Thalidomide in the treatment of erythema nodosum leprosum (ENL): systematic review of clinical trials and prospects of new investigations

FUNDAMENTOS: A hanseníase persiste como problema de saúde pública, e episódios de ENH são eventos agudos que ocorrem antes, durante e após PQT. Na última década, o uso da talidomida como agente imunomodulador foi expandido a outras doenças. OBJETIVOS: realizar revisão sistemática dos ensaios clínicos publicados sobre a eficácia e efeitos colaterais da talidomida no ENH. Descrever metodologia e resultados da triagem para recrutamento de ensaio clínico visando avaliar dose-resposta da talidomida seguida de desmame no ENH moderado e grave, realizado no Brasil. MÉTODOS: Analisaram-se ensaios publicados sobre talidomida no ENH. Foi delineado um ensaio clínico duplo-cego randomizado para avaliar dose de 100 thalid 300mg/dia de talidomida durante fase aguda de ENH, seguida de desmame da talidomida, thalid placebo. Para este ensaio clínico descreve-se metodologia e dados de recrutamento de pacientes, com ênfase na gravidade dos episódios de ENH. RESULTADOS: Os seis ensaios clínicos publicados nas décadas de 1960 e 1970 apontam para o benefício da talidomida no ENH, embora diferenças metodológicas dificultem a comparação. Na fase de recrutamento do ensaio brasileiro, dos 143 pacientes de ENH triados, 65% eram potencialmente elegíveis. A associação com neurite em 56,4% dos ENH moderados e graves exigiu co-intervenção com corticosteróide. CONCLUSÃO: O padrão de recrutamento dos pacientes evidenciou alta freqüência de neurite nos episódios de ENH. O esquema de talidomida isolada no ENH foi avaliado como infreqüente na prática clínica brasileira. O desafio atual é acumular evidências sobre a eficácia e efeitos colaterais da talidomida em associação com corticosteróides.BACKGROUND: Leprosy remains a public health problem. Episodes of erythema nodosum leprosum (ENL) are acute events that occur before, during and after polychemotherapy. In the last decade, the use of thalidomide as an immunomodulating agent was expanded to other diseases. OBJECTIVES: To perform a systematic review of published clinical trials on efficacy and side effects of thalidomide in ENL. To describe the methodology and screening results of recruiting for a clinical trial performed in Brazil, which aimed to assess the dose-response of thalidomide followed by tapering regimen in severe and moderate cases of ENL. METHODS: Published clinical trials on the use of thalidomide in ENL were analyzed. A randomized, double-blind clinical trial was designed to evaluate the doses of 100mg versus 300mg/day thalidomide during the acute stage of ENL, followed by thalidomide tapering regimen versus placebo. For this clinical trial, the methodology and data for enrollment of patients were described, with an emphasis on severity of ENL episodes. RESULTS: Six clinical trials published in the 1960's and 1970's indicated the benefits of thalidomide in ENL, although methodological differences made comparison difficult. In the enrollment stage of the Brazilian trial, 65% of patients were potentially eligible out of 143 ENL patients screened. The association with neuritis in 56.4% of moderate and severe cases of ENL required the co-intervention with steroids. CONCLUSION: The patients' enrollment pattern demonstrated high frequency of neuritis in ENL episodes. The treatment regimen with thalidomide in monotherapy for ENL was considered infrequent in the clinical practice in Brazil. The current challenge is to accumulate evidence about efficacy and side effects of thalidomide in combination with steroids

Status of the Development Program of a 60 kA HTSC current lead for the ITER Toroidal Field Coils

In the frame of the European Fusion Technology Programme, FZK Karlsruhe and CRPP Villigen have started a development program for design and construction of a 60 kA current lead for the ITER Toroidal Field Coils using High Temperature Superconductors. The task composes of four parts: material selection based on test results of 1 kA current leads, construction and test of a 10 kA and a 20 kA lead using the selected HTSC material giving proof of the modularity and scale-ability of the design, and finally construction and test of a 60 kA current lead which will replace an existing conventional lead in the TOSKA facility at FZK. As result of part one, Bi2223 tapes electrically stabilized by AgAu material was selected for the further development program. Two 10 kA HTSC modules have been manufactured in industry resp. are being fabricated in the laboratory using different conductor designs. The paper describes the status of the development program. Experimental results of the first step and f..

Distributed Keyword Search over RDF via MapReduce

Non expert users need support to access linked data available on the Web. To this aim, keyword-based search is considered an essential feature of database systems. The distributed nature of the Semantic Web demands query processing techniques to evolve towards a scenario where data is scattered on distributed data stores. Existing approaches to keyword search cannot guarantee scalability in a distributed environment, because, at runtime, they are unaware of the location of the relevant data to the query and thus, they cannot optimize join tasks. In this paper, we illustrate a novel distributed approach to keyword search over RDF data that exploits the MapReduce paradigm by switching the problem from graph-parallel to data-parallel processing. Moreover, our framework is able to consider ranking during the building phase to return directly the best (top-k) answers in the first (k) generated results, reducing greatly the overall computational load and complexity. Finally, a comprehensive evaluation demonstrates that our approach exhibits very good efficiency guaranteeing high level of accuracy, especially with respect to state-of-the-art competitors

A Human-Inspired Model to Represent Uncertain Knowledge in the Semantic Web

© 2018, Springer International Publishing AG, part of Springer Nature. One of the most evident and well-known limitations of the Semantic Web technology is its lack of capability to deal with uncertain knowledge. As uncertainty is often part of the knowledge itself or can be inducted by external factors, such a limitation may be a serious barrier for some practical applications. A number of approaches have been proposed to extend the capabilities in terms of uncertainty representation; some of them are just theoretical or not compatible with the current semantic technology; others focus exclusively on data spaces in which uncertainty is or can be quantified. Human-inspired models have been adopted in the context of different disciplines and domains (e.g. robotics and human-machine interaction) and could be a novel, still largely unexplored, pathway to represent uncertain knowledge in the Semantic Web. Human-inspired models are expected to address uncertainties in a way similar to the human one. Within this paper, we (i) briefly point out the limitations of the Semantic Web technology in terms of uncertainty representation, (ii) discuss the potentialities of human-inspired solutions to represent uncertain knowledge in the Semantic Web, (iii) present a human-inspired model and (iv) a reference architecture for implementations in the context of the legacy technology

The role of self-absorption in luminescent solar concentrators

Self-absorption or re-absorption of light by luminescent centers is a major loss mechanism in the luminescent solar concentrator (LSC). It leads to non-radiative energy losses governed by the luminescence quantum efficiency and radiative losses through escape cones. We have investigated the role of self-absorption in small (about 5cm x 5cm x 1mm) LSC samples containing nanorods. These samples were illuminated with a small laser spot, and position dependent measurements of the photocurrent and the emission spectrum were carried out. These measurements showed a rapid decrease in the LSC output with the distance of the illumination spot, which emphasizes the significance of self-absorption losses. A computational raytrace model was applied to simulate the experiment, and a good agreement with the experimental measurement was found

Luminescent solar concentrators - a review of recent results

Luminescent solar concentrators (LSCs) generally consist of transparent polymer sheets doped with luminescent species. Incident sunlight is absorbed by the luminescent species and emitted with high quantum efficiency, such that emitted light is trapped in the sheet and travels to the edges where it can be collected by solar cells. LSCs offer potentially lower cost per Wp. This paper reviews results mainly obtained within the framework of the Fullspectrum project. Two modeling approaches are presented, i.e., a thermodynamic and a ray-trace one, as well as experimental results, with a focus on LSC stability