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BACKGROUND: Maternal cigarette smoking during pregnancy (MSDP) is associated with numerous adverse health outcomes in infants and children with potential lifelong consequences. Negative effects of MSDP on placental DNA methylation (DNAm), placental structure, and function are well established. OBJECTIVE: Our aim was to develop biomarkers of MSDP using DNAm measured in placentas (N=96), collected as part of the Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function double-blind, placebo-controlled randomized clinical trial conducted between 2012 and 2016. We also aimed to develop a digital polymerase chain reaction (PCR) assay for the top ranking cytosine-guanine dinucleotide (CpG) so that large numbers of samples can be screened for exposure at low cost. METHODS: We compared the ability of four machine learning methods [logistic least absolute shrinkage and selection operator (LASSO) regression, logistic elastic net regression, random forest, and gradient boosting machine] to classify MSDP based on placental DNAm signatures. We developed separate models using the complete EPIC array dataset and on the subset of probes also found on the 450K array so that models exist for both platforms. For comparison, we developed a model using CpGs previously associated with MSDP in placenta. For each final model, we used model coefficients and normalized beta values to calculate placental smoking index (PSI) scores for each sample. Final models were validated in two external datasets: the Extremely Low Gestational Age Newborn observational study, N=426; and the Rhode Island Childrens Health Study, N=237. RESULTS: Logistic LASSO regression demonstrated the highest performance in cross-validation testing with the lowest number of input CpGs. Accuracy was greatest in external datasets when using models developed for the same platform. PSI scores in smokers only (n=72) were moderately correlated with maternal plasma cotinine levels. One CpG (cg27402634), with the largest coefficient in two models, was measured accurately by digital PCR compared with measurement by EPIC array (R2=0.98). DISCUSSION: To our knowledge, we have developed the first placental DNAm-based biomarkers of MSDP with broad utility to studies of prenatal disease origins. https://doi.org/10.1289/EHP13838.

Research experience provides critical training for new biomedical research scientists. Students from underrepresented populations studying science, technology, engineering, and mathematics (STEM) are increasingly recruited into research pathways to diversify STEM fields. However, support structures outside of research settings designed to help these students navigate biomedical research pathways are not always available; nor are program support components outside the context of laboratory technical skills training and formal mentorship well understood. This study leveraged a multi-institutional research training program, Enhancing Cross-Disciplinary Infrastructure and Training at Oregon (EXITO), to explore how nine institutions designed a new curricular structure (Enrichment) to meet a common goal of enhancing undergraduate research training and student success. EXITO undergraduates participated in a comprehensive, 3-year research training program with the Enrichment component offered across nine sites: three universities and six community colleges, highly diverse in size, demographics, and location. Sites' approaches to supporting students in the training program were studied over a 30-month period. All sites independently created their own nonformal curricular structures, implemented interprofessionally via facilitated peer groups. Site data describing design and implementation were thematically coded to identify essential programmatic components across sites, with student feedback used to triangulate findings. Enrichment offered students time to critically reflect on their interests, experiences, and identities in research; network with peers and professionals; and support negotiation of hidden and implicit curricula. Students reported the low-pressure setting and student-centered curriculum balanced the high demands associated with academics and research. Core curricular themes described Enrichment as fostering a sense of community among students, exposing students to career paths and skills, and supporting development of students' professional identities. The non-formal, interprofessional curricula enabled students to model diverse biomedical identities and pathways for each other while informing institutional structures to improve diverse undergraduate students' success in academia and research.

