A physics-based life prediction methodology for thermal barrier coating systems

A novel mechanistic approach is proposed for the prediction of the life of thermal barrier coating (TBC) systems. The life prediction methodology is based on a criterion linked directly to the dominant failure mechanism. It relies on a statistical treatment of the TBC's morphological characteristics, non-destructive stress measurements and on a continuum mechanics framework to quantify the stresses that promote the nucleation and growth of microcracks within the TBC. The last of these accounts for the effects of TBC constituents' elasto-visco-plastic properties, the stiffening of the ceramic due to sintering and the oxidation at the interface between the thermally insulating yttria stabilized zirconia (YSZ) layer and the metallic bond coat. The mechanistic approach is used to investigate the effects on TBC life of the properties and morphology of the top YSZ coating, metallic low-pressure plasma sprayed bond coat and the thermally grown oxide. Its calibration is based on TBC damage inferred from non-destructive fluorescence measurements using piezo-spectroscopy and on the numerically predicted local TBC stresses responsible for the initiation of such damage. The potential applicability of the methodology to other types of TBC coatings and thermal loading conditions is also discussed

Population Differences in Death Rates in HIV-Positive Patients with Tuberculosis.

SETTING: Randomised controlled clinical trial of Mycobacterium vaccae vaccination as an adjunct to anti-tuberculosis treatment in human immunodeficiency virus (HIV) positive patients with smear-positive tuberculosis (TB) in Lusaka, Zambia, and Karonga, Malawi. OBJECTIVE: To explain the difference in mortality between the two trial sites and to identify risk factors for death among HIV-positive patients with TB. DESIGN: Information on demographic, clinical, laboratory and radiographic characteristics was collected. Patients in Lusaka (667) and in Karonga (84) were followed up for an average of 1.56 years. Cox proportional hazard analyses were used to assess differences in survival between the two sites and to determine risk factors associated with mortality during and after anti-tuberculosis treatment. RESULTS: The case fatality rate was 14.7% in Lusaka and 21.4% in Karonga. The hazard ratio for death comparing Karonga to Lusaka was 1.47 (95% confidence interval [CI] 0.9-2.4) during treatment and 1.76 (95%CI 1.0-3.0) after treatment. This difference could be almost entirely explained by age and more advanced HIV disease among patients in Karonga. CONCLUSION: It is important to understand the reasons for population differences in mortality among patients with TB and HIV and to maximise efforts to reduce mortality

The political economy of competitiveness and social mobility

Social mobility has become a mainstream political and media issue in recent years in the United Kingdom. This article suggests that part of the reason for this is that it can serve as a mechanism to discuss policy concerns that appear to be about social justice without questioning important aspects of neo-liberal political economy. The article charts the policy rhetoric on social mobility under both New Labour and the current Coalition Government. It is argued first that under New Labour the apparent commitment to social mobility was in fact subsumed beneath the pursuit of neo-liberal competitiveness, albeit imperfectly realised in policy. Second, the article suggests that under the Coalition Government the commitment to raising levels of social mobility has been retained and the recently published Strategy for Social Mobility promises that social mobility is what the Coalition means when it argues that the austerity programme is balanced with ‘fairness’. Third, however, the Strategy makes clear that the Coalition define social mobility in narrower terms than the previous government. It is argued here that in narrowing the definition the connection with the idea of competitiveness, while still clearly desirable for the Coalition, is weakened. Fourth, a brief analysis of the Coalition's main policy announcements provides little evidence to suggest that even the narrow definition set out in the Strategy is being seriously pursued. Fifth, the international comparative evidence suggests that any strategy aimed at genuinely raising the level of social mobility would need to give much more serious consideration to narrowing levels of inequality. Finally, it is concluded that when considered in the light of the arguments above, the Strategy for Social Mobility – and therefore ‘Fairness’ itself – is merely a discursive legitimation of the wider political economy programme of austerity

ADRIC: Adverse Drug Reactions In Children - a programme of research using mixed methods

Aims To comprehensively investigate the incidence, nature and risk factors of adverse drug reactions (ADRs) in a hospital-based population of children, with rigorous assessment of causality, severity and avoidability, and to assess the consequent impact on children and families. We aimed to improve the assessment of ADRs by development of new tools to assess causality and avoidability, and to minimise the impact on families by developing better strategies for communication. Review methods Two prospective observational studies, each over 1 year, were conducted to assess ADRs in children associated with admission to hospital, and those occurring in children who were in hospital for longer than 48 hours. We conducted a comprehensive systematic review of ADRs in children. We used the findings from these studies to develop and validate tools to assess causality and avoidability of ADRs, and conducted interviews with parents and children who had experienced ADRs, using these findings to develop a leaflet for parents to inform a communication strategy about ADRs. Results The estimated incidence of ADRs detected in children on admission to hospital was 2.9% [95% confidence interval (CI) 2.5% to 3.3%]. Of the reactions, 22.1% (95% CI 17% to 28%) were either definitely or possibly avoidable. Prescriptions originating in the community accounted for 44 out of 249 (17.7%) of ADRs, the remainder originating from hospital. A total of 120 out of 249 (48.2%) reactions resulted from treatment for malignancies. Off-label and/or unlicensed (OLUL) medicines were more likely to be implicated in an ADR than authorised medicines [relative risk (RR) 1.67, 95% CI 1.38 to 2.02; p  48 hours, the overall incidence of definite and probable ADRs based on all admissions was 15.9% (95% CI 15.0 to 16.8). Opiate analgesic drugs and drugs used in general anaesthesia (GA) accounted for > 50% of all drugs implicated in ADRs. The odds ratio of an OLUL drug being implicated in an ADR compared with an authorised drug was 2.25 (95% CI 1.95 to 2.59; p < 0.001). Risk factors identified were exposure to a GA, age, oncology treatment and number of medicines. The systematic review estimated that the incidence rates for ADRs causing hospital admission ranged from 0.4% to 10.3% of all children [pooled estimate of 2.9% (95% CI 2.6% to 3.1%)] and from 0.6% to 16.8% of all children exposed to a drug during hospital stay. New tools to assess causality and avoidability of ADRs have been developed and validated. Many parents described being dissatisfied with clinician communication about ADRs, whereas parents of children with cancer emphasised confidence in clinician management of ADRs and the way clinicians communicated about medicines. The accounts of children and young people largely reflected parents’ accounts. Clinicians described using all of the features of communication that parents wanted to see, but made active decisions about when and what to communicate to families about suspected ADRs, which meant that communication may not always match families’ needs and expectations. We developed a leaflet to assist clinicians in communicating ADRs to parents. Conclusion The Adverse Drug Reactions In Children (ADRIC) programme has provided the most comprehensive assessment, to date, of the size and nature of ADRs in children presenting to, and cared for in, hospital, and the outputs that have resulted will improve the management and understanding of ADRs in children and adults within the NHS. Recommendations for future research: assess the values that parents and children place on the use of different medicines and the risks that they will find acceptable within these contexts; focusing on high-risk drugs identified in ADRIC, determine the optimum drug dose for children through the development of a gold standard practice for the extrapolation of adult drug doses, alongside targeted pharmacokinetic/pharmacodynamic studies; assess the research and clinical applications of the Liverpool Causality Assessment Tool and the Liverpool Avoidability Assessment Tool; evaluate, in more detail, morbidities associated with anaesthesia and surgery in children, including follow-up in the community and in the home setting and an assessment of the most appropriate treatment regimens to prevent pain, vomiting and other postoperative complications; further evaluate strategies for communication with families, children and young people about ADRs; and quantify ADRs in other settings, for example critical care and neonatology

Lightning driven inner radiation belt energy deposition into the atmosphere: regional and global estimates

International audienceIn this study we examine energetic electron precipitation fluxes driven by lightning, in order to determine the global distribution of energy deposited into the middle atmosphere. Previous studies using lightning-driven precipitation burst rates have estimated losses from the inner radiation belts. In order to confirm the reliability of those rates and the validity of the conclusions drawn from those studies, we have analyzed New Zealand data to test our global understanding of troposphere to magnetosphere coupling. We examine about 10000h of AbsPAL recordings made from 17 April 2003 through to 26 June 2004, and analyze subionospheric very-low frequency (VLF) perturbations observed on transmissions from VLF transmitters in Hawaii (NPM) and western Australia (NWC). These observations are compared with those previously reported from the Antarctic Peninsula. The perturbation rates observed in the New Zealand data are consistent with those predicted from the global distribution of the lightning sources, once the different experimental configurations are taken into account. Using lightning current distributions rather than VLF perturbation observations we revise previous estimates of typical precipitation bursts at L~2.3 to a mean precipitation energy flux of ~1×10-3 ergs cm-2s-1. The precipitation of energetic electrons by these bursts in the range L=1.9-3.5 will lead to a mean rate of energy deposited into the atmosphere of 3×10-4 ergs cm-2min-1, spatially varying from a low of zero above some ocean regions to highs of ~3-6×10-3 ergs cm-2min-1 above North America and its conjugate region

Longitudinal effect of CD4 by cotrimoxazole use on malaria incidence among HIV‑infected Ugandan adults on antiretroviral therapy: a randomized controlled study

Background The effect of CD4 count on malaria incidence in HIV infected adults on antiretroviral therapy (ART) was assessed in the context of a randomized controlled trial on the effect of stopping cotrimoxazole (CTX). Methods This study presents a sub-analysis of the COSTOP trial (ISRCTN44723643) which was carried out among HIV-infected Ugandan adults stable on ART with CD4 counts ≥250 cells/µl. Participants were randomized (1:1) to continue CTX or stop CTX and receive matching placebo, and were followed up for a minimum of 1 year (median 2.5 years). CD4 counts were measured at baseline, 3 months and then every 6 months. Clinical malaria was defined as fever and a positive blood slide. First, the relationship between current CD4 count during follow-up and malaria among participants on placebo was examined; using random effects Poisson regression to account for repeated episodes. Second, the effect of CD4 count at enrolment, CD4 count at ART initiation, and CD4 count during follow-up on malaria, was assessed within each trial arm; to examine whether the effect of CD4 count differed by CTX use. Results 2180 participants were enrolled into the COSTOP trial. The incidence of clinical malaria was approximately four episodes/100 person years in the CTX arm and 14 episodes/100 person years in the placebo arm. There was no evidence of an association of current CD4 and clinical malaria incidence (P = 0.56), or parasitaemia levels (P = 0.24), in the placebo arm. Malaria incidence did not differ by CD4 count at ART initiation, enrolment or during follow up, irrespective of CTX use. When compared with participants in the lowest CD4 stratum, rate ratios within each trial arm were all close to 1, and P values were all above P = 0.30. Conclusions The immune status of HIV infected participants who are stable on ART as measured by CD4 count was not associated with malaria incidence and did not modify the effect of stopping CTX on malaria. The decision of whether to stop or continue CTX prophylaxis for malaria in HIV infected individuals who are stable on ART should not be based on CD4 counts alone. COSTOP trial registration number ISRCTN4472364

WHO Clinical Staging of HIV Infection and Disease, Tuberculosis and Eligibility for Antiretroviral Treatment: Relationship to CD4 Lymphocyte Counts.

SETTING: Thyolo district, Malawi. OBJECTIVES: To determine in HIV-positive individuals aged over 13 years CD4 lymphocyte counts in patients classified as WHO Clinical Stage III and IV and patients with active and previous tuberculosis (TB). DESIGN: Cross-sectional study. METHODS: CD4 lymphocyte counts were determined in all consecutive HIV-positive individuals presenting to the antiretroviral clinic in WHO Stage III and IV. RESULTS: A CD4 lymphocyte count of < or = 350 cells/microl was found in 413 (90%) of 457 individuals in WHO Stage III and IV, 96% of 77 individuals with active TB, 92% of 65 individuals with a history of pulmonary TB (PTB) in the last year, 91% of 89 individuals with a previous history of PTB beyond 1 year, 81% of 32 individuals with a previous history of extra-pulmonary TB, 93% of 107 individuals with active or past TB with another HIV-related disease and 89% of 158 individuals with active or past TB without another HIV-related disease. CONCLUSIONS: In our setting, nine of 10 HIV-positive individuals presenting in WHO Stage III and IV and with active or previous TB have CD4 counts of < or = 350 cells/microl. It would thus be reasonable, in this or similar settings where CD4 counts are unavailable for clinical management, for all such patients to be considered eligible for antiretroviral therapy

Psychometric properties of multicomponent tools designed to assess frailty in older adults: a systematic review

