Distribution and abundance of sardine (Sardina pilchardus) eggs in the English Channel from Continuous Plankton Recorder sampling

Continuous Plankton Recorder (CPR) samples from the English Channel and adjacent Celtic shelf, taken over the period 1958-1980, were analysed for sardine (Sardina pilchardus) eggs. Results showed the progression of sardine spawning along the English Channel from west to east from March to August and a return from east to west from September to November. This corresponds with the two seasonal peaks of sardine egg abundance in the western Channel: the main summer peak being in May/June, with a smaller autumn peak in October/November. Long-term changes in sardine egg abundance in CPR samples showed a decline in summer spawning from the late 1960s, but no clear trend in autumn-spawned egg abundance. Similar patterns were observed in the numbers of sardine eggs sampled by conventional plankton net tows at the time-series Station L5 off Plymouth. This supports the use of the longer time-series of sardine egg data at L5 as being representative of a wider area and emphasizes the importance in continuation of the L5 time-series

Patient and Public Involvement Refines the Design of ProtOeus: A Proposed Phase II Trial of Proton Beam Therapy in Oesophageal Cancer

Background: Neoadjuvant chemoradiotherapy for oesophageal cancer significantly improves overall survival but is associated with severe post-operative complications. Proton beam therapy may reduce these toxicities by sparing normal tissues compared with standard radiotherapy. ProtOeus is a proposed randomised phase II study of neoadjuvant chemoradiotherapy in oesophageal cancer that compares proton beam therapy to standard radiotherapy techniques. As proton beam therapy services are often centralised in academic centres in major cities, proton beam therapy trials raise distinct challenges including patient acceptance of travelling for proton beam therapy, coordination of treatments with local centres and ensuring equity of access for patients. Methods: Focus groups were held early in the trial development process to establish patients’ views on the trial proposal. Topics discussed include perception of proton beam therapy, patient acceptability of the trial pathway and design, patient-facing materials, and common clinical scenarios. Focus groups were led by the investigators and facilitated by patient involvement teams from the institutions who are involved in this research. Responses for each topic were analysed, and fed back to the trial’s development group. Results: Three focus groups were held in separate locations in the UK (Manchester, Cardiff, Wigan). Proton beam therapy was perceived as superior to standard radiotherapy making the trial attractive. Patients felt strongly that travel costs should be reimbursed to ensure equity of access to proton beam therapy. They were very supportive of a shorter treatment schedule and felt that toxicity reduction was the most important endpoint. Discussion and Conclusions: Incorporating patient views early in the trial development process resulted in significant trial design refinements including travel/accommodation provisions, choice of primary endpoint, randomisation ratio and fractionation schedule. Focus groups are a reproducible and efficient method of incorporating the patient and public voice into research

The Promise of Proton Beam Therapy for Oesophageal Cancer: A Systematic Review of Dosimetric and Clinical Outcomes

AIMS: Due to its physical advantages over photon radiotherapy, proton beam therapy (PBT) has the potential to improve outcomes from oesophageal cancer. However, for many tumour sites, high-quality evidence supporting PBT use is limited. We carried out a systematic review of published literature of PBT in oesophageal cancer to ascertain potential benefits of this technology and to gauge the current state-of-the-art. We considered if further evaluation of this technology in oesophageal cancer is desirable. MATERIALS AND METHODS: A systematic literature search of Medline, Embase, Cochrane Library and Web of Science using structured search terms was carried out. Inclusion criteria included non-metastatic cancer, full articles and English language studies only. Articles deliberating technical aspects of PBT planning or delivery were excluded to maintain a clinical focus. Studies were divided into two sections: dosimetric and clinical studies; qualitatively synthesised. RESULTS: In total, 467 records were screened, with 32 included for final qualitative synthesis. This included two prospective studies with the rest based on retrospective data. There was heterogeneity in treatment protocols, including treatment intent (neoadjuvant or definitive), dose, fractionation and chemotherapy used. Compared with photon radiotherapy, PBT seemed to reduce dose to organs at risk, especially lung and heart, although not for all reported parameters. Toxicity outcomes, including postoperative complications, were reduced compared with photon radiotherapy. Survival outcomes were reported to be at least comparable with photon radiotherapy. CONCLUSION: There is a paucity of high-quality evidence supporting PBT use in oesophageal cancer. Wide variation in intent and treatment protocols means that the role and 'gold-standard' treatment protocol are yet to be defined. Current literature suggests significant benefit in terms of toxicity reduction, especially in the postoperative period, with comparable survival outcomes. PBT in oesophageal cancer holds significant promise for improving patient outcomes but requires robust systematic evaluation in prospective studies

What guidance are researchers given on how to present network meta-analyses to end-users such as policymakers and clinicians? A systematic review

© 2014 Sullivan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Introduction: Network meta-analyses (NMAs) are complex methodological approaches that may be challenging for non-technical end-users, such as policymakers and clinicians, to understand. Consideration should be given to identifying optimal approaches to presenting NMAs that help clarify analyses. It is unclear what guidance researchers currently have on how to present and tailor NMAs to different end-users. Methods: A systematic review of NMA guidelines was conducted to identify guidance on how to present NMAs. Electronic databases and supplementary sources were searched for NMA guidelines. Presentation format details related to sample formats, target audiences, data sources, analysis methods and results were extracted and frequencies tabulated. Guideline quality was assessed following criteria developed for clinical practice guidelines. Results: Seven guidelines were included. Current guidelines focus on how to conduct NMAs but provide limited guidance to researchers on how to best present analyses to different end-users. None of the guidelines provided reporting templates. Few guidelines provided advice on tailoring presentations to different end-users, such as policymakers. Available guidance on presentation formats focused on evidence networks, characteristics of individual trials, comparisons between direct and indirect estimates and assumptions of heterogeneity and/or inconsistency. Some guidelines also provided examples of figures and tables that could be used to present information. Conclusions: Limited guidance exists for researchers on how best to present NMAs in an accessible format, especially for non-technical end-users such as policymakers and clinicians. NMA guidelines may require further integration with end-users' needs, when NMAs are used to support healthcare policy and practice decisions. Developing presentation formats that enhance understanding and accessibility of NMAs could also enhance the transparency and legitimacy of decisions informed by NMAs.The Canadian Institute of Health Research (CIHR) Drug Safety and Effectiveness Network (Funding reference number – 116573)

