IMPORTANCE: The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) uses the Sequential Organ Failure Assessment (SOFA) score to grade organ dysfunction in adult patients ...with suspected infection. However, the SOFA score is not adjusted for age and therefore not suitable for children. OBJECTIVES: To adapt and validate a pediatric version of the SOFA score (pSOFA) in critically ill children and to evaluate the Sepsis-3 definitions in patients with confirmed or suspected infection. DESIGN, SETTING, AND PARTICIPANTS: This retrospective observational cohort study included all critically ill children 21 years or younger admitted to a 20-bed, multidisciplinary, tertiary pediatric intensive care unit between January 1, 2009 and August 1, 2016. Data on these children were obtained from an electronic health record database. The pSOFA score was developed by adapting the original SOFA score with age-adjusted cutoffs for the cardiovascular and renal systems and by expanding the respiratory criteria to include noninvasive surrogates of lung injury. Daily pSOFA scores were calculated from admission until day 28 of hospitalization, discharge, or death (whichever came first). Three additional pediatric organ dysfunction scores were calculated for comparison. EXPOSURES: Organ dysfunction measured by the pSOFA score, and sepsis and septic shock according to the Sepsis-3 definitions. MAIN OUTCOMES AND MEASURES: The primary outcome was in-hospital mortality. The daily pSOFA scores and additional pediatric organ dysfunction scores were compared. Performance was evaluated using the area under the curve. The pSOFA score was then used to assess the Sepsis-3 definitions in the subgroup of children with confirmed or suspected infection. RESULTS: In all, 6303 patients with 8711 encounters met inclusion criteria. Each encounter was treated independently. Of the 8482 survivors of hospital encounters, 4644 (54.7%) were male and the median (interquartile range IQR) age was 69 (17-156) months. Among the 229 nonsurvivors, 127 (55.4%) were male with a median (IQR) age of 43 (8-144) months. In-hospital mortality was 2.6%. The maximum pSOFA score had excellent discrimination for in-hospital mortality, with an area under the curve of 0.94 (95% CI, 0.92-0.95). The pSOFA score had a similar or better performance than other pediatric organ dysfunction scores. According to the Sepsis-3 definitions, 1231 patients (14.1%) were classified as having sepsis and had a mortality rate of 12.1%, and 347 (4.0%) had septic shock and a mortality rate of 32.3%. Patients with sepsis were more likely to die than patients with confirmed or suspected infection but no sepsis (odds ratio, 18; 95% CI, 11-28). Of the 229 patients who died during their hospitalization, 149 (65.0%) had sepsis or septic shock during their course. CONCLUSIONS AND RELEVANCE: The pSOFA score was adapted and validated with age-adjusted variables in critically ill children. Using the pSOFA score, the Sepsis-3 definitions were assessed in children with confirmed or suspected infection. This study is the first assessment, to date, of the Sepsis-3 definitions in critically ill children. Use of these definitions in children is feasible and shows promising results.
Abstract
Traditional 3D printing based on Digital Light Processing Stereolithography (DLP-SL) is unnecessarily limiting as applied to microfluidic device fabrication, especially for high-resolution ...features. This limitation is due primarily to inherent tradeoffs between layer thickness, exposure time, material strength, and optical penetration that can be impossible to satisfy for microfluidic features. We introduce a generalized 3D printing process that significantly expands the accessible spatially distributed optical dose parameter space to enable the fabrication of much higher resolution 3D components without increasing the resolution of the 3D printer. Here we demonstrate component miniaturization in conjunction with a high degree of integration, including 15 μm × 15 μm valves and a 2.2 mm × 1.1 mm 10-stage 2-fold serial diluter. These results illustrate our approach’s promise to enable highly functional and compact microfluidic devices for a wide variety of biomolecular applications.
