Efficacy and safety of DFN-11 (sumatriptan injection, 3 mg) in adults with episodic migraine: a multicenter, randomized, double-blind, placebo-controlled study.

BackgroundIn a previous randomized, double-blind, proof-of-concept study in rapidly escalating migraine, a 3 mg dose of subcutaneous sumatriptan (DFN-11) was associated with fewer and shorter triptan sensations than a 6 mg dose. The primary objective of the study was to assess the efficacy and safety of acute treatment with DFN-11 compared with placebo in episodic migraine.MethodsThis was a multicenter, randomized, double-blind, placebo-controlled efficacy and safety study of DFN-11 in the acute treatment of adults with episodic migraine (study RESTOR). The primary endpoint was the proportion of subjects taking DFN-11 who were pain free at 2 h postdose in the double-blind period compared with placebo. Secondary endpoints included earlier postdose timepoints, assessments of pain relief and subjects' freedom from their most bothersome symptom (MBS) (among nausea, photophobia, and phonophobia). Safety and tolerability were assessed.ResultsA total of 392 subjects was screened, 268 (68.4%) were randomized, and 234 (87.3% of those randomized) completed the double-blind treatment period. The proportion of subjects who were pain free at 2 h postdose was significantly greater in the DFN-11 group than in the placebo group (51.0% vs 30.8%, P  =  0.0023). Compared with placebo, significantly higher proportions of subjects treated with DFN-11 were also pain free at 30, 60, and 90 min postdose (P  ≤  0.0195). DFN-11 was significantly superior to placebo for pain relief at 60 min, 90 min, and 2 h postdose (P ≤ 0.0179). At 2 h postdose, DFN-11 was also significantly superior to placebo for freedom from photophobia (P  =  0.0056) and phonophobia (P  =  0.0167). Overall, 33.3% (37/111) who received DFN-11 and 13.4% (16/119) who received placebo experienced at least 1 treatment-emergent adverse event (TEAE), the most common of which were injection site swelling (7.2% vs 0.8%) and pain (7.2% vs 5.9%). Chest discomfort was about half as common in the DFN-11 treatment group as it was in the placebo group (0.9% vs 1.7%).ConclusionsThis study met its primary endpoint, pain freedom at 2 h postdose, with DFN-11 significantly better than placebo, and the incidence of TEAEs and triptan sensations with DFN-11 was low. The 3 mg dose of sumatriptan in DFN-11 appears to be an effective alternative to a 6 mg SC dose of sumatriptan, with good safety and tolerability. ( clinicaltrials.gov : NCT02569853; registered 07 October 2015)

Design, theory, and measurement of a polarization insensitive absorber for terahertz imaging

We present the theory, design, and realization of a polarization-insensitive metamaterial absorber for terahertz frequencies. We derive geometrical-independent conditions for effective medium absorbers in general, and for resonant metamaterials specically. Our fabricated design reaches and absorptivity of 78% at 1.145 ThzComment: 6 Pages, 5 figures; figures update

Who in Europe works beyond the state pension age and under which conditions? Results from SHARE

There is much research about those who exit the labour market prematurely, however, comparatively little is known about people working longer and about their employment and working conditions. In this paper, we describe the employment and working conditions of men and women working between 65 and 80 years, and compare them with previous conditions of those retired in the same age group. Analyses are based on wave 4 data from the Survey of Health, Ageing and Retirement in Europe (SHARE) with information collected between 2009 and 2011 from 17,625 older men and women across 16 European countries. Besides socio-demographic and health-related factors (physical and mental health), the focus lies on employment conditions (e.g. employment status, occupational position and working hours) and on stressful working conditions, measured in terms of low control at work and effort-reward imbalance. In case of retired people, information on working conditions refer to the last job before retirement. Following descriptive analyses, we then conduct multivariable analyses and investigate how working conditions and poor health are related to labour market participation (i.e. random intercept models accounting for country affiliation and adjusted for potential confounders). Results illustrate that people working between the ages of 65 and 80 are more likely to be self-employed (either with or without employees) and work in advantaged occupational positions. Furthermore, findings reveal that psychosocial working conditions are generally better than the conditions retired respondents had in their last job. Finally, in contrast to those who work, health tends to be worse among retired people. In conclusion, findings deliver empirical evidence that paid employment beyond age 65 is more common among self-employed workers throughout Europe, in advantaged occupations and under-favourable psychosocial circumstances, and that this group of workers are in considerably good mental and physical health. This highlights that policies aimed at increasing the state pension age beyond the age of 65 years put pressure on specific disadvantaged groups of men and women

The potential role of T-cells and their interaction with antigen-presenting cells in mediating immunosuppression following trauma-hemorrhage

