Development of an internationally agreed minimal dataset for juvenile dermatomyositis (JDM) for clinical and research use

Background: Juvenile dermatomyositis (JDM) is a rare autoimmune inflammatory disorder associated with significant morbidity and mortality. International collaboration is necessary to better understand the pathogenesis of the disease, response to treatment and long-term outcome. To aid international collaboration, it is essential to have a core set of data that all researchers and clinicians collect in a standardised way for clinical purposes and for research. This should include demographic details, diagnostic data and measures of disease activity, investigations and treatment. Variables in existing clinical registries have been compared to produce a provisional data set for JDM. We now aim to develop this into a consensus-approved minimum core dataset, tested in a wider setting, with the objective of achieving international agreement. Methods/Design: A two-stage bespoke Delphi-process will engage the opinion of a large number of key stakeholders through Email distribution via established international paediatric rheumatology and myositis organisations. This, together with a formalised patient/parent participation process will help inform a consensus meeting of international experts that will utilise a nominal group technique (NGT). The resulting proposed minimal dataset will be tested for feasibility within existing database infrastructures. The developed minimal dataset will be sent to all internationally representative collaborators for final comment. The participants of the expert consensus group will be asked to draw together these comments, ratify and 'sign off' the final minimal dataset. Discussion: An internationally agreed minimal dataset has the potential to significantly enhance collaboration, allow effective communication between groups, provide a minimal standard of care and enable analysis of the largest possible number of JDM patients to provide a greater understanding of this disease. The final approved minimum core dataset could be rapidly incorporated into national and international collaborative efforts, including existing prospective databases, and be available for use in randomised controlled trials and for treatment/protocol comparisons in cohort studies

Radiative Efficiency and Content of Extragalactic Radio Sources: Toward a Universal Scaling Relation Between Jet Power and Radio Power

We present an analysis of the energetics and particle content of the lobes of 24 radio galaxies at the cores of cooling clusters. The radio lobes in these systems have created visible cavities in the surrounding hot, X-ray-emitting gas, which allow direct measurement of the mechanical jet power of radio sources over six decades of radio luminosity, independently of the radio properties themselves. Using these measurements, we examine the ratio between radio power and total jet power (the radiative efficiency). We find that jet (cavity) power increases with radio synchrotron power approximately as P_jet ~ (L_radio)^beta, where 0.35 < beta < 0.70 depending on the bandpass of measurement and state of the source. However, the scatter about these relations caused by variations in radiative efficiency spans more than four orders of magnitude. After accounting for variations in synchrotron break frequency (age), the scatter is reduced by ~ 50%, yielding the most accurate scaling relation available between the lobe bolometric radio power and the jet (cavity) power. We place limits on the magnetic field strengths and particle content of the radio lobes using a variety of X-ray constraints. We find that the lobe magnetic field strengths vary between a few to several tens of microgauss depending on the age and dynamical state of the lobes. If the cavities are maintained in pressure balance with their surroundings and are supported by internal fields and particles in equipartition, the ratio of energy in electrons to heavy particles (k) must vary widely from approximately unity to 4000, consistent with heavy (hadronic) jets.Comment: 20 pages, 11 figures. Accepted for publication in Ap

Receptors for Hyaluronic Acid and Poliovirus: A Combinatorial Role in Glioma Invasion?

Background: CD44 has long been associated with glioma invasion while, more recently, CD155 has been implicated in playing a similar role. Notably, these two receptors have been shown closely positioned on monocytes. Methods and Findings: In this study, an up-regulation of CD44 and CD155 was demonstrated in established and earlypassage cultures of glioblastoma. Total internal reflected fluorescence (TIRF) microscopy revealed close proximity of CD44 and CD155. CD44 antibody blocking and gene silencing (via siRNA) resulted in greater inhibition of invasion than that for CD155. Combined interference resulted in 86 % inhibition of invasion, although in these investigations no obvious evidence of synergy between CD44 and CD155 in curbing invasion was shown. Both siRNA-CD44 and siRNA-CD155 treated cells lacked processes and were rounder, while live cell imaging showed reduced motility rate compared to wild type cells. Adhesion assay demonstrated that wild type cells adhered most efficiently to laminin, whereas siRNA-treated cells (p,0.0001 for both CD44 and CD155 expression) showed decreased adhesion on several ECMs investigated. BrdU assay showed a higher proliferation of siRNA-CD44 and siRNA-CD155 cells, inversely correlated with reduced invasion. Confocal microscopy revealed overlapping of CD155 and integrins (b1, avb1 and avb3) on glioblastoma cell processes whereas siRNAtransfected cells showed consequent reduction in integrin expression with no specific staining patterns. Reduced expression of Rho GTPases, Cdc42, Rac1/2/3, RhoA and RhoB, was seen in siRNA-CD44 and siRNA-CD155 cells. In contrast t

Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma

A pivotal role for starch in the reconfiguration of 14C-partitioning and allocation in Arabidopsis thaliana under short-term abiotic stress.

