Oral fumaric acid esters for psoriasis: abridged Cochrane systematic review including GRADE assessments

Fumaric acid esters (FAE) are licensed for the treatment of moderate to severe psoriasis in Germany but are also used off-label in many other countries. We conducted this systematic review to synthesize the highest quality evidence for the benefits and risks of FAE for psoriasis. Our primary outcomes were change in PASI score and drop-out rates due to adverse effects. Randomised controlled trials (RCTs) of FAE or dimethyl fumarate were included, with no restriction on age or psoriasis subtype. We searched The Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library, MEDLINE, EMBASE, LILACS, five trials registers and handsearched six conference proceedings. Six RCTs with 544 participants were included, four of which were published only as abstracts or brief reports, limiting study reporting. Five RCTs compared FAE with placebo and all demonstrated benefit in favour of FAE but meta-analysis was only possible for PASI 50 after 12-16 weeks, which was achieved by 64% of participants on FAE compared to 14% on placebo (risk ratio (RR) 4.55; 95% CI 2.80 to 7.40; 2 studies; 247 participants; low quality evidence). There was no difference in drop-out rates due to adverse effects (RR 5.36, 95% CI 0.28 to 102.12; 1 study; 27 participants; very low-quality evidence and wide confidence interval). More participants experienced nuisance adverse effects with FAE (76%) compared to placebo (16%) (RR 4.72, 95% CI 2.45 to 9.08; 1 study; 99 participants; moderate-quality evidence), mainly abdominal pain, diarrhoea and flushing. One head-to-head study of very low quality evidence comparing FAE with methotrexate reported comparable efficacy and drop-out rates, although FAE caused more flushing. The evidence in this review was limited and must be interpreted with caution; better designed and reported studies are needed

The Evolution of Early-Type Galaxies in Distant Clusters III.: M/L_V Ratios in the z=0.33 Cluster CL1358+62

Keck spectroscopy and Hubble Space Telescope WFPC2 imaging over a 1.5x1.5 Mpc field of CL1358+62 at z=0.33 are used to study the Fundamental Plane of galaxies based on a new, large sample of 53 galaxies. First, we have constructed the Fundamental Plane for the 30 E and S0 galaxies and find that it has the following shape: r_e = sigma**(1.31+-0.13) * _e**(-0.86+-0.10), similar to that found locally. The 1-sigma intrinsic scatter about this plane is 14% in M/L(V), comparable to that observed in Coma. We conclude that these E and S0 galaxies are structurally mature and homogeneous, like those observed in nearby clusters. The M/L(V) ratios of these early-type galaxies are offset from the Coma Fundamental Plane by delta log M/L(V) = -0.13+- 0.03 (q0=0.1), indicative of mild luminosity evolution. This evolution suggests a formation epoch for the stars of z > 1. We have also analyzed the M/L(V) ratios of galaxies of type S0/a and later. These early-type spirals follow a different plane from the E and S0 galaxies, with a scatter that is twice as large as the scatter for the E/S0s. The difference in the tilt between the plane of the spirals and the plane of the E/S0s is shown to be due to a systematic correlation of velocity dispersion with residual from the plane of the early-type galaxies. These residuals also correlate with the residuals from the Color-Magnitude relation. Thus for spirals in clusters, we see a systematic variation in the luminosity-weighted mean properties of the stellar populations with central velocity dispersion. If this is a relative age trend, then luminosity-weighted age is positively correlated with dispersion. [abridged version]Comment: 18 pages, 8 figures; revised version, accepted by ApJ on 13 August 199

The Host Galaxy of GRB 990123

We present deep images of the field of gamma-ray burst (GRB) 990123 obtained in a broad-band UV/visible bandpass with the Hubble Space Telescope, and deep near-infrared images obtained with the Keck-I 10-m telescope. Both the HST and Keck images show that the optical transient (OT) is clearly offset by 0.6 arcsec from an extended object, presumably the host galaxy. This galaxy is the most likely source of the metallic-line absorption at z = 1.6004 seen in the spectrum of the OT. With magnitudes V_{C} ~ 24.6 +/- 0.2 and K = 21.65 +/- 0.30 mag this corresponds to an L ~ 0.7 L_* galaxy, assuming that it is located at z = 1.6. The estimated unobscured star formation rate is SFR ~ 6 M_sun/yr, which is not unusually high for normal galaxies at comparable redshifts. The strength of the observed metallic absorption lines is suggestive of a relatively high metallicity of the gas, and thus of a chemically evolved system which may be associated with a massive galaxy. It is also indicative of a high column density of the gas, typical of damped Ly-alpha systems at high redshifts. We conclude that this is the host galaxy of GRB 990123. No other obvious galaxies are detected within the same projected radius from the OT. There is thus no evidence for strong gravitational lensing magnification of this burst, and some alternative explanation for its remarkable energetics may be required. The observed offset of the OT from the center of its apparent host galaxy, 5.5 +/- 0.9 proper kpc (projected) in the galaxy's rest-frame, both refutes the possibility that GRBs are related to galactic nuclear activity and supports models of GRBs which involve the death and/or merger of massive stars. Further, the HST image suggests an intimate connection of GRB 990123 and a star-forming region.Comment: Updated references. 12 pages including 3 Postscript figures. Camera- ready reproductions of the figures can be found at http://astro.caltech.edu/~jsb/GRB/grb990123.htm

