Jupiter's Low-Altitude Auroral Zones: Fields, Particles, Plasma Waves, and Density Depletions.

The Juno spacecraft's polar orbits have enabled direct sampling of Jupiter's low-altitude auroral field lines. While various data sets have identified unique features over Jupiter's main aurora, they are yet to be analyzed altogether to determine how they can be reconciled and fit into the bigger picture of Jupiter's auroral generation mechanisms. Jupiter's main aurora has been classified into distinct "zones", based on repeatable signatures found in energetic electron and proton spectra. We combine fields, particles, and plasma wave data sets to analyze Zone-I and Zone-II, which are suggested to carry upward and downward field-aligned currents, respectively. We find Zone-I to have well-defined boundaries across all data sets. H+ and/or H3 + cyclotron waves are commonly observed in Zone-I in the presence of energetic upward H+ beams and downward energetic electron beams. Zone-II, on the other hand, does not have a clear poleward boundary with the polar cap, and its signatures are more sporadic. Large-amplitude solitary waves, which are reminiscent of those ubiquitous in Earth's downward current region, are a key feature of Zone-II. Alfvénic fluctuations are most prominent in the diffuse aurora and are repeatedly found to diminish in Zone-I and Zone-II, likely due to dissipation, at higher altitudes, to energize auroral electrons. Finally, we identify significant electron density depletions, by up to 2 orders of magnitude, in Zone-I, and discuss their important implications for the development of parallel potentials, Alfvénic dissipation, and radio wave generation.

Immuno-transcriptomic profiling of extracranial pediatric solid malignancies.

We perform an immunogenomics analysis utilizing whole-transcriptome sequencing of 657 pediatric extracranial solid cancer samples representing 14 diagnoses, and additionally utilize transcriptomes of 131 pediatric cancer cell lines and 147 normal tissue samples for comparison. We describe patterns of infiltrating immune cells, T cell receptor (TCR) clonal expansion, and translationally relevant immune checkpoints. We find that tumor-infiltrating lymphocytes and TCR counts vary widely across cancer types and within each diagnosis, and notably are significantly predictive of survival in osteosarcoma patients. We identify potential cancer-specific immunotherapeutic targets for adoptive cell therapies including cell-surface proteins, tumor germline antigens, and lineage-specific transcription factors. Using an orthogonal immunopeptidomics approach, we find several potential immunotherapeutic targets in osteosarcoma and Ewing sarcoma and validated PRAME as a bona fide multi-pediatric cancer target. Importantly, this work provides a critical framework for immune targeting of extracranial solid tumors using parallel immuno-transcriptomic and -peptidomic approaches.

Genomic and Transcriptomic Analysis of Relapsed and Refractory Childhood Solid Tumors Reveals a Diverse Molecular Landscape and Mechanisms of Immune Evasion.

Children with treatment-refractory or relapsed (R/R) tumors face poor prognoses. As the genomic underpinnings driving R/R disease are not well defined, we describe here the genomic and transcriptomic landscapes of R/R solid tumors from 202 patients enrolled in Beat Childhood Cancer Consortium clinical trials. Tumor mutational burden (TMB) was elevated relative to untreated tumors at diagnosis, with one-third of tumors classified as having a pediatric high TMB. Prior chemotherapy exposure influenced the mutational landscape of these R/R tumors, with more than 40% of tumors demonstrating mutational signatures associated with platinum or temozolomide chemotherapy and two tumors showing treatment-associated hypermutation. Immunogenomic profiling found a heterogenous pattern of neoantigen and MHC class I expression and a general absence of immune infiltration. Transcriptional analysis and functional gene set enrichment analysis identified cross-pathology clusters associated with development, immune signaling, and cellular signaling pathways. While the landscapes of these R/R tumors reflected those of their corresponding untreated tumors at diagnosis, important exceptions were observed, suggestive of tumor evolution, treatment resistance mechanisms, and mutagenic etiologies of treatment. SIGNIFICANCE: Tumor heterogeneity, chemotherapy exposure, and tumor evolution contribute to the molecular profiles and increased mutational burden that occur in treatment-refractory and relapsed childhood solid tumors.

