Design and Characterization of a Liquid-Fueled Microcombustor

As part of an effort to develop a microscale gas turbine engine, this paper presents the design and experimental characterization of a microcombustor that catalytically burns JP8 fuel. Due to the high energy densities of hydrocarbon fuels, microscale heat engines based on them may enable compact power sources with specific energies higher than those of current battery systems. In addition, utilizing a commonly available logistics fuel would provide advantages for military applications. Thus, a microscale engine burning JP8 fuel is attractive as a portable power source. A liquid-fueled microcombustor with a combustion chamber volume of 1.4 cm 3 and an overall die size of 36.4×36.4×6.5 mm 3 was designed, microfabricated, and experimentally characterized. Two configurations were tested and compared, one with the combustion chamber entirely filled with a catalyst and the other with the combustion chamber partially filled with a catalyst. In the configuration filled with a catalyst, JP8 combustion was sustained at mass flow rates up to 0.1 g/s and an exit gas temperature of 780 K; an overall combustor efficiency of 19% and a power density of 43 MW/ m 3 were achieved. The primary limitation on increasing the mass flow rates and temperature further was the structural failure of the device due to thermal stresses. With the partially filled configuration, a mass flow rate of 0.2 g/s and a corresponding power density of 54 MW/ m 3 were obtained. The exit gas temperature for the partially filled configuration was as high as 720 K, and the maximum overall efficiency was over 22%. Although the reduced amount of catalyst led to incomplete combustion, smaller thermal losses resulted in an increase in the overall combustor efficiency and power density. A nondimensional operating map was constructed based on the experiment, and it suggests that improving the thermal efficiency would be necessary to achieve higher efficiencies in the device.United States. Defense Advanced Research Projects Agency (Contract DAAD19-01-2-0010)United States. Army Research Office (Contract DAAD19-01-2-0010

Endemicity of Zoonotic Diseases in Pigs and Humans in Lowland and Upland Lao PDR: Identification of Socio-cultural Risk Factors

In Lao People's Democratic Republic pigs are kept in close contact with families. Human risk of infection with pig zoonoses arises from direct contact and consumption of unsafe pig products. This cross-sectional study was conducted in Luang Prabang (north) and Savannakhet (central-south) Provinces. A total of 59 villages, 895 humans and 647 pigs were sampled and serologically tested for zoonotic pathogens including: hepatitis E virus (HEV), Japanese encephalitis virus (JEV) and Trichinella spiralis; In addition, human sera were tested for Taenia spp. and cysticercosis. Seroprevalence of zoonotic pathogens in humans was high for HEV (Luang Prabang: 48.6%, Savannakhet: 77.7%) and T. spiralis (Luang Prabang: 59.0%, Savannakhet: 40.5%), and lower for JEV (around 5%), Taenia spp. (around 3%) and cysticercosis (Luang Prabang: 6.1, Savannakhet 1.5%). Multiple correspondence analysis and hierarchical clustering of principal components was performed on descriptive data of human hygiene practices, contact with pigs and consumption of pork products. Three clusters were identified: Cluster 1 had low pig contact and good hygiene practices, but had higher risk of T. spiralis. Most people in cluster 2 were involved in pig slaughter (83.7%), handled raw meat or offal (99.4%) and consumed raw pigs' blood (76.4%). Compared to cluster 1, cluster 2 had increased odds of testing seropositive for HEV and JEV. Cluster 3 had the lowest sanitation access and had the highest risk of HEV, cysticercosis and Taenia spp. Farmers which kept their pigs tethered (as opposed to penned) and disposed of manure in water sources had 0.85 (95% CI: 0.18 to 0.91) and 2.39 (95% CI: 1.07 to 5.34) times the odds of having pigs test seropositive for HEV, respectively. The results have been used to identify entry-points for intervention and management strategies to reduce disease exposure in humans and pigs, informing control activities in a cysticercosis hyper-endemic village

Phase 1B, randomized, double-blind, dose-escalation trial of CPG 10101 in patients with chronic hepatitis C virus

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Why don't hospital staff activate the rapid response system (RRS)? How frequently is it needed and can the process be improved?

