UK guidelines for the management of soft tissue sarcomas

Soft tissue sarcomas (STS) are rare tumours arising in mesenchymal tissues, and can occur almost anywhere in the body. Their rarity, and the heterogeneity of subtype and location means that developing evidence-based guidelines is complicated by the limitations of the data available. However, this makes it more important that STS are managed by teams, expert in such cases, to ensure consistent and optimal treatment, as well as recruitment to clinical trials, and the ongoing accumulation of further data and knowledge. The development of appropriate guidance, by an experienced panel referring to the evidence available, is therefore a useful foundation on which to build progress in the field. These guidelines are an update of the previous version published in 2010 (Grimer et al. in Sarcoma 2010:506182, 2010). The original guidelines were drawn up following a consensus meeting of UK sarcoma specialists convened under the auspices of the British Sarcoma Group (BSG) and were intended to provide a framework for the multidisciplinary care of patients with soft tissue sarcomas. This current version has been updated and amended with reference to other European and US guidance. There are specific recommendations for the management of selected subtypes of disease including retroperitoneal and uterine sarcomas, as well as aggressive fibromatosis (desmoid tumours) and other borderline tumours commonly managed by sarcoma services. An important aim in sarcoma management is early diagnosis and prompt referral. In the UK, any patient with a suspected soft tissue sarcoma should be referred to one of the specialist regional soft tissues sarcoma services, to be managed by a specialist sarcoma multidisciplinary team. Once the diagnosis has been confirmed using appropriate imaging, plus a biopsy, the main modality of management is usually surgical excision performed by a specialist surgeon. In tumours at higher risk of recurrence or metastasis pre- or post-operative radiotherapy should be considered. Systemic anti-cancer therapy (SACT) may be utilized in some cases where the histological subtype is considered more sensitive to systemic treatment. Regular follow-up is recommended to assess local control, development of metastatic disease, and any late-effects of treatment. For local recurrence, and more rarely in selected cases of metastatic disease, surgical resection would be considered. Treatment for metastases may include radiotherapy, or systemic therapy guided by the sarcoma subtype. In some cases, symptom control and palliative care support alone will be appropriate

Cascading the use of Web 2.0 technology in secondary schools in the United Kingdom: identifying the barriers beyond pre-service training

This paper reports on research that took place at Nottingham Trent University and Sheffield Hallam University, United Kingdom, over two years. The research focuses on the use of Web 2.0 technology, specifically web logs, with pre-service teachers, both during their university programme and the first year of teaching as full-time newly qualified teachers (NQTs). The purpose of this research was to add a developing body of knowledge by identifying whether technology used by pre-service teachers during their training course can be cascaded into their practice once qualified. Key findings identify a number of enablers and barriers to cascading technology in the classroom; these include curriculum time, pupil skills and support. The research concludes that early professional support and development should be on-going and assumptions about new teachers as champions of cascading innovative use of Web 2 technologies into their practice as NQTs may be over optimisti

Genome-Resolved Proteomic Stable Isotope Probing of Soil Microbial Communities Using 13CO2 and 13C-Methanol.

Stable isotope probing (SIP) enables tracking the nutrient flows from isotopically labeled substrates to specific microorganisms in microbial communities. In proteomic SIP, labeled proteins synthesized by the microbial consumers of labeled substrates are identified with a shotgun proteomics approach. Here, proteomic SIP was combined with targeted metagenomic binning to reconstruct metagenome-assembled genomes (MAGs) of the microorganisms producing labeled proteins. This approach was used to track carbon flows from 13CO2 to the rhizosphere communities of Zea mays, Triticum aestivum, and Arabidopsis thaliana. Rhizosphere microorganisms that assimilated plant-derived 13C were capable of metabolic and signaling interactions with their plant hosts, as shown by their MAGs containing genes for phytohormone modulation, quorum sensing, and transport and metabolism of nutrients typical of those found in root exudates. XoxF-type methanol dehydrogenases were among the most abundant proteins identified in the rhizosphere metaproteomes. 13C-methanol proteomic SIP was used to test the hypothesis that XoxF was used to metabolize and assimilate methanol in the rhizosphere. We detected 7 13C-labeled XoxF proteins and identified methylotrophic pathways in the MAGs of 8 13C-labeled microorganisms, which supported the hypothesis. These two studies demonstrated the capability of proteomic SIP for functional characterization of active microorganisms in complex microbial communities

Mindfulness-Based Programs: Why, When, and How to Adapt?