Modeling the Images of Relativistic Jets Lensed by Galaxies with Different Mass Surface Density Distributions

The images of relativistic jets from extragalactic sources produced by gravitational lensing by galaxies with different mass surface density distributions are modeled. In particular, the following models of the gravitational lens mass distribution are considered: a singular isothermal ellipsoid, an isothermal ellipsoid with a core, two- and three-component models with a galactic disk, halo, and bulge. The modeled images are compared both between themselves and with available observations. Different sets of parameters are shown to exist for the gravitationally lensed system B0218+357 in multicomponent models. These sets allow the observed geometry of the system and the intensity ratio of the compact core images to be obtained, but they lead to a significant variety in the Hubble constant determined from the modeling results.Comment: 26 pages, 9 figures, will be published in the Astronomy Letters, 2011, v.37, N4, pp. 233-24

Mass-Selection and the Evolution of the Morphology-Density Relation from z=0.8 to z=0

We examined the morphology-density relations for galaxy samples selected by luminosity and by mass in each of five massive X-ray clusters from z=0.023 to 0.83 for 674 spectroscopically-confirmed members. Rest-frame optical colors and visual morphologies were obtained primarily from Hubble Space Telescope images. Morphology-density relations (MDR) are derived in each cluster from a complete, luminosity-selected sample of 452 galaxies with a magnitude limit M_V < M^{*}_{V} + 1. The change in the early-type fraction with redshift matches previous work for massive clusters of galaxies. We performed a similar analysis, deriving MDRs for complete, mass-selected samples of 441 galaxies with a mass-limit of 10^{10.6} M_{\sun}. Our mass limit includes faint objects, the equivalent of =~1 mag below L^{*} for the red cluster galaxies, and encompasses =~70% of the stellar mass in cluster galaxies. The MDRs in the mass-selected sample at densities of Sigma > 50 galaxies Mpc^{-2} are similar to those in the luminosity-selected sample but show larger early-type fractions. However, the trend with redshift in the fraction of elliptical and S0 galaxies with masses > 10^{10.6} M_{\sun} differs significantly between the mass- and luminosity-selected samples. The clear trend seen in the early-type fraction from z=0 to z=~ 0.8 is not found in mass-selected samples. The early-type galaxy fraction changes much less, and is consistent with being constant at 92% +/- 4% at \Sigma> 500 galaxies Mpc^{-2} and 83 +/- 3% at 50 < \Sigma < 500 galaxies Mpc^{-2}. This suggests that galaxies of mass lower than > 10^{10.6} M_{\sun} play a significant role in the evolution of the early-type fraction in luminosity-selected samples. (Abstract abridged)Comment: 18 pages in emulate ApJ format, with 10 color figures, Accepted to ApJ. Version updated to reflect published version, includes new references and a correction to table

The Color-Magnitude Relation in CL 1358+62 at z=0.33: Evidence for Significant Evolution in the S0 Population

We use a large mosaic of HST WFPC2 images to measure the colors and morphologies of 194 spectroscopically confirmed members of the rich galaxy cluster CL1358+62 at z=0.33. We study the color-magnitude (CM) relation as a function of radius in the cluster. The intrinsic scatter in the restframe B-V CM relation of the elliptical galaxies is very small: ~0.022 magnitudes. The CM relation of the ellipticals does not depend significantly on the distance from the cluster center. In contrast, the CM relation for the S0 galaxies does depend on radius: the S0s in the core follow a CM relation similar to the ellipticals, but at large radii (R>0.7Mpc) the S0s are systematically bluer and the scatter in the CM relation approximately doubles to ~0.043 magnitudes. The blueing of the S0s is significant at the 95% confidence level. These results imply that the S0 galaxies in the outer parts of the cluster have formed stars more recently than the S0s in the inner parts. A likely explanation is that clusters at z=0.33 continue to accrete galaxies and groups from the field and that infall extinguishes star formation. The apparent homogeneity of the elliptical galaxy population implies that star formation in recently accreted ellipticals was terminated well before accretion occurred. We have constructed models to explore the constraints that these observations place on the star formation history of cluster galaxies. We conclude that the population of S0s in clusters is likely to evolve as star forming galaxies are converted into passively evolving galaxies. Assuming a constant accretion rate after z=0.33, we estimate ~15% of the present day early-type galaxy population in rich clusters was accreted between z=0.33 and z=0. The ellipticals (and the brightest S0s) are probably a more stable population, at least since z=0.6.Comment: Accepted for publication in the ApJ. 20 pages, 12 figures. Full version and plates available at http://www.astro.rug.nl/~dokkum/papers.htm

HST Photometry and Keck Spectroscopy of the Rich Cluster MS1054-03: Morphologies, Butcher-Oemler Effect and the Color-Magnitude Relation at z=0.83

