Antiepileptogenic effects of trilostane in the kainic acid model of temporal lobe epilepsy

Objective: Epileptogenesis after status epilepticus (SE) has a faster onset in rats treated to reduce brain levels of the anticonvulsant neurosteroid allopregnanolone with the 5α-reductase inhibitor finasteride; however, it still has to be evaluated whether treatments aimed at increasing allopregnanolone levels could result in the opposite effect of delaying epileptogenesis. This possibility could be tested using the peripherally active inhibitor of 3β-hydroxysteroid dehydrogenase/Δ5-4 isomerase trilostane, which has been shown repeatedly to increase allopregnanolone levels in the brain. Methods: Trilostane (50 mg/kg) was administered subcutaneously once daily for up to six consecutive days, starting 10 min after intraperitoneal administration of kainic acid (15 mg/kg). Seizures were evaluated by video-electrocorticographic recordings for 70 days maximum, and endogenous neurosteroid levels were assessed by liquid chromatography–electrospray tandem mass spectrometry. Immunohistochemical staining was performed to evaluate the presence of brain lesions. Results: Trilostane did not alter the latency of kainic acid-induced SE onset or its overall duration. When compared to the vehicle-treated group, rats receiving six daily trilostane injections presented a remarkable delay of the first spontaneous electrocorticographic seizure and subsequent tonic–clonic spontaneous recurrent seizures (SRSs). Conversely, rats treated with only the first trilostane injection during SE did not differ from vehicle-treated rats in developing the SRSs. Notably, trilostane did not modify neuronal cell densities or the overall damage in the hippocampus. In comparison to the vehicle group, repeated administration of trilostane significantly decreased the activated microglia morphology in the subiculum. As expected, allopregnanolone and other neurosteroid levels were remarkably increased in the hippocampus and neocortex of rats treated for 6 days with trilostane, but pregnanolone was barely detectable. Neurosteroids returned to basal levels after a week of trilostane washout.. Significance: Overall, these results suggest that trilostane led to a remarkable increase in allopregnanolone brain levels, which was associated with protracted effects on epileptogenesis

Finite bisimulations for switched linear systems

In this paper, we consider the problem of constructing a finite bisimulation quotient for a discrete-time switched linear system in a bounded subset of its state space. Given a set of observations over polytopic subsets of the state space and a switched linear system with stable subsystems, the proposed algorithm generates the bisimulation quotient in a finite number of steps with the aid of sublevel sets of a polyhedral Lyapunov function. Starting from a sublevel set that includes the origin in its interior, the proposed algorithm iteratively constructs the bisimulation quotient for the region bounded by any larger sublevel set. We show how this bisimulation quotient can be used for synthesis of switching laws and verification with respect to specifications given as syntactically co-safe Linear Temporal Logic formulae over the observed polytopic subsets

The importance of contextual aspects in the care for patients with functional somatic symptoms

Functional somatic symptoms refer to physical symptoms that cannot be (bio) medically explained. The pattern or clustering of such symptoms may lead to functional syndromes like chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome, among many others. Since the underlying pathophysiology remains unknown, several explanatory models have been proposed, nearly all including social and psychological parameters. These models have stimulated effectiveness studies of several psychological and psychopharmacological therapies. While the evidence for their effectiveness is steadily growing, effect-sizes are at most moderate and many patients do not benefit. We hypothesize that the context in which interventions for functional somatic symptoms are delivered substantially influences their effectiveness. Although this hypothesis is in line with explanatory models of functional somatic symptoms, to our knowledge, studies primarily focusing on the influence of contextual aspects on treatment outcome are scarce. Contextual research in the field of somatic symptoms has (irrespective whether these symptoms can be medically explained or not), however, just begun and already yielded some valuable results. These findings can be organized according to Duranti's and Goodwin's theoretical approach to context in order to substantiate our hypothesis. Based on this approach, we categorized empirical findings in three contextual aspects, i.e. 1) the setting, 2) the behavioural environment, and 3) the language environment. Collectively, some support is found for the fact that early identification of patients with functional somatic symptoms, starting treatment as soon as possible, having a neat appearance and an organized office interior, a warm and friendly nonverbal approach and a language use without defensiveness are contextual parameters which enhance the assessment by the patient of the physician's competence to help. Nonetheless, in vivo studies addressing the most aspects, i.e. nonverbal behaviour and language, are needed for better understanding of these contextual aspect. Moreover, future research should address to what extent optimizing contextual aspects improve care for functional somatic symptoms

Explanations for medically unexplained symptoms:a qualitative study on GPs in daily practice consultations

