Parenteral and mucosal delivery of a novel multi-epitope M protein-based group A streptococcal vaccine construct: investigation of immunogenicity in mice

Primary vaccine strategies against group A streptococci (GAS) have focused on the M protein-the target of opsonic antibodies important for protective immunity. We have previously reported protection of mice against GAS infection following parenteral delivery of a multi-epitope vaccine construct, referred to as a heteropolymer. This current report has assessed mucosal (intranasal (i.n.) and oral) delivery of the heteropolymer in mice with regard to the induction and specificity of mucosal and systemic antibody responses, and compared this to parenteral delivery. GAS-specific IgA responses were detected in saliva and gut upon i.n. and oral delivery of the heteropolymer co-administered with cholera toxin B subunit, respectively. High titre serum IgG responses were elicited to the heteropolymer following all routes of delivery when administered with adjuvant. Moreover, as with parenteral delivery, serum IgG antibodies were detected to the individual heteropolymer peptides following i.n. but not oral delivery. These data support the potential of the i.n. route in the mucosal delivery of a GAS vaccine. (C) 2002 Elsevier Science Ltd. All rights reserved.

Enhancing the immunogenicity and modulating the fine epitope recognition of antisera to a helical group A streptococcal peptide vaccine candidate from the M protein using lipid-core peptide technology

A conserved helical peptide vaccine candidate from the M protein of group A streptococci, p145, has been described. Minimal epitopes within p145 have been defined and an epitope recognized by protective antibodies, but not by autoreactive T cells, has been identified. When administered to mice, p145 has low immunogenicity. Many boosts of peptide are required to achieve a high antibody titre (> 12 800). To attempt to overcome this low immunogenicity, lipid-core peptide technology was employed. Lipid-core peptides (LCP) consist of an oligomeric polylysine core, with multiple copies of the peptide of choice, conjugated to a series of lipoamino acids, which acts as an anchor for the antigen. Seven different LCP constructs based on the p145 peptide sequence were synthesized (LCP1-->LCP7) and the immunogenicity of the compounds examined. The most immunogenic constructs contained the longest alkyl side-chains. The number of lipoamino acids in the constructs affected the immunogenicity and spacing between the alkyl side-chains increased immunogenicity. An increase in immunogenicity (enzyme-linked immunosorbent assay (ELISA) titres) of up to 100-fold was demonstrated using this technology and some constructs without adjuvant were more immunogenic than p145 administered with complete Freund's adjuvant (CFA). The fine specificity of the induced antibody response differed for the different constructs but one construct, LCP4, induced antibodies of identical fine specificity to those found in endemic human serum. Opsonic activity of LCP4 antisera was more than double that of p145 antisera. These data show the potential for LCP technology to both enhance immunogenicity of complex peptides and to focus the immune response towards or away from critical epitopes.

NAD-glycohydrolase production and speA and speC distribution in group A streptococcus (GAS) isolates do not correlate with severe GAS diseases in the Australian population

Streptococcus pyogenes isolates from a tropical region and a subtropical region of Australia with high and low incidences of severe streptococcal diseases, respectively, were analyzed for speA, speB, and speC gene distributions and NAD-glycohydrolase expression. No direct correlation of these characteristics with a propensity to cause invasive diseases was observed.

Perceptions of younger, middle-aged, and older adults in Australia and Japan: Stereotypes and age group vitality

This study investigated the perceptions of young adults in Japan and Australia about their own age group, as well as middle-aged and older adults. Using a self-administered questionnaire, 155 Japanese and 171 Australian students rated people in the three age groups on traits of personal vitality and benevolence, and also rated their age group vitalities. Results indicated that Australians perceived both middle-aged and older adults in more positive terms than did Japanese and also perceived the vitality of these age groups as higher. On the other hand, both Japanese and Australian young people judged the vitality of their own group as lower than that of middle-aged adults. These results suggest that norms of filial piety, especially its respect dimension, in Japan may be eroding, whereas older Australians may be gaining in social stature.