Abstract Background The rapid response system (RRS) is a process of accessing help for health professionals when a patient under their care becomes severely ill. Recent studies and meta-analyses show a reduction in cardiac arrests by a one-third in hospitals that have introduced a rapid response team, although the effect on overall hospital mortality is less clear. It has been suggested that the difficulty in establishing the benefit of the RRS has been due to implementation difficulties and a reluctance of clinical staff to call for additional help. This assertion is supported by the observation that patients continue to have poor outcomes in our institution despite an established RRS being available. In many of these cases, the patient is often unstable for many hours or days without help being sought. These poor outcomes are often discovered in an ad hoc fashion, and the real numbers of patients who may benefit from the RRS is currently unknown. This study has been designed to answer three key questions to improve the RRS: estimate the scope of the problem in terms of numbers of patients requiring activation of the RRS; determine cognitive and socio-cultural barriers to calling the Rapid Response Team; and design and implement solutions to address the effectiveness of the RRS. Methods The extent of the problem will be addressed by establishing the incidence of patients who meet abnormal physiological criteria, as determined from a point prevalence investigation conducted across four hospitals. Follow-up review will determine if these patients subsequently require intensive care unit or critical care intervention. This study will be grounded in both cognitive and socio-cultural theoretical frameworks. The cognitive model of situation awareness will be used to determine psychological barriers to RRS activation, and socio-cultural models of interprofessional practice will be triangulated to inform further investigation. A multi-modal approach will be taken using reviews of clinical notes, structured interviews, and focus groups. Interventions will be designed using a human factors analysis approach. Ongoing surveillance of adverse outcomes and surveys of the safety climate in the clinical areas piloting the interventions will occur before and after implementation

How to use the Harmonising Outcome Measures for Eczema Core Outcome Set for atopic dermatitis trials: a users’ guide

BackgroundThe Harmonising Outcome Measures for Eczema (HOME) initiative has agreed upon the Core Outcome Set (COS) for use in atopic dermatitis (AD) clinical trials, but additional guidance is needed to maximize its uptake.ObjectivesTo provide answers to some of the commonly asked questions about using the HOME COS; to provide data to help with the interpretation of trial results; and to support sample size calculations for future trials.Methods and resultsWe provide practical guidance on the use of the HOME COS for investigators planning clinical trials in patients with AD. It answers some of the common questions about using the HOME COS, how to access the outcome measurement instruments, what training/resources are needed to use them appropriately and clarifies when the COS is applicable. We also provide exemplar data to inform sample size calculations for eczema trials and encourage standardized data collection and reporting of the COS.ConclusionsBy encouraging adoption of the COS and facilitating consistent reporting of outcome data, it is hoped that the results of eczema trials will be more comprehensive and readily combined in meta-analyses and that patient care will subsequently be improved

Effects of Icosapent Ethyl on Total Ischemic Events: From REDUCE-IT.

BACKGROUND: In time-to-first-event analyses, icosapent ethyl significantly reduced the risk of ischemic events, including cardiovascular death, among patients with elevated triglycerides receiving statins. These patients are at risk for not only first but also subsequent ischemic events. OBJECTIVES: Pre-specified analyses determined the extent to which icosapent ethyl reduced total ischemic events. METHODS: REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) randomized 8,179 statin-treated patients with triglycerides ≥135 and 40 and ≤100 mg/dl (median baseline of 75 mg/dl), and a history of atherosclerosis (71% patients) or diabetes (29% patients) to icosapent ethyl 4 g/day or placebo. The main outcomes were total (first and subsequent) primary composite endpoint events (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina) and total key secondary composite endpoint events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke). As a pre-specified statistical method, we determined differences in total events using negative binomial regression. We also determined differences in total events using other statistical models, including Andersen-Gill, Wei-Lin-Weissfeld (Li and Lagakos modification), both pre-specified, and a post hoc joint frailty analysis. RESULTS: In 8,179 patients, followed for a median of 4.9 years, 1,606 (55.2%) first primary endpoint events and 1,303 (44.8%) subsequent primary endpoint events occurred (which included 762 second events, and 541 third or more events). Overall, icosapent ethyl reduced total primary endpoint events (61 vs. 89 per 1,000 patient-years for icosapent ethyl versus placebo, respectively; rate ratio: 0.70; 95% confidence interval: 0.62 to 0.78; p < 0.0001). Icosapent ethyl also reduced totals for each component of the primary composite endpoint, as well as the total key secondary endpoint events (32 vs. 44 per 1,000 patient-years for icosapent ethyl versus placebo, respectively; rate ratio: 0.72; 95% confidence interval: 0.63 to 0.82; p < 0.0001). CONCLUSIONS: Among statin-treated patients with elevated triglycerides and cardiovascular disease or diabetes, multiple statistical models demonstrate that icosapent ethyl substantially reduces the burden of first, subsequent, and total ischemic events. (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial [REDUCE-IT]; NCT01492361)

