Safety and physiological effects of two different doses of elosulfase alfa in patients with morquio a syndrome: A randomized, double-blind, pilot study.

The primary treatment outcomes of a phase 2, randomized, double-blind, pilot study evaluating safety, physiological, and pharmacological effects of elosulfase alfa in patients with Morquio A syndrome are herewith presented. Patients aged ≥7 years and able to walk ≥200 m in the 6-min walk test (6MWT) were randomized to elosulfase alfa 2.0 or 4.0 mg/kg/week for 27 weeks. The primary objective was to evaluate the safety of both doses. Secondary objectives were to evaluate effects on endurance (6MWT and 3-min stair climb test [3MSCT]), exercise capacity (cardio-pulmonary exercise test [CPET]), respiratory function, muscle strength, cardiac function, pain, and urine keratan sulfate (uKS) levels, and to determine pharmacokinetic parameters. Twenty-five patients were enrolled (15 randomized to 2.0 mg/kg/week and 10 to 4.0 mg/kg/week). No new or unexpected safety signals were observed. After 24 weeks, there were no improvements versus baseline in the 6MWT, yet numerical improvements were seen in the 3MSCT with 4.0 mg/kg/week. uKS and pharmacokinetic data suggested no linear relationship over the 2.0-4.0 mg/kg dose range. Overall, an abnormal exercise capacity (evaluated in 10 and 5 patients in the 2.0 and 4.0 mg/kg/week groups, respectively), impaired muscle strength, and considerable pain were observed at baseline, and there were trends towards improvements in all domains after treatment. In conclusion, preliminary data of this small study in a Morquio A population with relatively good endurance confirmed the acceptable safety profile of elosulfase alfa and showed a trend of increased exercise capacity and muscle strength and decreased pain

A new fireworm (Amphinomidae) from the Cretaceous of Lebanon identified from three-dimensionally preserved myoanatomy

© 2015 Parry et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The attached file is the published version of the article

Speckle from phase ordering systems

The statistical properties of coherent radiation scattered from phase-ordering materials are studied in detail using large-scale computer simulations and analytic arguments. Specifically, we consider a two-dimensional model with a nonconserved, scalar order parameter (Model A), quenched through an order-disorder transition into the two-phase regime. For such systems it is well established that the standard scaling hypothesis applies, consequently the average scattering intensity at wavevector _k and time t' is proportional to a scaling function which depends only on a rescaled time, t ~ |_k|^2 t'. We find that the simulated intensities are exponentially distributed, with the time-dependent average well approximated using a scaling function due to Ohta, Jasnow, and Kawasaki. Considering fluctuations around the average behavior, we find that the covariance of the scattering intensity for a single wavevector at two different times is proportional to a scaling function with natural variables mt = |t_1 - t_2| and pt = (t_1 + t_2)/2. In the asymptotic large-pt limit this scaling function depends only on z = mt / pt^(1/2). For small values of z, the scaling function is quadratic, corresponding to highly persistent behavior of the intensity fluctuations. We empirically establish a connection between the intensity covariance and the two-time, two-point correlation function of the order parameter. This connection allows sensitive testing, either experimental or numerical, of existing theories for two-time correlations in systems undergoing order-disorder phase transitions. Comparison between theory and our numerical results requires no adjustable parameters.Comment: 18 pgs RevTeX, to appear in PR

Targeted search for continuous gravitational waves: Bayesian versus maximum-likelihood statistics

We investigate the Bayesian framework for detection of continuous gravitational waves (GWs) in the context of targeted searches, where the phase evolution of the GW signal is assumed to be known, while the four amplitude parameters are unknown. We show that the orthodox maximum-likelihood statistic (known as F-statistic) can be rediscovered as a Bayes factor with an unphysical prior in amplitude parameter space. We introduce an alternative detection statistic ("B-statistic") using the Bayes factor with a more natural amplitude prior, namely an isotropic probability distribution for the orientation of GW sources. Monte-Carlo simulations of targeted searches show that the resulting Bayesian B-statistic is more powerful in the Neyman-Pearson sense (i.e. has a higher expected detection probability at equal false-alarm probability) than the frequentist F-statistic.Comment: 12 pages, presented at GWDAW13, to appear in CQ

Searching for a Stochastic Background of Gravitational Waves with LIGO

The Laser Interferometer Gravitational-wave Observatory (LIGO) has performed the fourth science run, S4, with significantly improved interferometer sensitivities with respect to previous runs. Using data acquired during this science run, we place a limit on the amplitude of a stochastic background of gravitational waves. For a frequency independent spectrum, the new limit is $\Omega_{\rm GW} < 6.5 \times 10^{-5}$. This is currently the most sensitive result in the frequency range 51-150 Hz, with a factor of 13 improvement over the previous LIGO result. We discuss complementarity of the new result with other constraints on a stochastic background of gravitational waves, and we investigate implications of the new result for different models of this background.Comment: 37 pages, 16 figure