Objective: Trauma-hemorrhage results in depressed immune responses of antigen-presenting cells (APCs) and T-cells. Recent studies suggest a key role of depressed T-cell derived interferon (IFN)-g in this complex immune cell interaction. The aim of this study was to elucidate further the underlying mechanisms responsible for dysfunctional T-cells and their interaction with APCs following trauma-hemorrhage. Design: Adult C3H/HeN male mice were subjected to trauma-hemorrhage (3-cm midline laparotomy) followed by hemorrhage (blood pressure of 35�5mmHg for 90 min and resuscitation) or sham operation. At 24 h thereafter, spleens were harvested and T-cells (by Microbeads) and APCs (via adherence) were Isolated. Co-cultures of T-cells and APCs were established for 48 h and stimulated with concanavalin A and lipopolysaccharide. T-Cell specific cytokines known to affect APC function (i.e. interleukin(IL)-2, IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF)) were measured in culture supernatants by Multiplex assay. The expression of MHC class II as well as co-stimulatory surface molecules on T-cells and APCs was determined by flow cytometry. Results: The release of IL-4 and GM-CSF by T-cells was suppressed following trauma-hemorrhage, irrespective of whether sham or trauma-hemorrhage APCs were present. Antigen-presenting cells from animals subjected to trauma-hemorrhage did not affect T-cell derived cytokine release by sham T-cells. In contrast, T-cells from traumahemorrhage animals depressed MHC class II expression of CD11c(þ) cells, irrespective of whether APCs underwent sham or trauma-hemorrhage procedure. Surprisingly, co-stimulatory molecules on APCs (CD80, CD86) were not affected by trauma-hemorrhage. Conclusions: These results suggest that beside IFN-g other T-cell derived cytokines contribute to immunosuppression following trauma-hemorrhage causing diminished MHC II expression on APCs. Thus, T-cells appear to play an important role in this interaction at the time-point examined. Therapeutic approaches should aim at maintenance of T-cell function and their interaction with APCs to prevent extended immunosuppression following trauma-hemorrhage

CDM models with a steplike initial power spectrum

We investigate the properties of clusters of galaxies in the $\Lambda$CDM models with a steplike initial power spectrum. We examine the mass function, the peculiar velocities and the power spectrum of clusters in models with different values of the density parameter $\Omega_0$, the normalized Hubble constant h and the spectral parameter p, which describes the shape of the initial power spectrum. The results are compared with observations. We also investigate the rms bulk velocity in the models, where the properties of clusters are consistent with the observed data. We find that the power spectrum of clusters is in good agreement with the observed power spectrum of the Abell-ACO clusters, if the spectral parameter p is in the range p=0.6-0.8. The power spectrum and the rms peculiar velocity of clusters are consistent with observations only if $\Omega_0<0.4$. The $\Omega_0=0.3$ models are consistent with the observed properties of clusters, if h=0.50-0.63. For h=0.65, we find that $\Omega_0=0.20 -0.27$.Comment: 8 pages, 5 figures. Accepted for publication in MNRA

The Canada-France deep fields survey-I: 100,000 galaxies, 1 deg^2: a precise measurement of \omega(\theta) to IAB~25

(abridged) Using the UH8K mosaic camera, we have measured the angular correlation function \omega(\theta) for 100,000 galaxies over four widely separated fields totalling ~1\deg^2 and reaching IAB~25.5. With this sample we investigate the dependence of \omega(\theta) at 1', A_\omega(1'), on sample median IAB magnitude in the range 19.5<I(AB-med)<24. Our results show that A_\omega(1') decreases monotonically to IAB~25. At bright magnitudes, \omega(\theta) is consistent with a power-law of slope \delta = -0.8 for 0.2'<\theta<3.0' but at fainter magnitudes we find \delta ~ -0.6. At the 3\sigma level, our observations are still consistent with \delta=-0.8. Furthermore, in the magnitude ranges 18.5<IAB<24.0 and 18.5<IAB<23.0 we find galaxies with 2.6<(V-I)AB<2.9 have A_\omega(1')'s which are ~10x higher than field values. We demonstrate that our model redshift distributions for the faint galaxy population are in good agreement with current spectroscopic observations. Using these predictions, we find that for low-omega cosmologies and assuming r_0=4.3/h Mpc, in the range 19.5<I(AB-med)<22, the growth of galaxy clustering is \epsilon~0. However, at 22<I(AB-med)<24.0, our observations are consistent with \epsilon>1. Models with \epsilon~0 cannot simultaneously match both bright and faint measurements of A_\omega(1`). We show how this result is a natural consequence of the ``bias-free'' nature of the \epsilon formalism and is consistent with the field galaxy population in the range 22.0<IAB<24.0 being dominated by galaxies of low intrinsic luminosity.Comment: 20 pages, 21 figures, requires natbib.sty, accepted for publication in Astronomy and Astrophysic

An Inversion Method for Measuring Beta in Large Redshift Surveys

A precision method for determining the value of Beta= Omega_m^{0.6}/b, where b is the galaxy bias parameter, is presented. In contrast to other existing techniques that focus on estimating this quantity by measuring distortions in the redshift space galaxy-galaxy correlation function or power spectrum, this method removes the distortions by reconstructing the real space density field and determining the value of Beta that results in a symmetric signal. To remove the distortions, the method modifies the amplitudes of a Fourier plane-wave expansion of the survey data parameterized by Beta. This technique is not dependent on the small-angle/plane-parallel approximation and can make full use of large redshift survey data. It has been tested using simulations with four different cosmologies and returns the value of Beta to +/- 0.031, over a factor of two improvement over existing techniques.Comment: 16 pages including 6 figures Submitted to The Astrophysical Journa