Base resolution maps reveal the importance of 5-hydroxymethylcytosine in a human glioblastoma

Aberrant genetic and epigenetic variations drive malignant transformation and are hallmarks of cancer. Using PCR-free sample preparation we achieved the first in-depth whole genome (hydroxyl)-methylcytosine, single-base-resolution maps from a glioblastoma tumour/margin sample of a patient. Our data provide new insights into how genetic and epigenetic variations are interrelated. In the tumour, global hypermethylation with a depletion of 5-hydroxymethylcytosine was observed. The majority of single nucleotide variations were identified as cytosine-to-thymine deamination products within CpG context, where cytosine was preferentially methylated in the margin. Notably, we observe that cells neighbouring tumour cells display epigenetic alterations characteristic of the tumour itself although genetically they appear “normal”. This shows the potential transfer of epigenetic information between cells that contributes to the intratumour heterogeneity of glioblastoma. Together, our reference (epi)-genome provides a human model system for future studies that aim to explore the link between genetic and epigenetic variations in cancer progression.Cancer Research UK 236 (Grant ID: C14303/A17197), Wellcome Trust (Grant ID: 099232/z/12/z

The Glasgow Benefit Inventory: a systematic review of the use and value of an otorhinolaryngological generic patient-recorded outcome measure

The Glasgow Benefit Inventory (GBI) is a validated, generic patient-recorded outcome measure widely used in otolaryngology to report change in quality of life post-intervention.To date, no systematic review has made (i) a quality assessment of reporting of Glasgow Benefit Inventory outcomes; (ii) a comparison between Glasgow Benefit Inventory outcomes for different interventions and objectives; (iii) an evaluation of subscales in describing the area of benefit; (iv) commented on its value in clinical practice and research.Systematic review.'Glasgow Benefit Inventory' and 'GBI' were used as keywords to search for published, unpublished and ongoing trials in PubMed, EMBASE, CINAHL and Google in addition to an ISI citation search for the original validating Glasgow Benefit Inventory paper between 1996 and January 2015.Papers were assessed for study type and quality graded by a predesigned scale, by two authors independently. Papers with sufficient quality Glasgow Benefit Inventory data were identified for statistical comparisons. Papers with 50% and gave sufficient Glasgow Benefit Inventory total and subscales for meta-analysis. For five of the 11 operation categories (vestibular schwannoma, tonsillectomy, cochlear implant, middle ear implant and stapes surgery) that were most likely to have a single clear clinical objective, score data had low-to-moderate heterogeneity. The value in the Glasgow Benefit Inventory having both positive and negative scores was shown by an overall negative score for the management of vestibular schwannoma. The other six operations gave considerable heterogeneity with rhinoplasty and septoplasty giving the greatest percentages (98% and 99%) most likely because of the considerable variations in patient selection. The data from these operations should not be used for comparative purposes. Five papers also reported the number of patients that had no or negative benefit, a potentially a more clinically useful outcome to report. Glasgow Benefit Inventory subscores for tonsillectomy were significantly different from ear surgery suggesting different areas of benefitThe Glasgow Benefit Inventory has been shown to differentiate the benefit between surgical and medical otolaryngology interventions as well as 'reassurance'. Reporting benefit as percentages with negative, no and positive benefit would enable better comparisons between different interventions with varying objectives and pathology. This could also allow easier evaluation of factors that predict benefit. Meta-analysis data are now available for comparison purposes for vestibular schwannoma, tonsillectomy, cochlear implant, middle ear implant and stapes surgery. Fuller report of the Glasgow Benefit Inventory outcomes for non-surgical otolaryngology interventions is encouraged

Chronic subdural haematoma: disseminating and implementing best practice

Peter Hutchinson is supported by a Research Professorship from the National Institute for Health Research (NIHR), the NIHR Cambridge Biomedical Research Centre, a European Union Seventh Framework Program grant (CENTER-TBI; grant no. 602150), and the Royal College of Surgeons of England

Improved long-term survival with subdural drains following evacuation of chronic subdural haematoma

Background Chronic subdural haematoma (CSDH) is a common condition that is effectively managed by burrhole drainage but requires repeat surgery in a significant minority of patients. The Cambridge Chronic Subdural Haematoma Trial (CCSHT) was a randomised controlled study that showed placement of subdural drains for 48 h following burrhole evacuation significantly reduces the incidence of reoperation and improves survival at 6 months. The present study examined the long-term survival of the patients in the trial. Methods In the original trial patients at a single neurosurgical centre from 2004–2007 were randomly assigned to receive a drain (n = 108) or no drain (n = 107) following burrhole drainage of CSDH. We ascertained whether the trial patients were alive in February 2016—a minimum of 8 years following enrollment—via the UK NHS tracing service. Survival was compared between the trial groups and against expected survival for the UK general population matched for age and sex. Results At 5 years following surgery the drain group continued to have significantly better survival than the no drain patients (p = 0.027), but this was no longer apparent at 10 years. Survival of patients in the drain group did not differ significantly from that of the general population whereas patients who did not receive a drain had significantly lower survival than expected (p = 0.0006). Conclusion Subdural drains following CSDH evacuation are associated with improved long-term survival, which appears similar to that expected for the general population of the same age and sex. All patients having burrhole CSDH evacuation should receive a drain as standard practice unless specifically contraindicated

GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers

We describe methods with enhanced power and specificity to identify genes targeted by somatic copy-number alterations (SCNAs) that drive cancer growth. By separating SCNA profiles into underlying arm-level and focal alterations, we improve the estimation of background rates for each category. We additionally describe a probabilistic method for defining the boundaries of selected-for SCNA regions with user-defined confidence. Here we detail this revised computational approach, GISTIC2.0, and validate its performance in real and simulated datasets

Gasdynamic fusion propulsion system for space exploration

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76953/1/AIAA-23876-408.pd

Suboccipital craniotomy in the surgical treatment of Chiari I malformation

The object of this study was to present craniotomy for Chiari type I patients. Six patients with Chiari type I underwent suboccipital craniotomy. All patients showed clinical improvement, and none had any complications. Two patients had syringomyelia; it disappeared in entirety. We describe the procedure for posterior fossa decompression. Three-dimensional volumetric analysis using Vitrea workstation for postoperative posterior fossa volumes was calculated and was seen to have been increased on an average, from pre-operative (168 cc) to postoperative volume (192 cc). We thus conclude that suboccipital craniotomy results in resolution of the Chiari symptoms yet achieves effective expansion of posterior fossa

Digitalization and sustainability: a call for a digital green deal

The relation between digitalization and environmental sustainability is ambiguous. There is potential of various digital technologies to slow down the transgression of planetary boundaries. Yet resource and energy demand for digital hardware production and use of data-intensive applications is of substantial size. The world over, there is no comprehensive regulation that addresses opportunities and risks of digital technology for sustainability. In this perspective article, we call for a Digital Green Deal that includes strong, cross-sectoral green digitalization policies on all levels of governance. We argue that a Digital Green Deal should first and foremost aim at greater policy coherence: Current digital policy initiatives should include measures that service environmental goals, and environmental policies must address risks and advance opportunities of digital technologies to spur sustainability transformations