A new dawn for industrial photosynthesis

Several emerging technologies are aiming to meet renewable fuel standards, mitigate greenhouse gas emissions, and provide viable alternatives to fossil fuels. Direct conversion of solar energy into fungible liquid fuel is a particularly attractive option, though conversion of that energy on an industrial scale depends on the efficiency of its capture and conversion. Large-scale programs have been undertaken in the recent past that used solar energy to grow innately oil-producing algae for biomass processing to biodiesel fuel. These efforts were ultimately deemed to be uneconomical because the costs of culturing, harvesting, and processing of algal biomass were not balanced by the process efficiencies for solar photon capture and conversion. This analysis addresses solar capture and conversion efficiencies and introduces a unique systems approach, enabled by advances in strain engineering, photobioreactor design, and a process that contradicts prejudicial opinions about the viability of industrial photosynthesis. We calculate efficiencies for this direct, continuous solar process based on common boundary conditions, empirical measurements and validated assumptions wherein genetically engineered cyanobacteria convert industrially sourced, high-concentration CO2 into secreted, fungible hydrocarbon products in a continuous process. These innovations are projected to operate at areal productivities far exceeding those based on accumulation and refining of plant or algal biomass or on prior assumptions of photosynthetic productivity. This concept, currently enabled for production of ethanol and alkane diesel fuel molecules, and operating at pilot scale, establishes a new paradigm for high productivity manufacturing of nonfossil-derived fuels and chemicals

3,5-Dimethylisoxazoles Act As Acetyl-lysine-mimetic Bromodomain Ligands

Histone-lysine acetylation is a vital chromatin post-translational modification involved in the epigenetic regulation of gene transcription. Bromodomains bind acetylated lysines, acting as readers of the histone-acetylation code. Competitive inhibitors of this interaction have antiproliferative and anti-inflammatory properties. With 57 distinct bromodomains known, the discovery of subtype-selective inhibitors of the histone-bromodomain interaction is of great importance. We have identified the 3,5 dimethylisoxazole moiety as a novel acetyl-lysine bioisostere, which displaces acetylated histone-mimicking peptides from bromodomains. Using X-ray crystallographic analysis, we have determined the interactions responsible for the activity and selectivity of 4-substituted 3,5-dimethylisoxazoles against a selection of phylogenetically diverse bromodomains. By exploiting these interactions, we have developed compound 4d, which has IC50 values of &lt;5 μM for the bromodomain-containing proteins BRD2(1) and BRD4(1). These compounds are promising leads for the further development of selective probes for the bromodomain and extra C-terminal domain (BET) family and CREBBP bromodomains

Multimodal electrophysiological analyses reveal that reduced synaptic excitatory neurotransmission underlies seizures in a model of NMDAR antibody-mediated encephalitis

Seizures are a prominent feature in N-Methyl-D-Aspartate receptor antibody (NMDAR antibody) encephalitis, a distinct neuro-immunological disorder in which specific human autoantibodies bind and crosslink the surface of NMDAR proteins thereby causing internalization and a state of NMDAR hypofunction. To further understand ictogenesis in this disorder, and to test a potential treatment compound, we developed an NMDAR antibody mediated rat seizure model that displays spontaneous epileptiform activity in vivo and in vitro. Using a combination of electrophysiological and dynamic causal modelling techniques we show that, contrary to expectation, reduction of synaptic excitatory, but not inhibitory, neurotransmission underlies the ictal events through alterations in the dynamical behaviour of microcircuits in brain tissue. Moreover, in vitro application of a neurosteroid, pregnenolone sulphate, that upregulates NMDARs, reduced established ictal activity. This proof-of-concept study highlights the complexity of circuit disturbances that may lead to seizures and the potential use of receptor-specific treatments in antibody-mediated seizures and epilepsy