Simulator study of the low-speed handling qualities of a supersonic cruise arrow-wing transport configuration during approach and landing

A fixed-based simulator study was conducted to determine the low-speed flight characteristics of an advanced supersonic cruise transport having an arrow wing, a horizontal tail, and four dry turbojets with variable geometry turbines. The primary piloting task was the approach and landing. The statically unstable (longitudinally) subject configuration has unacceptable low-speed handling qualities with no augmentation. Therefore, a hardened stability augmentation system is required to achieve acceptable handling qualities, should the normal operational stability and control augmentation system fail. In order to achieve satisfactory handling qualities, considerable augmentation was required

Ground-based and in-flight simulator studies of low-speed handling characteristics of two supersonic cruise transport concepts

Conventional and powered lift concepts for supersonic approach and landing tasks are considered. Results indicated that the transport concepts had unacceptable low-speed handling qualities with no augmentation, and that in order to achieve satisfactory handling qualities, considerable augmentation was required. The available roll-control power was acceptable for the powered-lift concept

Fixed base simulator study of an externally blown flap STOL transport airplane during approach and landing

A fixed-base simulator study was conducted to determine the flight characteristics of a representative STOL transport having a high wing and equipped with an external-flow jet flap in combination with four high-bypass-ratio fan-jet engines during the approach and landing. Real-time digital simulation techniques were used. The computer was programed with equations of motion for six degrees of freedom and the aerodynamic inputs were based on measured wind-tunnel data. A visual display of a STOL airport was provided for simulation of the flare and touchdown characteristics. The primary piloting task was an instrument approach to a breakout at a 200-ft ceiling with a visual landing

Localization of overexpressed c-myc mRNA in polycystic kidneys of the cpk mouse

Localization of overexpressed c-myc mRNA in polycystic kidneys of the cpk mouse. The C57BL/6J-cpk mouse has a form of autosomal-recessive polycystic kidney disease characterized by the rapid growth of large collecting duct cysts and the development of severe renal failure usually by three to four weeks of age. Previous studies had shown higher steady-state levels of proto-oncogene mRNA in these cystic kidneys. It is now shown using nuclear run-on transcription that the c-fos and c-myc proto-oncogenes are transcribed at higher rates in cystic kidneys, and thus that increased transcription, in part, may account for the increased mRNA levels. c-myc mRNA was detected by in situ hybridization in nephron anlagen and elongating tubules of normal and cystic kidneys during late fetal and early neonatal kidney development. Localization of c-myc expression in the normal kidney decreased with age over the three-week postnatal period. By contrast, c-myc mRNA was found in cysts as early as three days of age, with increased levels at two and three weeks, c-myc expression was also elevated in apparently normal, non-dividing proximal tubules in three-week-old cystic animals. On the basis of these findings, we suggest that c-myc expression is linked to the proliferation of cells engaged in the primary cystogenic process, and that expression of this gene in proximal tubule cells of severely azotemic animals reflects the compensatory response of residual tubular epithelial cells to progressive renal dysfunction

Integrating evidence, politics and society: a methodology for the science–policy interface

There is currently intense debate over expertise, evidence and ‘post-truth’ politics, and how this is influencing policy formulation and implementation. In this article, we put forward a methodology for evidence-based policy making intended as a way of helping navigate this web of complexity. Starting from the premise of why it is so crucial that policies to meet major global challenges use scientific evidence, we discuss the socio-political difficulties and complexities that hinder this process. We discuss the necessity of embracing a broader view of what constitutes evidence—science and the evaluation of scientific evidence cannot be divorced from the political, cultural and social debate that inevitably and justifiably surrounds these major issues. As a pre-requisite for effective policy making, we propose a methodology that fully integrates scientific investigation with political debate and social discourse. We describe a rigorous process of mapping, analysis, visualisation and sharing of evidence, constructed from integrating science and social science data. This would then be followed by transparent evidence evaluation, combining independent assessment to test the validity and completeness of the evidence with deliberation to discover how the evidence is perceived, misunderstood or ignored. We outline the opportunities and the problems derived from the use of digital communications, including social media, in this methodology, and emphasise the power of creative and innovative evidence visualisation and sharing in shaping policy

The injectable-only contraceptive medroxyprogesterone acetate, unlike norethisterone acetate and progesterone, regulates inflammatory genes in endocervical cells via the glucocorticoid receptor