The current increasing interest in hydrogen utilization and increasing understanding of hydrogen combustion motivate this review of flammability characteristics of hydrogen. The intent is to present ...a thorough and self-contained tutorial that covers the existing fundamental knowledge in a uniform and concise manner. The presentation begins with an up-dated exposition of the elementary chemical mechanism of hydrogen oxidation, including the latest chemical-kinetic results, with evaluated selections of reaction-rate parameters. Understanding of the mechanism is emphasized through presentation of systematically reduced overall steps and their associated rates. Useful simplifications of the chemistry are thereby exposed and appraised, identifying applicable quasi-steady-state approximations. The status of our knowledge of the fundamental transport properties for hydrogen combustion is then summarized, with indication of the relevance of thermal diffusion for hydrogen. Hydrogen–oxygen autoignition processes are next analyzed, including the important differences found under conditions above and below the crossover temperature at which the rates of the branching and recombination steps are equal, with an explanation of the classical explosion diagram that exhibits three explosion limits. Time-dependent and counter-flow mixing layers are addressed in the context of ignition processes. Knowledge of hydrogen deflagrations is reviewed, including their flame structures, burning velocities, and flammability limits, with special emphasis on peculiarities and simplification that occur in the vicinity of the lean limit. Deflagration instabilities and effects of strain and curvature on deflagrations are described, resulting under appropriate circumstances in flame balls, the structures, characteristics, and importance of which are analyzed. The structures and stabilization mechanisms of hydrogen diffusion flames are reviewed, pointing out the current state of knowledge and current uncertainties in their extinction conditions. Hydrogen detonations also are considered, with explanations given of their detonation velocities, structures, and instabilities, including cellular detonations and emphasizing the importance of future studies of vibrational relaxation effects in these detonations. Finally, some comments and observations on the applications and future prospects for hydrogen usage are offered from viewpoints of safety and energy production.
Like cancer cells, virally infected cells have dramatically altered metabolic requirements. We analyzed global metabolic changes induced by latent infection with an oncogenic virus, Kaposi's ...Sarcoma-associated herpesvirus (KSHV). KSHV is the etiologic agent of Kaposi's Sarcoma (KS), the most common tumor of AIDS patients. Approximately one-third of the nearly 200 measured metabolites were altered following latent infection of endothelial cells by KSHV, including many metabolites of anabolic pathways common to most cancer cells. KSHV induced pathways that are commonly altered in cancer cells including glycolysis, the pentose phosphate pathway, amino acid production and fatty acid synthesis. Interestingly, over half of the detectable long chain fatty acids detected in our screen were significantly increased by latent KSHV infection. KSHV infection leads to the elevation of metabolites involved in the synthesis of fatty acids, not degradation from phospholipids, and leads to increased lipid droplet organelle formation in the infected cells. Fatty acid synthesis is required for the survival of latently infected endothelial cells, as inhibition of key enzymes in this pathway led to apoptosis of infected cells. Addition of palmitic acid to latently infected cells treated with a fatty acid synthesis inhibitor protected the cells from death indicating that the products of this pathway are essential. Our metabolomic analysis of KSHV-infected cells provides insight as to how oncogenic viruses can induce metabolic alterations common to cancer cells. Furthermore, this analysis raises the possibility that metabolic pathways may provide novel therapeutic targets for the inhibition of latent KSHV infection and ultimately KS tumors.
The intake of added sugars, such as from table sugar (sucrose) and high-fructose corn syrup has increased dramatically in the last hundred years and correlates closely with the rise in obesity, ...metabolic syndrome, and diabetes. Fructose is a major component of added sugars and is distinct from other sugars in its ability to cause intracellular ATP depletion, nucleotide turnover, and the generation of uric acid. In this article, we revisit the hypothesis that it is this unique aspect of fructose metabolism that accounts for why fructose intake increases the risk for metabolic syndrome. Recent studies show that fructose-induced uric acid generation causes mitochondrial oxidative stress that stimulates fat accumulation independent of excessive caloric intake. These studies challenge the long-standing dogma that "a calorie is just a calorie" and suggest that the metabolic effects of food may matter as much as its energy content. The discovery that fructose-mediated generation of uric acid may have a causal role in diabetes and obesity provides new insights into pathogenesis and therapies for this important disease.
A majority of children admitted to a single hospital in late 2021–early 2022 with acute hepatitis of unknown cause tested positive for adenovirus. This report describes the children’s illnesses and ...outcomes.
Viruses rely on host cellular metabolism to provide the energy and biosynthetic building blocks required for their replication. Dengue virus (DENV), a member of the Flaviviridae family, is one of the ...most important arthropod-borne human pathogens worldwide. We analyzed global intracellular metabolic changes associated with DENV infection of primary human cells. Our metabolic profiling data suggested that central carbon metabolism, particularly glycolysis, is strikingly altered during a time course of DENV infection. Glucose consumption is increased during DENV infection and depriving DENV-infected cells of exogenous glucose had a pronounced impact on viral replication. Furthermore, the expression of both glucose transporter 1 and hexokinase 2, the first enzyme of glycolysis, is upregulated in DENV-infected cells. Pharmacologically inhibiting the glycolytic pathway dramatically reduced DENV RNA synthesis and infectious virion production, revealing a requirement for glycolysis during DENV infection. Thus, these experiments suggest that DENV induces the glycolytic pathway to support efficient viral replication. This study raises the possibility that metabolic inhibitors, such as those that target glycolysis, could be used to treat DENV infection in the future.
