Imputation of a true endpoint from a surrogate: application to a cluster randomized controlled trial with partial information on the true endpoint

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background The Anglia Menorrhagia Education Study (AMES) is a randomized controlled trial testing the effectiveness of an education package applied to general practices. Binary data are available from two sources; general practitioner reported referrals to hospital, and referrals to hospital determined by independent audit of the general practices. The former may be regarded as a surrogate for the latter, which is regarded as the true endpoint. Data are only available for the true end point on a sub set of the practices, but there are surrogate data for almost all of the audited practices and for most of the remaining practices. Methods The aim of this paper was to estimate the treatment effect using data from every practice in the study. Where the true endpoint was not available, it was estimated by three approaches, a regression method, multiple imputation and a full likelihood model. Results Including the surrogate data in the analysis yielded an estimate of the treatment effect which was more precise than an estimate gained from using the true end point data alone. Conclusions The full likelihood method provides a new imputation tool at the disposal of trials with surrogate data.Published versio

The Environmental Kuznets Curve: Exploring a Fresh Specification

The objective of this paper is primarily methodological. Using a new specification, we reanalyze the data on worldwide environmental quality investigated by Gene Grossman and Alan Krueger in their well-known paper on the environmental Kuznets curve (which postulates an inverse U-shaped relationship between income level and pollution). This new specification avoids using nonlinear transformations of potentially nonstationary regressors in panel estimation, which is a major unresolved econometric problem plaguing much of the existing literature. We furthermore draw conclusions from fixed effects estimation, which had eluded Grossman and Krueger. Our estimation results indicate the presence of an EKC for only six of the fourteen pollutants, whereas Grossman and Krueger find support for all but one pollutan

Evidence for a Disk-Jet Interaction in the Microquasar GRS 1915+105

We report simultaneous X-ray and infrared (IR) observations of the Galactic microquasar GRS1915+105 using XTE and the Palomar 200-inch telescope on August 13-15, 1997 UTC. During the last two nights, the microquasar GRS 1915+105 exhibited quasi-regular X-ray/infrared (IR) flares with a spacing of $\sim 30$ minutes. While the physical mechanism triggering the flares is currently unknown, the one-to-one correspondence and consistent time offset between the X-ray and IR flares establish a close link between the two. At late times in the flares the X-ray and IR bands appear to ``decouple'', with the X-ray band showing large-amplitude fast oscillations while the IR shows a much smoother, more symmetrical decline. In at least three cases, the IR flare has returned to near its minimum while the X-rays continue in the elevated oscillatory state, ruling out thermal reprocessing of the X-ray flux as the source of IR flare. Furthermore, observations of similar IR and radio flares by Fender et al. (1997) imply that the source of the IR flux in such flares is synchrotron emission. The common rise and subsequent decoupling of the X-ray and IR flux and probable synchrotron origin of the IR emission is consistent with a scenario wherein the IR flux originates in a relativistic plasma which has been ejected from the inner accretion disk. In that case, these simultaneous X-ray/IR flares from a black-hole/relativistic-jet system are the first clear observational evidence linking of the time-dependent interaction of the jet and the inner disk in decades of quasar and microquasar studies.Comment: 15 pages, incl. 3 figures. To appear in ApJ Letter

HST/NICMOS Observations of Fast Infrared Flickering in the Microquasar GRS 1915+105

We report infrared observations of the microquasar GRS 1915+105 using the NICMOS instrument of the Hubble Space Telescope during 9 visits in April-June 2003. During epochs of high X-ray/radio activity near the beginning and end of this period, we find that the $1.87$\um infrared flux is generally low ($\sim 2$ mJy) and relatively steady. However, during the X-ray/radio ``plateau'' state between these epochs, we find that the infrared flux is significantly higher ($\sim 4-6$ mJy), and strongly variable. In particular, we find events with amplitudes $\sim 20-30$% occurring on timescales of $\sim 10-20$s (e-folding timescales of $\sim 30$s). These flickering timescales are several times faster than any previously-observed infrared variability in GRS 1915+105 and the IR variations exceed corresponding X-ray variations at the same ($\sim 8s$) timescale. These results suggest an entirely new type of infrared variability from this object. Based on the properties of this flickering, we conclude that it arises in the plateau-state jet outflow itself, at a distance $<2.5$ AU from the accretion disk. We discuss the implications of this work and the potential of further flickering observations for understanding jet formation around black holes.Comment: 19 pages, incl. 4 figures; accepted for publication in Ap

