Evidence for long-term variability in the ultra high energy photon flux from Cygnus X-3

A time-correlation analysis of atmospheric Cerenkov pulses by a wide-angle photomultiplier system was previously shown to have present in it a nonrandom component which seemed associated with the Right Ascension (RA) range approx. 20+or-04h. A recent examination of multi-muon events recorded by a photon-decay detector shows a similar time-dependent effect, closely matching the previous results, supporting the suggestion that the effect is of cosmic origin. However, even though Cyg. X-3 lies well inside the region of peak intensity, it does not seem possible to ascribe to it the whole effect, for the implied photon flux appears too large to be reconciled to various gamma-ray measurements of Cyg. X-3. The original data were subjected to a phase-histogram analysis and it as found that only 2.5% of overall recorded data are compatible with a phase-dependent emission from Cyg. X-3. Assuming these events to be gamma rays yields a detected flux of (2.6 + or - 0.3) x 10 to the minus 12th power gamma cm -2s-1 above 5 x 10 to the 14th power eV. Comparing this value with more recent ultra high energy (UHE) photon data from the same source, it is suggested that the available data generally favor a long-term reduction in the Cyg. X-3 inferred luminosity ( 10 to the 13th power eV) by a factor of (1.8 + or - 0.3) per year

Priorities and preferences for school-based mental health services in India: a multi-stakeholder study with adolescents, parents, school staff and mental health providers

Background Schools are important settings for increasing reach and uptake of adolescent mental health interventions. There is limited consensus on the focus and content of school-based mental health services (SBMHSs), particularly in low-resource settings. This study elicited the views of diverse stakeholders in two urban settings in India about their priorities and preferences for SBMHSs. Methods We completed semi-structured interviews and focus group discussions with adolescents (n=191), parents (n=9), teachers (n=78), school counsellors (n=15), clinical psychologists and psychiatrists (n=7). Qualitative data were obtained on prioritized outcomes, preferred content and delivery methods, and indicated barriers. Results All stakeholders indicated the need for and acceptability of SBMHSs. Adolescents prioritized resolution of life problems and preferred practical guidance. Parents and teachers emphasized functional outcomes and preferred to be involved in interventions. This contrasted with adolescents’ preferences for limited involvement from parents and teachers, to maintain confidentiality. Face-to-face counselling was the most acceptable delivery format; self-help was less frequently recommended but was more acceptable when blended with guidance or delivered as digital interventions. Structured sensitization was recommended to ensure adolescent engagement. Providers endorsed a stepped care approach to address different levels of mental health need among adolescents. Conclusion SBMHSs are desired by adolescents and adult stakeholders in this setting where few such services exist. Sensitization activities are required to support implementation. School counsellors have an important role in identifying and treating adolescents with different levels of mental health need, and a suite of interventions are needed to target these needs effectively and efficiently

Periodic gamma-ray emissions from Geminga at or = 10(12) eV

Analysis of data from an atmospheric Cerenkov telescope indicated the periodic emission of gamma rays of energy 10 to the 12th power eV, at 60.25 second period, from 2CG 195+4. The gamma ray flux at 99% confidence level is estimated to be 9.5 x 10 to 12 photons/sq cm/s

A prospective investigation of interleukin-8 levels in pediatric acute respiratory failure and acute respiratory distress syndrome

© 2019 The Author(s). Background: The association of plasma interleukin-8 (IL-8), or IL-8 genetic variants, with pediatric acute respiratory distress syndrome (PARDS) in children with acute respiratory failure at risk for PARDS has not been examined. The purpose of this study was to examine the association of early and sequential measurement of plasma IL-8 and/or its genetic variants with development of PARDS and other clinical outcomes in mechanically ventilated children with acute respiratory failure. Methods: This was a prospective cohort study of children 2 weeks to 17 years of age with acute airways and/or parenchymal lung disease done in 22 pediatric intensive care units participating in the multi-center clinical trial, Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE). Plasma IL-8 levels were measured within 24 h of consent and 24 and 48 h later. DNA was purified from whole blood, and IL-8 single nucleotide polymorphisms, rs4073, rs2227306, and rs2227307, were genotyped. Results: Five hundred forty-nine patients were enrolled; 480 had blood sampling. Plasma IL-8 levels ranged widely from 4 to 7373 pg/mL. Highest IL-8 levels were observed on the day of intubation with subsequent tapering. Levels of IL-8 varied significantly across primary diagnoses with the highest levels occurring in patients with sepsis and the lowest levels in those with asthma. Plasma IL-8 was strongly correlated with oxygenation defect and severity of illness. IL-8 was consistently higher in PARDS patients compared to those without PARDS; levels were 4-12 fold higher in non-survivors compared to survivors. On multivariable analysis, IL-8 was independently associated with death, duration of mechanical ventilation, and PICU length of stay on all days measured, but was not associated with PARDS development. There was no association between the IL-8 single nucleotide polymorphisms, rs4073, rs2227306, and rs2227307, and PARDS development or plasma IL-8 level. Conclusions: When measured sequentially, plasma IL-8 was robustly associated with multiple, relevant clinical outcomes including mortality, but was not associated with PARDS development. The wide range of plasma IL-8 levels exhibited in this cohort suggests that further study into the heterogeneity of this patient population and its impact on individual responses to PARDS treatment is warranted

Mapping genetic determinants of host susceptibility to Pseudomonas aeruginosa lung infection in mice.

Background: P. aeruginosa is one of the top three causes of opportunistic human bacterial infections. The remarkable variability in the clinical outcomes of this infection is thought to be associated with genetic predisposition. However, the genes underlying host susceptibility to P. aeruginosa infection are still largely unknown. Results: As a step towards mapping these genes, we applied a genome wide linkage analysis approach to a mouse model. A large F2 intercross population, obtained by mating P. aeruginosa-resistant C3H/HeOuJ, and susceptible A/J mice, was used for quantitative trait locus (QTL) mapping. The F2 progenies were challenged with a P. aeruginosa clinical strain and monitored for the survival time up to 7 days post-infection, as a disease phenotype associated trait. Selected phenotypic extremes of the F2 distribution were genotyped with high-density single nucleotide polymorphic (SNP) markers, and subsequently QTL analysis was performed. A significant locus was mapped on chromosome 6 and was named P. aeruginosa infection resistance locus 1 (Pairl1). The most promising candidate genes, including Dok1, Tacr1, Cd207, Clec4f, Gp9, Gata2, Foxp1, are related to pathogen sensing, neutrophils and macrophages recruitment and inflammatory processes. Conclusions: We propose a set of genes involved in the pathogenesis of P. aeruginosa infection that may be explored to complement human studie

Capsaicin- resistant arterial baroreceptors

BACKGROUND: Aortic baroreceptors (BRs) comprise a class of cranial afferents arising from major arteries closest to the heart whose axons form the aortic depressor nerve. BRs are mechanoreceptors that are largely devoted to cardiovascular autonomic reflexes. Such cranial afferents have either lightly myelinated (A-type) or non-myelinated (C-type) axons and share remarkable cellular similarities to spinal primary afferent neurons. Our goal was to test whether vanilloid receptor (TRPV1) agonists, capsaicin (CAP) and resiniferatoxin (RTX), altered the pressure-discharge properties of peripheral aortic BRs. RESULTS: Periaxonal application of 1 μM CAP decreased the amplitude of the C-wave in the compound action potential conducting at <1 m/sec along the aortic depressor nerve. 10 μM CAP eliminated the C-wave while leaving intact the A-wave conducting in the A-δ range (<12 m/sec). These whole nerve results suggest that TRPV1 receptors are expressed along the axons of C- but not A-conducting BR axons. In an aortic arch – aortic nerve preparation, intralumenal perfusion with 1 μM CAP had no effect on the pressure-discharge relations of regularly discharging, single fiber BRs (A-type) – including the pressure threshold, sensitivity, frequency at threshold, or maximum discharge frequency (n = 8, p > 0.50) but completely inhibited discharge of an irregularly discharging BR (C-type). CAP at high concentrations (10–100 μM) depressed BR sensitivity in regularly discharging BRs, an effect attributed to non-specific actions. RTX (≤ 10 μM) did not affect the discharge properties of regularly discharging BRs (n = 7, p > 0.18). A CAP-sensitive BR had significantly lower discharge regularity expressed as the coefficient of variation than the CAP-resistant fibers (p < 0.002). CONCLUSION: We conclude that functional TRPV1 channels are present in C-type but not A-type (A-δ) myelinated aortic arch BRs. CAP has nonspecific inhibitory actions that are unlikely to be related to TRV1 binding since such effects were absent with the highly specific TRPV1 agonist RTX. Thus, CAP must be used with caution at very high concentrations

Pulmonary Metagenomic Sequencing Suggests Missed Infections in Immunocompromised Children

This article is made available for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing.BACKGROUND: Despite improved diagnostics, pulmonary pathogens in immunocompromised children frequently evade detection, leading to significant mortality. Therefore, we aimed to develop a highly sensitive metagenomic next-generation sequencing (mNGS) assay capable of evaluating the pulmonary microbiome and identifying diverse pathogens in the lungs of immunocompromised children. METHODS: We collected 41 lower respiratory specimens from 34 immunocompromised children undergoing evaluation for pulmonary disease at 3 children's hospitals from 2014-2016. Samples underwent mechanical homogenization, parallel RNA/DNA extraction, and metagenomic sequencing. Sequencing reads were aligned to the National Center for Biotechnology Information nucleotide reference database to determine taxonomic identities. Statistical outliers were determined based on abundance within each sample and relative to other samples in the cohort. RESULTS: We identified a rich cross-domain pulmonary microbiome that contained bacteria, fungi, RNA viruses, and DNA viruses in each patient. Potentially pathogenic bacteria were ubiquitous among samples but could be distinguished as possible causes of disease by parsing for outlier organisms. Samples with bacterial outliers had significantly depressed alpha-diversity (median, 0.61; interquartile range [IQR], 0.33-0.72 vs median, 0.96; IQR, 0.94-0.96; P < .001). Potential pathogens were detected in half of samples previously negative by clinical diagnostics, demonstrating increased sensitivity for missed pulmonary pathogens (P < .001). CONCLUSIONS: An optimized mNGS assay for pulmonary microbes demonstrates significant inoculation of the lower airways of immunocompromised children with diverse bacteria, fungi, and viruses. Potential pathogens can be identified based on absolute and relative abundance. Ongoing investigation is needed to determine the pathogenic significance of outlier microbes in the lungs of immunocompromised children with pulmonary disease