Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum

Background The ability of T cells, acting independently of antibodies, to control malaria parasite growth in people has not been defined. If such cell-mediated immunity was shown to be effective, an additional vaccine strategy could be pursued. Our aim was to ascertain whether or not development of cell-mediated immunity to Plasmodium falciparum blood-stage infection could be induced in human beings by exposure to malaria parasites in very low density. Methods We enrolled five volunteers from the staff at our research institute who had never had malaria. We used a cryopreserved inoculum of red cells infected with P falciparum strain 3D7 to give them repeated subclinical infections of malaria that we then cured early with drugs, to induce cell-mediated immune responses. We tested for development of immunity by measurement of parasite concentrations in the blood of volunteers by PCR of the multicopy gene STEVOR and by following up the volunteers clinically, and by measuring antibody and cellular immune responses to the parasite. Findings After challenge and a extended period without drug cure, volunteers were protected against malaria as indicated by absence of parasites or parasite DNA in the blood, and absence of clinical symptoms. Immunity was characterised by absence of detectable antibodies that bind the parasite or infected red cells, but by the presence of a proliferative T-cell response, involving CD4+ and CD8+ T cells, a cytokine response, consisting of interferon gamma but not interleukin 4 or interleukin 10, induction of high concentrations of nitric oxide synthase activity in peripheral blood mononuclear cells, and a drop in the number of peripheral natural killer T cells. Interpretation People can be protected against the erythrocytic stage of malaria by a strong cell-mediated immune response, in the absence of detectable parasite-specific antibodies, suggesting an additional strategy for development of a malaria vaccine.

Human peripheral blood V alpha 24(+) V beta 11(+) NKT cells expand following administration of alpha-galactosylceramide-pulsed dendritic cells

Background and Objectives We have undertaken the first clinical trial involving the administration of alpha-GalactosylCeramine (alpha-GalCer)-pulsed dendritic cells (DCs) to human subjects, to determine safety, optimal dose, optimal administration route and immunological effects. Materials and Methods Subjects (n = 4) with metastatic malignancy received two infusions of alpha-GalCer-pulsed DCs intravenously, and two infusions intradermally. The percentages of Valpha24 Vbeta11 NKT cells in peripheral blood (PB) were determined by three-colour flow cytometry and the PB NKT cell numbers were calculated using the total number of PB lymphocytes/ml determined by automated full-blood counts. Results No serious treatment related adverse events were observed during the study period. Administration of alpha-GalCer-pulsed DCs in vivo can significantly (P < 0.03) increase PB Valpha24(+) Vbeta11(+) NKT cell numbers above pretreatment baseline levels after the transient fall in the NKT numbers within 48 h. Conclusions Administration of alpha-GalCer-pulsed DCs is well tolerated, modulates PB Valpha24(+) Vbeta11(+) NKT cells and may have a role in the therapy of malignancies sensitive to activities of Valpha24(+) Vbeta11(+) NKT cells, or for autoimmune diseases.

Systemic administration of interleukin-1 beta activates select populations of central amygdala afferents

The central nucleus of the amygdala (CeA) is activated robustly by an immune challenge such as the systemic administration of the proinflammatory cytokine interleukin-1beta (IL-1beta). Because IL-1beta is not believed to cross the blood-brain barrier in any significant amount, it is likely that IL-1beta elicits CeA cell recruitment by means of activation of afferents to the CeA. However, although many studies have investigated the origins of afferent inputs to the CeA, we do not know which of these also respond to IL-1beta. Therefore, to identify candidate neurons responsible for the recruitment of CeA cells by an immune challenge, we iontophoretically deposited a retrograde tracer, cholera toxin b-subunit (CTb), into the CeA of rats 7 days before systemic delivery of IL-1beta (1 mug/kg, i.a.). By using combined immunohistochemistry, we then quantified the number of Fos-positive CTb cells in six major regions known to innervate the CeA. These included the medial prefrontal cortex, paraventricular thalamus (PVT), ventral tegmental area, parabrachial nucleus (PB), nucleus tractus solitarius, and ventrolateral medulla. Our results show that after deposit of CTb into the CeA, the majority of double-labeled cells were located in the PB and the PVT, suggesting that CeA cell activation by systemic IL-1beta is likely to arise predominantly from cell bodies located in these regions. These findings may have significant implications in determining the central pathways involved in generating acute central responses to a systemic immune challenge. J. Comp. Neurol. 452:288-296, 2002. (C) 2002 Wiley-Liss, Inc.

??cole Nationale d'Administration Publique: d??velopper les comp??tences des fonctionnaires pour augmenter la capacit?? de L'Etat dans la gestion des politiques publiques

Plus d???une vingtaine d???ann??es d???existence d??di??es ?? la mission de d??velopper les comp??tences des fonctionnaires pour augmenter la capacit?? de l?????tat dans la gestion des politiques publiques fait de l???ENAP un mod??le dans le domaine de la formation. Rattach??e au Minist??re du Plan, du Budget et de la Gestion, l?????cole, d??s sa cr??ation en 1986, a re??ue 245 mille fonctionnaires de tout le pays. En 2007, 26 mille fonctionnaires de l???administration f??d??rale ont attendu un de nos 60 stages offerts.

Brazilian National School of Public Administration

The Brazilian National School of Public Administration (Escola Nacional de Administra????o P??blica ??? ENAP) is a public foundation linked to the Ministry of Planning, Budget and Management. Founded in 1986, its core mission is ???to develop competencies of civil servants in order to enhance government capacity for managing public policies???. To fulfill its mission, a wide program of learning and continued education is offered to public policy managers as well as e-learning and customized courses, in accordance to governmental and institutional strategic objectives. ENAP???s courses are framed according to governmental strategic demands for social inclusion, poverty reduction as well as economic development in order to strengthen the leading South American democracy. The range and diversity of its programs mirrors the challenges of deep changes in the jobs market and the work environment, faced by the current 550,000 federal civil servants and the over 7,000,000 state and municipal civil servants in Brazil, as last counted in 2006.

