CD105 (Endoglin) exerts prognostic effects via its role in the microvascular niche of paediatric high grade glioma

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

From the President…

Now that the new year is here and the Society’s President’s Annual Dinner is over, there is perhaps a tendency to feel that the high point of the Society’s year is passed. I would urge you however to resist such self-indulgent fancies and see that as a Society we have a function throughout the academic year.From my own point of view, it must be said, the Society’s 254th session started quite memorably with the Freshers’ Address and Party, at which, as some of you may remember, I pulled off one of the greatest publicity stunts of recent years with a well-timed lateral dislocation of my right patella whilst dancing in the Meeting Hall. The immediate correction of this somewhat painful and rather inconvenient anatomical anomaly necessitated a little trip across to those nice people in the Accident and Emergency Department, at the time undergoing one of their typically pleasant late night Friday sessions. Seeing A&amp;E from under the blankets for a change was rather enlightening. On reflection however I would advise you to be very sceptical of those in the profession who proclaim that a visit to hospital on the receiving end teaches you what it’s like to be a patient

The Role of the Halides as Addition Agents During the Electrodeposition of Copper

The amount of chloride ion incorporated into a copper electrodeposit prepared from an aqueous copper sulphate solution has been determined at low chloride concentrations by the use of radiotracers. It has been found that the electrodeposits have a surface layer which is enriched in chloride ion. Evidence has been obtained that incorporation of chloride is preceded by the formation of cuprous chloride. The incorporation of chloride has been found to be increased by the presence of organic additives in the solution. The polarization during the first 30 seconds of electolysis has been interpreted using the knowledge obtained from the radiotracer work.ThesisDoctor of Philosophy (PhD

Evaluation of a Pilot of the Oregon Department of Transportation’s Ecodrive Program

Economical, ecological, and safe driving – eco-driving – is aimed at reducing fuel consumption and greenhouse gas emissions (Martin, Chan, & Shaheen, 2012). The adoption of energy-efficient driving styles and practices has been recognized as a means of reducing energy consumption, and estimates of energy savings attributed to eco-driving have been reported to range from 5% to as high as 20%, depending on the driving context (Barkenbus, 2010; Stillwater & Kurani, 2013; van der Voort, Dougherty & van Maareseveen, 2001). Eco-driving is being promoted in partnership among the Oregon Department of Transportation (ODOT) (Planning, Safety and Motor Carrier Division), the Department of Environmental Quality, the Oregon Department of Energy, and the Clean Cities Program (“EcoDriving Agency Partners”) to address fuel consumption in fleet drivers of light vehicles. The EcoDrive program was created to increase fuel efficiency in organizational fleets. The intent of the EcoDrive Program is to design and introduce eco-driving educational materials specifically targeted at drivers of light vehicles. The materials highlight the “Top EcoDrive Tips” and reinforce the relevant actions and benefits of eco-driving. The purpose of this report is to provide information about the implementation of the EcoDrive Program at three sites (publicsector organizations) within the state of Oregon and provide a preliminary evaluation of the program. In particular, this report will highlight how the EcoDrive Program impacted fleet drivers in terms of attitudes, knowledge, and behavior and how the drivers responded to the eco-driving materials. Further, we discuss recommendations for future implementations of the materials, highlighting possible organizational environments that are important for the success of the EcoDrive Program

Highlights of children with Cancer UK’s workshop on drug delivery in paediatric brain tumours

The first Workshop on Drug Delivery in Paediatric Brain Tumours was hosted in London by the charity Children with Cancer UK. The goals of the workshop were to break down the barriers to treating central nervous system (CNS) tumours in children, leading to new collaborations and further innovations in this under-represented and emotive field. These barriers include the physical delivery challenges presented by the blood–brain barrier, the underpinning reasons for the intractability of CNS cancers, and the practical difficulties of delivering cancer treatment to the brains of children. Novel techniques for overcoming these problems were discussed, new models brought forth, and experiences compared

Living on the edge: utilising lidar data to assess the importance of vegetation structure for avian diversity in fragmented woodlands and their edges

