Faculty Bibliography

BACKGROUND:Feeding problems are common in early childhood, and some evidence suggests that feeding problems may be associated with psychopathology. Few prospective studies have explored whether toddler feeding problems predict later psychopathology. METHODS:Mothers of 1,136 children from the Upstate KIDS cohort study provided data when children were 2.5 and 8 years of age. Food refusal (picky eating) and mechanical/distress feeding problems and developmental delays were assessed at 2.5 years. Child eating behaviors (enjoyment of food, food fussiness, and emotional under and overeating) and child psychopathology (attention-deficit/hyperactivity (ADHD), oppositional-defiant (OD), conduct disorder (CD), and anxiety/depression) symptoms were assessed at 8 years. RESULTS:Mechanical/distress feeding problems at age 2.5, but not food refusal problems, were associated with ADHD, problematic behavior (OD/CD), and anxiety/depression symptoms at 8 years in models adjusting for eating behaviors at 8 years and child and family covariates. Associations with mechanical/distress feeding problems were larger for ADHD and problematic behavior than anxiety/depression symptoms, though all were modest. Model estimates were similar for boys and girls. CONCLUSIONS:Much of the research on feeding problems focuses on picky eating. This study suggests that early mechanical and mealtime distress problems may serve as better predictors of later psychopathology than food refusal. Parents and pediatricians could monitor children with mechanical/distress feeding problems for signs of developing psychopathology.

BACKGROUND:Gender composition among surgical academic leadership, including academic medical journals, disproportionately favors men and may inadvertently introduce a bias. An understanding of the factors associated with gender representation among urologic journals may aid in prioritizing an equitable balance. OBJECTIVE:To evaluate female representation on editorial boards of pre-eminent international urologic journals. DESIGN, SETTING, AND PARTICIPANTS/METHODS:The names and position descriptions of urologic journal leadership appointees were collected in October 2021. Gender was assessed using gender-api.com or through personal title, as available. Journal characteristics were summarized using SCImago, a bibliometric indicator database extracted from Scopus journal data. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS/METHODS:A multivariate logistic regression analysis was performed to describe associations between SCImago Journal Rank (SJR) quartile and geographic region with female gender representation. Quartile 1 (Q1) was considered the top quartile and Q4 the bottom quartile concordant with journal impact factor. RESULTS AND LIMITATIONS/CONCLUSIONS:A total of 105 urology-focused journals were identified with 5989 total editorial board members, including 877 (14.6%) female, 5112 (85.4%) male, and two nonbinary persons. Female representation differed significantly by journal leadership position, SJR quartile, and geographic region. On the multivariate analysis of overall female representation, Q1 journals had higher odds of female representation than Q2 and Q3 journals, and had no significant difference from Q4 journals. Additionally, compared with Western Europe, North American journals had 78% higher odds while Asiatic journals had 50% lower odds of female representation. This study is limited by the inability to account for outside factors that lead to invitation or acceptance of journal leadership positions. CONCLUSIONS:Contemporary female leadership at urology journals is about six times less common than male leadership across all journals, although trends in their proportion were noted when assessed by journal quartile and region. Addressing this gender imbalance represents an important step toward achieving gender equity in the field of urology. PATIENT SUMMARY/RESULTS:In this study, we looked at the gender balance of academic journal leaders who serve as gatekeepers for sharing urologic research with the public. We found that the most prestigious journals and those in western countries tended to have the highest female representation. We hope that these findings help the academic community recognize and improve gender representation.

Human papillomavirus (HPV) is currently linked to almost 35,000 new cases of cancer in women and men each year in the United States. Gardasil-9 (Merck & Company), the only HPV vaccine now available in the United States, is nearly 100% effective at preventing precancers caused by oncogenic HPV types. In the United States, however, only about one half of adolescents are up to date with HPV vaccination. It is well known that health care clinicians' recommendations play a significant role in parents' decisions regarding HPV vaccination. A growing body of literature examines specific communication strategies for promoting uptake of the HPV vaccine. A comprehensive review of the evidence for each of these strategies is needed. The authors searched the PubMed, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, and Web of Science Complete databases for original articles with a defined clinician communication strategy and an outcome of HPV vaccine uptake or intention to vaccinate (PROSPERO registry no. CRD42020107602). In total, 46 studies were included. The authors identified two main strategies with strong evidence supporting their positive impact on vaccine uptake: strong recommendation and presumptive recommendation. Determinations about a causal relationship were limited by the small numbers of randomized controlled trials. There is also opportunity for more research to determine the effects of motivational interviewing and cancer-prevention messaging.

