Blood pressure loci identified with a gene-centric array.

Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56 × 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56 × 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.

Polyphasic characterisation of Burkholderia cepaciacomplex species isolated from children with cystic fibrosis

Cystic fibrosis (CF) patients with Burkholderia cepacia complex (Bcc) pulmonary infections have high morbidity and mortality. The aim of this study was to compare different methods for identification of Bcc species isolated from paediatric CF patients. Oropharyngeal swabs from children with CF were used to obtain isolates of Bcc samples to evaluate six different tests for strain identification. Conventional (CPT) and automatised (APT) phenotypic tests, polymerase chain reaction (PCR)-recA, restriction fragment length polymorphism-recA, recAsequencing, and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) were applied. Bacterial isolates were also tested for antimicrobial susceptibility. PCR-recA analysis showed that 36 out of the 54 isolates were Bcc. Kappa index data indicated almost perfect agreement between CPT and APT, CPT and PCR-recA, and APT and PCR-recA to identify Bcc, and MALDI-TOF and recAsequencing to identify Bcc species. The recAsequencing data and the MALDI-TOF data agreed in 97.2% of the isolates. Based on recA sequencing, the most common species identified were Burkholderia cenocepacia IIIA (33.4%),Burkholderia vietnamiensis (30.6%), B. cenocepaciaIIIB (27.8%), Burkholderia multivorans (5.5%), and B. cepacia (2.7%). MALDI-TOF proved to be a useful tool for identification of Bcc species obtained from CF patients, although it was not able to identify B. cenocepacia subtypes.

Primary dengue virus infections induce differential cytokine production in Mexican patients

Severe dengue pathogenesis is not fully understood, but high levels of proinflammatory cytokines have been associated with dengue disease severity. In this study, the cytokine levels in 171 sera from Mexican patients with primary dengue fever (DF) and dengue haemorrhagic fever (DHF) from dengue virus (DENV) 1 (n = 116) or 2 (n = 55) were compared. DF and DHF were defined according to the patient’s clinical condition, the primary infections as indicated by IgG enzymatic immunoassay negative results, and the infecting serotype as assessed by real-time reverse transcription-polymerase chain reaction. Samples were analysed for circulating levels of interleukin (IL)-12p70, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, IL-6, and IL-8 using a commercial cytometric bead array. Significantly higher IFN-γ levels were found in patients with DHF than those with DF. However, significantly higher IL-12p70, TNF-α, and IL-6 levels were associated with DHF only in patients who were infected with DENV2 but not with DENV1. Moreover, patients with DF who were infected with DENV1 showed higher levels of IL-12p70, TNF-α, and IL-6 than patients with DHF early after-fever onset. The IL-8 levels were similar in all cases regardless of the clinical condition or infection serotype. These results suggest that the association between high proinflammatory cytokine levels and dengue disease severity does not always stand, and it once again highlights the complex nature of DHF pathogenesis.

Genetic interplay between HLA-C and MIR148A in HIV control and Crohn disease.

Variation in the 3' untranslated region (3'UTR) of the HLA-C locus determines binding of the microRNA Hsa-miR-148a, resulting in lower cell surface expression of alleles that bind miR-148a relative to those alleles that escape its binding. The HLA-C 3'UTR variant was shown to associate with HIV control, but like the vast majority of disease associations in a region dense with causal candidates, a direct effect of HLA-C expression level on HIV control was not proven. We demonstrate that a MIR148A insertion/deletion polymorphism associates with its own expression levels, affecting the extent to which HLA-C is down-regulated, the level of HIV control, and the risk of Crohn disease only among those carrying an intact miR-148a binding site in the HLA-C 3'UTR. These data illustrate a direct effect of HLA-C expression level on HIV control that cannot be attributed to other HLA loci in linkage disequilibrium with HLA-C and highlight the rich complexity of genetic interactions in human disease.

Ciclo de vida organizacional pautado no modelo de Lester, Parnell e Carraher (2003) e na lógica fuzzy: classificação de empresas de um segmento industrial de Santa Catarina

Neste estudo, objetiva-se identificar os estágios do ciclo de vida organizacional pautados no modelo de Lester, Parnell e Carraher (2003) das empresas do segmento industrial de máquinas, aparelhos e materiais elétricos do estado de Santa Catarina. Pesquisa descritiva, com abordagem quantitativa, foi realizada por meio de levantamento com aplicação de questionário aos gestores das empresas. A população constituiu-se das 264 empresas desse segmento econômico, listadas na Secretaria da Fazenda do Estado de Santa Catarina, e a amostra não aleatória das 40 empresas que responderam a pesquisa. As variáveis de identificação dos estágios de ciclo de vida utilizadas no questionário foram extraídas de Lester, Parnell e Carraher (2003). Os dados da pesquisa foram submetidos à técnica estatística denominada lógica fuzzy. Os resultados da pesquisa demonstraram que 57,5% das empresas foram classificadas no estágio do nascimento, 15% do, 7,5% da Maturidade, 10% do rejuvenescimento e 10% do declínio. Concluiu-se que determinados estágios do ciclo de vida organizacional estão próximos uns dos outros e que não se pode perceber claramente uma progressão determinista nas fases do ciclo de vida, como uma sequência única, definitiva e irreversível, no sentido tradicional biológico.