Biomanufacturing of value-added products from oils or fats: A case study on cellular and fermentation engineering of Yarrowia lipolytica.

The United States produces more than 10 million tons of waste oils and fats each year. This paper aims to establish a new biomanufacturing platform that converts waste oils or fats into a series of value-added products. Our research employs the oleaginous yeast Yarrowia lipolytica as a case study for citric acid (CA) production from waste oils. First, we conducted the computational fluid dynamics (CFD) simulation of the bioreactor system and identified that the extracellular mixing and mass transfer is the first limiting factor of an oil fermentation process due to the insolubility of oil in water. Based on the CFD simulation results, the bioreactor design and operating conditions were optimized and successfully enhanced oil uptake and bioconversion in fed-batch fermentation experiments. After that, we investigated the impacts of cell morphology on oil uptake, intracellular lipid accumulation, and CA formation by overexpressing and deleting the MHY1 gene in the wild type Y. lipolytica ATCC20362. Fairly good linear correlations (R2 > 0.82) were achieved between cell morphology and productivities of biomass, lipid, and CA. Finally, fermentation kinetics with both glucose and oil substrates were compared and the oil fermentation process was carefully evaluated. Our study suggests that waste oils or fats can be economical feedstocks for biomanufacturing of many high-value products.

AVIA 3.0: interactive portal for genomic variant and sample level analysis.

SUMMARY: The Annotation, Visualization and Impact Analysis (AVIA) is a web application combining multiple features to annotate and visualize genomic variant data. Users can investigate functional significance of their genetic alterations across samples, genes and pathways. Version 3.0 of AVIA offers filtering options through interactive charts and by linking disease relevant data sources. Newly incorporated services include gene, variant and sample level reporting, literature and functional correlations among impacted genes, comparative analysis across samples and against data sources such as TCGA and ClinVar, and cohort building. Sample and data management is now feasible through the application, which allows greater flexibility with sharing, reannotating and organizing data. Most importantly, AVIA's utility stems from its convenience for allowing users to upload and explore results without any a priori knowledge or the need to install, update and maintain software or databases. Together, these enhancements strengthen AVIA as a comprehensive, user-driven variant analysis portal. AVAILABILITYAND IMPLEMENTATION: AVIA is accessible online at https://avia-abcc.ncifcrf.gov.

Comparing Electron Energetics and UV Brightness in Jupiter's Northern Polar Region During Juno Perijove 5.

We compare electron and UV observations mapping to the same location in Jupiter's northern polar region, poleward of the main aurora, during Juno perijove 5. Simultaneous peaks in UV brightness and electron energy flux are identified when observations map to the same location at the same time. The downward energy flux during these simultaneous observations was not sufficient to generate the observed UV brightness; the upward energy flux was. We propose that the primary acceleration region is below Juno's altitude, from which the more intense upward electrons originate. For the complete interval, the UV brightness peaked at ~240 kilorayleigh (kR); the downward and upward energy fluxes peaked at 60 and 700 mW/m2, respectively. Increased downward energy fluxes are associated with increased contributions from tens of keV electrons. These observations provide evidence that bidirectional electron beams with broad energy distributions can produce tens to hundreds of kilorayleigh polar UV emissions.

Juno-UVS approach observations of Jupiter's auroras.

Juno ultraviolet spectrograph (UVS) observations of Jupiter's aurora obtained during approach are presented. Prior to the bow shock crossing on 24 June 2016, the Juno approach provided a rare opportunity to correlate local solar wind conditions with Jovian auroral emissions. Some of Jupiter's auroral emissions are expected to be controlled or modified by local solar wind conditions. Here we compare synoptic Juno-UVS observations of Jupiter's auroral emissions, acquired during 3-29 June 2016, with in situ solar wind observations, and related Jupiter observations from Earth. Four large auroral brightening events are evident in the synoptic data, in which the total emitted auroral power increases by a factor of 3-4 for a few hours. Only one of these brightening events correlates well with large transient increases in solar wind ram pressure. The brightening events which are not associated with the solar wind generally have a risetime of ~2 h and a decay time of ~5 h.

