Evaluation of a candidate breast cancer associated SNP in ERCC4 as a risk modifier in BRCA1 and BRCA2 mutation carriers. Results from the Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA)

BACKGROUND: In this study we aimed to evaluate the role of a SNP in intron I of the ERCC4 gene (rs744154), previously reported to be associated with a reduced risk of breast cancer in the general population, as a breast cancer risk modifier in BRCA1 and BRCA2 mutation carriers.

Propensity to Apply for Judicial Office under the new Northern Ireland Judicial Appointments System::A qualitative study for the Northern Ireland Judicial Appointments Commission October

The study of representation and participation in the judiciary is hardly novel. There have been substantial studies in a number of countries – often these have preceded the setting up of judicial appointment commissions – which have looked at the continuing problem of female representation in judicial posts. Prior to the setting up of the Northern Ireland Judicial Appointments Commission a study carried out by Dermot Feenan for the Commissioner for Judicial Appointments for Northern Ireland also looked into this topic and produced a large number of recommendations. What differs from the Feenan project, in this project, has been the number of individuals consulted in interviews and focus groups. This has allowed us to provide a detailed qualitative attitudinal perspective to enhance the questionnaire study undertaken as Stage 1 in this research project. Further, we have carried out this study after many of the recommendations made in previous research have been implemented.
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Our interviews and focus groups covered a broad range of individuals – solicitors outwith and within Belfast (private and public service), barristers in private practice and public service and also barristers no longer in practice. We also sought responses from student lawyers. In total there were 71 respondents, with a typical interview/focus group length of 60 minutes. The group included candidates who had little interest in applying for judicial office, those who might consider this in future, and candidates who had applied for one or more judicial posts and who may or may not consider reapplication. We did not seek the views of successful candidates for judicial posts under the new NIJAC process.
The timing of this project, with interviews and focus groups held between December 2007 and March 2008, offers an early perspective on the whether the creation of a NI Judicial Appointments Commission has affected, and if so, in what way, the decision to apply for a judicial post. Generally, we found that there was a significant impact upon attitudes to judicial application which had arisen from the creation of NIJAC and that this was more positive than negative.

Does pre-operative estimation of oesophageal tumour metabolic length using F-18-fluorodeoxyglucose PET/CT images compare with surgical pathology length?

PURPOSE:
The aim of the study was to compare the pre-operative metabolic tumour length on FDG PET/CT with the resected pathological specimen in patients with oesophageal cancer.

METHODS:
All patients diagnosed with oesophageal carcinoma who had undergone staging PET/CT imaging between the period of June 2002 and May 2008 who were then suitable for curative surgery, either with or without neo-adjuvant chemotherapy, were included in this study. Metabolic tumour length was assessed using both visual analysis and a maximum standardised uptake value (SUV(max)) cutoff of 2.5.

RESULTS:
Thirty-nine patients proceeded directly to curative surgical resection, whereas 48 patients received neo-adjuvant chemotherapy, followed by curative surgery. The 95% limits of agreement in the surgical arm were more accurate when the metabolic tumour length was visually assessed with a mean difference of -0.05 cm (SD 2.16 cm) compared to a mean difference of +2.42 cm (SD 3.46 cm) when assessed with an SUV(max) cutoff of 2.5. In the neo-adjuvant group, the 95% limits of agreement were once again more accurate when assessed visually with a mean difference of -0.6 cm (SD 1.84 cm) compared to a mean difference of +1.58 cm (SD 3.1 cm) when assessed with an SUV(max) cutoff of 2.5.

CONCLUSION:
This study confirms the high accuracy of PET/CT in measuring gross target volume (GTV) length. A visual method for GTV length measurement was demonstrated to be superior and more accurate than when using an SUV(max) cutoff of 2.5. This has the potential of reducing the planning target volume with dose escalation to the tumour with a corresponding reduction in normal tissue complication probability.

18F-fluorodeoxyglucose positron emission tomography/computed tomography-based radiotherapy target volume definition in non-small-cell lung cancer: delineation by radiation oncologists vs. joint outlining with a PET radiologist?

Purpose: F-18-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) has benefits in target volume (TV) definition in radiotherapy treatment planning (RTP) for non small-cell lung cancer (NSCLC); however, an optimal protocol for TV delineation has not been determined. We investigate volumetric and positional variation in gross tumor volume (GTV) delineation using a planning PET/CT among three radiation oncologists and a PET radiologist.