Adapting immunity with subunit vaccines: case studies with group A Streptococcus and malaria

Although vaccines have widely been regarded as the most cost-effective way to improve public health, for some organisms new technological advances in vaccine design and delivery, incurring additional developmental costs, will be essential. These organisms are typically those for which natural immunity is either slow to develop or does not develop at all. Clearly, such organisms have evolved strategies to evade immune responses and innovative approaches will be required to induce a type of immune response which is both different to that which develops naturally and is effective. This article describes some approaches to develop vaccines for two such organisms (malaria parasites and Streptococcus pyogenes (group A Streptococcus)) that are associated with widespread mortality and morbidity, mostly in the poorest countries of the world. At this stage, the challenges are primarily scientific, but if these hurdles are surmounted then the challenges will become financial ones - developing much needed vaccines for people least able to afford them. (C) 2002 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved.

Identifying the communication activities of older people with aphasia: Evidence from naturalistic observation

Background: Increasingly there is a call from clinicians and researchers for measures that document the impact of aphasia on a person's everyday communication. Do existing assessments of communication disability adequately sample communication activities relevant to our clients? Communication skills and networks change with age. A need exists to determine the everyday communication activities of older people and in particular those with aphasia. Aims: The primary aim of this study was to describe and compare the everyday communication activities of older people with aphasia and healthy older people who are living in the community. A secondary aim was to investigate the content validity of the American Speech-Language Hearing Association Functional Assessment of Communication Skills for Adults (ASHA FACS, 1997) for older Australians. Methods & Procedures: Naturalistic observation was the method of choice for detailing the everyday communication of 15 older people with chronic aphasia following stroke and a matched group of 15 healthy older people who were living in the community. Researchers, in the role of participant observer, took field notes for 8 hours, over three occasions within a week. A total of 240 hours of observation have been coded in terms of communication activity, topic, communication partners, and place of communication. A brief 5-day diary served to check the representativeness of the observational data. After each hour of observation, the researcher checked which ASHA FACS items had been observed. Outcomes & Results: Naturalistic observation provided a rich, rigorous, and systematic methodology for detailing the dynamics and complexities of authentic communication. The most common communication activities for both groups were conversations at home and in social groups. Real-life communication was revealed to serve the dual purposes of transaction and interaction. Results indicate that older people with aphasia engage in similar communication activities to healthy older people although differences were evident in the frequency of communication and in specific activities such as story telling, writing, commenting, and acknowledging. ASHA FACS items were generally relevant to older Australians living in the community. Conclusions: This study demonstrated that communication activity is multifaceted in terms of the type of communication and contextual factors. The observational data describe the effects of aphasia on a person's everyday communication activity and reveal the impact of aphasia on the social functions of communication including sharing information, maintaining and establishing relationships, and telling one's story. Functional communication assessment requires a greater focus on the interactional and uniquely interpersonal aspects of social communication.

Initiation of biological agents in patients with ankylosing spondylitis: results of a Delphi study by the ASAS Group

Background: There is ample evidence of important symptomatic efficacy of tumour necrosis factor alpha (TNFalpha) inhibition in ankylosing spondylitis (AS). Moreover, studies suggest that anti-TNF could be considered as the first disease controlling antirheumatic treatment (DC-ART) for AS. Objective: To determine precisely which patients with AS are most likely to benefit from anti-TNFalpha treatment because of the cost and possible long term side effects of such treatment. Methods: Assessment in Ankylosing Spondylitis (ASAS) members were asked to use a Delphi technique to name the characteristics of patients with AS for whom they would start DC-ART, in three different clinical presentations (isolated axial involvement, peripheral arthritis, enthesitis). Results: Among the 62 invited ASAS members, more than 50% actively participated in the four phases of definition according to the Delphi technique. For each of the three clinical presentations, a combination of five to six domains was proposed, with an evaluation instrument and a cut off point defining a minimum level of activity for each domain. Conclusion: This study provides a profile for a patient with AS for considering initiation of biological agents that reflects the opinion of the ASAS members, using a Delphi exercise. Further studies are required to assess their relevance and their consistency with clinical practice.