We present a study of 81 I selected, spectroscopically-confirmed members of the X-ray cluster MS1054-03 at z=0.83. Redshifts and spectral types were determined from Keck spectroscopy. Morphologies and accurate colors were determined from a large mosaic of HST WFPC2 images in F606W and F814W. Early-type galaxies constitute only 44% of this galaxy population. Thirty-nine percent are spiral galaxies, and 17% are mergers. The early-type galaxies follow a tight and well-defined color-magnitude relation, with the exception of a few outliers. The observed scatter is 0.029 +- 0.005 magnitudes in restframe U-B. Most of the mergers lie close to the CM relation defined by the early-type galaxies. They are bluer by only 0.07 +- 0.02 magnitudes, and the scatter in their colors is 0.07 +- 0.04 magnitudes. Spiral galaxies in MS1054-03 exhibit a large range in their colors. The bluest spiral galaxies are 0.7 magnitudes bluer than the early-type galaxies, but the majority is within +- 0.2 magnitudes of the early-type galaxy sequence. The red colors of the mergers and the majority of the spiral galaxies are reflected in the fairly low Butcher-Oemler blue fraction of MS1054-03: f_B=0.22 +- 0.05. The slope and scatter of the CM relation of early-type galaxies are roughly constant with redshift, confirming previous studies that were based on ground-based color measurements and very limited membership information. However, the scatter in the combined sample of early-type galaxies and mergers is twice as high as the scatter of the early-type galaxies alone. This is a direct demonstration of the ``progenitor bias'': high redshift early-type galaxies seem to form a homogeneous, old population because the progenitors of the youngest present-day early-type galaxies are not included in the sample.Comment: Accepted for publication in the ApJ. At http://astro.caltech.edu/~pgd/cm1054/ color figures can be obtaine

The Velocity Dispersion of MS1054-03: A Massive Galaxy Cluster at High Redshift

We present results from a dynamical study of the high redshift, massive, X-ray luminous galaxy cluster MS1054--03. We significantly increase the number of confirmed cluster members by adding 20 to an existing set of twelve; using the confirmed members, we estimate MS1054--03's redshift, velocity dispersion, and mass. We find that z=0.8329 +/- 0.0017, sigma = 1170 +/- 150 km/s, and the central mass is approximately 1.9 +/- 0.5 x 10^{15} h^{-1} M_{odot} (within R=1 h^{-1} Mpc; H_0 =100h km s^{-1} Mpc^{-1}, q_0=0.5). MS1054--03 is one of a handful of high redshift (z>0.5) clusters known that also has X-ray and weak-lensing observations (Donahue et al. 1998; Luppino & Kaiser 1997); we find our dynamical mass agrees with mass estimates from both studies. The confirmation of MS1054--03 as a massive cluster at z~0.8 is consistent with an open (Omega_M~0.3) or flat, Lambda-dominated (Omega_M+Omega_{Lambda}=1) universe. In addition, we compare MS1054--03's velocity dispersion and X-ray temperature to a sample of low and intermediate redshift galaxy clusters to test for evolution in the sigma - T_x relation; we find no evidence for evolution in this relation to z~0.8.Comment: 13 pages, 3 figures, LaTex; Accepted for Publication in the Astrophysical Journa

Integrating technology into complex intervention trial processes: a case study

This is the final version of the article. Available from BioMed Central via the DOI in this record.Background Trials of complex interventions are associated with high costs and burdens in terms of paperwork, management, data collection, validation, and intervention fidelity assessment occurring across multiple sites. Traditional data collection methods rely on paper-based forms, where processing can be time-consuming and error rates high. Electronic source data collection can potentially address many of these inefficiencies, but has not routinely been used in complex intervention trials. Here we present the use of an on-line system for managing all aspects of data handling and for the monitoring of trial processes in a multicentre trial of a complex intervention. We custom built a web-accessible software application for the delivery of ENGAGE-HD, a multicentre trial of a complex physical therapy intervention. The software incorporated functionality for participant randomisation, data collection and assessment of intervention fidelity. It was accessible to multiple users with differing levels of access depending on required usage or to maintain blinding. Each site was supplied with a 4G-enabled iPad for accessing the system. The impact of this system was quantified through review of data quality and collation of feedback from site coordinators and assessors through structured process interviews. Results The custom-built system was an efficient tool for collecting data and managing trial processes. Although the set-up time required was significant, using the system resulted in an overall data completion rate of 98.5% with a data query rate of 0.1%, the majority of which were resolved in under a week. Feedback from research staff indicated that the system was highly acceptable for use in a research environment. This was a reflection of the portability and accessibility of the system when using the iPad and its usefulness in aiding accurate data collection, intervention fidelity and general administration. Conclusions A combination of commercially available hardware and a bespoke online database designed to support data collection, intervention fidelity and trial progress provides a viable option for streamlining trial processes in a multicentre complex intervention trial. There is scope to further extend the system to cater for larger trials and add further functionality such as automatic reporting facilities and participant management support.The ENGAGE-HD trial was funded by Health and Social Care Wales, United Kingdom. The South East Wales Trials Unit is funded by the Wales Assembly Government through Health and Care Research Wales