Radiation-associated sarcoma of the skull base after irradiation for pituitary adenoma

Secondary, radiation-induced neoplasms represent a significant long-term risk after radiation treatment, and radiation-induced sarcomas (RAS) have an especially poor prognosis. These have rarely been reported after irradiation for pituitary adenomas

Comparison study of microarray meta-analysis methods

<p>Abstract</p> <p>Background</p> <p>Meta-analysis methods exist for combining multiple microarray datasets. However, there are a wide range of issues associated with microarray meta-analysis and a limited ability to compare the performance of different meta-analysis methods.</p> <p>Results</p> <p>We compare eight meta-analysis methods, five existing methods, two naive methods and a novel approach (mDEDS). Comparisons are performed using simulated data and two biological case studies with varying degrees of meta-analysis complexity. The performance of meta-analysis methods is assessed via ROC curves and prediction accuracy where applicable.</p> <p>Conclusions</p> <p>Existing meta-analysis methods vary in their ability to perform successful meta-analysis. This success is very dependent on the complexity of the data and type of analysis. Our proposed method, mDEDS, performs competitively as a meta-analysis tool even as complexity increases. Because of the varying abilities of compared meta-analysis methods, care should be taken when considering the meta-analysis method used for particular research.</p

A statistical framework for integrating two microarray data sets in differential expression analysis

<p>Abstract</p> <p>Background</p> <p>Different microarray data sets can be collected for studying the same or similar diseases. We expect to achieve a more efficient analysis of differential expression if an efficient statistical method can be developed for integrating different microarray data sets. Although many statistical methods have been proposed for data integration, the genome-wide concordance of different data sets has not been well considered in the analysis.</p> <p>Results</p> <p>Before considering data integration, it is necessary to evaluate the genome-wide concordance so that misleading results can be avoided. Based on the test results, different subsequent actions are suggested. The evaluation of genome-wide concordance and the data integration can be achieved based on the normal distribution based mixture models.</p> <p>Conclusion</p> <p>The results from our simulation study suggest that misleading results can be generated if the genome-wide concordance issue is not appropriately considered. Our method provides a rigorous parametric solution. The results also show that our method is robust to certain model misspecification and is practically useful for the integrative analysis of differential expression.</p

Integrated Genomic Analysis Implicates Haploinsufficiency of Multiple Chromosome 5q31.2 Genes in De Novo Myelodysplastic Syndromes Pathogenesis

Deletions spanning chromosome 5q31.2 are among the most common recurring cytogenetic abnormalities detectable in myelodysplastic syndromes (MDS). Prior genomic studies have suggested that haploinsufficiency of multiple 5q31.2 genes may contribute to MDS pathogenesis. However, this hypothesis has never been formally tested. Therefore, we designed this study to systematically and comprehensively evaluate all 28 chromosome 5q31.2 genes and directly test whether haploinsufficiency of a single 5q31.2 gene may result from a heterozygous nucleotide mutation or microdeletion. We selected paired tumor (bone marrow) and germline (skin) DNA samples from 46 de novo MDS patients (37 without a cytogenetic 5q31.2 deletion) and performed total exonic gene resequencing (479 amplicons) and array comparative genomic hybridization (CGH). We found no somatic nucleotide changes in the 46 MDS samples, and no cytogenetically silent 5q31.2 deletions in 20/20 samples analyzed by array CGH. Twelve novel single nucleotide polymorphisms were discovered. The mRNA levels of 7 genes in the commonly deleted interval were reduced by 50% in CD34+ cells from del(5q) MDS samples, and no gene showed complete loss of expression. Taken together, these data show that small deletions and/or point mutations in individual 5q31.2 genes are not common events in MDS, and implicate haploinsufficiency of multiple genes as the relevant genetic consequence of this common deletion

International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible

A mitochondrial mutator plasmid that causes senescence under dietary restricted conditions

BACKGROUND: Calorie or dietary restriction extends life span in a wide range of organisms including the filamentous fungus Podospora anserina. Under dietary restricted conditions, P. anserina isolates are several-fold longer lived. This is however not the case in isolates that carry one of the pAL2-1 homologous mitochondrial plasmids. RESULTS: We show that the pAL2-1 homologues act as 'insertional mutators' of the mitochondrial genome, which may explain their negative effect on life span extension. Sequencing revealed at least fourteen unique plasmid integration sites, of which twelve were located within the mitochondrial genome and two within copies of the plasmid itself. The plasmids were able to integrate in their entirety, via a non-homologous mode of recombination. Some of the integrated plasmid copies were truncated, which probably resulted from secondary, post-integrative, recombination processes. Integration sites were predominantly located within and surrounding the region containing the mitochondrial rDNA loci. CONCLUSION: We propose a model for the mechanism of integration, based on innate modes of mtDNA recombination, and discuss its possible link with the plasmid's negative effect on dietary restriction mediated life span extension

Detection of copy number variation from array intensity and sequencing read depth using a stepwise Bayesian model

Abstract Background Copy number variants (CNVs) have been demonstrated to occur at a high frequency and are now widely believed to make a significant contribution to the phenotypic variation in human populations. Array-based comparative genomic hybridization (array-CGH) and newly developed read-depth approach through ultrahigh throughput genomic sequencing both provide rapid, robust, and comprehensive methods to identify CNVs on a whole-genome scale. Results We developed a Bayesian statistical analysis algorithm for the detection of CNVs from both types of genomic data. The algorithm can analyze such data obtained from PCR-based bacterial artificial chromosome arrays, high-density oligonucleotide arrays, and more recently developed high-throughput DNA sequencing. Treating parameters--e.g., the number of CNVs, the position of each CNV, and the data noise level--that define the underlying data generating process as random variables, our approach derives the posterior distribution of the genomic CNV structure given the observed data. Sampling from the posterior distribution using a Markov chain Monte Carlo method, we get not only best estimates for these unknown parameters but also Bayesian credible intervals for the estimates. We illustrate the characteristics of our algorithm by applying it to both synthetic and experimental data sets in comparison to other segmentation algorithms. Conclusions In particular, the synthetic data comparison shows that our method is more sensitive than other approaches at low false positive rates. Furthermore, given its Bayesian origin, our method can also be seen as a technique to refine CNVs identified by fast point-estimate methods and also as a framework to integrate array-CGH and sequencing data with other CNV-related biological knowledge, all through informative priors.</p