Toward the Control of the Smoldering Front in the Reaction-Trailing Mode in Oil Shale Semicoke Porous Media

Results of an experimental investigation on the feasibility of propagating a smoldering front in reaction-trailing mode throughout an oil shale semicoke porous medium are reported. For oil recovery applications, this mode is particularly interesting to avoid low-temperature oxidation reactions, which appear simultaneously with organic matter devolatilization in the reaction-leading mode and are responsible for oxidation of part of the heavy oil. The particularity of this mode is that, contrary to the reaction-leading mode largely studied in the literature, the heat-transfer layer precedes the combustion layer. This leads to two separated high-temperature zones: (i) a devolatilization zone (free of oxygen), where the organic matter is thermally decomposed to incondensable gases, heavy oil, andfixed carbon, also called coke in the literature, without any oxidation, followed by (ii) an oxidation zone, where thefixed carbon left by devolatilization is oxidized. The transition from reaction-leading to reaction-trailing mode was obtained using low oxygen contents in the fed air. It is shown that two distinct layers, the heat-transfer layer and the combustion layer, propagate in a stable and repeatable way. The decrease of the oxygen fraction leads to a decrease of the smoldering temperature and to strongly limit the decarbonation of the mineral matrix. The CO2 emissions are limited. Regardless of the front temperature, all of the fed oxygen is consumed and all of thefixed carbon is oxidized at the passage of the smoldering front

A 'Performative' Social Movement: The Emergence of Collective Contentions within Collaborative Governance

The enmeshment of urban movements in networks of collaborative governance has been characterised as a process of co-option in which previously disruptive contentions are absorbed by regimes and reproduced in ways that do not threaten the stability of power relations. Applying a theoretical framework drawn from feminist philosopher Judith Butler this paper directs attention to the development of collective oppositional identities that remain embedded in conventional political processes. In a case study of the English tenants' movement, it investigates the potential of regulatory discourses that draw on market theories of performative voice to offer the collectivising narratives and belief in change that can generate the emotional identification of a social movement. The paper originates the concept of the ‘performative social movement’ to denote the contentious claims that continue to emerge from urban movements that otherwise appear quiescent

AWaRe-ness of antimicrobial stewardship challenges in pediatric emergency care: results from the PERFORM study assessing consistency and appropriateness of antibiotic prescribing across Europe

Objectives Optimization of antimicrobial stewardship (AMS) is key to tackling antimicrobial resistance (AMR), which is exacerbated by over-prescription of antibiotics in pediatric Emergency Departments (EDs). We described patterns of empiric antibiotic use in European EDs, and characterized appropriateness and consistency of prescribing. Methods Between August 2016 and December 2019 febrile children attending the ED in nine European countries with suspected infection were recruited into the PERFORM (Personalised Risk assessment in Febrile illness to Optimise Real-life Management) study. Empiric systemic antibiotic use was determined in view of assigned final ‘bacterial’ or ‘viral’ phenotype. Antibiotics were classified according to WHO AWaRe. Results Of 2130 febrile episodes (excluding children with non-bacterial/non-viral phenotypes), 1549 (72.7%) were assigned a ‘bacterial’ and 581 (27.3%) a ‘viral’ phenotype. A total of 1318/1549 (85.1%) episodes with a ‘bacterial’ and 269/581 (46.3%) with a ‘viral’ phenotype received empiric systemic antibiotics (first two days of admission). Of those, the majority (87.8% in ‘bacterial’ and 87.0% in ‘viral’ group) received parenteral antibiotics. The top three antibiotics prescribed were third-generation cephalosporins, penicillins and penicillin/beta-lactamase inhibitor combinations. Of those treated with empiric systemic antibiotics in the ‘viral’ group 216/269 (80.3%) received ≥ one Watch antibiotic. Conclusions Differentiating bacterial from viral etiology in febrile illness on initial ED presentation remains challenging, resulting in a substantial over-prescription of antibiotics. A significant proportion of patients with a ‘viral’ phenotype received systemic antibiotics, predominantly classified as WHO Watch. Rapid and accurate point-of-care tests in the ED differentiating between bacterial and viral etiology, could significantly improve AMS

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

External validation of a multivariable prediction model for identification of pneumonia and other serious bacterial infections in febrile immunocompromised children

