Template for Developing Guidelines for the Evaluation of the Clinical Efficacy of Psychophysiological Interventions

An essential function of both the Association for Applied Psychophysiology and Biofeedback (AAPB) and the Society for Neuronal Regulation (SNR) is the systematic evaluation of psychophysiological interventions that have been developed for the treatment of medical and psychiatric disorders. In order to address scientific concerns regarding the efficacy of specific clinical applications of biofeedback, these two societies formed and Efficacy Task Force. The process to be used in the assessment of treatment efficacy, specificity and clinical utility is presented in the form of a template that will serve as the foundation for a series of scientific reviews and practice guidlines to be published by both societies

Deconstructing interventions: approaches to studying behavior change techniques across obesity interventions

Deconstructing interventions into the specific techniques that are used to change behavior represents a new frontier in behavioral intervention research. This paper considers opportunities and challenges in employing the Behavior Change Techniques Taxonomy (BCTTv1) developed by Michie and colleagues, to code the behavior change techniques (BCTs) across multiple interventions addressing obesity and capture dose received at the technique level. Numerous advantages were recognized for using a shared framework for intervention description. Coding interventions at levels of the social ecological framework beyond the individual level, separate coding for behavior change initiation vs. maintenance, fidelity of BCT delivery, accounting for BCTs mode of delivery, and tailoring BCTs, present both challenges and opportunities. Deconstructing interventions and identifying the dose required to positively impact health-related outcomes could enable important gains in intervention science

The nature of the X-ray halo of the plerion G21.5-0.9 unveiled by XMM-Newton and Chandra

The nature of the radio-quiet X-ray halo around the plerionic SNR G21.5-0.9 is under debate. On the basis of spatial and spectral analysis of a large Chandra and XMM-Newton dataset of this source, we have developed a self-consistent scenario which explains all the observational features. We found that the halo is composed by diffuse extended emission due to dust scattering of X-rays from the plerion, by a bright limb which traces particle acceleration in the fast forward shock of the remnant, and by a bright spot (the ``North Spur'') which may be a knot of ejecta in adiabatic expansion. By applying a model of interaction between the PWN, the SNR and supernova environment, we argue that G21.5-0.9 progenitor may be of Type IIP or Ib/Ic, and that the remnant may be young (200-1000 yr).Comment: 11 pages, 10 figures, accepted by A&A, also avalaible at http://www.astropa.unipa.it/Library/OAPA_preprints/fb2870.ps.g

Inter- and intra-rater reliabilities of the Beighton Score compared to the Contompasis Score to assess Generalised Joint Hypermobility

Objectives: Generalized Joint Hypermobility [GJH] is a common connective tissue disorder associated with a range of musculoskeletal complaints. An effective screening tool to assess GJH may influence our understanding and choice of management. Diagnosis is clinical, using tools such as the Beighton Hypermobility Score and the Contompasis Scoring System. The comparable reliability of these tools has not been previously reported. The aim of the present study was to compare the intra- and the inter-rater reliability of the Beighton Score to the Contompasis Score to assess GJH. Methods: This was an observational study assessing 36 pain-free participants; 27 females and nine males; aged 18–32 years. Participants were assessed in random order, by two researchers over two sessions to determine intra- and inter-rater analyses. Intraclass Correlation Coefficient [ICC] and weighted Kappa statistics were used to calculate the level of agreement. Results: The intra- [ICC: 0.71–0.82] and the inter- [ICC: 0.72–0.80] rater reliability of the Beighton Score was substantial to almost perfect. The Contompasis Score displayed substantial to almost perfect intra-rater [ICC: 0.73–0.82] reliability and moderate to substantial inter-rater [ICC: 0.58–0.62] reliability. Conclusions: The present study provides an indication of the measurement capabilities of the Beighton and Contompasis Scores. The Beighton score appears to be superior compared with the Contompasis score particularly based on inter-rater reliability

Hard X-ray observations of PSR J1833-1034 and its associated pulsar wind nebula

PSR J1833-1034 and its associated Pulsar Wind Nebula (PWN) has been investigated in depth through X-ray observations ranging from 0.1 to 200 keV. The low energy X-ray data from Chandra reveal a complex morphology that is characterised by a bright central plerion, no thermal shell and an extended diffuse halo. The spectral emission from the central plerion softens with radial distance from the pulsar, with the spectral index ranging from $\Gamma$ = 1.61 in the central region to $\Gamma$ =2.36 at the edge of the PWN. At higher energy INTEGRAL detected the source in the 17--200 keV range. The data analysis clearly shows that the main contribution to the spectral emission in the hard X-ray energy range is originated from the PWN, while the pulsar is dominant above 200 keV. Recent HESS observations in the high energy gamma-ray domain show that PSR J1833-1034 is a bright TeV emitter, with a flux corresponding to $\sim$2 per cent of the Crab in 1--10 TeV range. In addition the spectral shape in the TeV energy region matches well with that in the hard X-rays observed by INTEGRAL. Based on these findings, we conclude that the emission from the pulsar and its associated PWN can be described in a scenario where hard X-rays are produced through synchrotron light of electrons with Lorentz factor $\gamma\sim10^{9}$ in a magnetic field of $\sim$10 micro Gauss. In this hypothesis the TeV emission is due to Inverse Compton interaction of the cooled electrons off the Cosmic Microwave Background photons. Search for PSR J1833-1034 X-ray pulsed emission, via RXTE and Swift X-ray observations, resulted in an upper limit that is about 50 per cent.Comment: 5 pages, 2 figures. Accepted for pubblication in MNRA

A double-sided silicon micro-strip super-module for the ATLAS inner detector upgrade in the high-luminosity LHC

The ATLAS experiment is a general purpose detector aiming to fully exploit the discovery potential of the Large Hadron Collider (LHC) at CERN. It is foreseen that after several years of successful data-taking, the LHC physics programme will be extended in the so-called High-Luminosity LHC, where the instantaneous luminosity will be increased up to 5 × 1034 cm−2 s−1. For ATLAS, an upgrade scenario will imply the complete replacement of its internal tracker, as the existing detector will not provide the required performance due to the cumulated radiation damage and the increase in the detector occupancy. The current baseline layout for the new ATLAS tracker is an all-silicon-based detector, with pixel sensors in the inner layers and silicon micro-strip detectors at intermediate and outer radii. The super-module is an integration concept proposed for the strip region of the future ATLAS tracker, where double-sided stereo silicon micro-strip modules are assembled into a low-mass local support structure. An electrical super-module prototype for eight double-sided strip modules has been constructed. The aim is to exercise the multi-module readout chain and to investigate the noise performance of such a system. In this paper, the main components of the current super-module prototype are described and its electrical performance is presented in detail

Discovery of Novel Biomarker Candidates for Liver Fibrosis in Hepatitis C Patients: A Preliminary Study

Background: Liver biopsy is the reference standard for assessing liver fibrosis and no reliable non-invasive diagnostic approach is available to discriminate between the intermediate stages of fibrosis. Therefore suitable serological biomarkers of liver fibrosis are urgently needed. We used proteomics to identify novel fibrosis biomarkers in hepatitis C patients with different degrees of liver fibrosis.Methodology/Principal Findings: Proteins in plasma samples from healthy control individuals and patients with hepatitis C virus (HCV) induced cirrhosis were analysed using a proteomics technique: two dimensional gel electrophoresis (2-DE). This technique separated the proteins in plasma samples of control and cirrhotic patients and by visualizing the separated proteins we were able to identify proteins which were increasing or decreasing in hepatic cirrhosis. Identified markers were validated across all Ishak fibrosis stages and compared to the markers used in FibroTest, Enhanced Liver Fibrosis (ELF) test, Hepascore and FIBROSpect by Western blotting. Forty four candidate biomarkers for hepatic fibrosis were identified of which 20 were novel biomarkers of liver fibrosis. Western blot validation of all candidate markers using plasma samples from patients across all Ishak fibrosis scores showed that the markers which changed with increasing fibrosis most consistently included lipid transfer inhibitor protein, complement C3d, corticosteroid-binding globulin, apolipoprotein J and apolipoprotein L1. These five novel fibrosis markers which are secreted in blood showed a promising consistent change with increasing fibrosis stage when compared to the markers used for the FibroTest, ELF test, Hepascore and FIBROSpect. These markers will be further validated using a large clinical cohort.Conclusions/Significance: This study identifies 20 novel fibrosis biomarker candidates. The proteins identified may help to assess hepatic fibrosis and eliminate the need for invasive liver biopsies.</br

Down-Regulation of DNA Mismatch Repair Enhances Initiation and Growth of Neuroblastoma and Brain Tumour Multicellular Spheroids

Multicellular tumour spheroid (MCTS) cultures are excellent model systems for simulating the development and microenvironmental conditions of in vivo tumour growth. Many documented cell lines can generate differentiated MCTS when cultured in suspension or in a non-adhesive environment. While physiological and biochemical properties of MCTS have been extensively characterized, insight into the events and conditions responsible for initiation of these structures is lacking. MCTS are formed by only a small subpopulation of cells during surface-associated growth but the processes responsible for this differentiation are poorly understood and have not been previously studied experimentally. Analysis of gene expression within spheroids has provided clues but to date it is not known if the observed differences are a cause or consequence of MCTS growth. One mechanism linked to tumourigenesis in a number of cancers is genetic instability arising from impaired DNA mismatch repair (MMR). This study aimed to determine the role of MMR in MCTS initiation and development. Using surface-associated N2a and CHLA-02-ATRT culture systems we have investigated the impact of impaired MMR on MCTS growth. Analysis of the DNA MMR genes MLH1 and PMS2 revealed both to be significantly down-regulated at the mRNA level compared with non-spheroid-forming cells. By using small interfering RNA (siRNA) against these genes we show that silencing of MLH1 and PMS2 enhances both MCTS initiation and subsequent expansion. This effect was prolonged over several passages following siRNA transfection. Down-regulation of DNA MMR can contribute to tumour initiation and progression in N2a and CHLA-02-ATRT MCTS models. Studies of surface-associated MCTS differentiation may have broader applications in studying events in the initiation of cancer foci

Resistance to ursodeoxycholic acid-induced growth arrest can also result in resistance to deoxycholic acid-induced apoptosis and increased tumorgenicity

BACKGROUND: There is a large body of evidence which suggests that bile acids increase the risk of colon cancer and act as tumor promoters, however, the mechanism(s) of bile acids mediated tumorigenesis is not clear. Previously we showed that deoxycholic acid (DCA), a tumorogenic bile acid, and ursodeoxycholic acid (UDCA), a putative chemopreventive agent, exhibited distinct biological effects, yet appeared to act on some of the same signaling molecules. The present study was carried out to determine whether there is overlap in signaling pathways activated by tumorogenic bile acid DCA and chemopreventive bile acid UDCA. METHODS: To determine whether there was an overlap in activation of signaling pathways by DCA and UDCA, we mutagenized HCT116 cells and then isolated cell lines resistant to UDCA induced growth arrest. These lines were then tested for their response to DCA induced apoptosis. RESULTS: We found that a majority of the cell lines resistant to UDCA-induced growth arrest were also resistant to DCA-induced apoptosis, implying an overlap in DCA and UDCA mediated signaling. Moreover, the cell lines which were the most resistant to DCA-induced apoptosis also exhibited a greater capacity for anchorage independent growth. CONCLUSION: We conclude that UDCA and DCA have overlapping signaling activities and that disregulation of these pathways can lead to a more advanced neoplastic phenotype