BACKGROUND: General practice is the centre of care for patients with medically unexplained symptoms (MUS). Providing explanations for MUS, i.e. making sense of symptoms, is considered to be an important part of care for MUS patients. However, little is known how general practitioners (GPs) do this in daily practice. OBJECTIVE: This study aimed to explore how GPs explain MUS to their patients during daily general practice consultations. METHODS: A thematic content analysis was performed of how GPs explained MUS to their patients based on 39 general practice consultations involving patients with MUS. RESULTS: GP provided explanations in nearly all consultations with MUS patients. Seven categories of explanation components emerged from the data: defining symptoms, stating causality, mentioning contributing factors, describing mechanisms, excluding explanations, discussing the severity of symptoms and normalizing symptoms. No pattern of how GPs constructed explanations with the various categories was observed. In general, explanations were communicated as a possibility and in a patient-specific way; however, they were not very detailed. CONCLUSION: Although explanations for MUS are provided in most MUS consultations, there seems room for improving the explanations given in these consultations. Further studies on the effectiveness of explanations and on the interaction between patients and GP in constructing these explanations are required in order to make MUS explanations more suitable in daily primary care practice

Secondary education reform in Lesotho and Zimbabwe and the needs of rural girls: Pronouncements, policy and practice

Analysis of the educational needs of rural girls in Lesotho and Zimbabwe suggests a number of shortcomings in the current form of secondary education, and ways in which it might be modified so as to serve this sizeable group of students better. Several of the shortcomings, notably in relation to curricular irrelevance and excessive focus on examinations, have long been recognised, including by politicians. Yet political pronouncements are seldom translated into policy, and even where policy is formulated, reforms are seldom implemented in schools. This paper makes use of interviews with educational decision-makers in the two southern African countries and a range of documentary sources to explore why, despite the considerable differences between the two contexts, much needed educational reforms have been implemented in neither

Finding Homogeneity in Heterogeneity—A New Approach to Quantifying Landscape Mosaics Developed for the Lao PDR

A key challenge for land change science in general and research on swidden agriculture in particular, is linking land cover information to human–environment interactions over larger spatial areas. In Lao PDR, a country facing rapid and multi-level land change processes, this hinders informed policy- and decision-making. Crucial information on land use types and people involved is still lacking. This article proposes an alternative approach for the description of landscape mosaics. Instead of analyzing local land use combinations, we studied land cover mosaics at a meso-level of spatial scale and interpreted these in terms of human–environmental interactions. These landscape mosaics were then overlaid with population census data. Results showed that swidden agricultural landscapes, involving 17% of the population, dominate 29% of the country, while permanent agricultural landscapes involve 74% of the population in 29% of the territory. Forests still form an important component of these landscape mosaics

An IAEA Multi-technique X-ray Spectrometry End-station at Elettra Sincrotrone Trieste: Benchmarking Results and Interdisciplinary Applications

The International Atomic Energy Agency (IAEA) jointly with the Elettra Sincrotrone Trieste (EST) operates a multipurpose X-ray spectrometry endstation at the X-ray Fluorescence beamline (10.1L). The facility has been available to external users since the beginning of 2015 through the peer-review process of EST. Using this collaboration framework, the IAEA supports and promotes synchrotron-radiation-based research and training activities for various research groups from the IAEA Member States, especially those who have limited previous experience and resources to access a synchrotron radiation facility. This paper aims to provide a broad overview about various analytical capabilities, intrinsic features and performance figures of the IAEA X-ray spectrometry endstation through the measured results. The IAEA-EST endstation works with monochromatic X-rays in the energy range 3.7-14keV for the Elettra storage ring operating at 2.0 or 2.4GeV electron energy. It offers a combination of different advanced analytical probes, e.g. X-ray reflectivity, X-ray absorption fine-structure measurements, grazing-incidence X-ray fluorescence measurements, using different excitation and detection geometries, and thereby supports a comprehensive characterization for different kinds of nanostructured and bulk materials.A broad overview of the various analytical capabilities, intrinsic features and performance figures of the IAEA X-ray spectrometry endstation operated at the X-ray Fluorescence beamline of Elettra Sincrotrone Trieste is given, and different applications are demonstrated to familiarize the user community with the applicable intersdisciplinary research.Fil: Karydas, A.. International Atomic Energy Agency; Austria. National Centre for Scientific Research "Demokritos"; GreciaFil: Czyzycki, M.. International Atomic Energy Agency; Austria. AGH University of Science and Technology. Faculty of Physics and Applied Computer Science ; PoloniaFil: Leani, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina. International Atomic Energy Agency; AustriaFil: Migliori, A.. International Atomic Energy Agency; Austria. Nuclear Spectrometry And Appications Lab, Iaea. Onu; AustriaFil: Osán, J.. Hungarian Academy of Sciences Centre for Energy Research; Hungría. International Atomic Energy Agency; AustriaFil: Bogovac, M.. International Atomic Energy Agency; AustriaFil: Wrobel, P.. AGH University of Science and Technology. Faculty of Physics and Applied Computer Science ; PoloniaFil: Vakula, N.. International Atomic Energy Agency; AustriaFil: Padilla Alvarez, R.. International Atomic Energy Agency; AustriaFil: Menk, Ralf Hendrik. Elettra-Sincrotrone Trieste SCpA di Interesse Nazionale; Italia. University of Saskatchewan; CanadáFil: Gol, M. G.. Iranian Light Source Facility; IránFil: Antonelli, M.. Istituto Nazionale di Fisica Nucleare; Italia. Elettra-Sincrotrone Trieste SCpA di Interesse Nazionale; ItaliaFil: Tiwari, M. K.. Raja Ramanna Centre for Advanced Technology; IndiaFil: Caliri, C.. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Vogel Mikuš, K.. Jozef Stefan Institute; Eslovenia. University of Ljubljana; EsloveniaFil: Darby, I.. Elettra-Sincrotrone Trieste SCpA di Interesse Nazionale; Italia. International Atomic Energy Agency; AustriaFil: Kaiser, R.. International Atomic Energy Agency; Austri

