Interaction between Tobacco and Alcohol Use and the Risk of Head and Neck Cancer: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium

Background: The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck cancers is not clear because studies have used various methods to quantify the excess head and neck cancer burden. Methods: We analyzed individual-level pooled data from 17 European and American case-control studies (11,221 cases and 16,168 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We estimated the multiplicative interaction parameter (psi) and population attributable risks (PAR). Results: A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer risk (psi = 2.15; 95% confidence interval, 1.53-3.04). The PAR for tobacco or alcohol was 72% (95% confidence interval, 61-79%) for head and neck cancer, of which 4% was due to alcohol alone, 33% was due to tobacco alone, and 35% was due to tobacco and alcohol combined. The total PAR differed by subsite (64% for oral cavity cancer, 72% for pharyngeal cancer, 89% for laryngeal cancer), by sex (74% for men, 57% for women), by age (33% for cases < 45 years, 73% for cases > 60 years), and by region (84% in Europe, 51% in North America, 83% in Latin America). Conclusions: Our results confirm that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk. However, a substantial proportion of head and neck cancers cannot be attributed to tobacco or alcohol use, particularly for oral cavity cancer and for head and neck cancer among women and among young-onset cases. (Cancer Epidemiol Biomarkers Prev 2009;18(2):541-50)

Type of Alcoholic Beverage and Risk of Head and Neck Cancer-025EFA Pooled Analysis Within the INHANCE Consortium

The authors pooled data from 15 case-control studies of head and neck cancer (9,107 cases, 14,219 controls) to investigate the independent associations with consumption of beer, wine, and liquor. In particular, they calculated associations with different measures of beverage consumption separately for subjects who drank beer only (858 cases, 986 controls), for liquor-only drinkers (499 cases, 527 controls), and for wine-only drinkers (1,021 cases, 2,460 controls), with alcohol never drinkers (1,124 cases, 3,487 controls) used as a common reference group. The authors observed similar associations with ethanol-standardized consumption frequency for beer-only drinkers (odds ratios (ORs) = 1.6, 1.9, 2.2, and 5.4 for <= 5, 6-15, 16-30, and > 30 drinks per week, respectively; P(trend) < 0.0001) and liquor-only drinkers (ORs = 1.6, 1.5, 2.3, and 3.6; P < 0.0001). Among wine-only drinkers, the odds ratios for moderate levels of consumption frequency approached the null, whereas those for higher consumption levels were comparable to those of drinkers of other beverage types (ORs = 1.1, 1.2, 1.9, and 6.3; P < 0.0001). Study findings suggest that the relative risks of head and neck cancer for beer and liquor are comparable. The authors observed weaker associations with moderate wine consumption, although they cannot rule out confounding from diet and other lifestyle factors as an explanation for this finding. Given the presence of heterogeneity in study-specific results, their findings should be interpreted with caution.

Early onset of primary hypogonadism revealed by serum anti-Mullerian hormone determination during infancy and childhood in trisomy 21

Male patients with an extra sex chromosome or autosome are expected to present primary hypogonadism at puberty owing to meiotic germ-cell failure. Scarce information is available on trisomy 21, a frequent autosomal aneuploidy. Our objective was to assess whether trisomy 21 presents with pubertal-onset, germ-cell specific, primary hypogonadism in males, or whether the hypogonadism is established earlier and affects other testicular cell populations. We assessed the functional status of the pituitary-testicular axis, especially Sertoli cell function, in 117 boys with trisomy 21 (ages: 2 months-20 year). To compare with an adequate control population, we established reference levels for serum anti-Mullerian hormone (AMH) in 421 normal males, from birth to adulthood, using a recently developed ultrasensitive assay. In trisomy 21, AMH was lower than normal, indicating Sertoli cell dysfunction, from early infancy, independently of the existence of cryptorchidism. The overall prevalence rate of AMH below the 3rd percentile was 64.3% in infants with trisomy 21. Follicle-stimulating hormone was elevated in patients <6 months and after pubertal onset. Testosterone was within the normal range, but luteinizing hormone was elevated in most patients <6 months and after pubertal onset, indicating a mild Leydig cell dysfunction. We conclude that in trisomy 21, primary hypogonadism involves a combined dysfunction of Sertoli and Leydig cells, which can be observed independently of cryptorchidism soon after birth, thus prompting the search for new hypotheses to explain the pathophysiology of gonadal dysfunction in autosomal trisomy.

