Impact of burnout and professional fulfillment on intent to leave among pediatric physicians: The findings of a quality improvement initiative.

BACKGROUND AND OBJECTIVES: Physician burnout is rampant, and physician retention is increasingly hard. It is unclear how burnout impacts intent to leave an organization. We sought to determine how physician burnout and professional fulfillment impact pediatric physicians' intent to leave (ITL) an organization. DESIGN AND METHODS: We performed 120, 1:1 semi-structured interviews of our pediatric faculty and used the themes therefrom to develop a Likert-scale based, 22-question battery of their current work experience. We created a faculty climate survey by combining those questions with a standardized instrument that assesses burnout and professional fulfillment. We surveyed pediatric and pediatric-affiliated (e.g. pediatric surgery, pediatric psychiatry, etc.) physicians between November 2 and December 9, 2022. We used standard statistical methods to analyze the data. An alpha-level of 0.05 was used to determine significance. RESULTS: A total of 142 respondents completed the survey, 129 (91%) were Department of Pediatrics faculty. Burnout was present in 41% (58/142) of respondents, whereas 30% (42/142) were professionally fulfilled. There was an inverse relationship between professional fulfillment and ITL, p < 0.001 for the trend. Among those who were not professionally fulfilled, the odds ratio of ITL in the next three years was 3.826 [95% CI 1.575-9.291], p = 0.003. There was a direct relationship between burnout and ITL, p < 0.001 for the trend. CONCLUSIONS: Among pediatric physicians, professional fulfillment is strongly, inversely related with ITL in the next three years. Similarly, burnout is directly related with ITL. These data suggest a lack of professional fulfillment and high burnout are strong predictors of pediatric physician turnover.

Synthesis of Tridecacene by Multistep Single-Molecule Manipulation.

Acenes represent a unique class of polycyclic aromatic hydrocarbons that have fascinated chemists and physicists due to their exceptional potential for use in organic electronics. While recent advances in on-surface synthesis have resulted in higher acenes up to dodecacene, a comprehensive understanding of their fundamental properties necessitates their expansion toward even longer homologues. Here, we demonstrate the on-surface synthesis of tridecacene via atom-manipulation-induced conformational preparation and dissociation of a trietheno-bridged precursor on a Au(111) surface. The generated tridecacene has been investigated by scanning tunneling microscopy and spectroscopy (STM/STS), combined with first-principles calculations. We observe that the STS transport gap (1.09 eV) shrinks again following the gap reopening of dodecacene (1.4 eV). Spin-polarized density functional theory calculations confirm an antiferromagnetic open-shell ground-state electronic configuration for tridecacene in the gas phase. Interestingly, tridecacene's open-shell character is significantly reduced upon interaction with the Au(111) surface despite being only physisorbed. The interaction with the surface leads to a lowering of the magnetization of tridecacene, a reduced gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), compared to the gas phase, and a reduced relative energy to the nonmagnetic state, making it nearly isoenergetic. These observations show qualitatively that the influence of the Au(111) substrate on the properties of long acenes is significant, which is important for interpreting the measured STS transport gaps. Our work contributes to a fundamental understanding of the electronic properties of long acenes, confirming a nonmonotonous length-dependent HOMO-LUMO gap, and to the development of multistep tip-assisted synthesis of elusive compounds.

Association of Elevated Serum Aldosterone Concentrations in Pregnancy with Hypertension.

Emerging evidence indicates a previously unrecognized, clinically relevant spectrum of abnormal aldosterone secretion associated with hypertension severity. It is not known whether excess aldosterone secretion contributes to hypertension during pregnancy. We quantified aldosterone concentrations and angiotensin peptides in serum (using liquid chromatography with tandem mass spectrometry) in a cohort of 128 pregnant women recruited from a high-risk obstetrics clinic and followed prospectively for the development of gestational hypertension, pre-eclampsia, superimposed pre-eclampsia, chronic hypertension, or remaining normotensive. The cohort was grouped by quartile of aldosterone concentration in serum measured in the first trimester, and blood pressure, angiotensin peptides, and hypertension outcomes compared across the four quartiles. Blood pressures and body mass index were greatest in the top and bottom quartiles, with the top quartile having the highest blood pressure throughout pregnancy. Further stratification of the top quartile based on increasing (13 patients) or decreasing (19 patients) renin activity over gestation revealed that the latter group was characterized by the highest prevalence of chronic hypertension, use of anti-hypertensive agents, pre-term birth, and intrauterine growth restriction. Serum aldosterone concentrations greater than 704 pmol/L, the 75th percentile defined within the cohort, were evident across all categories of hypertension in pregnancy, including normotensive. These findings suggest that aldosterone excess may underlie the development of hypertension in pregnancy in a significant subpopulation of individuals.

