The effect of magnesium vacancies on the intraband scattering in MgxB2 as determined by point contact Andreev reflection

In order to introduce structural defects into the band with minimal distortions in the band, bulk samples of varying magnesium content were prepared. Point contact Andreev reflection measurements reveal that the density of states of the band and the behavior of the energy gaps in field imply a relative increase of band to band scattering with increasing magnesium deficiency. The results are consistent with the observed increase of the low temperature Hc2 value in magnesium deficient MgB2

Extracting the diffusivity ratio from point contact Andreev reflection spectroscopy and upper critical field measurements in MgB2

The di®usivity ratio ´, which measures the relative intraband scattering in the ¼ and ¾ bands in MgB2 has been determined by ¯tting the Hc2(T) at T » Tc and by Point Contact Andreev Re°ection. We ¯nd a satisfactory agreement between the values for ´ obtained by both methods for c-axis orientated MgB2 thin ¯lms. Point contact Andreev Re°ection was then applied to bulk MgB2 containing Mg vacancies. Spectra obtained in zero ¯eld indicate a distribution of the two gaps ¢¾;¼ but no merging of the values with increased magnesium de¯ciency. Spectra ¯tted as a function of ¯eld are consistent with an increase in ¼ intraband scattering with increasing magnesium de¯ciency. Measurement of the point contact Andreev re°ection spectra as a function of temperature revealed features not immediately expected from current theoretical models

Prospective clinical testing and experimental validation of the Pediatric Sepsis Biomarker Risk Model

Sepsis remains a major public health problem with no major therapeutic advances over the last several decades. The clinical and biological heterogeneity of sepsis have limited success of potential new therapies. Accordingly, there is considerable interest in developing a precision medicine approach to inform more rational development, testing, and targeting of new therapies. We previously developed the Pediatric Sepsis Biomarker Risk Model (PERSEVERE) to estimate mortality risk and proposed its use as a prognostic enrichment tool in sepsis clinical trials; prognostic enrichment selects patients based on mortality risk independent of treatment. Here, we show that PERSEVERE has excellent performance in a diverse cohort of children with septic shock with potential for use as a predictive enrichment strategy; predictive enrichment selects patients based on likely response to treatment. We demonstrate that the PERSEVERE biomarkers are reliably associated with mortality in mice challenged with experimental sepsis, thus providing an opportunity to test precision medicine strategies in the preclinical setting. Using this model, we tested two clinically feasible therapeutic strategies, guided by the PERSEVERE-based enrichment, and found that mice identified as high risk for mortality had a greater bacterial burden and could be rescued by higher doses of antibiotics. The association between higher pathogen burden and higher mortality risk was corroborated among critically ill children with septic shock. This bedside to bench to bedside approach provides proof of principle for PERSEVERE-guided application of precision medicine in sepsis

Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2)

OBJECTIVES: We sought to update our 2015 work in the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS), considering new evidence and topic areas that were not previously addressed. DESIGN: International consensus conference series involving 52 multidisciplinary international content experts in PARDS and four methodology experts from 15 countries, using consensus conference methodology, and implementation science. SETTING: Not applicable. PATIENTS: Patients with or at risk for PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eleven subgroups conducted systematic or scoping reviews addressing 11 topic areas: 1) definition, incidence, and epidemiology; 2) pathobiology, severity, and risk stratification; 3) ventilatory support; 4) pulmonary-specific ancillary treatment; 5) nonpulmonary treatment; 6) monitoring; 7) noninvasive respiratory support; 8) extracorporeal support; 9) morbidity and long-term outcomes; 10) clinical informatics and data science; and 11) resource-limited settings. The search included MEDLINE, EMBASE, and CINAHL Complete (EBSCOhost) and was updated in March 2022. Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to summarize evidence and develop the recommendations, which were discussed and voted on by all PALICC-2 experts. There were 146 recommendations and statements, including: 34 recommendations for clinical practice; 112 consensus-based statements with 18 on PARDS definition, 55 on good practice, seven on policy, and 32 on research. All recommendations and statements had agreement greater than 80%. CONCLUSIONS: PALICC-2 recommendations and consensus-based statements should facilitate the implementation and adherence to the best clinical practice in patients with PARDS. These results will also inform the development of future programs of research that are crucially needed to provide stronger evidence to guide the pediatric critical care teams managing these patients.</p

Posterior fossa tumours in childhood: Associated speech and language disorders post-surgery

Six children aged between 6 and 16 years who had undergone surgery for the removal of a posterior fossa tumour were assessed at least one year postoperatively to determine the incidence and severity of any associated speech or language deficits. Five males and one female were included in the sample. The subjects were administered a battery of speech/language assessments including: a language screening test, an articulation test, a dysarthria assessment and a perceptual speech analysis. The results indicated that dysarthria and/or language impairment occurs in some cases subsequent to surgical removal of posterior fossa tumours. The occurrence of muteness immediately post-surgery would appear to indicate a poor prognosis for speech abilities. A possible link between the occurrence of long term language disabilities in these children and post-surgical radiotherapy is documented

Differential expression of the Nrf2-linked genes in pediatric septic shock.

INTRODUCTION: Experimental data from animal models of sepsis support a role for a transcription factor, nuclear erythroid-related factor 2 p45-related factor 2 (Nrf2), as a master regulator of antioxidant and detoxifying genes and intermediary metabolism during stress. Prior analysis of a pediatric septic shock transcriptomic database showed that the Nrf2 response is a top 5 upregulated signaling pathway in early pediatric septic shock. METHODS: We conducted a focused analysis of 267 Nrf2-linked genes using a multicenter, genome-wide expression database of 180 children with septic shock 10 years of age or younger and 53 healthy controls. The analysis involved RNA isolated from whole blood within 24 h of pediatric intensive care unit admission for septic shock and a false discovery rate of 5 %. We compared differentially expressed genes from (1) patients with septic shock and healthy controls and (2) across validated gene expression-based subclasses of pediatric septic shock (endotypes A and B) using several bioinformatic methods. RESULTS: We found upregulation of 123 Nrf2-linked genes in children with septic shock. The top gene network represented by these genes contained primarily enzymes with oxidoreductase activity involved in cellular lipid metabolism that were highly connected to the peroxisome proliferator activated receptor and the retinoic acid receptor families. Endotype A, which had higher organ failure burden and mortality, exhibited a greater downregulation of Nrf2-linked genes than endotype B, with 92 genes differentially regulated between endotypes. CONCLUSIONS: Our findings indicate that Nrf2-linked genes may contribute to alterations in oxidative signaling and intermediary metabolism in pediatric septic shock