Investigating The Relationship Between Hemodynamic And Metabolic Parameters In Portal Triade Occlusion Following Hemorrhagic Shock.

PURPOSE: To determine whether metabolic and hemodynamic parameters are "mathematically" coupled in rats submitted to portal triad occlusion following controlled hemorrhagic shock state. METHODS: Pearson's coefficient (r-value) analysis was performed. Differences considered significant at p r > 0.50. RESULTS: It was observed that there is a direct proportional relationship to HCO3- with pCO2 (r = 0.66), base deficit (r = 0.87) and inverse with serum lactate (r = -0.54). pCO2 was directly associated with MAP (r = 0.51), and inversely with pH (r = -0.64). Hematocrit was directly associated with HR (r = 0.72) and CI (r = 0.76), and serum lactated was inversely associated with base deficit (r = -0.61). CONCLUSION: In rats submitted to Pringle's maneuver during 15 minutes following hemorrhagic shock state, there is a mathematical coupling with a very good correlation between several hemodynamic and metabolic variables.201222

Fluticasone Propionate Orally Disintegrating Tablet (APT-1011) for Eosinophilic Esophagitis: Randomized Controlled Trial.

Topical steroids are effective treatments for eosinophilic esophagitis (EoE). The FLUTE (Fluticasone in EoE) trial evaluated safety and efficacy of APT-1011 (fluticasone propionate oral disintegrating tablet) vs placebo for treatment of EoE. In this randomized, double-blind, placebo-controlled, dose-finding, phase 2b trial, 106 adults with EoE received 1 of 4 APT-1011 doses or placebo for a 12-week induction period and 40 weeks of maintenance. Primary outcome was histologic response (≤6 eosinophils per high-power field) at Week 12. Secondary outcomes included endoscopic features and dysphagia frequency. Histologic response rates were 0% for placebo, 80% for APT-1011 3 mg twice daily (BID), 67% for 3 mg at bedtime (HS), 86% for 1.5 mg BID, 48% for 1.5 mg HS (P < .001 for all groups vs placebo). At Week 12, mean Edema/Rings/Exudates/Furrows/Strictures (EoE Endoscopic Reference Score) total score (max, 9.0) improved from 4.5 to 2.3 for 3 mg BID, 5.3 to 2.1 for 3 mg HS, 4.6 to 1.7 for 1.5 mg BID, 5.3 to 2.9 for 1.5 mg HS vs 5.2 to 4.5 for placebo. Mean dysphagia frequency over 14 days improved from baseline to Week 12 with all active groups improving more than placebo. Improvements were sustained to Week 52. APT-1011 was safe and well-tolerated, with higher incidence of candidiasis noted at the higher twice daily doses. APT-1011 dosing regimens were superior for histologic and endoscopic responses, and for reduction in dysphagia frequency vs placebo. Based on the symptom improvement and assessment of adverse events together with the histologic response rate, 3 mg once daily at bedtime dose showed the most favorable risk-benefit profile. gov, Number: NCT03191864

Quantum cryptography using balanced homodyne detection

We report an experimental quantum key distribution that utilizes balanced homodyne detection, instead of photon counting, to detect weak pulses of coherent light. Although our scheme inherently has a finite error rate, it allows high-efficiency detection and quantum state measurement of the transmitted light using only conventional devices at room temperature. When the average photon number was 0.1, an error rate of 0.08 and "effective" quantum efficiency of 0.76 were obtained.Comment: Errors in the sentence citing ref.[20] are correcte

Finger Burns Caused By Concentrated Hydrofluoric Acid, Treated With Intra-arterial Calcium Gluconate Infusion: Case Report [queimadura Digital Por ácido Fluorídrico Concentrado Tratada Com Infusão Intra-arterial De Gluconato De Cálcio: Relato De Caso]