Activation of the Renin-Angiotensin-Aldosterone System Is Attenuated in Hypertensive Compared with Normotensive Pregnancy.

Hypertension during pregnancy increases the risk of adverse maternal and fetal outcomes, but the mechanisms of pregnancy hypertension are not precisely understood. Elevated plasma renin activity and aldosterone concentrations play an important role in the normal physiologic adaptation to pregnancy. These effectors are reduced in patients with pregnancy hypertension, creating an opportunity to define the features of the renin-angiotensin-aldosterone system (RAAS) that are characteristic of this disorder. In the current study, we used a novel LC-MS/MS-based methodology to develop comprehensive profiles of RAAS peptides and effectors over gestation in a cohort of 74 pregnant women followed prospectively for the development of gestational hypertension and pre-eclampsia (HYP, 27 patients) versus those remaining normotensive (NT, 47 patients). In NT pregnancy, the plasma renin activity surrogate, (PRA-S, calculated from the sum of Angiotensin I + Angiotensin II) and aldosterone concentrations significantly increased from the first to the third trimester, accompanied by a modest increase in the concentrations of angiotensin peptide metabolites. In contrast, in HYP pregnancies, PRA-S and angiotensin peptides were largely unchanged over gestation, and third-trimester aldosterone concentrations were significantly lower compared with those in NT pregnancies. The results indicated that the predominant features of pregnancies that develop HYP are stalled or waning activation of the RAAS in the second half of pregnancy (accompanied by unchanging levels of angiotensin peptides) and the attenuated secretion of aldosterone.

Impact of in utero drug exposure on neonates requiring ECMO: A retrospective cohort study.

The incidence of in utero drug exposure (IUDE) and neonatal extracorporeal membrane oxygenation (ECMO) utilization have both increased over the past decade. However, there are no studies to date that examine the impact that IUDE has on neonates requiring ECMO. In this retrospective cohort study, we compared the clinic course and outcomes of neonates who were placed on ECMO with IUDE vs. neonates without IUDE. Analysis included data extracted from medical records from all neonatal ECMO runs between January 2014 and January 2021 at the University of Kentucky Children's Hospital. A total of 56 neonatal patients were placed on ECMO during this time period and there were a total of 57 ECMO runs. Nearly one-third of neonates (16) had documented IUDE. There were no differences in gestational age, length of ECMO run, survival to discharge, or number of major complications while on ECMO in the neonates with IUDE compared to those without. In contrast, greater use of sedative and analgesic adjuvant medications during ECMO was required for IUDE-ECMO cases (p < 0.01). Trending results indicated that post-ECMO feeding complications and total hospitalization length were also greater in the IUDE-ECMO group. These findings illustrate the complex influence of prenatal drug exposures on neonatal patient care and warrant the development of clinical care strategies optimized for this unique patient group.

Ultrasound-guided femoral access in patients with vascular closure devices: a prespecified analysis of the randomised UNIVERSAL trial.

BACKGROUND: Whether ultrasound (US)-guided femoral access compared to femoral access without US guidance decreases access site complications in patients receiving a vascular closure device (VCD) is unclear. AIMS: We aimed to compare the safety of VCD in patients undergoing US-guided versus non-US-guided femoral arterial access for coronary procedures. METHODS: We performed a prespecified subgroup analysis of the UNIVERSAL trial, a multicentre randomised controlled trial of 1:1 US-guided femoral access versus non-US-guided femoral access, stratified for planned VCD use, for coronary procedures on a background of fluoroscopic landmarking. The primary endpoint was a composite of major Bleeding Academic Research Consortium 2, 3 or 5 bleeding and vascular complications at 30 days. RESULTS: Of 621 patients, 328 (52.8%) received a VCD (86% ANGIO-SEAL, 14% ProGlide). In patients who received a VCD, those randomised to US-guided femoral access compared to non-US-guided femoral access experienced a reduction in major bleeding or vascular complications (20/170 [11.8%] vs 37/158 [23.4%], odds ratio [OR] 0.44, 95% confidence interval [CI]: 0.23-0.82). In patients who did not receive a VCD, there was no difference between the US- and non-US-guided femoral access groups, respectively (20/141 [14.2%] vs 13/152 [8.6%], OR 1.76, 95% CI: 0.80-4.03; interaction p=0.004). CONCLUSIONS: In patients receiving a VCD after coronary procedures, US-guided femoral access was associated with fewer bleeding and vascular complications compared to femoral access without US guidance. US guidance for femoral access may be particularly beneficial when VCD are used.