As políticas da insegurança : da Scuderie Detetive Le Cocq às masmorras do novo Espírito Santo

A presente dissertação tem como objetivo a análise das políticas de segurança pública e justiça criminal no Espírito Santo entre 1989 e 2013, utilizando metodologia historiográfica e observando a distância entre os objetivos oficiais e as consequências práticas. No primeiro capítulo, me concentro na contextualização histórica das políticas criminais, analisando a formação organizacional do sistema punitivo brasileiro. Coloco ênfase, de um lado, no processo de militarização, isto é, a adoção de hierarquia, disciplina e formação militares nas agências de segurança pública, e de outro lado, e nas sucessivas legislações penais aprovadas pelo Congresso Nacional. Tais processos nacionais se refletem no Espírito Santo, onde se difundiram “grupos de extermínio” como a Scuderie Le Cocq, mas não havia política de segurança pública. A primeira surge em meio a grave crise política, entre 1999 e 2002. Mas os seus propósitos são mais avançados com o processo de reforma administrativa após 2003, quando o governo se esforça por impôr modelos de gestão empresariais e parcerias público privadas à administração estadual, incluindo a segurança pública e sistema penitenciário. Com isto, ocorre uma rápida expansão do encarceramento seletivo em condições extremas de superlotação e violência, desenvolvendo uma indústria carcerária. No segundo capítulo, realizo uma análise na qual relaciono informações criminais, penitenciárias, econômicas e demográficas, tanto no contexto do Brasil quanto do Espírito Santo. Constato que a repressão estatal tem “preferência” por homens, negros, jovens e de baixa escolaridade; por crimes de drogas e contra o patrimônio, com a utilização cada vez maior da prisão provisória. No Espírito Santo o encarceramento seletivo cresce em maior velocidade que na média nacional, o que se reflete no perfil da população carcerária, sendo esta ainda mais negra, jovem, de baixa escolaridade e presa por tráfico e drogas e em regime provisório, com frequentes denúncias fundamentadas de torturas, mortes e desaparecimentos forçados entre as populações criminalizadas.

Security issues during Lula's administration: from the reactive to the assertive approach

Brazil's security agenda during Lula's administration was not homogeneous through the two mandates: the first tenure (2002-2006) revealed a reactive approach towards security topics, while the second one (2006-2010) was more assertive. More specifically, the shift occurred in terms of both its geographical scope - once it incorporated global issues in a more systematic way -, and instruments through which the security agenda was exercised, given the multilateral initiative of Unasur's CDS

Brazilian foreign policy towards South America during the Lula administration: caught between South America and Mercosur

The aim of this article is to analyze Brazil's foreign policy towards the South American region during President Lula's administration. As such, the article intends to highlight two specific dimensions: the extent to which foreign policy during this period has differed from previous periods and the relative importance granted by Brazilian diplomacy to recent cooperation and integration efforts, more specifically the Unasur and Mercosur. The article argues that the Lula administration has behaved differently from its predecessors by prioritizing the building up of Brazilian leadership in South America on several different fronts, especially by strengthening multilateral institutions in the region

Mapping the Obama administration's response to the Arab Spring

When the Arab Spring broke out, the United States was in a quandary over how to handle the crisis in its attempt to balance its moral obligations and ideals without undercutting its strategic interests and those of its close allies. Flaws in US diplomatic approach have contributed to one of the most serious foreign policy crisis for a US administration to date with consequential upheaval and erosion of the US-built balance of power. The reactions and policy responses of the Obama administration highlight the difficulties in grasping with the new reality in the Middle East and in enunciating a policy platform that could combine American interests and values.

Foucault’s Perspective of Performance Appraisal in Public Administration

The main purpose of performance appraisal in organizations is, or should be, to improve the engagement, learning process and progress of the employees and to align individual with team and organizational performance. However, performance appraisal can also be interpreted as an instrument of normalization, discipline and surveillance. This study thus aims to explore and discuss the complex schema of intrinsic and extrinsic objectives of performance appraisal system of the Portuguese public organizations (SIADAP - Performance Evaluation Integrated System). We have developed an exploratory and qualitative case study to capture appraisers and appraises perceptions. The data were analyzed in light of foucauldian theories. According to the qualitative data, namely the discourses of the appraisers and their subordinates, the SIADAP is seen as an instrument of control and dominance that aims to introduce political rationalities, limiting the career progression of the employees. Though some key points of Foucault’s perspective were identified, foucauldian framework revealed some limitations to capture all the complexity inherent to performance appraisal. This study opens new perspectives about the SIADAP and can be of major importance as far as political reflection about performance appraisal in public organizations is concerned.

Contemporary issues in the government and administration of Latin American megacities

This paper is the first to systematically analyze and compare the structures of city governance and administration for seven major cities in Latin America, four of which are megacities (population of over 10 million), and three others are large national capitals. U.S. and U. K. models of city administration are reviewed as baseline models against which differences in Latin American may be explored. Structures of Government in Latin America show several important features and trends: 1) the lack of metropolitan (cross jurisdictional) authority; 2) the existence of strong mayors and weak councils"; 3) high levels of partisanship; 4) overlapping rather than interlocking bureaucracies; 5) pressures towards the privatization of city services, but continuing tension over the desirability of public versus private control; 6) greater fiscal responsibility and autonomy; and 7), a continuing marginalization of public participation in megacity governance.In spite of these features, many cities throughout the region (regardless of whether they are megacity size or national capitals), are actively intensifying their efforts to develop more effective, accountable and democratic governance structures.