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.

Development of a quality use of medicines coding system to rate clinical pharmacists' medication review recommendations

Objective: To develop a 'quality use of medicines' coding system for the assessment of pharmacists' medication reviews and to apply it to an appropriate cohort. Method: A 'quality use of medicines' coding system was developed based on findings in the literature. These codes were then applied to 216 (111 intervention, 105 control) veterans' medication profiles by an independent clinical pharmacist who was supported by a clinical pharmacologist with the aim to assess the appropriateness of pharmacy interventions. The profiles were provided for veterans participating in a randomised, controlled trial in private hospitals evaluating the effect of medication review and discharge counselling. The reliability of the coding was tested by two independent clinical pharmacists in a random sample of 23 veterans from the study population. Main outcome measure: Interrater reliability was assessed by applying Cohen's kappa score on aggregated codes. Results: The coding system based on the literature consisted of 19 codes. The results from the three clinical pharmacists suggested that the original coding system had two major problems: (a) a lack of discrimination for certain recommendations e. g. adverse drug reactions, toxicity and mortality may be seen as variations in degree of a single effect and (b) certain codes e. g. essential therapy were in low prevalence. The interrater reliability for an aggregation of all codes into positive, negative and clinically non-significant codes ranged from 0.49-0.58 (good to fair). The interrater reliability increased to 0.72-0.79 (excellent) when all negative codes were excluded. Analysis of the sample of 216 profiles showed that the most prevalent recommendations from the clinical pharmacists were a positive impact in reducing adverse responses (31.9%), an improvement in good clinical pharmacy practice (25.5%) and a positive impact in reducing drug toxicity (11.1%). Most medications were assigned the clinically non-significant code (96.6%). In fact, the interventions led to a statistically significant difference in pharmacist recommendations in the categories; adverse response, toxicity and good clinical pharmacy practice measured by the quality use of medicine coding system. Conclusion: It was possible to use the quality use of medicine coding system to rate the quality and potential health impact of pharmacists' medication reviews, and the system did pick up differences between intervention and control patients. The interrater reliability for the summarised coding system was fair, but a larger sample of medication regimens is needed to assess the non-summarised quality use of medicines coding system.

Geometric isomers of chloro(6-methyl-1,4,8,11-tetraazacyclotetradecane-6-amine)cobalt(III) tetrachlorozincate(II)

The crystal structures of a pair of cis and trans isomers of the macrocyclic chloropentaamine title complex, as their tetrachlorozincate(II) salts, [CoCl(C11H27N5)][ZnCl4], are reported. The two distinct isomeric forms lead to significant variations in the Co-N bond lengths and, furthermore, hydrogen bonding between the complex ions is influenced by the folded (cis) or planar (trans) conformations of the coordinated ligand.

Isomers of 1,4,8,11-tetraazacyclotetradecane-6,13-dicarboxylate characterized as cobalt(III) complexes

The major trans (1) and minor cis (2) isomers of 1,4,8,11-tetraazacyclotetradecane-6,13-dicarboxylate have been characterized as the complexes [Co(1)](ClO4) and [Co(H-2)(OH2)]Cl(ClO4).H2O. The former crystallized in the C-2/c space group and the latter in the P2(1)/c space group, with cell parameters a 16.258(7), b 9.050(3), c 15.413(6) Angstrom, beta133.29(3)degrees, and a 9.694(4), b 16.135(1), c 12.973(5) Angstrom, beta 93.00(2)degrees, respectively. Their characterization completes identification of the respective trans and cis isomers for the series of C-pendant macrocycles also including 1,4,8,11-tetraazacyclotetradecane-6-amine-13-carboxylate ((3), (4)) and 1,4,8,11-tetraazacyclotetradecane-6,13-diamine ((5), (6)). The complexes show limited distortion from octahedral geometry with the strain in the presence of the coordinated C-pendant carboxylate significantly reduced compared with that for the C-pendant amine in analogues, a consequence mainly of six-membered as opposed to five-membered chelate rings involving the pendant donor. A comparison of the physical properties for the trans isomers of the octahedral complexes of (1), (3), and (5), which reflect progressively increasing strain, is presented.

Apocalypse forever? International relations implications of 11 September

This is a contribution to ongoing discussion of the international relations issues raised by the terrorist attacks of 11 September 2001. It acknowledges apparent failings (of analysis or prediction) in the IR literature but then suggests the shortcomings are really the product of divergent traditions of analysis (behaviouralism, structuralism and evolutionism) which isolate different aspects of phenomena for attention. The paper then discusses the contrast between hard power and soft power - to help identify the distinctiveness of the new forms of terrorism (their non-linear objectives and the lack of proportionality involved). It concludes on an encouraging note by urging international cooperation as a solution, even in cases where the protagonists' resentments have tended to militate against conventional channels of dispute resolution.

Melhoria de gest??o com foco no trin??mio: pessoas, processos e tecnologia de informa????o

