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.

Family history of cancer: Pooled analysis in the International Head and Neck Cancer Epidemiology consortium

Alcohol and tobacco consumption are well-recognized risk factors for head and neck cancer (HNC). Evidence suggests that genetic predisposition may also play a role. Only a few epidemiologic studies, however, have considered the relation between HNC risk and family history of HNC and other cancers. We pooled individual-level data across 12 case-control studies including 8,967 HNC cases and 13,627 controls. We obtained pooled odds ratios (OR) using fixed and random effect models and adjusting for potential confounding factors. All statistical tests were two-sided. A family history of HNC in first-degree relatives increased the risk of HNC (OR = 1.7, 95% confidence interval, CI, 1.2-2.3). The risk was higher when the affected relative was a sibling (OR = 2.2, 95% CI 1.6-3.1) rather than a parent (OR = 1.5, 95% CI 1.1-1.8) and for more distal HNC anatomic sites (hypopharynx and larynx). The risk was also higher, or limited to, in subjects exposed to tobacco. The OR rose to 7.2 (95% CI 5.5-9.5) among subjects with family history, who were alcohol and tobacco users. A weak but significant association (OR = 1.1, 95% CI 1.0-1.2) emerged for family history of other tobacco-related neoplasms, particularly with laryngeal cancer (OR = 1.3, 95% CI 1.1-1.5). No association was observed for family history of nontobacco-related neoplasms and the risk of HNC (OR = 1.0, 95% CI 0.9-1.1). Familial factors play a role in the etiology of HNC. In both subjects with and without family history of HNC, avoidance of tobacco and alcohol exposure may be the best way to avoid HNC. (C) 2008 Wiley-Liss, Inc,

Involuntary smoking and head and neck cancer risk: Pooled analysis in the International Head and Neck Cancer Epidemiology Consortium

Although active tobacco smoking has been identified as a major risk factor for head and neck cancer, involuntary smoking has not been adequately evaluated because of the relatively low statistical power in previous studies. We took advantage of data pooled in the International Head and Neck Cancer Epidemiology Consortium to evaluate the role of involuntary smoking in head and neck carcinogenesis. Involuntary smoking exposure data were pooled across six case-control studies in Central Europe, Latin America, and the United States. Adjusted odds ratios (OR) and 95% confidence interval (95% CI) were estimated for 542 cases and 2,197 controls who reported never using tobacco, and the heterogeneity among the study-specific ORs was assessed. In addition, stratified analyses were done by subsite. No effect of ever involuntary smoking exposure either at home or at work was observed for head and neck cancer overall. However, long duration of involuntary smoking exposure at home and at work was associated with an increased risk (OR for >15 years at home, 1.60; 95% CI, 1.12-2.28; P(trend) <0-01; OR for >15 years at work, 1.55; 95% CI, 1.04-2.30; P(trend) = 0.13). The effect of duration of involuntary smoking exposure at home was stronger for pharyngeal and laryngeal cancers than for other subsites. An association between involuntary smoking exposure and the risk of head and neck cancer, particularly pharyngeal and laryngeal cancers, was observed for long duration of exposure. These results are consistent with those for active smoking and suggest that elimination of involuntary smoking exposure might reduce head and neck cancer risk among never smokers.

A Sex-Specific Association between a 15q25 Variant and Upper Aerodigestive Tract Cancers

Background: Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.003) with little effect in men (OR = 1.04, P = 0.35). Methods: In a coordinated genotyping study within the International Head and Neck Cancer Epidemiology (INHANCE) consortium, we have sought to replicate these findings in an additional 4,604 cases and 6,239 controls from 10 independent UADT cancer case-control studies. Results: rs16969968 was again associated with UADT cancers in women (OR = 1.21, 95% CI = 1.08-1.36, P = 0.001) and a similar lack of observed effect in men [OR = 1.02, 95% CI = 0.95-1.09, P = 0.66; P-heterogeneity (P(het)) = 0.01]. In a pooled analysis of the original and current studies, totaling 8,572 UADT cancer cases and 11,558 controls, the association was observed among females (OR = 1.22, 95% CI = 1.12-1.34, P = 7 x 10(-6)) but not males (OR = 1.02, 95% CI = 0.97-1.08, P = 0.35; P(het) = 6 x 10(-4)). There was little evidence for a sex difference in the association between this variant and cigarettes smoked per day, with male and female rs16969968 variant carriers smoking approximately the same amount more in the 11,991 ever smokers in the pooled analysis of the 14 studies (P(het) = 0.86). Conclusions: This study has confirmed a sex difference in the association between the 15q25 variant rs16969968 and UADT cancers. Impact: Further research is warranted to elucidate the mechanisms underlying these observations. Cancer Epidemiol Biomarkers Prev; 20(4); 658-64. (C) 2011 AACR.

