A temperature sensitive live-attenuated canine influenza virus H3N8 vaccine

Canine influenza is a respiratory disease of dogs caused by canine influenza virus (CIV). CIV subtypes responsible for influenza in dogs include H3N8, which originated from the transfer of H3N8 equine influenza virus to dogs; and the H3N2 CIV, which is an avian-origin virus that adapted to infect dogs. Influenza infections are most effectively prevented through vaccination to reduce transmission and future infection. Currently, only inactivated influenza vaccines (IIVs) are available for the prevention of CIV in dogs. However, the efficacy of IIVs is suboptimal, and novel approaches are necessary for the prevention of disease caused by this canine respiratory pathogen. Using reverse genetics techniques, we have developed a live-attenuated CIV vaccine (LACIV) for the prevention of H3N8 CIV. The H3N8 LACIV replicates efficiently in canine cells at 33°C but is impaired at temperatures of 37 to 39°C and was attenuated compared to wild-type H3N8 CIV in vivo and ex vivo. The LACIV was able to induce protection against H3N8 CIV challenge with a single intranasal inoculation in mice. Immunogenicity and protection efficacy were better than that observed with a commercial CIV H3N8 IIV but provided limited cross-reactive immunity and heterologous protection against H3N2 CIV. These results demonstrate the feasibility of implementing a LAIV approach for the prevention and control of H3N8 CIV in dogs and suggest the need for a new LAIV for the control of H3N2 CIV. Importance: Two influenza A virus subtypes has been reported in dogs in the last 16 years: the canine influenza viruses (CIV) H3N8 and H3N2 of equine and avian origins, respectively. To date, only inactivated influenza vaccines (IIVs) are available to prevent CIV infections. Here, we report the generation of a recombinant, temperature-sensitive H3N8 CIV as a live-attenuated influenza vaccine (LAIV), which was attenuated in mice and dog tracheal, explants compared to CIV H3N8 wild type. A single dose of H3N8 LACIV showed immunogenicity and protection against a homologous challenge that was better than that conferred with an H3N8 IIV, demonstrating the feasibility of implementing a LAIV approach for the improved control of H3N8 CIV infections in dogs

A five year longitudinal study investigating the prevalence of childhood obesity: comparison of BMI and waist circumference.

Objective: The purpose of this study was to examine the prevalence of obesity over time in the same individuals comparing body mass index (BMI), waist circumference (WC) and waist to height ratio (WHtR). Study design: Five year longitudinal repeated measures study (2005–2010). Children were aged 11–12 (Y7) years at baseline and measurements were repeated at age 13–14 (Y9) years and 15–16 (Y11) years. Methods: WC and BMI measurements were carried out by the same person over the five years and raw values were expressed as standard deviation scores (sBMI and sWC) against the growth reference used for British children. Results: Mean sWC measurements were higher than mean sBMI measurements for both sexes and at all assessment occasions and sWC measurements were consistently high in girls compared to boys. Y7 sWC = 0.792 [95% confidence interval (CI) 0.675–0.908], Y9 sWC = 0.818 (95%CI 0.709–0.928), Y11 sWC = 0.943 (95%CI 0.827–1.06) for boys; Y7 sWC = 0.843 (0.697–0.989), Y9 sWC = 1.52 (95%CI 1.38–0.67), Y11 sWC = 1.89 (95%CI 1.79–2.04) for girls. Y7 sBMI = 0.445 (95%CI 0.315–0.575), Y9 sBMI = 0.314 (95%CI 0.189–0.438), Y11 sBMI = 0.196 (95%CI 0.054–0.337) for boys; Y7 sBMI = 0.353 (0.227–0.479), Y9 sBMI = 0.343 (95%CI 0.208–0.478), Y11 sBMI = 0.256 (95%CI 0.102–0.409) for girls. The estimated prevalence of obesity defined by BMI decreased in boys (18%, 12% and 10% in Y 7, 9 and 11 respectively) and girls (14%, 15% and 11% in Y 7, 9 and 11). In contrast, the prevalence estimated by WC increased sharply (boys; 13%, 19% and 23%; girls, 20%, 46% and 60%). Conclusion: Central adiposity, measured by WC is increasing alongside a stabilization in BMI. Children appear to be getting fatter and the additional adiposity is being stored centrally which is not detected by BMI. These substantial increases in WC are a serious concern, especially in girls

Area-level deprivation and adiposity in children: is the relationship linear?

