Interaction of SN Ib 2004dk with a Previously Expelled Envelope.

The interaction between the expanding supernova (SN) ejecta with the circumstellar material (CSM) that was expelled from the progenitor prior to explosion is a long-sought phenomenon, yet observational evidence is scarce. Here we confirm a new example: SN 2004dk, originally a hydrogen-poor, helium-rich Type Ib SN that reappeared as a strong Hα-emitting point source on narrowband Hα images. We present follow-up optical spectroscopy that reveals the presence of a broad Hα component with full width at half maximum of ~ 290 km s-1 in addition to the narrow Hα+[N ii] emission features from the host galaxy. Such a broad component is a clear sign of an ejecta-CSM interaction. We also present observations with the XMM-Newton Observatory, the Swift satellite, and the Chandra X-ray Observatory that span 10 days to 15 years after discovery. The detection of strong radio, X-ray, and Hα emission years after explosion allows various constraints to be put on pre-SN mass-loss processes. We present a wind-bubble model in which the CSM is "pre-prepared" by a fast wind interacting with a slow wind. Much of the outer density profile into which the SN explodes corresponds to no steady-state mass-loss process. We estimate that the shell of compressed slow wind material was ejected ~1400 yr prior to explosion, perhaps during carbon burning, and that the SN shock had swept up about 0.04 M ⊙ of material. The region emitting the Hα has a density of order 10-20 g cm-3.

X-ray emission from SN 2012ca: A Type Ia-CSM supernova explosion in a dense surrounding medium.

X-ray emission is one of the signposts of circumstellar interaction in supernovae (SNe), but until now, it has been observed only in core-collapse SNe. The level of thermal X-ray emission is a direct measure of the density of the circumstellar medium (CSM), and the absence of X-ray emission from Type Ia SNe has been interpreted as a sign of a very low density CSM. In this paper, we report late-time (500-800 d after discovery) X-ray detections of SN 2012ca in Chandra data. The presence of hydrogen in the initial spectrum led to a classification of Type Ia-CSM, ostensibly making it the first SN Ia detected with X-rays. Our analysis of the X-ray data favours an asymmetric medium, with a high-density component which supplies the X-ray emission. The data suggest a number density >108 cm-3 in the higher density medium, which is consistent with the large observed Balmer decrement if it arises from collisional excitation. This is high compared to most core-collapse SNe, but it may be consistent with densities suggested for some Type IIn or superluminous SNe. If SN 2012ca is a thermonuclear SN, the large CSM density could imply clumps in the wind, or a dense torus or disc, consistent with the single-degenerate channel. A remote possibility for a core-degenerate channel involves a white dwarf merging with the degenerate core of an asymptotic giant branch star shortly before the explosion, leading to a common envelope around the SN.

Supernova SN 2011fe from an exploding carbon-oxygen white dwarf star.

Type Ia supernovae have been used empirically as 'standard candles' to demonstrate the acceleration of the expansion of the Universe even though fundamental details, such as the nature of their progenitor systems and how the stars explode, remain a mystery. There is consensus that a white dwarf star explodes after accreting matter in a binary system, but the secondary body could be anything from a main-sequence star to a red giant, or even another white dwarf. This uncertainty stems from the fact that no recent type Ia supernova has been discovered close enough to Earth to detect the stars before explosion. Here we report early observations of supernova SN 2011fe in the galaxy M101 at a distance from Earth of 6.4 megaparsecs. We find that the exploding star was probably a carbon-oxygen white dwarf, and from the lack of an early shock we conclude that the companion was probably a main-sequence star. Early spectroscopy shows high-velocity oxygen that slows rapidly, on a timescale of hours, and extensive mixing of newly synthesized intermediate-mass elements in the outermost layers of the supernova. A companion paper uses pre-explosion images to rule out luminous red giants and most helium stars as companions to the progenitor.

Exclusion of a luminous red giant as a companion star to the progenitor of supernova SN 2011fe.

Type Ia supernovae are thought to result from a thermonuclear explosion of an accreting white dwarf in a binary system, but little is known of the precise nature of the companion star and the physical properties of the progenitor system. There are two classes of models: double-degenerate (involving two white dwarfs in a close binary system) and single-degenerate models. In the latter, the primary white dwarf accretes material from a secondary companion until conditions are such that carbon ignites, at a mass of 1.38 times the mass of the Sun. The type Ia supernova SN 2011fe was recently detected in a nearby galaxy. Here we report an analysis of archival images of the location of SN 2011fe. The luminosity of the progenitor system (especially the companion star) is 10-100 times fainter than previous limits on other type Ia supernova progenitor systems, allowing us to rule out luminous red giants and almost all helium stars as the mass-donating companion to the exploding white dwarf.

Safety, pharmacokinetics, and antitumor activity of AMG 386, a selective angiopoietin inhibitor, in adult patients with advanced solid tumors.