Preterm and term neonates transplacentally acquire IgG antibodies specific to LPS from Klebsiella pneumoniae, Escherichia coli and Pseudomonas aeruginosa

High incidences of Gram-negative bacteria are found in neonatal nosocomial infections. Our aim was to investigate placental transmission of immunoglobulin G (IgG) reactive with lipopolysaccharide from Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia colt O111, O6 and O26. The total and lipopolysaccharide-specific IgM and IgG were determined in 11 maternal/umbilical-cord sera aged <= 33 weeks (GI); 21 aged > 33 and < 37 weeks (GII); and 32 term newborns (GIII). The total and lipopolysaccharide-specific IgM concentrations were equivalent in maternal sera. The total IgG concentrations were equivalent in maternal and newborn sera, with the exception of GIII newborns as compared with their mothers (P < 0.0001) and with neonates from GI and GII (P < 0.05). Lipopolysaccharide-specific IgG concentrations were lower in GI neonates than in their mothers (P < 0.01) and lower in GII (P < 0.05). Lower lipopolysaccharide-specific IgG levels were observed among neonates only for O111 in GI (P < 0.05) and for 026 and Pseudomonas in GII, both as compared with GIII (P < 0.05). The anti-lipopolysaccharide IgG transfer ratios were lower in GI (except for 026) and in GII (except for Klebsiella and O111) as compared with GIII (P < 0.05). Our results suggest that the greater susceptibility to infections in preterm infants is influenced (besides the humoral response) by factors intrinsic and extrinsic to the condition of prematurity.

Use of Acoustic Doppler Sonography to Ascertain the Feasibility of the Pedicled Nasoseptal Flap After Prior Bilateral Sphenoidotomy

Objectives/Hypothesis: Blood supply to the Hadad-Bassagasteguy pedicled nasoseptal flap may be interrupted by surgery of the pterygopalatine fossa, posterior septectomy, or large sphenoidotomies. This would preclude its use for reconstruction of skull base defects after expanded endonasal approaches (EEA). We present a novel method to ascertain the patency of the nasoseptal artery after prior surgery, and consequently the availability of the nasoseptal flap, using acoustic Doppler sonography. Study Design: Retrospective clinical review. Methods: Four patients who underwent EEAs were evaluated intraoperatively with acoustic Doppler sonography. The mucosa that covers the inferior aspect of the rostrum of the sphenoid sinus was scanned with the tip of the probe. Reflection of sound waves representing intravascular blood flow was assessed. Results: In three patients, the artery was identified in at least one side. One remaining patient showed no acoustic signal suggesting loss of the nasoseptal artery bilaterally, therefore necessitating the use of a fat graft for the reconstruction. Conclusions: Acoustic Doppler sonography seems to be a feasible and effective way to ascertain the availability of the nasoseptal artery. It is a relatively inexpensive and simple technique that can be performed by any endoscopic surgeon.

De novo copy number variants identify new genes and loci in isolated sporadic tetralogy of Fallot

Tetralogy of Fallot (TOF), the most common severe congenital heart malformation, occurs sporadically, without other anomaly, and from unknown cause in 70% of cases. Through a genome-wide survey of 114 subjects with TOF and their unaffected parents, we identified 11 de novo copy number variants (CNVs) that were absent or extremely rare (<0.1%) in 2,265 controls. We then examined a second, independent TOF cohort (n = 398) for additional CNVs at these loci. We identified CNVs at chromosome 1q21.1 in 1% (5/512, P = 0.0002, OR = 22.3) of nonsyndromic sporadic TOF cases. We also identified recurrent CNVs at 3p25.1, 7p21.3 and 22q11.2. CNVs in a single subject with TOF occurred at six loci, two that encode known (NOTCH1, JAG1) disease-associated genes. Our findings predict that at least 10% (4.5-15.5%, 95% confidence interval) of sporadic nonsyndromic TOF cases result from de novo CNVs and suggest that mutations within these loci might be etiologic in other cases of TOF.

Constitutional hypomorphic telomerase mutations in patients with acute myeloid leukemia

