Paediatric high grade glioma (pHGG) (World Health Organisation astrocytoma grades III and IV) remains poor prognosis tumours, with a median survival of only 15 months following diagnosis. Current investigation of anti-angiogenic strategies has focused on adult glioblastoma multiforme (GBM) with phase III trials targeting vascular endothelial growth factor continuing. In this study we investigated whether the degree of vascularity correlated with prognosis in a large cohort of pHGG (n = 150) and whether different vessel markers carried different prognostic value. We found that CD105 (endoglin) had a strongly significant association with poor prognosis on multivariate analysis (p = <0.001). Supervised hierarchical clustering of genome wide gene expression data identified 13 genes associated with differential degrees of vascularity in the cohort. The novel angiogenesis-associated genes identified in this analysis (including MIPOL-1 and ENPP5) were validated by realtime polymerase chain reaction. We also demonstrate that CD105 positive blood vessels associate with CD133 positive tumour cells and that a proportion of CD105 positive vessel cells demonstrates co-positivity for CD133, suggesting that the recently described phenomenon of vasculogenic mimicry occurs in pHGG. Together, the data suggest that targeting angiogenesis, and in particular CD105, is a valid therapeutic strategy for pHGG.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-012-0952-1) contains supplementary material, which is available to authorized users.

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simulation is an emerging tool used to test systems, improve patient safety outcomes and prepare staff working in new clinical environments The aim of the study was to use simulated learning events (SLEs) to assess the effect of a new environment on performance, interpersonal skills and system-based practice. As part of the wider paediatric improvement plan, the simulation programme has been used to enhance teamwork and implement a change to maximize patient safety.Five multi-disciplinary SLEs based on paediatric and neonatal emergencies were held over a month following the opening of the new PAU. The simulations were low fidelity and Ten latent errors were identified pertaining to the availability of equipment and medications; all were rectified within 2 weeks. Operational errors were also identified, including unfamiliarity with the new PAU location within the wider emergency team, leading to delayed attendance to the simulation. The time taken to attend the PAU by the anaesthetic team decreased by 69% once the emergency bleep message was amended with location instructions. We observed that, with each SLE, there were successive improvements in teamwork and operational behaviours. The teams were able to familiarize themselves with each other and the new working environment, consequently leading to reduced times on acquiring equipment for the emergency. There were a total of 20 participants from paediatric, anaesthetic and nursing backgrounds. Feedback was received from 55% of participants, of which all agreed or strongly agreed that the SLEs and debriefs contributed to their learning and helped develop their team-working and leadership skills.SLE is an effective tool for systems testing in a new clinical environment and helps to identify potential critical and non-critical safety risks. We will continue to develop our simulation programme to assess a variety of clinical environments and share learning from the latent strengths and errors with the multi-disciplinary team, to improve clinical processes, team working and patient safety outcomes.