This paper makes an outline case for the need for a low-cost, easy to administer method for detecting dementia within the growing at risk population. It proposes two methods for electroencephalogram (EEG) analysis for detecting dementia that could fulfil such a need. The paper describes a fractal dimension-based method for analyzing the EEG waveforms of subjects with dementia and reports on an assessment which demonstrates that an appropriate fractal dimension measure could achieve 67% sensitivity to probable Alzheimer's disease (as suggested by clinical psychometric testing and EEG findings) with a specificity of 99.9%. An alternative method based on the probability density function of the zero-crossing intervals is shown to achieve 78% sensitivity to probable Alzheimer's disease and an estimated sensitivity to probable Vascular (or mixed) dementia of 35% (as suggested by clinical psychometric testing and EEG findings) with a specificity of 99.9%. This compares well with other studies, reported by the American Academy of Neurology, which typically provide a sensitivity of 81% and specificity of 70%. The EEG recordings used to assess these methods included artefacts and had no a priori selection of elements "suitable for analysis." This approach gives a good prediction of the usefulness of the methods, as they would be used in practice. A total of 39 patients (30 probable Alzheimer's Disease, six Vascular Dementia and three mixed dementia) and 42 healthy volunteers were involved in the study. However, although results from the preliminary evaluation of the methods are promising, there is a need for a more extensive study to validate the methods using EEGs from a larger and more varied patient cohorts with neuroimaging results, to exclude other causes and cognitive scores to correlate results with severity of cognitive status.

The number of people that now go on to develop Alzheimer's disease (AD) and other types of dementia is rapidly rising. For maximum benefits from new treatments, the disease should be diagnosed as early as possible, but this is difficult with current clinical criteria. Potentially, the EEG can serve as an objective, first line of decision support tool to improve diagnosis. It is non-invasive, widely available, low-cost and could be carried out rapidly in the high-risk age group that will develop AD. Changes in the EEG due to the dementing process could be quantified as an index or marker. In this paper, we investigate two information theoretic methods (Tsallis entropy and universal compression algorithm) as a way to generate potentially robust markers from the EEG. The hypothesis is that the information theoretic makers for AD are significantly different to those of normal subjects. An attraction of the information theoretic approach is that, unlike most existing methods, there may be a natural link between the underlying ideas of information theoretic methods, the physiology of AD and its impact on brain functions. Data compression has not been investigated as a means of generating EEG markers before and is attractive because it does not require a priori knowledge of the source model. In this paper, we focus on the LZW algorithm because of its sound theoretical foundation. We used the LZW algorithm and Tsallis model to compute the markers (compression ratios and normalized entropies, respectively) from two EEG datasets.

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Worldwide, the number of people that develop Alzheimer's disease and other types of dementia is rapidly rising and will create a considerable financial burden on the health and social services. The availability of new drugs that may slow or even halt the disease progression makes accurate early detection crucial. Objective methods are needed to support clinical diagnosis and care for patients; to quantify severity, monitor progression and response to new treatments. Electrophysiological markers have an important role to play in the objective assessment and care for dementia. The EEG provides a measure of brain dysfunction and EEG changes could be detected fairly early in the dementing process. Subject-specific EEG analysis offers the possibility of using objective methods to assess and care for dementia on an individual basis. The main objectives of this paper are: (i) to introduce the concepts of subject-specific EEG analysis as a basis for improving diagnosis and care for dementia; and (ii) present two novel methods for deriving suitable subject-specific electrophysiological markers analysis of fractal dimension and zero crossing interval density of the EEG. We present findings that indicate that the methods are potentially good candidates for the development of individualized, low-cost, easy to administer and reasonably accurate methods for detecting dementia within the growing at risk population.

Approximately 10 percent of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2. However, the impact of these mutations on ovarian cancer prognosis remains unclear.

Rare germline mutations in the breast and ovarian cancer predisposition genes BRCA1 and BRCA2 are present in roughly 5 percent of ovarian cancer patients. Both genes play key roles in DNA damage repair but appear to have distinct, although often complementary, functions. The risks of breast and ovarian cancer have been shown to differ between BRCA1 and BRCA2 carriers, and mutation-specific effects have also been suggested for both groups. Published reports comparing the survival of ovarian cancer patients with and without BRCA1/2 mutations generally show a survival advantage among mutation carriers. This is thought to be related to an improved response of carriers to platinum-based therapies. Since it is not known whether BRCA1 and BRCA2 carriers show similar survival patterns, we have performed a large, multicenter study to investigate the impact of germline BRCA1 and BRCA2 mutations on ovarian cancer survival. 3,531 invasive epithelial ovarian cancer cases (1,178 BRCA1, 367 BRCA2 and 1,986 BRCA-negative) with survival time data from twenty-four studies in the U.S.A, Europe, Israel and Asia were included. In our main analysis, we excluded patients who were known or who were likely to have not received platinum-based therapy. Compared to non-carriers, BRCA1 and BRCA2 carriers were more likely to present with advanced stage (BRCA1; p=2×10−4, BRCA2; p=4×10−6), high grade (BRCA1; p=4×10−9, BRCA2; p=1×10−4), serous disease (BRCA1; p=3×10−6, BRCA2; p=0.003). BRCA1 carriers were younger at diagnosis (p=2×10−9) and BRCA2 slightly older at diagnosis (p=0.002) than non-carriers. BRCA1 and BRCA2 carriers did not differ in terms of tumor stage, grade or histology but did show differences in the age at diagnosis (p=2×10−14). In an unadjusted analysis, neither BRCA1 nor BRCA2 carriers differed from non-carriers in overall survival (BRCA1: HR=1.02, p=0.77, BRCA2: HR=0.89, p=0.36). After adjusting for stage, grade, histology and age at diagnosis, BRCA1 carriers showed a modest, non-significant, survival advantage (HR=0.84, p=0.12) while BRCA2 carriers showed a marked improvement (HR=0.57, p=6×10−4) compared to non-carriers. This survival advantage was also seen when comparing BRCA2 carriers to BRCA1 carriers after adjustment for age at diagnosis (HR=0.69, p=5×10−4). Similar results were obtained when we restricted the analysis to high grade, advanced stage, serous cases. The survival differences we observed between BRCA1 and BRCA2 carriers could be related to differences in tumor biology or chemo-sensitivity. Additional analyses investigating the later will be presented in addition to mutation-specific effects within BRCA1 and BRCA2. In this study, we provide strong evidence for genetic heterogeneity of survival effects in ovarian cancer patients with BRCA mutations. This could be applied to both clinical prediction and to aid our understanding of the complex biology of BRCA mutations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2752. doi:10.1158/1538-7445.AM2011-2752

The primary aim of this paper is to present a new concept, bioprofiling over Grid, and to illustrate how Grid computing may be used to support individualisation of healthcare in future, with the aid of a new test bed, the BIOPATTERN Grid. The BIOPATTERN Grid is designed to facilitate seamless sharing of geographically distributed bioprofile databases and to support the analysis of bioprofiles to combat major diseases such as brain diseases and cancer within a major EU project, BIOPATTERN (www.biopattern.org). The main objectives in this paper are 1) to report the development of the BIOPATTERN Grid for biopattern analysis and bioprofiling in support of individualisation of healthcare; 2) to illustrate how the BIOPAT-TERN Grid could be used for biopattern analysis and bioprofiling for early detection of dementia. We present the architecture and general functionalities of BIOPATTERN Grid, and the development of a prototype test bed (including a Grid Portal and Grid services for early detection of dementia). We illustrate the concept of bioprofiling over Grid and discuss issues such as scalability in high throughput computing for biodata analysis associated with bioprofiling for dementia. Results show benefits in both high throughput computing in biodata analysis and for individualisation of healthcare using Grid computing which makes it possible to access geographically distributed patient's information for subject-specific data analysis for early detection of dementia.