Radar plots: A novel modality for displaying disparate data on the efficacy of eluxadoline for the treatment of irritable bowel syndrome with diarrhea

BackgroundPatients with irritable bowel syndrome with diarrhea (IBS‐D) experience a range of abdominal and bowel symptoms; successful management requires alleviation of this constellation of symptoms. Eluxadoline, a locally active mixed μ‐ and κ‐opioid receptor agonist and δ‐opioid receptor antagonist, is approved for the treatment of IBS‐D in adults based on the results of 2 Phase 3 studies. Radar plots can facilitate comprehensive, visual evaluation of diverse but interrelated efficacy endpoints.MethodsTwo double‐blind, placebo‐controlled, Phase 3 trials (IBS‐3001 and IBS‐3002) randomized patients meeting Rome III criteria for IBS‐D to twice‐daily eluxadoline 75 or 100 mg or placebo. Radar plots were prepared showing pooled Weeks 1‐26 response rates for the primary efficacy composite endpoint (simultaneous improvement in abdominal pain and stool consistency), stool consistency, abdominal pain, urgency‐free days, and adequate relief, and change from baseline to Week 26 in IBS‐D global symptom score, abdominal discomfort, abdominal pain, abdominal bloating, and daily number of bowel movements.Key ResultsThe studies enrolled 2428 patients. Eluxadoline increased Weeks 1‐26 responder proportions vs placebo for the composite endpoint, stool consistency, abdominal pain, urgency‐free days, and adequate relief. Changes from baseline to Week 26 in IBS‐D global symptom score, abdominal discomfort, abdominal pain, abdominal bloating, and number of bowel movements were greater with eluxadoline vs placebo.Conclusions and InferencesData presentation in radar plot format facilitates interpretation across multiple domains, demonstrating that eluxadoline treatment led to improvements vs placebo across 13 endpoints representing the range of symptoms experienced by patients with IBS‐D.Data presentation in radar plot format can facilitate evaluation of the diverse array of symptoms and outcomes that are relevant to a symptom‐based condition like irritable bowel syndrome with diarrhea (IBS‐D). In 2 Phase 3 trials, eluxadoline treatment improved stool consistency and frequency, abdominal pain, bloating and discomfort, feelings of urgency, global symptom score, and adequate relief. Radar plots provide a visual demonstration of improvements with eluxadoline across 13 endpoints encompassing the diverse constellation of symptoms experienced by patients with IBS‐D.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145265/1/nmo13331_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145265/2/nmo13331.pd

Tunneling into Current-Carrying Surface States of High Tc_c Superconductors

Theoretical results for the ab-plane tunneling conductance in the d-wave model for high Tc superconductors are presented. The d-wave model predicts surface bound states below the maximum gap. A sub-dominant order parameter, stabilized by the surface, leads to a splitting of the zero-bias conductance peak (ZBCP) in zero external field and to spontaneous surface currents. In a magnetic field screening currents shift the quasiparticle bound state spectrum and lead to a voltage splitting of the ZBCP that is linear in H at low fields, and saturates at a pairbreaking critical field of order 3 Tesla. Comparisons with recent experimental results on Cu/YBCO junctions are presented.Comment: 4 pages in a RevTex (3.0) file plus 3 Figures in PostScript. To appear in Phys. Rev. Let

Local density of states for the corner geometry interface of d-wave superconductors, within the extended Hubbard model

The spatial variations of the order parameter, and the local density of states (LDOS) on the corner of s-wave or $d_{x^2-y^2}$-wave superconductors, as well as in superconductor-insulator-normal metal interfaces, are calculated self consistently using the Bogoliubov-deGennes formalism within the two dimensional extended Hubbard model. The exact diagonalization method is used. Due to the suppression of the dominant d-wave order parameter, the extended s-wave order parameter is induced near the surface, that alternates its sign for the topmost sites at adjacent edges of the lattice and decays to zero in the bulk. The presence of surface roughness results into the appearance of the zero band conduction peak (ZBCP) near the corner surface which lacks from the predictions of the quasiclassical theory.Comment: 13 pages with 17 figure

