A Possible Regenerative, Molten-Salt, Thermoelectric Fuel Cell

Molten or fused salts have been evaluated as possible thermoelectric materials because of the relatively good values of their figures of merit, their chemical stability, their long liquid range, and their ability to operate in conjunction with a nuclear reactor to produce heat. In general, molten salts are electrolytic conductors; therefore, there will be a transport of materials and subsequent decomposition with the passage of an electric current. It is possible nonetheless to overcome this disadvantage by using the decomposition products of the molten-salt electrolyte in a fuel cell. The combination of a thermoelectric converter and a fuel cell would lead to a regenerative system that may be useful

PREDICT: a new UK prognostic model that predicts survival following surgery for invasive breast cancer.

INTRODUCTION: The aim of this study was to develop and validate a prognostication model to predict overall and breast cancer specific survival for women treated for early breast cancer in the UK. METHODS: Using the Eastern Cancer Registration and Information Centre (ECRIC) dataset, information was collated for 5,694 women who had surgery for invasive breast cancer in East Anglia from 1999 to 2003. Breast cancer mortality models for oestrogen receptor (ER) positive and ER negative tumours were derived from these data using Cox proportional hazards, adjusting for prognostic factors and mode of cancer detection (symptomatic versus screen-detected). An external dataset of 5,468 patients from the West Midlands Cancer Intelligence Unit (WMCIU) was used for validation. RESULTS: Differences in overall actual and predicted mortality were <1% at eight years for ECRIC (18.9% vs. 19.0%) and WMCIU (17.5% vs. 18.3%) with area under receiver-operator-characteristic curves (AUC) of 0.81 and 0.79 respectively. Differences in breast cancer specific actual and predicted mortality were <1% at eight years for ECRIC (12.9% vs. 13.5%) and <1.5% at eight years for WMCIU (12.2% vs. 13.6%) with AUC of 0.84 and 0.82 respectively. Model calibration was good for both ER positive and negative models although the ER positive model provided better discrimination (AUC 0.82) than ER negative (AUC 0.75). CONCLUSIONS: We have developed a prognostication model for early breast cancer based on UK cancer registry data that predicts breast cancer survival following surgery for invasive breast cancer and includes mode of detection for the first time. The model is well calibrated, provides a high degree of discrimination and has been validated in a second UK patient cohort.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

The Urea Carboxylase and Allophanate Hydrolase Activities of Urea Amidolyase Are Functionally Independent

Urea amidolyase (UAL) is a multifunctional biotin-dependent enzyme that contributes to both bacterial and fungal pathogenicity by catalyzing the ATP-dependent cleavage of urea into ammonia and CO2. UAL is comprised of two enzymatic components: urea carboxylase (UC) and allophanate hydrolase (AH). These enzyme activities are encoded on separate but proximally related genes in prokaryotes while, in most fungi, they are encoded by a single gene that produces a fusion enzyme on a single polypeptide chain. It is unclear whether the UC and AH activities are connected through substrate channeling or other forms of direct communication. Here, we use multiple biochemical approaches to demonstrate that there is no substrate channeling or interdomain/intersubunit communication between UC and AH. Neither stable nor transient interactions can be detected between prokaryotic UC and AH and the catalytic efficiencies of UC and AH are independent of one another. Furthermore, an artificial fusion of UC and AH does not significantly alter the AH enzyme activity or catalytic efficiency. These results support the surprising functional independence of AH from UC in both the prokaryotic and fungal UAL enzymes and serve as an important reminder that the evolution of multifunctional enzymes through gene fusion events does not always correlate with enhanced catalytic function

CD27 Expression Promotes Long-Term Survival of Functional Effector–Memory CD8+Cytotoxic T Lymphocytes in HIV-infected Patients

Human immunodeficiency virus (HIV)-specific CD8+ T cells persist in high frequencies in HIV-infected patients despite impaired CD4+ T helper response to the virus, but, unlike other differentiated effector cytotoxic T lymphocytes, most continue to express the tumor necrosis factor receptor family member CD27. Because the ligand for CD27 (CD70) is also overexpressed in HIV-infected hosts, we examined the nature of expression and potential functional consequences of CD27 expression on HIV-specific CD8+ T cells. Analysis of CD27+ and CD27− T cells derived from the same HIV-specific clone revealed that retention of CD27 did not interfere with acquisition of effector functions, and that after T cell receptor stimulation, CD27+ cells that concurrently were triggered via CD27 exhibited more resistance to apoptosis, interleukin 2 production, and proliferation than CD27− T cells. After transfer back into an HIV-infected patient, autologous HIV-specific CD27− T cells rapidly disappeared, but CD27+ T cells derived from the same clone persisted at high frequency. Our findings suggest that the CD27–CD70 interaction in HIV infection may provide CD27+ CD8+ T cells with a survival advantage and compensate for limiting or absent CD4+ T help to maintain the CD8 response

A New WIMP Population in the Solar System and New Signals for Dark-Matter Detectors

We describe in detail how perturbations due to the planets can cause a sub-population of WIMPs captured by scattering in surface layers of the Sun to evolve to have orbits which no longer intersect the Sun. We argue that such WIMPs, if their orbit has a semi-major axis less than 1/2 of Jupiter's, can persist in the solar system for cosmological timescales. This leads to a new, previously unanticipated WIMP population intersecting the Earth's orbit. The WIMP-nucleon cross sections required for this population to be significant are precisely those in the range predicted for SUSY dark matter, lying near the present limits obtained by direct underground dark matter searches using cyrogenic detectors. Thus, if a WIMP signal is observed in the next generation of detectors, a potentially measurable signal due to this new population must exist. This signal, lying in the keV range for Germanium detectors, would be complementary to that of galactic halo WIMPs. A comparison of event rates, anisotropies, and annual modulations would not only yield additional confirmation that any claimed signal is indeed WIMP-based, but would also allow one to gain information on the nature of the underlying dark matter model.Comment: Revtex, 37 pages including 6 figures, accepted by Phys. Rev D. (version to be published, including changes made in response to referees reports

How should we evaluate research on counselling and the treatment of depression? A case study on how NICE’s draft 2018 guideline considered what counts as best evidence

Background: Health guidelines are developed to improve patient care by ensuring the most recent and “best available evidence” is used to guide treatment recommendations (NICE Guidance, 2017). NICE’s revised guideline development methodology acknowledges that evidence needed to answer one question (treatment efficacy) may be different from evidence needed to answer another (cost effectiveness, treatment acceptability to patients; NICE, 2014/2017). This review uses counselling in the treatment of depression as a case study, and interrogates the constructs of ‘best’ evidence and ‘best’ guideline methodologies. Method: The review comprises six sections: (1) the implications of diverse definitions of counselling in research; (2) research findings from meta-analyses and randomised controlled trials (RCTs); (3) limitations to trials-based evidence; (4) findings from large routine outcome datasets; (5) the inclusion of qualitative research that emphasises service-user voices; and (6) conclusions and recommendations. Results: Research from meta-analyses and RCTs reviewed in the draft 2018 NICE guideline is limited but positive in relation to the effectiveness of counselling in the treatment for depression. The weight of evidence suggests little, if any, advantage to CBT over counselling once bias and researcher allegiance are taken into account. A growing body of evidence from large NHS datasets also evidences that counselling is both effective and cost-effective when delivered in NHS settings. Conclusion: Recommendations in NICE’s own updated procedures suggest that sole reliance on RCTs and meta-analyses as best methodologies is no longer adequate. There is a need to include large standardised collected datasets from routine practice as well as the voice of patients via high-quality qualitative research