Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial

Background Homozygous familial hypercholesterolaemia is a rare genetic disorder in which both LDL-receptor alleles are defective, resulting in very high concentrations of LDL cholesterol in plasma and premature coronary artery disease. This study investigated whether an antisense inhibitor of apolipoprotein B synthesis, mipomersen, is effective and safe as an adjunctive agent to lower LDL cholesterol concentrations in patients with this disease. Methods This randomised, double-blind, placebo-controlled, phase 3 study was undertaken in nine lipid clinics in seven countries. Patients aged 12 years and older with clinical diagnosis or genetic confirmation of homozygous familial hypercholesterolaemia, who were already receiving the maximum tolerated dose of a lipid-lowering drug, were randomly assigned to mipomersen 200 mg subcutaneously every week or placebo for 26 weeks. Randomisation was computer generated and stratified by weight (<50 kg vs >= 50 kg) in a centralised blocked randomisation, implemented with a computerised interactive voice response system. All clinical, medical, and pharmacy personnel, and patients were masked to treatment allocation. The primary endpoint was percentage change in LDL cholesterol concentration from baseline. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00607373. Findings 34 patients were assigned to mipomersen and 17 to placebo; data for all patients were analysed. 45 patients completed the 26-week treatment period (28 mipomersen, 17 placebo). Mean concentrations of LDL cholesterol at baseline were 11.4 mmol/L (SD 3.6) in the mipomersen group and 10.4 mmol/L (3.7) in the placebo group. The mean percentage change in LDL cholesterol concentration was significantly greater with mipomersen (-24.7%, 95% CI 31.6 to 17.7) than with placebo (-3.3%, 12.1 to 5.5; p=0.0003). The most common adverse events were injection-site reactions (26 [76%] patients in mipomersen group vs four [24%] in placebo group). Four (12%) patients in the mipomersen group but none in the placebo group had increases in concentrations of alanine aminotransferase of three times or more the upper limit of normal. Interpretation Inhibition of apolipoprotein B synthesis by mipomersen represents a novel, effective therapy to reduce LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia who are already receiving lipid-lowering drugs, including high-dose statins.

Is the unfolding of the group discussion off-pattern? Improving coordination support in educational forums using mobile devices

A forum is a valuable tool to foster reflection in an in-depth discussion; however, it forces the course mediator to continually pay close attention in order to coordinate learners` activities. Moreover, monitoring a forum is time consuming given that it is impossible to know in advance when new messages are going to be posted. Additionally, a forum may be inactive for a long period and suddenly receive a burst of messages forcing forum mediators to frequently log on in order to know how the discussion is unfolding to intervene whenever it is necessary. Mediators also need to deal with a large amount of messages to identify off-pattern situations. This work presents a piece of action research that investigates how to improve coordination support in a forum using mobile devices for mitigating mediator`s difficulties in following the status of a forum. Based on summarized information extracted from message meta-data, mediators consult visual information summaries on PDAs and receive textual notifications in their mobile phone. This investigation revealed that mediators used the mobile-based coordination support to keep informed on what is taking place within the forum without the need to log on their desktop computer. (C) 2009 Elsevier Ltd. All rights reserved.

A calibration approach based on Takagi-Sugeno fuzzy inference system for digital electronic compasses

Recently, the development of industrial processes brought on the outbreak of technologically complex systems. This development generated the necessity of research relative to the mathematical techniques that have the capacity to deal with project complexities and validation. Fuzzy models have been receiving particular attention in the area of nonlinear systems identification and analysis due to it is capacity to approximate nonlinear behavior and deal with uncertainty. A fuzzy rule-based model suitable for the approximation of many systems and functions is the Takagi-Sugeno (TS) fuzzy model. IS fuzzy models are nonlinear systems described by a set of if then rules which gives local linear representations of an underlying system. Such models can approximate a wide class of nonlinear systems. In this paper a performance analysis of a system based on IS fuzzy inference system for the calibration of electronic compass devices is considered. The contribution of the evaluated IS fuzzy inference system is to reduce the error obtained in data acquisition from a digital electronic compass. For the reliable operation of the TS fuzzy inference system, adequate error measurements must be taken. The error noise must be filtered before the application of the IS fuzzy inference system. The proposed method demonstrated an effectiveness of 57% at reducing the total error based on considered tests. (C) 2011 Elsevier Ltd. All rights reserved.

