Lessons From the First Decade of the Native American Summer Research Internship at the University of Utah.

PROBLEM: American Indian/Alaska Native (AI/AN) populations are facing multiple health crises, including limited access to care, high rates of chronic disease, and early mortality that is far worse than other underrepresented minorities in the United States. According to the Association of American Indian Physicians, AI/AN people represent 2.0% of the U.S. population but only 0.2% of medical students and 0.1% of full-time faculty at MD-granting institutions. Increasing the number of AI/AN clinicians and scientists is one strategy to improve health outcomes in the AI/AN population and address these crises. APPROACH: In 2010, the University of Utah partnered with research, cultural, and professional mentors to create a 10-week summer Native American Research Internship (NARI) program for AI/AN college students across the United States who are interested in pursuing biomedical careers. NARI attracts and supports AI/AN students by offering mentored summer research internships in an innovative, culturally aware framework that adapts to observed challenges to optimize educational experiences and support biomedical career aspirations. OUTCOMES: During the first decade of the NARI program, 128 students from 22 U.S. states, representing 46 tribal nations and 57 colleges and universities, participated. Of those 128 students, 113 (88%) have completed a bachelor's degree and the remaining 15 (12%) are currently working toward a bachelor's degree. No NARI student has dropped out of college. Twenty-six (20%) NARI alumni have matriculated to medical school and 30 (23%) to graduate school. Eight (6%) participants have completed medical school, and 3 (2%) are pursuing a PhD in science. An additional 36 (28%) have gained employment in biomedical research fields. NEXT STEPS: The NARI program has increased the participation of AI/AN students in medicine and the biomedical sciences. The innovative, culturally aware, and adaptive framework is a model for other programs for AI/AN students and students in other underrepresented communities.

Children With Medical Complexity: The 10-Year Experience of a Single Center.

Children with medical complexity (CMC) have chronic, multisystem health conditions, substantial health care needs, major functional limitations, and high resource use. They represent <1% of US children yet account for more than one-third of total pediatric health care costs. Health care systems designed for typical children do not meet the unique needs of CMC. In this special article, we describe the experience of our Comprehensive Care Program for CMC in a pediatric tertiary care center, from its launch in 2007 to its present model. We review the literature, describe our collective lessons learned, and offer suggestions for future directions.

Development, Implementation, and Use of a Neurology Therapeutics Committee.

Innovative therapeutics are transforming care of children with previously untreatable neurological disorders. However, there are challenges in the use of new therapies: the medicine may not be effective in all patients, administration may not be tolerated, and matching therapy choice to patient is complex. Finally, costs are high, which imposes financial burdens on insurance companies, families, and the health-care system. Our objective was to address challenges for clinical implementation of the new therapeutics. We sought to develop a process that would be personalized for patient and disease, encourage appropriate use of a therapeutic agent while mitigating pressure on a clinician to prescribe the therapy in all instances, and assist third-party payers in approving therapeutic use based on safety and efficacy. We report our creation of a Neurology Therapeutics Committee for pediatric patients. We review the committee's mechanisms, describe its use and report outcomes, and suggest the Neurology Therapeutics Committee's broader applicability.

Financial Analysis of Pediatric Resident Physician Primary Care Longitudinal Outpatient Experience.

OBJECTIVE: To determine whether residency training represents a net positive or negative cost to academic medical centers, we analyzed the cost of a residency program and clinical productivity of residents and faculty in an outpatient primary care practice with or without residents. METHODS: Patient volume and revenue data (Current Procedural Terminology codes) from an academic primary care general pediatric clinic were evaluated for faculty clinics (faculty only) and resident teaching clinics (longitudinal outpatient experience [LOE]) with 1 to 4 residents per faculty. A detailed cost per resident was determined using a departmental financial model that included salary, benefits, faculty and administrative staff effort, nonpersonnel costs, and institutional graduate medical education support. RESULTS: The LOE clinics had a greater mean number of patient visits (11.6 vs 6.8) than faculty clinics per faculty member. In the LOE clinic, the number of patient visits per clinic was directly proportional to the number of residents per faculty. The cost for each resident was $250 per clinic ($112 per resident, $88 per medical assistant per resident, and $50 per room per resident). When factoring in clinic costs and faculty supervision time, the LOE clinics (average 3.5 residents with 1 supervising faculty) had greater average cost (+$687.00) and revenue (+$319.45) and lower operating margin (revenue minus cost, -$367.55) than the faculty clinics (1 faculty member). CONCLUSIONS: Pediatric resident LOE clinics had a greater average number of patient visits and revenue per faculty member but higher costs and lower operating margins than faculty clinics.

Semantic closure demonstrated by the evolution of a universal constructor architecture in an artificial chemistry.