Body mass index percentiles versus body composition assessments: Challenges for disease risk classifications in children.

Background: Identifying at-risk children with optimal specificity and sensitivity to allow for the appropriate intervention strategies to be implemented is crucial to improving the health and well-being of children. We determined relationships of body mass indexes for age and sex percentile (BMI%) classifications to actual body composition using validated and convenient methodologies and compared fat and non-fat mass estimates to normative cut-off reference values to determine guideline reliability. We hypothesized that we would achieve an improved ability to identify at-risk children using simple, non-invasive body composition and index measures. Methods: Cross-sectional study of a volunteer convenience sample of 1,064 (537 boys) young children comparing Body Fat Percentage (BF%), Fat Mass Index (FMI), Fat-Free Mass Index (FFMI), determined via rapid bioimpedance methods vs. BMI% in children. Comparisons determined among weight classifications and boys vs. girls. Results: Amongst all subjects BMI% was generally correlated to body composition measures and indexes but nearly one quarter of children in the low-risk classifications (healthy weight or overweight BMI%) had higher BF% and/or lower FFMI than recommended standards. Substantial evidence of higher than expected fatness and or sarcopenia was found relative to risk status. Inaccuracies were more common in girls than boys and girls were found to have consistently higher BF% at any BMI%. Conclusions: The population studied raises concerns regarding actual risks for children of healthy or overweight categorized BMI% since many had higher than expected BF% and potential sarcopenia. When body composition and FMI and FFMI are used in conjunction with BMI% improved sensitivity, and accuracy of identifying children who may benefit from appropriate interventions results. These additional measures could help guide clinical decision making in settings of disease-risks stratifications and interventions.

Routine Ultrasonography Guidance for Femoral Vascular Access for Cardiac Procedures: The UNIVERSAL Randomized Clinical Trial.

Importance: A significant limitation of femoral artery access for cardiac interventions is the increased risk of vascular complications and bleeding compared with radial access. Strategies to make femoral access safer are needed. Objective: To determine whether routinely using ultrasonography guidance for femoral arterial access for coronary angiography/intervention reduces bleeding or vascular complications. Design, Setting, and Participants: The Routine Ultrasound Guidance for Vascular Access for Cardiac Procedures (UNIVERSAL) randomized clinical trial is a multicenter, prospective, open-label trial of ultrasonography-guided femoral access vs no ultrasonography for coronary angiography or intervention with planned femoral access. Patients were randomized from June 26, 2018, to April 26, 2022. Patients with ST-elevation myocardial infarction were not eligible. Interventions: Ultrasonography guidance vs no ultrasonography guidance for femoral arterial access on a background of fluoroscopic landmarking. Main Outcomes and Measures: The primary composite outcome is the composite of major bleeding based on the Bleeding Academic Research Consortium 2, 3, or 5 criteria or major vascular complications within 30 days. Results: A total of 621 patients were randomized at 2 centers in Canada (mean [SD] age, 71 [10.24] years; 158 [25.4%] female). The primary outcome occurred in 40 of 311 patients (12.9%) in the ultrasonography group vs 50 of 310 patients (16.1%) without ultrasonography (odds ratio, 0.77 [95% CI, 0.49-1.20]; P = .25). The rates of Bleeding Academic Research Consortium 2, 3, or 5 bleeding were 10.0% (31 of 311) vs 10.7% (33 of 310) (odds ratio, 0.93 [95% CI, 0.55-1.56]; P = .78). The rates of major vascular complications were 6.4% (20 of 311) vs 9.4% (29 of 310) (odds ratio, 0.67 [95% CI, 0.37-1.20]; P = .18). Ultrasonography improved first-pass success (277 of 311 [86.6%] vs 222 of 310 [70.0%]; odds ratio, 2.76 [95% CI, 1.85-4.12]; P < .001) and reduced the number of arterial puncture attempts (mean [SD], 1.2 [0.5] vs 1.4 [0.8]; mean difference, -0.26 [95% CI, -0.37 to -0.16]; P < .001) and venipuncture (10 of 311 [3.1%] vs 37 of 310 [11.7%]; odds ratio, 0.24 [95% CI, 0.12-0.50]; P < .001) with similar times to access (mean [SD], 114 [185] vs 129 [206] seconds; mean difference, -15.1 [95% CI, -45.9 to 15.8]; P = .34). All prerandomization prespecified subgroups were consistent with the overall finding. Conclusions and Relevance: In this randomized clinical trial, use of ultrasonography for femoral access did not reduce bleeding or vascular complications. However, ultrasonography did reduce the risk of venipuncture and number of attempts. Larger trials may be required to demonstrate additional potential benefits of ultrasonography-guided access. Trial Registration: ClinicalTrials.gov Identifier: NCT03537118.

