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Item Aberrant Neural Activity in Cortico-Striatal-Limbic Circuitry Underlies Behavioral Deficits in a Mouse Model of Neurofibromatosis Type 1(2022-05) Drozd, Hayley Paulina; McKinzie, David L.; Clapp, D. Wade; Shekhar, Anantha; Lukkes, Jodi L.; Lapish, Christopher L.; Block, Michelle L.Nearly 18% of children are diagnosed with developmental disabilities. Autism spectrum disorders (ASDs) and attention deficit hyperactivity disorder (ADHD) are increasingly common developmental disabilities, but neither is well understood. ADHD and ASD are both prevalent in the genetic disorder Neurofibromatosis type 1 (NF1) which impairs the Ras-MAPK/ERK pathway through mutation of the neurofibromin gene (NF1+/−). More broadly, syndromic forms of developmental disorders are often caused by mutations of proteins in pathways interconnected with Ras including TSC1/2, FMR1, and SynGAP. Of NF1 patients, around 30-50% are diagnosed with ASDs and more than 60% with ADHD. These studies are the first to show that male mice haploinsufficient for the Nf1 gene (Nf1+/−) exhibit deficits in behavioral inhibition in multiple contexts, a key feature of ADHD. They exhibit hyperactivity and impulsivity in an open field, delay discounting task, and cliff avoidance reaction test, rescuable through treatment with the clinically effective ADHD drug, guanfacine (α2A adrenergic receptor agonist). Previous experiments in our lab identified social deficits including deficits in consolidation of social memory. Using optogenetics and awake behaving electrode recordings, we explored the role of the cortico-striatal-limbic circuitry in impulsivity and in social deficits in male Nf1+/− mice. Manipulation of the prefrontal cortex, nucleus accumbens, or basolateral amygdala through optogenetics rescued social deficits. These studies are the first to record brain activity in a preclinical model of NF1 during impulsive behavior, finding broad spectrum changes across slow, delta, theta, and gamma oscillatory frequencies and decreased synchrony of the prefrontal cortex and nucleus accumbens during a delay discounting task. Overall, Nf1+/− male mice with deletion of a single NF1 gene recapitulate cognitive phenotypes of NF1 patients and are a useful model system to identify alterations in neural circuitry associated with ASD and ADHD.Item Acceptance of Behavior Guidance Techniques Used in Pediatric Dentistry by Parents From Diverse Backgrounds(Sage, 2019-08) Martinez Mier, E. Angeles; Walsh, Christopher R.; Farah, Christopher C.; Vinson, LaQuia A.; Soto-Rojas, Armando E.; Jones, James E.; Cariology, Operative Dentistry and Dental Public Health, School of DentistryObjective. To investigate if parental background affects acceptance of behavior guidance techniques. Background. Behavior guidance techniques are used for the safe and effective treatment of pediatric patients. Acceptance of these techniques may vary by racial and ethnic background. Methods. A total of 142 parents were recruited and asked to rate videos showing: active restraint/protective stabilization (AR), general anesthesia (GA), nitrous oxide sedation (N2O), oral premedication/sedation (OP), passive restraint/protective stabilization (PR), tell-show-do (TSD), and voice control (VC) techniques. Results. Hispanic parents rated VC most acceptable, followed by TSD, PR, and pharmacologic techniques. Black and white parents rated TSD, followed by N2O, as most acceptable, and AR and PR as least favorable. Hispanics found GA significantly less acceptable than whites or blacks. Hispanics were less accepting of AR than blacks; but more accepting of PR than whites. TSD was highly rated among all 3 cohorts. Parental background affected acceptance of the techniques in this study.Item Acceptance of HIV Testing for Children Ages 18 Months to 13 Years Identified Through Voluntary, Home-Based HIV Counseling and Testing in Western Kenya(2010-10) Vreeman, Rachel C.; Nyandiko, Winstone M.; Braitstein, Paula; Were, Martin C.; Ayaya, Samwel O.; Ndege, Samson K.; Wiehe, Sarah E.Background Home-based, voluntary counseling and testing (HCT) presents a novel approach to early diagnosis. We sought to describe uptake of pediatric HIV testing, associated factors, and HIV prevalence