Development and performance of the Clinical Trials ESSDAI (ClinTrialsESSDAI), consisting of frequently active clinical domains, in two randomised controlled trials in primary Sjogren's syndrome

Objective. To develop and evaluate the Clinical Trials EULAR Sjogren's Syndrome Disease Activity Index (ClinTrialsESSDAI), consisting of frequently active clinical domains of the ESSDAI, using two randomised controlled trials in primary Sjogren's syndrome (pSS). Methods. The ASAP-III trial in abatacept (80 pSS patients) and TRACTISS trial in rituximab (133 pSS patients) were analysed. The most frequently active clinical domains were selected, and ClinTrialsESSDAI total score was calculated using existing weightings of the ClinESSDAI (which also excludes the biological domain). Performance of the ClinTrialsESSDAI was compared to ClinESSDAI and ESSDAI. Responsiveness was assessed using standardised response mean (SRM), and discrimination was assessed using adjusted mean difference. Results. Besides the biological domain, the most frequently active domains were glandular, articular, haematological, constitutional, lymphadenopathy and cutaneous. These domains were selected for the ClinTrialsESSDAI. At primary endpoint visits, SRM values of ClinTrialsESSDAI, ClinESSDAI and ESSDAI were respectively -0.65/-0.59, -0.63/-0.59 and - 0.64/-0.61 for abatacept/placebo and -0.33/-0.13, -0.34/0.12 and -0.41/-0.16 for rituximab/placebo. Adjusted mean differences between active treatment and placebo groups were respectively -1.7, -1.4 and -1.1 for ASAP-III and -1.1, -1.1 and -1.2 for TRACTISS. Conclusion. The ClinTrialsESSDAI, consisting of six frequently active clinical domains of the ESSDAI, shows closely similar responsiveness and discrimination between treatment groups compared to the ClinESSDAI and ESSDAI. Therefore, this ClinTrialsESSDAI is not preferable to ClinESSDAI and ESSDAI for use as primary endpoint. A composite endpoint combining response at multiple clinically relevant items seems more suitable as primary study endpoint in pSS

The Gerasimov-Drell-Hearn Sum Rule and the Spin Structure of the Nucleon

The Gerasimov-Drell-Hearn sum rule is one of several dispersive sum rules that connect the Compton scattering amplitudes to the inclusive photoproduction cross sections of the target under investigation. Being based on such universal principles as causality, unitarity, and gauge invariance, these sum rules provide a unique testing ground to study the internal degrees of freedom that hold the system together. The present article reviews these sum rules for the spin-dependent cross sections of the nucleon by presenting an overview of recent experiments and theoretical approaches. The generalization from real to virtual photons provides a microscope of variable resolution: At small virtuality of the photon, the data sample information about the long range phenomena, which are described by effective degrees of freedom (Goldstone bosons and collective resonances), whereas the primary degrees of freedom (quarks and gluons) become visible at the larger virtualities. Through a rich body of new data and several theoretical developments, a unified picture of virtual Compton scattering emerges, which ranges from coherent to incoherent processes, and from the generalized spin polarizabilities on the low-energy side to higher twist effects in deep inelastic lepton scattering.Comment: 32 pages, 19 figures, review articl

Compton Scattering by the Proton using a Large-Acceptance Arrangement

Compton scattering by the proton has been measured using the tagged-photon facility at MAMI (Mainz) and the large-acceptance arrangement LARA. The new data are interpreted in terms of dispersion theory based on the SAID-SM99K parameterization of photo-meson amplitudes. It is found that two-pion exchange in the t-channel is needed for a description of the data in the second resonance region. The data are well represented if this channel is modeled by a single pole with mass parameter m(sigma)=600 MeV. The asymptotic part of the spin dependent amplitude is found to be well represented by pi-0-exchange in the t-channel. A backward spin-polarizability of gamma(pi)=(-37.1+-0.6(stat+syst)+-3.0(model))x10^{-4}fm^4 has been determined from data of the first resonance region below 455 MeV. This value is in a good agreement with predictions of dispersion relations and chiral pertubation theory. From a subset of data between 280 and 360 MeV the resonance pion-photoproduction amplitudes were evaluated leading to a E2/M1 multipole ratio of the p-to-Delta radiative transition of EMR(340 MeV)=(-1.7+-0.4(stat+syst)+-0.2(model))%. It was found that this number is dependent on the parameterization of photo-meson amplitudes. With the MAID2K parameterization an E2/M1 multipole ratio of EMR(340 MeV)=(-2.0+-0.4(stat+syst)+-0.2(model))% is obtained

Origin Of The Far Off-Axis GRB171205A

We show that observed properties of the low luminosity GRB171205A and its afterglow, like those of most other low-luminosity (LL) gamma ray bursts (GRBs) associate with a supernova (SN), indicate that it is an ordinary SN-GRB, which was produced by inverse Compton scattering of glory light by a highly relativistic narrowly collimated jet ejected in a supernova explosion and viewed from a far off-axis angle. As such, VLA/VLBI follow-up radio observations of a superluminal displacement of its bright radio afterglow from its parent supernova, will be able to test clearly whether it is an ordinary SN-GRB viewed from far off-axis or it belongs to a distinct class of GRBs, which are different from ordinary GRBs, and cannot be explained by standard fireball models of GRBs as ordinary GRBsComment: 5 pages, 6 figures, updated data in Fig. 3, Corrected GRB angular distance used in Fig.

Acute sensitivity of the oral mucosa to oncogenic K-ras.

Mouse models of cancer represent powerful tools for analysing the role of genetic alterations in carcinogenesis. Using a mouse model that allows tamoxifen-inducible somatic activation (by Cre-mediated recombination) of oncogenic K-ras(G12D) in a wide range of tissues, we observed hyperplasia of squamous epithelium located in moist or frequently abraded mucosa, with the most dramatic effects in the oral mucosa. This epithelium showed a sequence of squamous hyperplasia followed by squamous papilloma with dysplasia, in which some areas progressed to early invasive squamous cell carcinoma, within 14 days of widespread oncogenic K-ras activation. The marked proliferative response of the oral mucosa to K-ras(G12D) was most evident in the basal layers of the squamous epithelium of the outer lip with hair follicles and wet mucosal surface, with these cells staining positively for pAKT and cyclin D1, showing Ras/AKT pathway activation and increased proliferation with Ki-67 and EdU positivity. The stromal cells also showed gene activation by recombination and immunopositivity for pERK indicating K-Ras/ERK pathway activation, but without Ki-67 positivity or increase in stromal proliferation. The oral neoplasms showed changes in the expression pattern of cytokeratins (CK6 and CK13), similar to those observed in human oral tumours. Sporadic activation of the K-ras(G12D) allele (due to background spontaneous recombination in occasional cells) resulted in the development of benign oral squamous papillomas only showing a mild degree of dysplasia with no invasion. In summary, we show that oral mucosa is acutely sensitive to oncogenic K-ras, as widespread expression of activated K-ras in the murine oral mucosal squamous epithelium and underlying stroma can drive the oral squamous papilloma-carcinoma sequence

Quasi-free Compton Scattering and the Polarizabilities of the Neutron

Differential cross sections for quasi-free Compton scattering from the proton and neutron bound in the deuteron have been measured using the Glasgow/Mainz tagging spectrometer at the Mainz MAMI accelerator together with the Mainz 48 cm $\oslash$ $\times$ 64 cm NaI(Tl) photon detector and the G\"ottingen SENECA recoil detector. The data cover photon energies ranging from 200 MeV to 400 MeV at $\theta^{LAB}_\gamma=136.2^\circ$. Liquid deuterium and hydrogen targets allowed direct comparison of free and quasi-free scattering from the proton. The neutron detection efficiency of the SENECA detector was measured via the reaction $p(\gamma,\pi^+ n)$. The "free" proton Compton scattering cross sections extracted from the bound proton data are in reasonable agreement with those for the free proton which gives confidence in the method to extract the differential cross section for free scattering from quasi-free data. Differential cross sections on the free neutron have been extracted and the difference of the electromagnetic polarizabilities of the neutron have been obtained to be $\alpha-\beta= 9.8\pm 3.6(stat){}^{2.1}_1.1(syst)\pm 2.2(model)$ in units $10^{-4}fm^3$. In combination with the polarizability sum $\alpha +\beta=15.2\pm 0.5$ deduced from photoabsorption data, the neutron electric and magnetic polarizabilities, $\alpha_n=12.5\pm 1.8(stat){}^{+1.1}_{-0.6}\pm 1.1(model)$ and $\beta_n=2.7\mp 1.8(stat){}^{+0.6}_{-1.1}(syst)\mp 1.1(model)$ are obtained. The backward spin polarizability of the neutron was determined to be $\gamma^{(n)}_\pi=(58.6\pm 4.0)\times 10^{-4}fm^4$