Detection of ultrafine plastics ingested by seabirds using tissue digestion.

Plastic debris is a major global threat to marine ecosystems and species. However, our knowledge of this issue may be incomplete due to a lack of a standardized method for quantifying ingested ultrafine particles (1 μm - 1 mm) in wildlife. This study provides the first quantification of ultrafine plastic in seabirds using chemical and biological digestion treatments to extract plastic items from seabird gizzards. The alkaline agent, potassium hydroxide, outperformed the enzyme corolase, based on cost and efficiency (e.g., digestion time). Ultrafine plastics were observed in 7.0% of Flesh-footed Shearwater (Ardenna carneipes) gizzards collected from Lord Howe Island, Australia and accounted for 3.6% of all plastic items recovered (13 out of 359 items). Existing methods for extracting ingested plastic from seabirds do not account for ultrafine particles, therefore our results indicate current seabird plastic loads, and the associated physical and biological impacts, are underestimated.The attached document is the author(’s’) final accepted/submitted version of the journal article. You are advised to consult the publisher’s version if you wish to cite from it

Clinical and cost effectiveness of mechanical support for severe ankle sprains: design of a randomised controlled trial in the emergency department [ISRCTN 37807450]

Background The optimal management for severe sprains (Grades II and III) of the lateral ligament complex of the ankle is unclear. The aims of this randomised controlled trial are to estimate (1) the clinical effectiveness of three methods of providing mechanical support to the ankle (below knee cast, Aircast® brace and Bledsoe® boot) in comparison to Tubigrip®, and (2) to compare the cost of each strategy, including subsequent health care costs. Methods/design Six hundred and fifty people with a diagnosis of severe sprain are being identified through emergency departments. The study has been designed to complement routine practice in the emergency setting. Outcomes are recovery of mobility (primary outcome) and usual activity, residual symptoms and need for further medical, rehabilitation or surgical treatment. Parallel economic and qualitative studies are being conducted to aid interpretation of the results and to evaluate the cost-effectiveness of the interventions. Discussion This paper highlights the design, methods and operational aspects of a clinical trial of acute injury management in the emergency department

Thorium Energy Futures

The potential for thorium as an alternative or supplement to uranium in fission power generation has long been recognised, and several reactors, of various types, have already operated using thorium-based fuels. Accelerator Driven Subcritical (ADS) systems have benefits and drawbacks when compared to conventional critical thorium reactors, for both solid and molten salt fuels. None of the four options – liquid or solid, with or without an accelerator – can yet be rated as better or worse than the other three, given today's knowledge. We outline the research that will be necessary to lead to an informed choice

Ethical issues in implementation research: a discussion of the problems in achieving informed consent

Background: Improved quality of care is a policy objective of health care systems around the world. Implementation research is the scientific study of methods to promote the systematic uptake of clinical research findings into routine clinical practice, and hence to reduce inappropriate care. It includes the study of influences on healthcare professionals' behaviour and methods to enable them to use research findings more effectively. Cluster randomized trials represent the optimal design for evaluating the effectiveness of implementation strategies. Various codes of medical ethics, such as the Nuremberg Code and the Declaration of Helsinki inform medical research, but their relevance to cluster randomised trials in implementation research is unclear. This paper discusses the applicability of various ethical codes to obtaining consent in cluster trials in implementation research. Discussion: The appropriate application of biomedical codes to implementation research is not obvious. Discussion of the nature and practice of informed consent in implementation research cluster trials must consider the levels at which consent can be sought, and for what purpose it can be sought. The level at which an intervention is delivered can render the idea of patient level consent meaningless. Careful consideration of the ownership of information, and rights of access to and exploitation of data is required. For health care professionals and organizations, there is a balance between clinical freedom and responsibility to participate in research. Summary: While ethical justification for clinical trials relies heavily on individual consent, for implementation research aspects of distributive justice, economics, and political philosophy underlie the debate. Societies may need to trade off decisions on the choice between individualized consent and valid implementation research. We suggest that social sciences codes could usefully inform the consideration of implementation research by members of Research Ethics Committees

Application and investigation of a bound for outcome reporting bias

BACKGROUND: Direct empirical evidence for the existence of outcome reporting bias is accumulating and this source of bias is recognised as a potential threat to the validity of meta-analysis of randomised clinical trials. METHODS: A method for calculating the maximum bias in a meta-analysis due to publication bias is adapted for the setting where within-study selective non-reporting of outcomes is suspected, and compared to the alternative approach of missing data imputation. The properties of both methods are investigated in realistic small sample situations. RESULTS: The results suggest that the adapted Copas and Jackson approach is the preferred method for reviewers to apply as an initial assessment of robustness to within-study selective non-reporting. CONCLUSION: The Copas and Jackson approach is a useful method for systematic reviewers to apply to assess robustness to outcome reporting bias

Survey of the quality of experimental design, statistical analysis and reporting of research using animals

For scientific, ethical and economic reasons, experiments involving animals should be appropriately designed, correctly analysed and transparently reported. This increases the scientific validity of the results, and maximises the knowledge gained from each experiment. A minimum amount of relevant information must be included in scientific publications to ensure that the methods and results of a study can be reviewed, analysed and repeated. Omitting essential information can raise scientific and ethical concerns. We report the findings of a systematic survey of reporting, experimental design and statistical analysis in published biomedical research using laboratory animals. Medline and EMBASE were searched for studies reporting research on live rats, mice and non-human primates carried out in UK and US publicly funded research establishments. Detailed information was collected from 271 publications, about the objective or hypothesis of the study, the number, sex, age and/or weight of animals used, and experimental and statistical methods. Only 59% of the studies stated the hypothesis or objective of the study and the number and characteristics of the animals used. Appropriate and efficient experimental design is a critical component of high-quality science. Most of the papers surveyed did not use randomisation (87%) or blinding (86%), to reduce bias in animal selection and outcome assessment. Only 70% of the publications that used statistical methods described their methods and presented the results with a measure of error or variability. This survey has identified a number of issues that need to be addressed in order to improve experimental design and reporting in publications describing research using animals. Scientific publication is a powerful and important source of information; the authors of scientific publications therefore have a responsibility to describe their methods and results comprehensively, accurately and transparently, and peer reviewers and journal editors share the responsibility to ensure that published studies fulfil these criteria