OBJECTIVE: It has been suggested that childhood obesity is inversely associated with deprivation, such that the prevalence is higher in more deprived groups. However, comparatively few studies actually use an area-level measure of deprivation, limiting the scope to assess trends in the association with obesity for this indicator. Furthermore, most assume a linear relationship. Therefore, the aim of this study was to investigate associations between area-level deprivation and three measures of adiposity in children: body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR). DESIGN: This is a cross-sectional study in which data were collected on three occasions a year apart (2005-2007). SUBJECTS: Data were available for 13,333 children, typically aged 11-12 years, from 37 schools and 542 lower super-output areas (LSOAs). MEASURES: Stature, mass and WC. Obesity was defined as a BMI and WC exceeding the 95th centile according to British reference data. WHtR exceeding 0.5 defined obesity. The Index of Multiple Deprivation affecting children (IDACI) was used to determine area-level deprivation. RESULTS: Considerable differences in the prevalence of obesity exist between the three different measures. However, for all measures of adiposity the highest probability of being classified as obese is in the middle of the IDACI range. This relationship is more marked in girls, such that the probability of being obese for girls living in areas at the two extremes of deprivation is around half that at the peak, occurring in the middle. CONCLUSION: These data confirm the high prevalence of obesity in children and suggest that the relationship between obesity and residential area-level deprivation is not linear. This is contrary to the 'deprivation theory' and questions the current understanding and interpretation of the relationship between obesity and deprivation in children. These results could help make informed decisions at the local level

Connectionist natural language parsing

The key developments of two decades of connectionist parsing are reviewed. Connectionist parsers are assessed according to their ability to learn to represent syntactic structures from examples automatically, without being presented with symbolic grammar rules. This review also considers the extent to which connectionist parsers offer computational models of human sentence processing and provide plausible accounts of psycholinguistic data. In considering these issues, special attention is paid to the level of realism, the nature of the modularity, and the type of processing that is to be found in a wide range of parsers

Evidence for a compact jet dominating the broadband spectrum of the black hole accretor XTE J1550-564

[abridged] The black hole X-ray binary XTE J1550-564 was monitored extensively at X-ray, optical and infrared wavelengths throughout its outburst in 2000. We show that it is possible to separate the optical/near-infrared (OIR) jet emission from the OIR disc emission. Focussing on the jet component, we find that as the source fades in the X-ray hard state, the OIR jet emission has a spectral index consistent with optically thin synchrotron emission (alpha ~ -0.6 to -0.7, where F_nu \propto nu^alpha). This jet emission is tightly and linearly correlated with the X-ray flux; L_OIR,jet \propto L_X^(0.98 +- 0.08) suggesting a common origin. This is supported by the OIR, X-ray and OIR to X-ray spectral indices being consistent with a single power law (alpha = -0.73). Ostensibly the compact, synchrotron jet could therefore account for ~ 100 % of the X-ray flux at low luminosities in the hard state. At the same time, (i) an excess is seen over the power law decay of the X-ray flux at the point in which the jet would start to dominate, (ii) the X-ray spectrum slightly softens, which seems to be due to a high energy cut-off or break shifting to a lower energy, and (iii) the X-ray rms variability increases. This may be the strongest evidence to date of synchrotron emission from the compact, steady jet dominating the X-ray flux of an X-ray binary. For XTE J1550-564, this is likely to occur within the luminosity range ~ (2 e-4 - 2 e-3) L_Edd on the hard state decline of this outburst. However, on the hard state rise of the outburst and initially on the hard state decline, the synchrotron jet can only provide a small fraction (~ a few per cent) of the X-ray flux. Both thermal Comptonization and the synchrotron jet can therefore produce the hard X-ray power law in accreting black holes.Comment: MNRAS accepted, 12 pages, 9 figure

Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy

OBJECTIVE To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene. METHODS Patients with a phenotype suggestive of a motor, non-length-dependent neuronopathy predominantly affecting the lower limbs were identified at participating neuromuscular centers and referred for targeted sequencing of DYNC1H1. RESULTS We report a cohort of 30 cases of SMA-LED from 16 families, carrying mutations in the tail and motor domains of DYNC1H1, including 10 novel mutations. These patients are characterized by congenital or childhood-onset lower limb wasting and weakness frequently associated with cognitive impairment. The clinical severity is variable, ranging from generalized arthrogryposis and inability to ambulate to exclusive and mild lower limb weakness. In many individuals with cognitive impairment (9/30 had cognitive impairment) who underwent brain MRI, there was an underlying structural malformation resulting in polymicrogyric appearance. The lower limb muscle MRI shows a distinctive pattern suggestive of denervation characterized by sparing and relative hypertrophy of the adductor longus and semitendinosus muscles at the thigh level, and diffuse involvement with relative sparing of the anterior-medial muscles at the calf level. Proximal muscle histopathology did not always show classic neurogenic features. CONCLUSION Our report expands the clinical spectrum of DYNC1H1-related SMA-LED to include generalized arthrogryposis. In addition, we report that the neurogenic peripheral pathology and the CNS neuronal migration defects are often associated, reinforcing the importance of DYNC1H1 in both central and peripheral neuronal functions