Observations of Rapid Disk-Jet Interaction in the Microquasar GRS 1915+105

We present evidence that ~ 30 minute episodes of jet formation in the Galactic microquasar GRS 1915+105 may sometimes entirely be a superposition of smaller, faster phenomena. We base this conclusion on simultaneous X-ray and infrared observations in July 2002, using the Rossi X-ray Timing Explorer and the Palomar 5 meter telescope. On two nights, we observed quasi-periodic infrared flares from GRS 1915+105, each accompanied by a set of fast oscillations in the X-ray light curve (indicating an interaction between the jet and accretion disk). In contrast to similar observations in 1997, we find that the duration of each X-ray cycle matches the duration of its accompanying infrared flare, and we observed one instance in which an isolated X-ray oscillation occurred at the same time as a faint infrared "subflare" (of duration ~ 150 seconds) superimposed on one of the main flares. From these data, we are able to conclude that each X-ray oscillation had an associated faint infrared flare and that these flares blend together to form, and entirely comprise, the ~ 30 minute events we observed. Part of the infrared emission in 1997 also appears to be due to superimposed small flares, but it was overshadowed by infrared-bright ejections associated with the appearance of a sharp "trigger" spike in each X-ray cycle that were not present in 2002. We also study the evolution of the X-ray spectrum and find significant differences in the high energy power law component, which was strongly variable in 1997 but not in 2002. Taken together, these observations reveal the diversity of ways in which the accretion disk and jet in black hole systems are capable of interacting and solidify the importance of the trigger spike for large ejections to occur on ~ 30 minute timescales in GRS 1915+105.Comment: 17 pages, 9 figures; accepted for publication in The Astrophysical Journa

A Transient Sub-Eddington Black Hole X-ray Binary Candidate in the Dust Lanes of Centaurus A

We report the discovery of a bright X-ray transient, CXOU J132527.6-430023, in the nearby early-type galaxy NGC 5128. The source was first detected over the course of five Chandra observations in 2007, reaching an unabsorbed outburst luminosity of 1-2*10^38 erg/s in the 0.5-7.0 keV band before returning to quiescence. Such luminosities are possible for both stellar-mass black hole and neutron star X-ray binary transients. Here, we attempt to characterize the nature of the compact object. No counterpart has been detected in the optical or radio sky, but the proximity of the source to the dust lanes allows for the possibility of an obscured companion. The brightness of the source after a >100 fold increase in X-ray flux makes it either the first confirmed transient non-ULX black hole system in outburst to be subject to detailed spectral modeling outside the Local Group, or a bright (>10^38 erg/s) transient neutron star X-ray binary, which are very rare. Such a large increase in flux would appear to lend weight to the view that this is a black hole transient. X-ray spectral fitting of an absorbed power law yielded unphysical photon indices, while the parameters of the best-fit absorbed disc blackbody model are typical of an accreting ~10 Msol black hole in the thermally dominant state.Comment: 8 pages, 6 figures, accepted for publication in Ap

