Impact of the innate environment on maintaining memory T-cell numbers in the female genital tract: implications for mucosal vaccine efficacy?

Preventative HIV vaccines aim to elicit long-lived protective immune responses at the site of HIV transmission, capable of responding quickly to HIV challenge, but which remain stable at effector sites of the genital mucosa. The genital mucosa is, however, commonly confronted with innate immune modifiers and inflammatory agents including sexually-transmitted infections, behavioural and hygiene practices. We investigated the impact of mucosal inflammation and homeostatic cytokines on local T-cell phenotype, proliferation, exhaustion and activation

Integrating coaching and positive psychology: Concepts and practice

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City Energy Demand Simulation (CEDS) Feasibility Study

CEDS - The City Energy Demand Simulation - provides cities and local authorities with the means to visualise future energy demand (including gas and electricity) for any geographic area ranging from a street, to a district, to the city itself, including both residential and industrial/commercial energy demand.CEDS allows planners and decision makers to easily visualise the impacts of alternative demand and supply side energy investment strategies on overall energy costs, emissions, and fuel poverty levels. This will be important for cities and planners because the innovative features of CEDS will enable planners to understand the impacts of new energy technology deployments on the energy demand of buildings. - CEDS can demonstrate the relative economic and environmental attractiveness of local energy supply schemes such as district heating combined with power versus importing electricity from the grid; - CEDS can illuminate the impacts of technology deployment by social geography within the city boundaries Therefore, CEDS will allow cities and local authorities to clearly identify how to deploy limited capital budgets to greatest effect when developing low carbon, cost effective local energy infrastructure. By modelling future demand, supply and cost scenarios, cities will be able to prioritise the development of local energy assets, such as district heating networks, energy from waste, retrofit and new build locations. CEDS will enable cities to understand how they can deliver on their priorities for ensuring there are cost effective locations for business and industry, with a secure supply, whilst also helping tackle fuel poverty and reducing carbon emissions and energy costs

The genealogy of judgement: towards a deep history of academic freedom

The classical conception of academic freedom associated with Wilhelm von Humboldt and the rise of the modern university has a quite specific cultural foundation that centres on the controversial mental faculty of 'judgement'. This article traces the roots of 'judgement' back to the Protestant Reformation, through its heyday as the signature feature of German idealism, and to its gradual loss of salience as both a philosophical and a psychological concept. This trajectory has been accompanied by a general shrinking in the scope of academic freedom from the promulgation of world-views to the offering of expert opinion

Mep72, a metzincin protease that is preferentially secreted by biofilms of Pseudomonas aeruginosa.

In this work, we compared the profile of proteins secreted by planktonic and biofilm cultures of Pseudomonas aeruginosa using two-dimensional difference gel electrophoresis (2D-DiGE). This revealed that a novel metzincin protease, Mep72, was secreted during biofilm growth. Subsequent Western blotting and reverse transcription-PCR (RT-PCR) analyses demonstrated that Mep72 was expressed only during biofilm growth. Mep72 has a tridomain structure comprised of a metzincin protease-like domain and two tandem carbohydrate-binding domains. Unlike the only other metzincin (alkaline protease; AprA) in P. aeruginosa, Mep72 is secreted through the type II pathway and undergoes processing during export. During this processing, the metzincin domain is liberated from the carbohydrate-binding domains. This processing may be self-catalyzed, since purified Mep72 autodegraded in vitro. This autodegradation was retarded in the presence of alginate (an extracellular matrix component of many P. aeruginosa biofilms). The expression of full-length mep72 in Escherichia coli was toxic. However, this toxicity could be alleviated by coexpression of mep72 with the adjacent gene, bamI. Mep72 and BamI were found to form a protein-protein complex in vitro. 2D-DiGE revealed that the electrophoretic mobility of several discrete protein spots was altered in the biofilm secretome of an mep72 mutant, including type III secretion proteins (PopD, PcrV, and ExoS) and a flagellum-associated protein (FliD). Mep72 was found to bind directly to ExoS and PcrV and to affect the processing of these proteins in the biofilm secretome. We conclude that Mep72 is a secreted biofilm-specific regulator that affects the processing of a very specific subset of virulence factors.This study was funded by the BBSRC, the Isaac Newton Trust (Cambridge), and a grant from the Japanese Society for Acute Infection to K.N.The paper was originally published by the American Society for Microbiology in the Journal of Bacteriology with a CC-BY licence (IJ Passmore, K Nishikawa, KS Lilley, SD Bowden, JCS Chung, M Welch, Journal of Bacteriology 2015, 197, 762–773

