Tandem Fan Applications in Advanced STOVL Fighter Configurations

The series/parallel tandem fan engine is evaluated for application in advanced STOVL supersonic fighter aircraft. Options in engine cycle parameters and design of the front fan flow diverter are examined for their effects on engine weight, dimensions, and other factors in integration of the engine with the aircraft. Operation of the engine in high-bypass flow mode during cruise and loiter flight is considered as a means of minimizizng fuel consumption. Engine thrust augmentation by burning in the front fan exhaust is discussed. Achievement of very sort takeoff with vectored thrust in briefly reviewed for tandem fan engine configurations with vectorable front fan nozzles. Examples are given of two aircraft configuration planforms, a delta-canard, and a forward-swept wing, to illustrate the major features. design considerations, and potential performance of the tandem fan installation in each. Full realization of the advantages of tandem fan propulsion are found to depend on careful selection of the aircraft configuration, since integration requirements can strongly influence the engine performance

Postmortem tissue distribution of morphine and its metabolites in a series of heroin related deaths

The abuse of heroin (diamorphine) and heroin deaths are growing around the world. The interpretation of the toxicological results from suspected heroin deaths is notoriously difficult especially in cases where there may be limited samples. In order to help forensic practitioners with heroin interpretation we determined the concentration of morphine (M), morphine‐3‐glucuronide (M3G) and morphine‐6‐glucuronide (M6G) in blood (femoral and cardiac), brain (thalamus), liver (deep right lobe), bone marrow (sternum), skeletal muscle (psoas) and vitreous humor in 44 heroin related deaths. The presence of 6‐monoacetylmorphine (6‐MAM) in any of the postmortem samples was used as confirmation of heroin use. Quantitation was carried out using a validated LC‐MS/MS method with solid phase extraction. We also determined the presence of papaverine, noscapine and codeine in the samples, substances often found in illicit heroin and that may help determine illicit heroin use. The results of this study show that vitreous is the best sample to detect 6‐MAM (100% of cases), and thus heroin use. The results of the M, M3G and M6G quantitation in this study allow a degree of interpretation when samples are limited. However in some cases it may not be possible to determine heroin/morphine use as in 4 cases in muscle (3 cases in bone marrow) no morphine, morphine‐3‐glucuronide or morphine‐6‐glucuronide was detected, even though they were detected in other case samples. As always postmortem cases of suspected morphine/heroin intoxication should be interpreted with care and with as much case knowledge as possible

How safe and effective is ondansetron for nausea and vomiting in pregnancy?

Q: How safe and effective is ondansetron for nausea and vomiting in pregnancy? Evidence-based answer: oral ondansetron is more effective than a combination of pyridoxine and doxylamine for outpatient treatment of nausea and vomiting in pregnancy (strength of recommendation [SOR]: B, randomized controlled trial [RCT]). For moderate to severe nausea and vomiting, intravenous (IV) ondansetron is at least as effective as IV metoclopramide and may cause fewer adverse reactions (SOR: B, RCTs). Disease registry, case-control, and cohort studies report a slight increase in the risk of cardiac defects with ondansetron use in first-trimester pregnancies, but no major or other birth defects are associated with ondansetron exposure (SOR: B, a systematic review of observational trials and a single retrospective cohort study). A specialty society guideline recommends weighing the risks and benefits of ondansetron use before 10 weeks' gestational age and suggests reserving ondansetron for patients who have persistent nausea and vomiting unresponsive to first- and second-line treatments (SOR: C, expert opinion).Kimberly L. Collins, MD; Megan Wilson, MD; E. Chris Vincent, MD, University of Washington, Seattle ; Sarah Safranek, MLIS, University of Washington, SeattleIncludes bibliographical reference

Backlash against the #MeToo Movement: How Women’s Voice Causes Men to Feel Victimized

Three studies examined whether perceived increase in women’s “voice” (i.e., being heard and taken seriously about sexual assault) contributes to perceptions of bias against men. In Study 1, both men and women who perceived women to have a greater voice related to sexual assault, perceived greater victimization of men. This relationship was stronger for relatively conservative participants. In Study 2, relatively conservative (but not relatively liberal) participants who read about #MeToo perceived greater men’s victimization than those in the control condition. Study 3 examined responses to perceiving that men are victimized by #MeToo. For relatively conservative (but not liberal) men, perceptions of men’s victimhood led to less willingness to work alone with a woman and less willingness to combat sexual assault (relative to a control condition). Thus, while the #MeToo movement brings awareness of issues of sexual assault, it also generates a backlash among the more conservative, and may accentuate gender disparities

