Preliminary assessment of cognitive impairments in canine idiopathic epilepsy

In humans, epilepsy can induce or accelerate cognitive impairment (CI). There is emerging evidence of CI in dogs with idiopathic epilepsy (IE) from recent epidemiological studies. The aim of our study was to assess CI in dogs with IE using two tests of cognitive dysfunction designed for use in a clinical setting. Dogs with IE (n=17) were compared against controls (n=18) in their performance in two tasks; a spatial working memory task and a problem-solving task. In addition, owners completed the Canine Cognitive Dysfunction Rating (CCDR) scale for their dog. The groups did not differ statistically with respect to age and breed. Dogs with IE performed significantly worse than controls on the spatial working memory task (P=0.016), but not on the problem solving task (P=0.683). CCDR scores were significantly higher in the IE group (P=0.016); however, no dogs reach the recommended threshold score for CCD diagnosis. Our preliminary data suggest that dogs with IE exhibit impairments in a spatial working memory task. Further research is required to explore the effect of IE on other cognitive abilities in dogs with a larger sample, characterising the age of onset, nature and progression of any impairments and the impact of anti-epileptic drugs

Transmission dynamics and prospects for the elimination of canine rabies

Rabies has been eliminated from domestic dog populations in Western Europe and North America, but continues to kill many thousands of people throughout Africa and Asia every year. A quantitative understanding of transmission dynamics in domestic dog populations provides critical information to assess whether global elimination of canine rabies is possible. We report extensive observations of individual rabid animals in Tanzania and generate a uniquely detailed analysis of transmission biology, which explains important epidemiological features, including the level of variation in epidemic trajectories. We found that the basic reproductive number for rabies, R<sub>0</sub>, is very low in our study area in rural Africa (∼1.2) and throughout its historic global range (<2). This finding provides strong support for the feasibility of controlling endemic canine rabies by vaccination, even near wildlife areas with large wild carnivore populations. However, we show that rapid turnover of domestic dog populations has been a major obstacle to successful control in developing countries, thus regular pulse vaccinations will be required to maintain population-level immunity between campaigns. Nonetheless our analyses suggest that with sustained, international commitment, global elimination of rabies from domestic dog populations, the most dangerous vector to humans, is a realistic goal

Clinical and magnetic resonance imaging characteristics of thoracolumbar intervertenral disk extrusions and protrusions in large breed dogs

It has recently been shown that the fat-derived hormone adiponectin has the ability to decrease hyperglycemia and to reverse insulin resistance. However, bacterially produced full-length adiponectin is functionally inactive. Here, we show that endogenous adiponectin secreted by adipocytes is post-translationally modified into eight different isoforms, as shown by two-dimensional gel electrophoresis. Carbohydrate detection revealed that six of the adiponectin isoforms are glycosylated. The glycosylation sites were mapped to several lysines (residues 68, 71, 80, and 104) located in the collagenous domain of adiponectin, each having the surrounding motif of GXKGE(D). These four lysines were found to be hydroxylated and subsequently glycosylated. The glycosides attached to each of these four hydroxylated lysines are possibly glucosylgalactosyl groups. Functional analysis revealed that full-length adiponectin produced by mammalian cells is much more potent than bacterially generated adiponectin in enhancing the ability of subphysiological concentrations of insulin to inhibit gluconeogenesis in primary rat hepatocytes, whereas this insulin-sensitizing ability was significantly attenuated when the four glycosylated lysines were substituted with arginines. These results indicate that full-length adiponectin produced by mammalian cells is functionally active as an insulin sensitizer and that hydroxylation and glycosylation of the four lysines in the collagenous domain might contribute to this activity.link_to_subscribed_fulltex

MCO gas composition for low reactive surface areas

This calculation adjusts modeled output (HNF-SD-SNF-TI-040, Rev. 2) by considering lower reactive fuel surface areas and by increasing the input helium backfill overpressure from 0.5 to 1.5 atm (2.5 atm abs) to verify that MCO gas-phase oxygen concentrations can remain below 4 mole % over a 40 year interim period under a worst case condition of zero reactive surface area. Added backfill gas will dilute any gases generated during interim storage and is a strategy within the current design capability. The zero reactive surface area represents a hypothetical worst case example where there is no fuel scrap and/or damaged spent fuel rods in an MCO. Also included is a hypothetical case where only K East fuel exists in an MCO with an added backfill overpressure of 0.5 atm (1.5 atm abs)

A molecular biology and phase II trial of lapatinib in children with refractory CNS malignancies: a pediatric brain tumor consortium study.

