Non-linear magnetohydrodynamic simulations of density evolution in Tore Supra sawtoothing plasmas

The plasma density evolution in sawtooth regime on the Tore Supra tokamak is analyzed. The density is measured using fast-sweeping X-mode reflectometry which allows tomographic reconstructions. There is evidence that density is governed by the perpendicular electric flows, while temperature evolution is dominated by parallel diffusion. Postcursor oscillations sometimes lead to the formation of a density plateau, which is explained in terms of convection cells associated with the kink mode. A crescent-shaped density structure located inside q = 1 is often visible just after the crash and indicates that some part of the density withstands the crash. 3D full MHD nonlinear simulations with the code XTOR-2F recover this structure and show that it arises from the perpendicular flows emerging from the reconnection layer. The proportion of density reinjected inside the q = 1 surface is determined, and the implications in terms of helium ash transport are discussed. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4766893]

The Seville Expert Workshop for Progress in Posttransplant Lymphoproliferative Disorders

Posttransplant lymphoproliferative disorders (PTLDs) are associated with significant morbidity and mortality among solid-organ transplant patients, but approaches to diagnosis and management vary considerably. An international multidisciplinary panel evaluated current understanding of risk factors and classification systems and developed recommendations to aid in PTLD prevention. We considered evidence on PTLD risk factors including Epstein- Barr virus serostatus and immunosuppression and identified knowledge gaps for future research. Recommendations address prophylactic and preemptive strategies to minimize PTLD development, including modulation of immunosuppression and antiviral drug regimens. Finally, new classification criteria were outlined that may help facilitate standardized reporting and improve our understanding of PTLD.

An anatomical analysis of the mini-modified orbitozygomatic and supra-orbital approaches

Seven sides of cadaver heads were used to compare the surgical exposures provided by the mini-modified orbitozygomatic (MOz) and supra-orbital (SO) approaches. The Optotrak 3020 computerized tracking system (Northern Digital, Waterloo, ON, Canada) was utilized to evaluate the area of anatomical exposure defined by six points: (1) ipsilateral sphenoid ridge; (2) most distal point of the ipsilateral middle cerebral artery (MCA); (3) most distal point of the ipsilateral posterior cerebral artery (PCA); (4) most distal point of the contralateral PCA; (5) most distal point of the contralateral MCA; and (6) contralateral sphenoid ridge. Additionally, angles of approach for the ipsilateral MCA bifurcation, ipsilateral ICA bifurcation, basilar artery tip, contralateral MCA and ICA bifurcation and anterior communicating artery (AcomA) were evaluated, first for SO and then for MOz. An image guidance system was used to evaluate the limits of surgical exposure. No differences in the area of surgical exposure were noted (p > 0.05). Vertical angles were significantly wider for the ipsilateral and contralateral ICA bifurcation, AcomA, contralateral MCA and basilar tip (p < 0.05) for MOz. No differences in horizontal angles were observed between the approaches for the six targets (p > 0.05). There were no differences in the limits of exposure. MOz affords no additional surgical working space. However, our results demonstrate systematically that vertical exposure is improved. The MOz should be performed while planning an approach to these regions and a wider exposure in the vertical axis is needed. (C) 2012 Elsevier Ltd. All rights reserved.

Towards a precise test for malaria diagnosis in the Brazilian Amazon: comparison among field microscopy, a rapid diagnostic test, nested PCR, and a computational expert system based on artificial neural networks

Abstract Background Accurate malaria diagnosis is mandatory for the treatment and management of severe cases. Moreover, individuals with asymptomatic malaria are not usually screened by health care facilities, which further complicates disease control efforts. The present study compared the performances of a malaria rapid diagnosis test (RDT), the thick blood smear method and nested PCR for the diagnosis of symptomatic malaria in the Brazilian Amazon. In addition, an innovative computational approach was tested for the diagnosis of asymptomatic malaria. Methods The study was divided in two parts. For the first part, passive case detection was performed in 311 individuals with malaria-related symptoms from a recently urbanized community in the Brazilian Amazon. A cross-sectional investigation compared the diagnostic performance of the RDT Optimal-IT, nested PCR and light microscopy. The second part of the study involved active case detection of asymptomatic malaria in 380 individuals from riverine communities in Rondônia, Brazil. The performances of microscopy, nested PCR and an expert computational system based on artificial neural networks (MalDANN) using epidemiological data were compared. Results Nested PCR was shown to be the gold standard for diagnosis of both symptomatic and asymptomatic malaria because it detected the major number of cases and presented the maximum specificity. Surprisingly, the RDT was superior to microscopy in the diagnosis of cases with low parasitaemia. Nevertheless, RDT could not discriminate the Plasmodium species in 12 cases of mixed infections (Plasmodium vivax + Plasmodium falciparum). Moreover, the microscopy presented low performance in the detection of asymptomatic cases (61.25% of correct diagnoses). The MalDANN system using epidemiological data was worse that the light microscopy (56% of correct diagnoses). However, when information regarding plasma levels of interleukin-10 and interferon-gamma were inputted, the MalDANN performance sensibly increased (80% correct diagnoses). Conclusions An RDT for malaria diagnosis may find a promising use in the Brazilian Amazon integrating a rational diagnostic approach. Despite the low performance of the MalDANN test using solely epidemiological data, an approach based on neural networks may be feasible in cases where simpler methods for discriminating individuals below and above threshold cytokine levels are available.

