Run-in periods and clinical outcomes of antipsychotics in dementia:A meta-epidemiological study of placebo-controlled trials

PURPOSE: Run-in periods are used to identify placebo-responders and washout. Our aim was to assess the association of run-in periods with clinical outcomes of antipsychotics in dementia. METHODS: We searched randomized placebo-controlled trials of conventional and atypical antipsychotics for neuropsychiatric symptoms (NPS) in dementia in electronic sources and references of selected articles. We extracted (a) the presence of a run-in period, use of placebo/investigated drug during run-in (versus washout only), and run-in duration (1 week or more) and (b) the reduction in NPS, number of participants with somnolence, extrapyramidal symptoms (EPS), and deaths per treatment group. We pooled clinical outcomes comparing antipsychotic and placebo groups in trials with and without run-in. RESULTS: We identified 35 trials. Twenty-nine trials used run-in. The pooled standardized mean difference in the reduction of NPS was -0.170 (95% CI, -0.227 to -0.112) in trials with run-in and -0.142 (95% CI, -0.331 to 0.047) in trials without run-in. The pooled odds ratio for somnolence was 2.8 (95% CI, 2.3-3.5) in trials with run-in and 3.5 (95% CI, 1.2-10.7) in trials without run-in; for EPS, these ORs were 1.8 (95% CI, 1.4-2.2) and 2.0 (95% CI, 1.3-3.1) respectively, and for mortality 1.4 (95% CI, 1.0-2.0) and 1.6 (95% CI, 0.7-3.4). The use of placebo/investigated drug during run-in and run-in duration did not affect the estimates in a consistent way. CONCLUSIONS: The use of run-in in trials might have led to overestimated efficacy and especially underestimated risks of side effects of antipsychotics compared with placebo for NPS in dementia

The Young, Massive, Star Cluster Sandage-96 After the Explosion of SN 2004dj in NGC 2403

The bright Type II-plateau supernova (SN) 2004dj occurred within the young, massive stellar cluster Sandage-96 in a spiral arm of NGC 2403. New multi-wavelength observations obtained with several ground-based and space-based telescopes are combined to study the radiation from Sandage-96 after SN 2004dj faded away. Sandage-96 started to dominate the flux in the optical bands starting September 2006 (~800 d after explosion). The optical fluxes are equal to the pre-explosion ones within the observational uncertainties. An optical Keck spectrum obtained ~900 d after explosion shows the dominant blue continuum from the cluster stars shortward of 6000 \AA as well as strong SN nebular emission lines redward. The integrated spectral energy distribution (SED) of the cluster has been extended into the ultraviolet region by archival XMM-Newton and new Swift observations, and compared with theoretical models. The outer parts of the cluster have been resolved by the Hubble Space Telescope, allowing the construction of a color-magnitude diagram. The fitting of the cluster SED with theoretical isochrones results in cluster ages between 10--40 Myr, depending on metallicity and the model family. The isochrone fitting indicates that the resolved part of the cluster has a bimodal age distribution: a younger population at ~10--16 Myr, and an older one at ~32--100 Myr which is similar to the age distribution of the nearby field stars. These stars may have been captured from the field during the cluster formation. The young age of Sandage-96 suggest 12 < M_prog < 20 M_\odot as the most probable mass range for the progenitor of SN 2004dj. This is consistent with, but perhaps slightly higher than, most of the other Type II-plateau SN progenitor masses determined so far.Comment: accepted in Ap

Observation of light echoes around very young stars

The goal of the paper is to present new results on light echoes from young stellar objects. Broad band CCD images were obtained over three months at one-to-two week intervals for the field of NGC 6726, using the large field-of-view remotely-operated telescope on top of Cerro Burek. We detected scattered light echoes around two young, low-amplitude, irregular variable stars. Observations revealed not just one, but multiple light echoes from brightness pulses of the T Tauri star S CrA and the Herbig Ae/Be star R CrA. Analysis of S CrA's recurring echoes suggests that the star is located 138 +/- 16 pc from Earth, making these the closest echoes ever detected. The environment that scatters the stellar light from S CrA is compatible with an incomplete dust shell or an inclined torus some 10,000 AU in radius and containing $\sim$ $2 \times 10^{-3}$ M_{\sun} of dust. The cause of such concentration at $\sim$ 10,000AU from the star is unknown. It could be the remnant of the envelope from which the star formed, but the distance of the cloud is remarkably similar to the nominal distance of the Oort cloud to the Sun, leading us to also speculate that the dust (or ice) seen around S CrA might have the same origin as the Solar System Oort cloud.Comment: A&A, in press Received: 16 March 2010 / Accepted: 01 June 201

