Laser ablation of Diamond and Genesis concentrator target material

UV laser ablations of CVD diamond using two wavelengths of radiation (266 nm and 213 nm) have been compared. The impetus for this work is the 2004 return of Genesis and extraction of solar-wind oxygen implanted in diamond

Surface enhancement of oxygen exchange and diffusion in the ionic conductor La2Mo2O9

Isotopic surface oxygen exchange and its subsequent diffusion have been measured using secondary ion mass spectrometry in the fast ionic conductor La2Mo2O9. A silver coating was applied to the sample surface to enhance the surface exchange process for dry oxygen. Contrary to previous studies performed using a wet atmosphere, no grain boundary diffusion tail was observed under these optimized dry exchange conditions. The activation energy for oxygen diffusion was found to be 0.66(+/- 0.09) eV at high temperature (>570 degrees C), and 1.25(+/- 0.01)eV at low temperature (<570 degrees C). Time-of-Flight secondary ion mass spectrometry was employed to investigate the correlation between the silver coating and the O-18 concentration on the sample surface. A close correlation between the presence of silver and oxygen incorporation on the surface was observed. (C) 2010 Elsevier B.V. All rights reserved

Sidechain control of porosity closure in multiple peptide-based porous materials by cooperative folding

Porous materials find application in separation, storage and catalysis. We report a crystalline porous solid formed by coordination of metal centres with a glycylserine dipeptide. We prove experimentally that the structure evolves from a solvated porous into a non-porous state as result of ordered displacive and conformational changes of the peptide that suppress the void space in response to environmental pressure. This cooperative closure, which recalls the folding of proteins, retains order in three-dimensions and is driven by the hydroxyl groups acting as H-bond donors in the peptide sequence through the serine residue. This ordered closure is also displayed by multipeptide solid solutions in which the combination of different sequences of amino acids controls their guest response in a non-linear way. This functional control can be compared to the effect of single point mutations in proteins, where the exchange of single amino acids can radically alter structure and functio

Study protocol for evaluation of aid to diagnosis for developmental dysplasia of the hip in general practice: controlled trial randomised by practice

Introduction: In the UK, a compulsory ‘6-week hip check’ is performed in primary care for the detection of developmental dysplasia of the hip (DDH). However, missed diagnoses and infants incorrectly labelled with DDH remain a problem, potentially leading to adverse consequences for infants, their families and the National Health Service. National policy states that infants should be referred to hospital if the 6-week check suggests DDH, though there is no available tool to aid examination or offer guidelines for referral. We developed standardised diagnostic criteria for DDH, based on international Delphi consensus, and a 9-item checklist that has the potential to enable non-experts to diagnose DDH in a manner approaching that of experts. / Methods and analysis: We will conduct a controlled trial randomised by practice that will compare a diagnostic aid against standard care for the hip check. The primary objective is to determine whether an aid to the diagnosis of DDH reduces the number of clinically insignificant referrals from primary care to hospital and the number of late diagnosed DDH. The trial will include a qualitative process evaluation, an assessment of professional behavioural change and a full health economic evaluation. We will recruit 152 general practitioner practices in England. These will be randomised to conduct the hip checks with use of the study diagnostic aid and/or as per usual practice. The total number of infants seen during a 15-month recruitment period will be 110 per practice. Two years after the 6-week hip check, we will measure the number of referred infants that are (1) clinically insignificant for DDH and (2) those that constitute appropriate referrals. / Ethics and dissemination: This study has approval from the Health Research Authority (16/1/2020) and the Confidentiality Advisory Group (18/2/2020). Results will be published in peer-reviewed academic journals, disseminated to patient organisations and the media. / Trial registration number: NCT04101903; Pre-results

Decreased glutathione biosynthesis contributes to EGFR T790M-driven erlotinib resistance in non-small cell lung cancer

Epidermal growth factor receptor (EGFR) inhibitors such as erlotinib are novel effective agents in the treatment of EGFR-driven lung cancer, but their clinical impact is often impaired by acquired drug resistance through the secondary T790M EGFR mutation. To overcome this problem, we analysed the metabonomic differences between two independent pairs of erlotinib-sensitive/resistant cells and discovered that glutathione (GSH) levels were significantly reduced in T790M EGFR cells. We also found that increasing GSH levels in erlotinib-resistant cells re-sensitised them, whereas reducing GSH levels in erlotinib-sensitive cells made them resistant. Decreased transcription of the GSH-synthesising enzymes (GCLC and GSS) due to the inhibition of NRF2 was responsible for low GSH levels in resistant cells that was directly linked to the T790M mutation. T790M EGFR clinical samples also showed decreased expression of these key enzymes; increasing intra-tumoural GSH levels with a small-molecule GST inhibitor re-sensitised resistant tumours to erlotinib in mice. Thus, we identified a new resistance pathway controlled by EGFR T790M and a therapeutic strategy to tackle this problem in the clinic

The multiple sclerosis risk sharing scheme monitoring study - early results and lessons for the future

Background: Risk sharing schemes represent an innovative and important approach to the problems of rationing and achieving cost-effectiveness in high cost or controversial health interventions. This study aimed to assess the feasibility of risk sharing schemes, looking at long term clinical outcomes, to determine the price at which high cost treatments would be acceptable to the NHS. Methods: This case study of the first NHS risk sharing scheme, a long term prospective cohort study of beta interferon and glatiramer acetate in multiple sclerosis ( MS) patients in 71 specialist MS centres in UK NHS hospitals, recruited adults with relapsing forms of MS, meeting Association of British Neurologists (ABN) criteria for disease modifying therapy. Outcome measures were: success of recruitment and follow up over the first three years, analysis of baseline and initial follow up data and the prospect of estimating the long term cost-effectiveness of these treatments. Results: Centres consented 5560 patients. Of the 4240 patients who had been in the study for a least one year, annual review data were available for 3730 (88.0%). Of the patients who had been in the study for at least two years and three years, subsequent annual review data were available for 2055 (78.5%) and 265 (71.8%) patients respectively. Baseline characteristics and a small but statistically significant progression of disease were similar to those reported in previous pivotal studies. Conclusion: Successful recruitment, follow up and early data analysis suggest that risk sharing schemes should be able to deliver their objectives. However, important issues of analysis, and political and commercial conflicts of interest still need to be addressed

Evaluating a multi-component intervention to reduce and break up office workers' sitting with sit-stand desks using the APEASE criteria

Objective: Sedentary workplace interventions have had success in reducing excessive sitting time in office workers, but barriers to implementation and uptake remain. This study formally assessed a theory-derived, sit-stand desk intervention using the APEASE (Acceptability, Practicability, Effectiveness, Affordability, Side-effects, Equity) criteria. / Methods: Thirteen adults (eight female, mean age 38 ± 10 years) from the treatment arm of a sedentary behaviour intervention participated in semi-structured interviews. Thematic codes were inductively assigned to data items followed by deductive charting using the APEASE criteria. / Results: The intervention was highly acceptable, practicable, safe to deploy, and helped workers reduce workplace sitting time, though individual preferences and workload mediated engagement. Affordability of sit-stand desks and Equity of access were potential barriers to uptake. / Conclusions: Through the lens of the APEASE criteria, this theory-derived, multi-component sit-stand desk intervention showed acceptability, practicability and effectiveness in reducing and breaking up sedentary time at work with minimal side effects. Using this approach with further tailoring and personalisation may help workers achieve greater reductions in workplace sitting, though affordability and equity should be considered further