Patterns of care and survival for patients aged under 40 years with bone sarcoma in Britain, 1980–1994

The purpose of the study was to calculate population-based survival rates for osteosarcoma (OS) and Ewing's sarcoma (ES) in Great Britain during 1980–1994, determine proportions of patients treated at specialist centres or entered in national and international clinical trials, and investigate effects of these factors on survival. Data on a population-based series of 1349 patients with OS and 849 with ES were compiled from regional and national cancer registries, UK Children's Cancer Study Group, regional bone tumour registries and clinical trials. Follow-up was through population registers. Survival was analysed by actuarial analysis with log-rank tests and by Cox's proportional hazards analysis. Five-year survival rates during 1980–1984, 1985–1989 and 1990–1994 were 42% (95% CI: 37, 46), 54% (95% CI: 50, 59) and 53% (95% CI: 48, 57), respectively, for OS and 31% (95% CI: 26, 37), 46% (95% CI: 40, 51) and 51% (95% CI: 45, 57) for ES. Proportions of patients treated at a supraregional bone tumour centre or a paediatric oncology centre in the three quinquennia were 36, 56 and 67% for OS and 41, 60 and 69% for ES. In 1983–1992, 48% of OS patients were entered in a national trial; for ES, 27% were entered in 1980–1986 and 54% in 1987–1994. Survival was similar for trial and nontrial patients with OS. For ES, trial patients had consistently higher 5-year survival than nontrial patients: 1980–1986, 42 vs 30%; 1987–1992, 59 vs 42%; 1993–1994, 54 vs 43%. During 1985–1994, patients with OS or ES whose main treatment centre was a nonteaching hospital had lower survival rates. In multivariate analyses of patients diagnosed during 1985–1994 that also included age, sex, primary site, surgical treatment centre, the results relating to main treatment centre for both OS and ES retained significance but the survival advantage of trial entry for ES became nonsignificant. For both OS and ES diagnosed since 1985, patients whose main treatment centre was a nonspecialist hospital had a lower survival rate

Become the best coach you can be: the role of coach training and coaching experience in workplace coaching quality and quality control

This paper explores whether coach training or coaching experience leads to better coaching quality and quality control. In two large studies, both coaches (N1 = 2267) and personnel managers who book coaches for their company (N2 = 754) answered questions about coaching quality and quality control. The results show that more coach training leads to not only a better self-perceived coaching quality (Study 1) but also a better other-perceived coaching-quality (Study 2); moreover, more coach training positively affects quality control. It is remarkable that coaching experience showed no significant relation regarding other-perceived coaching quality and quality control. Study 2 further revealed that references lead to more recommendations but not to a better coaching quality or quality control. Thus, coach training is an essential factor when selecting organizational coaches. Further research is needed to understand the impact of different approaches to coach trainings on coaching outcomes

Correlation of fluvial sequences in the Mediterranean basin over the last 200 ka and their relationship to climate change

This paper presents a new correlation of Late and Middle Pleistocene fluvial sedimentary sequences in Greek, Libyan and Spanish river basins and evaluates river response to climate change over the Last Interglacial–Glacial Cycle. Over the past 200,000 years there have been at least 13 major alluviation episodes in the Mediterranean, although the amplitude, frequency and possibly, duration of these events varied significantly across the region. Parts of Oxygen Isotope Stage (OIS) 5 appears to have been periods of pronounced landscape change in many Mediterranean catchments with major river aggradation occurring atB109–111 ka (during OIS 5d) and most notably at B88 ka (OIS 5b/5a boundary). Other parts of OIS 5 appear to have been periods of relative fluvial inactivity. OIS 2 and 3 were both characterised by an apparent increase in the number of alluviation events, and this record of river behaviour parallels many other palaeoenvironmental records in the region which also show more frequent climate fluctuations between B12 and 65 ka. There is evidence for a high degree of synchrony in major river aggradation events across the Mediterranean in catchments with very different sizes, tectonic regimes and histories. Climate-related changes in catchmen