Jupiter's interior and deep atmosphere: The initial pole-to-pole passes with the Juno spacecraft.

On 27 August 2016, the Juno spacecraft acquired science observations of Jupiter, passing less than 5000 kilometers above the equatorial cloud tops. Images of Jupiter's poles show a chaotic scene, unlike Saturn's poles. Microwave sounding reveals weather features at pressures deeper than 100 bars, dominated by an ammonia-rich, narrow low-latitude plume resembling a deeper, wider version of Earth's Hadley cell. Near-infrared mapping reveals the relative humidity within prominent downwelling regions. Juno's measured gravity field differs substantially from the last available estimate and is one order of magnitude more precise. This has implications for the distribution of heavy elements in the interior, including the existence and mass of Jupiter's core. The observed magnetic field exhibits smaller spatial variations than expected, indicative of a rich harmonic content.

[Reasons for low usage of strep A rapid antigen detection tests for pharyngitis in private medical practice]. / Motifs de la mauvaise utilisation des tests de diagnostic rapide du streptocoque de groupe A en médecine libérale.

UNLABELLED: Rapid group A Streptococcus (GAS) antigen detection tests (RDT) have high diagnostic performance for the management of acute pharyngitis and are recommended before any antibiotic (ATB) prescription in France to reduce ATB use. The rate of general practitioners (GPs) using GAS RDT is low and decreasing. Our aims were to describe the reasons for pediatricians and GPs not using RDT or for prescribing ATB despite of a negative RDT. METHODS: In 2011, a survey was conducted in a random sample of 368 GPs plus all ambulatory pediatricians (n=82) in the Nord-Pas-de-Calais region of France. RESULTS: Response rates were 74% (n=61) for pediatricians and 18% (n=68) for GPs. RDTs for pharyngitis were used by 75% [95% CI: 63-85] of pediatricians and 53% [95% CI: 41-64] of GPs (P<0.001). RDTs were systematically used in children 3years of age and older by only 59% of all physicians using RDTs. An ATB was systematically prescribed in case of positive RDT by 96% of physicians and eventually prescribed in case of negative RDT by 74%. The main reasons for ATB prescription in case of negative RDT were association with otitis media (51%), second visit for the same pharyngitis (45%), and high clinical suspicion of GAS pharyngitis (36%). Forty percent of non-RDT users had used them in the past. The 3 main reasons for not using RDT were the lack of time (57%), high confidence in clinical data to discriminate GAS pharyngitis (48%), and low confidence in RDT (27%). DISCUSSION: This survey highlights the lack of knowledge about low and high discriminant values of clinical data and RDT, respectively, especially the excellent negative predictive value of RDTs, and an erroneous assessment of the low risk of missing GAS pharyngitis compared to the consequences of inappropriate ATB use.

[Systemic adverse effects of topical ocular instillation of atropine in two children]. / Effets systémiques des collyres mydriatiques atropiniques chez deux enfants.

A medication-related cause must be sought when unusual symptoms occur. Topical treatments, including eye drops, whose side effects are more common in exposed children, need to be verified. We report here the cases of two children who developed systemic symptoms after the administration of atropine-based mydriatic eye drops. A 6-month-old boy was admitted to the emergency department with acute urine retention lasting 36h. Investigations identified only eye drop treatment 3h before the onset of symptoms, with 2 drops of homatropine 1 %, as a cause. No other urinary retention was observed during the 1-year follow-up. A 2-year-old boy was admitted to the emergency department for drowsiness, thirst, and dry mouth 30min after the administration of three eye drops of atropine 1 % instead of atropine 0.3 % (error made by the pharmacy). Symptoms disappeared after 6h. Both observations highlight the possible side effects related to mydriatic eye drops. Indeed, because of small penetration of such medications in the eye, a high concentration of the active part of the medication is contained in each drop. In young children, at least 20 to 40 % of the volume of a drop drains into the nasolacrimal duct and thereby into the systemic circulation, without passage through the liver. A close national pharmacologic vigilance follow-up has been set up for atropine-based mydriatic eye drops in young children, who are the most exposed to systemic and potentially severe complications of these medications. We emphasize the appropriate procedure for the use of eye drops in young children to limit systemic passage, with only a 0.3 % maximum atropine concentration in infants, compression of the internal angle of the eye for at least 1min, and at least a 15-mins interval between two eye drop administrations.

Impact of travel on the seroprevalence of hepatitis A in children.

BACKGROUND: Recent data about hepatitis A virus (HAV) seroprevalence in industrialized countries and the impact of travels to endemic areas are sparse or absent, particularly for children. OBJECTIVE: To determine the impact of travel to endemic areas on HAV seroprevalence and estimate the overall HAV seroprevalence in children in France. To identify risk factors for positive HAV serologic results. STUDY DESIGN: This prospective multicentre cross-sectional seroprevalence study took place in eight paediatric emergency units throughout France. Children 1-16 years of age following all inclusion and exclusion criteria were included. Demographic, socioeconomic, and travel data were prospectively collected with a standardized questionnaire before measurement of specific HAV antibodies. HAV seroprevalence was determined and its association with diverse variables assessed by univariate and multivariate analyses. RESULTS: 430 children were included, of whom 116 had travelled to endemic areas. The HAV seroprevalence in the overall population was 5% (95%CI, 3-7) and was higher among the travellers (12% [95%CI, 6-18]) than among the others (2% [95%CI, 0-3]), OR=7.0 [95%CI, 2.6-18.8]. Risk factors identified for positive serologic results for HAV were travel to an endemic area >7 days (adjusted OR [aOR]=4.3 [95%CI, 1.5-12]), age of 14-16 years (aOR=7.7 [95%CI, 1.6-38.3]) and mother's birth in an endemic area (aOR=5.2 [95%CI, 1.8-14.8]). CONCLUSION: Statistical evidence showed that travel to endemic areas and parents' place of birth both play a role in HAV serologic results in children with a significant difference of HAV seroprevalence between traveller and non-traveller children in France.

Effectiveness of multifunction paediatric short-stay units: a French multicentre study.

AIM: To describe the characteristics of the activities of multifunction paediatric 'short-stay units' (SSU) including observation unit (OU), medical assessment and planning unit (MAPU) and holding unit (HU), to evaluate their effectiveness and to explore predictors of inappropriate admissions for OU patients. METHODS: Admissions to nine French paediatric SSUs were analysed. The main outcome measures were SSU length of stay with associated outcome for all patients and appropriate admission rate for OU patients. RESULTS: Of 1084 patients included in the study, 66% were OU patients (n = 718), 21% MAPU patients (n = 225) and 13% HU patients (n = 141). The OU patients constituted the majority of the SSU admissions. The appropriate OU admission rates ranged from 52% to 86%. Head trauma and seizure were the conditions with the highest appropriate OU admission rates (82%). Age <1 year, and need for IV fluids or medications, CT-Scan or MRI and cardiorespiratory monitoring were associated with an increased risk of inappropriate OU admission. Eighteen per cent of the MAPU patients and 5% of the HU patients were discharged home within 24 h. CONCLUSION: By providing extended and easily available facilities for diagnostics and early treatment for a wide range of sick children, the French paediatric SSU is an effective model for 'observation medicine' in emergency department-managed units. The experience and principles may be applicable to similar units in other health care systems.

[Organization and resource utilization of pediatric emergency care: a French nationwide survey in 2008]. / Organisation et moyens de l'accueil des urgences pédiatriques : enquête nationale française en 2008.

