Faculty Bibliography

Advances in genomics have enabled the development of polygenic scores (PGS), sometimes called polygenic risk scores, in the context of multifactorial diseases and disorders such as cancer, cardiovascular disease, and schizophrenia. PGS estimate an individual's genetic predisposition, as compared to other members of a population, for conditions which are influenced by both genetic and environmental factors. There is significant interest in using genetic risk prediction afforded through PGS in public health, clinical care, and research settings, yet many acknowledge the need to thoughtfully consider and address ethical, legal, and social implications (ELSI). To contribute to this effort, this paper reports on a narrative review of the literature, with the aim of identifying and categorizing ELSI relating to genetic risk prediction in the context of multifactorial disease, which have been raised by scholars in the field. Ninety-two articles, spanning from 1977 to 2021, met the inclusion criteria for this study. Identified ELSI included potential benefits, challenges and risks that focused on concerns about interpretation and use, and ethical obligations to maximize benefits, minimize risks, promote justice, and support autonomy. This research will support geneticists, clinicians, genetic counselors, patients, patient advocates, and policymakers in recognizing and addressing ethical concerns associated with PGS; it will also guide future empirical and normative research.

BACKGROUND/UNASSIGNED:Aggression is a major public health concern that emerges early in development and lacks optimized treatment, highlighting need for improved mechanistic understanding regarding the etiology of aggression. The present study leveraged fetal resting-state functional magnetic resonance imaging to identify candidate neurocircuitry for the onset of aggressive behaviors before symptom emergence. METHODS/UNASSIGNED: = 79). Independent component analysis was used to define frontal and limbic regions of interest. RESULTS/UNASSIGNED:Child aggression was not related to within-network connectivity of subcortical limbic regions or within-medial prefrontal network connectivity in fetuses. However, weaker functional coupling between the subcortical limbic network and medial prefrontal network in fetuses was prospectively associated with greater maternal-rated child aggression at 3 years of age even after controlling for maternal emotion dysregulation and toddler language ability. We observed similar, but weaker, associations between fetal frontolimbic functional connectivity and toddler internalizing symptoms. CONCLUSIONS/UNASSIGNED:Neural correlates of aggressive behavior may be detectable in utero, well before the onset of aggression symptoms. These preliminary results highlight frontolimbic connections as potential candidate neurocircuitry that should be further investigated in relation to the unfolding of child behavior and psychiatric risk.

OBJECTIVE:Suboptimal provider-parent communication contributes to poor parent comprehension of pediatric discharge instructions, which can lead to adverse outcomes. Residency is a critical window to acquire and learn to utilize key communication skills, potentially supported by formal training programs or visual reminders. Few studies have examined resident counseling practices or predictors of counseling quality. Our objectives were to (1) examine pediatric resident counseling practices and (2) determine how formal training and presence of discharge templates with domain-specific prompts are associated with counseling. METHODS:). Predictor variables were (1) formal discharge-related training (e.g., lectures) and (2) hospital discharge instruction template with space for individual domains. Logistic regression analyses, utilizing generalized estimating equations when appropriate to account for multiple domains (adjusting for resident gender, postgraduate year), were performed. KEY RESULTS/RESULTS:= 317) (13.9%) reported formal training. Over 25% of residents infrequently counsel on side effects, diagnosis, and restrictions. Resident reported use of communication strategies was infrequent: drawing pictures (24.1%), demonstration (15.8%), Teach Back (36.8%), Show Back (11.4%). Designated spaces in instruction templates for individual domains were associated with frequent domain-specific counseling (adjusted odds ratio [aOR] 4.1 [95% confidence interval: 3.5-4.8]). Formal training was associated with frequent Teach Back (aOR 2.6 [1.4-5.1]) and Show Back (aOR 2.7 [1.2-6.2]). CONCLUSIONS:

Food contact materials (FCMs) and food contact articles are ubiquitous in today's globalized food system. Chemicals migrate from FCMs into foodstuffs, so called food contact chemicals (FCCs), but current regulatory requirements do not sufficiently protect public health from hazardous FCCs because only individual substances used to make FCMs are tested and mostly only for genotoxicity while endocrine disruption and other hazard properties are disregarded. Indeed, FCMs are a known source of a wide range of hazardous chemicals, and they likely contribute to highly prevalent non-communicable diseases. FCMs can also include non-intentionally added substances (NIAS), which often are unknown and therefore not subject to risk assessment. To address these important shortcomings, we outline how the safety of FCMs may be improved by (1) testing the overall migrate, including (unknown) NIAS, of finished food contact articles, and (2) expanding toxicological testing beyond genotoxicity to multiple endpoints associated with non-communicable diseases relevant to human health. To identify mechanistic endpoints for testing, we group chronic health outcomes associated with chemical exposure into Six Clusters of Disease (SCOD) and we propose that finished food contact articles should be tested for their impacts on these SCOD. Research should focus on developing robust, relevant, and sensitive in-vitro assays based on mechanistic information linked to the SCOD, e.g., through Adverse Outcome Pathways (AOPs) or Key Characteristics of Toxicants. Implementing this vision will improve prevention of chronic diseases that are associated with hazardous chemical exposures, including from FCMs.

