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.

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.

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 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.

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.

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.

[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.

[An excessive diagnosis of constipation in children complaining of abdominal pain in a pediatric emergency department: an example of practice patterns]. / Une prévalence excessive du diagnostic de constipation chez les enfants consultant pour douleurs abdominales aux urgences: un exemple d'évaluation des pratiques.

UNLABELLED: Prescriptions of abdominal x-ray and diagnosis of constipation seemed too frequent in children evaluated for abdominal pain (AP) in a paediatric emergency unit. OBJECTIVE: To evaluate the prevalence of constipation in children with AP, to determine clinical and radiological signs related to this diagnosis, and to compare frequencies of clinical criteria of functional chronic constipation (FCC) in children with AP with those of controls (children with mild traumatisms without AP). METHODS: This prospective observational study included children older than 4 years of age consulting for AP. RESULTS: Among 196 patients with AP, 53% had a diagnosis of constipation on discharge (28% isolated and 25% associated with an other diagnosis), and 88% had a plain abdominal x-ray. A faecal retention was considered by emergency practitioners in 92% of children with the diagnosis of constipation vs 22% with other diagnosis (OR=38; CI 95%: 15-101). Clinical criteria of FCC were associated with the diagnosis of constipation (OR=2.7; CI 95%: 1.4-5.2). A FCC was as prevalent in the control population as in AP population (32 vs 34%). CONCLUSION: An excessive prevalence of diagnosis of constipation was mainly associated with contestable x-ray diagnosis of faecal retention secondary to inappropriate indications of abdominal x-ray.

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.

[Usefulness of procalcitonin for the diagnosis of acute pyelonephritis in children]. / Apport du dosage de la procalcitonine pour le diagnostic de pyélonéphrite aiguë de l'enfant.

BACKGROUND: Acute pyelonephritis can induce parenchymal scarring. The aim of this study was to evaluate the usefulness of procalcitonin (PCT) to predict renal involvement in febrile children with urinary tract infection (UTI). METHODS: In a prospective study serum PCT was measured and compared with others commonly used inflammatory markers in children admitted to the emergency unit with acute pyelonephritis. Renal parenchymal involvement was assessed by a (99 m)Tc-labeled dimercaptosuccinic acid (DMSA) renal scar performed in the first 3 days after the admission. RESULTS: Among 42 enrolled patients, 19 (45%) had acute renal involvement (Group A) ; 23 (55%) (Group B) had normal DMSA scan (n = 16), or old scarring (n = 4) or various anomalies related to uropathy (n = 3). In group A, the mean PCT level was significantly higher than in the group B (5.4 ng/ml, vs 0.4 ng /ml, p < 10(-5)). In these 2 groups, mean C reactive protein (CRP) levels were 99.1 mg/l and 44.6 mg/l respectively (p < 0.001). For a level of serum PCT > or = 0.5 ng/ml, the sensitivity and specificity to predict the renal involvement were 100% and 87% respectively; for a level> or= 20 mg/l CRP had a sensitivity of 94% but a specificity of 30%. CONCLUSION: Serum PCT levels were significantly increased in febrile children with UTI when acute renal parenchymal involvement was present. PCT seems a better marker than CRP for the prediction of patients at risk of renal lesions.

Protein C and S deficiency in severe infectious purpura of children: a collaborative study of 40 cases.

We studied, in 40 children (mean age: 52 months) with severe infectious purpura, the relationships between protein C (PC) and protein S (PS) levels, and shock, disseminated intravascular coagulation (DIC) and outcome. We determined, on admission, PC antigen (ELISA) and activity (chromogenic test), and total PS (ELISA). Results were expressed as % of normal adult values. Statistical analysis was performed with SAS. Thirty children were in shock, 20 had DIC. All children with DIC, and 10 without DIC were in shock. Of 20 children who were in shock and had DIC, 7 died and 3 had an amputation. PC antigen was significantly decreased in shock children (p less than 0.05), in children with DIC (p less than 0.0005), and in non-survivors (p less than 0.05). PC activity was significantly decreased in shock children (p less than 0.05), in children with DIC (p less than 0.0005), and in non-survivors (p less than 0.005). Total PS was not decreased in shock children, but was significantly decreased in children with DIC (p less than 0.005), and in non-survivors (p less than 0.005). We conclude that PC and PS levels were decreased in our children, and that PC levels were significantly decreased in the presence of shock, DIC, and fatal outcome. PC and antithrombin III (AT III) supplementation, should be evaluated in children with severe infectious purpura with shock and DIC.

