Browsing by Author "Schmidt, Rebecca J."

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    Development and Validation of a Novel Placental DNA Methylation Biomarker of Maternal Smoking during Pregnancy in the ECHO Program
    (EHP, 2024) Shorey-Kendrick, Lyndsey E.; Davis, Brett; Gao, Lina; Park, Byung; Vu, Annette; Morris, Cynthia D.; Breton, Carrie V.; Fry, Rebecca; Garcia, Erika; Schmidt, Rebecca J.; O'Shea, T. Michael; Tepper, Robert S.; McEvoy, Cindy T.; Spindel, Eliot R.; Pediatrics, School of Medicine
    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 Children’s 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.
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    Existing Transplant Nephrology Compensation Models and Opportunities for Equitable Pay
    (Wolters Kluwer, 2022) Josephson, Michelle A.; Wiseman, Alexander C.; Tucker, J. Kevin; Segal, Mark S.; Schmidt, Rebecca J.; Mujtaba, Muhammad A.; Gurley, Susan B.; Gaston, Robert S.; Doshi, Mona D.; Brennan, Daniel C.; Moe, Sharon M.; Medicine, School of Medicine
    The American Society of Nephrology (ASN) formed the ASN Task Force on Academic Nephrologist Compensation and Productivity in 2020 to understand how the subspecialty is evolving and where there are needs for alignment in compensation in US transplant centers. The task force's review of the roles and responsibilities of transplant nephrologists is in the companion perspective (1). Transplant nephrologists are required for successful kidney transplantation, the ideal treatment from a survival and quality-of-life perspective for patients with kidney failure (2,3). Unfortunately, work relative value unit (wRVU) requirements for compensation models vary tremendously across institutions and limit the ability to adequately staff programs. This article addresses transplant nephrology models of care, how different models affect funds flow and compensation, and opportunities to more equitably compensate transplant nephrologists.
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    The Importance of Transplant Nephrology to a Successful Kidney Transplant Program
    (Wolters Kluwer, 2022) Moe, Sharon M.; Brennan, Daniel C.; Doshi, Mona D.; Gaston, Robert S.; Gurley, Susan B.; Mujtaba, Muhammad A.; Schmidt, Rebecca J.; Segal, Mark S.; Tucker, J. Kevin; Wiseman, Alexander C.; Josephson, Michelle A.; Medicine, School of Medicine
    Nephrologists are responsible for the care of patients with a diverse array of systemic diseases, comorbidities, and kidney issues across a variety of service locations (clinic, inpatient, dialysis unit). As the field of nephrology becomes increasingly complex, there has been a need for advanced training and subspecialization, similar to the transformation cardiology experienced with heart failure, electrophysiology, and interventional cardiology. As a result, the American Society of Nephrology (ASN) formed the ASN Task Force on Academic Nephrologist Compensation and Productivity to begin to understand the needed transformation, especially as it relates to assessing clinical productivity and compensation. Members of the task force included nephrology division chiefs, transplant program directors, and transplant nephrologists, representing academic and community transplant programs across the United States. The group met virtually throughout 2021 to discuss specific job functions, roles, responsibilities, and compensation models, and the discussion and conclusions follow. The flow of transplant funds from the hospital to the physician and transplant nephrology models of care are further discussed in a companion Perspective.