This paper provides a framework for understanding why, when and how to adapt mindfulness-based programs (MBPs) to specific populations and contexts, based on research that developed and adapted multiple MBPs. In doing so, we hope to support teachers, researchers and innovators who are considering adapting an MBP to ensure that changes made are necessary, acceptable, effective, cost-effective, and implementable. Specific questions for reflection are provided such as (1) Why is an adaptation needed? (2) Does the theoretical premise underpinning mainstream MBPs extend to the population you are considering? (3) Do the benefits of the proposed adaptation outweigh the time and costs involved to all in research and implementation? (4) Is there already an evidenced-based approach to address this issue in the population or context? Fundamental knowledge that is important for the adaptation team to have includes the following: (1) essential ingredients of MBPs, (2) etiology of the target health outcome, (3) existing interventions that work for the health outcome, population, and context, (4) delivery systems and settings, and (5) culture, values, and communication patterns of the target population. A series of steps to follow for adaptations is provided, as are case examples. Adapting MBPs happens not only by researchers, but also by MBP teachers and developers, who endeavor to best serve the populations and contexts they work within. We hope that these recommendations for best practice provide a practical framework for skilfully understanding why, when, and how to adapt MBPs; and that this careful approach to adaptation maximizes MBP safety and efficacy

Phase II trial of the oral platinum complex JM216 in non-small-cell lung cancer: An EORTC early clinical studies group investigation

Background JM216 is a new oral platinum complex with dose-limiting toxicity myelosuppresssion, now undergoing phase II evaluation. Patients and methods JM216 was evaluated as first line therapy in non-small-cell lung cancer. Seventeen patients received 120 mg/m2/day for five days repeated every three weeks. Results Toxicity was manageable, the commonest side-effects being nausea, vomiting, diarrhoea, constipation and asthenia. Myelososuppression was generally grade <2 and there were no cases of neutropenic sepsis or bleeding. Thirteen patients were fully evaluable for response. No sustained objective responses were reported. One patient was reported as stable disease had a partial response after three courses but was progressing again after four. An additional five patients had stable disease (46.2%). Conclusions Although some patients may have had useful palliation, JM216 did not appear to have significant antitumour activity in non-small-cell lung cance

Hormonal impact of the 17α-hydroxylase/C17,20-lyase inhibitor abiraterone acetate (CB7630) in patients with prostate cancer

A series of three dose escalating studies were conducted to investigate the ability of the 17-hydroxylase/C17,20-lyase inhibitor abiraterone acetate, to cause maximum suppression of testosterone synthesis when delivered to castrate and noncastrate males with prostate cancer. Study A was a single dose study in castrate males. Study B was a single dose study in noncastrate males and study C was a multiple dose study in noncastrate males. The drug was given orally in a once-daily dose and blood samples taken to assess pharmacokinetic (PK) parameters and hormone levels in all patients. The study drug was well tolerated with some variability in PKs. Suppression of testosterone levels to <0.14 nmol l-1 was seen in four out of six castrate males treated with a single dose of 500 mg. At 800 mg given days 1–12 in noncastrate males, target suppression was achieved in three out of three patients, but a two- to three-fold increase of Luteinising Hormone (LH) levels in two out of three patients overcame suppression within 3 days. All patients in the multiple dose study developed an abnormal response to a short Synacthen test by day 11, although baseline cortisol levels remained normal. This is the first report of the use of a specific 17-hydroxylase/17,20-lyase inhibitor in humans. Repeated treatment of men with intact gonadal function with abiraterone acetate at a dose of 800 mg can successfully suppress testosterone levels to the castrate range. However, this level of suppression may not be sustained in all patients due to compensatory hypersecretion of LH. The enhanced testosterone suppression achieved in castrate men merits further clinical study as a second-line hormonal treatment for prostate cancer. Adrenocortical suppression may necessitate concomitant administration of replacement glucocorticoid