BACKGROUND:Living in neighborhoods with higher levels of walkability has been associated with a reduced risk of obesity and higher levels of physical activity. Obesity has been linked to increased risk of 13 cancers in women. However, long-term prospective studies of neighborhood walkability and risk for obesity-related cancer are scarce. OBJECTIVES:We evaluated the association between long-term average neighborhood walkability and obesity-related cancer risk in women. METHODS:The New York University Women's Health Study (NYUWHS) is a prospective cohort with 14,274 women recruited between 1985 and 1991 in New York City and followed over nearly three decades. We geocoded residential addresses for each participant throughout follow-up and calculated an average annual measure of neighborhood walkability across years of follow-up using data on population density and accessibility to destinations associated with geocoded residential addresses. We used ICD-9 codes to characterize first primary obesity-related cancers and employed Cox proportional hazards models to assess the association between average neighborhood walkability and risk of overall and site-specific obesity-related cancers. RESULTS: DISCUSSION:Our study highlights a potential protective role of neighborhood walkability in preventing obesity-related cancers in women. https://doi.org/10.1289/EHP11538.

BACKGROUND:Screening MRI as an adjunct to mammography is recommended by the ACS for patients with a lifetime risk for breast cancer > 20%. While the benefits are clear, MRI screening is associated with an increase in false-positive results. The purpose of this study was to analyze our institutional database of high-risk patients and assess the uptake of screening MRI examinations and the results of those screenings. METHODS:Our institutional review board-approved High-Risk Breast Cancer Database was queried for patients enrolled from January 2017 to January 2023 who were at high risk for breast cancer in a comparative analysis between those who were screened versus not screened with MRIs. Variables of interest included risk factor, background, MRI screening uptake, and frequency and results of image-guided breast biopsies. RESULTS:A total of 254 of 1106 high-risk patients (23%) had MRI screening. Forty-six of 852 (5.3%) patients in the non-MRI-screened cohort and nine of 254 (3.5%) patients in the MRI-screened cohort were diagnosed with a malignant lesion after image-guided biopsy (p = 0.6). There was no significant difference between MRI and non-MRI guided biopsies in detecting breast cancer. All malignant lesions were T1 or in situ disease. The 254 patients in the MRI-screened group underwent 185 biopsies. Fifty-seven percent of MRI-guided biopsies yielded benign results. CONCLUSIONS:Although the addition of MRI screening in our high-risk cohort did not produce a significant number of additional cancer diagnoses, patients monitored in our high-risk cohort who developed breast cancer were diagnosed at very early stages of disease, underscoring the benefit of participation in the program.

RATIONALE & OBJECTIVE/UNASSIGNED:Proteomics could provide pathophysiologic insight into the increased risk of mortality in patients with chronic kidney disease (CKD). This study aimed to investigate associations between the circulating proteome and all-cause mortality among patients with CKD. STUDY DESIGN/UNASSIGNED:Observational cohort study. SETTING & PARTICIPANTS/UNASSIGNED:Primary analysis in 703 participants in the African American Study of Kidney Disease and Hypertension (AASK) and validation in 1,628 participants with CKD in the Atherosclerosis Risk in Communities (ARIC) study who attended visit 5. EXPOSURE/UNASSIGNED:Circulating proteins. OUTCOME/UNASSIGNED:All-cause mortality. ANALYTICAL APPROACH/UNASSIGNED:Among AASK participants, we evaluated the associations of 6,790 circulating proteins with all-cause mortality using multivariable Cox proportional hazards models. Proteins with significant associations were further studied in ARIC Visit 5 participants with CKD. RESULTS/UNASSIGNED:-microglobulin, spondin-1, and N-terminal pro-brain natriuretic peptide) were available in the ARIC data, with all 3 significantly associated with death in ARIC. LIMITATIONS/UNASSIGNED:Possibility of unmeasured confounding. Cause of death was not known. CONCLUSIONS/UNASSIGNED:Using large-scale proteomic analysis, proteins were reproducibly associated with mortality in 2 cohorts of participants with CKD. PLAIN-LANGUAGE SUMMARY/UNASSIGNED:-microglobulin, spondin-1, and N-terminal pro-brain natriuretic peptide (BNP)) were also measured in ARIC and were significantly associated with death. Additional studies assessing biomarkers associated with mortality among patients with CKD are needed to evaluate their use in clinical practice.

PURPOSE/OBJECTIVE:Breast cancer survivors may demonstrate elevated psychological distress, which can also hinder adherence to survivorship care plans. Our goal was to study heterogeneity of behavioral health and functioning in breast cancer survivors, and identify both risk and protective factors to improve targets for wellness interventions. METHODS:Breast cancer survivors (n = 187) consented to complete self-reported psychological measures and to access their medical records. Latent class analysis (LCA) was used to classify heterogeneous subpopulations based on levels of depression, post-traumatic stress, fear of cancer recurrence, cancer-related pain, and fatigue. Multinomial logistic regression and auxiliary analysis in a 3-step modeling conditional approach was used to identify characteristics of the group based on demographics, treatment history and characteristics, and current medication prescriptions. RESULTS:Three subpopulations of breast cancer survivors were identified from the LCA: a modal Resilient group (48.2%, n = 90), a Moderate Symptoms group (34%, n = 65), and an Elevated Symptoms group (n = 17%, n = 32) with clinically-relevant impairment. Results from the logistic regression indicated that individuals in the Elevated Symptoms group were less likely to have a family history of breast cancer; they were more likely to be closer to time of diagnosis and younger, have received chemotherapy and psychotropic prescriptions, and have higher BMI. Survivors in the Elevated Symptoms group were also less likely to be prescribed estrogen inhibitors than the Moderate Symptoms group. CONCLUSIONS:This study identified subgroups of breast cancer survivors based on behavioral, psychological, and treatment-related characteristics, with implications for targeted monitoring and survivorship care plans. IMPLICATIONS FOR CANCER SURVIVORS/CONCLUSIONS:Results showed the majority of cancer survivors were resilient, with minimal psychological distress. Results also suggest the importance of paying special attention to younger patients getting chemotherapy, especially those without a family history of breast cancer.