Computational diagnosis and risk evaluation for canine lymphoma

The canine lymphoma blood test detects the levels of two biomarkers, the acute phase proteins (C-Reactive Protein and Haptoglobin). This test can be used for diagnostics, for screening, and for remission monitoring as well. We analyze clinical data, test various machine learning methods and select the best approach to these problems. Three family of methods, decision trees, kNN (including advanced and adaptive kNN) and probability density evaluation with radial basis functions, are used for classification and risk estimation. Several pre-processing approaches were implemented and compared. The best of them are used to create the diagnostic system. For the differential diagnosis the best solution gives the sensitivity and specificity of 83.5% and 77%, respectively (using three input features, CRP, Haptoglobin and standard clinical symptom). For the screening task, the decision tree method provides the best result, with sensitivity and specificity of 81.4% and >99%, respectively (using the same input features). If the clinical symptoms (Lymphadenopathy) are considered as unknown then a decision tree with CRP and Hapt only provides sensitivity 69% and specificity 83.5%. The lymphoma risk evaluation problem is formulated and solved. The best models are selected as the system for computational lymphoma diagnosis and evaluation the risk of lymphoma as well. These methods are implemented into a special web-accessed software and are applied to problem of monitoring dogs with lymphoma after treatment. It detects recurrence of lymphoma up to two months prior to the appearance of clinical signs. The risk map visualisation provides a friendly tool for explanatory data analysis.Comment: 24 pages, 86 references in the bibliography, Significantly extended version with review of lymphoma biomarkers and data mining methods (Three new sections are added: 1.1. Biomarkers for canine lymphoma, 1.2. Acute phase proteins as lymphoma biomarkers and 3.1. Data mining methods for biomarker cancer diagnosis. Flowcharts of data analysis are included as supplementary material (20 pages

Assessment of proliferating cell nuclear antigen and its relationship with proinflammatory cytokines and parameters of disease activity in multiple myeloma patients

Multiple myeloma (MM) is a malignant plasma cell disease. Several proinflammatory cytokines produced by malignant plasma cells and bone marrow (BM) stromal cells are involved in the pathogenesis of the disease. We evaluated serum levels of the proinflammatory cytokines Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Interleukin-8 (IL-8), macrophage inflammatory protein-1α (MIP-1α), in MM patients before treatment, and determined its significance in tumor progression. We also analyzed the correlation between measured parameters with proliferating cell nuclear antigen (PCNA). Forty-four MM patients and 20 healthy controls were studied. Serum levels of the proinflammatory cytokines were measured using enzyme-linked immunosorbent assay (ELISA), whereas PCNA value in the BM was determined by immunohistochemistry staining. The mean concentrations of the measured cytokines were significantly different among the three stages of disease, with higher values in advanced disease stage. Furthermore, patients with MM had significantly higher serum levels of the measured cytokines than in controls. A positive correlation was found between IL-6 with IL-1β, IL-8 and MIP-1α. Similarly, IL-8 and MIP-1α were positively correlated with markers of disease activity such as β2 microglobulin and LDH. The proliferation index, determined by PCNA immunostaining, was higher in advanced disease stage. Furthermore PCNA value correlated significantly with β2 microglobulin, LDH and the levels of the measured cytokines. Our results showed that the proliferative activity, as measured with PCNA, increases in parallel with disease stage. The positive correlation between PCNA and other measured mediators supports the involvement of these factors in the biology of myeloma cell growth and can be used as markers of disease activity and as possible therapeutic targets

Miliary tuberculosis with no pulmonary involvement in myelodysplastic syndromes: a curable, yet rarely diagnosed, disease: case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Although tuberculosis is not uncommon among patients with myelodysplastic syndrome (MDS), only a few reports of such patients suffering from miliary tuberculosis (MT) exist. MT often presents as a fever of unknown origin and it is a curable disease, yet fatal if left untreated.</p> <p>Case presentation</p> <p>We report a case of MT with no clinical or laboratory indications of pulmonary involvement in a patient with MDS, and review the relevant literature. <it>Mycobacterium tuberculosis </it>was isolated from the liquid culture of a bone marrow aspirate.</p> <p>Conclusion</p> <p>Even if the initial diagnostic investigation for a fever of obscure etiology is negative, MT should not be excluded from the differential diagnosis list. Since it is a curable disease, persistent and vigorous diagnostic efforts are warranted. In suspected cases, mycobacterial blood cultures should be collected as soon as possible after hospital admission and early bone marrow aspirate with mycobacterial cultures is advocated.</p

Simulations of Weighted Tree Automata

Simulations of weighted tree automata (wta) are considered. It is shown how such simulations can be decomposed into simpler functional and dual functional simulations also called forward and backward simulations. In addition, it is shown in several cases (fields, commutative rings, Noetherian semirings, semiring of natural numbers) that all equivalent wta M and N can be joined by a finite chain of simulations. More precisely, in all mentioned cases there exists a single wta that simulates both M and N. Those results immediately yield decidability of equivalence provided that the semiring is finitely (and effectively) presented.Comment: 17 pages, 2 figure

Thermal dependence of large scale freckle defect formation

The fundamental mechanisms governing macroscopic freckle defect formation during directional solidification are studied experimentally in a Hele-Shaw cell for a low melting point Ga-25wt.%In alloy, and modelled numerically in 3D using a microscopic parallelised Cellular Automata lattice Boltzmann method. The size and distribution of freckles (long solute channels, or chimneys) is shown to be strongly dependent on the thermal profile of the casting, with flat, concave and convex isotherms being considered. For the flat isotherm case, no large-scale freckles form, while for concave or convex isotherms large freckles appear but in different locations. The freckle formation mechanism is as expected buoyancy-driven, but the chimney stability, its long-term endurance and its location, are shown to depend critically on the detailed convective transport through the inter-dendritic region. Flow is generated by curved isopleths of solute concentration. As solute density is different from that of the bulk fluid, gravity causes ‘uphill´ or ‘downhill’ lateral flow from the sample centre to the edges through the mush, feeding the freckle. An excellent agreement is obtained between the numerical model and real-time x-ray observations of a solidifying sample under strictly controlled temperature conditions

The Impact of an Extreme Storm Event on the Barrier Beach of the Lefkada Lagoon, NE Ionian Sea (Greece)

The present investigation examines the characteristics of a high energy storm event, that took place on November 9-11, 2007 in the NE Ionian Sea (eastern Mediterranean), and its impact upon the barrier beach that separates the Lefkada lagoon from the open Ionian Sea. The storm event was caused by NW winds with speeds exceeding 20 m/s (40 knots), which have an annual frequency of occurrence less than 0.015%. This high energy event produced waves with >5 m significant offshore height and 9.5 s period; these waves developed on 10th November during the rapid rise of barometric pressure (~1.4 hPa/hr), which followed the barometric pressure drop from 1020.5 hPa at 06:00 (UTC) of 9th November to 1001.7 hPa at 06:00 h (UTC) of 10th November. Secondary breaking at the shoreline produced wave heights >1.5 m, associated with a surge of >0.4 m and a run-up capability of >2.4 m. The waves managed to overtop the barrier beach (elevations ~2.5 m), lowering the seaward side of the barrier beach by 10-30 cm and causing a coastline retreat of 0.9 to 2.2 m; these morphological changes correspond volumetrically to a sediment loss of approximately 8 m3/m of coastline length from the sub-aerial part of the beach. During the last three decades a significant change in the frequency of occurrence and direction (from S-SW-W to N-NW-NE) of severe storms with wind speeds exceeding 40 knots has been recorded, affecting the sediment transport pattern and contributing to the erosion of the north beaches of Lefkada

