Protection From Clinical Peripheral Sensory Neuropathy in Alström Syndrome in Contrast to Early-Onset Type 2 Diabetes

OBJECTIVE—Alström syndrome, with type 2 diabetes, and blindness could confer a high risk of foot ulceration. Clinical testing for neuropathy in Alström syndrome and matched young-onset type 2 diabetic subjects was therefore undertaken

Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design.

Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)-many of which are refractory to current standard-of-care treatments-from high-risk childhood cancers. Here, we genomically characterize 261 PDX models from 37 unique pediatric cancers; demonstrate faithful recapitulation of histologies and subtypes; and refine our understanding of relapsed disease. In addition, we use expression signatures to classify tumors for TP53 and NF1 pathway inactivation. We anticipate that these data will serve as a resource for pediatric oncology drug development and will guide rational clinical trial design for children with cancer

Establishing Alpha Oph as a Prototype Rotator: Improved Astrometric Orbit

The nearby star Alpha Oph (Ras Alhague) is a rapidly rotating A5IV star spinning at ~89% of its breakup velocity. This system has been imaged extensively by interferometric techniques, giving a precise geometric model of the star's oblateness and the resulting temperature variation on the stellar surface. Fortuitously, Alpha Oph has a previously known stellar companion, and characterization of the orbit provides an independent, dynamically-based check of both the host star and the companion mass. Such measurements are crucial to constrain models of such rapidly rotating stars. In this study, we combine eight years of Adaptive Optics imaging data from the Palomar, AEOS, and CFHT telescopes to derive an improved, astrometric characterization of the companion orbit. We also use photometry from these observations to derive a model-based estimate of the companion mass. A fit was performed on the photocenter motion of this system to extract a component mass ratio. We find masses of 2.40^{0.23}_{0.37} solar masses and 0.85^{0.06}_{0.04} solar masses for Alpha Oph A and Alpha Oph B, respectively. Previous orbital studies of this system found a mass too high for this system, inconsistent with stellar evolutionary calculations. Our measurements of the host star mass are more consistent with these evolutionary calculations, but with slightly higher uncertainties. In addition to the dynamically-derived masses, we use IJHK photometry to derive a model-based mass for Alpha Oph B, of 0.77 +/- 0.05 solar masses marginally consistent with the dynamical masses derived from our orbit. Our model fits predict a periastron passage on 2012 April 19, with the two components having a ~50 milliarcsec separation from March to May 2012. A modest amount of interferometric and radial velocity data during this period could provide a mass determination of this star at the few percent level.Comment: Accepted to ApJ, 6 pages, 4 figure

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

Discovery and Characterization of a Faint Stellar Companion to the A3V Star Zeta Virginis

Through the combination of high-order Adaptive Optics and coronagraphy, we report the discovery of a faint stellar companion to the A3V star zeta Virginis. This companion is ~7 magnitudes fainter than its host star in the H-band, and infrared imaging spanning 4.75 years over five epochs indicates this companion has common proper motion with its host star. Using evolutionary models, we estimate its mass to be 0.168+/-.016 solar masses, giving a mass ratio for this system q = 0.082. Assuming the two objects are coeval, this mass suggests a M4V-M7V spectral type for the companion, which is confirmed through integral field spectroscopic measurements. We see clear evidence for orbital motion from this companion and are able to constrain the semi-major axis to be greater than 24.9 AU, the period > 124$ yrs, and eccentricity > 0.16. Multiplicity studies of higher mass stars are relatively rare, and binary companions such as this one at the extreme low end of the mass ratio distribution are useful additions to surveys incomplete at such a low mass ratio. Moreover, the frequency of binary companions can help to discriminate between binary formation scenarios that predict an abundance of low-mass companions forming from the early fragmentation of a massive circumstellar disk. A system such as this may provide insight into the anomalous X-ray emission from A stars, hypothesized to be from unseen late-type stellar companions. Indeed, we calculate that the presence of this M-dwarf companion easily accounts for the X-ray emission from this star detected by ROSAT.Comment: 9 pages, 6 figures, Accepted to Ap

Lower age at menarche affects survival in older Australian women: results from the Australian Longitudinal Study of Ageing

Extent: 10p.Background: While menarche indicates the beginning of a woman's reproductive life, relatively little is known about the association between age at menarche and subsequent morbidity and mortality. We aimed to examine the effect of lower age at menarche on all-cause mortality in older Australian women over 15 years of follow-up. Methods: Data were drawn from the Australian Longitudinal Study of Ageing (n = 1,031 women aged 65-103 years). We estimated the hazard ratio (HR) associated with lower age at menarche using Cox proportional hazards models, and adjusted for a broad range of reproductive, demographic, health and lifestyle covariates. Results: During the follow-up period, 673 women (65%) died (average 7.3 years (SD 4.1) of follow-up for decedents). Women with menses onset < 12 years of age (10.7%; n = 106) had an increased hazard of death over the follow-up period (adjusted HR 1.28; 95%CI 0.99-1.65) compared with women who began menstruating aged ≥ 12 years (89.3%; n = 883). However, when age at menarche was considered as a continuous variable, the adjusted HRs associated with the linear and quadratic terms for age at menarche were not statistically significant at a 5% level of significance (linear HR 0.76; 95%CI 0.56 - 1.04; quadratic HR 1.01; 95%CI 1.00-1.02). Conclusion: Women with lower age at menarche may have reduced survival into old age. These results lend support to the known associations between earlier menarche and risk of metabolic disease in early adulthood. Strategies to minimise earlier menarche, such as promoting healthy weights and minimising family dysfunction during childhood, may also have positive longer-term effects on survival in later life.Lynne C Giles, Gary FV Glonek, Vivienne M Moore, Michael J Davies and Mary A Luszc

Doll Play narratives about starting school in children of socially anxious mothers, and their relation to subsequent child school-based anxiety

Background: Child social anxiety is common, and predicts later emotional and academic impairment. Offspring of socially anxious mothers are at increased risk. It is important to establish whether individual vulnerability to disorder can be identified in young children. Method: The responses of 4.5 year-old children of mothers with social phobia (N = 62) and non-anxious mothers (N = 60) were compared, two months before school entry, using a Doll Play (DP) procedure focused on the social challenge of starting school. DP responses were examined in relation to teacher reports of anxious-depressed symptoms and social worries at the end of the child’s first school term. The role of earlier child behavioral inhibition and attachment, assessed at 14 months, was also considered. Results: Compared to children of non-anxious mothers, children of mothers with social phobia were significantly more likely to give anxiously negative responses in their school DP (OR = 2.57). In turn, negative DP predicted teacher reported anxious-depressed and social worry problems. There were no effects of infant behavioral inhibition or attachment. Conclusion: Vulnerability in young children at risk of anxiety can be identified using Doll Play narratives

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

Phylogenetic Analysis of the Neks Reveals Early Diversification of Ciliary-Cell Cycle Kinases

NIMA-related kinases (Neks) have been studied in diverse eukaryotes, including the fungus Aspergillus and the ciliate Tetrahymena. In the former, a single Nek plays an essential role in cell cycle regulation; in the latter, which has more than 30 Neks in its genome, multiple Neks regulate ciliary length. Mammalian genomes encode an intermediate number of Neks, several of which are reported to play roles in cell cycle regulation and/or localize to centrosomes. Previously, we reported that organisms with cilia typically have more Neks than organisms without cilia, but were unable to establish the evolutionary history of the gene family