PURPOSE AMG 386 is an investigational peptide-Fc fusion protein (ie, peptibody) that inhibits angiogenesis by preventing the interaction of angiopoietin-1 and angiopoietin-2 with their receptor, Tie2. This first-in-human study evaluated the safety, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of AMG 386 in adults with advanced solid tumors. PATIENTS AND METHODS Patients in sequential cohorts received weekly intravenous AMG 386 doses of 0.3, 1, 3, 10, or 30 mg/kg. Results Thirty-two patients were enrolled on the study and received AMG 386. One occurrence of dose-limiting toxicity was seen at 30 mg/kg: respiratory arrest, which likely was caused by tumor burden that was possibly related to AMG 386. The most common toxicities were fatigue and peripheral edema. Proteinuria (n = 11) was observed without clinical sequelae. Only four patients (12%) experienced treatment-related toxicities greater than grade 1. A maximum-tolerated dose was not reached. PK was dose-linear and the mean terminal-phase elimination half-life values ranged from 3.1 to 6.3 days. Serum AMG 386 levels appeared to reach steady-state after four weekly doses, and there was minimal accumulation. No anti-AMG 386 neutralizing antibodies were detected. Reductions in volume transfer constant (K(trans); measured by dynamic contrast-enhanced magnetic resonance imaging) were observed in 10 patients (13 lesions) 48 hours to 8 weeks after treatment. One patient with refractory ovarian cancer achieved a confirmed partial response (ie, 32.5% reduction by Response Evaluation Criteria in Solid Tumors) and withdrew from the study with a partial response after 156 weeks of treatment; four patients experienced stable disease for at least 16 weeks. CONCLUSION Weekly AMG 386 appeared well tolerated, and its safety profile appeared distinct from that of vascular endothelial growth factor-axis inhibitors. AMG 386 also appeared to impact tumor vascularity and showed antitumor activity in this patient population.

The utility of MRI in predicting radiographic erosions in the metatarsophalangeal joints of the rheumatoid foot: a prospective longitudinal cohort study.

INTRODUCTION: Magnetic resonance imaging (MRI) may reveal rheumatoid arthritis (RA) changes in the feet when hands are normal. The purpose of this study was to determine the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of a metatarsophalangeal (MTP) erosion on MRI to predict a subsequent radiographic erosion in the same joint. Similar analyses were performed for bone marrow edema, predicting a subsequent MRI erosion. Descriptive results of other lesions are reported. METHODS: Fifty patients with RA of less than 5 years' duration who were rheumatoid factor-positive and/or anti-cyclic citrullinated peptide-positive were recruited. Patients on anti-tumor necrosis factor (TNF) therapy were excluded. Anti-TNF therapy could begin after enrollment. MRI and radiographs of the 3rd, 4th, and 5th MTP joints bilaterally were taken at baseline and at 6, 12, and 24 months. Clinical data were collected. RESULTS: Fifty patients were recruited; 46 patients had suitable data. Results for MRI erosions predicting subsequent radiographic erosions for 6, 12, and 24 months, respectively, were as follows: sensitivity 0.75, 0.60, 0.75; specificity 0.93, 0.94, 0.94; PPV 0.086, 0.10, 0.17; NPV 0.998, 0.995, 0.995. Results for MRI bone marrow edema predicting MRI erosions at 6 and 12 months, respectively, revealed sensitivity 0.50, 0.67; specificity 0.97, 0.97; PPV 0.25, 0.50; NPV 0.99, 0.99. Synovitis was the most common finding and, when present in isolation, resolved on 67.3% of subsequent studies. MRI erosions persisted on subsequent studies with one exception. Forty-six percent of the cohort was on anti-TNF therapy after study inception. CONCLUSIONS: The PPV of MRI erosions to predict subsequent radiographic erosions was low. Similarly, the PPV of bone marrow edema to predict a later MRI erosion was low. Alternatively, the NPV of the absence of an MRI erosion or bone marrow edema predicts that a later radiographic erosion or MRI erosion will likely not develop. Anti-TNF therapies may have resulted in the lower-than-anticipated PPVs. MRI descriptions of bone edema may represent a more critical time to treat in order to avoid damage, whereas an MRI erosion represents more permanent damage. This study suggests that imaging modalities more sensitive than radiographs are necessary to monitor disease in the biologic era.

Small airways response to naturalistic cat allergen exposure in subjects with asthma.

BACKGROUND: It is currently unclear whether the small airways (diameter <2 microm) contribute significantly to late asthmatic reactions to inhaled allergen. OBJECTIVES: We sought to determine whether naturalistic exposure to cat allergen induced late responses in the small airways as measured by pulmonary function testing and high-resolution computed tomography (HRCT) of the chest performed at end-expiration. METHODS: In a group of 10 subjects with cat-induced asthma, physiologic studies (spirometry and lung volumes, including closing volume) and HRCT were performed before and 6 and 23 hours after a cat room challenge that caused a 20% or greater acute fall in FEV(1). RESULTS: There was no significant decline in FEV(1) at 6 or 23 hours after cat exposure. Forced expiratory flow at 25% to 75% of forced vital capacity was significantly decreased at 6 hours after the challenge and returned to normal by 23 hours. HRCT image analysis as well as closing volume demonstrated increased air trapping from baseline at both 6 and 23 hours after the challenge. In addition, image analysis demonstrated a significant increase in small airways hyperresponsiveness to methacholine at 23 hours after the challenge. No significant mean changes were noted in lung volumes at either 6 or 23 hours or in PC(20) FEV(1) at 23 hours postchallenge. CONCLUSION: These findings demonstrate that naturalistic exposure to cat allergen results in significant small airways obstruction and hyperresponsiveness persisting for at least 23 hours, at which time these changes cannot be detected by conventional physiologic measures. CLINICAL IMPLICATIONS: Physiologically silent distal lung inflammation persists after an antigenic challenge.