Long-term maintenance of certolizumab pegol safety and efficacy, in combination with methotrexate and as monotherapy, in rheumatoid arthritis patients

Introduction The safety and efficacy of certolizumab pegol (CZP) 400 mg every 4 weeks (Q4W) monotherapy (FAST4WARD/NCT00548834) and in combination with methotrexate (MTX) (014/NCT00544154) in active rheumatoid arthritis (RA) has been published previously. This report outlines final long-term outcomes from the open-label extension (OLE) study (015/NCT00160693), which enrolled patients from these randomized controlled trials (RCTs). Methods Patients who withdrew from or completed the 24-week 014/FAST4WARD RCTs were enrolled and received CZP 400 mg Q4W with/without MTX. Exposure-adjusted event rates (ER) per 100 patient-years (PYs) of adverse events (AEs) and serious AEs (SAEs) were reported for all patients receiving ≥1 dose of CZP in RCTs or OLE (N = 427) between first CZP dose and up to 24 weeks after last CZP dose or study withdrawal. Efficacy assessments included clinical (ACR20/50/70 response rates, TJC, SJC) and patient-reported outcomes (HAQ-DI, PtGADA, pain, fatigue) to week 304 (5.8 years) in the CZP intent-to-treat population. SDAI and CDAI outcomes were analyzed post hoc. Outcomes for CZP monotherapy and CZP+MTX combination-therapy were compared. Results Globally, ERs of AEs and SAEs were 408.1 and 25.2 per 100 PY, respectively. Eleven patients had AEs leading to death (ER 0.6). Improvements in clinical and patient-reported outcomes during the 24-week RCTs were maintained to week 304, and were similar between all subpopulations. Conclusions The longest exposure duration to date with CZP 400 mg Q4W treatment confirmed the safety profile observed in previous studies. Initial improvements in signs and symptoms of RA, including PROs, were maintained in both CZP monotherapy and CZP + MTX combination-therapy patients

The Transit Ingress and the Tilted Orbit of the Extraordinarily Eccentric Exoplanet HD 80606b

We present the results of a transcontinental campaign to observe the 2009 June 5 transit of the exoplanet HD 80606b. We report the first detection of the transit ingress, revealing the transit duration to be 11.64 +/- 0.25 hr and allowing more robust determinations of the system parameters. Keck spectra obtained at midtransit exhibit an anomalous blueshift, giving definitive evidence that the stellar spin axis and planetary orbital axis are misaligned. The Keck data show that the projected spin-orbit angle is between 32-87 deg with 68.3% confidence and between 14-142 deg with 99.73% confidence. Thus the orbit of this planet is not only highly eccentric (e=0.93), but is also tilted away from the equatorial plane of its parent star. A large tilt had been predicted, based on the idea that the planet's eccentric orbit was caused by the Kozai mechanism. Independently of the theory, it is noteworthy that all 3 exoplanetary systems with known spin-orbit misalignments have massive planets on eccentric orbits, suggesting that those systems migrate differently than lower-mass planets on circular orbits.Comment: ApJ, in press [13 pg

Validation of Kepler's Multiple Planet Candidates. III: Light Curve Analysis & Announcement of Hundreds of New Multi-planet Systems

The Kepler mission has discovered over 2500 exoplanet candidates in the first two years of spacecraft data, with approximately 40% of them in candidate multi-planet systems. The high rate of multiplicity combined with the low rate of identified false-positives indicates that the multiplanet systems contain very few false-positive signals due to other systems not gravitationally bound to the target star (Lissauer, J. J., et al., 2012, ApJ 750, 131). False positives in the multi- planet systems are identified and removed, leaving behind a residual population of candidate multi-planet transiting systems expected to have a false-positive rate less than 1%. We present a sample of 340 planetary systems that contain 851 planets that are validated to substantially better than the 99% confidence level; the vast majority of these have not been previously verified as planets. We expect ~2 unidentified false-positives making our sample of planet very reliable. We present fundamental planetary properties of our sample based on a comprehensive analysis of Kepler light curves and ground-based spectroscopy and high-resolution imaging. Since we do not require spectroscopy or high-resolution imaging for validation, some of our derived parameters for a planetary system may be systematically incorrect due to dilution from light due to additional stars in the photometric aperture. None the less, our result nearly doubles the number of verified exoplanets.Comment: 138 pages, 8 Figures, 5 Tables. Accepted for publications in the Astrophysical Journa

A First Comparison of Kepler Planet Candidates in Single and Multiple Systems

In this letter we present an overview of the rich population of systems with multiple candidate transiting planets found in the first four months of Kepler data. The census of multiples includes 115 targets that show 2 candidate planets, 45 with 3, 8 with 4, and 1 each with 5 and 6, for a total of 170 systems with 408 candidates. When compared to the 827 systems with only one candidate, the multiples account for 17 percent of the total number of systems, and a third of all the planet candidates. We compare the characteristics of candidates found in multiples with those found in singles. False positives due to eclipsing binaries are much less common for the multiples, as expected. Singles and multiples are both dominated by planets smaller than Neptune; 69 +2/-3 percent for singles and 86 +2/-5 percent for multiples. This result, that systems with multiple transiting planets are less likely to include a transiting giant planet, suggests that close-in giant planets tend to disrupt the orbital inclinations of small planets in flat systems, or maybe even to prevent the formation of such systems in the first place.Comment: 13 pages, 13 figures, submitted to ApJ Letter