Search for gravitational wave bursts in LIGO's third science run

We report on a search for gravitational wave bursts in data from the three LIGO interferometric detectors during their third science run. The search targets subsecond bursts in the frequency range 100-1100 Hz for which no waveform model is assumed, and has a sensitivity in terms of the root-sum-square (rss) strain amplitude of hrss ~ 10^{-20} / sqrt(Hz). No gravitational wave signals were detected in the 8 days of analyzed data.Comment: 12 pages, 6 figures. Amaldi-6 conference proceedings to be published in Classical and Quantum Gravit

Evolution of speckle during spinodal decomposition

Time-dependent properties of the speckled intensity patterns created by scattering coherent radiation from materials undergoing spinodal decomposition are investigated by numerical integration of the Cahn-Hilliard-Cook equation. For binary systems which obey a local conservation law, the characteristic domain size is known to grow in time $\tau$ as $R = [B \tau]^n$ with n=1/3, where B is a constant. The intensities of individual speckles are found to be nonstationary, persistent time series. The two-time intensity covariance at wave vector ${\bf k}$ can be collapsed onto a scaling function $Cov(\delta t,\bar{t})$, where $\delta t = k^{1/n} B |\tau_2-\tau_1|$ and $\bar{t} = k^{1/n} B (\tau_1+\tau_2)/2$. Both analytically and numerically, the covariance is found to depend on $\delta t$ only through $\delta t/\bar{t}$ in the small-$\bar{t}$ limit and $\delta t/\bar{t} ^{1-n}$ in the large-$\bar{t}$ limit, consistent with a simple theory of moving interfaces that applies to any universality class described by a scalar order parameter. The speckle-intensity covariance is numerically demonstrated to be equal to the square of the two-time structure factor of the scattering material, for which an analytic scaling function is obtained for large $\bar{t}.$ In addition, the two-time, two-point order-parameter correlation function is found to scale as $C(r/(B^n\sqrt{\tau_1^{2n}+\tau_2^{2n}}),\tau_1/\tau_2)$, even for quite large distances $r$. The asymptotic power-law exponent for the autocorrelation function is found to be $\lambda \approx 4.47$, violating an upper bound conjectured by Fisher and Huse.Comment: RevTex: 11 pages + 12 figures, submitted to PR

Quantum state preparation and macroscopic entanglement in gravitational-wave detectors

Long-baseline laser-interferometer gravitational-wave detectors are operating at a factor of 10 (in amplitude) above the standard quantum limit (SQL) within a broad frequency band. Such a low classical noise budget has already allowed the creation of a controlled 2.7 kg macroscopic oscillator with an effective eigenfrequency of 150 Hz and an occupation number of 200. This result, along with the prospect for further improvements, heralds the new possibility of experimentally probing macroscopic quantum mechanics (MQM) - quantum mechanical behavior of objects in the realm of everyday experience - using gravitational-wave detectors. In this paper, we provide the mathematical foundation for the first step of a MQM experiment: the preparation of a macroscopic test mass into a nearly minimum-Heisenberg-limited Gaussian quantum state, which is possible if the interferometer's classical noise beats the SQL in a broad frequency band. Our formalism, based on Wiener filtering, allows a straightforward conversion from the classical noise budget of a laser interferometer, in terms of noise spectra, into the strategy for quantum state preparation, and the quality of the prepared state. Using this formalism, we consider how Gaussian entanglement can be built among two macroscopic test masses, and the performance of the planned Advanced LIGO interferometers in quantum-state preparation

Improving the sensitivity to gravitational-wave sources by modifying the input-output optics of advanced interferometers

We study frequency dependent (FD) input-output schemes for signal-recycling interferometers, the baseline design of Advanced LIGO and the current configuration of GEO 600. Complementary to a recent proposal by Harms et al. to use FD input squeezing and ordinary homodyne detection, we explore a scheme which uses ordinary squeezed vacuum, but FD readout. Both schemes, which are sub-optimal among all possible input-output schemes, provide a global noise suppression by the power squeeze factor, while being realizable by using detuned Fabry-Perot cavities as input/output filters. At high frequencies, the two schemes are shown to be equivalent, while at low frequencies our scheme gives better performance than that of Harms et al., and is nearly fully optimal. We then study the sensitivity improvement achievable by these schemes in Advanced LIGO era (with 30-m filter cavities and current estimates of filter-mirror losses and thermal noise), for neutron star binary inspirals, and for narrowband GW sources such as low-mass X-ray binaries and known radio pulsars. Optical losses are shown to be a major obstacle for the actual implementation of these techniques in Advanced LIGO. On time scales of third-generation interferometers, like EURO/LIGO-III (~2012), with kilometer-scale filter cavities, a signal-recycling interferometer with the FD readout scheme explored in this paper can have performances comparable to existing proposals. [abridged]Comment: Figs. 9 and 12 corrected; Appendix added for narrowband data analysi

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy