Non-neutralizing antibodies elicited by recombinant Lassa-Rabies vaccine are critical for protection against Lassa fever

Lassa fever (LF), caused by Lassa virus (LASV), is a viral hemorrhagic fever for which no approved vaccine or potent antiviral treatment is available. LF is a WHO priority disease and, together with rabies, a major health burden in West Africa. Here we present the development and characterization of an inactivated recombinant LASV and rabies vaccine candidate (LASSARAB) that expresses a codon-optimized LASV glycoprotein (coGPC) and is adjuvanted by a TLR-4 agonist (GLA-SE). LASSARAB elicits lasting humoral response against LASV and RABV in both mouse and guinea pig models, and it protects both guinea pigs and mice against LF. We also demonstrate a previously unexplored role for non-neutralizing LASV GPC-specific antibodies as a major mechanism of protection by LASSARAB against LF through antibody-dependent cellular functions. Overall, these findings demonstrate an effective inactivated LF vaccine and elucidate a novel humoral correlate of protection for LF.NIH grants R01 AI105204 to M.J.S., by the Jefferson Vaccine Center, and by the Fundação para a Ciência e Tecnologia (FCT) scholarship PD/BD/105847/2014 (to T.A.-M.). This work was also funded in part through the NIAID Division of Intramural Research and the NIAID Division of Clinical Research, Battelle Memorial Institute’s prime contract with the U.S. National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272200700016Iinfo:eu-repo/semantics/publishedVersio

Effectiveness of physical therapy interventions for children with cerebral palsy: A systematic review

Background To assess the effectiveness of physical therapy (PT) interventions on functioning in children with cerebral palsy (CP). Methods A search was made in Medline, Cinahl, PEDro and the Cochrane library for the period 1990 to February 2007. Only randomized controlled trials (RCTs) on PT interventions in children with diagnosed CP were included. Two reviewers independently assessed the methodological quality and extracted the data. The outcomes measured in the trials were classified using the International Classification of Functioning, Disability and Health (ICF). Results Twenty-two trials were identified. Eight intervention categories were distinguished. Four trials were of high methodological quality. Moderate evidence of effectiveness was established for two intervention categories: effectiveness of upper extremity treatments on attained goals and active supination, and of prehensile hand treatment and neurodevelopmental therapy (NDT) or NDT twice a week on developmental status, and of constraint-induced therapy on amount and quality of hand use. Moderate evidence of ineffectiveness was found of strength training on walking speed and stride length. Conflicting evidence was found for strength training on gross motor function. For the other intervention categories the evidence was limited due to low methodological quality and the statistically insignificant results of the studies. Conclusion Due to limitations in methodological quality and variations in population, interventions and outcomes, mostly limited evidence on the effectiveness of most PT interventions is available through RCTs. Moderate evidence was found for some effectiveness of upper extremity training. Well-designed trials are needed especially for focused PT interventions.BioMed Central Open acces

The journeys of three ASPIRE winning medical schools toward excellence in student assessment

Introduction: ASPIRE Excellence Awards in Student Assessment are offered to medical schools with innovative and comprehensive assessment programmes adjudged by international experts, using evidence-based criteria. The journeys of three ASPIRE-winning medical schools toward “assessment excellence” are presented. These schools include Aga Khan University Medical College (AKU-MC), Pakistan, Southern Illinois University School of Medicine (SIUSOM), USA, and University of Leeds School of Medicine, UK. Methods: The unfolding journeys highlighting achievements, innovations, and essential components of each assessment programme were compared to identify differences and commonalities. Results: Cultural contextual differences included developed-versus-developing country, east-west, type of regulatory bodies, and institutional-versus-national certifying/licensing examinations, which influence curricula and assessments. In all, 12 essential commonalities were found: alignment with institutional vision; sustained assessment leadership; stakeholder engagement; communication between curriculum and assessment; assessment-for-learning and feedback; longitudinal student profiling of outcome achievement; assessment rigor and robustness; 360° feedback from-and-to assessment; continuous enrichment through rigorous quality assurance; societal sensitivity; influencing others; and a “wow factor.” Conclusions: Although the journeys of the three medical schools were undertaken in different cultural contexts, similar core components highlight strong foundations in student assessment. The journeys continue as assessment programmes remain dynamic and measurement science expands. This article may be helpful to other institutions pursuing excellence in assessment