Three Dimensional Electrical Impedance Tomography

The electrical resistivity of mammalian tissues varies widely and is correlated with physiological function. Electrical impedance tomography (EIT) can be used to probe such variations in vivo, and offers a non-invasive means of imaging the internal conductivity distribution of the human body. But the computational complexity of EIT has severe practical limitations, and previous work has been restricted to considering image reconstruction as an essentially two-dimensional problem. This simplification can limit significantly the imaging capabilities of EIT, as the electric currents used to determine the conductivity variations will not in general be confined to a two-dimensional plane. A few studies have attempted three-dimensional EIT image reconstruction, but have not yet succeeded in generating images of a quality suitable for clinical applications. Here we report the development of a three-dimensional EIT system with greatly improved imaging capabilities, which combines our 64-electrode data-collection apparatus with customized matrix inversion techniques. Our results demonstrate the practical potential of EIT for clinical applications, such as lung or brain imaging and diagnostic screening

How acceptable are antiretrovirals for the prevention of sexually transmitted HIV? A review of research on the acceptability of oral pre-exposure prophylaxis and treatment as prevention

Recent research has demonstrated how antiretrovirals (ARVs) could be effective in the prevention of sexually transmitted HIV. We review research on the acceptability of oral pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) for HIV prevention amongst potential users. We consider with whom, where and in what context this research has been conducted, how acceptability has been approached, and what research gaps remain. Findings from 33 studies show a lack of TasP research, PrEP studies which have focused largely on men who have sex with men (MSM) in a US context, and varied measures of acceptability. In order to identify when, where and for whom PrEP and TasP would be most appropriate and effective, research is needed in five areas: acceptability of TasP to people living with HIV; motivation for PrEP use and adherence; current perceptions and management of risk; the impact of broader social and structural factors; and consistent definition and operationalisation of acceptability which moves beyond adherence

Multiple structure alignment and consensus identification for proteins

<p>Abstract</p> <p>Background</p> <p>An algorithm is presented to compute a multiple structure alignment for a set of proteins and to generate a consensus (pseudo) protein which captures common substructures present in the given proteins. The algorithm represents each protein as a sequence of triples of coordinates of the alpha-carbon atoms along the backbone. It then computes iteratively a sequence of transformation matrices (i.e., translations and rotations) to align the proteins in space and generate the consensus. The algorithm is a heuristic in that it computes an approximation to the optimal alignment that minimizes the sum of the pairwise distances between the consensus and the transformed proteins.</p> <p>Results</p> <p>Experimental results show that the algorithm converges quite rapidly and generates consensus structures that are visually similar to the input proteins. A comparison with other coordinate-based alignment algorithms (MAMMOTH and MATT) shows that the proposed algorithm is competitive in terms of speed and the sizes of the conserved regions discovered in an extensive benchmark dataset derived from the HOMSTRAD and SABmark databases.</p> <p>The algorithm has been implemented in C++ and can be downloaded from the project's web page. Alternatively, the algorithm can be used via a web server which makes it possible to align protein structures by uploading files from local disk or by downloading protein data from the RCSB Protein Data Bank.</p> <p>Conclusions</p> <p>An algorithm is presented to compute a multiple structure alignment for a set of proteins, together with their consensus structure. Experimental results show its effectiveness in terms of the quality of the alignment and computational cost.</p

AIDS-Related Tuberculosis in Rio de Janeiro, Brazil

BACKGROUND: We studied the incidence of tuberculosis, AIDS, AIDS deaths and AIDS-TB co-infection at the population level in Rio de Janeiro, Brazil where universal and free access to combination antiretroviral therapy has been available since 1997. METHODOLOGY/PRINCIPAL FINDINGS: This was a retrospective surveillance database match of Rio de Janeiro databases from 1995-2004. Proportions of tuberculosis occurring within 30 days and between 30 days and 1 year after AIDS diagnosis were determined. Generalized additive models fitted with cubic splines with appropriate estimating methods were used to describe rates and proportions over time. Overall, 90,806 tuberculosis cases and 16,891 AIDS cases were reported; 3,125 tuberculosis cases within 1 year of AIDS diagnosis were detected. Tuberculosis notification rates decreased after 1997 from a fitted rate (fR per 100,000) of 166.5 to 138.8 in 2004. AIDS incidence rates increased 26% between 1995 and 1998 (30.7 to 38.7) followed by a 33.3% decrease to 25.8 in 2004. AIDS mortality rates decreased dramatically after antiretroviral therapy was introduced between 1995 (27.5) and 1999 (13.4). The fitted proportion (fP) of patients with tuberculosis diagnosed within one year of AIDS decreased from 1995 (24.4%) to 1998 (15.2%), remaining stable since. Seventy-five percent of tuberculosis diagnoses after an AIDS diagnosis occurred within 30 days of AIDS diagnosis. CONCLUSIONS/SIGNIFICANCE: Our results suggest that while combination ART should be considered an essential component of the response to the HIV and HIV/tuberculosis epidemics, it may not be sufficient alone to prevent progression from latent TB to active disease among HIV-infected populations. When tuberculosis is diagnosed prior to or at the same time as AIDS and ART has not yet been initiated, then ART is ineffective as a tuberculosis prevention strategy for these patients. Earlier HIV/AIDS diagnosis and ART initiation may reduce TB incidence in HIV/AIDS patients. More specific interventions will be required if HIV-related tuberculosis incidence is to continue to decline

Optimally splitting cases for training and testing high dimensional classifiers

<p>Abstract</p> <p>Background</p> <p>We consider the problem of designing a study to develop a predictive classifier from high dimensional data. A common study design is to split the sample into a training set and an independent test set, where the former is used to develop the classifier and the latter to evaluate its performance. In this paper we address the question of what proportion of the samples should be devoted to the training set. How does this proportion impact the mean squared error (MSE) of the prediction accuracy estimate?</p> <p>Results</p> <p>We develop a non-parametric algorithm for determining an optimal splitting proportion that can be applied with a specific dataset and classifier algorithm. We also perform a broad simulation study for the purpose of better understanding the factors that determine the best split proportions and to evaluate commonly used splitting strategies (1/2 training or 2/3 training) under a wide variety of conditions. These methods are based on a decomposition of the MSE into three intuitive component parts.</p> <p>Conclusions</p> <p>By applying these approaches to a number of synthetic and real microarray datasets we show that for linear classifiers the optimal proportion depends on the overall number of samples available and the degree of differential expression between the classes. The optimal proportion was found to depend on the full dataset size (n) and classification accuracy - with higher accuracy and smaller <it>n </it>resulting in more assigned to the training set. The commonly used strategy of allocating 2/3rd of cases for training was close to optimal for reasonable sized datasets (<it>n </it>≥ 100) with strong signals (i.e. 85% or greater full dataset accuracy). In general, we recommend use of our nonparametric resampling approach for determing the optimal split. This approach can be applied to any dataset, using any predictor development method, to determine the best split.</p

Gene expression profiling identifies distinct molecular subgroups of leiomyosarcoma with clinical relevance

YesBackground: Soft tissue sarcomas are heterogeneous and a major complication in their management is that the existing classification scheme is not definitive and is still evolving. Leiomyosarcomas, a major histologic category of soft tissue sarcomas, are malignant tumours displaying smooth muscle differentiation. Although defined as a single group, they exhibit a wide range of clinical behaviour. We aimed to carry out molecular classification to identify new molecular subgroups with clinical relevance. Methods: We used gene expression profiling on 20 extra-uterine leiomyosarcomas and cross-study analyses for molecular classification of leiomyosarcomas. Clinical significance of the subgroupings was investigated. Results: We have identified two distinct molecular subgroups of leiomyosarcomas. One group was characterised by high expression of 26 genes that included many genes from the sub-classification gene cluster proposed by Nielsen et al. These sub-classification genes include genes that have importance structurally, as well as in cell signalling. Notably, we found a statistically significant association of the subgroupings with tumour grade. Further refinement led to a group of 15 genes that could recapitulate the tumour subgroupings in our data set and in a second independent sarcoma set. Remarkably, cross-study analyses suggested that these molecular subgroups could be found in four independent data sets, providing strong support for their existence. Conclusions: Our study strongly supported the existence of distinct leiomyosarcoma molecular subgroups, which have clinical association with tumour grade. Our findings will aid in advancing the classification of leiomyosarcomas and lead to more individualised and better management of the disease.Alexander Boag Sarcoma Fund

Gingival crevicular fluid MMP-8-concentrations in patients after acute myocardial infarction

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to determine the presence of matrix metalloproteinase-8 in the gingival crevicular fluid (GCF) of patients after acute myocardial infarction (AMI).</p> <p>Methods</p> <p>A total of 48 GCF samples from 20 AMI patients, hospitalized at the Department of Cardiology and Angiology of the Johannes Gutenberg University Mainz, were investigated. Besides the myocardial infarction all patients suffered from chronic periodontal disease. Fifty-one GCF samples from 20 healthy age matched individuals with similar periodontal conditions served as controls. The dental examination included the assessment of oral hygiene, gingival inflammation, probing pocket depth, clinical attachment level and X-ray examination. The study was only carried out after the positive consent of the regional ethic commission. A quantitative assessment of aMMP-8 levels in the gingival crevicular fluid was performed with the help of the DentoAnalyzer (Dentognostics GmbH, Jena, Germany), utilising an immunological procedure.</p> <p>Results</p> <p>The aMMP-8 concentrations found in the gingival crevicular fluid of the AMI patients significantly differed (p = 0.001; mean value 30.33 ± 41.99 ng/ml aMMP-8) from the control group (mean value 10.0 ± 10.7 ng/ml aMMP-8). These findings suggest that periodontal inflammation in AMI patients might be associated with higher MMP-8-values compared to the healthy controls.</p> <p>Conclusions</p> <p>The acute myocardial infarction seems to influence the degree of periodontal inflammation, thus the measurement of the gingival crevicular fluid MMP8 levels seems to be a helpful biochemical test to obtain information about the severity of the periodontal disease.</p

Level spacings for weakly asymmetric real random matrices and application to two-color QCD with chemical potential

We consider antisymmetric perturbations of real symmetric matrices in the context of random matrix theory and two-color quantum chromodynamics. We investigate the level spacing distributions of eigenvalues that remain real or become complex conjugate pairs under the perturbation. We work out analytical surmises from small matrices and show that they describe the level spacings of large random matrices. As expected from symmetry arguments, these level spacings also apply to the overlap Dirac operator for two-color QCD with chemical potential.Comment: 23 pages, 6 figures, 1 animation; minor corrections, references added, as published in JHE

Significance testing in ridge regression for genetic data.

Published versio