Synthesis of the [11]Cyclacene Framework by Repetitive Diels-Alder Cycloadditions.

The Diels-Alder cycloaddition between bisdienes and bisdienophile incorporating the 7-oxa-bicyclo[2.2.1]heptane unit are well known to show high diastereoselectivity that can be exploited for the synthesis of molecular belts. The related bisdiene 5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octene is a valuable building block for the synthesis of photoprecursors for acenes, but it has not been employed for the synthesis of molecular belts. The present work investigates by computational means the Diels-Alder reaction between these bisdiene building blocks with syn-1,4,5,8-tetrahydro-1,4:5,8-diepoxyanthracene, which shows that the diastereoselectivity of the Diels-Alder reaction of the etheno-bridged bisdiene is lower than that of the epoxy-bridged bisdiene. The reaction of the etheno-bridged bisdiene and syn-1,4,5,8-tetrahydro-1,4:5,8-diepoxyanthracene in 2:1 ratio yields two diastereomers that differ in the orientation of the oxa and etheno bridges based on NMR and X-ray crystallography. The all-syn diastereomer can be transformed into a molecular belt by inter- and intramolecular Diels-Alder reactions with a bifunctional building block. The molecular belt could function as a synthetic intermediate en route to a [11]cyclacene photoprecursor.

Impact of Pediatric Obesity on Diurnal Blood Pressure Assessment and Cardiovascular Risk Markers.

Background: The prevalence of hypertension is increasing particularly among obese children and adolescents. Obese children and adolescents with hypertension are likely to remain hypertensive as they reach adulthood and hypertension is linked to an increased risk for cardiovascular disease. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) has become one of the most important tools in diagnosing hypertension in children and adolescents and circadian patterns of blood pressure may be important disease-risk predictors. Methods: A retrospective chart review was conducted in patients aged 6-21 years who underwent 24-h ABPM at Kentucky Children's Hospital (KCH) from August 2012 through June 2017. Exclusion criteria included conditions that could affect blood pressure including chronic kidney disease and other renal abnormalities, congenital heart disease, cancer, and thyroid disease. Subjects were categorized by body mass index into normal (below 85th percentile), overweight (85th-95th percentile), stage I obesity (95th-119th percentile), stage II obesity (120th-139th) and stage III obesity (>140th). Non-dipping was defined as a nocturnal BP reduction of <10%. Results: Two hundred and sixty-three patients (156 male patients) were included in the analysis, of whom 70 were normal weight, 33 overweight, 55 stage I obesity, 53 stage II, and 52 stage III obesity. Although there was no significant difference between normal weight and obese groups for prevalence of hypertension, there was a greater prevalence of SBP non-dipping in obese patients as BMI increased (p = 0.008). Furthermore, non-dippers had a significantly elevated LVMI as well as abnormal lab values for uric acid, blood lipid panel, creatinine, and TSH (p < 0.05). Conclusions: These findings demonstrate that obese children and adolescents constitute a large proportion of hypertensive children and adolescents and the severity of pediatric obesity is associated with nocturnal BP non-dipping. Additionally, obesity in children is linked to several cardiovascular risk factors including left ventricular hypertrophy, dyslipidemia, and elevated uric acid levels. Further studies utilizing ABPM measures on risk stratification in this very high-risk population are warranted.

Intermittent Hypoxemia in Preterm Infants: A Potential Proinflammatory Process.

