Validation of a novel scoring system for changes in skeletal manifestations of hypophosphatasia in newborns, infants, and children: The Radiographic Global Impression of Change scale

Hypophosphatasia (HPP) is the heritable metabolic disease characterized by impaired skeletal mineralization due to low activity of the tissue-nonspecific isoenzyme of alkaline phosphatase. Although HPP during growth often manifests with distinctive radiographic skeletal features, no validated method was available to quantify them, including changes over time. We created the Radiographic Global Impression of Change (RGI-C) scale to assess changes in the skeletal burden of pediatric HPP. Site-specific pairs of radiographs of newborns, infants, and children with HPP from three clinical studies of asfotase alfa, an enzyme replacement therapy for HPP, were obtained at baseline and during treatment. Each pair was scored by three pediatric radiologists ( raters ), with nine raters across the three studies. Intrarater and interrater agreement was determined by weighted Kappa coefficients. Interrater reliability was assessed using intraclass correlation coefficients (ICCs) and by two-way random effects analysis of variance (ANOVA) and a mixed-model repeated measures ANOVA. Pearson correlation coefficients evaluated relationships of the RGI-C to the Rickets Severity Scale (RSS), Pediatric Outcomes Data Collection Instrument Global Function Parent Normative Score, Childhood Health Assessment Questionnaire Disability Index, 6-Minute Walk Test percent predicted, and Z-score for height in patients aged 6 to 12 years at baseline. Eighty-nine percent (8/9) of raters showed substantial or almost perfect intrarater agreement of sequential RGI-C scores (weighted Kappa coefficients, 0.72 to 0.93) and moderate or substantial interrater agreement (weighted Kappa coefficients, 0.53 to 0.71) in patients aged 0 to 12 years at baseline. Moderate-to-good interrater reliability was observed (ICC, 0.57 to 0.65). RGI-C scores were significantly (p ≤ 0.0065) correlated with the RSS and with measures of global function, disability, endurance, and growth in the patients aged 6 to 12 years at baseline. Thus, the RGI-C is valid and reliable for detecting clinically important changes in skeletal manifestations of severe HPP in newborns, infants, and children, including during asfotase alfa treatment. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc

ANTIBACTERIAL PROPERTIES AND DRYING EFFECTS OF FLAX DENIM AND ANTIBACTERIAL PROPERTIES OF NONWOVEN FLAX FABRIC

A modification of “AATCC Test Method 100-1999” was used for assaying for bacteriostatic/antibacterial properties of denim containing various flax concentrations. Since no direct evidence that increasing the flax content of fabric imparted the fabric with increased bacteriostatic properties was found against the control bacteria, Staphylococcus aureus and Klebsiella pneumoniae, other possible explanations for the long held presumption that flax fabric exhibited antibacterial properties was sought. Because the appearance of having antibacterial or bacteriostatic properties might be imitated if the flax content would decrease the time fabric would be moist enough for bacterial growth, the effect of drying was evaluated. When flax fabric was saturated and the moisture lost during incubation was measured, there was no improved drying associated with increased flax content. When untreated nonwoven flax was evaluated as possibly containing more ‘antibacterial’ or bacteriostatic components than scoured nonwoven flax material, the population densities increased. This increase suggests that the unscoured nonwoven flax contain compo-nents that support bacterial growth to the extent that bacteriostatic or antibacterial components, if any, are overwhelmed by the components that support bacterial growth. In tests involving the control bacteria, Staphylococcus aureus and Klebsiella pneumoniae, increasing the flax content of flax fabric did not demonstrate increased antibacterial properties

Protein Delivery of an Artificial Transcription Factor Restores Widespread Ube3a Expression in an Angelman Syndrome Mouse Brain.