Genomic deletions at 1p and 14q are associated with an abnormal cDNA microarray gene expression pattern in meningiomas but not in schwannomas

The molecular pathology of meningiomas and shwannomas involve the inactivation of the NF2 gene to generate grade I tumors. Genomic losses at 1p and 14q are observed in both neoplasms, although more frequently in meningiomas. The inactivation of unidentified genes located in these regions appears associated with tumor progression in meningiomas, but no clues to its molecular/clinical meaning are available in schwannomas. Recent microarray gene expression studies have demonstrated the existence of molecular subgroups in both entities. In the present study, we correlated the presence of genomic deletions at 1p, 14q, and 22q with the expression patterns of 96 tumor-related genes obtained by cDNA low-density microarrays in a series of 65 tumors including 42 meningiomas and 23 schwannomas. Two expression pattern groups were identified by cDNA mycroarray analysis when compared to the expression pattern in normal control RNA in both meningiomas and schwannomas, each one with patterns similar and different from the normal control. Meningioma and schwannoma subgroups differed in the expression of 38 and 16 genes, respectively. Using MLPA and microsatellites, we identified genomic losses at 1p, 14q, and 22q at nonrandom frequencies (12.5-69%) in meningiomas and schwannomas. Losses at 22q were almost equally frequent in both molecular expression subgroups in both neoplasms. However, deletions at 1p and 14q accumulated in meningiomas with a gene expression pattern different from the normal pattern, whereas the inverse situation occurred in schwannomas. Those anomalies characterized the schwannomas with expression pattern similar to the normal control. These findings suggest that deletions at 1p and 14q enhance the development of an abnormal tumor-related gene expression pattern in meningiomas, but this fact is not corroborated in schwannomas. (C) 2010 Elsevier Inc. All rights reserved.

Allelic status of 1p and 19q in oligodendrogliomas and glioblastomas: multiplex ligation-dependent probe amplification versus loss of heterozygosity

Identification of the 1p/19q allelic status in gliomas, primarily those with a major oligodendroglial component, has become an excellent molecular complement to tumor histology in order to identify those cases sensitive to chemotherapy. In addition to loss of heterozygosity (LOH), fluorescence in situ hybridization (FISH), or comparative genomic hybridization (CGH), multiplex ligation-dependent probe amplification (MLPA) has been shown to be an alternative methodology to identify deletions of those chromosome arms. We used MLPA to explore the 1p and 19q glioblastomas, and a series of 76 gliomas: 41 tumors with a major oligodendroglial component, 34 glioblastomas, and one low-grade astrocytoma. We compared the MLPA findings of the oligodendroglial cases with those previously obtained using LOH in the same samples. Thirty-eight of 41 oligodendrogliomas displayed identical findings by both LOH and MLPA, and losses at either 1p and/or 19q were identified in 12 of 35 (34%) astrocytic tumors. These findings agree with data previously reported comparing MLPA versus FISH or CGH in gliomas and suggest that MLPA can be used in the identification 1p/19q allelic deletions on these brain neoplams. (c) 2009 Elsevier Inc. All rights reserved. reserved.

Meningiomas and schwannomas: Molecular subgroup classification found by expression arrays

Microarray gene expression profiling is a high-throughput system used to identify differentially expressed genes and regulation patterns, and to discover new tumor markers. As the molecular pathogenesis of meningiomas and schwannomas, characterized by NF2 gene alterations, remains unclear and suitable molecular targets need to be identified, we used low density cDNA microarrays to establish expression patterns of 96 cancer-related genes on 23 schwannomas, 42 meningiomas and 3 normal cerebral meninges. We also performed a mutational analysis of the NF2 gene (PCR, dHPLC, Sequencing and MLPA), a search for 22q LOH and an analysis of gene silencing by promoter hypermethylation (MS-MLPA). Results showed a high frequency of NF2 gene mutations (40%), increased 22q LOH as aggressiveness increased, frequent losses and gains by MLPA in benign meningiomas, and gene expression silencing by hypermethylation. Array analysis showed decreased expression of 7 genes in meningiomas. Unsupervised analyses identified 2 molecular subgroups for both meningiomas and schwannomas showing 38 and 20 differentially expressed genes, respectively, and 19 genes differentially expressed between the two tumor types. These findings provide a molecular subgroup classification for meningiomas and schwannomas with possible implications for clinical practice.