Denaturing high performance liquid chromatography for the detection of microsatellite instability using Bethesda and pentaplex marker panels

Microsatellite instability (MSI) is a characteristic molecular phenotype of tumors from the hereditary nonpolyposis colorectal cancer (Lynch) syndrome. Routine MSI screening of tumors in patients is an efficient prescreening tool for the population-based detection of Lynch syndrome in the absence of family cancer history. We describe here the optimization of a denaturing high performance liquid chromatography (DHPLC) assay for MSI analysis with the

Detection of BRAF V600E mutation by pyrosequencing

Introduction: Detection of the V600E hotspot mutation in BRAF oncogene is extremely useful for the screening of hereditary non-polyposis colorectal cancer (Lynch's syndrome) and for the prediction of sensitivity to MEK inhibitors. Here we describe a method for detecting this mutation based upon pyrosequencing technology.

Mitochondrial translation initiation factor 3 polymorphism and Parkinson's disease

Mitochondrial dysfunction has been proposed to play a role in the pathogenesis of Parkinson s disease (PD) Supportive of this hypothesis several genetic variants that regulate mitochondrial function and homeostasis have been described to alter PD susceptibility A recent report demonstrated association of a single nucleotide polymorphism in the mitochondrial translation initiation factor 3 (MTIF3) gene with PD risk The protein encoded by this nuclear gene is essential for initiation complex formation on the mitochondrial 55S ribosome and regulates translation of proteins within the mitochondria Changes in the function or expression of the MTIF3 protein may result in altered mitochondrial function ATP production or formation of reactive oxygen species thereby affecting susceptibility to PD We examined the association of rs7669 with sporadic PD in three Caucasian case control series (n = 2434) A significant association was observed in the largest series (Norwegian n = 1650) when comparing CC vs CT/TT genotypes with the Irish and US series having a similar but non-significant trend The combined series also revealed an association with risk of PD (P = 0 01) supporting the possible involvement of this gene in PD etiology Published by Elsevier Ireland Ltd

Genetic Evidence Implicates the Immune System and Cholesterol Metabolism in the Aetiology of Alzheimer's Disease

Background: Late Onset Alzheimer's disease (LOAD) is the leading cause of dementia. Recent large genome-wide association studies (GWAS) identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes. Methodology: We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset.

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P = 1 × 10(-5). We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10(-17); including ADGC data, meta P = 5.0 × 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10(-14); including ADGC data, meta P = 1.2 × 10(-16)) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10(-4); including ADGC data, meta P = 8.6 × 10(-9)), CD33 (GERAD+, P = 2.2 × 10(-4); including ADGC data, meta P = 1.6 × 10(-9)) and EPHA1 (GERAD+, P = 3.4 × 10(-4); including ADGC data, meta P = 6.0 × 10(-10)).

Form Follows Media::What is The Matrix as Film, Animation, Game and Comics?

In the digital age, the hyperspace of virtual reality systems stands out as a new spatial notion creating a parallel world to the space we live in. In this alternative realm, the body transforms into a hyperbody, and begins to follow the white rabbit. Not only in real world but also in the Matrix world. The Matrix project of Andy and Larry Wachowski started with a feature film released in 1999. However, The Matrix is not only a film (trilogy). It is a concept, a universe that brings real space and hyperspace together. It is a world represented not only in science fiction films but also in The Animatrix that includes nine animated Matrix films directed by Peter Chung, Andy Jones, Yoshiaki Kawajiri and others, four of which are written by the Wachowskis. The same universe is used in Enter the Matrix, a digital game whose script was written and directed by the brothers and a comic book, The Matrix Comics, which includes twelve different stories by artists like Neil Gaiman and Goef Darrow. The Wachowskis played an active role in the creation and realization of all these “products” of different media. The comic book came last (November 2003), however it is possible to argue that everything came out of comics – the storyboards of the original film. After all the Wachowskis have a background in comics.

In this study, I will focus on the formal analysis of the science fiction world of The Matrix - as a representation of hyperspace - in different media, feature film, animated film, digital game and comic book, focusing on diverse forms of space that come into being as a result of medium differences. To unfold the different formal characters of film, animation, game and comics, concepts and features including framing, flattening, continuity, movement, montage, sound/text, light and color will be discussed. An analysis of these products will help to open up a discussion on the relation of form, media and representation.

No Evidence that Extended Tracts of Homozygosity are Associated with Alzheimer’s Disease.

We sought to investigate the contribution of extended runs of homozygosity in a genome-wide association dataset of 1,955 Alzheimer's disease cases and 955 elderly screened controls genotyped for 529,205 autosomal single nucleotide polymorphisms. Tracts of homozygosity may mark regions inherited from a common ancestor and could reflect disease loci if observed more frequently in cases than controls. We found no excess of homozygous tracts in Alzheimer's disease cases compared to controls and no individual run of homozygosity showed association to Alzheimer's disease.