We present a novel stringmol-based artificial chemistry system modelled on the universal constructor architecture (UCA) first explored by von Neumann. In a UCA, machines interact with an abstract description of themselves to replicate by copying the abstract description and constructing the machines that the abstract description encodes. DNA-based replication follows this architecture, with DNA being the abstract description, the polymerase being the copier, and the ribosome being the principal machine in expressing what is encoded on the DNA. This architecture is semantically closed as the machine that defines what the abstract description means is itself encoded on that abstract description. We present a series of experiments with the stringmol UCA that show the evolution of the meaning of genomic material, allowing the concept of semantic closure and transitions between semantically closed states to be elucidated in the light of concrete examples. We present results where, for the first time in an in silico system, simultaneous evolution of the genomic material, copier and constructor of a UCA, giving rise to viable offspring.

A Matrix Mentoring Model That Effectively Supports Clinical and Translational Scientists and Increases Inclusion in Biomedical Research: Lessons From the University of Utah.

Physician-scientists and scientists in all the health professions are vital members of the U.S. biomedical workforce, but their numbers at academic health centers are declining. Mentorship has been identified as a key component in retention of faculty members at academic health centers. Effective mentoring may promote the retention of clinician-scientists in the biomedical workforce. The authors describe a holistic institutional mentoring program to support junior faculty members engaged in clinical and translational science at the University of Utah. The clinical and translational scholars (CATS) program leverages the resources of the institution, including the Center for Clinical and Translational Science, to augment departmental resources to support junior faculty investigators and uses a multilevel mentoring matrix that includes self, senior, scientific, peer, and staff mentorship. Begun in the Department of Pediatrics, the program was expanded in 2013 to include all departments in the school of medicine and the health sciences. During the two-year program, scholars learn management essentials and have leadership training designed to develop principal investigators. Of the 86 program participants since fiscal year 2008, 92% have received extramural awards, 99% remain in academic medicine, and 95% remain at the University of Utah. The CATS program has also been associated with increased inclusion of women and underrepresented minorities in the institutional research enterprise. The CATS program manifests institutional collaboration and coordination of resources, which have benefited faculty members and the institution. The model can be applied to other academic health centers to support and sustain the biomedical workforce.

Exploring the associations between microRNA expression profiles and environmental pollutants in human placenta from the National Children's Study (NCS).

The placenta is the principal regulator of the in utero environment, and disruptions to this environment can result in adverse offspring health outcomes. To better characterize the impact of in utero perturbations, we assessed the influence of known environmental pollutants on the expression of microRNA (miRNA) in placental samples collected from the National Children's Study (NCS) Vanguard birth cohort. This study analyzed the expression of 654 miRNAs in 110 term placentas. Environmental pollutants measured in these placentas included dichlorodiphenyldichloroethylene (DDE), bisphenol A (BPA), polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), arsenic (As), mercury (Hg), lead (Pb), and cadmium (Cd). A moderated t-test was used to identify a panel of differentially expressed miRNAs, which were further analyzed using generalized linear models. We observed 112 miRNAs consistently expressed in >70% of the samples. Consistent with the literature, miRNAs located within the imprinted placenta-specific C19MC cluster, specifically mir-517a, mir-517c, mir-522, and mir-23a, are among the top expressed miRNA in our study. We observed a positive association between PBDE 209 and miR-188-5p and an inverse association between PBDE 99 and let-7c. Both PCBs and Cd were positively associated with miR-1537 expression level. In addition, multiple let-7 family members were downregulated with increasing levels of Hg and Pb. We did not observe DDE or BPA levels to be associated with placental miRNA expression. This is the first birth cohort study linking environmental pollutants and placental expression of miRNAs. Our results suggest that placental miRNA profiles may signal in utero exposures to environmental chemicals.

Fetal aortic distensibility, compliance and pulse pressure assessment during the second half of pregnancy.

The objective of the study was to measure fetal aortic pulse wave velocity and lumen diameter waveforms and subsequently calculate local distensibility, compliance and pulse pressure. A dedicated algorithm for optimizing lumen diameter assessment from radiofrequency ultrasound data is described. Biplane raw data were obtained from a matrix array transducer. We evaluated 83 confirmed, normally developing pregnancies at 22-38 wk. Fetal aortic pulse wave velocity (PWV, m/s) = 0.047 × gestational age (wk) + 1.241, and the distensibility coefficient (1/kPa) = 1/(1.04 × PWV(2)). The logarithm of the local compliance index (mm(2)/kPa) and the pulse pressure (kPa) were both linearly related to gestational age as 0.022 × GA (wk) - 0.343 and 0.012 × GA (wk) + 0.931, respectively. In conclusion, fetal aortic elastic properties can be derived from phase-sensitive radiofrequency data and multiline diameter assessment. Future studies may shed further light on the developmental origins of vascular health and disease.