A histidine residue and a tetranuclear cuprous‐thiolate cluster dominate the copper loading landscape of a copper storage protein from Streptomyces lividans

The chemical basis for protecting organisms against the toxic effect imposed by excess cuprous ions is to constrain this through high‐affinity binding sites that use cuprous‐thiolate coordination chemistry. In bacteria, a family of cysteine rich four‐helix bundle proteins utilise thiolate chemistry to bind up to 80 cuprous ions. These proteins have been termed copper storage proteins (Csp). The present study investigates cuprous ion loading to the Csp from Streptomyces lividans (SlCsp) using a combination of X‐ray crystallography, site‐directed mutagenesis and stopped‐flow reaction kinetics with either aquatic cuprous ions or a chelating donor. We illustrate that at low cuprous ion concentrations, copper is loaded exclusively into an outer core region of SlCsp via one end of the four‐helix bundle, facilitated by a set of three histidine residues. X‐ray crystallography reveals the existence of polynuclear cuprous‐thiolate clusters culminating in the assembly of a tetranuclear [Cu4(μ2‐S‐Cys)4(Νδ1‐His)] cluster in the outer core. As more cuprous ions are loaded, the cysteine lined inner core of SlCsp fills with cuprous ions but in a fluxional and dynamic manner with no evidence for the assembly of further intermediate polynuclear cuprous‐thiolate clusters as observed in the outer core. Using site‐directed mutagenesis a key role for His107 in the efficient loading of cuprous ions from a donor is established. A model of copper loading to SlCsp is proposed and discussed

Exposure to Household Air Pollution from Biomass Cookstoves and Levels of Fractional Exhaled Nitric Oxide (FeNO) among Honduran Women

Household air pollution is estimated to be responsible for nearly three million premature deaths annually. Measuring fractional exhaled nitric oxide (FeNO) may improve the limited understanding of the association of household air pollution and airway inflammation. We evaluated the cross-sectional association of FeNO with exposure to household air pollution (24-h average kitchen and personal fine particulate matter and black carbon; stove type) among 139 women in rural Honduras using traditional stoves or cleaner-burning Justastoves. We additionally evaluated interaction by age. Results were generally consistent with a null association; we did not observe a consistent pattern for interaction by age. Evidence from ambient and household air pollution regarding FeNO is inconsistent, and may be attributable to differing study populations, exposures, and FeNO measurement procedures (e.g., the flow rate used to measure FeNO)

The atypical chemokine receptor Ackr2 constrains NK cell migratory activity and promotes metastasis

Chemokines have been shown to be essential players in a range of cancer contexts. In this study, we demonstrate that mice deficient in the atypical chemokine receptor Ackr2 display impaired development of metastasis in vivo in both cell line and spontaneous models. Further analysis reveals that this relates to increased expression of the chemokine receptor CCR2, specifically by KLRG1+ NK cells from the Ackr2−/− mice. This leads to increased recruitment of KLRG1+ NK cells to CCL2-expressing tumors and enhanced tumor killing. Together, these data indicate that Ackr2 limits the expression of CCR2 on NK cells and restricts their tumoricidal activity. Our data have important implications for our understanding of the roles for chemokines in the metastatic process and highlight Ackr2 and CCR2 as potentially manipulable therapeutic targets in metastasis

A systematic review of pharmacotherapeutic clinical trial end-points for bronchiectasis in adults

Bronchiectasis is an increasing clinical problem, but multiple recent clinical trials have failed to reach their primary end-point. Difficulties in achieving “positive” bronchiectasis trials is reflected in a lack of agreement from trialists and regulators on what are the optimal end-points. To evaluate the use of end-points in bronchiectasis trials, we conducted a systematic review of published bronchiectasis trials from 2008 to 2018 and extracted end-points used, definitions, methods of analysis and responsiveness. Our analysis shows that quality of life and exacerbation end-points are most frequently used. Trials using exacerbation end-points have been characterised by varying definitions, multiple methods of analysis and durations of follow-up. There are multiple quality of life tools for bronchiectasis (Quality of Life – Bronchiectasis questionnaire, St George's Respiratory Questionnaire, etc.). The majority of studies measure lung function (e.g. forced expiratory volume in 1 s), but this is shown to be nonresponsive to the majority of interventions. Microbiology end-points frequently show statistically significant differences in phase 2 antibiotic studies but their correlation with clinical end-points is unknown. This systematic review demonstrates a need for guidance to standardise definitions and design features to improve reproducibility and increase the likelihood of demonstrating statistically significant benefits with new therapies