MiMiR - an integrated platform for microarray data sharing, mining and analysis

Background: Despite considerable efforts within the microarray community for standardising data format, content and description, microarray technologies present major challenges in managing, sharing, analysing and re-using the large amount of data generated locally or internationally. Additionally, it is recognised that inconsistent and low quality experimental annotation in public data repositories significantly compromises the re-use of microarray data for meta-analysis. MiMiR, the Microarray data Mining Resource was designed to tackle some of these limitations and challenges. Here we present new software components and enhancements to the original infrastructure that increase accessibility, utility and opportunities for large scale mining of experimental and clinical data.Results: A user friendly Online Annotation Tool allows researchers to submit detailed experimental information via the web at the time of data generation rather than at the time of publication. This ensures the easy access and high accuracy of meta-data collected. Experiments are programmatically built in the MiMiR database from the submitted information and details are systematically curated and further annotated by a team of trained annotators using a new Curation and Annotation Tool. Clinical information can be annotated and coded with a clinical Data Mapping Tool within an appropriate ethical framework. Users can visualise experimental annotation, assess data quality, download and share data via a web-based experiment browser called MiMiR Online. All requests to access data in MiMiR are routed through a sophisticated middleware security layer thereby allowing secure data access and sharing amongst MiMiR registered users prior to publication. Data in MiMiR can be mined and analysed using the integrated EMAAS open source analysis web portal or via export of data and meta-data into Rosetta Resolver data analysis package.Conclusion: The new MiMiR suite of software enables systematic and effective capture of extensive experimental and clinical information with the highest MIAME score, and secure data sharing prior to publication. MiMiR currently contains more than 150 experiments corresponding to over 3000 hybridisations and supports the Microarray Centre's large microarray user community and two international consortia. The MiMiR flexible and scalable hardware and software architecture enables secure warehousing of thousands of datasets, including clinical studies, from microarray and potentially other -omics technologies

Psychosocial drivers for change: understanding and promoting stakeholder engagement in local adaptation to climate change in three European Mediterranean case studies

Stakeholder engagement in the processes of planning local adaptation to climate change faces many challenges. The goal of this work was to explore whether or not the intention of engaging could be understood (Study 1) and promoted (Study 2), by using an extension of the theory of planned behaviour. In Study 1, stakeholders from three European Mediterranean case studies were surveyed: Baixo Vouga Lagunar (Portugal), SCOT Provence Méditerranée (France), and the island of Crete (Greece) (N = 115). Stakeholders' intention of engaging was significantly predicted by subjective norm (which was predicted by injunctive normative beliefs towards policy-makers and stakeholders) and by perceived behavioural control (which was predicted by knowledge of policy and instruments). Study 2 was conducted in the Baixo Vouga Lagunar case study and consisted of a two-workshop intervention where issues on local and regional adaptation, policies, and engagement were presented and discussed. A within-participants comparison of initial survey results with results following the workshops (NT1 = 12, NT2 = 15, NT3 = 12) indicated that these were successful in increasing stakeholders' intention of engaging. This increase was paired with a) an increase in injunctive normative beliefs towards policy-makers and consequently in subjective norm, and to b) a decrease in perceived complexity of planning local adaptation and an increase in knowledge regarding adaptation to climate change.info:eu-repo/semantics/acceptedVersio

Membranous nephropathy and lupus-like syndrome after hematopoietic cell transplantation: a case report

<p>Abstract</p> <p>Introduction</p> <p>The kidney is increasingly recognised as a target organ of chronic graft-versus-host disease after hematopoietic cell transplantation in the context of the development of the nephrotic syndrome. Chronic graft-versus-host disease is associated with autoimmune phenomena similar, but not identical, to those observed in various rheumatologic disorders, implicating autoimmunity as an important component of the disease.</p> <p>Case presentation</p> <p>We report the case of a 57-year-old Caucasian man who developed the nephrotic syndrome due to membranous nephropathy in association with recurrent chronic graft-versus-host disease, along with a lupus-like syndrome manifested with pancytopenia, hair loss, positive anti-DNA antibodies and sub-epithelial and mesangial immune deposits. To the best of our knowledge, this is the first case reported in the literature. The nephrotic syndrome subsided soon after he was treated with a short course of cyclosporin with steroids. Unfortunately he died seven months later due to a relapse of leukemia.</p> <p>Conclusions</p> <p>Our case report confirms the notion that chronic graft-versus-host disease is characterized by the appearance of autoimmune phenomena similar, but not identical, to those seen in autoimmune diseases. The decision for more immunosuppression has to be weighed against the need for preservation of the graft versus leukemia phenomenon.</p