O trabalho iniciou-se em junho de 2005, na GMEFH1, cuja metodologia se pautava na revis??o dos processos de trabalho, levantados a partir de reuni??es semanais com um grupo representativo, na defini????o de pap??is e responsabilidades dos colaboradores da ??rea, no desenvolvimento de um sistema de informa????o que possibilitasse a consolida????o dos procedimentos e uniformiza????o de condutas e, por fim, no treinamento de uma pr??tica gestora, com estabelecimento de metas, registro e revis??o de procedimentos, bem como o monitoramento de prazos e resultados. O cen??rio anterior apresentava grande descontrole do fluxo do processo de trabalho, aus??ncia de padr??o nos procedimentos, n??mero desconhecido das peti????es sem an??lise (passivo), infraestrutura impr??pria, subjetividade na an??lise t??cnica, inexist??ncia de planejamento estrat??gico, entre outros. Ap??s a realiza????o do trabalho, foram observados os seguintes resultados: acr??scimo significativo da produtividade, apesar da redu????o do quadro-geral de pessoas (de 38 para 30) e do n??mero de t??cnicos (de 34 para 23) desempenhando a atividade-fim (an??lise 100 t??cnica para concess??o de registro de medicamentos); tratamento do passivo com redu????o de 89% das peti????es que iriam para a an??lise; grande diminui????o do tempo de resposta ao setor regulado; e padroniza????o nos procedimentos de an??lise t??cnica, trazendo uniformidade na conduta t??cnica, tema recorrentemente requisitado pelo setor regulado

A????es premiadas no 11?? Concurso Inova????o na Gest??o P??blica Federal 2006

Nesta publica????o, referente ao 11?? Concurso Inova????o na Gest??o P??blica Federal, o leitor encontrar?? iniciativas inovadoras nas seguintes ??reas: Arranjos institucionais para coordena????o e implementa????o de pol??ticas p??blicas (intra e inter-governamental); atendimento ao usu??rio; avalia????o e monitoramento de pol??ticas p??blicas; cidadania e inclus??o social; controle de resultados; estabelecimento de padr??es e atendimento de servi??os; implementa????o de melhoria cont??nua; planejamento e gest??o estrat??gica

Texto para discuss??o 11: governabilidade, governan??a e capacidade governativa: algumas notas

Prop??e para fins anal??ticos, o conceito capacidade governativa, definido de maneira ampla, de forma a englobar tanto os aspectos operacionais do aparelho do Estado ??? a?? inclu??dos os requisitos organizacionais e gerenciais ??? como suas dimens??es econ??mica e pol??tica. Indica, ainda, a ambi??ncia mais ou menos democr??tica do sistema pol??tico. Esse conceito operacional permite, assim, a an??lise da efici??ncia e efic??cia do Estado em ajustar a economia, redefinir seu tamanho e suas fun????es, resgatar a d??vida social e manter-se em ambiente democr??tico, desafios impostos e assumidos por todos os governantes do Brasil p??s-constituinte.

Reforma do Estado no setor de sa??de: os casos da Catalunha, Canad??, Reino Unido e Estados Unidos

Colet??nea de textos que abordam diversas experi??ncias que t??m sido implementadas na reforma dos sistemas de sa??de ao redor do mundo, e que representam a ado????o progressiva de novas formas de gest??o empresarial no sistema sanit??rio, acarretando uma s??rie de empreendimentos inovadores. A busca da efici??ncia atrelada a uma maior eq??idade em sa??de, bem como concep????es diferenciadas do papel do Estado na ??rea social, ilustram cada um dos casos apresentados.

Resolu????o simplificadora de formalidades e procedimentos relativos aos atos de que trata o art. 54 da Lei n?? 8.884 de 11 de junho 1994

O controle de ag??ncias de defesa da concorr??ncia sobre a estrutura dos mercados constitui pr??tica comum em pa??ses maduros e vem ganhando import??ncia crescente em economias emergentes. Tal atividade envolve exame de atos de concentra????o econ??mica tais como fus??es, aquisi????es, joint ventures ou incorpora????es. No Brasil este tipo de controle ?? recente, tendo sido institu??do pela Lei n?? 8.884, de junho de 1994. Desde ent??o, o Conselho Administrativo de Defesa da Concorr??ncia - CADE julgou 29 (vinte e nove) atos de concentra????o, em contraste com a experi??ncia secular de pa??ses como EUA, Canad?? e Austr??lia e de v??rias d??cadas nas na????es europ??ias depois da Segunda Guerra. A exemplo de v??rias outras ??reas de pol??tica p??blica, tornou-se imperativo agilizar os ??rg??os de defesa da concorr??ncia. Isto decorre, entre outros fatores, do intenso processo de reestrutura????o produtiva em curso no pa??s associados ?? desestatiza????o e abertura da economia. Diante das circunst??ncias descritas, ?? preciso assegurar agilidade, transpar??ncia, excel??ncia t??cnica no processo decis??rio e estabilidade de regras, todos ingredientes indispens??veis para gerar seguran??a jur??dica. Esta ??ltima, por seu turno, diminui o risco do investimento, estimulando invers??es, produ????o e emprego. Nesse sentido, o CADE promoveu mudan??as importantes no procedimento de an??lise de atos de concentra????o em colabora????o com a Secretaria de Direito Econ??mico do Minist??rio da Justi??a (SDE) e a Secretaria de Acompanhamento Econ??mico do Minist??rio da Fazenda (SEAE) mediante a edi????o da Resolu????o 5, de 28 de agosto de 1996

M??dulo 11 - os autos do processo de licita????o: curso legisla????o aplicada ?? log??stica de suprimentos lei n?? 8.666/93, preg??o e registro de pre??os

Este documento trata de: aspectos conceituais da lei: finalidade, import??ncia e hierarquia da lei.; no????es gerais da lei de licita????es - Lei n?? 8.666/93; tipos de licita????o:menor pre??o, melhor t??cnica, t??cnica e pre??o e maior lance ou oferta; modalidades de licita????o: concorr??ncia, tomada de pre??os, convite, concurso e leil??o; exce????es ?? obrigatoriedade de licita????o: dispensa e inexigibilidade; regime de execu????o indireta; comiss??o de licita????o; etapas do processo licitat??rio: edital, procedimentos/documentos do certame, registro cadastral, habilita????o dos interessados, julgamento e encerramento; preg??o; registro de pre??os