SN 2007od: A Type IIP SN with Circumstellar Interaction

SN 2007od exhibits characteristics that have rarely been seen in a Type IIP supernova (SN). Optical V band photometry reveals a very steep brightness decline between the plateau and nebular phases of ~4.5 mag, likely due to SN 2007od containing a low mass of 56Ni. The optical spectra show an evolution from normal Type IIP with broad Halpha emission, to a complex, four component Halpha emission profile exhibiting asymmetries caused by dust extinction after day 232. This is similar to the spectral evolution of the Type IIn SN 1998S, although no early-time narrow (~200 km s-1) Halpha component was present in SN 2007od. In both SNe, the intermediate-width Halpha emission components are thought to arise in the interaction between the ejecta and its circumstellar medium (CSM). SN 2007od also shows a mid-IR excess due to new dust. The evolution of the Halpha profile and the presence of the mid-IR excess provide strong evidence that SN 2007od formed new dust before day 232. Late-time observations reveal a flattening of the visible lightcurve. This flattening is a strong indication of the presence of a light echo, which likely accounts for much of the broad, underlying Halpha component seen at late-times. We believe the multi-peaked Halpha emission is consistent with the interaction of the ejecta with a circumstellar ring or torus (for the inner components at \pm1500 km s-1), and a single blob or cloud of circumstellar material out of the plane of the CSM ring (for the outer component at -5000 km s-1). The most probable location for the formation of new dust is in the cool dense shell created by the interaction between the expanding ejecta and its CSM. Monte Carlo radiative transfer modeling of the dust emission from SN 2007od implies that up to 4x 10-4Msun of new dust has formed. This is similar to the amounts of dust formed in other CCSNe such as SNe 1999em, 2004et, and 2006jc.Comment: 35 pages, 6 figures. Accepted for publication in Ap

The pathogenesis of oral lichen planus

Both antigen-specific and non-specific mechanisms may be involved in the pathogenesis of oral lichen planus (OLP). Antigen-specific mechanisms in OLP include antigen presentation by basal keratinocytes and antigen-specific keratinocyte killing by CD8(+) cytotoxic T-cells. Non-specific mechanisms include mast cell degranulation and matrix metalloproteinase (MMP) activation in OLP lesions. These mechanisms may combine to cause T-cell accumulation in the superficial lamina propria, basement membrane disruption, intra-epithelial T-cell migration, and keratinocyte apoptosis in OLP. OLP chronicity may be due, in part, to deficient antigen-specific TGF-beta1-mediated immunosuppression. The normal oral mucosa may be an immune privileged site (similar to the eye, testis, and placenta), and breakdown of immune privilege could result in OLP and possibly other autoimmune oral mucosal diseases. Recent findings in mucocutaneous graft-versus-host disease, a clinical and histological correlate of lichen planus, suggest the involvement of TNF-alpha, CD40, Fas, MMPs, and mast cell degranulation in disease pathogenesis. Potential roles for oral Langerhans cells and the regional lymphatics in OLP lesion formation and chronicity are discussed. Carcinogenesis in OLP may be regulated by the integrated signal from various tumor inhibitors (TGF-beta1, TNF-alpha, IFN-gamma, IL-12) and promoters (MIF, MMP-9). We present our recent data implicating antigen-specific and non-specific mechanisms in the pathogenesis of OLP and propose a unifying hypothesis suggesting that both may be involved in lesion development. The initial event in OLP lesion formation and the factors that determine OLP susceptibility are unknown

The Double Dust Envelopes of R Coronae Borealis Stars

The study of extended, cold dust envelopes surrounding R Coronae Borealis (RCB) stars began with their discovery by the Infrared Astronomical Satellite. RCB stars are carbon-rich supergiants characterized by their extreme hydrogen deficiency and their irregular and spectacular declines in brightness (up to 9 mag). We have analyzed new and archival Spitzer Space Telescope and Herschel Space Observatory data of the envelopes of seven RCB stars to examine the morphology and investigate the origin of these dusty shells. Herschel, in particular, has revealed the first-ever bow shock associated with an RCB star with its observations of SU Tauri. These data have allowed the assembly of the most comprehensive spectral energy distributions (SEDs) of these stars with multiwavelength data from the ultraviolet to the submillimeter. Radiative transfer modeling of the SEDs implies that the RCB stars in this sample are surrounded by an inner warm (up to 1200 K) and an outer cold (up to 200 K) envelope. The outer shells are suggested to contain up to 10-3 M o of dust and have existed for up to 105 years depending on the expansion rate of the dust. This age limit indicates that these structures have most likely been formed during the RCB phase