among children offered HCT in Kenya. Methods The USAID-AMPATH Partnership conducted HCT in western Kenya in 2008. Children 18 months to 13 years were offered HCT if their mother was known to be dead, her living status was unknown, mother was HIV-infected or of unknown HIV status. This retrospective analysis describes the cohort of children encountered and tested. Results HCT was offered to 2,289 children and accepted for 1,294 (57%). Children were more likely to be tested if more information was available about a suspected or confirmed maternal HIV-infection (for HIV-infected, living mothers OR=3.20, 95% CI: 1.64–6.23), if parents were not in household (OR=1.50, 95% CI: 1.40–1.63), if they were grandchildren of head of household (OR=4.02, 95% CI: 3.06–5.28), or if their father was not in household (OR=1.41, 95% CI: 1.24–1.56). Of the eligible children tested, 60 (4.6%) were HIV-infected. Conclusions HCT provides an opportunity to identify HIV among high-risk children; however, acceptance of HCT for children was limited. Further investigation is needed to identify and overcome barriers to testing uptake.Item Adolescent transgender health: Awareness does not equal resources(Springer Verlag, 2016-12) Chen, Melinda; Fuqua, John; Pediatrics, School of MedicineItem Association of Extubation Failure Rates With High-Flow Nasal Cannula, Continuous Positive Airway Pressure, and Bilevel Positive Airway Pressure vs Conventional Oxygen Therapy in Infants and Young Children: A Systematic Review and Network Meta-Analysis(American Medical Association, 2023-06-05) Iyer, Narayan Prabhu; Rotta, Alexandre T.; Essouri, Sandrine; Fioretto, Jose Roberto; Craven, Hannah J.; Whipple, Elizabeth C.; Ramnarayan, Padmanabhan; Abu-Sultaneh, Samer; Khemani, Robinder G.IMPORTANCE: Extubation failure (EF) has been associated with worse outcomes in critically ill children. The relative efficacy of different modes of noninvasive respiratory support (NRS) to prevent EF is unknown. OBJECTIVE: To study the reported relative efficacy of different modes of NRS (high-flow nasal cannula [HFNC], continuous positive airway pressure [CPAP], and bilevel positive airway pressure [BiPAP]) compared to conventional oxygen therapy (COT). DATA SOURCES: MEDLINE, Embase, and CINAHL Complete through May 2022. STUDY SELECTION: Randomized clinical trials that enrolled critically ill children receiving invasive mechanical ventilation for more than 24 hours and compared the efficacy of different modes of postextubation NRS. DATA EXTRACTION AND SYNTHESIS: Random-effects models were fit using a bayesian network meta-analysis framework. Between-group comparisons were estimated using odds ratios (ORs) or mean differences with 95% credible intervals (CrIs). Treatment rankings were assessed by rank probabilities and the surface under the cumulative rank curve (SUCRA). MAIN OUTCOMES AND MEASURES: The primary outcome was EF (reintubation within 48 to 72 hours). Secondary outcomes were treatment failure (TF, reintubation plus NRS escalation or crossover to another NRS mode), pediatric intensive care unit (PICU) mortality, PICU and hospital length of stay, abdominal distension, and nasal injury. RESULTS: A total of 11 615 citations were screened, and 9 randomized clinical trials with a total of 1421 participants were included. Both CPAP and HFNC were found to be more effective than COT in reducing EF and TF (CPAP: OR for EF, 0.43; 95% CrI, 0.17-1.0 and OR for TF 0.27, 95% CrI 0.11-0.57 and HFNC: OR for EF, 0.64; 95% CrI, 0.24-1.0 and OR for TF, 0.34; 95% CrI, 0.16- 0.65). CPAP had the highest likelihood of being the best intervention for both EF (SUCRA, 0.83) and TF (SUCRA, 0.91). Although not statistically significant, BiPAP was likely to be better than COT for preventing both EF and TF. Compared to COT, CPAP and BiPAP were reported as showing a modest increase (approximately 3%) in nasal injury and abdominal distension. CONCLUSIONS AND RELEVANCE: The studies included in this systematic review and network meta-analysis found that compared with COT, EF and TF rates were lower with modest increases in abdominal distension and nasal injury. Of the modes evaluated, CPAP was associated with the lowest rates of EF and TF.Item Association of Vitamin E Intake at Early Childhood with