Approximately 400 million people are infected with dengue virus (DENV) annually, and more than one-third of the global population is at risk of infection. As there are currently no effective vaccines or specific antiviral therapies for DENV, we investigated the impact DENV has on the host cellular metabolome to identify metabolic pathways that are critical for the virus life cycle. We report an essential role for glycolysis during DENV infection. DENV activates the glycolytic pathway, and inhibition of glycolysis significantly blocks infectious DENV production. This study provides further evidence that viral metabolomic analyses can lead to the discovery of novel therapeutic targets to block the replication of medically important human pathogens.
Advanced ceramics have been extensively used in industry applications due to their properties of high resistance to wear and hardness. However, there is still a high added cost related to the ...workpiece finish, which is usually performed by the grinding process, the only economically viable process that produces surfaces of high quality and geometric precision. Companies have been looking for optimization in the grinding process, for example in the reduction of the cutting fluid used, in this case also in order to meet the world environmental preservation requirements, without compromising the quality of the finished part. In this context, the present research sought to exploit the technique of minimum quantity of lubrication (MQL) in the external cylindrical plunge grinding of ceramics with diamond grinding wheels. Two methods of cooling-lubrication were used: the conventional and MQL, with three different feed rates (
V
f1
,
V
f2
, and
V
f3
) for each condition. A conventional nozzle and a proper nozzle for MQL with uniform output jet were used. Variables were analyzed as the surface roughness, roundness deviation, scanning electron microscopy (SEM), G ratio, and output acoustic emission. The results showed that the conventional cooling-lubrication gives the best results for the output variables analyzed, comparing with the MQL. However, the MQL still presented satisfactory results that may be sufficient in several cases. Considering the economic, health, and environmental benefits presented by this technique, MQL comes as a strong tendency for ceramic grinding processes.
Adaptive immunity is mediated by T- and B-cells, which are immune cells capable of developing pathogen-specific memory that confers immunological protection. Memory and effector functions of B- and ...T-cells are predicated on the recognition through specialized receptors of specific targets (antigens) in pathogens. More specifically, B- and T-cells recognize portions within their cognate antigens known as epitopes. There is great interest in identifying epitopes in antigens for a number of practical reasons, including understanding disease etiology, immune monitoring, developing diagnosis assays, and designing epitope-based vaccines. Epitope identification is costly and time-consuming as it requires experimental screening of large arrays of potential epitope candidates. Fortunately, researchers have developed in silico prediction methods that dramatically reduce the burden associated with epitope mapping by decreasing the list of potential epitope candidates for experimental testing. Here, we analyze aspects of antigen recognition by T- and B-cells that are relevant for epitope prediction. Subsequently, we provide a systematic and inclusive review of the most relevant B- and T-cell epitope prediction methods and tools, paying particular attention to their foundations.
► Pyrolysis of lignocellulosic biomass and marine biomass was studied by TGA–MS. ► The main gases produced were identified in the temperature range 200–450°C. ► CO2, H2O and light hydrocarbons were ...the main products detected. ► H2 was also observed at high temperatures due to secondary reactions. ► A multiple-step model was used to predict the pyrolysis of biomass.
The pyrolysis characteristics of three lignocellulosic biomasses (fir wood, eucalyptus and pine bark) and a marine biomass (Nannochloropsis gaditana microalgae) were investigated by thermogravimetric analysis coupled with mass spectrometry (TGA–MS). Thermal degradation of lignocellulosic biomass was divided into four zones, corresponding to the decomposition of their main components (cellulose, hemicellulose and lignin) and a first step associated to water removal. Differences in volatile matter and cellulose content of lignocellulosic species resulted in different degradation rates. Microalgae pyrolysis occurred in three stages due to the main components of them (proteins), which are greatly different from lignocellulosic biomass. Heating rate effect was also studied. The main gaseous products formed were CO2, light hydrocarbons and H2O. H2 was detected at high temperatures, being associated to secondary reactions (char self-gasification). Pyrolysis kinetics were studied using a multiple-step model. The proposed model successfully predicted the pyrolytic behaviour of these samples resulting to be statistically meaningful.
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