Cytochrome P450(cin) (CYP176A), isolation, expression, and characterization

Cytochromes P450 are members of a superfamily of hemoproteins involved in the oxidative metabolism of various physiologic and xenobiotic compounds in eukaryotes and prokaryotes. Studies on bacterial P450s, particularly those involved in monoterpene oxidation, have provided an integral contribution to our understanding of these proteins, away from the problems encountered with eukaryotic forms. We report here a novel cytochrome P450 (P450(cin), CYP176A1) purified from a strain of Citrobacter braakii that is capable of using cineole 1 as its sole source of carbon and energy. This enzyme has been purified to homogeneity and the amino acid sequences of three tryptic peptides determined. By using this information, a PCR-based cloning strategy was developed that allowed the isolation of a 4-kb DNA fragment containing the cytochrome P450(cin) gene (cinA). Sequencing revealed three open reading frames that were identified on the basis of sequence homology as a cytochrome P450, an NADPH-dependent flavodoxin/ferrodoxin reductase, and a flavodoxin. This arrangement suggests that P450(cin) may be the first isolated P450 to use a flavodoxin as its natural redox partner. Sequencing also identified the unprecedented substitution of a highly conserved, catalytically, important active site threonine with an asparagine residue. The P450 gene was subcloned and heterologously expressed in Escherichia coli at similar to2000 nmol/liter of original culture, and purification was achieved by standard protocols. Postulating the native E. coli flavodoxin/flavodoxin reductase system might mimic the natural redox partners of P450,in, it was expressed in E. coli in the presence of cineole 1. A product was formed in vivo that was tentatively identified by gas chromatography-mass spectrometry as 2-hydroxycineole 2. Examination of P450(cin) by UV-visible spectroscopy revealed typical spectra characteristic of P450s, a high affinity for cineole 1 (K-D = 0.7 mum), and a large spin state change of the heme iron associated with binding of cineole 1. These facts support the hypothesis that cineole 1 is the natural substrate for this enzyme and that P450(cin) catalyzes the initial monooxygenation of cineole 1 biodegradation. This constitutes the first characterization of an enzyme involved in this pathway.

Role of complement C5 and T lymphocytes in pathogenesis of disseminated and mucosal candidiasis in susceptible DBA/2 mice

The aims of the study were to compare the pathogenesis of Candida albicans infection in various organs and anatomical regions of C5-deficient (DBA/2) and C5-sufficient (BALB/c) mice, and to evaluate the importance of complement C5 and T lymphocytes as factors that determine host susceptibility or resistance. The kidneys of DBA/2 mice showed higher colonisation and more severe tissue damage than those of BALB/c, but infection at other sites, including oral and vaginal mucosa, was generally similar in the two strains. Passive transfer of C5-sufficient serum into DBA/2 mice decreased the fungal burden in the kidney, and prolonged survival of the reconstituted animals. Depletion of CD4(+) and/or CD8(+) cells did not exacerbate either systemic or mucosal infection when compared to controls, and passive transfer of splenocytes from infected donors caused only a small and transient reduction in numbers of yeasts recovered from the kidney of sub-lethally infected recipients. It is concluded that the acute susceptibility of the kidneys in this mouse strain is due to C5 deficiency expressed on a susceptible genetic background. T lymphocytes, however, appear to have minimal influence on recovery from systemic infection with this isolate of C. albicans. (C) 2003 Elsevier Science Ltd. All rights reserved.