When is an optimization not an optimization? Evaluation of clinical implications of information content (signal-to-noise ratio) in optimization of cardiac resynchronization therapy, and how to measure and maximize it

Impact of variability in the measured parameter is rarely considered in designing clinical protocols for optimization of atrioventricular (AV) or interventricular (VV) delay of cardiac resynchronization therapy (CRT). In this article, we approach this question quantitatively using mathematical simulation in which the true optimum is known and examine practical implications using some real measurements. We calculated the performance of any optimization process that selects the pacing setting which maximizes an underlying signal, such as flow or pressure, in the presence of overlying random variability (noise). If signal and noise are of equal size, for a 5-choice optimization (60, 100, 140, 180, 220 ms), replicate AV delay optima are rarely identical but rather scattered with a standard deviation of 45 ms. This scatter was overwhelmingly determined (ρ = −0.975, P < 0.001) by Information Content, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\frac{\text{Signal}}{{{\text{Signal}} + {\text{Noise}}}}}$$\end{document}, an expression of signal-to-noise ratio. Averaging multiple replicates improves information content. In real clinical data, at resting, heart rate information content is often only 0.2–0.3; elevated pacing rates can raise information content above 0.5. Low information content (e.g. <0.5) causes gross overestimation of optimization-induced increment in VTI, high false-positive appearance of change in optimum between visits and very wide confidence intervals of individual patient optimum. AV and VV optimization by selecting the setting showing maximum cardiac function can only be accurate if information content is high. Simple steps to reduce noise such as averaging multiple replicates, or to increase signal such as increasing heart rate, can improve information content, and therefore viability, of any optimization process

Spectral density and Sobolev inequalities for pure and mixed states

We prove some general Sobolev-type and related inequalities for positive operators A of given ultracontractive spectral decay, without assuming e^{-tA} is submarkovian. These inequalities hold on functions, or pure states, as usual, but also on mixed states, or density operators in the quantum mechanical sense. This provides universal bounds of Faber-Krahn type on domains, that apply to their whole Dirichlet spectrum distribution, not only the first eigenvalue. Another application is given to relate the Novikov-Shubin numbers of coverings of finite simplicial complexes to the vanishing of the torsion of some l^{p,2}-cohomology

A survey of free software for the design, analysis, modelling, and simulation of an unmanned aerial vehicle

The objective of this paper is to analyze free software for the design, analysis, modelling, and simulation of an unmanned aerial vehicle (UAV). Free software is the best choice when the reduction of production costs is necessary; nevertheless, the quality of free software may vary. This paper probably does not include all of the free software, but tries to describe or mention at least the most interesting programs. The first part of this paper summarizes the essential knowledge about UAVs, including the fundamentals of flight mechanics and aerodynamics, and the structure of a UAV system. The second section generally explains the modelling and simulation of a UAV. In the main section, more than 50 free programs for the design, analysis, modelling, and simulation of a UAV are described. Although the selection of the free software has been focused on small subsonic UAVs, the software can also be used for other categories of aircraft in some cases; e.g. for MAVs and large gliders. The applications with an historical importance are also included. Finally, the results of the analysis are evaluated and discussed—a block diagram of the free software is presented, possible connections between the programs are outlined, and future improvements of the free software are suggested. © 2015, CIMNE, Barcelona, Spain.Internal Grant Agency of Tomas Bata University in Zlin [IGA/FAI/2015/001, IGA/FAI/2014/006