Loss-of-function mutations in telomerase complex genes can cause bone marrow failure, dyskeratosis congenita, and acquired aplastic anemia, both diseases that predispose to acute myeloid leukemia. Loss of telomerase function produces short telomeres, potentially resulting in chromosome recombination, end-to-end fusion, and recognition as damaged DNA. We investigated whether mutations in telomerase genes also occur in acute myeloid leukemia. We screened bone marrow samples from 133 consecutive patients with acute myeloid leukemia and 198 controls for variations in TERT and TERC genes. An additional 89 patients from a second cohort, selected based on cytogenetic status, and 528 controls were further examined for mutations. A third cohort of 372 patients and 384 controls were specifically tested for one TERT gene variant. In the first cohort, 11 patients carried missense TERT gene variants that were not present in controls (P<0.0001); in the second cohort, TERT mutations were associated with trisomy 8 and inversion 16. Mutation germ-line origin was demonstrated in 5 patients from whom other tissues were available. Analysis of all 3 cohorts (n = 594) for the most common gene variant (A1062T) indicated a prevalence 3 times higher in patients than in controls (n = 1,110; P = 0.0009). Introduction of TERT mutants into telomerase-deficient cells resulted in loss of enzymatic activity by haploinsufficiency. Inherited mutations in TERT that reduce telomerase activity are risk factors for acute myeloid leukemia. We propose that short and dysfunctional telomeres limit normal stem cell proliferation and predispose for leukemia by selection of stem cells with defective DNA damage responses that are prone to genome instability.

Sensitivity and uncertainty analyses for burden of disease and risk factor estimates

Epidemiological studies report confidence or uncertainty intervals around their estimates. Estimates of the burden of diseases and risk factors are subject to a broader range of uncertainty because of the combination of multiple data sources and value choices. Sensitivity analysis can be used to examine the effects of social values that have been incorporated into the design of the disability–adjusted life year (DALY). Age weight, where a year of healthy life lived at one age is valued differently from at another age, is the most controversial value built into the DALY. The discount rate, which addresses the difference in value of current versus future health benefits, also has been criticized. The distribution of the global disease burden and rankings of various conditions are largely insensitive to alternate assumptions about the discount rate and age weighting. The major effects of discounting and age weighting are to enhance the importance of neuropsychiatric conditions and sexually transmitted infections. The Global Burden of Disease study also has been criticized for estimating mortality and disease burden for regions using incomplete and uncertain data. Including uncertain results, with uncertainty quantified to the extent possible, is preferable, however, to leaving blank cells in tables intended to provide policy makers with an overall assessment of burden of disease. No estimate is generally interpreted as no problem. Greater investment in getting the descriptive epidemiology of diseases and injuries correct in poor countries will do vastly more to reduce uncertainty in disease burden assessments than a philosophical debate about the appropriateness of social value

A population-based study of the biochemical and clinical expression of the H63D hemochromatosis mutation

Background & Aims: Two major mutations are defined within the hemochromatosis gene, HFE. Although the effects of the C282Y mutation have been well characterized, the effects of the H63D mutation remain unclear. We accessed a well-defined population in Busselton, Australia, and determined the frequency of the H63D mutation and its influence on total body iron stores. Methods: Serum transferrin saturation and ferritin levels were correlated with the H63D mutation in 2531 unrelated white subjects who did not possess the C282Y mutation. Results: Sixty-two subjects (2.1%) were homozygous for the H63D mutation, 711 (23.6%) were heterozygous, and 1758 (58.4%) were wild-type for the H63D mutation. Serum transferrin saturation was significantly increased in male and female H63D homozygotes and heterozygotes compared with wild-types. Serum ferritin levels within each gender were not influenced by H63D genotypes. Elevated transferrin saturation greater than or equal to45% was observed in a greater proportion of male H63D carriers than male wild-types. Male H63D homozygotes (9%) and heterozygotes (3%) were more likely to have both elevated transferrin saturation and elevated ferritin greater than or equal to300 ng/mL than male wild-types (0.7%). Homozygosity for H63D was not associated with the development of clinically significant iron overload. Conclusions: Presence of the H63D mutation results in a significant increase in serum transferrin saturation but does hot result in significant iron overload. In the absence of the C282Y mutation, the H63D mutation is not clinically significant.

Padrão de frugivoria por Tapirus terrestris na Mata Atlântica do norte do Espírito Santo, Brasil