Neck-cooling improves repeated sprint performance in the heat

The present study evaluated the effect of neck-cooling during exercise on repeated sprint ability in a hot environment. Seven team-sport playing males completed two experimental trials involving repeated sprint exercise (5 × 6 s) before and after two 45 min bouts of a football specific intermittent treadmill protocol in the heat (33.0 ± 0.2°C; 53 ± 2% relative humidity). Participants wore a neck-cooling collar in one of the trials (CC). Mean power output and peak power output declined over time in both trials but were higher in CC (540 ± 99 v 507 ± 122 W, d = 0.32; 719 ± 158 v 680 ± 182 W, d = 0.24 respectively). The improved power output was particularly pronounced (d = 0.51–0.88) after the 2nd 45 min bout but the CC had no effect on % fatigue. The collar lowered neck temperature and the thermal sensation of the neck (P 0.05). There were no trial differences but interaction effects were demonstrated for prolactin concentration and rating of perceived exertion (RPE). Prolactin concentration was initially higher in the collar cold trial and then was lower from 45 min onwards (interaction trial × time P = 0.04). RPE was lower during the football intermittent treadmill protocol in the collar cold trial (interaction trial × time P = 0.01). Neck-cooling during exercise improves repeated sprint performance in a hot environment without altering physiological or neuroendocrinological responses. RPE is reduced and may partially explain the performance improvement

Investigating the association between obesity and asthma in 6- to 8-year-old Saudi children:a matched case-control study

Background: Previous studies have demonstrated an association between obesity and asthma, but there remains considerable uncertainty about whether this reflects an underlying causal relationship. Aims: To investigate the association between obesity and asthma in pre-pubertal children and to investigate the roles of airway obstruction and atopy as possible causal mechanisms. Methods: We conducted an age- and sex-matched case–control study of 1,264 6- to 8-year-old schoolchildren with and without asthma recruited from 37 randomly selected schools in Madinah, Saudi Arabia. The body mass index (BMI), waist circumference and skin fold thickness of the 632 children with asthma were compared with those of the 632 control children without asthma. Associations between obesity and asthma, adjusted for other potential risk factors, were assessed separately in boys and girls using conditional logistic regression analysis. The possible mediating roles of atopy and airway obstruction were studied by investigating the impact of incorporating data on sensitisation to common aeroallergens and measurements of lung function. Results: BMI was associated with asthma in boys (odds ratio (OR)=1.14, 95% confidence interval (CI), 1.08–1.20; adjusted OR=1.11, 95% CI, 1.03–1.19) and girls (OR=1.37, 95% CI, 1.26–1.50; adjusted OR=1.38, 95% CI, 1.23–1.56). Adjusting for forced expiratory volume in 1 s had a negligible impact on these associations, but these were attenuated following adjustment for allergic sensitisation, particularly in girls (girls: OR=1.25; 95% CI, 0.96–1.60; boys: OR=1.09, 95% CI, 0.99–1.19). Conclusions: BMI is associated with asthma in pre-pubertal Saudi boys and girls; this effect does not appear to be mediated through respiratory obstruction, but in girls this may at least partially be mediated through increased risk of allergic sensitisation

Selenium uptake by edible plants from enriched peat.

As a constituent of selenoproteins, selenium (Se) is considered an essential element for human health.The main way that Se enters the body is via the consumption of vegetables, whose concentration of thiselement depends on soil Se content. We grew cabbage, lettuce, chard and parsley, in peat enriched in Seby means of the additive Selcote Ultra®and Na2SeO3and Na2SeO4. Total Se in plants was determinedby acidic digestion and Se speciation by an enzymatic extraction. Both were measured by ICP/MS. Theconcentration ranges were between 0.1 mg Se kg−1and 30 mg Se kg−1for plants grown in Selcote Ultra®media, and between 0.4 mg Se kg−1and 1606 mg Se kg−1for those grown in peat enriched with Se sodiumsalts. We found Se (IV), Se (VI) and SeMet in all the extracts. Peat fortified with Selcote Ultra®gave slightlyhigher Se concentration than natural content values. For plants grown with selenium sodium salts, Secontent increases with the Se added and part of the inorganic Se was converted mainly to SeMet. A highSe fortification can damage or inhibit plant growth. Cabbage showed the greatest tolerance to Se