A Feature-Pooling and Signature-Pooling Method for Feature Selection for Quantitative Image Analysis: Application to a Radiomics Model for Survival in Glioma

We proposed a pooling-based radiomics feature selection method and showed how it would be applied to the clinical question of predicting one-year survival in 130 patients treated for glioma by radiotherapy. The method combines filter, wrapper and embedded selection in a comprehensive process to identify useful features and build them into a potentially predictive signature. The results showed that non-invasive CT radiomics were able to moderately predict overall survival and predict WHO tumour grade. This study reveals an associative inter-relationship between WHO tumour grade, CT-based radiomics and survival, that could be clinically relevant

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research

Second malignant neoplasms after a first cancer in childhood: temporal pattern of risk according to type of treatment

The variation in the risk of solid second malignant neoplasms (SMN) with time since first cancer during childhood has been previously reported. However, no study has been performed that controls for the distribution of radiation dose and the aggressiveness of past chemotherapy, which could be responsible for the observed temporal variation of the risk. The purpose of this study was to investigate the influence of the treatment on the long-term pattern of the incidence of solid SMN after a first cancer in childhood. We studied a cohort of 4400 patients from eight centres in France and the UK. Patients had to be alive 3 years or more after a first cancer treated before the age of 17 years and before the end of 1985. For each patient in the cohort, the complete clinical, chemotherapy and radiotherapy history was recorded. For each patient who had received external radiotherapy, the dose of radiation received by 151 sites of the body were estimated. After a mean follow-up of 15 years, 113 children developed a solid SMN, compared to 12.3 expected from general population rates. A similar distribution pattern was observed among the 1045 patients treated with radiotherapy alone and the 2064 patients treated with radiotherapy plus chemotherapy; the relative risk, but not the excess absolute risk, of solid SMN decreased with time after first treatment; the excess absolute risk increased during a period of at least 30 years after the first cancer. This pattern remained after controlling for chemotherapy and for the average dose of radiation to the major sites of SMN. It also remained when excluding patients with a first cancer type or an associated syndrome known to predispose to SMN. When compared with radiotherapy alone, the addition of chemotherapy increases the risk of solid SMN after a first cancer in childhood, but does not significantly modify the variation of this risk during the time after the first cancer. © 1999 Cancer Research Campaig

Agenda setting and framing of gender-based violence in Nepal: how it became a health issue.

: Gender-based violence (GBV) has been addressed as a policy issue in Nepal since the mid 1990s, yet it was only in 2010 that Nepal developed a legal and policy framework to combat GBV. This article draws on the concepts of agenda setting and framing to analyse the historical processes by which GBV became legitimized as a health policy issue in Nepal and explored factors that facilitated and constrained the opening and closing of windows of opportunity. The results presented are based on a document analysis of the policy and regulatory framework around GBV in Nepal. A content analysis was undertaken. Agenda setting for GBV policies in Nepal evolved over many years and was characterized by the interplay of political context factors, actors and multiple frames. The way the issue was depicted at different times and by different actors played a key role in the delay in bringing health onto the policy agenda. Women's groups and less powerful Ministries developed gender equity and development frames, but it was only when the more powerful human rights frame was promoted by the country's new Constitution and the Office of the Prime Minister that legislation on GBV was achieved and a domestic violence bill was adopted, followed by a National Plan of Action. This eventually enabled the health frame to converge around the development of implementation policies that incorporated health service responses. Our explicit incorporation of framing within the Kindgon model has illustrated how important it is for understanding the emergence of policy issues, and the subsequent debates about their resolution. The framing of a policy problem by certain policy actors, affects the development of each of the three policy streams, and may facilitate or constrain their convergence. The concept of framing therefore lends an additional depth of understanding to the Kindgon agenda setting model.<br/

Data management for prospective research studies using SAS® software

<p>Abstract</p> <p>Background</p> <p>Maintaining data quality and integrity is important for research studies involving prospective data collection. Data must be entered, erroneous or missing data must be identified and corrected if possible, and an audit trail created.</p> <p>Methods</p> <p>Using as an example a large prospective study, the Missouri Lower Respiratory Infection (LRI) Project, we present an approach to data management predominantly using SAS software. The Missouri LRI Project was a prospective cohort study of nursing home residents who developed an LRI. Subjects were enrolled, data collected, and follow-ups occurred for over three years. Data were collected on twenty different forms. Forms were inspected visually and sent off-site for data entry. SAS software was used to read the entered data files, check for potential errors, apply corrections to data sets, and combine batches into analytic data sets. The data management procedures are described.</p> <p>Results</p> <p>Study data collection resulted in over 20,000 completed forms. Data management was successful, resulting in clean, internally consistent data sets for analysis. The amount of time required for data management was substantially underestimated.</p> <p>Conclusion</p> <p>Data management for prospective studies should be planned well in advance of data collection. An ongoing process with data entered and checked as they become available allows timely recovery of errors and missing data.</p