Evaluating the structure and magnitude of the ash plume during the initial phase of the 2010 Eyjafjallajökull eruption using lidar observations and NAME simulations

The Eyjafjallajökull volcano in Iceland erupted explosively on 14 April 2010, emitting a plume of ash into the atmosphere. The ash was transported from Iceland toward Europe where mostly cloud-free skies allowed ground-based lidars at Chilbolton in England and Leipzig in Germany to estimate the mass concentration in the ash cloud as it passed overhead. The UK Met Office's Numerical Atmospheric-dispersion Modeling Environment (NAME) has been used to simulate the evolution of the ash cloud from the Eyjafjallajökull volcano during the initial phase of the ash emissions, 14–16 April 2010. NAME captures the timing and sloped structure of the ash layer observed over Leipzig, close to the central axis of the ash cloud. Relatively small errors in the ash cloud position, probably caused by the cumulative effect of errors in the driving meteorology en route, result in a timing error at distances far from the central axis of the ash cloud. Taking the timing error into account, NAME is able to capture the sloped ash layer over the UK. Comparison of the lidar observations and NAME simulations has allowed an estimation of the plume height time series to be made. It is necessary to include in the model input the large variations in plume height in order to accurately predict the ash cloud structure at long range. Quantitative comparison with the mass concentrations at Leipzig and Chilbolton suggest that around 3% of the total emitted mass is transported as far as these sites by small (<100 μm diameter) ash particles

A randomised controlled study of the effectiveness of breathing retraining exercises taught by a physiotherapist either by instructional DVD or in face-to-face sessions in the management of asthma in adults.

BACKGROUND: Asthma control is suboptimal, resulting in quality of life (QoL) impairment and costs. Breathing retraining exercises have evidence of effectiveness as adjuvant treatment, but are infrequently used. OBJECTIVES: To transfer the contents of a brief (three-session) physiotherapist-delivered breathing retraining programme to a digital versatile disc (DVD) and booklet format; to compare the effectiveness of the self-guided intervention with that of 'face-to-face' physiotherapy and usual care for QoL and other asthma-related outcomes; to perform a health economic assessment of both interventions; and to perform a process evaluation using quantitative and qualitative methods. DESIGN: Parallel-group three-arm randomised controlled trial. SETTING: General practice surgeries in the UK. PARTICIPANTS: In total, 655 adults currently receiving asthma treatment with impaired asthma-related QoL were randomly allocated to the DVD (n = 261), physiotherapist (n = 132) and control (usual care) (n = 262) arms in a 2 : 1 : 2 ratio. It was not possible to blind participants but data collection and analysis were performed blinded. INTERVENTIONS: Physiotherapy-based breathing retraining delivered through three 'face-to-face' respiratory physiotherapist sessions or a self-guided programme (DVD plus our theory-based behaviour change booklet) developed by the research team, with a control of usual care. MAIN OUTCOME MEASURES: The primary outcome measure was asthma-specific QoL, measured using the Asthma Quality of Life Questionnaire (AQLQ). Secondary outcomes included asthma symptom control [Asthma Control Questionnaire (ACQ)], psychological state [Hospital Anxiety and Depression Scale (HADS)], hyperventilation symptoms (Nijmegen questionnaire), generic QoL [EuroQol-5 Dimensions (EQ-5D)], assessments of airway physiology (spirometry) and inflammation (exhaled nitric oxide) and health resource use and costs. Assessments were carried out at baseline and at 3, 6 and 12 months post randomisation. Patient engagement and experience were also assessed using quantitative and qualitative methods. RESULTS: Primary efficacy analysis was between-group comparison of changes in AQLQ scores from baseline to 12 months in the intention-to-treat population with adjustments for prespecified covariates. Significant improvements occurred in the DVD group compared with the control group [adjusted mean difference 0.28, 95% confidence interval (CI) 0.11 to 0.44; p < 0.001] and in the face-to-face physiotherapy group compared with the control group (adjusted mean difference 0.24, 95% CI 0.04 to 0.44; p < 0.05), with equivalence between the DVD and the face-to-face physiotherapy groups (adjusted mean difference 0.04, 95% CI -0.16 to 0.24). In all sensitivity analyses, both interventions remained significantly superior to the control and equivalence between the interventions was maintained. In other questionnaire outcome measures and in the physiological measures assessed, there were no significant between-group differences. Process evaluations showed that participants engaged well with both of the active interventions, but that some participants in the DVD arm would have liked to receive tuition from a professional. Asthma health-care costs were lower in both intervention arms than in the control group, indicating 'dominance' for both of the interventions compared with the control, with lowest costs in the DVD arm. The rate of adverse events was lower in the DVD and face-to-face physiotherapy groups than in the control group. CONCLUSIONS: Only 10% of the potentially eligible population responded to the study invitation. However, breathing retraining exercises improved QoL and reduced health-care costs in adults with asthma whose condition remains uncontrolled despite standard pharmacological therapy, were engaged with well by patients and can be delivered effectively as a self-guided intervention. The intervention should now be transferred to an internet-based platform and implementation studies performed. Interventions for younger patients should be developed and trialled. TRIAL REGISTRATION: Current Controlled Trials ISRCTN88318003. FUNDING: This project was primarily funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 53. See the NIHR Journals Library website for further project information. Additional financial support was received from Comprehensive Local Research Networks

A phase I trial of antibody directed enzyme prodrug therapy (ADEPT) in patients with advanced colorectal carcinoma or other CEA producing tumours