OBJECTIVE: A major consequence of prematurity is intermittent hypoxemia (IH). Data from both adult studies and neonatal animal models suggest that IH is proinflammatory; however, there is limited data in preterm infants. Here, we assess the relationship between IH and systemic inflammation, namely, serum C-reactive protein (CRP) in preterm infants. STUDY DESIGN: Serum CRP was measured at 30 days of life, at the time of peak IH frequency. IH measures (e.g., per cent time in hypoxemia, frequency, duration) were calculated the week prior to CRP collection. Statistical analyses were based on Spearman's correlation. RESULTS: A total of 26 infants were included. Median gestational age and birth weight were 274/7 weeks and 980 g, respectively. There were positive correlations between primary IH measures and CRP levels, especially for events longer than 1-minute duration (r range: 0.56-0.74, all p < 0.01). CONCLUSION: We demonstrate that IH is associated with increased CRP for the first time in preterm infants. Our findings are consistent with studies from adults and neonatal animal models suggesting that IH is a proinflammatory process. KEY POINTS: · IH events are common.. · IH is associated with elevated C-reactive protein.. · Longer IH events (>1 min) are of most significance..

Investigations of an inducible intact dystrophin gene excision system in cardiac and skeletal muscle in vivo.

We sought here to induce the excision of a large intragenic segment within the intact dystrophin gene locus, with the ultimate goal to elucidate dystrophin protein function and stability in striated muscles in vivo. To this end, we implemented an inducible-gene excision methodology using a floxed allele approach, demarcated by dystrophin exons 2-79, in complementation with a cardiac and skeletal muscle directed gene deletion system for spatial-temporal control of dystrophin gene excision in vivo. Main findings of this study include evidence of significant intact dystrophin gene excision, ranging from ~ 25% in heart muscle to ~ 30-35% in skeletal muscles in vivo. Results show that despite evidence of significant dystrophin gene excision, no significant decrease in dystrophin protein content was evident by Western blot analysis, at three months post excision in skeletal muscles or by 6 months post gene excision in heart muscle. Challenges of in vivo dystrophin gene excision revealed acute deleterious effects of tamoxifen on striated muscles, including a transient down regulation in dystrophin gene transcription in the absence of dystrophin gene excision. In addition, technical limitations of incomplete dystrophin gene excision became apparent that, in turn, tempered interpretation. Collectively, these findings are in keeping with earlier studies suggesting the dystrophin protein to be long-lived in striated muscles in vivo; however, more rigorous quantitative analysis of dystrophin stability in vivo will require future works in which more complete gene excision can be demonstrated, and without significant off-target effects of the gene deletion experimental platform per se.

Serum untargeted metabolomic changes in response to diet intervention in dogs with preclinical myxomatous mitral valve disease.

Myocardial energy deprivation plays a causal role in the development of heart failure. A cardiac protection blend (CPB) of nutrients including medium chain triglycerides, fish oil and other key nutrients was developed to slow the progression of canine myxomatous mitral valve disease (MMVD). A six-month dietary intervention demonstrated efficacy of CPB in slowing MMVD progression. Untargeted metabolomic analysis of serum from these dogs identified 102 differential metabolites (adjusted P < 0.05). The ratios of omega-6 to omega-3 fatty acid (FA) changed from 2.41 and 1.46 in control and CPB groups at baseline to 4.30 and 0.46 at 6 months respectively. A 2.7-fold increase of α-aminobutyrate, a myocardial modulator of glutathione homeostasis, was found in CPB dogs compared to 1.3-fold increase in control dogs. Arginine and citrulline, precursors of nitric oxide biosynthesis, were both increased 2-fold; caprate, a medium chain FA, was increased 3-fold; and deoxycarnitine, precursor of carnitine biosynthesis, was increased 2.5-fold in CPB dogs. Margarate and methylpalmitate decreased in response to CPB, a potential benefit in MMVD dogs as positive correlations were found between changes in both these FAs and left atrial diameter (r = 0.69, r = 0.87 respectively, adjusted P < 0.05). Sphingomyelins with very long chain saturated FAs associated with decreased risk of heart failure in humans were increased in MMVD dogs fed the CPB diet. Our data supports the hypothesis that CPB improves FA utilization and energetics, reduces oxidative stress and inflammation in MMVD dogs. More studies are needed to understand the roles of specific metabolites in MMVD.