BackgroundLong-term follow-up for clinician-scientist training programs is sparse. We describe the outcomes of clinician-scientist scholars in the National Heart Lung and Blood Institute (NHLBI) K12 program in emergency care research up to 8.7 years after matriculation in the program.MethodsThis was a cohort study of faculty clinician-scientist scholars enrolled in a NHLBI K12 research training program at 6 sites across the US, with median follow-up 7.7 years (range 5.7-8.7 years) from the date of matriculation. Scholars completed electronic surveys in 2017 and 2019, with the 2019 survey collecting information for their current work setting, percent time for research, and grant funding from all sources. We used NIH RePorter and online resources to verify federal grants through March 2021. The primary outcome was a funded career development award (CDA) or research project grant (RPG) where the scholar was principal investigator. We included funding from all federal sources and national foundations.ResultsThere were 43 scholars, including 16 (37%) women. Over the follow-up period, 32 (74%) received an individual CDA or RPG, with a median of 36 months (range 9-83 months) after entering the program. Of the 43 scholars, 23 (54%) received a CDA and 22 (51%) received an RPG, 7 (16%) of which were R01s. Of the 23 scholars who received a CDA, 13 (56%) subsequently had an RPG funded. Time to CDA or RPG did not differ by sex (women vs. men log-rank test p = 0.27) or specialty training (emergency medicine versus other specialties, p = 0.59).ConclusionsAfter 7 years of follow-up for this NHLBI K12 emergency care research training program, three quarters of clinician-scientist scholars had obtained CDA or RPG funding, with no notable differences by sex or clinical training.

Study objectiveWe assess the productivity, outcomes, and experiences of participants in the National Institutes of Health/National Heart, Lung, and Blood Institute-funded K12 institutional research training programs in emergency care research.MethodsWe used a mixed-methods study design to evaluate the 6 K12 programs, including 2 surveys, participant interviews, scholar publications, grant submissions, and funded grants. The training program lasted from July 1, 2011, through June 30, 2017. We tracked scholars for a minimum of 3 years and up to 5 years, beginning with date of entry into the program. We interviewed program participants by telephone using open-ended prompts.ResultsThere were 94 participants, including 43 faculty scholars, 13 principal investigators, 30 non-principal investigator primary mentors, and 8 program administrators. The survey had a 74% overall response rate, including 95% of scholars. On entry to the program, scholars were aged a median of 37 years (interquartile range [IQR] 34 to 40 years), with 16 women (37%), and represented 11 disciplines. Of the 43 scholars, 40 (93%) submitted a career development award or research project grant during or after the program; 26 (60%) have secured independent funding as of August 1, 2017. Starting with date of entry into the program, the median time to grant submission was 19 months (IQR 11 to 27 months) and time to funding was 33 months (IQR 27 to 39 months). Cumulative median publications per scholar increased from 7 (IQR 4 to 15.5) at program entry to 21 (IQR 11 to 33.5) in the first post-K12 year. We conducted 57 semistructured interviews and identified 7 primary themes.ConclusionThis training program produced 43 interdisciplinary investigators in emergency care research, with demonstrated productivity in grant funding and publications.

Purpose: Environmental factors such as bathing may play a role in atopic dermatitis (AD) development. This analysis utilized data from the Community Assessment of Skin Care, Allergies, and Eczema (CASCADE) Trial (NCT03409367), a randomized controlled trial of emollient therapy for AD prevention in the general population, to estimate bathing frequency and associated factors within the first 9 weeks of life. Methods: Data were collected from 909 parent/newborn dyads recruited from 25 pediatric and family medicine clinics from the Meta‐network Learning and Research Center (Meta‐LARC) practice‐based research network (PBRN) consortium in Oregon, North Carolina, Colorado, and Wisconsin for the CASCADE trial. Ordinal logistic regression was used to conduct a cross‐sectional analysis of the association between bathing frequency (measured in baths per week) and demographic, medical, and lifestyle information about the infant, their family, and their household. Variables were selected using a backwards‐stepwise method and estimates from the reduced model are reported in the text. Results: Moisturizer use (OR = 2.03, 95% CI: 1.54–2.68), Hispanic or Latino ethnicity (OR = 1.97, 95% CI: 1.42–2.72), a parental education level lower than a 4‐year college degree (OR = 2.48, 95% CI: 1.70–3.62), living in North Carolina or Wisconsin (compared to Oregon; OR = 2.12 and 1.47, 95% CI: 1.53–2.93 and 1.04–2.08, respectively), and increasing child age (in days; OR = 1.02, 95% CI: 1.01–1.02) were significantly associated with more frequent bathing, while pet ownership (OR = 0.67, 95% CI: 0.52–0.87) was significantly associated with less frequent bathing. Conclusions: We found significant ethnic, geographic, and socioeconomic variation in bathing frequency before 9 weeks of age that may be of relevance to AD prevention studies. [ABSTRACT FROM AUTHOR]