Context: Hydrofluoric acid (HF) is widely used in industry and at home. Severe lesions can occur after contact with highly concentrated solutions, leading to tissue necrosis and bone destruction. Specific treatment is based on neutralization of fluoride ions with calcium or magnesium solutions. Case report: A 41-year-old male was seen at the emergency department 35 minutes after skin contact with 70% HF, showing whitened swollen lesions on the middle and fourth fingers of his right hand with severe pain starting immediately after contact. 2.5% calcium gluconate ointment was applied. Twenty-four hours later, the patient was still in severe pain and the lesions had worsened. Considering the high concentration of the solution, early start of severe pain, lesion characteristics and impossibility of administering calcium gluconate subcutaneously because of the lesion location, the radial artery was catheterized and 2% calcium gluconate was administered via infusion pump for 36 hours, until the pain subsided. No adverse effects were seen during the procedure. Ten days later, the lesions were stable, without bone abnormalities on X-rays. Six months later, a complete recovery was seen. Conclusions: Intra-arterial calcium gluconate might be considered for finger burns caused by concentrated HF. Complete recovery of wounded fingers can be achieved with this technique even if started 24 hours after the exposure. However, controlled clinical trials are needed to confirm the effectiveness and safety of this intervention.1276379381Anderson, W.J., Anderson, J.R., Hydrofluoric acid burns of the hand: Mechanism of injury and treatment (1988) J Hand Surg Am, 13 (1), pp. 52-57Sheridan, R.L., Ryan, C.M., Quinby Jr., W.C., Blair, J., Tompkins, R.G., Burke, J.F., Emergency management of major hydrofluoric acid exposures (1995) Burns, 21 (1), pp. 62-64Lin, T.M., Tsai, C.C., Lin, S.D., Lai, C.S., Continuous intra-arterial infusion therapy in hydrofluoric acid burns (2000) J Occup Environ Med, 42 (9), pp. 892-897Roblin, I., Urban, M., Flicoteau, D., Martin, C., Pradeau, D., Topical treatment of experimental hydrofluoric acid skin burns by 2.5% calcium gluconate (2006) J Burn Care Res, 27 (6), pp. 889-894Vance, M.V., Curry, S.C., Kunkel, D.B., Ryan, P.J., Ruggeri, S.B., Digital hydrofluoric acid burns: Treatment with intraarterial calcium infusion (1986) Ann Emerg Med, 15 (8), pp. 890-896Graudins, A., Burns, M.J., Aaron, C.K., Regional intravenous infusion of calcium gluconate for hydrofluoric acid burns of the upper extremity (1997) Ann Emerg Med, 30 (5), pp. 604-60

Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is an allergen-mediated inflammatory disease with no approved treatment in the United States. Dupilumab, a VelocImmune-derived human monoclonal antibody against the interleukin (IL) 4 receptor, inhibits IL4 and IL13 signaling. Dupilumab is effective in the treatment of allergic, atopic, and type 2 diseases, so we assessed its efficacy and safety in patients with EoE. We performed a phase 2 study of adults with active EoE (2 episodes of dysphagia/week with peak esophageal eosinophil density of 15 or more eosinophils per high-power field), from May 12, 2015, through November 9, 2016, at 14 sites. Participants were randomly assigned to groups that received weekly subcutaneous injections of dupilumab (300 mg, n = 23) or placebo (n = 24) for 12 weeks. The primary endpoint was change from baseline to week 10 in Straumann Dysphagia Instrument (SDI) patient-reported outcome (PRO) score. We also assessed histologic features of EoE (peak esophageal intraepithelial eosinophil count and EoE histologic scores), endoscopically visualized features (endoscopic reference score), esophageal distensibility, and safety. The mean SDI PRO score was 6.4 when the study began. In the dupilumab group, SDI PRO scores were reduced by a mean value of 3.0 at week 10 compared with a mean reduction of 1.3 in the placebo group (P = .0304). At week 12, dupilumab reduced the peak esophageal intraepithelial eosinophil count by a mean 86.8 eosinophils per high-power field (reduction of 107.1%; P < .0001 vs placebo), the EoE-histologic scoring system (HSS) severity score by 68.3% (P < .0001 vs placebo), and the endoscopic reference score by 1.6 (P = .0006 vs placebo). Dupilumab increased esophageal distensibility by 18% vs placebo (P < .0001). Higher proportions of patients in the dupilumab group developed injection-site erythema (35% vs 8% in the placebo group) and nasopharyngitis (17% vs 4% in the placebo group). In a phase 2 trial of patients with active EoE, dupilumab reduced dysphagia, histologic features of disease (including eosinophilic infiltration and a marker of type 2 inflammation), and abnormal endoscopic features compared with placebo. Dupilumab increased esophageal distensibility and was generally well tolerated. ClinicalTrials.gov, Number: NCT02379052

Development and validation of a symptom-based activity index for adults with eosinophilic esophagitis.