OBJECTIVES/OBJECTIVE:To examine racial and ethnic differences in maternal social support in infancy and the relationship between social support and mother-infant health behaviors. METHODS:Secondary analysis of baseline data from a multisite obesity prevention trial that enrolled mothers and their two-month-old infants. Behavioral and social support data were collected via questionnaire. We used modified Poisson regression to determine association between health behaviors and financial and emotional social support, adjusted for sociodemographic characteristics. RESULTS:826 mother-infant dyads (27.3% Non-Hispanic Black, 18.0% Non-Hispanic White, 50.1% Hispanic and 4.6% Non-Hispanic Other). Half of mothers were born in the U.S.; 87% were Medicaid-insured. There were no racial/ethnic differences in social support controlling for maternal nativity. U.S.-born mothers were more likely to have emotional and financial support (rate ratio [RR] 1.14 95% confidence interval [CI]: 1.07, 1.21 and RR 1.23 95% CI: 1.11, 1.37, respectively) versus mothers born outside the U.S. Mothers with financial support were less likely to exclusively feed with breast milk (RR 0.62; 95% CI: 0.45, 0.87) yet more likely to have tummy time ≥12min (RR 1.28; 95% CI: 1.02, 1.59) versus mothers without financial support. Mothers with emotional support were less likely to report feeding with breast milk (RR 0.82; 95% CI: 0.69, 0.97) versus mothers without emotional support. CONCLUSIONS:Nativity, not race or ethnicity, is a significant determinant of maternal social support. Greater social support was not universally associated with healthy behaviors. Interventions may wish to consider the complex nature of social support and population-specific social support needs.

BACKGROUND:Melamine, melamine derivatives, and aromatic amines are nitrogen-containing compounds with known toxicity and widespread commercial uses. Nevertheless, biomonitoring of these chemicals is lacking, particularly during pregnancy, a period of increased susceptibility to adverse health effects. OBJECTIVES/OBJECTIVE:We aimed to measure melamine, melamine derivatives, and aromatic amine exposure in pregnant women across the United States (U.S.) and evaluate associations with participant and urine sample collection characteristics. METHODS:We measured 43 analytes, representing 45 chemicals (i.e., melamine, three melamine derivatives, and 41 aromatic amines), in urine from pregnant women in nine diverse ECHO cohorts during 2008-2020 (N = 171). To assess relations with participant and urine sample collection characteristics, we used generalized estimating equations to estimate prevalence ratios (PRs) for analytes dichotomized at the detection limit, % differences (%Δ) for continuous analytes, and 95% confidence intervals. Multivariable models included age, race/ethnicity, marital status, urinary cotinine, and year of sample collection. RESULTS:Twelve chemicals were detected in >60% of samples, with near ubiquitous detection of cyanuric acid, melamine, aniline, 4,4'-methylenedianiline, and a composite of o-toluidine and m-toluidine (99-100%). In multivariable adjusted models, most chemicals were associated with higher exposures among Hispanic and non-Hispanic Black participants. For example, concentrations of 3,4-dichloroaniline were higher among Hispanic (%Δ: +149, 95% CI: +17, +431) and non-Hispanic Black (%Δ: +136, 95% CI: +35, +311) women compared with non-Hispanic White women. We observed similar results for ammelide, o-/m-toluidine, 4,4'-methylenedianiline, and 4-chloroaniline. Most chemicals were positively associated with urinary cotinine, with strongest associations observed for o-/m-toluidine (%Δ: +23; 95% CI: +16, +31) and 3,4-dichloroaniline (%Δ: +25; 95% CI: +17, +33). Some chemicals exhibited annual trends (e.g., %Δ in melamine per year: -11; 95% CI: -19, -1) or time of day, seasonal, and geographic variability. DISCUSSION/CONCLUSIONS:Exposure to melamine, cyanuric acid, and some aromatic amines was ubiquitous in this first investigation of these analytes in pregnant women. Future research should expand biomonitoring, identify sources of exposure disparities by race/ethnicity, and evaluate potential adverse health effects.