The VCAM-1 gene that encodes the vascular cell adhesion molecule is a target of the Sry-related high mobility group box gene, Sox18

VCAM-1 (vascular cell adhesion molecule-1) and Sox18 are involved in vascular development. VCAM-1 is an important adhesion molecule that is expressed on endothelial cells and has a critical role in endothelial activation, inflammation, lymphatic pathophysiology, and atherogenesis. The Sry-related high mobility group box factor Sox18 has previously been implicated in endothelial pathologies. Mutations in human and mouse Sox18 leads to hypotrichosis and lymphedema. Furthermore, both Sox18 and VCAM-1 have very similar spatio-temporal patterns of expression, which is suggestive of crosstalk. We use biochemical techniques, cell culture systems, and the ragged opossum (RaOP) mouse model with a naturally occurring mutation in Sox18 to demonstrate that VCAM-1 is an important target of Sox18. Transfection, site-specific mutagenesis, and gel shift analyses demonstrated that Sox18 directly targeted and trans-activated VCAM-1 expression. Importantly, the naturally occurring Sox18 mutant attenuates the expression and activation of VCAM-1 in vitro. Furthermore, in vivo quantitation of VCAM-1 mRNA levels in wild type and RaOP mice demonstrates that RaOP animals show a dramatic and significant reduction in VCAM-1 mRNA expression in lung, skin, and skeletal muscle. Our observation that the VCAM-1 gene is an important target of SOX18 provides the first molecular insights into the vascular abnormalities in the mouse mutant ragged and the human hypotrichosis-lymphedematelangiectasia disorder.

Putting the group back into unions: A social psychological contribution to understanding union support

Industrial relations research that attempts to grapple with individuals' union-related sentiments and activities often draws on one of two traditions of psychological research—the individual-level factors tradition (for example, personality and attitude-behaviour relations) and the social context tradition (for example, frustration-aggression and relative deprivation). This paper provides an overview of research conducted from within these traditions to explain union-related phenomena and identifies some of the limitations that arise as a consequence of a shared tendency to treat people in an atomistic fashion. The paper argues for an understanding of the psychological processes that underpin group-based action. To this end, it elaborates a theoretical framework based on social identity theory and self-categorisation theory that would allow us to examine the dynamic interplay between the individual, their cognitions and their environment. The paper concludes with a brief discussion of a specific case of union mobilisation, to indicate how this theoretical framework might aid empirical analysis.

Olhares acerca do processo de construção dos Projetos Políticos Pedagógicos dos cursos Técnicos Integrados ao Ensino Médio de Jovens e Adultos no contexto do Ifes campus Vitória

Este trabalho é resultado da investigação que teve como objetivo analisar o processo de construção dos Projetos Políticos Pedagógicos dos cursos do Proeja no contexto do Ifes campus Vitória. O problema de pesquisa buscou captar os movimentos e as experiências desencadeados nesse processo. No percurso metodológico, com ênfase na pesquisa qualitativa, foi necessário entrelaçar duas abordagens: a etnografia escolar e a pesquisa-ação em função da atuação profissional da pesquisadora no lócus de estudo. Variados instrumentos foram utilizados para levantamento e a produção dos dados, dentre os quais: questionários, entrevistas, diário de campo das observações, pesquisa bibliográfica e documental. Participaram da pesquisa aproximadamente 80 pessoas, entre docentes, alunos e gestores, abordados em contextos específicos: o grupo de formação continuada, a comissão dos projetos, o encontros dos alunos, a reunião intermediária dentre outros. O referencial teórico-metodológico pautado na perspectiva do materialismo histórico dialético embasou toda a trajetória investigativa, em coerência com a base da produção das pesquisas sobre trabalho e educação e por se constituir a referência que fundamenta os princípios estruturantes do currículo integrado na perspectiva da formação humana. Por meio da metáfora dos observatórios, focamos nossas lentes sobre as questões que desafiaram a construção dos projetos políticos pedagógicos e sua coerência com os princípios epistemológicos, políticos e pedagógicos do Proeja. Nesse movimento, diversos olhares foram captados, possibilitando-nos levantar os seguintes resultados: o percurso de construção dos projetos foi marcado por contradições que perpassam todo o processo e que constituíram um debate profícuo que tenciona a gestão pedagógica, administrativa e financeira do Ifes campus Vitória. O movimento se constituiu também em um processo de construção, partilha de saberes e experiências, impulsionado pela busca da apreensão dos sentidos da integração, que contraditoriamente não alcançou seus objetivos, embora não se possa negar os resultados positivos do processo no interior da Instituição. Dessa forma, os desafios para efetivação da formação integrada no Ifes persistem. Ganha centralidade nessa discussão os sujeitos a quem o programa se volta e suas demandas de formação, bem como as condições materiais de oferta dos cursos e de forma especial as condições de envolvimento dos professores com o programa e as reflexões sobre suas práticas.

Formação, educação física e inclusão : compreendendo os processos inclusivos

No intuito de contribuir para a problematização da Educação, numa perspectiva inclusiva, esta dissertação procura conhecer e analisar a prática pedagógica inclusiva experimentada pelos professores de Educação Física na escola, por meio de suas narrativas, em uma ação de formação continuada. O projeto de extensão intitulado Formação Continuada de Professores de Educação Física para a Educação Inclusiva foi a estratégia utilizada para a criação de um grupo de estudos, denominado Grupo Operativo de Formação (GOF). A ação de formação continuada foi realizada durante o período de julho a dezembro de 2011, em um encontro presencial semanal, totalizando dezesseis encontros, com uma carga horária final de 90h. Participaram da ação de formação quatro professores da Secretaria Municipal de Educação de Vitória-ES. A pesquisa baseia-se em elementos da pesquisa-ação, utilizando como instrumentos e procedimentos para a produção dos dados a narrativa, o diário de campo, o memorial e a entrevista. Da análise dos dados produzidos identifica três categorias norteadoras das discussões: a) o trabalho coletivo como possibilidade para inclusão; b) trilhando caminhos para o desenvolvimento de práticas inclusivas: o autismo como foco do percurso; c) o olhar dos professores sobre a ação de formação experimentada no GOF. As análises realizadas revelam que essa ação de formação traz resultados que sinalizam positivamente para sua efetivação como instrumento ativo no processo de formação de professores para a educação básica, na perspectiva da inclusão. Portanto, essa é uma interessante ferramenta a ser utilizada pelas redes de ensino como alternativa metodológica em programas de formação continuada. Além disso, a proposta promove momentos para a prática reflexiva dos professores, representando uma rica oportunidade, capaz de fazer com que eles se apropriem de teorias educacionais que poderão contribuir na elaboração de suas aulas.

Hibridizando o ensino de inglês na Escola de Aprendizes- Marinheiros do Espírito Santo

Esta pesquisa teve por objetivo avaliar o desempenho em inglês como L2 de alunos submetidos a atividades em uma abordagem híbrida com o uso de ferramentas da internet na Escola de Aprendizes-Marinheiros do Espírito Santo. Quarenta alunos de duas turmas intactas foram divididos em dois grupos, o experimental (ensino tradicional + ambiente virtual) e o controle (ensino tradicional apenas). O referencial teórico revisou a literatura sobre a abordagem de ensino de línguas estrangeiras baseada em tarefas, metodologias híbridas de ensino de L2, multiletramentos e novas tecnologias. A metodologia de pesquisa usada foi mista com dados qualitativos e quantitativos. O estudo avaliou o impacto de atividades on-line na aprendizagem de L2 e no desenvolvimento da autonomia e do letramento digital. Três tarefas usando variados sítios da internet foram administradas ao grupo experimental, seguidas de um questionário para cada uma, usado para a avaliação qualitativa. A análise quantitativa foi feita por meio de pré e pós-testes analisados estatisticamente. Para esta pesquisa-ação, foram utilizados questionários, entrevistas semiestruturadas e o diário da professora-pesquisadora como instrumentos de coleta de dados. De forma geral, os resultados não mostraram ganhos estatisticamente significativos no tratamento, porém a análise qualitativa das impressões dos alunos-participantes sobre as tarefas realizadas revelou que a abordagem híbrida de ensino de L2 pode ajudar os alunos a desenvolver a autonomia, motivação, um maior contato com a língua-alvo e o letramento digital.