Spontaneous flux in a d-wave superconductor with time-reversal-symmetry-broken pairing state at {110} boundaries

The induction of an s-wave component in a d-wave superconductor is considered. Near the {110}-oriented edges of such a sample, the induced s-wave order parameter together with d-wave component forms a complex combination d+e^{i\phi} s, which breaks the time reversal symmetry (BTRS) of the pairing state. As a result, the spontaneous current is created. We numerically study the current distribution and the formation of the spontaneous flux induced by the current. We show that the spontaneous flux formed from a number of defect lines with {110} orientation has a measurable strength. This result may provide a unambiguous way to check the existence of BTRS pairing state at {110}-oriented boundaries.Comment: 4 pages, 2 ps-figures, content changed, references adde

The Effect of Major Mergers on Age and Metallicity Across the Fundamental Plane

Recent low-redshift observations have attempted to determine the star formation histories of elliptical galaxies by tracking correlations between the stellar population parameters (age and metallicity) and the structural parameters that enter the fundamental plane (size and velocity dispersion). These studies have found that velocity dispersion, rather than effective radius or dynamical mass, is the main predictor of a galaxy's stellar age and metallicity. In this work, we apply an analytic model that predicts the structural properties of remnants formed in major mergers to progenitor disk galaxies with properties taken from two different semi-analytic models. We predict the effective radius, velocity dispersion, luminosity, age, and metallicity of the merger remnants, enabling us to compare directly to observations of early-type galaxies. While we find a tight correlation between age and velocity dispersion, we find a stronger dependence of age and metallicity on effective radius than observations report. The correlations arise as a result of the dependence of gas fraction, age, and metallicity on the stellar mass in the progenitor disk galaxies. These dependences induce a rotation in the radius-velocity plane between the correlations with effective radius and circular velocity in the disk galaxy progenitors, and the correlations with effective radius and velocity dispersion in the elliptical galaxy remnants. The differences between our results and those from observations suggest that major mergers alone cannot produce the observed lack of correlation between effective radius and stellar population parameters. Simulations have suggested that subsequent minor mergers introduce scatter in the effective radius while leaving the velocity dispersion essentially unchanged. Incorporating such minor mergers into the model may, then, bring the simulations into closer agreement with observations.Comment: 20 pages, 17 figures. Submitted to MNRA

Subharmonic gap structure in d-wave superconductors

We present a self-consistent theory of current-voltage characteristics of d-wave/d-wave contacts at arbitrary transparency. In particular, we address the open problem of the observation of subharmonic gap structure (SGS) in cuprate junctions. Our analysis shows that: (i) the SGS is possible in d-wave superconductors, (ii) the existence of bound states within the gap results in an even-odd effect in the SGS, (iii) elastic scattering mechanisms, like impurities or surface roughness, may suppress the SGS, and (iv) in the presence of a magnetic field the Doppler shift of the Andreev bound states leads to a very peculiar splitting of the SGS, which is an unambiguous fingerprint of d-wave superconductivity.Comment: Revtex4, 4 pages, 5 figure

Observation of Bound Surface States in Grain Boundary Junctions of High Temperature Superconductors

We have performed a detailed study of the tunneling spectra of bicrystal grain boundary junctions (GBJs) fabricated from the HTS YBCO, BSCCO, LSCO, and NCCO. In all experiments the tunneling direction was along the CuO planes. With the exception of NCCO, for all materials a pronounced zero bias conductance peak was observed which decreases with increasing temperature and disappears at the critical temperature. These results can be explained by the presence of a dominating d-wave symmetry of the order parameter resulting in the formation of zero energy Andreev bound states at surfaces and interfaces of HTS. The absence of a ZBCP for NCCO is consistent with a dominating s-wave symmetry of the pair potential in this material. The observed nonlinear shift of spectral weight to finite energies by applying a magnetic field is in qualitative agreement with recent theoretical predictions.Comment: 4 pages, 4 figures, to be published in Phys. Rev.