Aromatherapy as an adjunctive therapy for neonatal abstinence syndrome: A pilot study.

OBJECTIVE: To determine if aromatherapy added to the current standard of care for opioid withdrawal syndrome decreases hospitali-zation and need for opioid replacement in neonates. DESIGN: Nonblinded, randomized control trial. SETTING: Level 4 neonatal intensive care unit (NICU). PATIENTS AND PARTICIPANTS: Thirty eight patients met inclusion criteria of greater than or equal to 36 weeks of gestation, history of in-trauterine opioid exposure, primary diagnosis of neonatal abstinence syndrome (NAS), and parental permission to participate. INTERVENTIONS: Infants were randomized to either a standard therapy group or a standard therapy plus aromatherapy. MAIN OUTCOME MEASURE(S): Duration of therapy and length of stay. RESULTS: Our pilot study showed that the use of aromatherapy in conjunction with standard therapy reduced the duration of medica-tion treatment by 41 percent and hospital length of stay in the NICU by 36 percent. CONCLUSIONS: The use of aromatherapy appears to help mitigate symptoms of NAS and offers to be a viable treatment modality when used with conventional therapy.

Acute kidney injury, fluid balance and risks of intraventricular hemorrhage in premature infants.

OBJECTIVE: Evaluate association between fluid balance and intraventricular hemorrhage (IVH). STUDY DESIGN: Retrospective review of infants <30 weeks gestation admitted to Kentucky Children's Hospital Neonatal Intensive Care Unit. RESULTS: Infants with acute kidney injury (AKI) had a 2.4-fold increased risk of IVH (OR 2.38, 95% CI 1.46-3.87) and a 3.5-fold increased risk of severe IVH (OR 3.45, 95% CI 1.98-6.04). Infants above birthweight on day 4 had a 1.9-fold increased risk of IVH (OR 1.86, 95% CI 1.05-3.27) and a 2.0-fold increased risk of severe IVH (OR 1.96, 95% CI 1.03-3.74). When controlling for confounding factors, infants with AKI or above birthweight on day 4 had a 4.6-fold (aOR 4.60, 95% CI 1.80-11.78) and 3.0-fold (aOR 2.96, 95% CI 1.01-8.65) increased risk of severe IVH, respectively. CONCLUSION: Infants with AKI during the first week of life had a higher association of severe IVH even after controlling for confounding factors.

Case series of therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy during extracorporeal life support.

Therapeutic hypothermia initiated within 6 hours of birth is currently the standard of care for the management of neonates with hypoxic-ischemic encephalopathy. Neonates undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy are also at risk for severe respiratory failure and need for extracorporeal life support. The risks and benefits of therapeutic hypothermia for hypoxic-ischemic encephalopathy during extracorporeal life support are still not well defined. We report our experience of a case series of six neonates who underwent therapeutic hypothermia for hypoxic-ischemic encephalopathy during extracorporeal life support. We also report long-term neurodevelopmental follow-up from 6 to 24 months and add to the current body of evidence regarding feasibility, clinical experience, and short-term complications.

Secondhand Smoke Exposure and Sleep-Related Breathing Problems in Toddlers.

BACKGROUND: Adequate sleep during childhood is an important component of overall health and wellbeing for children. Secondhand smoke (SHS) exposure has been linked to a greater risk of sleep-disordered breathing. OBJECTIVE: Our objective was to investigate relationships between SHS exposure and sleep-related breathing problems in healthy toddlers aged 2 to 5 years. We hypothesized that there is an independent relationship between objectively measured SHS exposure and presence of sleep-related breathing problems by parental report. METHODS: A convenience sample of 149 healthy children ages 2 to 5 years was recruited from an academic pediatric primary care center for this cross-sectional study; 138 had complete data that were analyzed. Current SHS exposure was determined by hair nicotine level. Presence of sleep-related breathing problems was assessed by 1 survey item. Inflammation was determined by serum C-reactive protein (CRP) level. Analysis in Stata 15 included a series of multivariate logistic regression models, controlling for individual-level demographics and body mass index z scores according to mediation analysis procedures for dichotomous outcomes. RESULTS: Approximately 24% of parents reported their child snored, gasped, or had difficulty breathing at night sometimes, most of the time, or almost always. Regression models with mediation analysis indicate that SHS exposure significantly increased the odds of reporting the child had sleep-related breathing problems, and 18% of this relationship is explained by log serum CRP levels. CONCLUSIONS: Although the cross-sectional nature of this study limits causality, evidence suggests a relationship exists between SHS exposure, as measured by log hair nicotine and sleep-related breathing problems at night.