RR Lyrae Variables in the Globular Clusters of M31: a First Detection of Likely Candidates

The purpose of this paper is to show that RR Lyrae variables exist and can be detected in M31 globular clusters. We report on the first tentative identification of RR Lyrae candidates in four globular clusters of the Andromeda galaxy, i.e. G11, G33, G64 and G322. Based on HST-WFPC2 archive observations in the F555W and F814W filters spanning a total interval of about 5 consecutive hours we find evidence for 2, 4, 11 and 8 RR Lyrae variables of both ab and c Bailey types in G11, G33, G64 and G322, respectively. Several more candidates can be found by relaxing slightly the selection criteria. These numbers are quite consistent with the horizontal branch morphology exhibited by the four clusters, starting from the very blue HB in G11, and progressively moving to redder HBs in G64, G33 and G322.Comment: 4 pages, 3 included figures, accepted for publication by ApJ Letter

The long-period Galactic Cepheid RS Puppis - II. 3D structure and mass of the nebula from VLT/FORS polarimetry

The long-period Cepheid RS Pup is surrounded by a large dusty nebula reflecting the light from the central star. Due to the changing luminosity of the central source, light echoes propagate into the nebula. This remarkable phenomenon was the subject of Paper I.The origin and physical properties of the nebula are however uncertain: it may have been created through mass loss from the star itself, or it could be the remnant of a pre-existing interstellar cloud. Our goal is to determine the 3D structure of the nebula, and estimate its mass. Knowing the geometrical shape of the nebula will also allow us to retrieve the distance of RS Pup in an unambiguous manner using a model of its light echoes (in a forthcoming work). The scattering angle of the Cepheid light in the circumstellar nebula can be recovered from its degree of linear polarization. We thus observed the nebula surrounding RS Pup using the polarimetric imaging mode of the VLT/FORS instrument, and obtained a map of the degree and position angle of linear polarization. From our FORS observations, we derive a 3D map of the distribution of the dust, whose overall geometry is an irregular and thin layer. The nebula does not present a well-defined symmetry. Using a simple model, we derive a total dust mass of M(dust) = 2.9 +/- 0.9 Msun for the dust within 1.8 arcmin of the Cepheid. This translates into a total mass of M(gas+dust) = 290 +/- 120 Msun, assuming a dust-to-gas ratio of 1.0 +/- 0.3 %. The high mass of the dusty nebula excludes that it was created by mass-loss from the star. However, the thinness nebula is an indication that the Cepheid participated to its shaping, e.g. through its radiation pressure or stellar wind. RS Pup therefore appears as a regular long-period Cepheid located in an exceptionally dense interstellar environment.Comment: 14 pages, 21 figures. Accepted for publication in A&

Time evolution of the line emission from the inner circumstellar ring of SN 1987A and its hot spots

We present seven epochs between October 1999 and November 2007 of high resolution VLT/UVES echelle spectra of the ejecta-ring collision of SN 1987A. The fluxes of most of the narrow lines from the unshocked gas decreased by a factor of 2-3 during this period, consistent with the decay from the initial ionization by the shock break-out. However, [O III] in particular shows an increase up to day ~6800. This agrees with radiative shock models where the pre-shocked gas is heated by the soft X-rays from the shock. The line emission from the shocked gas increases rapidly as the shock sweeps up more gas. We find that the neutral and high ionization lines follow the evolution of the Balmer lines roughly, while the intermediate ionization lines evolve less rapidly. Up to day ~6800, the optical light curves have a similar evolution to that of the soft X-rays. The break between day 6500 and day 7000 for [O III] and [Ne III] is likely due to recombination to lower ionization levels. Nevertheless, the evolution of the [Fe XIV] line, as well as the lines from the lowest ionization stages, continue to follow that of the soft X-rays, as expected. There is a clear difference in the line profiles between the low and intermediate ionization lines, and those from the coronal lines at the earlier epochs. This shows that these lines arise from regions with different physical conditions, with at least a fraction of the coronal lines coming from adiabatic shocks. At later epochs the line widths of the low ionization lines, however, increase and approach those of the high ionization lines of [Fe X-XIV]. The H-alpha line profile can be traced up to ~500 km/s at the latest epoch. This is consistent with the cooling time of shocks propagating into a density of (1-4)x10^4 cm-3.Comment: 25 Pages, 12 Figures, accepted for publication in A&