Antibody-directed enzyme prodrug therapy is a targeted therapy in which a prodrug is activated selectively at the tumour site by an enzyme, which has been targeted to the tumour by an antibody (antibody-enzyme conjugate). Previous clinical trials have shown evidence of tumour response, however, the activated drug had a long half-life, which resulted in dose-limiting myelosuppression. Also, the targeting system, although giving high tumour to blood ratios of antibody-enzyme conjugate (10 000 : 1) required administration of a clearing antibody in addition to the antibody-enzyme conjugate. The purpose of this current study therefore was to attempt tumour targeting of the antibody-enzyme conjugate without the clearing antibody, and to investigate a new prodrug (bis-iodo phenol mustard, ZD2767P) whose activated form is highly potent and has a short half-life. Twenty-seven patients were treated with antibody-directed enzyme prodrug therapy using A5CP antibody-enzyme conjugate and ZD2767P prodrug, in a dose-escalating phase I trial. The maximum tolerated dose of ZD2767P was reached at 15.5 mg m−2×three administrations with a serum carboxypeptidase G2 level of 0.05 U ml−1. Myelosuppression limited dose escalation. Other toxicities were mild. Patients' quality of life was not adversely affected during the trial as assessed by the measures used. There were no clinical or radiological responses seen in the study, but three patients had stable disease at day 56. Human anti-mouse antibody and human anti-carboxypeptidase G2 antibody were produced in response to the antibody enzyme conjugate (A5CP). The antibody-enzyme conjugate localisation data (carboxypeptidase G2 enzyme levels by HPLC on tumour and normal tissue samples, and gamma camera analysis of I-131 radiolabelled conjugate) are consistent with inadequate tumour localisation (median tumour: normal tissue ratios of antibody-enzyme conjugate of less than 1). A clearance system is therefore desirable with this antibody-enzyme conjugate or a more efficient targeting system is required. ZD2767P was shown to clear rapidly from the circulation and activated drug was not measurable in the blood. ZD2767P has potential for use in future antibody-directed enzyme prodrug therapy systems

Unconscious bias and the medical model: How the social model may hold the key to transformative thinking about disability discrimination

This article seeks to gain access to a new way to engage with disability discrimination and the legal approaches to it by focusing on the two central models: the medical and social models. It discusses how the law has based the definition of disability on the medical model and suggests that this may strengthen some of the underlying factors that contribute to segregation and discrimination of disabled people. This article argues that the law should now switch focus to the social model, in an attempt to transform people’s attitudes towards disabled people and become a positive force to reduce discrimination. It makes reference to the reasonable adjustment duty contained in sections 20 and 21 Equality Act 2010, the Framework Directive and by way of comparison the American with Disabilities Act 1990. Relevant critical theories are integrated as a means to explore the conception and the hierarchy that exist between able-bodied individuals and disabled individuals

An evaluation of alcohol attendances to an inner city emergency department before and after the introduction of the UK Licensing Act 2003

Background: The Licensing Act 2003 (The Act) was implemented on the 24th November 2005 across England and Wales. The Act allowed more flexible and longer opening hours for licensed premises. We investigated the effect of The Act on alcohol related attendances to an inner city emergency department in Birmingham, UK. \ud \ud Methods: We compared the proportion and time of alcohol related emergency department attendances in one week periods in January 2005 and 2006, before and after the implementation of The Licensing Act 2003. An alcohol related attendance was defined as any attendance where there was any documentation of the patient having consumed alcohol before presenting to the emergency department, if they appeared intoxicated on examination, or if alcohol attributed to their final diagnosis. \ud \ud Results: The total weekly attendances increased slightly from 1,912 in 2005 to 2,146 in 2006. There was non-significant reduction in the proportion of alcohol related attendances between 2005 (3.6%) and 2006 (2.9%). A significantly greater proportion of attendances occurred at the weekend between 18.00 and 23.59 in 2005 (61.4%) than in 2006 (17.2%). There was a corresponding significant increase in the weekend proportion of attendances occurring between 03.00 to 05.59 in 2006. \ud \ud Conclusion: Our findings show that there was a change in the pattern of alcohol related attendances to the emergency department around the time of implementation of the Licensing Act 2003, which has implications for delivery of emergency department services

Gain and Loss Learning Differentially Contribute to Life Financial Outcomes

Emerging findings imply that distinct neurobehavioral systems process gains and losses. This study investigated whether individual differences in gain learning and loss learning might contribute to different life financial outcomes (i.e., assets versus debt). In a community sample of healthy adults (n = 75), rapid learners had smaller debt-to-asset ratios overall. More specific analyses, however, revealed that those who learned rapidly about gains had more assets, while those who learned rapidly about losses had less debt. These distinct associations remained strong even after controlling for potential cognitive (e.g., intelligence, memory, and risk preferences) and socioeconomic (e.g., age, sex, ethnicity, income, education) confounds. Self-reported measures of assets and debt were additionally validated with credit report data in a subset of subjects. These findings support the notion that different gain and loss learning systems may exert a cumulative influence on distinct life financial outcomes

Leaf yellowing of the wheat cultivar Mace in the absence of yellowspot disease

The wheat variety Mace is currently dominating the southern wheat growing regions of Australia. It is high yielding in most environments and resistant to many diseases including yellow spot (also known as tan spot). However, observations of foliar yellowing of Mace have recently been reported in the field. This has raised concerns over a possible breakdown of resistance to yellow spot, which is caused by the necrotrophic fungal pathogen Pyrenophora triticirepentis. West Australian field samples of yellowing Mace leaves were evaluated for P. triticirepentis infection, and this pathogen was determined to be absent. Instead, Alternaria spp. were isolated from the wheat leaves. Pathogenicity assays showed that the recovered Alternaria spp. were unable to cause disease symptoms on Mace. Furthermore, spontaneous foliar lesions were observed in Mace grown in the absence of pathogens. It is therefore likely that such yellowing is a physiological trait, which will not respond to fungicide application. A marginal impact on yield cannot be excluded