UNLABELLED: Organization and resource utilization of pediatric emergency departments (PEDs) have been poorly evaluated. OBJECTIVES: To assess the access to appropriate pediatric emergency care in France and the degree of preparedness of PEDs and general emergency departments (GEDs) without separate pediatric emergency facilities. METHODS: A closed-response survey was e-mailed and/or posted to 256 hospitals with pediatric wards. RESULTS: A total of 120 useable surveys were returned (93 % of PEDs and 29 % of GEDs). In the PEDs surveyed (n=67, 33 university hospitals [UHs] and 34 non-university hospitals), disease recruitment was medical and surgical with trauma (84 %) or medical only (16 %). The medical directors of the PEDs were pediatricians (99 %). The average number of visits in 2007 was 20,200±10,600 per PED (+13 % within 5 years), and the average number of medical practitioners was 4±3. However, in only 76 % of PEDs was at least one pediatrician present after midnight. Medical staffing of PEDs in UHs did not include a pediatric resident in 30 % and a pediatric attending physician in 63 % of these units. Approximately, 48 % of PEDs had a short-stay observation unit (median, five beds). In GEDs (n=53), children were admitted 24h a day in the GED (41 %) and directly in the pediatric ward during the day and in the GED at night (28 %). Traumas were admitted in 98 % of the GEDs. CONCLUSION: Pediatric coverage 24h a day is still insufficient in PEDs. The training and experience of pediatricians were restricted by the lack of pediatric residency and physician positions in pediatric emergency care. A different access to pediatric emergency care during the day and night was frequent in hospitals without a PED.

[Syncope and pre-syncope in children and adolescents: a prospective study in a pediatric emergency care unit]. / Syncopes et lipothymies chez l'enfant et l'adolescent : étude prospective dans une unité d'urgence pédiatrique.

OBJECTIVES: To assess in a pediatric emergency care unit (PECU): 1. The frequency of syncope and pre-syncope, 2. The incidence of diagnoses, 3. The value of investigations and cardiology and neurology consultations. METHODS: The data of PECU patients aged 2 years to 15 years and 3 months were prospectively collected over 1 year. Standard electrocardiogram and serum glucose were compulsory investigations. Schellong's orthostatic test was performed whenever possible. RESULTS: One hundred and fity-nine children (mean age, 11+/-4 years) were included, accounting for 0.8% of the PECU's visits: 48% had syncope, 52% had pre-syncope. The most common cause was neurally mediated syncope - 98 patients (62%), with vasovagal syncope for 80 patients - followed by neurological causes: 29 patients (18%). Neither cardiac arrhythmia nor obstructive cardiomyopathy was diagnosed. There were discrepancies between cardiologists' and pediatricians' ECG interpretations in 9% of cases. Diagnoses differed between cardiologists and pediatricians in 54% of 41 consultations. Diagnoses differed between neurologists and pediatricians in 54% of 42 consultations. No investigation except Schellong's orthostatic test led to modification of a previous diagnosis. CONCLUSION: This study emphasizes that the routine workup of pediatric syncope should focus on the patient's history and physical examination. Diagnostic testing should be minimal: ECG and Schellong's orthostatic test. The leading cause was neurocardiogenic syncope.

[Improvement in the management of acute diarrhoea in France?]. / Prise en charge des diarrhées aiguës en France: quels progrés?

The management of acute diarrhoea in France improved during the last ten years, with a large increase of oral rehydration solution (ORS) prescription in infants. Severity assessment is too often based on an uncertain evaluation of weight loss instead of a clinical determination. Telephone triage is not accurate without use of protocols and decision-making guidelines. Laboratory tests are rare in ambulatory management but still too frequent in hospital management of children with oral rehydration. ORS prescription of general practitioners regularly increased: 16% in 1988, 29% in 1996, 39% in 2001; and 71% in 2005 (after their reimbursement). The quality of oral rehydration advice remains insufficient. Intravenous rehydration on admission remains still too frequent. Drugs prescriptions include 2 or 3 drugs, with a decrease of loperamide and antibiotics, and an increase of racecadotril (81%). Lactose-free milk prescriptions in infants dropped from 46% in 1996 to 16% in 2005. Isolation and disinfection procedures are insufficient. Rotavirus nosocomial infections incidence is high: 1,6 to 6,3/1000 children less than 5 years of age, contributing to high direct costs.