Lethal skeletal dysplasia in mice and humans lacking the golgin GMAP-210.

BACKGROUND: Establishing the genetic basis of phenotypes such as skeletal dysplasia in model organisms can provide insights into biologic processes and their role in human disease. METHODS: We screened mutagenized mice and observed a neonatal lethal skeletal dysplasia with an autosomal recessive pattern of inheritance. Through genetic mapping and positional cloning, we identified the causative mutation. RESULTS: Affected mice had a nonsense mutation in the thyroid hormone receptor interactor 11 gene (Trip11), which encodes the Golgi microtubule-associated protein 210 (GMAP-210); the affected mice lacked this protein. Golgi architecture was disturbed in multiple tissues, including cartilage. Skeletal development was severely impaired, with chondrocytes showing swelling and stress in the endoplasmic reticulum, abnormal cellular differentiation, and increased cell death. Golgi-mediated glycosylation events were altered in fibroblasts and chondrocytes lacking GMAP-210, and these chondrocytes had intracellular accumulation of perlecan, an extracellular matrix protein, but not of type II collagen or aggrecan, two other extracellular matrix proteins. The similarities between the skeletal and cellular phenotypes in these mice and those in patients with achondrogenesis type 1A, a neonatal lethal form of skeletal dysplasia in humans, suggested that achondrogenesis type 1A may be caused by GMAP-210 deficiency. Sequence analysis revealed loss-of-function mutations in the 10 unrelated patients with achondrogenesis type 1A whom we studied. CONCLUSIONS: GMAP-210 is required for the efficient glycosylation and cellular transport of multiple proteins. The identification of a mutation affecting GMAP-210 in mice, and then in humans, as the cause of a lethal skeletal dysplasia underscores the value of screening for abnormal phenotypes in model organisms and identifying the causative mutations.

Defining the critical hurdles in cancer immunotherapy.

Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer.

Risco de lesões em motociclistas nas ocorrências de trânsito

Este estudo teve como objetivo identificar entre os motociclistas envolvidos em ocorrências de trânsito fatores associados ao risco de lesões. No ano de 2004, foram identificados, em Maringá-PR, um total de 2.362 motociclistas envolvidos em ocorrências de trânsito com registro nos boletins da Polícia Militar. Para identificar os fatores associados à presença de lesão, foi utilizada a análise multivariada. Uma probabilidade, significantemente mais elevada de motociclistas se ferirem, foi observada entre aqueles envolvidos em colisão (Odds Ratio = 11,19) e quedas (Odds Ratio = 3,81); para o sexo feminino, a razão de chance estimada foi em torno de 4, e aqueles que estiveram envolvidos em ocorrências com até dois veículos, mostraram 2,63 vezes mais chances de apresentar lesões que os demais. Mulheres, envolvidas em ocorrências com motocicleta do tipo quedas e colisões com até dois veículos destacaram-se como grupo de risco para apresentar lesões.

Fatores associados ao óbito de motociclistas nas ocorrências de trânsito

Para identificar fatores associados ao óbito em motociclistas envolvidos em ocorrências de trânsito, em Maringá-PR, foi realizado estudo retrospectivo incluindo os motociclistas envolvidos em acidentes no ano de 2004. As fontes de dados foram os registros da Polícia Militar, do SIATE e do Instituto Médico Legal. Foram realizadas análises bivariadas e regressão logística binária. Identificaram-se 2.362 motociclistas nos Boletins de Ocorrência e, destes, 1.743 tinham registros nos Relatórios de Atendimento do Socorrista. As vítimas fatais diferiram das demais quanto à faixa etária, ao local de residência, ao tempo de habilitação e as suas condições fisiológicas na cena da ocorrência. No modelo final permaneceram as seguintes variáveis: Escala de Coma de Glasgow (ECGl), Revised Trauma Score (RTS), pulso e saturação de O2 no sangue. As condições fisiológicas das vítimas na cena do acidente se destacaram no modelo final e a ECGl superou o RTS na associação com óbito.

Premissas historicas do surgimento e desenvolvimento dos mass-media nos paises lusofonos

A nossa investigacao esta dedicada a paises que falam essencialmente a lingua portuguesa, nao sera de admirar que a maioria dos livros por nos usados sejam de autores e ediccao portuguesa. No decorrer deste trabalho recorremos a livros e trabalhos academicos de autores como: Carvalho, Arons de: A Censura À Imprensa Na Época Marcelista; Minerva,Coimbra, 1999; Evora, Silvino Lopes: As fontes jornalísticas na televisão caboverdiana, ediccoes FCC, Universidade do Minho,2004; Fontcuberta: Mar de, A Notícia – Pistas para compreender o mundo; Editorial Notícias “Tradução de Fernando Cascais”,Lisboa, 1999; Mata, Maria José: A Autocrítica no Jornalismo – O ombudsman na imprensa nacional e estrangeira; Minerva Editora,Coimbra, 2002; Pigeat, Henri: Médias et Déontologie – Règles du jeu ou jeu sans règles; Presses Universitaires Francaises, Paris, 1997; Sodré, Nelson Werneck. História da imprensa no Brasil. 2ª ed., Rio de Janeiro: Graal, 1977; Sousa, Jorge Pedro: As Notícias e os seus Efeitos; Minerva Editora,Coimbra, 2000; Veiga Manuel: Cabo Verde insularidade e Literatura, editions Karthala, Paris, 1998; Bem como, um conjunto de leis e projectos de lei ligados a comunicacao social, e algumas entrevistas. Estrutura do trabalho: Esta tese e constituida de: introducao, tres capitulos, conclusao, bibliografia e alguns anexos num total de . Na introducao explica-se a escolha do tema, a sua actualidade, o objecto de investigacao e claro a sua inovacao. No primeiro capitulo estudamos o context do aparecimento dos media nos paises lusofonos nos exemplos de Cabo Verde, Brasil, e Portugal. No Segundo cappitulo, analizamos as leis, os processos de controlo e financiamento dos mass-media e a regulacao dos conteudos dos programas de radio e televisao. No terceiro capitulo, a situacao actual dos meios de comunicacao social e do Jornalismo na CPLP, nele esta tambem exposta a parte practica do trabalho ou seja a analize da relacao do publico com os media e o nivel de confianca do publico na informacao por eles veiculada.

As forças armadas num Estado em “Interrogação”

Analisar as constantes sobressaltos político-militar na Guiné-Bissau, cujo desfecho se mantem numa incognita é o que se pretende escurtinar neste trabalho. Um País onde as forças armadas, funciona como o centro do poder, invertendo e comprometendo o funcionamento normal das instituições da República. Uma interpretação e analise também do processo democratico, sob a sombra permanente dos militares e o olhar da comunidade internacional merecerá substancialmente uma atenção especial, num momento em que a Guiné-Bissau caminha para uma indefinição preocupante. Procurará também abordar a questão étnica que caracteriza o país e especialmente as forças armadas...

Functional independence measure in patients with intermittent claudication

AbstractOBJECTIVEOf this study were to evaluate the functional independence of patients with intermittent claudication and to verify its association with sociodemographic and clinical variables, walking ability and physical activity level.METHODThis was a descriptive, exploratory, cross-sectional study with a quantitative approach. Fifty participants (66.4 years; 68% male) were recruited from Claudication Unit of a tertiary hospital. Functional Independence Measure were used to evaluate functional incapacity; the Baltimore Activity Scale, to estimate the physical activity level and the Walking Impairement Questionnaire, the walking ability.RESULTSParticipants had complete functional independence (124.8 + 2.0), low levels of physical activity (4.2 + 2.0), and impairment of walking ability; the worst performance was found in walking velocity domain (21.2 + 16.4). The functional independence score was associated with physical activity (r=0,402) and walking ability scores (distance, r=0,485; speed, r=0,463; stairs, r=0,337).CONCLUSIONIn conclusion, the level of functionality is associated with functional capacity in these patients.

LSTA Five Year Plan 2003-2007, 2007

The Iowa Commission of Libraries, the State Library’s governing board, convened the Library Services Task Force in August 2000. This group consisted of 46 Iowans from across the state, including librarians from all types of libraries, library trustees, legislators, members of Iowa Regional Library system (now called Library Service Areas) and Area Education Agencies, and citizens. Their mission was to make recommendations to the Commission on positioning libraries to effectively and efficiently meet the future needs of Iowans. Needs and expectations of Iowa Library customers and funding authorities were identified and examined by the Task Force, and are reflected in its recommendations. The Commission received the Task Force recommendations in December 2000, carefully studied them, solicited input from the Iowa library community, and with a few changes, forwarded the recommendations to the Governor and the Iowa General Assembly. These recommendations are now known as Iowa Commission of Libraries priorities and serve as a blueprint for future development of the Iowa library system. A second need assessment was conducted in 2001 as part of the process to formulate the joint Library Service Area – State Library Plan of Service 2003-2005. Biennial development of this plan is mandated by the Code of Iowa. In 2001, Library Service Area and Library Development staff from the State Library chose to completely revamp this plan, and used the process outlined in the The New Planning for Results by Sandra Nelson (the Public Library Association planning model) to do so. The group conducted a strengths/weaknesses/opportunities/threat analysis of the Iowa library situation, identified needs and put them in priority order, and identified service responses. Needs identified by the Library Services Task Force were similar to those identified by the Library Service Area and Library Development staff group. These needs were further analyzed and documented by State Library staff during the development of the LSTA plan. Sources consulted are identified in the text of the LSTA plan and/or listed at the close of this document. The text of the Library Services Task Force report and the documents created during the development of the Plan of Service 2003-2005 are cited in the appendix to this document.