled BP at baseline, white females vs. males (RR 0.60, 95% CI 0.46-0.78) and Black participants with chronic kidney disease vs. without (RR 0.58, 95% CI 0.36-0.93) were less likely to have incident controlled BP. CONCLUSIONS:BP control decreased among white and Black older adults. Black individuals with diabetes or chronic kidney disease were less likely to have controlled BP at follow-up. Higher treatment goals may have contributed to these findings and unintended differences by race.

The LUCINDA Trial (Leuprolide plus Cholinesterase Inhibition to reduce Neurologic Decline in Alzheimer's) is a 52 week, randomized, placebo-controlled trial of leuprolide acetate (Eligard) in women with Alzheimer's disease (AD). Leuprolide acetate is a gonadotropin analogue commonly used for hormone-sensitive conditions such as prostate cancer and endometriosis. This repurposed drug demonstrated efficacy in a previous Phase II clinical trial in those women with AD who also received a stable dose of the acetylcholinesterase inhibitor donepezil (Bowen et al., 2015). Basic biological, epidemiological and clinical trial data suggest leuprolide acetate mediates improvement and stabilization of neuropathology and cognitive performance via the modulation of gonadotropin and/or gonadotropin-releasing hormone signaling. LUCINDA will enroll 150 women with mild-moderate AD who are receiving a stable dose of donepezil from three study sites in the United States. Cognition and function are the primary outcome measures as assessed by the Alzheimer's Disease Assessment Scale-Cognitive Subscale. Blood and MRI biomarkers are also measured to assess hormonal, inflammatory and AD biomarker changes. We present the protocol for LUCINDA and discuss trial innovations and challenges including changes necessitated by the covid-19 pandemic and study drug procurement issues.