Clinical studies suggest that the injectable contraceptive medroxyprogesterone acetate (MPA) increases susceptibility to infections such as HIV-1, unlike the injectable contraceptive norethisterone enanthate (NET-EN). We investigated the differential effects, molecular mechanism of action and steroid receptor involvement in gene expression by MPA as compared to NET and progesterone (P4) in the End1/E6E7 cell line model for the endocervical epithelium, a key point of entry for pathogens in the female genital mucosa. MPA, unlike NET-acetate (NET-A) and P4, increases mRNA expression of the anti-inflammatory GILZ and IκBα genes. Similarly, MPA unlike NET-A, decreases mRNA expression of the pro-inflammatory IL-6, IL-8 and RANTES genes, and IL-6 and IL-8 protein levels. The predominant steroid receptor expressed in the End1/E6E7 and primary endocervical epithelial cells is the glucocorticoid receptor (GR), and GR knockdown experiments show that the anti-inflammatory effects of MPA are mediated by the GR. Chromatin-immunoprecipitation results suggest that MPA, unlike NET-A and P4, represses pro-inflammatory cytokine gene expression in cervical epithelial cells via a mechanism involving recruitment of the GR to cytokine gene promoters, like the GR agonist dexamethasone. This is at least in part consistent with direct effects on transcription, without a requirement for new protein synthesis. Dose response analysis shows that MPA has a potency of ∼24 nM for transactivation of the anti-inflammatory GILZ gene and ∼4-20 nM for repression of the pro-inflammatory genes, suggesting that these effects are likely to be relevant at injectable contraceptive doses of MPA. These findings suggest that in the context of the genital mucosa, these GR-mediated glucocorticoid-like effects of MPA in cervical epithelial cells are likely to play a critical role in discriminating between the effects on inflammation caused by different progestins and P4 and hence susceptibility to genital infections, given the predominant expression of the GR in primary endocervical epithelial cells

Measuring and optimising the efficiency of community hospital inpatient care for older people: the MoCHA mixed-methods study

Background: Community hospitals are small hospitals providing local inpatient and outpatient services. National surveys report that inpatient rehabilitation for older people is a core function but there are large differences in key performance measures. We have investigated these variations in community hospital ward performance. Objectives: (1) To measure the relative performance of community hospital wards (studies 1 and 2); (2) to identify characteristics of community hospital wards that optimise performance (studies 1 and 3); (3) to develop a web-based interactive toolkit that supports operational changes to optimise ward performance (study 4); (4) to investigate the impact of community hospital wards on secondary care use (study 5); and (5) to investigate associations between short-term community (intermediate care) services and secondary care utilisation (study 5). Methods: Study 1 – we used national data to conduct econometric estimations using stochastic frontier analysis in which a cost function was modelled using significant predictors of community hospital ward costs. Study 2 – a national postal survey was developed to collect data from a larger sample of community hospitals. Study 3 – three ethnographic case studies were performed to provide insight into less tangible aspects of community hospital ward care. Study 4 – a web-based interactive toolkit was developed by integrating the econometrics (study 1) and case study (study 3) findings. Study 5 – regression analyses were conducted using data from the Atlas of Variation Map 61 (rate of emergency admissions to hospital for people aged ≥ 75 years with a length of stay of < 24 hours) and the National Audit of Intermediate Care. Results: Community hospital ward efficiency is comparable with the NHS acute hospital sector (mean cost efficiency 0.83, range 0.72–0.92). The rank order of community hospital ward efficiencies was distinguished to facilitate learning across the sector. On average, if all community hospital wards were operating in line with the highest cost efficiency, savings of 17% (or £47M per year) could be achieved (price year 2013/14) for our sample of 101 wards. Significant economies of scale were found: a 1% rise in output was associated with an average 0.85% increase in costs. We were unable to obtain a larger community hospital sample because of the low response rate to our national survey. The case studies identified how rehabilitation was delivered through collaborative, interdisciplinary working; interprofessional communication; and meaningful patient and family engagement. We also developed insight into patients’ recovery trajectories and care transitions. The web-based interactive toolkit was established [http://mocha. nhsbenchmarking.nhs.uk/ (accessed 9 September 2019)]. The crisis response team type of intermediate care, but not community hospitals, had a statistically significant negative association with emergency admissions. Limitations: The econometric analyses were based on cross-sectional data and were also limited by missing data. The low response rate to our national survey means that we cannot extrapolate reliably from our community hospital sample. Conclusions: The results suggest that significant community hospital ward savings may be realised by improving modifiable performance factors that might be augmented further by economies of scale. Future work: How less efficient hospitals might reduce costs and sustain quality requires further research