Transcriptional effects of 1,25 dihydroxyvitamin D3 physiological and supra-physiological concentrations in breast cancer organotypic culture

Background Vitamin D transcriptional effects were linked to tumor growth control, however, the hormone targets were determined in cell cultures exposed to supra physiological concentrations of 1,25(OH)2D3 (50-100nM). Our aim was to evaluate the transcriptional effects of 1,25(OH)2D3 in a more physiological model of breast cancer, consisting of fresh tumor slices exposed to 1,25(OH)2D3 at concentrations that can be attained in vivo. Methods Tumor samples from post-menopausal breast cancer patients were sliced and cultured for 24 hours with or without 1,25(OH)2D3 0.5nM or 100nM. Gene expression was analyzed by microarray (SAM paired analysis, FDR≤0.1) or RT-qPCR (p≤0.05, Friedman/Wilcoxon test). Expression of candidate genes was then evaluated in mammary epithelial/breast cancer lineages and cancer associated fibroblasts (CAFs), exposed or not to 1,25(OH)2D3 0.5nM, using RT-qPCR, western blot or immunocytochemistry. Results 1,25(OH)2D3 0.5nM or 100nM effects were evaluated in five tumor samples by microarray and seven and 136 genes, respectively, were up-regulated. There was an enrichment of genes containing transcription factor binding sites for the vitamin D receptor (VDR) in samples exposed to 1,25(OH)2D3 near physiological concentration. Genes up-modulated by both 1,25(OH)2D3 concentrations were CYP24A1, DPP4, CA2, EFTUD1, TKTL1, KCNK3. Expression of candidate genes was subsequently evaluated in another 16 samples by RT-qPCR and up-regulation of CYP24A1, DPP4 and CA2 by 1,25(OH)2D3 was confirmed. To evaluate whether the transcripitonal targets of 1,25(OH)2D3 0.5nM were restricted to the epithelial or stromal compartments, gene expression was examined in HB4A, C5.4, SKBR3, MDA-MB231, MCF-7 lineages and CAFs, using RT-qPCR. In epithelial cells, there was a clear induction of CYP24A1, CA2, CD14 and IL1RL1. In fibroblasts, in addition to CYP24A1 induction, there was a trend towards up-regulation of CA2, IL1RL1, and DPP4. A higher protein expression of CD14 in epithelial cells and CA2 and DPP4 in CAFs exposed to 1,25(OH)2D3 0.5nM was detected. Conclusions In breast cancer specimens a short period of 1,25(OH)2D3 exposure at near physiological concentration modestly activates the hormone transcriptional pathway. Induction of CYP24A1, CA2, DPP4, IL1RL1 expression appears to reflect 1,25(OH)2D3 effects in epithelial as well as stromal cells, however, induction of CD14 expression is likely restricted to the epithelial compartment.

Niemann-Pick disease type C symptomatology: an expert-based clinical description

Niemann-Pick disease type C (NP-C) is a rare, progressive, irreversible disease leading to disabling neurological manifestations and premature death. The estimated disease incidence is 1:120,000 live births, but this likely represents an underestimate, as the disease may be under-diagnosed due to its highly heterogeneous presentation. NP-C is characterised by visceral, neurological and psychiatric manifestations that are not specific to the disease and that can be found in other conditions. The aim of this review is to provide non-specialists with an expert-based, detailed description of NP-C signs and symptoms, including how they present in patients and how they can be assessed. Early disease detection should rely on seeking a combination of signs and symptoms, rather than isolated findings. Examples of combinations which are strongly suggestive of NP-C include: splenomegaly and vertical supranuclear gaze palsy (VSGP); splenomegaly and clumsiness; splenomegaly and schizophrenia-like psychosis; psychotic symptoms and cognitive decline; and ataxia with dystonia, dysarthria/dysphagia and cognitive decline. VSGP is a hallmark of NP-C and becomes highly specific of the disease when it occurs in combination with other manifestations (e.g. splenomegaly, ataxia). In young infants (<2 years), abnormal saccades may first manifest as slowing and shortening of upward saccades, long before gaze palsy onset. While visceral manifestations tend to predominate during the perinatal and infantile period (2 months–6 years of age), neurological and psychiatric involvement is more prominent during the juvenile/adult period (>6 years of age). Psychosis in NP-C is atypical and variably responsive to treatment. Progressive cognitive decline, which always occurs in patients with NP-C, manifests as memory and executive impairment in juvenile/adult patients. Disease prognosis mainly correlates with the age at onset of the neurological signs, with early-onset forms progressing faster. Therefore, a detailed and descriptive picture of NP-C signs and symptoms may help improve disease detection and early diagnosis, so that therapy with miglustat (Zavesca®), the only available treatment approved to date, can be started as soon as neurological symptoms appear, in order to slow disease progression.

Pedagogização do pedagógico: sobre o jogo do expert no governamento docente

O artigo objetiva colocar em causa a razão imanente entre as práticas educacionais atuais e o âmbito da governamentalidade, por meio da problematização dos processos de pedagogização aí levados a cabo. Mais especificamente, visa analisar o jogo do expert como modalidade privilegiada do governamento docente na atualidade. Para tanto, toma como objeto empírico entrevistas concedidas por especialistas à revista Nova Escola entre 2005 e 2009. A discussão indica uma espécie de saturação pedagogizante do campo escolar, sempre com vistas a um (auto)governamento flexível, porém obstinado, das condutas docentes, operando a reboque da autoridade indefectível do expert, da lógica da desqualificação/requalificação profissional e da apologia da formação permanente, as quais, somadas, redundarão numa acirrada pedagogização do pedagógico