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

Frontal lobe damage impairs process and content in semantic memory: evidence from category specific effects in progressive nonfluent aphasia

t r a c t Portions of left inferior frontal cortex have been linked to semantic memory both in terms of the content of conceptual representation (e.g., motor aspects in an embodied semantics framework) and the cognitive processes used to access these representations (e.g., response selection). Progressive non-fluent aphasia (PNFA) is a neurodegenerative condition characterized by progressive atrophy of left inferior frontal cortex. PNFA can, therefore, provide a lesion model for examining the impact of frontal lobe damage on semantic processing and content. In the current study we examined picture naming in a cohort of PNFA patients across a variety of semantic categories. An embodied approach to semantic memory holds that sensorimotor features such as self-initiated action may assume differential importance for the representation of manufactured artifacts (e.g., naming hand tools). Embodiment theories might therefore predict that patients with frontal damage would be differentially impaired on manufactured artifacts relative to natural kinds, and this prediction was borne out. We also examined patterns of naming errors across a wide range of semantic categories and found that naming error distributions were heterogeneous. Although PNFA patients performed worse overall on naming manufactured artifacts, there was no reliable relationship between anomia and manipulability across semantic categories. These results add to a growing body of research arguing against a purely sensorimotor account of semantic memory, suggesting instead a more nuanced balance of process and content in how the brain represents conceptual knowledge. Please cite this article in press as: Reilly J, et al., Frontal lobe damage impairs process and content in semantic memory: Evidence from category-specific effects in progressive non-fluent aphasia, Cortex (2010)

Intraoperative manufacturing of patient specific instrumentation for shoulder arthroplasty: a novel mechatronic approach

Optimal orthopaedic implant placement is a major contributing factor to the long term success of all common joint arthroplasty procedures. Devices such as three-dimensional (3D) printed, bespoke guides and orthopaedic robots are extensively described in the literature and have been shown to enhance prosthesis placement accuracy. These technologies, however, have significant drawbacks, such as logistical and temporal inefficiency, high cost, cumbersome nature and difficult theatre integration. A new technology for the rapid intraoperative production of patient specific instrumentation, which overcomes many of the disadvantages of existing technologies, is presented here. The technology comprises a reusable table side machine, bespoke software and a disposable element comprising a region of standard geometry and a body of mouldable material. Anatomical data from Computed Tomography (CT) scans of 10 human scapulae was collected and, in each case, the optimal glenoid guidewire position was digitally planned and recorded. The achieved accuracy compared to the preoperative bespoke plan was measured in all glenoids, from both a conventional group and a guided group. The technology was successfully able to intraoperatively produce sterile, patient specific guides according to a pre-operative plan in 5 minutes, with no additional manufacturing required prior to surgery. Additionally, the average guide wire placement accuracy was 1.58 mm and 6.82◦ degrees in the manual group, and 0.55 mm and 1.76◦ degrees in the guided group, also demonstrating a statistically significant improvement

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

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

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

Impact of polygenic risk for coronary artery disease and cardiovascular medication burden on cognitive impairment in psychotic disorders

Background: Cognitive impairment is a core deficit across psychotic disorders, the causes and therapeutics of which remain unclear. Epidemiological observations have suggested associations between cognitive dysfunction in psychotic disorders and cardiovascular risk factors, but an underlying etiology has not been established. Methods: Neuropsychological performance using the Brief Assessment of Cognition in Schizophrenia (BACS) was assessed in 616 individuals of European ancestry (403 psychosis, 213 controls). Polygenic risk scores for coronary artery disease (PRSCAD) were quantified for each participant across 13 p-value thresholds (PT 0.5-5e-8). Cardiovascular and psychotropic medications were categorized for association analyses. Each PRSCAD was examined in relation to the BACS and the optimized PT was confirmed with five-fold cross-validation and independent validation. Functional enrichment analyses were used to identify biological mechanisms linked to PRSCAD-cognition associations. Multiple regression analyses examined PRSCAD under the optimal PT and medication burden in relation to the BACS composite and subtest scores. Results: Higher PRSCAD was associated with lower BACS composite scores (p = 0.001) in the psychosis group, primarily driven by the Verbal Memory subtest (p \u3c 0.001). Genes linked to multiple nervous system related processes and pathways were significantly enriched in PRSCAD. After controlling for PRSCAD, a greater number of cardiovascular medications was also correlated with worse BACS performance in patients with psychotic disorders (p = 0.029). Conclusions: Higher PRSCAD and taking more cardiovascular medications were both significantly associated with cognitive impairment in psychosis. These findings indicate that cardiovascular factors may increase the risk for cognitive dysfunction and related functional outcomes among individuals with psychotic disorders

Characterizing Nonfluent Speech in Aphasia: Variables that Affect Rater Judgment

Judging speech fluency is an important characteristic of the evaluation of aphasic speech. However, it is a complex task since fluency is comprised of several speech dimensions. This study investigated five variables that contribute to judging fluency: speech rate, audible struggle, syllable type token ratio, speech productivity, and filler ratio. Twenty healthy older adults and 27 nonfluent aphasic speakers described the Cookie Theft picture (BDAE). Speech rate, audible struggle, and speech productivity were rated as significantly different between the two groups. Future studies with larger samples and broader populations are needed to support the predictive values in determining speech fluency