278 research outputs found

    Cancer gene prioritization by integrative analysis of mRNA expression and DNA copy number data: a comparative review

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    A variety of genome-wide profiling techniques are available to probe complementary aspects of genome structure and function. Integrative analysis of heterogeneous data sources can reveal higher-level interactions that cannot be detected based on individual observations. A standard integration task in cancer studies is to identify altered genomic regions that induce changes in the expression of the associated genes based on joint analysis of genome-wide gene expression and copy number profiling measurements. In this review, we provide a comparison among various modeling procedures for integrating genome-wide profiling data of gene copy number and transcriptional alterations and highlight common approaches to genomic data integration. A transparent benchmarking procedure is introduced to quantitatively compare the cancer gene prioritization performance of the alternative methods. The benchmarking algorithms and data sets are available at http://intcomp.r-forge.r-project.orgComment: PDF file including supplementary material. 9 pages. Preprin

    Diffusion of hydrogen in crystalline silicon

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    The coefficient of diffusion of hydrogen in crystalline silicon is calculated using tight-binding molecular dynamics. Our results are in good quantitative agreement with an earlier study by Panzarini and Colombo [Phys. Rev. Lett. 73, 1636 (1994)]. However, while our calculations indicate that long jumps dominate over single hops at high temperatures, no abrupt change in the diffusion coefficient can be observed with decreasing temperature. The (classical) Arrhenius diffusion parameters, as a consequence, should extrapolate to low temperatures.Comment: 4 pages, including 5 postscript figures; submitted to Phys. Rev. B Brief Repor

    A crucial role for the cortico-striato-cortical loop in the pathogenesis of stroke-related neurogenic stuttering

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    Neurogenic stuttering is an acquired speech disorder characterized by the occurrence of stuttering-like dysfluencies following brain damage. Because the onset of stuttering in these patients is associated with brain lesions, this condition provides a unique opportunity to study the neural processes underlying speech dysfluencies. Lesion localizations of 20 stroke subjects with neurogenic stuttering and 17 control subjects were compared using voxel-based lesion symptom mapping. The results showed nine left-hemisphere areas associated with the presen ce of neurogenic stuttering. These areas were largely overlapping with the cortico-basal ganglia-cortical network comprising the inferior frontal cortex, superior temporal cortex, intraparietal cortex, basal ganglia, and their white matter interconnections through the superior longitudinal fasciculus and internal capsule. These results indicated that stroke-induced neurogenic stuttering is not associated with neural dysfunction in one specific brain area but can occur following one or more lesion throughout the cortico-basal ganglia-cortical network. It is suggested that the onset of neurogenic stuttering in stroke subjects results from a disintegration of neural functions necessary for fluent speech. © 2012 Wiley Periodicals, Inc

    Brain activation during non-habitual speech production: Revisiting the effects of simulated disfluencies in fluent speakers

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    Over the past decades, brain imaging studies in fluently speaking participants have greatly advanced our knowledge of the brain areas involved in speech production. In addition, complementary information has been provided by investigations of brain activation patterns associated with disordered speech. In the present study we specifically aimed to revisit and expand an earlier study by De Nil and colleagues, by investigating the effects of simulating disfluencies on the brain activation patterns of fluent speakers during overt and covert speech production. In contrast to the De Nil et al. study, the current findings show that the production of voluntary, self-generated disfluencies by fluent speakers resulted in increased recruitment and activation of brain areas involved in speech production. These areas show substantial overlap with the neural networks involved in motor sequence learning in general, and learning of speech production, in particular. The implications of these findings for the interpretation of brain imaging studies on disordered and non-habitual speech production are discussed

    Genomic aberrations relate early and advanced stage ovarian cancer

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    Background Because of the distinct clinical presentation of early and advanced stage ovarian cancer, we aim to clarify whether these disease entities are solely separated by time of diagnosis or whether they arise from distinct molecular events. Methods Sixteen early and sixteen advanced stage ovarian carcinomas, matched for histological subtype and differentiation grade, were included. Genomic aberrations were compared for each early and advanced stage ovarian cancer by array comparative genomic hybridization. To study how the aberrations correlate to the clinical characteristics of the tumors we clustered tumors based on the genomic aberrations. Results The genomic aberration patterns in advanced stage cancer equalled those in early stage, but were more frequent in advanced stage (p=0.012). Unsupervised clustering based on genomic aberrations yielded two clusters that significantly discriminated early from advanced stage (p= 0.001), and that did differ significantly in survival (p= 0.002). These clusters however did give a more accurate prognosis than histological subtype or differentiation grade. Conclusion This study indicates that advanced stage ovarian cancer either progresses from early stage or from a common precursor lesion but that they do not arise from distinct carcinogenic molecular events. Furthermore, we show that array comparative genomic hybridization has the potential to identify clinically distinct patients

    Reducing unnecessary prescriptions of antibiotics for acute cough: Adaptation of a leaflet aimed at Turkish immigrants in Germany

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    <p>Abstract</p> <p>Background</p> <p>The reduction in the number of unnecessary prescriptions of antibiotics has become one of the most important objectives for primary health care. German GPs report that they are under "pressure to prescribe" antibiotics particularly in consultations with Turkish immigrants. And so a qualitative approach was used to learn more about the socio-medical context of Turkish patients in regard to acute coughs. A German leaflet designed to improve the doctor-patient communication has been positively tested and then adapted for Turkish patients.</p> <p>Methods</p> <p>The original leaflet was first translated into Turkish. Then 57 patients belonging to 8 different GPs were interviewed about the leaflet using a semi-standardised script. The material was audio recorded, fully transcribed, and analysed by three independent researchers. As a first step a comprehensive content analysis was performed. Secondly, elements crucial to any Turkish version of the leaflet were identified.</p> <p>Results</p> <p>The interviews showed that the leaflets' messages were clearly understood by all patients irrespective of age, gender, and educational background. We identified no major problems in the perception of the translated leaflet but identified several minor points which could be improved. We found that patients were starting to reconsider their attitudes after reading the leaflet.</p> <p>Conclusion</p> <p>The leaflet successfully imparted relevant and new information to the target patients. A qualitative approach is a feasible way to prove general acceptance and provides additional information for its adaptation to medico-cultural factors.</p
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