457 research outputs found
Extending the Activity Theory Based Model for Serious Games Design in Engineering to Integrate Analytics
Serious Games (SG) have been shown to have instructional potential and a number of formal models, frameworks and methodologies have emerged to support their design and analysis. The Activity Theory-based Model of Serious Games (ATMSG) facilitates a systematic and detailed representation of educational SG describing how game elements are connected together to contribute to pedagogical goals. This paper proposes and presents an extension to the ATMSG framework to facilitate the identification, selection and integration of analytics into serious games. A practical example of the approach in use in the analysis and design phase of a SG for engineering is demonstrated
Strengthening the Reporting of Genetic Risk Prediction Studies: The GRIPS Statement
Cecile Janssens and colleagues present the GRIPS Statement, a checklist to help strengthen the reporting of genetic risk prediction studies
A New Vaccine for Tuberculosis: The Challenges of Development and Deployment
Tuberculosis (TB) is one of the world’s leading causes of death due to infection and efforts to control TB would be substantially aided by the availability of an improved TB vaccine. There are currently nine new TB vaccines in clinical development, and the first efficacy trials are due to commence in 2009. There are many complex ethical issues which arise at all stages of TB vaccine development, from the need to conduct trials in developing countries to informed consent and the process of ethical review. While it is important that these issues are discussed, it may also be timely to consider the challenges which may arise if a vaccine in clinical development proves to be highly effective. We examine a number of scenarios where decisions on the deployment of a new TB vaccine may impact on the rights and liberty of the individual
Mitigation of Quantum Dot Cytotoxicity by Microencapsulation
When CdSe/ZnS-polyethyleneimine (PEI) quantum dots (QDs) are microencapsulated in polymeric microcapsules, human fibroblasts are protected from acute cytotoxic effects. Differences in cellular morphology, uptake, and viability were assessed after treatment with either microencapsulated or unencapsulated dots. Specifically, QDs contained in microcapsules terminated with polyethylene glycol (PEG) mitigate contact with and uptake by cells, thus providing a tool to retain particle luminescence for applications such as extracellular sensing and imaging. The microcapsule serves as the “first line of defense” for containing the QDs. This enables the individual QD coating to be designed primarily to enhance the function of the biosensor
A systematic review of biomarkers for disease progression in Parkinson's disease
Peer reviewedPublisher PD
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
Dual Neonate Vaccine Platform against HIV-1 and M. tuberculosis
Acquired immunodeficiency syndrome and tuberculosis (TB) are two of the
world's most devastating diseases. The first vaccine the majority of
infants born in Africa receive is Mycobacterium bovis bacillus
Calmette-Guérin (BCG) as a prevention against TB. BCG protects against
disseminated disease in the first 10 years of life, but provides a variable
protection against pulmonary TB and enhancing boost delivered by recombinant
modified vaccinia virus Ankara (rMVA) expressing antigen 85A (Ag85A) of
M. tuberculosis is currently in phase IIb evaluation in
African neonates. If the newborn's mother is positive for human
immunodeficiency virus type 1 (HIV-1), the baby is at high risk of acquiring
HIV-1 through breastfeeding. We suggested that a vaccination consisting of
recombinant BCG expressing HIV-1 immunogen administered at birth followed by a
boost with rMVA sharing the same immunogen could serve as a strategy for
prevention of mother-to-child transmission of HIV-1 and rMVA expressing an
African HIV-1-derived immunogen HIVA is currently in phase I trials in African
neonates. Here, we aim to develop a dual neonate vaccine platform against HIV-1
and TB consisting of BCG.HIVA administered at birth followed by a boost with
MVA.HIVA.85A. Thus, mMVA.HIVA.85A and sMVA.HIVA.85A vaccines were constructed,
in which the transgene transcription is driven by either modified H5 or short
synthetic promoters, respectively, and tested for immunogenicity alone and in
combination with BCG.HIVA222. mMVA.HIVA.85A was produced markerless
and thus suitable for clinical manufacture. While sMVA.HIVA.85A expressed higher
levels of the immunogens, it was less immunogenic than mMVA.HIVA.85A in BALB/c
mice. A BCG.HIVA222–mMVA.HIVA.85A prime-boost regimen induced
robust T cell responses to both HIV-1 and M. tuberculosis.
Therefore, proof-of-principle for a dual anti-HIV-1/M.
tuberculosis infant vaccine platform is established. Induction of
immune responses against these pathogens soon after birth is highly desirable
and may provide a basis for lifetime protection maintained by boosts later in
life
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