A weight resistance strength test for use in secondary schools.

Thesis (Ed.M.)--Boston Universit

Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in mycobacterium tuberculosis–infected individuals

Copyright © 2009 by the American Thoracic Society.Rationale: An effective new tuberculosis (TB) vaccine regimen must be safe in individuals with latent TB infection (LTBI) and is a priority for global health care. Objectives: To evaluate the safety and immunogenicity of a leading new TB vaccine, recombinant Modified Vaccinia Ankara expressing Antigen 85A (MVA85A) in individuals with LTBI. Methods: An open-label, phase I trial of MVA85A was performed in 12 subjects with LTBI recruited from TB contact clinics in Oxford and London or by poster advertisements in Oxford hospitals. Patients were assessed clinically and had blood samples drawn for immunological analysis over a 52-week period after vaccination with MVA85A. Thoracic computed tomography scans were performed at baseline and at 10 weeks after vaccination. Safety of MVA85A was assessed by clinical, radiological, and inflammatory markers. The immunogenicity of MVA85A was assessed by IFNγ and IL-2 ELISpot assays and FACS. Measurements and Main Results: MVA85A was safe in subjects with LTBI, with comparable adverse events to previous trials of MVA85A. There were no clinically significant changes in inflammatory markers or thoracic computed tomography scans after vaccination. MVA85A induced a strong antigen-specific IFN-γ and IL-2 response that was durable for 52 weeks. The magnitude of IFN-γ response was comparable to previous trials of MVA85A in bacillus Calmette-Guérin–vaccinated individuals. Antigen 85A–specific polyfunctional CD4+ T cells were detectable prior to vaccination with statistically significant increases in cell numbers after vaccination. Conclusions: MVA85A is safe and highly immunogenic in individuals with LTBI. These results will facilitate further trials in TB-endemic areas.Oxford Biomedical Research Centre, Wellcome Trust, and AFTBVAC

Autoantibody detection for diagnosis in direct immunofluorescence negative mucous membrane pemphigoid: ocular and other sites compared

Objective: To assess whether a panel of serum pemphigoid autoantibody tests could be used to confirm an immunopathological diagnosis of mucous membrane pemphigoid (MMP) in direct immunofluorescent negative (DIF-) MMP patients. / Design: Prospective cross-sectional study. / Subjects and controls: 76 patients with MMP involving ocular and non-ocular sites with 45 matched controls. / Tests: Enzyme linked immunosorbent assays (ELISA) for BP180 and BP230 (MBL International®), IgA and IgG indirect immunofluorescence on human salt-split skin (IIF SSS) and the keratinocyte footprint assay for anti-laminin 332 antibodies. / Main outcome measures: Sensitivity and specificity of autoantibody detection; significant differences for individual tests and test combinations for MMP involving different sites. / Results: All DIF- Cases (24/76, 31.8%) had either ocular only disease or ocular involvement in multi-site disease. Serum pemphigoid autoantibodies were detected in 29/76 (38.2%) of all MMP patients compared to 3/45 (6.7%) of controls. Autoantibody reactivity detected by any one or more of the tests was present in 6/24 (25%) DIF- cases compared to 22/49 (44.9%) in DIF positive (DIF+). Compared to controls ocular only MMP serum reactivity was not significantly different for any test or test combination whereas DIF- multisite ocular MMP differed for one ELISA and 3/7 test combinations. By contrast, for DIF+ non ocular MMP all the individual tests, apart from IgA IIF, and all test combinations were significantly different compared to controls. For the whole MMP cohort the sensitivity of all tests was low having a maximum of 21.05% for BP180 reactivity, increasing to 38.16% for an optimal test combination. Disease activity was strongly associated with positive serology findings. / Conclusions: Pemphigoid serum autoantibody tests did not provide alternative immunopathological evidence of MMP in ocular only MMP patients but had limited value in DIF- multisite ocular MMP. The requirement for immunopathological confirmation of MMP by autoantibody detection is inappropriate for DIF- ocular only MMP resulting in missed diagnoses, delayed therapy and poor outcomes. Alternative diagnostic criteria for MMP with ocular involvement are required, to exclude the other causes of scarring conjunctivitis, until more sensitive and specific immunopathology tests become available

The effect of video-guidance on passive movement in patients with cerebral palsy: fMRI study

In patients with cerebral palsy (CP), neuroimaging studies have demonstrated that passive movement and action–observation tasks have in common to share neuronal activation in all or part of areas involved in motor system. Action observation with simultaneous congruent passive movements may have additional effects in the recruitment of brain motor areas. The aim of this functional magnetic resonance imaging (fMRI) study was to examine brain activation in patients with unilateral CP during passive movement with and without simultaneous observation of simple hand movement. Eighteen patients with unilateral CP (fourteen male, mean age 14 years and 2 months) participated in the study. Using fMRI block design, brain activation following passive simple opening–closing hand movement of either the paretic or nonparetic hand with and without simultaneous observation of a similar movement performed by either the left or right hand of an actor was compared. Passive movement of the paretic hand performed simultaneously to the observation of congruent movement activated more “higher motor areas” including contralesional pre-supplementary motor area, superior frontal gyrus (extending to premotor cortex), and superior and inferior parietal regions than nonvideo-guided passive movement of the paretic hand. Passive movement of the paretic hand recruited more ipsilesional sensorimotor areas compared to passive movement of the nonparetic hand. Our study showed that the combination of observation of congruent hand movement simultaneously to passive movement of the paretic hand recruits more motor areas, giving neuronal substrate to propose video-guided passive movement of paretic hand in CP rehabilitation

A High Power Density Power System Electronics for NASA's Lunar Reconnaissance Orbiter