Angelman syndrome (AS) is a neurological genetic disorder caused by loss of expression of the maternal copy of UBE3A in the brain. Due to brain-specific genetic imprinting at this locus, the paternal UBE3A is silenced by a long antisense transcript. Inhibition of the antisense transcript could lead to unsilencing of paternal UBE3A, thus providing a therapeutic approach for AS. However, widespread delivery of gene regulators to the brain remains challenging. Here, we report an engineered zinc finger-based artificial transcription factor (ATF) that, when injected i.p. or s.c., crossed the blood-brain barrier and increased Ube3a expression in the brain of an adult mouse model of AS. The factor displayed widespread distribution throughout the brain. Immunohistochemistry of both the hippocampus and cerebellum revealed an increase in Ube3a upon treatment. An ATF containing an alternative DNA-binding domain did not activate Ube3a. We believe this to be the first report of an injectable engineered zinc finger protein that can cause widespread activation of an endogenous gene in the brain. These observations have important implications for the study and treatment of AS and other neurological disorders

Digging by Debating: Linking massive datasets to specific arguments

We will develop and implement a multi-scale workbench, called "InterDebates", with the goal of digging into data provided by hundreds of thousands, eventually millions, of digitized books, bibliographic databases of journal articles, and comprehensive reference works written by experts. Our hypotheses are: that detailed and identifiable arguments drive many aspects of research in the sciences and the humanities; that argumentative structures can be extracted from large datasets using a mixture of automated and social computing techniques; and, that the availability of such analyses will enable innovative interdisciplinary research, and may also play a role in supporting better-informed critical debates among students and the general public. A key challenge tackled by this project is thus to uncover and represent the argumentative structure of digitized documents, allowing users to find and interpret detailed arguments in the broad semantic landscape of books and articles

Stellar Diameters and Temperatures. I. Main-Sequence A, F, and G Stars

We have executed a survey of nearby, main-sequence A-, F-, and G-type stars with the CHARA Array, successfully measuring the angular diameters of forty-four stars with an average precision of ~1.5%. We present new measures of the bolometric flux, which in turn leads to an empirical determination of the effective temperature for the stars observed. In addition, these CHARA-determined temperatures, radii, and luminosities are fit to Yonsei-Yale model isochrones to constrain the masses and ages of the stars. These results are compared to indirect estimates of these quantities obtained by collecting photometry of the stars and applying them to model atmospheres and evolutionary isochrones. We find that for most cases, the models overestimate the effective temperature by ~1.5%-4% when compared to our directly measured values. The overestimated temperatures and underestimated radii in these works appear to cause an additional offset in the star's surface gravity measurements, which consequently yield higher masses and younger ages, in particular for stars with masses greater than ~1.3 M_☉. Additionally, we compare our measurements to a large sample of eclipsing binary stars, and excellent agreement is seen within both data sets. Finally, we present temperature relations with respect to (B – V) and (V – K) colors as well as spectral type, showing that calibration of effective temperatures with errors ~1% is now possible from interferometric angular diameters of stars

Sheep Updates 2006 -Part 1

This session covers seven papers from different authors: PLENARY 1. Making Dollars from Merinos, David Sackett, Holmes Sackett & Associates Pty Limited, Wagga Wagga, NSW 2. A new variety of sulla (Hedysarun coronarium)for forage production in southern Australia, Kevin Foster, Ron Yates, Phil Nichols, Department of Agriculture and Food, WA and Centre for Legumes in Mediterranean Agriculture, UWA 3. Mating - Short and fast is better, Graeme Martin, John Milton, Faculty of Natural & Agricultural Sciences, The University of Western Australia 4. Breech strike protection in sheep post 2010, Scott Williams, Program Manager Animal Health and Welfare, Australian Wool Innovation Limited 5. How the West can win!, Garry McAlister, Meat & Livestock Australia Limited, New South Wales. 6. The Merino Company (TMC) - Active Marketing and supply chain management, Mark Suttie, General Manager Marketing – The Merino Company (TMC) 7. Driving on-farm productivity: the next 20 years, Peter Fennessy, Jack Cocks, AbacusBio Limited, Dunedin, New Zealan