Inhaled nitric oxide for a severe respiratory syncytial virus infection in an infant with bronchopulmonary dysplasia.

OBJECTIVE: To report the first case of ARDS in children treated with nitric oxide (NO) inhalation. METHODS: A 13-months infant presented with BPD and severe hypoxemia related to RSV infection and ARDS. Inhaled NO was delivered in the ventilatory circuit of a continuous flow ventilator (Babylog 8000, Dräger) in a concentration of 20-80 ppm for 7 days. NO and NO2 were continuously monitored (Polyton Draeger). Respiratory mechanics were evaluated by using the method of passive inflation by the ventilator. RESULTS: NO inhalation improved oxygenation (tcSaO2) and reduced respiratory system resistance without affecting arterial pressure. NO2 level remained below 5 ppm, and methaemoglobin level below 1%. The child survived without neurologic sequela. CONCLUSIONS: Two mechanisms to explain oxygenation improvement can be suggested: selective improvement in perfusion of ventilated regions and bronchodilation.

Sudden death revealing Chiari type 1 malformation in two children.

We report the first two fatal cases of sudden unprovoked cardiorespiratory arrest in children with previously undiagnosed Arnold-Chiari type 1 malformation. This diagnosis should be considered in children with unexplained cardiorespiratory arrest. The risk of sudden death in Arnold-Chiari type 1 malformation reinforces the indication for early neurosurgical procedure.

Spondylodiscitis and mediastinitis after esophageal perforation owing to a swallowed radiolucent foreign body.

A 6-year-old boy with aphagia presented with a radiolucent foreign body, esophageal perforation, mediastinitis, and a C6-C7 spondylodiscitis. A rigid plastic gear wheel was removed via thoracotomy, and the mediastinal abscess was drained through the esophagomediastinal fistula. Treatment included antibiotics as well as nonsurgical orthopedic management of the spondylodiscitis. The recovery period was uneventful, and the patient has remained asymptomatic for 2 years. Physicians must be aware of radiolucent foreign bodies. Computed tomography is very helpful in establishing the diagnosis of radiolucent foreign body, mediastinal abscess, and spondylodiscitis.

Pulmonary hypertension of the newborn and urogenital anomalies in two male siblings: a new family with misalignment of pulmonary vessels.

The association of pelvi-ureteric junction obstruction (PUJO) and rapidly fatal persistent pulmonary hypertension of the newborn (PPHN) has been observed in two male siblings. PUJO was also observed in a maternal uncle, whose daughter suffered from vesico-ureteral reflux (VUR). In both patients, histopathologic study of the lungs showed misalignment of pulmonary veins (MAPV), which is a rare autosomal recessive condition leading to severe PPHN and death within the neonatal period. It has occasionally been described associated with PUJO. The authors point out that: i: MAPV has to be carefully searched in case of PPHN; ii: PUJO could be an important finding associated with MAPV, and the only prenatal indication of this lethal condition.

[Paediatricians involvement in paediatric emergency care. A study in hospitals and paediatricians offices in the North of France]. / Implication des pédiatres dans l'accueil des urgences. Enquête "un jour donné" auprès des centres hospitaliers et des pédiatres libéraux de la région Nord - Pas de Calais.