Objective To externally validate and update the Feverkids tool clinical prediction model for differentiating bacterial pneumonia and other serious bacterial infections (SBIs) from non-SBI causes of fever in immunocompromised children. Design International, multicentre, prospective observational study embedded in PErsonalised Risk assessment in Febrile illness to Optimise Real-life Management across the European Union (PERFORM). Setting Fifteen teaching hospitals in nine European countries. Participants Febrile immunocompromised children aged 0–18 years. Methods The Feverkids clinical prediction model predicted the probability of bacterial pneumonia, other SBI or no SBI. Model discrimination, calibration and diagnostic performance at different risk thresholds were assessed. The model was then re-fitted and updated. Results Of 558 episodes, 21 had bacterial pneumonia, 104 other SBI and 433 no SBI. Discrimination was 0.83 (95% CI 0.71 to 0.90) for bacterial pneumonia, with moderate calibration and 0.67 (0.61 to 0.72) for other SBIs, with poor calibration. After model re-fitting, discrimination improved to 0.88 (0.79 to 0.96) and 0.71 (0.65 to 0.76) and calibration improved. Predicted risk 10% ruled in bacterial pneumonia with specificity 0.91 (0.88 to 0.94) and positive LR 6.51 (3.71 to 10.3). Predicted risk 30% ruled in other SBIs with specificity 0.89 (0.86 to 0.92) and positive LR 2.86 (1.91 to 4.25). Conclusion Discrimination and calibration were good for bacterial pneumonia but poorer for other SBIs. The rule-out thresholds have the potential to reduce unnecessary investigations and antibiotics in this high-risk group

Febrile illness in high-risk children: a prospective, international observational study

To assess and describe the aetiology and management of febrile illness in children with primary or acquired immunodeficiency at high risk of serious bacterial infection, as seen in emergency departments in tertiary hospitals. Prospective data on demographics, presenting features, investigations, microbiology, management, and outcome of patients within the ‘Biomarker Validation in HR patients’ database in PERFORM, were analysed. Immunocompromised children (< 18 years old) presented to fifteen European hospitals in nine countries, and one Gambian hospital, with fever or suspected infection and clinical indication for blood investigations. Febrile episodes were assigned clinical phenotypes using the validated PERFORM algorithm. Logistic regression was used to assess the effect size of predictive features of proven/presumed bacterial or viral infection. A total of 599 episodes in 482 children were analysed. Seventy-eight episodes (13.0%) were definite bacterial, 67 episodes probable bacterial (11.2%), and 29 bacterial syndrome (4.8%). Fifty-five were definite viral (9.2%), 49 probable viral (8.2%), and 23 viral syndrome (3.8%). One hundred ninety were unknown bacterial or viral infections (31.7%), and 108 had inflammatory or other non-infectious causes of fever (18.1%). Predictive features of proven/presumed bacterial infection were ill appearance (OR 3.1 (95% CI 2.1–4.6)) and HIV (OR 10.4 (95% CI 2.0–54.4)). Ill appearance reduced the odds of having a proven/presumed viral infection (OR 0.5 (95% CI 0.3–0.9)). A total of 82.1% had new empirical antibiotics started on admission (N = 492); 94.3% proven/presumed bacterial (N = 164), 66.1% proven/presumed viral (N = 84), and 93.2% unknown bacterial or viral infections (N = 177). Mortality was 1.9% (N = 11) and 87.1% made full recovery (N = 522)

Carbonyl reductase 1 catalyzes 20β-reduction of glucocorticoids, modulating receptor activation and metabolic complications of obesity

Carbonyl Reductase 1 (CBR1) is a ubiquitously expressed cytosolic enzyme important in exogenous drug metabolism but the physiological function of which is unknown. Here, we describe a role for CBR1 in metabolism of glucocorticoids. CBR1 catalyzes the NADPH-dependent production of 20 beta-dihydrocortisol (20 beta-DHF) from cortisol. CBR1 provides the major route of cortisol metabolism in horses and is up-regulated in adipose tissue in obesity in horses, humans and mice. We demonstrate that 20 beta-DHF is a weak endogenous agonist of the human glucocorticoid receptor (GR). Pharmacological inhibition of CBR1 in diet-induced obesity in mice results in more marked glucose intolerance with evidence for enhanced hepatic GR signaling. These findings suggest that CBR1 generating 20 beta-dihydrocortisol is a novel pathway modulating GR activation and providing enzymatic protection against excessive GR activation in obesity