CANDLE/Supervisor: a workflow framework for machine learning applied to cancer research.

BACKGROUND: Current multi-petaflop supercomputers are powerful systems, but present challenges when faced with problems requiring large machine learning workflows. Complex algorithms running at system scale, often with different patterns that require disparate software packages and complex data flows cause difficulties in assembling and managing large experiments on these machines. RESULTS: This paper presents a workflow system that makes progress on scaling machine learning ensembles, specifically in this first release, ensembles of deep neural networks that address problems in cancer research across the atomistic, molecular and population scales. The initial release of the application framework that we call CANDLE/Supervisor addresses the problem of hyper-parameter exploration of deep neural networks. CONCLUSIONS: Initial results demonstrating CANDLE on DOE systems at ORNL, ANL and NERSC (Titan, Theta and Cori, respectively) demonstrate both scaling and multi-platform execution.

Plasma Brain-Derived Neurotrophic Factor Levels in Newborn Infants with Neonatal Abstinence Syndrome.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a type of growth factor that promotes growth and survival of neurons. Fetal exposure to opiates can lead to postnatal withdrawal syndrome, which is referred as neonatal abstinence syndrome (NAS). Preclinical and clinical studies have shown an association between opiates exposure and alteration in BDNF expression in the brain and serum levels in adult. However, to date, there are no data available on the effects of opiate exposure on BDNF levels in infant who are exposed to opiates in utero and whether BDNF level may correlate with the severity of NAS. OBJECTIVE: To compare plasma BDNF levels among NAS and non-NAS infants and to determine the correlation of BDNF levels and the severity of NAS. METHODS: This is a prospective cohort study with no intervention involved. Infants ≥35 weeks of gestation were enrolled. BDNF level was measured using enzyme-linked immunosorbent assay technique from blood samples drawn within 48 h of life. The severity of NAS was determined by the length of hospital stay, number of medications required to treat NAS. RESULTS: 67 infants were enrolled, 34 NAS and 33 non-NAS. Mean gestational age did not differ between the two groups. Mean birth weight of NAS infants was significantly lower than the non-NAS infants (3,070 ± 523 vs. 3,340 ± 459 g, p = 0.028). Mean BDNF level in NAS group was 252.2 ± 91.6 ng/ml, significantly higher than 211.3 ± 66.3 ng/ml in the non-NAS group (p = 0.04). There were no differences in BDNF levels between NAS infants that required one medication vs. more than one medication (254 ± 91 vs. 218 ± 106 ng/ml, p = 0.47). There was no correlation between the BDNF levels and length of hospital stay (p = 0.68) among NAS infants. Overall, there were no significant correlations between BDNF levels and NAS scores except at around 15 h after admission (correlation 0.35, p = 0.045). CONCLUSION: Plasma BDNF level was significantly increased in NAS infants during the first 48 h when compared to non-NAS infants. The correlations between plasma BDNF levels and the severity of NAS warrant further study. These results suggest that BDNF may play a neuromodulatory role during withdrawal after in utero opiate exposure.

Neurological consequences of systemic inflammation in the premature neonate.

Despite substantial progress in neonatal care over the past two decades leading to improved survival of extremely premature infants, extreme prematurity continues to be associated with long term neurodevelopmental impairments. Cerebral white matter injury is the predominant form of insult in preterm brain leading to adverse neurological consequences. Such brain injury pattern and unfavorable neurologic sequelae is commonly encountered in premature infants exposed to systemic inflammatory states such as clinical or culture proven sepsis with or without evidence of meningitis, prolonged mechanical ventilation, bronchopulmonary dysplasia, necrotizing enterocolitis and chorioamnionitis. Underlying mechanisms may include cytokine mediated processes without direct entry of pathogens into the brain, developmental differences in immune response and complex neurovascular barrier system that play a critical role in regulating the cerebral response to various systemic inflammatory insults in premature infants. Understanding of these pathologic mechanisms and clinical correlates of such injury based on serum biomarkers or brain imaging findings on magnetic resonance imaging will pave way for future research and translational therapeutic opportunities for the developing brain.