Effects of alteplase for acute stroke according to criteria defining the European Union and United States marketing authorizations: individual-patient-data meta-analysis of randomized trials

Background: The recommended maximum age and time window for intravenous alteplase treatment of acute ischemic stroke differs between the Europe Union and United States. Aims: We compared the effects of alteplase in cohorts defined by the current Europe Union or United States marketing approval labels, and by hypothetical revisions of the labels that would remove the Europe Union upper age limit or extend the United States treatment time window to 4.5 h. Methods: We assessed outcomes in an individual-patient-data meta-analysis of eight randomized trials of intravenous alteplase (0.9 mg/kg) versus control for acute ischemic stroke. Outcomes included: excellent outcome (modified Rankin score 0–1) at 3–6 months, the distribution of modified Rankin score, symptomatic intracerebral hemorrhage, and 90-day mortality. Results: Alteplase increased the odds of modified Rankin score 0–1 among 2449/6136 (40%) patients who met the current European Union label and 3491 (57%) patients who met the age-revised label (odds ratio 1.42, 95% CI 1.21−1.68 and 1.43, 1.23−1.65, respectively), but not in those outside the age-revised label (1.06, 0.90−1.26). By 90 days, there was no increased mortality in the current and age-revised cohorts (hazard ratios 0.98, 95% CI 0.76−1.25 and 1.01, 0.86–1.19, respectively) but mortality remained higher outside the age-revised label (1.19, 0.99–1.42). Similarly, alteplase increased the odds of modified Rankin score 0-1 among 1174/6136 (19%) patients who met the current US approval and 3326 (54%) who met a 4.5-h revised approval (odds ratio 1.55, 1.19−2.01 and 1.37, 1.17−1.59, respectively), but not for those outside the 4.5-h revised approval (1.14, 0.97−1.34). By 90 days, no increased mortality remained for the current and 4.5-h revised label cohorts (hazard ratios 0.99, 0.77−1.26 and 1.02, 0.87–1.20, respectively) but mortality remained higher outside the 4.5-h revised approval (1.17, 0.98–1.41). Conclusions: An age-revised European Union label or 4.5-h-revised United States label would each increase the number of patients deriving net benefit from alteplase by 90 days after acute ischemic stroke, without excess mortality

Eccentric, nonspinning, inspiral, Gaussian-process merger approximant for the detection and characterization of eccentric binary black hole mergers

We present $\texttt{ENIGMA}$, a time domain, inspiral-merger-ringdown waveform model that describes non-spinning binary black holes systems that evolve on moderately eccentric orbits. The inspiral evolution is described using a consistent combination of post-Newtonian theory, self-force and black hole perturbation theory. Assuming eccentric binaries that circularize prior to coalescence, we smoothly match the eccentric inspiral with a stand-alone, quasi-circular merger, which is constructed using machine learning algorithms that are trained with quasi-circular numerical relativity waveforms. We show that $\texttt{ENIGMA}$ reproduces with excellent accuracy the dynamics of quasi-circular compact binaries. We validate $\texttt{ENIGMA}$ using a set of $\texttt{Einstein Toolkit}$ eccentric numerical relativity waveforms, which describe eccentric binary black hole mergers with mass-ratios between $1 \leq q \leq 5.5$, and eccentricities $e_0 \lesssim 0.2$ ten orbits before merger. We use this model to explore in detail the physics that can be extracted with moderately eccentric, non-spinning binary black hole mergers. We use $\texttt{ENIGMA}$ to show that GW150914, GW151226, GW170104, GW170814 and GW170608 can be effectively recovered with spinning, quasi-circular templates if the eccentricity of these events at a gravitational wave frequency of 10Hz satisfies $e_0\leq \{0.175,\, 0.125,\,0.175,\,0.175,\, 0.125\}$, respectively. We show that if these systems have eccentricities $e_0\sim 0.1$ at a gravitational wave frequency of 10Hz, they can be misclassified as quasi-circular binaries due to parameter space degeneracies between eccentricity and spin corrections. Using our catalog of eccentric numerical relativity simulations, we discuss the importance of including higher-order waveform multipoles in gravitational wave searches of eccentric binary black hole mergers.Comment: 19 pages, 10 figures, 1 Appendix. v2: we use numerical relativity simulations to quantify the importance of including higher-order waveform multipoles for the detection of eccentric binary black hole mergers, references added. Accepted to Phys. Rev.

The REASONS Survey : resolved millimeter observations of a large debris disk around the nearby F Star HD 170773

Debris disks are extrasolar analogs to our own Kuiper Belt and they are detected around at least 17% of nearby Sun-like stars. The morphology and dynamics of a disk encode information about its history, as well as that of any exoplanets within the system. We used the Atacama Large Millimeter/submillimeter Array (ALMA) to obtain 1.3 mm observations of the debris disk around the nearby F5V star HD 170773. We image the face-on ring and determine its fundamental parameters by forward-modeling the interferometric visibilities through a Markov Chain Monte Carlo approach. Using a symmetric Gaussian surface density profile, we find a 71 ± 4 au wide belt with a radius of {193}-3+2 au, a relatively large radius compared with most other millimeter-resolved belts around late A/early F type stars. This makes HD 170773 part of a group of four disks around A and F stars with radii larger than expected from the recently reported planetesimal belt radius—stellar luminosity relation. Two of these systems are known to host directly imaged giant planets, which may point to a connection between large belts and the presence of long-period giant planets. We also set upper limits on the presence of CO and CN gas in the system, which imply that the exocomets that constitute this belt have CO and HCN ice mass fractions of <77% and <3%, respectively. This is consistent with solar system comets and other exocometary belts