Cortical thickness, surface area and volume measures in Parkinson's disease, multiple system atrophy and progressive supranuclear palsy

OBJECTIVE Parkinson's disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) are neurodegenerative diseases that can be difficult to distinguish clinically. The objective of the current study was to use surface-based analysis techniques to assess cortical thickness, surface area and grey matter volume to identify unique morphological patterns of cortical atrophy in PD, MSA and PSP and to relate these patterns of change to disease duration and clinical features. METHODS High resolution 3D T1-weighted MRI volumes were acquired from 14 PD patients, 18 MSA, 14 PSP and 19 healthy control participants. Cortical thickness, surface area and volume analyses were carried out using the automated surface-based analysis package FreeSurfer (version 5.1.0). Measures of disease severity and duration were assessed for correlation with cortical morphometric changes in each clinical group. RESULTS Results show that in PSP, widespread cortical thinning and volume loss occurs within the frontal lobe, particularly the superior frontal gyrus. In addition, PSP patients also displayed increased surface area in the pericalcarine. In comparison, PD and MSA did not display significant changes in cortical morphology. CONCLUSION These results demonstrate that patients with clinically established PSP exhibit distinct patterns of cortical atrophy, particularly affecting the frontal lobe. These results could be used in the future to develop a useful clinical application of MRI to distinguish PSP patients from PD and MSA patients

Improving the use of research evidence in guideline development: 11. Incorporating considerations of cost-effectiveness, affordability and resource implications

BACKGROUND: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the 11(th )of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. OBJECTIVES: We reviewed the literature on incorporating considerations of cost-effectiveness, affordability and resource implications in guidelines and recommendations. METHODS: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct systematic reviews ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. KEY QUESTIONS AND ANSWERS: When is it important to incorporate cost-effectiveness, resource implications and affordability considerations in WHO guidelines (which topics)? • For cost-effectiveness: The need for cost/effectiveness information should be dictated by the specific question, of which several may be addressed in a single guideline. It is proposed that the indications for undertaking a cost-effectiveness analysis (CEA) could be a starting point for determining which recommendation(s) in the guideline would benefit from such analysis. • For resource implications/affordability: The resource implications of each individual recommendation need to be considered when implementation issues are being discussed. How can cost-effectiveness, resource implications and affordability be explicitly taken into account in WHO guidelines? • For cost-effectiveness: ∘ If data are available, the ideal time to consider cost-effectiveness is during the evidence gathering and synthesizing stage. However, because of the inconsistent availability of CEAs and the procedural difficulty associated with adjusting results from different CEAs to make them comparable, it is also possible for cost-effectiveness to be considered during the stage of developing recommendations. ∘ Depending on the quantity and quality and relevance of the data available, such data can be considered in a qualitative way or in a quantitative way, ranging from a listing of the costs to a modelling exercise. At the very least, a qualitative approach like a commentary outlining the economic issues that need to be considered is necessary. If a quantitative approach is to be used, the full model should be transparent and comprehensive. • For resource implications/affordability: ∘ Resource implications, including health system changes, for each recommendation in a WHO guideline should be explored. At the minimum, a qualitative description that can serve as a gross indicator of the amount of resources needed, relative to current practice, should be provided. How does one provide guidance in contextualizing guideline recommendations at the country level based on considerations of cost-effectiveness, resource implications and affordability? • All models should be made available and ideally are designed to allow for analysts to make changes in key parameters and reapply results in their own country. • In the global guidelines, scenarios and extensive sensitivity/uncertainty analysis can be applied. Resource implications for WHO • From the above, it is clear that guidelines development groups will need a health economist. There is need to ensure that this is included in the budget for guidelines and that there is in-house support for this as well

Economic evaluation of fulvestrant as an extra step in the treatment sequence for ER-positive advanced breast cancer

Drug therapies for advanced breast cancer in hormone-receptor-positive disease include both hormonal and chemotherapies. Current UK practice is to minimise toxicity by using sequential hormonal agents for as long as clinically appropriate. A Markov model was developed to investigate the cost effectiveness of different sequences of therapies, particularly exploring the effects of adding an additional hormonal agent, fulvestrant, to the treatment pathway. A systematic review was undertaken and a panel of seven UK oncologists validated assumptions used for treatment efficacy, treatment pathways and resources used. Fulvestrant was found to be a cost-effective treatment option when added to the treatment sequence as a second- or third-line hormonal therapy for advanced disease. For a cohort of 1000 patients, fulvestrant as a second-line hormone therapy provided an additional 47 life years and 41 quality-adjusted life years (QALYs), at an additional cost of £301 359. This equated to £6500 per life years gained and £7500 per QALY. When used as a third-line option, the fulvestrant arm was dominant providing an increase in health benefit of 27 QALYs for the whole cohort, at a mean overall cost reduction of £430 per patient. Sensitivity analyses showed these results to be robust, demonstrating that fulvestrant is an economically viable additional endocrine option in the United Kingdom for the treatment of hormone responsive advanced breast cancer