Background Frailty is widely recognised as a distinct multifactorial clinical syndrome that implies vulnerability. The links between frailty and adverse outcomes such as death and institutionalisation have been widely evidenced. There is currently no gold standard frailty assessment tool; optimizing the assessment of frailty in older people therefore remains a research priority. The objective of this systematic review is to identify existing multi-component frailty assessment tools that were specifically developed to assess frailty in adults aged ≥60 years old and to systematically and critically evaluate the reliability and validity of these tools. Methods A systematic literature review was conducted using the standardised COnsensus‐based Standards for the selection of health Measurement INstruments (COSMIN) checklist to assess the methodological quality of included studies. Results Five thousand sixty-three studies were identified in total: 73 of which were included for review. 38 multi-component frailty assessment tools were identified: Reliability and validity data were available for 21 % (8/38) of tools. Only 5 % (2/38) of the frailty assessment tools had evidence of reliability and validity that was within statistically significant parameters and of fair-excellent methodological quality (the Frailty Index-Comprehensive Geriatric Assessment [FI-CGA] and the Tilburg Frailty Indicator [TFI]). Conclusions The TFI has the most robust evidence of reliability and validity and has been the most extensively examined in terms of psychometric properties. However, there is insufficient evidence at present to determine the best tool for use in research and clinical practice. Further in-depth evaluation of the psychometric properties of these tools is required before they can fulfil the criteria for a gold standard assessment tool

Cannabidiol modulates mitochondrial redox and dynamics in MCF7 cancer cells: a study using fluorescence lifetime imaging microscopy of NAD(P)H

The cannabinoid, cannabidiol (CBD), is part of the plant's natural defence system that when given to animals has many useful medicinal properties, including activity against cancer cells, modulation of the immune system, and efficacy in epilepsy. Although there is no consensus on its precise mode of action as it affects many cellular targets, CBD does appear to influence mitochondrial function. This would suggest that there is a cross-kingdom ability to modulate stress resistance systems that enhance homeostasis. As NAD(P)H autofluorescence can be used as both a metabolic sensor and mitochondrial imaging modality, we assessed the potential of this technique to study the in vitro effects of CBD using 2-photon excitation and fluorescence lifetime imaging microscopy (2P-FLIM) of NAD(P)H against more traditional markers of mitochondrial morphology and cellular stress in MCF7 breast cancer cells. 2P-FLIM analysis revealed that the addition of CBD induced a dose-dependent decrease in bound NAD(P)H, with 20 µM treatments significantly decreasing the contribution of bound NAD(P)H by 14.6% relative to control (p<0.001). CBD also increased mitochondrial concentrations of reactive oxygen species (ROS) (160 ± 53 vs. 97.6 ± 4.8%, 20 µM CBD vs. control, respectively, p<0.001) and Ca2+ (187 ± 78 vs. 105 ± 10%, 20 µM CBD vs. control, respectively, p<0.001); this was associated with significantly decreased mitochondrial branch length and increased fission. These are all suggestive of mitochondrial stress. Our results support the use of NAD(P)H autofluorescence as an investigative tool and provide further evidence that CBD can modulate mitochondrial function and morphology in a dose dependent manner, with clear evidence of it inducing oxidative stress at higher concentrations. This continues to support emerging data in the literature and may provide further insight into its overall mode of action, not only in cancer, but potentially its function in the plant and why it can act as a medicine

European Non-native Species in Aquaculture Risk Analysis Scheme - a summary of assessment protocols and decision support tools for use of alien species in aquaculture

The European Non-native Species in Aquaculture Risk Analysis Scheme (ENSARS) was developed in response to European 'Council Regulation No. 708/2007 of 11 June 2007 concerning use of alien and locally absent species in aquaculture' to provide protocols for identifying and evaluating the potential risks of using non-native species in aquaculture. ENSARS is modular in structure and adapted from non-native species risk assessment schemes developed by the European and Mediterranean Plant Protection Organisation and for the UK. Seven of the eight ENSARS modules contain protocols for evaluating the risks of escape, introduction to and establishment in open waters, of any non-native aquatic organism being used (or associated with those used) in aquaculture, that is, transport pathways, rearing facilities, infectious agents, and the potential organism, ecosystem and socio-economic impacts. A concluding module is designed to summarise the risks and consider management options. During the assessments, each question requires the assessor to provide a response and confidence ranking for that response based on expert opinion. Each module can also be used individually, and each requires a specific form of expertise. Therefore, a multidisciplinary assessment team is recommended for its completion