A high power density, modular and state-of-the-art Power System Electronics (PSE) has been developed for the Lunar Reconnaissance Orbiter (LRO) mission. This paper addresses the hardware architecture and performance, the power handling capabilities, and the fabrication technology. The PSE was developed by NASA s Goddard Space Flight Center (GSFC) and is the central location for power handling and distribution of the LRO spacecraft. The PSE packaging design manages and distributes 2200W of solar array input power in a volume less than a cubic foot. The PSE architecture incorporates reliable standard internal and external communication buses, solid state circuit breakers and LiIon battery charge management. Although a single string design, the PSE achieves high reliability by elegantly implementing functional redundancy and internal fault detection and correction. The PSE has been environmentally tested and delivered to the LRO spacecraft for the flight Integration and Test. This modular design is scheduled to flight in early 2009 on board the LRO and Lunar Crater Observation and Sensing Satellite (LCROSS) spacecrafts and is the baseline architecture for future NASA missions such as Global Precipitation Measurement (GPM) and Magnetospheric MultiScale (MMS)

Roles for Treg expansion and HMGB1 signaling through the TLR1-2-6 axis in determining the magnitude of the antigen-specific immune response to MVA85A

© 2013 Matsumiya et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedA better understanding of the relationships between vaccine, immunogenicity and protection from disease would greatly facilitate vaccine development. Modified vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel tuberculosis vaccine candidate designed to enhance responses induced by BCG. Antigen-specific interferon-γ (IFN-γ) production is greatly enhanced by MVA85A, however the variability between healthy individuals is extensive. In this study we have sought to characterize the early changes in gene expression in humans following vaccination with MVA85A and relate these to long-term immunogenicity. Two days post-vaccination, MVA85A induces a strong interferon and inflammatory response. Separating volunteers into high and low responders on the basis of T cell responses to 85A peptides measured during the trial, an expansion of circulating CD4+ CD25+ Foxp3+ cells is seen in low but not high responders. Additionally, high levels of Toll-like Receptor (TLR) 1 on day of vaccination are associated with an increased response to antigen 85A. In a classification model, combined expression levels of TLR1, TICAM2 and CD14 on day of vaccination and CTLA4 and IL2Rα two days post-vaccination can classify high and low responders with over 80% accuracy. Furthermore, administering MVA85A in mice with anti-TLR2 antibodies may abrogate high responses, and neutralising antibodies to TLRs 1, 2 or 6 or HMGB1 decrease CXCL2 production during in vitro stimulation with MVA85A. HMGB1 is released into the supernatant following atimulation with MVA85A and we propose this signal may be the trigger activating the TLR pathway. This study suggests an important role for an endogenous ligand in innate sensing of MVA and demonstrates the importance of pattern recognition receptors and regulatory T cell responses in determining the magnitude of the antigen specific immune response to vaccination with MVA85A in humans.This work was funded by the Wellcome Trust. MM has a Wellcome Trust PhD studentship and HM is a Wellcome Trust Senior Fello

NEWS AND NOTES 1994, VOL.4, NO.16

https://digitalcommons.rockefeller.edu/news_and_notes_1994/1002/thumbnail.jp

Effect of motor imagery in children with unilateral cerebral palsy: fMRI study

Background Motor imagery is considered as a promising therapeutic tool for rehabilitation of motor planning problems in patients with cerebral palsy. However motor planning problems may lead to poor motor imagery ability. Aim The aim of this functional magnetic resonance imaging study was to examine and compare brain activation following motor imagery tasks in patients with hemiplegic cerebral palsy with left or right early brain lesions. We tested also the influence of the side of imagined hand movement. Method Twenty patients with clinical hemiplegic cerebral palsy (sixteen males, mean age 12 years and 10 months, aged 6 years 10 months to 20 years 10 months) participated in this study. Using block design, brain activations following motor imagery of a simple opening-closing hand movement performed by either the paretic or nonparetic hand was examined. Results During motor imagery tasks, patients with early right brain damages activated bilateral fronto-parietal network that comprise most of the nodes of the network well described in healthy subjects. Inversely, in patients with left early brain lesion brain activation following motor imagery tasks was reduced, compared to patients with right brain lesions. We found also a weak influence of the side of imagined hand movement. Conclusion Decreased activations following motor imagery in patients with right unilateral cerebral palsy highlight the dominance of the left hemisphere during motor imagery tasks. This study gives neuronal substrate to propose motor imagery tasks in unilateral cerebral palsy rehabilitation at least for patients with right brain lesions

Effect of observation of simple hand movement on brain activations in patients with unilateral cerebral palsy: an fMRI study

The aim of this functional magnetic resonance imaging (fMRI) study was to examine and compare brain activation in patients with unilateral cerebral palsy (CP) during observation of simple hand movement performed by the paretic and nonparetic hand. Nineteen patients with clinical unilateral CP (14 male, mean age 14 years, 7–21 years) participated in the study. Hand motor impairment was assessed using the sequential finger opposition task. Using fMRI block design, brain activation was examined following observation at rest of a simple opening-closing hand movement, performed by either the left or right hand of an actor. Eighteen fMRI dataset were analyzed. Observing hand movement produced large bilateral activations in temporo-parieto-fronto-occipital network, comprising most of the nodes of the well described action-observation network. For either side, observing hand movements recruits the primary motor cortex (M1), contralateral to the viewed hand, as would be expected in healthy persons. Viewing movement performed by an actor\u27s hand representing the paretic side of patients activated more strongly ipsilesional M1 than viewing movement performed by an actor\u27s hand representing the nonparetic side of patients. Observation of hand movement in patients with CP engaged the motor execution network regardless of the degree of motor impairment