Alanine Aminotransferase Levels at Mid-Childhood(Wiley, 2017) Woo Baidal, Jennifer A.; Cheng, Erika R.; Rifas-Shiman, Sheryl L.; Oken, Emily; Gillman, Matthew W.; Taveras, Elsie M.; Pediatrics, School of MedicineThe extent to which vitamin E (alpha-tocopherol) intake early in childhood is associated with alanine aminotransferase (ALT) level later in childhood is unknown. The objective of this research is to test the hypothesis that higher alpha-tocopherol intake during early childhood is associated with lower odds of elevated ALT levels during mid-childhood, and to examine how body mass index (BMI) influences these relationships. We studied 528 children in Project Viva. Mothers reported child dietary intake at early childhood visits (median 3.1 years) using a validated food frequency questionnaire. At mid-childhood (median 7.6 years), we collected child blood and anthropometric data. The main outcome was elevated sex-specific mid-childhood ALT level (≥ 22.1 units/liter for females and ≥ 25.8 units/liter for males). In multivariable logistic regression models, we assessed the association of energy-adjusted alpha-tocopherol intake with ALT levels, adjusting for child age, sex, race/ethnicity, diet, and age-adjusted, sex-specific BMIz at mid-childhood. Among children in this study, 48% were female, 63% were non-Hispanic white, 19% were non-Hispanic black, and 4% Hispanic/Latino. Mean alpha-tocopherol intake was 3.7±1.0 mg/day (range 1.4-9.2) at early childhood. At mid-childhood, mean BMIz was 0.41±1.0 units and 22% had an elevated ALT level. In multivariable-adjusted logistic regression models, children with higher early childhood vitamin E intake had lower odds of elevated mid-childhood ALT [adjusted odds ratio (AOR) 0.62 (95% CI: 0.39-0.99)] for quartiles 2-4 compared with the lowest quartile of intake. Findings persisted after accounting for early childhood diet [0.62 (0.36, 1.08)] and were strengthened after additionally accounting for mid-childhood BMIz [0.56 (0.32, 0.99)]. Conclusion: In this cohort, higher early childhood intake of alpha-tocopherol was associated with lower odds of elevated mid-childhood ALT level.Item Availability of mobile phones for discharge follow-up of pediatric Emergency Department patients in western Kenya(PeerJ, 2015-03) House, Darlene R.; Cheptinga, Philip; Rusyniak, Daniel E.; Department of Emergency Medicine, IU School of MedicineObjective. Mobile phones have been successfully used for Emergency Department (ED) patient follow-up in developed countries. Mobile phones are widely available in developing countries and may offer a similar potential for follow-up and continued care of ED patients in low and middle-income countries. The goal of this study was to determine the percentage of families with mobile phones presenting to a pediatric ED in western Kenya and rate of response to a follow-up phone call after discharge. Methods. A prospective, cross-sectional observational study of children presenting to the emergency department of a government referral hospital in Eldoret, Kenya was performed. Documentation of mobile phone access, including phone number, was recorded. If families had access, consent was obtained and families were contacted 7 days after discharge for follow-up. Results. Of 788 families, 704 (89.3%) had mobile phone access. Of those families discharged from the ED, successful follow-up was made in 83.6% of cases. Conclusions. Mobile phones are an available technology for follow-up of patients discharged from a pediatric emergency department in resource-limited western Kenya.Item Biomechanical Root Cause Analysis of Complications in Head Immobilization Devices for Pediatric Neurosurgery(ASME, 2018-06) Abdulhafez, Moataz; Zaazoue, Mohamed; Kadry, Karim; Goumnerova, Liliana C.; Bedewy, Mostafa; Neurological Surgery, School of MedicinePrecise and firm fixation of the cranium is critical during craniotomy and delicate brain neurosurgery making head immobilization devices (HIDs) a staple instrument in brain neurosurgical operations today. However, despite their popularity, there is no standard procedure for their use and many complications arise from using HIDs in pediatric neurosurgery. In this paper, we identify biomechanical causes of complications and quantify risks