Resenha de estudos sobre o executivo

Este artigo ?? uma resenha da literatura sobre o Executivo que discute o impacto dos sistemas parlamentarista e presidencialista na capacidade governamental de formular e implementar pol??ticas p??blicas. Ao longo do texto, busca-se identificar fatores que permitem ou bloqueiam o exerc??cio de uma fun????o coordenadora e unificadora de a????es, analisando a rela????o entre os poderes Executivo e Legislativo, a estrutura do poder Executivo e as rela????es entre o Executivo pol??tico e a burocracia. Os estudos sobre parlamentarismo enfocam: import??ncia dos partidos, papel dos ministros, extens??o do poder do primeiro ministro e papel coletivo do gabinete. J?? os trabalhos sobre presidencialismo v??o de pesquisas sobre o Congresso norte-americano, envolvendo infer??ncias estat??sticas e an??lises baseadas na teoria institucional a estudos de caso sobre a American Politics (presid??ncia e lideran??a). Apesar das diferen??as entre parlamentarismo e presidencialismo, a literatura indica que mecanismos institucionais de controle de agenda produzem os mesmos efeitos nos dois sistemas.

Educa????o a dist??ncia: o estado da arte e o futuro necess??rio

Este artigo analisa alguns desafios que cercam a ado????o da Educa????o a Dist??ncia por institui????es de ensino, unidades de forma????o e qualifica????o profissional e de educa????o corporativa. Al??m disto, ?? sugerida uma agenda de pesquisa sobre EAD. O artigo trata do papel da EAD na educa????o continuada de adultos e na amplia????o do acesso ?? aprendizagem, em fun????o da possibilidade de intera????es ass??ncronas, mediadas por tecnologias da informa????o e comunica????o. Uma an??lise da situa????o EAD no Brasil mostra um grande crescimento da modalidade. Observa-se que ainda s??o raras as pesquisas sobre EAD no servi??o p??blico. H?? informa????es sugerindo que, em ??rg??os p??blicos com pr??ticas institucionalizadas de EAD, a modalidade representa uma valiosa e eficaz estrat??gia de inclus??o de pessoas em atividades de ensino-aprendizagem. S??o analisados alguns importantes desafios ligados ?? implementa????o e ao desenho de cursos a dist??ncia, e, al??m disto, ?? apresentada uma agenda de pesquisas para a ??rea.

Burocracia profissional e a livre nomea????o para cargos de confian??a no Brasil e nos EUA

A problem??tica do emprego de cargos de livre nomea????o e exonera????o para assegurar o comando pol??tico e administrativo na m??quina p??blica tem sido objeto, tanto no Brasil quanto nos EUA, de diversos questionamentos. Este artigo debate a situa????o em ambos os pa??ses, com base em alguns dados esclarecedores obtidos pela compara????o entre as estruturas de cargos comissionados e suas quantidades e formas de provimento existentes, no n??vel do governo federal, relativos ?? quantidade, tipos e emprego dos cargos em comiss??o, destacando-se a diferencia????o no que se refere ao uso desses cargos, assim como promove, a partir da literatura da ??rea, um exame da influ??ncia da utiliza????o dos cargos de livre provimento sob o aspecto do conflito entre compet??ncia ???neutra??? e ???compet??ncia responsiva???. A partir dos avan??os alcan??ados desde 1998 no Brasil, conclui-se pela necessidade do aprofundamento da profissionaliza????o das estruturas de comissionamento, tendo em vista a possibilidade de que uma estrutura menos vulner??vel ??s injun????es da pol??tica clientelista possa melhor atender aos princ??pios da efici??ncia e da transpar??ncia.

Evas??o em cursos de educa????o continuada a dist??ncia: um estudo na Escola Nacional de Administra????o P??blica

A an??lise da literatura brasileira sobre educa????o a dist??ncia ?? ainda limitada no que diz respeito a estudos que investiguem o fen??meno da evas??o, em especial, em contextos de escolas de governo. Este artigo procura identificar e analisar os fatores que contribuem para a evas??o de participantes nos cursos de educa????o continuada a dist??ncia em uma organiza????o governamental respons??vel pela capacita????o dos servidores da administra????o p??blica federal. A ??nfase das investiga????es encontra-se nas vari??veis referentes ??s dificuldades pessoais, profissionais e tecnol??gicas, ??s peculiaridades do curso e caracter??sticas da clientela, contrastadas com as vari??veis demogr??ficas referentes ?? evas??o em cursos a dist??ncia mediados por tecnologias da informa????o e da comunica????o. O trabalho ?? embasado em metodologia quantitativa, por meio de pesquisa descritiva de campo junto aos participantes, valendo-se do uso de question??rio eletr??nico. Procura contribuir para investiga????es sobre o tema, em especial no que se refere aos servidores p??blicos.

