development of measures of polyneuropathy impairment in hattr amyloidosis from nis to mnis 7

Abstract Hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) is a rare, life-threatening disease, caused by point mutations in the transthyretin gene. It is a heterogeneous, multisystem disease with rapidly progressing polyneuropathy (including sensory, motor, and autonomic impairments) and cardiac dysfunction. Measures used to assess polyneuropathy in other diseases have been tested as endpoints in hATTR amyloidosis clinical trials (i.e. Neuropathy Impairment Score [NIS], NIS-lower limb, and NIS + 7), yet the unique nature of the polyneuropathy in this disease has necessitated modifications to these scales. In particular, the heterogeneous impairment and the aggressive disease course have been key drivers in developing scales that better capture the disease burden and progression of polyneuropathy in hATTR amyloidosis. The modified NIS + 7 (mNIS + 7) scale was specifically designed to assess polyneuropathy impairment in patients with hATTR amyloidosis, and has been the primary endpoint in two recent, phase III studies in this disease. The mNIS + 7 uses highly standardized, quantitative, and referenced assessments to quantify decreased muscle weakness, muscle stretch reflexes, sensory loss, and autonomic impairment. Physicians using this scale in clinical trials should be specifically trained and monitored to minimize variability. This article discusses the different scales that have been/are being used to assess polyneuropathy in patients with hATTR amyloidosis, their correlation with other disease assessments, and reflects on how and why scales have evolved to the latest iteration of mNIS + 7

Quantum Logic with a Single Trapped Electron

We propose the use of a trapped electron to implement quantum logic operations. The fundamental controlled-NOT gate is shown to be feasible. The two quantum bits are stored in the internal and external (motional) degrees of freedom.Comment: 7 Pages, REVTeX, No Figures, To appear in Phys. Rev.

Electron diffraction and high-resolution transmission electron microscopy of the high temperature crystal structures of GexSb2Te3+x (x=1,2,3) phase change material

The crystal structures of GeSb2Te4, Ge2Sb2Te5, and Ge3Sb2Te6 were determined using electron diffraction and high-resolution transmission electron microscopy. The structure determined for the former two crystals deviates from the ones proposed in the literature. These crystal structures were developed jointly upon cooling of liquid Ge2Sb2Te5. A stacking disorder parallel to the basal plane was observed that increases with increasing cooling rates. For the GexSb2Te3+x (x=1,2,3) crystals it is shown that an a,b,c stacking holds with an alternating stacking of x GeTe double layers identically present in binary GeTe and one Te-Sb-Te-Te-Sb- repeat unit also present in binary Sb2Te3. A stacking disorder is a logical consequence of building crystals with these two principal units. On the other hand, it is likely that all stable crystals of the Ge-Sb-Te systems are an ordered sequence of these two units. Some of the implications of these findings of the stable and metastable crystal structures that develop from amorphous Ge2Sb2Te5 are presented so as to understand the crucial crystallization process in Ge2Sb2Te5 phase change material

Childcare, choice and social class: Caring for young children in the UK

This paper draws on the results of two qualitative research projects examining parental engagements with the childcare market in the UK. Both projects are located in the same two London localities. One project focuses on professional middle class parents, and the other on working class families, and we discuss the key importance of social class in shaping parents' differential engagement with the childcare market, and their understandings of the role childcare plays in their children's lives. We identify and discuss the different "circuits" of care (Ball et al 1995) available to and used by families living physically close to each other, but in social class terms living in different worlds. We also consider parents' relationships with carers, and their social networks. We conclude that in order to fully understand childcare policies and practices and families' experiences of care, an analysis which encompasses social class and the workings of the childcare market is needed

A New Photomechanical Molecular Switch Based on a Linear {\pi}-Conjugated System

We report the electronic transport properties of a new photo-addressable molecular switch. The switching process relies on a new concept based on linear {\pi}-conjugated dynamic systems, in which the geometry and hence the electronic properties of an oligothiophene chain can be reversibly modified by the photochemical trans-cis isomerization of an azobenzene unit fixed in a lateral loop. Electron transport measurements through self-assembled monolayers on gold, contacted with eGaIn top contact, show switching with a conductance ratio up to 1E3. Ab initio calculations have been used to identify the most energetically stable conformations of the molecular switch, the corresponding calculated conductances qualitatively explain the trend observed in the photo-switching experiments.Comment: Full manuscript and supporting information, J. Phys. Chem. C,published on line (2017