in pin-type HIDs including clamping force selection, positioning and age effects. Based on our root cause analysis, we develop a framework to address the biomechanical factors that influence complications and understand the biomechanics of the clamping process. We develop an age-dependent finite element model (FEM) of a single pin on a cranial bone disc with the representative properties and skull thickness depending on age. This model can be utilized to reduce risk of complications by design as well as to provide recommendations for current practices.Item A Bottom-Up Approach in Pediatric Ethics Education: Residents Leading Ethics Curriculum Development - A Pilot Project(2020-03-06) Allison, Lyle; Ali, Sarah; Zeynep, SalihItem Cambridge hybrid closed-loop algorithm in children and adolescents with type 1 diabetes: a multicentre 6-month randomised controlled trial.(Elsevier, 2022-04) Ware, Julia; Boughton, Charlotte K.; Allen, Janet M.; Wilinska, Malgorzata E.; Tauschmann, Martin; Denvir, Louise; Thankamony, Ajay; Campbell, Fiona M.; Wadwa, R. Paul; Buckingham, Bruce A.; Davis, Nikki; DiMeglio, Linda A.; Mauras, Nelly; Besser, Rachel E. J.; Ghatak, Atrayee; Weinzimer, Stuart A.; Hood, Korey K.; Fox, D. Steven; Kanapka, Lauren; Kollman, Craig; Sibayan, Judy; Beck, Roy W.; Hovorka, Roman; Pediatrics, School of MedicineBackground Closed-loop insulin delivery systems have the potential to address suboptimal glucose control in children and adolescents with type 1 diabetes. We compared safety and efficacy of the Cambridge hybrid closed-loop algorithm with usual care over 6 months in this population. Methods In a multicentre, multinational, parallel randomised controlled trial, participants aged 6–18 years using insulin pump therapy were recruited at seven UK and five US paediatric diabetes centres. Key inclusion criteria were diagnosis of type 1 diabetes for at least 12 months, insulin pump therapy for at least 3 months, and screening HbA1c levels between 53 and 86 mmol/mol (7·0–10·0%). Using block randomisation and central randomisation software, we randomly assigned participants to either closed-loop insulin delivery (closed-loop group) or to usual care with insulin pump therapy (control group) for 6 months. Randomisation was stratified at each centre by local baseline HbA1c. The Cambridge closed-loop algorithm running on a smartphone was used with either (1) a modified Medtronic 640G pump, Medtronic Guardian 3 sensor, and Medtronic prototype phone enclosure (FlorenceM configuration), or (2) a Sooil Dana RS pump and Dexcom G6 sensor (CamAPS FX configuration). The primary endpoint was change in HbA1c at 6 months combining data from both configurations. The primary analysis was done in all randomised patients (intention to treat). Trial registration ClinicalTrials.gov, NCT02925299. Findings Of 147 people initially screened, 133 participants (mean age 13·0 years [SD 2·8]; 57% female, 43% male) were randomly assigned to either the closed-loop group (n=65) or the control group (n=68). Mean baseline HbA1c was 8·2% (SD 0·7) in the closed-loop group and 8·3% (0·7) in the control group. At 6 months, HbA1c was lower in the closed-loop group than in the control group (between-group difference −3·5 mmol/mol (95% CI −6·5 to −0·5 [–0·32 percentage points, −0·59 to −0·04]; p=0·023). Closed-loop usage was low with FlorenceM due to failing phone enclosures (median 40% [IQR 26–53]), but consistently high with CamAPS FX (93% [88–96]), impacting efficacy. A total of 155 adverse events occurred after randomisation (67 in the closed-loop group, 88 in the control group), including seven severe hypoglycaemia events (four in the closed-loop group, three in the control group), two diabetic ketoacidosis events (both in the closed-loop group), and two non-treatment-related serious adverse events. There were 23 reportable hyperglycaemia events (11 in the closed-loop group, 12 in the control group), which did not meet criteria for diabetic ketoacidosis. Interpretation The Cambridge hybrid closed-loop algorithm had an acceptable safety profile, and improved glycaemic control in children and adolescents with type 1 diabetes. To ensure optimal efficacy of the closed-loop system, usage needs to be consistently high, as demonstrated with CamAPS FX.