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Background: EMBRACE (NCT02462759) Part 1 is a randomized, double-blind, sham-procedure controlled study assessing safety/tolerability of intrathecal nusinersen (12-mg equivalent dose) in symptomatic infants/children with SMA who were not eligible to participate in ENDEAR or CHERISH. Methods: Eligible participants had onset of SMA symptoms at ≤6 months with 3 SMN2 copies; onset at ≤6 months, age >7 months and 2 copies; or onset at >6 months, age ≤18 months, and 2/3 copies. Safety/tolerability was the primary endpoint. Exploratory endpoints included Hammersmith Infant Neurological Examination Section 2 (HINE-2) motor milestone attainment, change in ventilator use, and growth. Results: EMBRACE Part 1 was terminated early based on positive results from ENDEAR. Safety/tolerability was similar to previous trials. More nusinersen-treated (11/14;79%) vs. sham–treated individuals (2/7;29%) were HINE-2 motor milestone responders. Between Day 183 and 302, mean (SD) hours of ventilator use changed by +1.236 (3.712) hours in nusinersen-treated (n=12) and +2.123 (3.023) hours in sham–treated individuals (n=7). Similar increases in weight and body length were observed in nusinersen-treated and sham–treated individuals by Day 183. Conclusions: In EMBRACE Part 1, nusinersen demonstrated a favorable benefit-risk profile. These results add to the aggregated efficacy, safety/tolerability data of nusinersen in SMA.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
While a number of site testing campaigns are in progress throughout the world, the dominant efforts seem to be associated with plans for very large telescopes. These plans, improved telescope technology, and the realization that astronomical observations from space will put increasing demands on ground-based observing facilities have given new impetus to site identification and to the optimum utilization of existing sites. A most excellent review of the factors involved in site identification is now available in the Proceedings of the ESO Workshop on Site Testing for Future Large Telescopes, edited by A. Ardeberg and L. Woltjer 1981. These Proceedings and Woolf’s review (1982, Ann. Rev. Astron. Astrophys. 20 367) provide a solid background of current site evaluation factors.
As usual, this report contains contributions from a number of authors, as follows: § 2, P. D. Jackson and M. P. FitzGerald; §§ 3 and 4, F. J. Kerr and D. L. Crawford; §5, P. O. Lindblad; §§ 6A and C, R. Wielen; §§ 6B and 7, J. Einasto; §§ 6D and E, K. C. Freeman, § 6F, M Fujimoto. The layout follows previous practice, except that a new Section 7 on the galactic environment has been added. A longer version of the Report will be published by the University of Maryland and will be distributed to all members of Commission 33 and to astronomical institutions.
The Parkes multibeam pulsar survey uses a 13-element receiver operating at a wavelength of 20 cm to survey the inner Galactic plane with remarkable sensitivity. To date we have collected and analyzed data from 45% of the survey region (|b| < 5°; 260° < l < 50°), and have discovered 440 pulsars, in addition to re-detecting 190 previously known ones. Most of the newly discovered pulsars are at great distances, as inferred from a median dispersion measure (DM) of 400 cm−3 pc.
Evidence supporting the temperature dependent defect mechanism of nonstoichiometry on the potassium and oxygen sublattices in KTP is presented. The primary compensating defects for the formation of vacant potassium sites in typical flux grown KTP are vacant oxygen sites. Protons (OH-) are the principal defect compensating for the formation of vacant potassium sites in high temperature hydrothermal KTP. A model of the ionic conductivity in high temperature hydrothermal KTP is proposed in which specific protons participate in cooperative motion over a limited distance with the potassium vacancies migrating along the “channels” in the structure in the Z-direction. The higher activation energy measured for ionic conductivity in flux grown KTP (0.5 eV) relative to high temperature hydrothermal (0.3 eV) is suggested to be due to the energy required to dissociate from a defect complex, such as a (VO - VK). The correlation of ionic conductivity to damage susceptibility appears to be due to the levels of compensating defects for vacant potassium sites in KTP, which are related to the concentrations of Ti3+ formed in the crystals. Further study is ongoing to understand the specific mechanisms involved in the ionic conductivity and damage in KTP grown by the flux and hydrothermal techniques.
We report infrared (IR) measurements of protons (H+), present as OH−, in KTiOPO4 grown by various techniques. The IR spectra are sensitive to the growth technique used. In high temperature hydrothermally grown crystals we observe IR bands which have strongly temperature dependent linewidths. The Arrhenius-type activation energies for these linewidths are small (6–15 meV). The IR bands are polarized and this information can aid in making OH− site assignments.
KTiOPO4 (KTP) is a nonlinear optical crystal presently used for second harmonic generation and electro-optic applications. The properties (ionic conductivity and damage susceptibility) of KTP crystals can vary depending on the specific technique and conditions used for growth. Consistent defect mechanisms have been determined to explain the observed AC conductivity and damage results of KTP grown by the flux and high and low temperature hydrothermal techniques. The presence of nonstoichiometry on the K and O sublattices in KTP, increasing in magnitude with temperature, is proposed. Using these defect mechanisms, the predominant defects compensating for the formation of vacant potassium sites (VK's) in flux and hydrothermal materials are vacant oxygen sites (VO's) and OH−'s, respectively. The presence of a more varied distribution of OH− sites at room temperature in high temperature hydrothermal material with higher AC conductivity indicates the importance of specific OH− sites in the lattice that may enhance the mobility of ionic carriers. The correlation of higher AC conductivity to increased average current and damage in electric field treated KTP is explained on the basis of the proposed compensating defects (VO 's and OH− 's) which set the [VK] and [Ti3+]. The similarity of the linear optical properties of KTP grown by the various techniques is confirmed by the insensitivity of the absorption edge to the nonstoichiometry or defects present.