Another thread in the tapestry of stellar feedback: X-ray binaries

We consider X-ray binaries (XBs) as potential sources of stellar feedback. XBs observationally appear able to deposit a high fraction of their power output into their local interstellar medium, which may make them a non-negligible source of energy input. The formation rate of the most luminous XBs rises with decreasing metallicity, which should increase their significance during galaxy formation in the early universe. We also argue that stochastic effects are important to XB feedback (XBF) and may dominate the systematic changes due to metallicity in many cases. Large stochastic variation in the magnitude of XBF at low absolute star formation rates provides a natural reason for diversity in the evolution of dwarf galaxies which were initially almost identical, with several percent of such halos experiencing energy input from XBs roughly two orders of magnitude above the most likely value. These probability distributions suggest that the effect of XBF is most commonly significant for total stellar masses between ~10^7 and 10^8 Msun, which might resolve a current problem with modelling populations of such galaxies. We explain how XBs might inject energy before luminous supernovae (SNe) contribute significantly to feedback and how XBs can assist in keeping gas hot long after the last core-collapse SN has exploded. [...] XBF could be especially important to some dwarf galaxies, potentially heating gas without expelling it; the properties of XBF also match those previously derived as allowing episodic star formation. We also argue that the efficiency of SN feedback (SNF) might be reduced when XBF has had the opportunity to act first. In addition, we note that the effect of SNF is unlikely to be scale-free; galaxies smaller than ~100 pc might well experience less effective SNF. (Slightly abbreviated to fit arXiv size limit.)Comment: Very belatedly updated to include a note added in proof and additional reference. The definitive version is at: mnras.oxfordjournals.org/content/423/2/164

Triangulation of gravitational wave sources with a network of detectors

There is significant benefit to be gained by pursuing multi-messenger astronomy with gravitational wave and electromagnetic observations. In order to undertake electromagnetic follow-ups of gravitational wave signals, it will be necessary to accurately localize them in the sky. Since gravitational wave detectors are not inherently pointing instruments, localization will occur primarily through triangulation with a network of detectors. We investigate the expected timing accuracy for observed signals and the consequences for localization. In addition, we discuss the effect of systematic uncertainties in the waveform and calibration of the instruments on the localization of sources. We provide illustrative results of timing and localization accuracy as well as systematic effects for coalescing binary waveforms.Comment: 20 pages, 5 figure

Prognostic value of the 6-gene OncoMasTR test in hormone receptor–positive HER2-negative early-stage breast cancer: Comparative analysis with standard clinicopathological factors

Aim: The aim of the study was to assess the prognostic performance of a 6-gene molecular score (OncoMasTR Molecular Score [OMm]) and a composite risk score (OncoMasTR Risk Score [OM]) and to conduct a within-patient comparison against four routinely used molecular and clinicopathological risk assessment tools: Oncotype DX Recurrence Score, Ki67, Nottingham Prognostic Index and Clinical Risk Category, based on the modified Adjuvant! Online definition and three risk factors: patient age, tumour size and grade. Methods: Biospecimens and clinicopathological information for 404 Irish women also previously enrolled in the Trial Assigning Individualized Options for Treatment [Rx] were provided by 11 participating hospitals, as the primary objective of an independent translational study. Gene expression measured via RT-qPCR was used to calculate OMm and OM. The prognostic value for distant recurrence-free survival (DRFS) and invasive disease-free survival (IDFS) was assessed using Cox proportional hazards models and Kaplan-Meier analysis. All statistical tests were two-sided ones. Results: OMm and OM (both with likelihood ratio statistic [LRS] P Discussion: Both OncoMasTR scores were significantly prognostic for DRFS and IDFS and provided additional prognostic information to the molecular and clinicopathological risk factors/tools assessed. OM was also the most accurate risk classification tool for identifying DR. A concise 6-gene signature with superior risk stratification was shown to increase prognosis reliability, which may help clinicians optimise treatment decisions. Trial registration: ClinicalTrials.gov NCT02050750 NCT00310180.</p

Polarimetry of binary systems: polars, magnetic CVs, XRBs

Polarimetry provides key physical information on the properties of interacting binary systems, sometimes difficult to obtain by any other type of observation. Indeed, radiation processes such as scattering by free electrons in the hot plasma above accretion discs, cyclotron emission by mildly relativistic electrons in the accretion shocks on the surface of highly magnetic white dwarfs and the optically thin synchrotron emission from jets can be observed. In this review, I will illustrate how optical/near-infrared polarimetry allows one to estimate magnetic field strengths and map the accretion zones in magnetic Cataclysmic Variables as well as determine the location and nature of jets and ejection events in X-ray binaries.Comment: 26 pages, 16 figures; to be published in Astrophysics and Space Science Library 460, Astronomical Polarisation from the Infrared to Gamma Rays, Editors: Mignani, R., Shearer, A., S{\l}owikowska, A., Zane,