High expression of ERBB2 has been reported in medulloblastoma and ependymoma; EGFR is amplified and over-expressed in brainstem glioma suggesting these proteins as potential therapeutic targets. We conducted a molecular biology (MB) and phase II study to estimate inhibition of tumor ERBB signaling and sustained responses by lapatinib in children with recurrent CNS malignancies. In the MB study, patients with recurrent medulloblastoma, ependymoma, and high-grade glioma (HGG) undergoing resection were stratified and randomized to pre-resection treatment with lapatinib 900 mg/m(2) dose bid for 7-14 days or no treatment. Western blot analysis of ERBB expression and pathway activity in fresh tumor obtained at surgery estimated ERBB receptor signaling inhibition in vivo. Drug concentration was simultaneously assessed in tumor and plasma. In the phase II study, patients, stratified by histology, received lapatinib continuously, to assess sustained response. Eight patients, on the MB trial (four medulloblastomas, four ependymomas), received a median of two courses (range 1-6+). No intratumoral target inhibition by lapatinib was noted in any patient. Tumor-to-plasma ratios of lapatinib were 10-20 %. In the 34 patients (14 MB, 10 HGG, 10 ependymoma) in the phase II study, lapatinib was well-tolerated at 900 mg/m(2) dose bid. The median number of courses in the phase II trial was two (range 1-12). Seven patients (three medulloblastoma, four ependymoma) remained on therapy for at least four courses range (4-26). Lapatinib was well-tolerated in children with recurrent or CNS malignancies, but did not inhibit target in tumor and had little single agent activity.Fil: Fouladi, Maryam. St. Jude Children’s Research Hospital; Estados UnidosFil: Stewart, Clinton F.. St. Jude Children’s Research Hospital; Estados UnidosFil: Blaney, Susan M.. Baylor College of Medicine. Texas Children’s Cancer Center; Estados UnidosFil: Onar Thomas, Arzu. St. Jude Children’s Research Hospital; Estados UnidosFil: Schaiquevich, Paula Susana. St. Jude Children’s Research Hospital; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Packer, Roger J.. Children’s National Medical Center; Estados UnidosFil: Goldman, Stewart. Anne and Robert H. Lurie Children’s Hospital of Chicago; Estados UnidosFil: Geyer, J. Rusell. Children’s Hospital and Regional Medical Center; Estados UnidosFil: Gajjar, Amar. St. Jude Children’s Research Hospital; Estados UnidosFil: Kun, Larry E.. St. Jude Children’s Research Hospital; Estados UnidosFil: Boyett, James M.. St. Jude Children’s Research Hospital; Estados UnidosFil: Gilbertson, Richard J.. St. Jude Children’s Research Hospital; Estados Unido

On twisted Fourier analysis and convergence of Fourier series on discrete groups

We study norm convergence and summability of Fourier series in the setting of reduced twisted group $C^*$-algebras of discrete groups. For amenable groups, F{\o}lner nets give the key to Fej\'er summation. We show that Abel-Poisson summation holds for a large class of groups, including e.g. all Coxeter groups and all Gromov hyperbolic groups. As a tool in our presentation, we introduce notions of polynomial and subexponential H-growth for countable groups w.r.t. proper scale functions, usually chosen as length functions. These coincide with the classical notions of growth in the case of amenable groups.Comment: 35 pages; abridged, revised and update

Thyroid hormone regulates distinct paths to maturation in pigment cell lineages

Thyroid hormone (TH) regulates diverse developmental events and can drive disparate cellular outcomes. In zebrafish, TH has opposite effects on neural crest derived pigment cells of the adult stripe pattern, limiting melanophore population expansion, yet increasing yellow/orange xanthophore numbers. To learn how TH elicits seemingly opposite responses in cells having a common embryological origin, we analyzed individual transcriptomes from thousands of neural crest-derived cells, reconstructed developmental trajectories, identified pigment cell-lineage specific responses to TH, and assessed roles for TH receptors. We show that TH promotes maturation of both cell types but in distinct ways. In melanophores, TH drives terminal differentiation, limiting final cell numbers. In xanthophores, TH promotes accumulation of orange carotenoids, making the cells visible. TH receptors act primarily to repress these programs when TH is limiting. Our findings show how a single endocrine factor integrates very different cellular activities during the generation of adult form

Is it possible to model the impact of calorie-reduction interventions on childhood obesity at a population level and across the range of deprivation: Evidence from the Avon Longitudinal Study of Parents and Children (ALSPAC)

BACKGROUND: Simulated interventions using observational data have the potential to inform policy and public health interventions where randomised controlled trials are not feasible. National childhood obesity policy is one such area. Overweight and obesity are primarily caused by energy-rich and low-nutrient diets that contribute to a positive net energy imbalance. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we investigated whether causal modelling techniques could be applied to simulate the potential impact of policy-relevant calorie-reduction interventions on population prevalence and inequalities in obesity in childhood. METHODS: Predicted probabilities of obesity at age 11 (UK90 cut offs) were estimated from logistic marginal structural models (MSM) accounting for observed calorie consumption at age 7 and confounding, overall and by maternal occupational social class. A series of population intervention scenarios were modelled to simulate daily calorie-reduction interventions that differed in effectiveness, targeting mechanism and programme uptake level. RESULTS: The estimated effect of maternal social class on obesity after accounting for confounding and observed calorie intake was provided by the controlled direct effect (CDE), in which, 18.3% of children were living with obesity at age 11 years,. A universal simulation to lower median intake to the estimated average requirement (EAR) (a 6.1% reduction in daily calories) with 75% uptake reduced overall obesity prevalence by 0.6%; there was little impact on inequalities. A targeted intervention to limit consumption to the EAR for children with above average intake reduced population obesity prevalence at 11 years by 1.5% but inequalities remained broadly unchanged. A targeted intervention for children of low-income families reduced prevalence by 0.7% and was found to slightly reduce inequalities. CONCLUSIONS: MSMs allow estimation of effects of simulated calorie-reduction interventions on childhood obesity prevalence and inequalities, although estimates are limited by the accuracy of reported calorie intake. Further work is needed to understand causal pathways and opportunities for intervention. Nevertheless, simulated intervention techniques have promise for informing national policy where experimental data are not available