Distinct groups of autoantigens as drivers of ocular adnexal MALT lymphoma pathogenesis

Chronic B-cell receptor signals incited by cognate antigens are believed to play a crucial role in the pathogenesis of mucosa-associated lymphoid tissue lymphomas. We have explored the immunoglobulin variable regions (IGHV) expressed by 124 ocular adnexal MALT lymphomas (OAML) and tested the in vitro reactivity of recombinant IgM derived from 23 OAMLs. Six of 124 OAMLs (5%) were found to express a high-affinity stereotyped rheumatoid factor. OAMLs have a biased IGHV4-34 usage, which confers intrinsic super auto-antigen reactivity with poly-N-acetyllactosamine (NAL) epitopes, present on cell surface glycoproteins of erythrocytes and B cells. Twenty-one OAMLs (17%) expressed IGHV4-34-encoded B-cell receptors. Five of the 23 recombinant OAML IgMs expressed IGHV4-34, four of which bound to the linear NAL i epitope expressed on B cells but not to the branched NAL I epitope on erythrocytes. One non-IGHV4-34-encoded OAML IgM was also reactive with B cells. Interestingly, three of the 23 OAML IgMs (13%) specifically reacted with proteins of U1-/U-snRNP complexes, which have been implicated as cognate-antigens in various autoimmune diseases such as systemic lupus erythematosus and mixed connective tissue disease. The findings indicate that local autoimmune reactions are instrumental in the pathogenesis of a substantial fraction of OAMLs.</p

Electronic voting to encourage interactive lectures: a randomised trial

Background: Electronic Voting Systems have been used for education in a variety of disciplines. Outcomes from these studies have been mixed. Because results from these studies have been mixed, we examined whether an EVS system could enhance a lecture's effect on educational outcomes. Methods: A cohort of 127 Year 5 medical students at the University of Adelaide was stratified by gender, residency status and academic record then randomised into 2 groups of 64 and 63 students. Each group received consecutive 40-minute lectures on two clinical topics. One group received the EVS for both topics. The other group received traditional teaching only. Evaluation was undertaken with two, 15-question multiple-choice questionnaires (MCQ) assessing knowledge and problem solving and undertaken as a written paper immediately before and after the lectures and repeated online 8–12 weeks later. Standardised institutional student questionnaires were completed for each lecture and independent observers assessed student behaviour during the lectures. Lecturer's opinions were assessed by a questionnaire developed for this study. Results: Two-thirds of students randomised to EVS and 59% of students randomised to traditional lectures attended. One-half of the students in the EVS group and 41% in the traditional group completed all questionnaires. There was no difference in MCQ scores between EVS and traditional lectures (p = 0.785). The cervical cancer lectures showed higher student ranking in favour of EVS in all parameters. The breast cancer lectures showed higher ranking in favour of traditional lectures in 5 of 7 parameters (p < 0.001). The observed higher-order lecturer-students interactions were increased in the EVS lecture for one lecturer and reduced for the other. Both lecturers felt that the EVS lectures were difficult to prepare, that they were able to keep to time in the traditional lectures, that the educational value of both lecture styles was similar, and that they were neutral-to-slightly favourably disposed to continue with the EVS technology. The 2 lecturers disagreed regarding the ease of preparation of the traditional lecture, their ability to keep to time in the EVS lecture, and personal satisfaction with the EVS lecture. The lecturers felt that EVS encouraged student participation and helped identify where students were having difficulty. Conclusion: In this setting, EVS technology used in large group lectures did not offer significant advantages over the more traditional lecture format.Paul M Duggan, Edward Palmer and Peter Devit

Probing quantum and thermal noise in an interacting many-body system

The probabilistic character of the measurement process is one of the most puzzling and fascinating aspects of quantum mechanics. In many-body systems quantum mechanical noise reveals non-local correlations of the underlying many-body states. Here, we provide a complete experimental analysis of the shot-to-shot variations of interference fringe contrast for pairs of independently created one-dimensional Bose condensates. Analyzing different system sizes we observe the crossover from thermal to quantum noise, reflected in a characteristic change in the distribution functions from Poissonian to Gumbel-type, in excellent agreement with theoretical predictions based on the Luttinger liquid formalism. We present the first experimental observation of quasi long-range order in one-dimensional atomic condensates, which is a hallmark of quantum fluctuations in one-dimensional systems. Furthermore, our experiments constitute the first analysis of the full distribution of quantum noise in an interacting many-body system

Examining intra-rater and inter-rater response agreement: A medical chart abstraction study of a community-based asthma care program

<p>Abstract</p> <p>Background</p> <p>To assess the intra- and inter-rater agreement of chart abstractors from multiple sites involved in the evaluation of an Asthma Care Program (ACP).</p> <p>Methods</p> <p>For intra-rater agreement, 110 charts randomly selected from 1,433 patients enrolled in the ACP across eight Ontario communities were re-abstracted by 10 abstractors. For inter-rater agreement, data abstractors reviewed a set of eight fictitious charts. Data abstraction involved information pertaining to six categories: physical assessment, asthma control, spirometry, asthma education, referral visits, and medication side effects. Percentage agreement and the kappa statistic (κ) were used to measure agreement. Sensitivity and specificity estimates were calculated comparing results from all raters against the gold standard.</p> <p>Results</p> <p>Intra-rater re-abstraction yielded an overall kappa of 0.81. Kappa values for the chart abstraction categories were: physical assessment (κ 0.84), asthma control (κ 0.83), spirometry (κ 0.84), asthma education (κ 0.72), referral visits (κ 0.59) and medication side effects (κ 0.51). Inter-rater abstraction of the fictitious charts produced an overall kappa of 0.75, sensitivity of 0.91 and specificity of 0.89. Abstractors demonstrated agreement for physical assessment (κ 0.88, sensitivity and specificity 0.95), asthma control (κ 0.68, sensitivity 0.89, specificity 0.85), referral visits (κ 0.77, sensitivity 0.88, specificity 0.95), and asthma education (κ 0.49, sensitivity 0.87, specificity 0.77).</p> <p>Conclusion</p> <p>Though collected by multiple abstractors, the results show high sensitivity and specificity and substantial to excellent inter- and intra-rater agreement, assuring confidence in the use of chart abstraction for evaluating the ACP.</p

Explorative visual analytics on interval-based genomic data and their metadata

Background: With the wide-spreading of public repositories of NGS processed data, the availability of user-friendly and effective tools for data exploration, analysis and visualization is becoming very relevant. These tools enable interactive analytics, an exploratory approach for the seamless "sense-making" of data through on-the-fly integration of analysis and visualization phases, suggested not only for evaluating processing results, but also for designing and adapting NGS data analysis pipelines. Results: This paper presents abstractions for supporting the early analysis of NGS processed data and their implementation in an associated tool, named GenoMetric Space Explorer (GeMSE). This tool serves the needs of the GenoMetric Query Language, an innovative cloud-based system for computing complex queries over heterogeneous processed data. It can also be used starting from any text files in standard BED, BroadPeak, NarrowPeak, GTF, or general tab-delimited format, containing numerical features of genomic regions; metadata can be provided as text files in tab-delimited attribute-value format. GeMSE allows interactive analytics, consisting of on-the-fly cycling among steps of data exploration, analysis and visualization that help biologists and bioinformaticians in making sense of heterogeneous genomic datasets. By means of an explorative interaction support, users can trace past activities and quickly recover their results, seamlessly going backward and forward in the analysis steps and comparative visualizations of heatmaps. Conclusions: GeMSE effective application and practical usefulness is demonstrated through significant use cases of biological interest. GeMSE is available at http://www.bioinformatics.deib.polimi.it/GeMSE/ , and its source code is available at https://github.com/Genometric/GeMSEunder GPLv3 open-source license

Neural correlates of evidence accumulation during value-based decisions revealed via simultaneous EEG-fMRI

Current computational accounts posit that, in simple binary choices, humans accumulate evidence in favour of the different alternatives before committing to a decision. Neural correlates of this accumulating activity have been found during perceptual decisions in parietal and prefrontal cortex; however the source of such activity in value-based choices remains unknown. Here we use simultaneous EEG–fMRI and computational modelling to identify EEG signals reflecting an accumulation process and demonstrate that the within- and across-trial variability in these signals explains fMRI responses in posterior-medial frontal cortex. Consistent with its role in integrating the evidence prior to reaching a decision, this region also exhibits task-dependent coupling with the ventromedial prefrontal cortex and the striatum, brain areas known to encode the subjective value of the decision alternatives. These results further endorse the proposition of an evidence accumulation process during value-based decisions in humans and implicate the posterior-medial frontal cortex in this process

Identification of Pax6-Dependent Gene Regulatory Networks in the Mouse Lens

Lineage-specific DNA-binding transcription factors regulate development by activating and repressing particular set of genes required for the acquisition of a specific cell type. Pax6 is a paired domain and homeodomain-containing transcription factor essential for development of central nervous, olfactory and visual systems, as well as endocrine pancreas. Haploinsufficiency of Pax6 results in perturbed lens development and homeostasis. Loss-of-function of Pax6 is incompatible with lens lineage formation and results in abnormal telencephalic development. Using DNA microarrays, we have identified 559 genes expressed differentially between 1-day old mouse Pax6 heterozygous and wild type lenses. Of these, 178 (31.8%) were similarly increased and decreased in Pax6 homozygous embryonic telencephalon [Holm PC, Mader MT, Haubst N, Wizenmann A, Sigvardsson M, Götz M (2007) Loss- and gain-of-function analyses reveals targets of Pax6 in the developing mouse telencephalon. Mol Cell Neurosci 34: 99–119]. In contrast, 381 (68.2%) genes were differently regulated between the lens and embryonic telencephalon. Differential expression of nine genes implicated in lens development and homeostasis: Cspg2, Igfbp5, Mab21l2, Nrf2f, Olfm3, Spag5, Spock1, Spon1 and Tgfb2, was confirmed by quantitative RT-PCR, with five of these genes: Cspg2, Mab21l2, Olfm3, Spag5 and Tgfb2, identified as candidate direct Pax6 target genes by quantitative chromatin immunoprecipitation (qChIP). In Mab21l2 and Tgfb2 promoter regions, twelve putative individual Pax6-binding sites were tested by electrophoretic mobility shift assays (EMSAs) with recombinant Pax6 proteins. This led to the identification of two and three sites in the respective Mab21l2 and Tgfb2 promoter regions identified by qChIPs. Collectively, the present studies represent an integrative genome-wide approach to identify downstream networks controlled by Pax6 that control mouse lens and forebrain development