A New Photomechanical Molecular Switch Based on a Linear {\pi}-Conjugated System

We report the electronic transport properties of a new photo-addressable molecular switch. The switching process relies on a new concept based on linear {\pi}-conjugated dynamic systems, in which the geometry and hence the electronic properties of an oligothiophene chain can be reversibly modified by the photochemical trans-cis isomerization of an azobenzene unit fixed in a lateral loop. Electron transport measurements through self-assembled monolayers on gold, contacted with eGaIn top contact, show switching with a conductance ratio up to 1E3. Ab initio calculations have been used to identify the most energetically stable conformations of the molecular switch, the corresponding calculated conductances qualitatively explain the trend observed in the photo-switching experiments.Comment: Full manuscript and supporting information, J. Phys. Chem. C,published on line (2017

Direct detection of a magnetic field in the photosphere of the single M giant EK Boo: How common is magnetic activity among M giants?

We study the fast rotating M5 giant EK Boo by means of spectropolarimetry to obtain direct and simultaneous measurements of both the magnetic field and activity indicators, in order to infer the origin of the activity in this fairly evolved giant. We used the new spectropolarimeter NARVAL at the Bernard Lyot Telescope (Observatoire du Pic du Midi, France) to obtain a series of Stokes I and Stokes V profiles for EK Boo. Using the Least Square Deconvolution technique we were able to detect the Zeeman signature of the magnetic field. We measured its longitudinal component by means of the averaged Stokes V and Stokes I profiles. The spectra also permitted us to monitor the CaII K&H chromospheric emission lines, which are well known as indicators of stellar magnetic activity. From ten observations obtained between April 2008 and March 2009, we deduce that EK Boo has a magnetic field, which varied in the range of -0.1 to -8 G. We also determined the initial mass and evolutionary stage of EK Boo, based on up-to-date stellar evolution tracks. The initial mass is in the range of 2.0-3.6 M_sun, and EK Boo is either on the asymptotic giant branch (AGB), at the onset of the thermal pulse phase, or at the tip of the first (or red) giant branch (RGB). The fast rotation and activity of EK Boo might be explained by angular momentum dredge-up from the interior, or by the merging of a binary. In addition, we observed eight other M giants, which are known as X-ray emitters, or to be rotating fast for their class. For one of these, beta And, presumably also an AGB star, we have a marginal detection of magnetic field, and a longitudinal component Bl of about 1G was measured. More observations like this will answer the question whether EK Boo is a special case, or whether magnetic activity is, rather, more common among M giants than expected.Comment: Accepted for publication in Astronomy & Astrophysics, 10 pages, 8 figure

Chromosphere of K giant stars Geometrical extent and spatial structure detection

We aim to constrain the geometrical extent of the chromosphere of non-binary K giant stars and detect any spatial structures in the chromosphere. We performed observations with the CHARA interferometer and the VEGA beam combiner at optical wavelengths. We observed seven non-binary K giant stars. We measured the ratio of the radii of the photosphere to the chromosphere using the interferometric measurements in the Halpha and the Ca II infrared triplet line cores. For beta Ceti, spectro-interferometric observations are compared to an non-local thermal equilibrium (NLTE) semi-empirical model atmosphere including a chromosphere. The NLTE computations provide line intensities and contribution functions that indicate the relative locations where the line cores are formed and can constrain the size of the limb-darkened disk of the stars with chromospheres. We measured the angular diameter of seven K giant stars and deduced their fundamental parameters: effective temperatures, radii, luminosities, and masses. We determined the geometrical extent of the chromosphere for four giant stars. The chromosphere extents obtained range between 16% to 47% of the stellar radius. The NLTE computations confirm that the Ca II/849 nm line core is deeper in the chromosphere of ? Cet than either of the Ca II/854 nm and Ca II/866 nm line cores. We present a modified version of a semi-empirical model atmosphere derived by fitting the Ca II triplet line cores of this star. In four of our targets, we also detect the signature of a differential signal showing the presence of asymmetries in the chromospheres. Conclusions. It is the first time that geometrical extents and structure in the chromospheres of non-binary K giant stars are determined by interferometry. These observations provide strong constrains on stellar atmosphere models.Comment: 10 pages, 12 figure