Autonomic Nervous System Dysfunction in Pediatric Sepsis

The autonomic nervous system (ANS) plays a major role in maintaining homeostasis through key adaptive responses to stress, including severe infections and sepsis. The ANS-mediated processes most relevant during sepsis include regulation of cardiac output and vascular tone, control of breathing and airway resistance, inflammation and immune modulation, gastrointestinal motility and digestion, and regulation of body temperature. ANS dysfunction (ANSD) represents an imbalanced or maladaptive response to injury and is prevalent in pediatric sepsis. Most of the evidence on ANSD comes from studies of heart rate variability, which is a marker of ANS function and is inversely correlated with organ dysfunction and mortality. In addition, there is evidence that other measures of ANSD, such as respiratory rate variability, skin thermoregulation, and baroreflex and chemoreflex sensitivity, are associated with outcomes in critical illness. The relevance of understanding ANSD in the context of pediatric sepsis stems from the fact that it might play an important role in the pathophysiology of sepsis, is associated with outcomes, and can be measured continuously and noninvasively. Here we review the physiology and dysfunction of the ANS during critical illness, discuss methods for measuring ANS function in the intensive care unit, and review the diagnostic, prognostic, and therapeutic value of understanding ANSD in pediatric sepsis

Identification of a new snake fossil from the Canary Islands using micro-CT techniques

Abstract and keywords in English and SpanishThere are no native snakes on the Canary Islands today. The recovery of a boid vertebra from Miocene deposits on Fuertaventura suggested snakes could have been present in the past, but this single small vertebra could have reached the island from the nearby African continent in the gut of a bird. Now, however, the articulated remains of a snake have been found in a volcanic cave on Fuerteventura. The specimen is covered by a calcitic matrix and is of uncertain age. Given the fragility of the remains and the difficulty of removing the matrix, we used micro-Ct scans to make three-dimensional digital models for study. These reveal that the bones belong to a 'colubrid' snake. = En el Mioceno de las Islas Canarias se ha citado la presencia de una vértebra de boido, que por su pequeño temaño pudo haber llegado a las islas desde el cercano continente africano en el tracto digestivo de un ave. Sin embargo, en un tubo volcánico de Fuerteventura se han encontrado restos de vértebras y costillas articuladas, cubiertas por una capa de calcita y de edad incierta, que pertenecen a una seriente de la familia 'Colubridae'. Para su estudio, dadas la fragilidad de los restos y la dificultad para eliminar la calcita, se utilizó un escáner micro CT para obtener modelos digitales tridimensionales.Evans, S.E., Martín-González, E., Jones, M.E.H., Sánchez-Pinto, L. & García-Talavera, F

GEMS: The Size Evolution of Disk Galaxies

We combine HST imaging from the GEMS survey with photometric redshifts from COMBO-17 to explore the evolution of disk-dominated galaxies since z<1.1. The sample is comprised of all GEMS galaxies with Sersic indices n<2.5, derived from fits to the galaxy images. We account fully for selection effects through careful analysis of image simulations; we are limited by the depth of the redshift and HST data to the study of galaxies with absolute magnitudes M(V)10. We find strong evolution in the magnitude-size scaling relation for galaxies with M(V)<-20, corresponding to a brightening of 1 mag per sqarcsec in rest-frame V-band by z=1. Yet, disks at a given absolute magnitude are bluer and have lower stellar mass-to-light ratios at z=1 than at the present day. As a result, our findings indicate weak or no evolution in the relation between stellar mass and effective disk size for galaxies with log(M)>10 over the same time interval. This is strongly inconsistent with the most naive theoretical expectation, in which disk size scales in proportion to the halo virial radius, which would predict that disks are a factor of two denser at fixed mass at z=1. The lack of evolution in the stellar mass-size relation is consistent with an ``inside-out'' growth of galaxy disks on average (galaxies increasing in size as they grow more massive), although we cannot rule out more complex evolutionary scenarios.Comment: 22 pages, 16 figures, submitted to Ap

Features of the opportunistic behaviour of the marine bacterium marinobacter algicola in the microalga ostreococcus tauri phycosphere

Although interactions between microalgae and bacteria are observed in both natural environment and the laboratory, the modalities of coexistence of bacteria inside microalgae phycospheres in laboratory cultures are mostly unknown. Here, we focused on well-controlled cultures of the model green picoalga Ostreococcus tauri and the most abundant member of its phycosphere, Marinobacter algicola. The prevalence of M. algicola in O. tauri cultures raises questions about how this bacterium maintains itself under laboratory conditions in the microalga culture. The results showed that M. algicola did not promote O. tauri growth in the absence of vitamin B12 while M. algicola depended on O. tauri to grow in synthetic medium, most likely to obtain organic carbon sources provided by the microalgae. M. algicola grew on a range of lipids, including triacylglycerols that are known to be produced by O. tauri in culture during abiotic stress. Genomic screening revealed the absence of genes of two particular modes of quorum-sensing in Marinobacter genomes which refutes the idea that these bacterial communication systems operate in this genus. To date, the ‘opportunistic’ behaviour of M. algicola in the laboratory is limited to several phytoplanktonic species including Chlorophyta such as O. tauri. This would indicate a preferential occurrence of M. algicola in association with these specific microalgae under optimum laboratory conditions

Renal Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference

CONTEXT Renal dysfunction is associated with poor outcomes in critically ill children. OBJECTIVE To evaluate the current evidence for criteria defining renal dysfunction in critically ill children and association with adverse outcomes. To develop contemporary consensus criteria for renal dysfunction in critically ill children. DATA SOURCES PubMed and Embase were searched from January 1992 to January 2020. STUDY SELECTION Included studies evaluated critically ill children with renal dysfunction, performance characteristics of assessment tools for renal dysfunction, and outcomes related to mortality, functional status, or organ-specific or other patient-centered outcomes. Studies with adults or premature infants (≤36 weeks' gestational age), animal studies, reviews, case series, and studies not published in English with inability to determine eligibility criteria were excluded. DATA EXTRACTION Data were extracted from included studies into a standard data extraction form by task force members. RESULTS The systematic review supported the following criteria for renal dysfunction: (1) urine output <0.5 mL/kg per hour for ≥6 hours and serum creatinine increase of 1.5 to 1.9 times baseline or ≥0.3 mg/dL, or (2) urine output <0.5 mL/kg per hour for ≥12 hours, or (3) serum creatinine increase ≥2 times baseline, or (4) estimated glomerular filtration rate <35 mL/minute/1.73 m2, or (5) initiation of renal replacement therapy, or (6) fluid overload ≥20%. Data also support criteria for persistent renal dysfunction and for high risk of renal dysfunction. LIMITATIONS All included studies were observational and many were retrospective. CONCLUSIONS We present consensus criteria for renal dysfunction in critically ill children

Derivation, validation, and clinical relevance of a pediatric sepsis phenotype with persistent hypoxemia, encephalopathy, and shock

OBJECTIVES: Untangling the heterogeneity of sepsis in children and identifying clinically relevant phenotypes could lead to the development of targeted therapies. Our aim was to analyze the organ dysfunction trajectories of children with sepsis-associated multiple organ dysfunction syndrome (MODS) to identify reproducible and clinically relevant sepsis phenotypes and determine if they are associated with heterogeneity of treatment effect (HTE) to common therapies. DESIGN: Multicenter observational cohort study. SETTING: Thirteen PICUs in the United States. PATIENTS: Patients admitted with suspected infections to the PICU between 2012 and 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used subgraph-augmented nonnegative matrix factorization to identify candidate trajectory-based phenotypes based on the type, severity, and progression of organ dysfunction in the first 72 hours. We analyzed the candidate phenotypes to determine reproducibility as well as prognostic, therapeutic, and biological relevance. Overall, 38,732 children had suspected infection, of which 15,246 (39.4%) had sepsis-associated MODS with an in-hospital mortality of 10.1%. We identified an organ dysfunction trajectory-based phenotype (which we termed persistent hypoxemia, encephalopathy, and shock) that was highly reproducible, had features of systemic inflammation and coagulopathy, and was independently associated with higher mortality. In a propensity score-matched analysis, patients with persistent hypoxemia, encephalopathy, and shock phenotype appeared to have HTE and benefit from adjuvant therapy with hydrocortisone and albumin. When compared with other high-risk clinical syndromes, the persistent hypoxemia, encephalopathy, and shock phenotype only overlapped with 50%-60% of patients with septic shock, moderate-to-severe pediatric acute respiratory distress syndrome, or those in the top tier of organ dysfunction burden, suggesting that it represents a nonsynonymous clinical phenotype of sepsis-associated MODS. CONCLUSIONS: We derived and validated the persistent hypoxemia, encephalopathy, and shock phenotype, which is highly reproducible, clinically relevant, and associated with HTE to common adjuvant therapies in children with sepsis

Precision measurement of the neutrino velocity with the ICARUS detector in the CNGS beam

During May 2012, the CERN-CNGS neutrino beam has been operated for two weeks for a total of 1.8 10^17 pot in bunched mode, with a 3 ns narrow width proton beam bunches, separated by 100 ns. This tightly bunched beam structure allows a very accurate time of flight measurement of neutrinos from CERN to LNGS on an event-by-event basis. Both the ICARUS-T600 PMT-DAQ and the CERN-LNGS timing synchronization have been substantially improved for this campaign, taking ad-vantage of additional independent GPS receivers, both at CERN and LNGS as well as of the deployment of the "White Rabbit" protocol both at CERN and LNGS. The ICARUS-T600 detector has collected 25 beam-associated events; the corresponding time of flight has been accurately evaluated, using all different time synchronization paths. The measured neutrino time of flight is compatible with the arrival of all events with speed equivalent to the one of light: the difference between the expected value based on the speed of light and the measured value is tof_c - tof_nu = (0.10 \pm 0.67stat. \pm 2.39syst.) ns. This result is in agreement with the value previously reported by the ICARUS collaboration, tof_c - tof_nu = (0.3 \pm 4.9stat. \pm 9.0syst.) ns, but with improved statistical and systematic errors.Comment: 21 pages, 13 figures, 1 tabl

Understanding clinical and biological heterogeneity to advance precision medicine in paediatric acute respiratory distress syndrome

Paediatric acute respiratory distress syndrome (PARDS) is a heterogeneous clinical syndrome that is associated with high rates of mortality and long-term morbidity. Factors that distinguish PARDS from adult acute respiratory distress syndrome (ARDS) include changes in developmental stage and lung maturation with age, precipitating factors, and comorbidities. No specific treatment is available for PARDS and management is largely supportive, but methods to identify patients who would benefit from specific ventilation strategies or ancillary treatments, such as prone positioning, are needed. Understanding of the clinical and biological heterogeneity of PARDS, and of differences in clinical features and clinical course, pathobiology, response to treatment, and outcomes between PARDS and adult ARDS, will be key to the development of novel preventive and therapeutic strategies and a precision medicine approach to care. Studies in which clinical, biomarker, and transcriptomic data, as well as informatics, are used to unpack the biological and phenotypic heterogeneity of PARDS, and implementation of methods to better identify patients with PARDS, including methods to rapidly identify subphenotypes and endotypes at the point of care, will drive progress on the path to precision medicine.</p