UNLABELLED: Paediatrician involvement in paediatric emergency care is often considered insufficient. OBJECTIVES: To assess paediatrician involvement in paediatric emergency care, and how paediatric emergencies were dealt with in emergency department, paediatric emergency department, paediatric department and paediatrician offices. METHODS: Prospective multicentric study, January 29th, 2001, including all the emergency visits of children admitted to an emergency department, paediatric emergency department, paediatric department or in paediatrician offices. RESULTS: Paediatricians examined an average number of 21 children, 58% were considered as "urgent" (mean: 53% +/- 25% by paediatrician). Thirty five percent of paediatricians were available on call that night. In the 18 hospitals, 705 children were admitted that day, 42% to an emergency department, 40% to a paediatric emergency department, 18% to a paediatric department. The mean age was 6 years +/- 5 years. Trauma represented 40% of all cases and was more frequent in emergency department than in paediatric emergency department or paediatric department (63% versus 33% and 2%, p < 10(-8)). Hospitalisation rate was lower in paediatric emergency department than in emergency department and paediatric department, especially for non-traumatic conditions. CONCLUSION: Our findings prove paediatrician involvement in paediatric emergency care, in paediatrician offices and in hospital. This study points out the complementarity and insufficiencies of these different services.

[Evaluation of the ambulatory treatment of acute diarrhea in infants. Réseau interhospitalier d'evaluation des pratigues médicales dans les affections courantes de l'enfant]. / Evaluation du traitement ambulatoire des diarrhées aiguës du nourrisson. Réseau interhospitalier d'évaluation des pratiques médicales dans les affections courantes de l'enfant.

BACKGROUND: Gastroenteritis remains a common and expensive illness. Oral rehydration solutions (ORS) have been shown to be effective in the prevention and treatment of dehydration, the prime cause for diarrhea-related morbidity and mortality. OBJECTIVE: To evaluate the ambulatory management of acute gastroenteritis in infants, and particularly practices concerning oral fluid therapy. METHODS: This prospective, multicenter study included 326 infants (mean age: 10 +/- 6 months), examined in a hospital for acute gastroenteritis, with or without dehydration. RESULTS: Before admission, 81% had previously been examined by a practitioner, and 89% of these practitioners had written a prescription. This prescription included ORS in 35% and was not different according to the age of the infant. Pediatricians prescribed ORS more frequently than general practitioners (respectively 58% vs 29%; P < 0.001). The failure rate of ORS prescription was 25% (two parents did not observe, ten children refused to drink, and eight stopped treatment because of vomiting). Lactose-free milks were prescribed in 46% of infants and the observance was 82%. At least one drug was prescribed in 94% of infants, with a mean of 2.6 drugs per infant; one antibiotic was prescribed in 33% of infants. Infants were admitted to hospital without any previous consultation in 18%, on the parents' initiative but after at least one previous medical examination in 52%, and on the physician's initiative in 30%. Thirty-three percent were dehydrated; one infant died and two had sequellae. CONCLUSION: The use of ORS remains insufficient. Efforts to improve use of ORS should be expanded beyond physician education.

[Effectiveness of a short-stay observation unit in a pediatric emergency department]. / Utilité d'une unité d'hospitalisation de courte durée aux urgences pédiatriques.

UNLABELLED: Short-Stay Observation Units (SSOUs) in paediatric emergency departments are effective in reducing inpatient admissions but can also generate excessive short-stay hospitalisations. The aim of the study was to evaluate both these consequences and the different missions of SSOUs. METHODS: This prospective study included all children admitted in a 10-bed-medico-surgical SSOU of a tertiary-care paediatric emergency department from September 4, to October 31, 2001. At the time of SSOU admission, the physician indicated the purpose of the admission and which decision he would have made in the absence of a SSOU. RESULTS: Five hundred and nine children (median age = 4 years, chronic disease: 26%, trauma: 34%) were included, accounting for 15% of admissions. The mean length of stay was 14 +/- 8h. The decision in the absence of a SSOU would have been: inpatient hospitalization (77%), transfer to another hospital in the absence of inpatient room vacancy (7%), discharge home (10%), prolonged waiting in the emergency ward (4%), do not know or not indicated (2%). The SSOU admission was deemed appropriate in 81%: discharge home within 24h was likely in 65% and the final orientation of the child was uncertain in 16%. The admission was debatable in 13% and inappropriate in 6%. Sixty six per cent of children were discharged home. CONCLUSION: The SSOU reduced inpatient hospitalisations, generated few inappropriate short stay hospitalisations, and seemed particularly efficient for paediatric diseases. Proposed indicators should allow inter-hospital comparisons.