Developing future clinician scientists while supporting a research infrastructure.

BACKGROUND: Supporting clinical research is a national priority. Clinician scientists are rare and clinical trials in academic medical centers (AMC) often fail to meet enrollment goals. Undergraduate students interested in biomedical careers often lack opportunities to perform clinical research. OBJECTIVE: Describe an innovative undergraduate course that supports clinical research in an AMC. METHODS: The course, Clinical Research Methods and Practice, offers undergraduate students the opportunity to learn clinical research through didactic and practical experiences. The students in turn support clinician scientists' conduct of clinical studies in an AMC. Clinician scientists receive research support and participate in mentoring sessions for students. RESULTS: Over seven semesters, 128 students have assisted in 21 clinical studies located in outpatient and inpatient units of two hospitals. Students identified and screened eligible patients, collected clinical data, assisted in obtaining informed consent, and transported specimens. Many of the clinician scientists have met their enrollment goals and several have been top-enrollers in multicenter clinical trials as a result of student support. CONCLUSIONS: The Clinical Research Methods and Practice class addresses barriers to clinical research in AMC. This may be a model for institutions committed to mentoring students early in their career and to developing infrastructures for clinical research.

Costs and infant outcomes after implementation of a care process model for febrile infants.

OBJECTIVE: Febrile infants in the first 90 days may have life-threatening serious bacterial infection (SBI). Well-appearing febrile infants with SBI cannot be distinguished from those without by examination alone. Variation in care resulting in both undertreatment and overtreatment is common. METHODS: We developed and implemented an evidence-based care process model (EB-CPM) for the management of well-appearing febrile infants in the Intermountain Healthcare System. We report an observational study describing changes in (1) care delivery, (2) outcomes of febrile infants, and (3) costs before and after implementation of the EB-CPM in a children's hospital and in regional medical centers. RESULTS: From 2004 through 2009, 8044 infants had 8431 febrile episodes, resulting in medical evaluation. After implementation of the EB-CPM in 2008, infants in all facilities were more likely to receive evidence-based care including appropriate diagnostic testing, determination of risk for SBI, antibiotic selection, decreased antibiotic duration, and shorter hospital stays (P < .001 for all). In addition, more infants had a definitive diagnosis of urinary tract infection or viral illness (P < .001 for both). Infant outcomes improved with more admitted infants positive for SBI (P = .011), and infants at low risk for SBI were more often managed without antibiotics (P < .001). Although hospital admissions were shortened by 27%, there were no cases of missed SBI. Health Care costs were also reduced, with the mean cost per admitted infant decreasing from $7178 in 2007 to $5979 in 2009 (-17%, P < .001). CONCLUSIONS: The EB-CPM increased evidence-based care in all facilities. Infant outcomes improved and costs were reduced, substantially improving value.

Linking supermarket sales data to nutritional information: an informatics feasibility study.

Grocery sales are a data source of potential value to dietary assessment programs in public health informatics. However, the lack of a computable method for mapping between nutrient and food item information represents a major obstacle. We studied the feasibility of linking point-of-sale data to USDA-SR nutrient database information in a sustainable way. We analyzed 2,009,533 de-identified sales items purchased by 32,785 customers over a two-week period. We developed a method using the item category hierarchy in the supermarket's database to link purchased items to records from the USDA-SR. We describe our methodology and its rationale and limitations. Approximately 70% of all items were mapped and linked to the SR; approximately 90% of all items could be mapped with an equivalent expenditure of additional effort. 100% of all items were mapped to USDA standard food groups. We conclude that mapping grocery sales data to nutritional information is feasible.

Who will care for me next? Transitioning to adulthood with hydrocephalus.

OBJECTIVES: Hydrocephalus is a prototypical chronic condition that follows children into adulthood. The objectives of this study were to (1) review how the health care needs of young adults with hydrocephalus are not being met, (2) estimate the numbers of adults with childhood-onset hydrocephalus, (3) describe a novel program to provide care for young adults with hydrocephalus and other chronic pediatric conditions, and (4) propose national strategies to promote successful hydrocephalus transition care. RESULTS: Adults with hydrocephalus need continuous access to expert surgical and medical providers. Existing care models fail to meet this need. The number of young adults who have hydrocephalus, are aged 18 to 35 and need treatment in the United States is predicted to exceed 40000 annually within the next 2 decades. We are developing integrated teams of pediatric and adult medical and surgical specialists to provide continuous, coordinated, comprehensive care for individuals with hydrocephalus in a pediatric setting. This setting will train our future physician workforce on optimal transition care. Coordinated national efforts are also needed. CONCLUSIONS: Providers need to implement appropriate management and transition care for individuals with hydrocephalus. We must work at local and national levels to transform the care model, improve the quality of health care delivery, and improve outcomes for young adults with hydrocephalus.