Context: In agricultural landscapes, small woodland patches can be important wildlife refuges. Their value in maintaining biodiversity may, however, be compromised by isolation, and so knowledge about the role of habitat structure is vital to understand the drivers of diversity. This study examined how avian diversity and abundance were related to habitat structure in four small woods in an agricultural landscape in eastern England. Objectives: The aims were to examine the edge effect on bird diversity and abundance, and the contributory role of vegetation structure. Specifically: what is the role of vegetation structure on edge effects, and which edge structures support the greatest bird diversity? Methods: Annual breeding bird census data for 28 species were combined with airborne lidar data in linear mixed models fitted separately at (i) the whole wood level, and (ii) for the woodland edges only. Results: Despite relatively small woodland areas (4.9–9.4 ha), bird diversity increased significantly towards the edges, being driven in part by vegetation structure. At the whole woods level, diversity was positively associated with increased vegetation above 0.5 m and especially with increasing vegetation density in the understorey layer, which was more abundant at the woodland edges. Diversity along the edges was largely driven by the density of vegetation below 4 m. Conclusions: The results demonstrate that bird diversity was maximised by a diverse vegetation structure across the wood and especially a dense understorey along the edge. These findings can assist bird conservation by guiding habitat management of remaining woodland patches

Recapitulation of tumor heterogeneity and molecular signatures in a 3D brain cancer model with decreased sensitivity to histone deacetylase inhibition

INTRODUCTION Physiologically relevant pre-clinical ex vivo models recapitulating CNS tumor micro-environmental complexity will aid development of biologically-targeted agents. We present comprehensive characterization of tumor aggregates generated using the 3D Rotary Cell Culture System (RCCS). METHODS CNS cancer cell lines were grown in conventional 2D cultures and the RCCS and comparison with a cohort of 53 pediatric high grade gliomas conducted by genome wide gene expression and microRNA arrays, coupled with immunohistochemistry, ex vivo magnetic resonance spectroscopy and drug sensitivity evaluation using the histone deacetylase inhibitor, Vorinostat. RESULTS Macroscopic RCCS aggregates recapitulated the heterogeneous morphology of brain tumors with a distinct proliferating rim, necrotic core and oxygen tension gradient. Gene expression and microRNA analyses revealed significant differences with 3D expression intermediate to 2D cultures and primary brain tumors. Metabolic profiling revealed differential profiles, with an increase in tumor specific metabolites in 3D. To evaluate the potential of the RCCS as a drug testing tool, we determined the efficacy of Vorinostat against aggregates of U87 and KNS42 glioblastoma cells. Both lines demonstrated markedly reduced sensitivity when assaying in 3D culture conditions compared to classical 2D drug screen approaches. CONCLUSIONS Our comprehensive characterization demonstrates that 3D RCCS culture of high grade brain tumor cells has profound effects on the genetic, epigenetic and metabolic profiles of cultured cells, with these cells residing as an intermediate phenotype between that of 2D cultures and primary tumors. There is a discrepancy between 2D culture and tumor molecular profiles, and RCCS partially re-capitulates tissue specific features, allowing drug testing in a more relevant ex vivo system

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.Postprint (published version

Impact of the COVID-19 pandemic on diagnosis and management of new brain tumours in children and young people (aged &lt; 16 years old) in the UK

Objective: This study aims to understand the impact of the COVID-19 pandemic on the diagnosis, management, and clinical outcomes of children and young people (CYP) with brain tumours in England.Design: UK-based retrospective observational study with two components. Nationwide brain tumour incidence data from the National Disease Registration Service was obtained (2015–2020) to study trends in newly diagnosed cases. Regional data from three paediatric neurosurgical centres was used to compare CYP newly diagnosed with a brain tumour before and those during the pandemic (March 2019–February 2021). Participants: No change in national incidence during the first year of the pandemic was seen. Regional data totalled 159 CYP, 88 diagnosed before the pandemic, 71 during (median age 7.0 years before, 7.8 years during the pandemic). Results: The commonest tumour types in both groups were low grade glioma (including pilocytic astrocytoma), medulloblastoma, and ependymoma. Symptoms at diagnosis were similar, the commonest overall being headache (52.3 vs 50.7%). Number of symptoms at diagnosis was comparable. Rates of complications (28.4 vs 40.8%, p = 0.129) and poor outcome (13.6 vs 22.5%; p = 0.143) were not significantly different. Time to diagnosis and treatment were similar between cohorts. Conclusion: This is the first UK study investigating the effects of the COVID-19 pandemic on CYP with a new brain tumour diagnosis. CYP diagnosed during the pandemic had comparable clinical presentations, times to diagnosis and treatment, and clinical outcomes. This suggests that acute paediatric neuro-oncology services were resilient in the face of pandemic-related restrictions and service adaptations