Background Nearly all colorectal and most pancreatic and lung cancers express carcinoembryonic antigen (CEA). However, due to its expression in normal gut epithelial cells, CEAtargeted therapies have resulted in on-target, off-tumor toxicity. To overcome this, we have developed TmodTM, a logicgated T-cell therapy platform. Tmod constructs are composed of an activating CAR or T-cell receptor that targets a tumor antigen and an inhibitory receptor recognizing an antigen expressed on normal healthy tissues, but not on tumor cells due to loss of heterozygosity (LOH).1,2 A2B530 is a CEAdirected Tmod construct utilizing an LIR-1-based inhibitory receptor (blocker) targeting human leukocyte antigen A*02 (HLA-A*02). Methods To generate CEA Tmod, T cells from HLA-A*02(+) donors were transduced with a single lentivirus to express i) the CAR, ii) the blocker, and iii) an shRNA targeting b2M. Cytotoxicity was measured by culturing CEA(+) target cell line pairs (A*02[-] and A*02[+]), expressing either GFP or RFP, with engineered T cells and quantifying live target cells over time. In vivo activity was examined using NSG mice subcutaneously implanted with normal (CEA[+]A*02[+]) and tumor cells (CEA[+]A*02[-]), in the right and left flanks. Mice were treated intravenously with CEA Tmod cells or control T cells. Results Control CEA CAR T cells killed CEA(+) target cell lines in vitro irrespective of HLA-A*02 expression. In contrast, CEA Tmod cells selectively killed tumor cells (CEA[+]A*02[-]) while sparing normal cells (CEA[+]A*02[+]). In mixed target cell cultures, CEA Tmod cells killed only the A*02(-) target cells, whereas the CEA CAR T cells killed both the A*02(- ) and A*02(+) cell lines. Further, CEA Tmod cells exhibited bidirectional control between the activated and blocked states. While mice treated with control CEA CAR T cells experienced a reduction in volume and bioluminescence of both normal and tumor grafts, CEA Tmod cells specifically cleared A*02(-) tumors in mice (table 1). Finally, although expansion of Tmod cells in peripheral blood trended lower than CAR and TCR controls, anti-tumor activity was comparable in these groups. Conclusions A2B530 is an autologous CEA Tmod cell product that exploits common LOH at the HLA locus in cancer cells, enabling these engineered T cells to discriminate between normal and tumor cells. BASECAMP-1 (NCT04981119), an observational study identifying patients with somatic HLA LOH, is recruiting. Eligible patients with metastatic colorectal, pancreatic, or non-small cell lung cancer will be apheresed for a future A2B530 EVEREST-1 interventional study

BACKGROUND:The first 1000 days of a child's life are increasingly recognized as a critical window for establishing a healthy growth trajectory to prevent childhood obesity and its associated long-term comorbidities. The purpose of this manuscript is to detail the methods for a multi-site, comparative effectiveness trial designed to prevent childhood overweight and obesity from birth to age 2 years. METHODS:This study is a multi-site, individually randomized trial testing the comparative effectiveness of two active intervention arms: 1) the Greenlight intervention; and 2) the Greenlight Plus intervention. The Greenlight intervention is administered by trained pediatric healthcare providers at each well-child visit from 0 to 18 months and consists of a low health literacy toolkit used during clinic visits to promote shared goal setting. Families randomized to Greenlight Plus receive the Greenlight intervention plus a health information technology intervention, which includes: 1) personalized, automated text-messages that facilitate caregiver self-monitoring of tailored and age-appropriate child heath behavior goals; and 2) a web-based, personalized dashboard that tracks child weight status, progress on goals, and electronic Greenlight content access. We randomized 900 parent-infant dyads, recruited from primary care clinics across six academic medical centers. The study's primary outcome is weight for length trajectory from birth through 24 months. CONCLUSIONS:By delivering a personalized and tailored health information technology intervention that is asynchronous to pediatric primary care visits, we aim to achieve improvements in child growth trajectory through two years of age among a sample of geographically, socioeconomically, racially, and ethnically diverse parent-child dyads.