Dependence of aortic arch morphogenesis on intracardiac blood flow in the left atrial ligated chick embryo.

Partial left atrial ligation before cardiac septation redistributes intracardiac blood flow and produces left ventricular hypoplasia in the chick. We hypothesized that redistributed intracardiac blood flow adversely alters aortic arch development. We ligated the left atrial appendage with a 10-0 nylon suture at stage 21 chick embryos, then reincubated up to stage 34. Sham embryos had a suture tied adjacent to the atrial wall, and normal controls were unoperated. We measured simultaneous atrioventricular (AV) and dorsal aortic (DAo) blood velocities from stage 24 embryos with an ultrasound pulsed-Doppler flow meter; and the left and right third and fourth aortic arch blood flow with a laser-Doppler flow meter. Ventricular and atrial cross-sectional areas were measured from sequential video fields for planimetry. Intracardiac flow patterns were imaged on video by injecting India ink into the vitelline vein. In separate embryos, radiopaque microfil was injected into the cardiovascular system for micro-CT scanning. We analyzed the morphologic characteristics of the heart at stage 34. Active AV and DAo stroke volume (mm(3)), right third and fourth aortic arch blood flow (mm(3)/s) were all decreased in ligated embryos (P < 0.05) when compared with normal and sham embryos. Ventricular end-diastolic volume versus normal and sham embryos decreased by 45% and 46%, respectively (P < 0.05). India ink injection revealed altered right aortic arch flow patterns in the ligated embryos compared with normal embryos. micro-CT imaging confirmed altered arch morphogenesis. Alterations in intracardiac blood flow disrupt both early cardiac morphogenesis and aortic arch selection.

Application of the magnitude-squared coherence function between uterine and umbilical flow velocity waveforms for predicting placental dysfunction: a preliminary study.

To examine whether the magnitude-squared coherence between uterine and umbilical blood flow velocity waveforms can, in conjunction with estimated fetal weight, uterine and umbilical pulsatility indices, fetal and maternal heart rates, diastolic notching and the amniotic fluid index, create a sensitive and specific model for the prediction of placental dysfunction. Binary logistic prediction models are created for preeclampsia, pregnancy induced hypertension and intrauterine growth restriction in a study group of 284 unselected midtrimester pregnancies. In each study group, the median value of derived parameters were compared with the uncomplicated pregnancy control group. The magnitude-squared coherence function between the uterine and umbilical flow velocity waveforms was found to be a statistically significant predictor of preeclampsia during the midtrimester of pregnancy. The magnitude-squared coherence did not improve the prediction of intrauterine growth restriction or pregnancy induced hypertension. The inclusion of magnitude-squared coherence as one of the prediction parameters may improve the early identification of pregnancies subsequently complicated by preeclampsia.

The National Children's Study: a 21-year prospective study of 100,000 American children.

Prospective, multiyear epidemiologic studies have proven to be highly effective in discovering preventable risk factors for chronic disease. Investigations such as the Framingham Heart Study have produced blueprints for disease prevention and saved millions of lives and billions of dollars. To discover preventable environmental risk factors for disease in children, the US Congress directed the National Institute of Child Health and Human Development, through the Children's Health Act of 2000, to conduct the National Children's Study. The National Children's Study is hypothesis-driven and will seek information on environmental risks and individual susceptibility factors for asthma, birth defects, dyslexia, attention-deficit/hyperactivity disorder, autism, schizophrenia, and obesity, as well as for adverse birth outcomes. It will be conducted in a nationally representative, prospective cohort of 100,000 US-born children. Children will be followed from conception to 21 years of age. Environmental exposures (chemical, physical, biological, and psychosocial) will be assessed repeatedly during pregnancy and throughout childhood in children's homes, schools, and communities. Chemical assays will be performed by the Centers for Disease Control and Prevention, and banks of biological and environmental samples will be established for future analyses. Genetic material will be collected on each mother and child and banked to permit study of gene-environment interactions. Recruitment is scheduled to begin in 2007 at 7 Vanguard Sites and will extend to 105 sites across the United States. The National Children's Study will generate multiple satellite studies that explore methodologic issues, etiologic questions, and potential interventions. It will provide training for the next generation of researchers and practitioners in environmental pediatrics and will link to planned and ongoing prospective birth cohort studies in other nations. Data from the National Children's Study will guide development of a comprehensive blueprint for disease prevention in children.