We report on the change in electrical resistance of tin doped indium oxide thin films on polymer substrates with increasing uniaxial strain. The resistance increases rapidly but continuously above a threshold strain. The threshold strain at which the resistance increases is correlated to the onset of cracking in the oxide film. The strain for cracking and increase in resistance depend upon film thickness. We have measured the distance between neighboring ITO cracks as a function of strain in situ using an optical microscope. At high uniaxial strains the ITO layer fails in the orthogonal direction due to lateral contraction of the polymer substrate. The gradual increase in resistance is modeled assuming there is a conducting layer at the polymer/ITO interface.
We discuss recent advances in reflective holographically-formed polymer dispersed liquid crystal materials in the context of their suitability for reflective display applications. A dual-domain phenomenon resulting in a broadened reflection peak is presented. A simple phenomenological model is developed to explain this unusual effect The effect of monomer functionality on the reflectance characteristics of these materials is also discussed. Monomers of effective functionality ∼4.5 yield the brightest holograms, however, the data suggests that these systems are currently far from optimal.
Light emitting electroluminescent devices have been studied in which the conjugated light emitting polymer is separated on both sides from the device electrodes by a film of nonconducting polyaniline. The devices operate under an AC applied potential.Aluminum, copper or gold serve as the metal electrodes. Flexible, completely organic polymer dispersed liquid crystal light valves have been fabricated from transparent plastic substrates on which a conducting film of polypyrrole has been deposited. A new concept, “microcontact printing”, is being investigated for patterning the polypyrrole.
Holographically formed polymer dispersed liquid crystal (H-PDLC) displays are investigated in terms of their electro-optic performance parameters and their potential as capable full color display systems. It is demonstrated that the transmission-voltage curve can be modified by low concentrations of chiral dopants, increasing the steepness of the response curve. To probe the details of full-color reflective H-PDLC displays, we invoke a generalized colorimetric/photometric analysis to estimate the display reflectance, white-point, and chromaticity diagram for a vertically integrated stack of red, green, and blue H-PDLC displays.
Multiparticle diffusion equations were modeled to simulate the dynamics of phase coarsening. Local environmental information and particle interactions within the microstructure are included in our simulations. These studies reveal that the growth rates of particles with the same radii can differ, and that particles with the average radius can grow, shrink, or remain conditionally stable. These results are in contrast to mean-field predictions, where particle growth rates are strictly deterministic. Multiparticle simulations prove that fluctuations occur in the particle growth rates, even at extremely low microstructural densities. Multiplicative noise provides a good basis to describe microstructural fluctuations.
The Keck Interferometer Nuller (KIN) is one of the major scientific and technical precursors to the Terrestrial Planet Finder Interferometer (TPF-I) mission. KIN's primary objective is to measure the level of exo-zodiacal mid-infrared emission around nearby main sequence stars, which requires deep broad-band nulling of astronomical sources of a few Janskys at 10 microns. A number of new capabilitites are needed in order to reach that goal with the Keck telescopes: mid-infrared coherent recombination, interferometric operation in “split pupil” mode, N-band optical path stabilization using K-band fringe tracking and internal metrology, and eventually, active atmospheric dispersion correction. We report here on the progress made implementing these new functionalities, and discuss the initial levels of extinction achieved on the sky.
Concerns about violent conduct of service users towards healthcare staff have prompted a ‘zero tolerance’ policy within the National Health Service. This policy specifically excludes users of mental health services. We attempt to challenge artificial distinctions between users of mental health and other services, and propose an ethical underpinning to the implementation of this policy.
To compare the costs with the benefits of using chlorhexidine gluconate dressings on central venous catheters and to determine the effectiveness of these dressings in reducing local infections and catheter-related bloodstream infections (CRBSIs), costs, and mortality.
Cost–benefit analysis using randomized, controlled trial data on chlorhexidine dressing prevention of local infection and CRBSI, data on cost of chlorhexidine dressing versus standard treatment, data on averted cost of treating local infection and CRBSI, and data on mortality attributable to CRBSI. Decision analysis evaluated averted CRBSI treatment cost per patient resulting from chlorhexidine dressing use. Sensitivity analyses demonstrated net benefit of chlorhexidine dressing, varying baseline rate of CRBSI, incremental cost of treating CRBSI, and number of catheters, and evaluated mortality preventable through chlorhexidine dressing use, varying baseline rate of CRBSI, number of catheters, and mortality attributable to CRBSI.
Patients and Setting:
Patients of all Philadelphia area hospitals and one Philadelphia academic medical center.
Estimated potential annual U.S. net benefits from chlorhexidine dressing use ranged from $275 million to approximately $1.97 billion. Cost–benefit findings persisted in sensitivity analyses varying baseline rate of CRBSI, incremental cost of treating CRBSI, and overall number of catheters used. Preventable mortality analyses showed potential decreases of between 329 and 3,906 U.S. deaths annually as a result of nationwide use of chlorhexidine dressing.
Chlorhexidine dressings would reduce costs, local infections and CRBSIs, and deaths. Use of chlorhexidine dressings should be considered to prevent infections among patients with catheters.
Patients with a clinical diagnosis of Alzheimer's disease were studied using MRI, SPECT, and psychometric tests. Significant correlations between focal perfusion deficits and focal cognitive deficits were found. Significant correlations between regional relaxation time of white matter and psychometric tests of diffuse and focal categories were also found. Pathological examination confirmed Alzheimer's disease as the only diagnosis.