WRITING ELECTRONIC FERROMAGNETIC STATES IN A HIGH-TEMPERATURE PARAMAGNETIC NUCLEAR SPIN SYSTEM

In this paper, we use Nuclear Magnetic Resonance (NMR) to write electronic states of a ferromagnetic system into high-temperature paramagnetic nuclear spins. Through the control of phase and duration of radio frequency pulses, we set the NMR density matrix populations, and apply the technique of quantum state tomography to experimentally obtain the matrix elements of the system, from which we calculate the temperature dependence of magnetization for different magnetic fields. The effects of the variation of temperature and magnetic field over the populations can be mapped in the angles of spin rotations, carried out by the RF pulses. The experimental results are compared to the Brillouin functions of ferromagnetic ordered systems in the mean field approximation for two cases: the mean field is given by (i) B = B(0) + lambda M and (ii) B = B(0) + lambda M + lambda`M(3), where B(0) is the external magnetic field, and lambda, lambda` are mean field parameters. The first case exhibits second order transition, whereas the second case has first order transition with temperature hysteresis. The NMR simulations are in good agreement with the magnetic predictions.

Fuzzy Control System for Voltage Regulation In Power Transformers

A fuzzy control strategy for voltage regulation in electric power distribution systems is introduced in this article. This real-time controller would act on power transformers equipped with under-load tap changers. The fuzzy system was employed to turn the voltage-control relays into adaptive devices. The scope of the present study has been limited to the power distribution substation, and both the voltage measurements and control actions are carried out on the secondary bus. The capacity of fuzzy systems to handle approximate data, together with their unique ability to interpret qualitative information, make it possible to design voltage control strategies that satisfy both the requirements of the Brazilian regulatory bodies and the real concerns of the electric power distribution companies. A prototype based on the fuzzy control strategy proposed in this paper has also been implemented for validation purposes and its experimental results were highly satisfactory.

Automatic tuning method for the design of supplementary damping controllers for flexible alternating current transmission system devices

The design of supplementary damping controllers to mitigate the effects of electromechanical oscillations in power systems is a highly complex and time-consuming process, which requires a significant amount of knowledge from the part of the designer. In this study, the authors propose an automatic technique that takes the burden of tuning the controller parameters away from the power engineer and places it on the computer. Unlike other approaches that do the same based on robust control theories or evolutionary computing techniques, our proposed procedure uses an optimisation algorithm that works over a formulation of the classical tuning problem in terms of bilinear matrix inequalities. Using this formulation, it is possible to apply linear matrix inequality solvers to find a solution to the tuning problem via an iterative process, with the advantage that these solvers are widely available and have well-known convergence properties. The proposed algorithm is applied to tune the parameters of supplementary controllers for thyristor controlled series capacitors placed in the New England/New York benchmark test system, aiming at the improvement of the damping factor of inter-area modes, under several different operating conditions. The results of the linear analysis are validated by non-linear simulation and demonstrate the effectiveness of the proposed procedure.

Expert system for the assessment of power transformer insulation condition based on type-2 fuzzy logic systems

An efficient expert system for the power transformer condition assessment is presented in this paper. Through the application of Duval`s triangle and the method of the gas ratios a first assessment of the transformer condition is obtained in the form of a dissolved gas analysis (DGA) diagnosis according IEC 60599. As a second step, a knowledge mining procedure is performed, by conducting surveys whose results are fed into a first Type-2 Fuzzy Logic System (T2-FLS), in order to initially evaluate the condition of the equipment taking only the results of dissolved gas analysis into account. The output of this first T2-FLS is used as the input of a second T2-FLS, which additionally weighs up the condition of the paper-oil system. The output of this last T2-FLS is given in terms of words easily understandable by the maintenance personnel. The proposed assessing methodology has been validated for several cases of transformers in service. (C) 2010 Elsevier Ltd. All rights reserved.

An RFID Bulk Cargo Supervising System

In this work, a system using active RFID tags to supervise truck bulk cargo is described. The tags are attached to the bodies of the trucks and readers are distributed in the cargo buildings and attached to weighs and the discharge platforms. PDAs with camera and support to a WiFi network are provided to the inspectors and access points are installed throughout the discharge area to allow effective confirmations of unload actions and the acquisition of pictures for future audit. Broadband radio equipments are used to establish efficient communication links between the weighs and cargo buildings which are usually located very far from each other in the field. A web application software was especially developed to enable robust communication between the equipments for efficient device management, data processing and reports generation to the operating personal. The system was deployed in a cargo station of a Brazilian seashore port. The obtained results prove the effectiveness of the proposed system.

SKAN: Skin Scanner - System for Skin Cancer Detection Using Adaptive Techniques

SKAN: Skin Scanner - System for Skin Cancer Detection Using Adaptive Techniques - combines computer engineering concepts with areas like dermatology and oncology. Its objective is to discern images of skin cancer, specifically melanoma, from others that show only common spots or other types of skin diseases, using image recognition. This work makes use of the ABCDE visual rule, which is often used by dermatologists for melanoma identification, to define which characteristics are analyzed by the software. It then applies various algorithms and techniques, including an ellipse-fitting algorithm, to extract and measure these characteristics and decide whether the spot is a melanoma or not. The achieved results are presented with special focus on the adaptive decision-making and its effect on the diagnosis. Finally, other applications of the software and its algorithms are presented.

A decision support system to facilitate management of patients with acute gastrointestinal bleeding

Objective: To develop a model to predict the bleeding source and identify the cohort amongst patients with acute gastrointestinal bleeding (GIB) who require urgent intervention, including endoscopy. Patients with acute GIB, an unpredictable event, are most commonly evaluated and managed by non-gastroenterologists. Rapid and consistently reliable risk stratification of patients with acute GIB for urgent endoscopy may potentially improve outcomes amongst such patients by targeting scarce health-care resources to those who need it the most. Design and methods: Using ICD-9 codes for acute GIB, 189 patients with acute GIB and all. available data variables required to develop and test models were identified from a hospital medical records database. Data on 122 patients was utilized for development of the model and on 67 patients utilized to perform comparative analysis of the models. Clinical data such as presenting signs and symptoms, demographic data, presence of co-morbidities, laboratory data and corresponding endoscopic diagnosis and outcomes were collected. Clinical data and endoscopic diagnosis collected for each patient was utilized to retrospectively ascertain optimal management for each patient. Clinical presentations and corresponding treatment was utilized as training examples. Eight mathematical models including artificial neural network (ANN), support vector machine (SVM), k-nearest neighbor, linear discriminant analysis (LDA), shrunken centroid (SC), random forest (RF), logistic regression, and boosting were trained and tested. The performance of these models was compared using standard statistical analysis and ROC curves. Results: Overall the random forest model best predicted the source, need for resuscitation, and disposition with accuracies of approximately 80% or higher (accuracy for endoscopy was greater than 75%). The area under ROC curve for RF was greater than 0.85, indicating excellent performance by the random forest model Conclusion: While most mathematical models are effective as a decision support system for evaluation and management of patients with acute GIB, in our testing, the RF model consistently demonstrated the best performance. Amongst patients presenting with acute GIB, mathematical models may facilitate the identification of the source of GIB, need for intervention and allow optimization of care and healthcare resource allocation; these however require further validation. (c) 2007 Elsevier B.V. All rights reserved.

Effectiveness of sealing active proximal caries lesions with an adhesive system: 1-year clinical evaluation

The objective of this study was to evaluate the effectiveness of a therapeutic sealant to arrest non-cavitated proximal carious lesion progression. The study population comprised 44 adolescents who had bitewing radiographs taken for caries diagnosis. Non-cavitated lesions extending up to half of dentin thickness were included in the sample. In the experimental group (n = 33), the proximal caries-lesion surfaces were sealed with an adhesive (OptiBond Solo, Kerr) after tooth separation. The control group (n = 11) received no treatment, except for oral hygiene instructions including use of dental floss. Follow-up radiographs were taken after one year and were analyzed in comparison with baseline radiographs. In a blind study setting, visual readings were performed by two examiners, blinded to whether the examined radiograph was baseline or follow-up, and whether it concerned a test or control lesion. The efficacy of sealing treatment was evaluated by the McNemar test (0.05). About 22% of the sealed lesions showed reduction, 61% showed no change and 16% showed progression. For the control lesions, the corresponding values were 27%, 36% and 36% respectively. The number of lesions that showed reduction and no changes were merged and therefore 83.3% of the sealed lesions and 63.6% of the control lesions were considered clinically successful. No statistical significance was detected (p > 0.05). In the course of 1 year, sealing proximal caries lesions was not shown to be superior to lesion monitoring.

Neural networks and statistical analysis for classification of corneal videokeratography maps based on Zernike coefficients: a quantitative comparison

PURPOSE: The main goal of this study was to develop and compare two different techniques for classification of specific types of corneal shapes when Zernike coefficients are used as inputs. A feed-forward artificial Neural Network (NN) and discriminant analysis (DA) techniques were used. METHODS: The inputs both for the NN and DA were the first 15 standard Zernike coefficients for 80 previously classified corneal elevation data files from an Eyesys System 2000 Videokeratograph (VK), installed at the Departamento de Oftalmologia of the Escola Paulista de Medicina, São Paulo. The NN had 5 output neurons which were associated with 5 typical corneal shapes: keratoconus, with-the-rule astigmatism, against-the-rule astigmatism, "regular" or "normal" shape and post-PRK. RESULTS: The NN and DA responses were statistically analyzed in terms of precision ([true positive+true negative]/total number of cases). Mean overall results for all cases for the NN and DA techniques were, respectively, 94% and 84.8%. CONCLUSION: Although we used a relatively small database, results obtained in the present study indicate that Zernike polynomials as descriptors of corneal shape may be a reliable parameter as input data for diagnostic automation of VK maps, using either NN or DA.

ScriptLattes: an open-source knowledge extraction system from the Lattes platform

The Lattes platform is the major scientific information system maintained by the National Council for Scientific and Technological Development (CNPq). This platform allows to manage the curricular information of researchers and institutions working in Brazil based on the so called Lattes Curriculum. However, the public information is individually available for each researcher, not providing the automatic creation of reports of several scientific productions for research groups. It is thus difficult to extract and to summarize useful knowledge for medium to large size groups of researchers. This paper describes the design, implementation and experiences with scriptLattes: an open-source system to create academic reports of groups based on curricula of the Lattes Database. The scriptLattes system is composed by the following modules: (a) data selection, (b) data preprocessing, (c) redundancy treatment, (d) collaboration graph generation among group members, (e) research map generation based on geographical information, and (f) automatic report creation of bibliographical, technical and artistic production, and academic supervisions. The system has been extensively tested for a large variety of research groups of Brazilian institutions, and the generated reports have shown an alternative to easily extract knowledge from data in the context of Lattes platform. The source code, usage instructions and examples are available at http://scriptlattes.sourceforge.net/.

The Coupled Aerosol and Tracer Transport model to the Brazilian developments on the Regional Atmospheric Modeling System (CATT-BRAMS) - Part 2: Model sensitivity to the biomass burning

We describe an estimation technique for biomass burning emissions in South America based on a combination of remote-sensing fire products and field observations, the Brazilian Biomass Burning Emission Model (3BEM). For each fire pixel detected by remote sensing, the mass of the emitted tracer is calculated based on field observations of fire properties related to the type of vegetation burning. The burnt area is estimated from the instantaneous fire size retrieved by remote sensing, when available, or from statistical properties of the burn scars. The sources are then spatially and temporally distributed and assimilated daily by the Coupled Aerosol and Tracer Transport model to the Brazilian developments on the Regional Atmospheric Modeling System (CATT-BRAMS) in order to perform the prognosis of related tracer concentrations. Three other biomass burning inventories, including GFEDv2 and EDGAR, are simultaneously used to compare the emission strength in terms of the resultant tracer distribution. We also assess the effect of using the daily time resolution of fire emissions by including runs with monthly-averaged emissions. We evaluate the performance of the model using the different emission estimation techniques by comparing the model results with direct measurements of carbon monoxide both near-surface and airborne, as well as remote sensing derived products. The model results obtained using the 3BEM methodology of estimation introduced in this paper show relatively good agreement with the direct measurements and MOPITT data product, suggesting the reliability of the model at local to regional scales.

NMR quadrupolar system described as Bose-Einstein-condensate-like system

This paper presents a description of nuclear magnetic resonance (NMR) of quadrupolar systems using the Holstein-Primakoff (HP) formalism and its analogy with a Bose-Einstein condensate (BEC) system. Two nuclear spin systems constituted of quadrupolar nuclei I=3/2 ((23)Na) and I=7/2 ((133)Cs) in lyotropic liquid crystals were used for experimental demonstrations. Specifically, we derived the conditions necessary for accomplishing the analogy, executed the proper experiments, and compared with quantum mechanical prediction for a Bose system. The NMR description in the HP representation could be applied in the future as a workbench for BEC-like systems, where the statistical properties may be obtained using the intermediate statistic, first established by Gentile. The description can be applied for any quadrupolar systems, including new developed solid-state NMR GaAS nanodevices.