The HST/ACS Coma Cluster Survey. II. Data Description and Source Catalogs

The Coma cluster was the target of a HST-ACS Treasury program designed for deep imaging in the F475W and F814W passbands. Although our survey was interrupted by the ACS instrument failure in 2007, the partially completed survey still covers ~50% of the core high-density region in Coma. Observations were performed for 25 fields that extend over a wide range of cluster-centric radii (~1.75 Mpc) with a total coverage area of 274 arcmin^2. The majority of the fields are located near the core region of Coma (19/25 pointings) with six additional fields in the south-west region of the cluster. In this paper we present reprocessed images and SExtractor source catalogs for our survey fields, including a detailed description of the methodology used for object detection and photometry, the subtraction of bright galaxies to measure faint underlying objects, and the use of simulations to assess the photometric accuracy and completeness of our catalogs. We also use simulations to perform aperture corrections for the SExtractor Kron magnitudes based only on the measured source flux and half-light radius. We have performed photometry for ~73,000 unique objects; one-half of our detections are brighter than the 10-sigma point-source detection limit at F814W=25.8 mag (AB). The slight majority of objects (60%) are unresolved or only marginally resolved by ACS. We estimate that Coma members are 5-10% of all source detections, which consist of a large population of unresolved objects (primarily GCs but also UCDs) and a wide variety of extended galaxies from a cD galaxy to dwarf LSB galaxies. The red sequence of Coma member galaxies has a constant slope and dispersion across 9 magnitudes (-21<M_F814W<-13). The initial data release for the HST-ACS Coma Treasury program was made available to the public in 2008 August. The images and catalogs described in this study relate to our second data release.Comment: Accepted for publication in ApJS. A high-resolution version is available at http://archdev.stsci.edu/pub/hlsp/coma/release2/PaperII.pd

Acute hospital admissions among nursing home residents: a population-based observational study

<p>Abstract</p> <p>Background</p> <p>Nursing home residents are prone to acute illness due to their high age, underlying illnesses and immobility. We examined the incidence of acute hospital admissions among nursing home residents versus the age-matched community dwelling population in a geographically defined area during a two years period. The hospital stays of the nursing home population are described according to diagnosis, length of stay and mortality. Similar studies have previously not been reported in Scandinavia.</p> <p>Methods</p> <p>The acute hospitalisations of the nursing home residents were identified through ambulance records. These were linked to hospital patient records for inclusion of demographics, diagnosis at discharge, length of stay and mortality. Incidence of hospitalisation was calculated based on patient-time at risk.</p> <p>Results</p> <p>The annual hospital admission incidence was 0.62 admissions per person-year among the nursing home residents and 0.26 among the community dwellers. In the nursing home population we found that dominant diagnoses were respiratory diseases, falls-related and circulatory diseases, accounting for 55% of the cases. The median length of stay was 3 days (interquartile range = 4). The in-hospital mortality rate was 16% and 30 day mortality after discharge 30%.</p> <p>Conclusion</p> <p>Acute hospital admission rate among nursing home residents was high in this Scandinavian setting. The pattern of diagnoses causing the admissions appears to be consistent with previous research. The in-hospital and 30 day mortality rates are high.</p

Planetary Candidates Observed by Kepler, III: Analysis of the First 16 Months of Data

New transiting planet candidates are identified in sixteen months (May 2009 - September 2010) of data from the Kepler spacecraft. Nearly five thousand periodic transit-like signals are vetted against astrophysical and instrumental false positives yielding 1,091 viable new planet candidates, bringing the total count up to over 2,300. Improved vetting metrics are employed, contributing to higher catalog reliability. Most notable is the noise-weighted robust averaging of multi-quarter photo-center offsets derived from difference image analysis which identifies likely background eclipsing binaries. Twenty-two months of photometry are used for the purpose of characterizing each of the new candidates. Ephemerides (transit epoch, T_0, and orbital period, P) are tabulated as well as the products of light curve modeling: reduced radius (Rp/R*), reduced semi-major axis (d/R*), and impact parameter (b). The largest fractional increases are seen for the smallest planet candidates (197% for candidates smaller than 2Re compared to 52% for candidates larger than 2Re) and those at longer orbital periods (123% for candidates outside of 50-day orbits versus 85% for candidates inside of 50-day orbits). The gains are larger than expected from increasing the observing window from thirteen months (Quarter 1-- Quarter 5) to sixteen months (Quarter 1 -- Quarter 6). This demonstrates the benefit of continued development of pipeline analysis software. The fraction of all host stars with multiple candidates has grown from 17% to 20%, and the paucity of short-period giant planets in multiple systems is still evident. The progression toward smaller planets at longer orbital periods with each new catalog release suggests that Earth-size planets in the Habitable Zone are forthcoming if, indeed, such planets are abundant.Comment: Submitted to ApJS. Machine-readable tables are available at http://kepler.nasa.gov, http://archive.stsci.edu/kepler/results.html, and the NASA Exoplanet Archiv

The Lantern Vol. 50, No. 2, Spring 1984

• The Storm • Je ne sais pas • The Ghetious Blastious • An Empty Cradle • The Playing Hands • Battle Hymn • A Limerick • Parting Thoughts • The River • Miss You • De la Tristeza • Two So Special • Time of the Unicorn • The Absence • Thru The Breeze • Is the World Really a Round Ball? • Brother • To Michael • Gravity • Refuge • Der Witwer • Plastic Flowers Never Die • Book on the Shelfhttps://digitalcommons.ursinus.edu/lantern/1124/thumbnail.jp