Planet Populations as a Function of Stellar Properties

Exoplanets around different types of stars provide a window into the diverse environments in which planets form. This chapter describes the observed relations between exoplanet populations and stellar properties and how they connect to planet formation in protoplanetary disks. Giant planets occur more frequently around more metal-rich and more massive stars. These findings support the core accretion theory of planet formation, in which the cores of giant planets form more rapidly in more metal-rich and more massive protoplanetary disks. Smaller planets, those with sizes roughly between Earth and Neptune, exhibit different scaling relations with stellar properties. These planets are found around stars with a wide range of metallicities and occur more frequently around lower mass stars. This indicates that planet formation takes place in a wide range of environments, yet it is not clear why planets form more efficiently around low mass stars. Going forward, exoplanet surveys targeting M dwarfs will characterize the exoplanet population around the lowest mass stars. In combination with ongoing stellar characterization, this will help us understand the formation of planets in a large range of environments.Comment: Accepted for Publication in the Handbook of Exoplanet

The role of phonology in lexical access in teenagers with a history of dyslexia

We examined phonological recoding during silent sentence reading in teenagers with a history of dyslexia and their typically developing peers. Two experiments are reported in which participants’ eye movements were recorded as they read sentences containing correctly spelled words (e.g., church), pseudohomophones (e.g., cherch), and spelling controls (e.g., charch). In Experiment 1 we examined foveal processing of the target word/nonword stimuli, and in Experiment 2 we examined parafoveal pre-processing. There were four participant groups–older teenagers with a history of dyslexia, older typically developing teenagers who were matched for age, younger typically developing teenagers who were matched for reading level, and younger teenagers with a history of dyslexia. All four participant groups showed a pseudohomophone advantage, both from foveal processing and parafoveal pre-processing, indicating that teenagers with a history of dyslexia engage in phonological recoding for lexical identification during silent sentence reading in a comparable manner to their typically developing peers

Systematic techniques for assisting recruitment to trials (START): study protocol for embedded, randomized controlled trials

BACKGROUND: Randomized controlled trials play a central role in evidence-based practice, but recruitment of participants, and retention of them once in the trial, is challenging. Moreover, there is a dearth of evidence that research teams can use to inform the development of their recruitment and retention strategies. As with other healthcare initiatives, the fairest test of the effectiveness of a recruitment strategy is a trial comparing alternatives, which for recruitment would mean embedding a recruitment trial within an ongoing host trial. Systematic reviews indicate that such studies are rare. Embedded trials are largely delivered in an ad hoc way, with interventions almost always developed in isolation and tested in the context of a single host trial, limiting their ability to contribute to a body of evidence with regard to a single recruitment intervention and to researchers working in different contexts. METHODS/DESIGN: The Systematic Techniques for Assisting Recruitment to Trials (START) program is funded by the United Kingdom Medical Research Council (MRC) Methodology Research Programme to support the routine adoption of embedded trials to test standardized recruitment interventions across ongoing host trials. To achieve this aim, the program involves three interrelated work packages: (1) methodology - to develop guidelines for the design, analysis and reporting of embedded recruitment studies; (2) interventions - to develop effective and useful recruitment interventions; and (3) implementation - to recruit host trials and test interventions through embedded studies. DISCUSSION: Successful completion of the START program will provide a model for a platform for the wider trials community to use to evaluate recruitment interventions or, potentially, other types of intervention linked to trial conduct. It will also increase the evidence base for two types of recruitment intervention. TRIAL REGISTRATION: The START protocol covers the methodology for embedded trials. Each embedded trial is registered separately or as a substudy of the host trial

Galaxy And Mass Assembly (GAMA): trends in galaxy colours, morphology, and stellar populations with large-scale structure, group, and pair environments

We explore trends in galaxy properties with Mpc-scale structures using catalogues of environment and large-scale structure from the Galaxy And Mass Assembly (GAMA) survey. Existing GAMA catalogues of large-scale structure, group, and pair membership allow us to construct galaxy stellar mass functions for different environmental types. To avoid simply extracting the known underlying correlations between galaxy properties and stellar mass, we create a mass matched sample of galaxies with stellar masses within 9.5 ≤ log M*/h−2 M⊙ ≤ 11 for each environmental population. Using these samples, we show that mass normalized galaxies in different large-scale environments have similar energy outputs, u − r colours, luminosities, and morphologies. Extending our analysis to group and pair environments, we show that galaxies that are not in groups or pairs exhibit similar characteristics to each other regardless of broader environment. For our mass controlled sample, we fail to see a strong dependence of Sérsic index or galaxy luminosity on halo mass, but do find that it correlates very strongly with colour. Repeating our analysis for galaxies that have not been mass controlled introduces and amplifies trends in the properties of galaxies in pairs, groups, and large-scale structure, indicating that stellar mass is the most important predictor of the galaxy properties we examine, as opposed to environmental classifications

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes