Randomised controlled trial of gabapentin in Complex Regional Pain Syndrome type 1 [ISRCTN84121379]

BACKGROUND: Complex Regional Pain Syndrome type one (CRPS I) or formerly Reflex Sympathetic Dystrophy (RSD) is a disabling syndrome, in which a painful limb is accompanied by varying symptoms. Neuropathic pain is a prominent feature of CRPS I, and is often refractory to treatment. Since gabapentin is an anticonvulsant with a proven analgesic effect in various neuropathic pain syndromes, we sought to study the efficacy of the anticonvulsant gabapentin as treatment for pain in patients with CRPS I. METHODS: We did a randomized double blind placebo controlled crossover study with two three-weeks treatment periods with gabapentin and placebo separated by a two-weeks washout period. Patients started at random with gabapentin or placebo, which was administered in identical capsules three times daily. We included 58 patients with CRPS type 1. RESULTS: Patients reported significant pain relief in favor of gabapentin in the first period. Therapy effect in the second period was less; finally resulting in no significant effect combining results of both periods. The CRPS patients had sensory deficits at baseline. We found that this sensory deficit was significantly reversed in gabapentin users in comparison to placebo users. CONCLUSIONS: Gabapentin had a mild effect on pain in CRPS I. It significantly reduced the sensory deficit in the affected limb. A subpopulation of CRPS patients may benefit from gabapentin

Isotropy of the velocity of light and the Sagnac effect

In this paper, it is shown, using a geometrical approach, the isotropy of the velocity of light measured in a rotating frame in Minkowski space-time, and it is verified that this result is compatible with the Sagnac effect. Furthermore, we find that this problem can be reduced to the solution of geodesic triangles in a Minkowskian cylinder. A relationship between the problems established on the cylinder and on the Minkowskian plane is obtained through a local isometry.Comment: LaTeX, 13 pages, 3 eps figures; typos corrected, added references, minor changes; to appear in "Relativity in Rotating Frames", ed. G. Rizzi G. and M.L. Ruggiero, Kluwer Academic Publishers, Dordrecht (2003

Solar Wind and its Evolution

By using our previous results of magnetohydrodynamical simulations for the solar wind from open flux tubes, I discuss how the solar wind in the past is different from the current solar wind. The simulations are performed in fixed one-dimensional super-radially open magnetic flux tubes by inputing various types of fluctuations from the photosphere, which automatically determines solar wind properties in a forward manner. The three important parameters which determine physical properties of the solar wind are surface fluctuation, magnetic field strengths, and the configuration of magnetic flux tubes. Adjusting these parameters to the sun at earlier times in a qualitative sense, I infer that the quasi-steady-state component of the solar wind in the past was denser and slightly slower if the effect of the magneto-centrifugal force is not significant. I also discuss effects of magneto-centrifugal force and roles of coronal mass ejections.Comment: 6 pages, 1 figure, Earth, Planets, & Space in press (based on 5th Alfven Conference) correction of discussion on a related pape

LifeCLEF 2016: Multimedia Life Species Identification Challenges

International audienceUsing multimedia identification tools is considered as one of the most promising solutions to help bridge the taxonomic gap and build accurate knowledge of the identity, the geographic distribution and the evolution of living species. Large and structured communities of nature observers (e.g., iSpot, Xeno-canto, Tela Botanica, etc.) as well as big monitoring equipment have actually started to produce outstanding collections of multimedia records. Unfortunately, the performance of the state-of-the-art analysis techniques on such data is still not well understood and is far from reaching real world requirements. The LifeCLEF lab proposes to evaluate these challenges around 3 tasks related to multimedia information retrieval and fine-grained classification problems in 3 domains. Each task is based on large volumes of real-world data and the measured challenges are defined in collaboration with biologists and environmental stakeholders to reflect realistic usage scenarios. For each task, we report the methodology, the data sets as well as the results and the main outcom

In silico assessment of potential druggable pockets on the surface of α1-Antitrypsin conformers

The search for druggable pockets on the surface of a protein is often performed on a single conformer, treated as a rigid body. Transient druggable pockets may be missed in this approach. Here, we describe a methodology for systematic in silico analysis of surface clefts across multiple conformers of the metastable protein α1-antitrypsin (A1AT). Pathological mutations disturb the conformational landscape of A1AT, triggering polymerisation that leads to emphysema and hepatic cirrhosis. Computational screens for small molecule inhibitors of polymerisation have generally focused on one major druggable site visible in all crystal structures of native A1AT. In an alternative approach, we scan all surface clefts observed in crystal structures of A1AT and in 100 computationally produced conformers, mimicking the native solution ensemble. We assess the persistence, variability and druggability of these pockets. Finally, we employ molecular docking using publicly available libraries of small molecules to explore scaffold preferences for each site. Our approach identifies a number of novel target sites for drug design. In particular one transient site shows favourable characteristics for druggability due to high enclosure and hydrophobicity. Hits against this and other druggable sites achieve docking scores corresponding to a Kd in the µM–nM range, comparing favourably with a recently identified promising lead. Preliminary ThermoFluor studies support the docking predictions. In conclusion, our strategy shows considerable promise compared with the conventional single pocket/single conformer approach to in silico screening. Our best-scoring ligands warrant further experimental investigation

Digital PCR methods improve detection sensitivity and measurement precision of low abundance mtDNA deletions

Mitochondrial DNA (mtDNA) mutations are a common cause of primary mitochondrial disorders, and have also been implicated in a broad collection of conditions, including aging, neurodegeneration, and cancer. Prevalent among these pathogenic variants are mtDNA deletions, which show a strong bias for the loss of sequence in the major arc between, but not including, the heavy and light strand origins of replication. Because individual mtDNA deletions can accumulate focally, occur with multiple mixed breakpoints, and in the presence of normal mtDNA sequences, methods that detect broad-spectrum mutations with enhanced sensitivity and limited costs have both research and clinical applications. In this study, we evaluated semi-quantitative and digital PCR-based methods of mtDNA deletion detection using double-stranded reference templates or biological samples. Our aim was to describe key experimental assay parameters that will enable the analysis of low levels or small differences in mtDNA deletion load during disease progression, with limited false-positive detection. We determined that the digital PCR method significantly improved mtDNA deletion detection sensitivity through absolute quantitation, improved precision and reduced assay standard error

‘Warrant’ revisited: Integrating mathematics teachers’ pedagogical and epistemological considerations into Toulmin’s model for argumentation

In this paper, we propose an approach to analysing teacher arguments that takes into account field dependence—namely, in Toulmin’s sense, the dependence of warrants deployed in an argument on the field of activity to which the argument relates. Freeman, to circumvent issues that emerge when we attempt to determine the field(s) that an argument relates to, proposed a classification of warrants (a priori, empirical, institutional and evaluative). Our approach to analysing teacher arguments proposes an adaptation of Freeman’s classification that distinguishes between: epistemological and pedagogical a priori warrants, professional and personal empirical warrants, epistemological and curricular institutional warrants, and evaluative warrants. Our proposition emerged from analyses conducted in the course of a written response and interview study that engages secondary mathematics teachers with classroom scenarios from the mathematical areas of analysis and algebra. The scenarios are hypothetical, grounded on seminal learning and teaching issues, and likely to occur in actual practice. To illustrate our proposed approach to analysing teacher arguments here, we draw on the data we collected through the use of one such scenario, the Tangent Task. We demonstrate how teacher arguments, not analysed for their mathematical accuracy only, can be reconsidered, arguably more productively, in the light of other teacher considerations and priorities: pedagogical, curricular, professional and personal

Young neutron stars with soft gamma ray emission and anomalous X-ray pulsar

The observational properties of Soft Gamma Repeaters and Ano\-malous X-ray Pulsars (SGR/AXP) indicate to necessity of the energy source different from a rotational energy of a neutron star. The model, where the source of the energy is connected with a magnetic field dissipation in a highly magnetized neutron star (magnetar) is analyzed. Some observational inconsistencies are indicated for this interpretation. The alternative energy source, connected with the nuclear energy of superheavy nuclei stored in the nonequilibrium layer of low mass neutron star is discussed.Comment: 29 pages, 13 figures, Springer International Publishing Switzerland 2016 A.W. Alsabti, P. Murdin (eds.), Handbook of Supernova