BACKGROUND & AIMS: Standardized instruments are needed to assess the activity of eosinophilic esophagitis (EoE) and to provide end points for clinical trials and observational studies. We aimed to develop and validate a patient-reported outcome (PRO) instrument and score, based on items that could account for variations in patient assessments of disease severity. We also evaluated relationships between patient assessment of disease severity and EoE-associated endoscopic, histologic, and laboratory findings. METHODS: We collected information from 186 patients with EoE in Switzerland and the United States (69.4% male; median age, 43 y) via surveys (n = 135), focus groups (n = 27), and semistructured interviews (n = 24). Items were generated for the instruments to assess biologic activity based on physician input. Linear regression was used to quantify the extent to which variations in patient-reported disease characteristics could account for variations in patient assessment of EoE severity. The PRO instrument was used prospectively in 153 adult patients with EoE (72.5% male; median age, 38 y), and validated in an independent group of 120 patients with EoE (60.8% male; median age, 40.5 y). RESULTS: Seven PRO factors that are used to assess characteristics of dysphagia, behavioral adaptations to living with dysphagia, and pain while swallowing accounted for 67% of the variation in patient assessment of disease severity. Based on statistical consideration and patient input, a 7-day recall period was selected. Highly active EoE, based on endoscopic and histologic findings, was associated with an increase in patient-assessed disease severity. In the validation study, the mean difference between patient assessment of EoE severity (range, 0-10) and PRO score (range, 0-8.52) was 0.15. CONCLUSIONS: We developed and validated an EoE scoring system based on 7 PRO items that assess symptoms over a 7-day recall period. Clinicaltrials.gov number: NCT00939263

Creating a multi-center rare disease consortium - the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR).

 Eosinophilic gastrointestinal disorders (EGIDs) affect various segments of the gastrointestinal tract. Since these disorders are rare, collaboration is essential to enroll subjects in clinical studies and study the broader population. The Rare Diseases Clinical Research Network (RDCRN), a program of the National Center for Advancing Translational Sciences (NCATS), funded the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) in 2014 to advance the field of EGIDs. CEGIR facilitates collaboration among various centers, subspecialties, patients, professional organizations and patient-advocacy groups and includes 14 clinical sites. It has successfully initiated two large multi-center clinical studies looking to refine EGID diagnoses and management. Several pilot studies are underway that focus on various aspects of EGIDs including novel therapeutic interventions, diagnostic and monitoring methods, and the role of the microbiome in pathogenesis. CEGIR currently nurtures five physician-scholars through a career training development program and has published more than 40 manuscripts since its inception. This review focuses on CEGIR's operating model and progress and how it facilitates a framework for exchange of ideas and stimulates research and innovation. This consortium provides a model for progress on other potential clinical areas

Denial of long-term issues with agriculture on tropical peatlands will have devastating consequences

Non peer reviewe

The Physics of Star Cluster Formation and Evolution

© 2020 Springer-Verlag. The final publication is available at Springer via https://doi.org/10.1007/s11214-020-00689-4.Star clusters form in dense, hierarchically collapsing gas clouds. Bulk kinetic energy is transformed to turbulence with stars forming from cores fed by filaments. In the most compact regions, stellar feedback is least effective in removing the gas and stars may form very efficiently. These are also the regions where, in high-mass clusters, ejecta from some kind of high-mass stars are effectively captured during the formation phase of some of the low mass stars and effectively channeled into the latter to form multiple populations. Star formation epochs in star clusters are generally set by gas flows that determine the abundance of gas in the cluster. We argue that there is likely only one star formation epoch after which clusters remain essentially clear of gas by cluster winds. Collisional dynamics is important in this phase leading to core collapse, expansion and eventual dispersion of every cluster. We review recent developments in the field with a focus on theoretical work.Peer reviewe