Pr??-equidade de g??nero: incorporando pol??ticas de a????o afirmativa no mundo do trabalho

A institui????o do Programa Pr??-equidade de G??nero ?? o reconhecimento p??blico da desigualdade de tratamento e de oportunidades, que ainda permanece entre mulheres e homens. A implementa????o ?? consolidada com a coloca????o em pr??tica dos planos de a????es firmados entre a Secretaria Especial de Pol??ticas para as Mulheres (SPM) e as organiza????es aderentes. A pesquisa explorat??ria teve como objetivo apresentar o programa e discuti-lo com base no modelo "policy cycle como aprendizado", de Silva e Melo (2000). Os resultados subsidiar??o pesquisa futura sobre a avalia????o do programa. Dentro da estrat??gia adotada, a coleta de dados ocorreu em documentos institucionais e dados bibliogr??ficos em mar??o de 2009, com o seguinte resultado: a avalia????o n??o trata de forma clara da efetividade e da sustentabilidade do programa. Este trabalho est?? dividido em seis partes: descri????o do m??todo utilizado; apresenta????o do Programa Pro-equidade de G??nero; avalia????o de suas duas primeiras edi????es; breve contextualiza????o das pol??ticas p??blicas no Brasil e o modelo "policy cicle como aprendizado"; rela????es entre o programa e o modelo; e considera????es finais.

??tica na pesquisa agropecu??ria: percep????o dos pesquisadores da Embrapa

Esse trabalho apresenta os resultados de um estudo sobre a percep????o dos pesquisadores da Empresa Brasileira de Pesquisa Agropecu??ria (Embrapa) a respeito da ??tica na pesquisa agropecu??ria. O estudo foi explorat??rio e adotou abordagens qualitativa e quantitativa. A pesquisa qualitativa utilizou entrevistas individuais semiestruturadas com 21 formadores de opini??o (dirigentes, ex-dirigentes e ocupantes ou ex-ocupantes de cargos estrat??gicos) e serviu de base para a constru????o do question??rio para a pesquisa quantitativa. Da popula????o estudada, 1.846 pesquisadores, houve um retorno de 26,65% dos question??rios. Os resultados da pesquisa revelaram grande interesse entre os pesquisadores ouvidos pelo tema objeto do estudo e ao mesmo tempo uma falta de clareza de parte deles sobre o que seria ??tica na pesquisa agropecu??ria. O estudo recomenda uma ampla discuss??o na Empresa sobre o tema, culminando na implanta????o de ???gest??o da ??tica??? na pesquisa.

Conhecimentos, habilidades e atitudes: o conceito de compet??ncias no trabalho e seu uso no setor p??blico

Este estudo tem dois objetivos: revisar criticamente a produ????o cient??fica nacional sobre o tema ???compet??ncias no trabalho e nas organiza????es???; e apresentar o conceito e discutir sua utiliza????o no setor p??blico. Para tanto foram analisados relatos de pesquisa emp??rica e ensaios nacionais e estrangeiros ??? em peri??dicos de psicologia e administra????o. Foram discutidos: enfoques te??ricos, instrumentos de coleta de dados, procedimentos de an??lise, entre outros aspectos. Na an??lise da produ????o nacional, constatou-se que, em sua maioria, as pesquisas: descrevem compet??ncias ocupacionais ou profissionais; possuem desenho survey; apresentam pluralidade quanto ?? natureza da pesquisa e utiliza????o de m??todos e t??cnicas para coleta e an??lise de dados; e s??o realizadas principalmente no setor terci??rio da economia. Verificou-se, ainda, a converg??ncia do conceito de compet??ncia, diante da complexidade e fragmenta????o te??rica previamente constatadas na literatura. Entretanto, mesmo em evid??ncia, a produ????o cient??fica brasileira sobre o tema ?? recente e ainda h?? uma lacuna sobre a discuss??o do construto e sua aplica????o no setor p??blico, em especial no caso brasileiro, quando se trata da administra????o p??blica federal, direta, aut??rquica e fundacional.