Plant carbon status is optimized for normal growth but is affected by abiotic stress. Here, we used 14C-labeling to provide the first holistic picture of carbon use changes during short-term osmotic, salinity, and cold stress in Arabidopsis thaliana. This could inform on the early mechanisms plants use to survive adverse environment, which is important for efficient agricultural production. We found that carbon allocation from source to sinks, and partitioning into major metabolite pools in the source leaf, sink leaves and roots showed both conserved and divergent responses to the stresses examined. Carbohydrates changed under all abiotic stresses applied; plants re-partitioned 14C to maintain sugar levels under stress, primarily by reducing 14C into the storage compounds in the source leaf, and decreasing 14C into the pools used for growth processes in the roots. Salinity and cold increased 14C-flux into protein, but as the stress progressed, protein degradation increased to produce amino acids, presumably for osmoprotection. Our work also emphasized that stress regulated the carbon channeled into starch, and its metabolic turnover. These stress-induced changes in starch metabolism and sugar export in the source were partly accompanied by transcriptional alteration in the T6P/SnRK1 regulatory pathway that are normally activated by carbon starvation

Chemical gradients in the Milky Way from the RAVE data

Aims. We aim at measuring the chemical gradients of the elements Mg, Al, Si, and Fe along the Galactic radius to provide new constraints on the chemical evolution models of the Galaxy and Galaxy models such as the Besancon model. Thanks to the large number of stars of our RAVE sample we can study how the gradients vary as function of the distance from the Galactic plane. Methods. We analysed three different samples selected from three independent datasets: a sample of 19 962 dwarf stars selected from the RAVE database, a sample of 10 616 dwarf stars selected from the Geneva-Copenhagen Survey (GCS) dataset, and a mock sample (equivalent to the RAVE sample) created by using the GALAXIA code, which is based on the Besancon model. The three samples were analysed by using the very same method for comparison purposes. We integrated the Galactic orbits and obtained the guiding radii (R-g) and the maximum distances from the Galactic plane reached by the stars along their orbits (Z(max)). We measured the chemical gradients as functions of R-g at different Z(max). Results. We found that the chemical gradients of the RAVE and GCS samples are negative and show consistent trends, although they are not equal: at Z(max) < 0.4 kpc and 4.5 < R-g(kpc) < 9.5, the iron gradient for the RAVE sample is d[Fe/H]/dR(g) = -0.065 dex kpc(-1), whereas for the GCS sample it is d[Fe/H]/dR(g) = -0.043 dex kpc(-1) with internal errors of +/-0.002 and +/-0.004 dex kpc(-1), respectively. The gradients of the RAVE and GCS samples become flatter at larger Z(max). Conversely, the mock sample has a positive iron gradient of d[Fe/H]/dR(g) = +0.053 +/- 0.003 dex kpc(-1) at Z(max) < 0.4 kpc and remains positive at any Z(max). These positive and unrealistic values originate from the lack of correlation between metallicity and tangential velocity in the Besancon model. In addition, the low metallicity and asymmetric drift of the thick disc causes a shift of the stars towards lower R-g and metallicity which, together with the thin-disc stars with a higher metallicity and R-g, generates a fictitious positive gradient of the full sample. The flatter gradient at larger Z(max) found in the RAVE and the GCS samples may therefore be due to the superposition of thin-and thick-disc stars, which mimicks a flatter or positive gradient. This does not exclude the possibility that the thick disc has no chemical gradient. The discrepancies between the observational samples and the mock sample can be reduced by i) decreasing the density; ii) decreasing the vertical velocity; and iii) increasing the metallicity of the thick disc in the Besancon model

Catalog of Radio Galaxies with z>0.3. I:Construction of the Sample

The procedure of the construction of a sample of distant ($z>0.3$) radio galaxies using NED, SDSS, and CATS databases for further application in statistical tests is described. The sample is assumed to be cleaned from objects with quasar properties. Primary statistical analysis of the list is performed and the regression dependence of the spectral index on redshift is found.Comment: 9 pages, 6 figures, 2 table