INTRODUCTION/BACKGROUND:Extended venous thromboembolism prophylaxis (eVTEp) is recommended for select patients who have undergone major abdominopelvic surgery to prevent postdischarge venous thromboembolism (pdVTE). Criteria for selection of these patients are untested for this purpose and may be ineffective. To address this gap, we investigated the effectiveness of eVTEp on pdVTE rates. METHODS:A retrospective cohort study of patients undergoing abdominopelvic surgery from January 2016 to February 2020 was performed using data from the Michigan Surgical Quality Collaborative. pdVTE was the main outcome. Our exposure variable, eVTEp, was compared dichotomously. Length of stay (LOS) was compared categorically using clinically relevant groups. Age, race, cancer occurrence, inflammatory bowel disease, surgical approach, and surgical time were covariates among other variables. Descriptive statistics, propensity score matching, and multivariable logistic regression were performed to compare pdVTE rates. RESULTS:A total of 45,637 patients underwent abdominopelvic surgery. Of which, 3063 (6.71%) were prescribed eVTEp. Two hundred eighty-five (0.62%) had pdVTE. Of the 285, 59 (21%) patients received eVTEp, while 226 (79%) patients did not. After propensity score matching, multivariable logistic regression analysis showed pdVTE was associated with eVTEp and LOS of 5 d or more (P < 0.001). eVTEp was not associated with LOS. Further analysis showed increased risk of pdVTE with increasing LOS independent of prescription of eVTEp based on known risk factors. CONCLUSIONS:pdVTE was associated with increasing LOS but not with other VTE risk factors after propensity score matching. Current guidelines for eVTEp do not include LOS. Our findings suggest that LOS >5 d should be added to the criteria for eVTEp.

The Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) program is an NCI-funded initiative with an objective to develop tools to optimize low-dose CT (LDCT) lung cancer screening. Here, we describe the rationale and design for the Risk Biomarker and Nodule Malignancy projects within INTEGRAL. The overarching goal of these projects is to systematically investigate circulating protein markers to include on a panel for use (i) pre-LDCT, to identify people likely to benefit from screening, and (ii) post-LDCT, to differentiate benign versus malignant nodules. To identify informative proteins, the Risk Biomarker project measured 1161 proteins in a nested-case control study within 2 prospective cohorts (n = 252 lung cancer cases and 252 controls) and replicated associations for a subset of proteins in 4 cohorts (n = 479 cases and 479 controls). Eligible participants had a current or former history of smoking and cases were diagnosed up to 3 years following blood draw. The Nodule Malignancy project measured 1078 proteins among participants with a heavy smoking history within four LDCT screening studies (n = 425 cases diagnosed up to 5 years following blood draw, 430 benign-nodule controls, and 398 nodule-free controls). The INTEGRAL panel will enable absolute quantification of 21 proteins. We will evaluate its performance in the Risk Biomarker project using a case-cohort study including 14 cohorts (n = 1696 cases and 2926 subcohort representatives), and in the Nodule Malignancy project within five LDCT screening studies (n = 675 cases, 680 benign-nodule controls, and 648 nodule-free controls). Future progress to advance lung cancer early detection biomarkers will require carefully designed validation, translational, and comparative studies.

Understanding of human brain development has advanced rapidly as the field of developmental cognitive neuroscience (DCN) has matured into an established scientific discipline. Despite substantial progress, DCN lags behind other related disciplines in terms of diverse representation, standardized reporting requirements for socio-demographic characteristics of participants in pediatric neuroimaging studies, and use of intentional sampling strategies to more accurately represent the socio-demographic, ethnic, and racial composition of the populations from which participants are sampled. Additional efforts are needed to shift DCN towards a more inclusive field that facilitates the study of individual differences across a variety of cultural and contextual experiences. In this commentary, we outline and discuss barriers within our current scientific practice (e.g., research methods) and beliefs (i.e., what constitutes good science, good scientists, and good research questions) that contribute to under-representation and limited diversity within pediatric neuroimaging studies and propose strategies to overcome those barriers. We discuss strategies to address barriers at intrapersonal, interpersonal, community, systemic, and structural levels. Highlighting strength-based models of inclusion and recognition of the value of diversity in DCN research, along with acknowledgement of the support needed to diversify the field is critical for advancing understanding of neurodevelopment and reducing health inequities.