A anta Tapirus terrestris (Linnaeus, 1758), último representante da megafauna Pleistocênica na região Neotropical, representa um importante grupo funcional, pois dispersam uma grande variedade de espécies vegetais, especialmente frutos. No entanto, o padrão de frugivoria da espécie pode variar entre diferentes áreas. Dessa forma, nosso interesse foi investigar o grau de frugivoria da espécie em duas diferentes áreas no estado do Espírito Santo e a sua importância para a dinâmica florestal. Para isso, foram coletadas amostras fecais, através de busca ativa em diferentes ambientes na Reserva Biológica do Córrego do Veado (Rebio Córrego do Veado) e na Reserva Particular do Patrimônio Natural Recanto das Antas (RPPN Recanto das Antas), durante o período de janeiro de 2011 a novembro de 2013. Após a triagem do material biológico, as sementes foram individualizadas, classificadas quanto às características e grupos ecológicos e identificadas até o menor nível taxonômico possível. Foi obtido um esforço amostral de 130 dias, resultando em 325 amostras fecais coletadas, sendo 53,2% da Rebio Córrego do Veado e 46,8% da RPPN Recanto das Antas. Do total de amostras, 41,8% estavam depositadas dentro ou próximas a corpos d’água e 58,2% na serrapilheira/substrato seco. A dieta da anta foi composta por 94,1% de fibras e 5,9% de frutos. Foram encontradas duas vezes mais amostras contendo sementes na RPPN Recanto das Antas do que na Rebio Córrego do Veado. Das 30 morfoespécies encontradas nas amostras, 15 foram identificadas em nível específico, as quais estão distribuídas em oito famílias. As famílias mais representativas foram Anacardiaceae, Fabaceae e Myrtaceae. As espécies mais freqüentemente encontradas nas amostras foram Spondias macrocarpa Engl. e S. venulosa (Engl.) Engl. Do total de sementes encontradas 60% apresentam dispersão zoocórica e 46,7% são sementes grandes e muito grandes e 50% possuem fruto do tipo carnoso. Das morfoespécies encontradas, sete foram registradas em ambas as unidades de conservação, 21 foram encontradas apenas na RPPN Recanto das Antas e duas foram encontradas na Rebio Córrego do Veado. Isso pode indicar que o ambiente na RPPN Recanto das Antas pode fornecer mais frutos que na Rebio Córrego do Veado, o que pode ser um resultado do histórico de perturbações da última reserva. Na década de 1980, 80% da Rebio Córrego do Veado foi queimada em um incêndio e, atualmente, o entorno da reserva é composto principalmente por pastagens. Ao contrário, a RPPN Recanto das Antas, apesar de sua área ter sofrido extração seletiva na década de 50, está inserida no maior remanescente de Mata Atlântica do Espírito Santo. Ainda que a anta possua uma dieta composta por uma variedade de frutos nas áreas de estudo, ela aparenta ser menos frugívora do que em outras áreas da Mata Atlântica. Contudo, é evidente a importância de T. terrestris na dispersão de um grande número de espécies vegetais, especialmente as espécies com sementes grandes, aumentando o recrutamento de espécies de plantas que não são dispersadas por outras espécies animais.

Teste do CAPM condicional dos retornos de carteiras dos mercados brasileiro, argentino e chileno, comparando-os com o mercado norte-americano

Nas últimas décadas, o modelo Capital Asset Pricing Model (CAPM) tem despertado grande interesse por parte da comunidade científica. Apesar das críticas, o aprimoramento do CAPM estático deu origem a novos modelos dinâmicos que trazem maior segurança para o investidor ao longo do ciclo de negócios. Atualmente, encontramos adaptações mais complexas do modelo CAPM, as quais nos permitem ter respostas sobre questões em finanças que por muito tempo permaneceram não solucionadas. Diante desse panorama e considerando todo o debate acerca da validade do CAPM, este trabalho tem como objetivo testar o modelo CAPM condicional de Jagannathan e Wang (1996), incorporando variáveis macroeconômicas e financeiras, para o mercado brasileiro, argentino, chileno, e norte americano.

Catálogo das coleções entomológicas da Faculdade de Saúde Pública da Universidade de São Paulo - (2ª Série II): Culicidae

Subfamília ANOPHELINAE: Gênero Anopheles Meigen, 1818; Subfamília CULICINAE: Tribo AEDEOMYIINI: Gênero Aedeomyia Theobald, 1901; Tribo AEDINI: Gênero Aedes Meigen, 1818; Gênero Haemagogus Williston, 1896; Gênero Psorophora Robineau-Desvoidy, 1827; Tribo CULICINI: Gênero Culex Linnaeus, 1758; Gênero Deinocerites Theobald, 1901; Tribo MANSONIINI: Gênero Coquillettidia Dyar, 1905; Gênero Mansonia Blanchard, 1901; Tribo ORTHO-PODOMYIINI: Gênero Orthopodomyia Theobald, 1904; Tribo SABETHINI: Gênero Limatus Theobald, 1901; Gênero Phoniomyia Theobald, 1903; Gênero Runchomyia Theobald, 1903; Gênero Sabethes Robineau-Desvoidy, 1827; Gênero Shannoniana Lane e Cerqueira, 1942; Gênero Trichoprosopon Theobald, 1901; Gênero Wyeomyia Theobald, 1901; Tribo URANOTAENIINI: Gênero Uranotaenia Lynch Arribalzaga, 1891.

CVD of CrO2 thin films: Influence of the deposition parameters on their structural and magnetic properties

This work reports on the synthesis of CrO2 thin films by atmospheric pressure CVD using chromium trioxide (CrO3) and oxygen. Highly oriented (100) CrO2 films containing highly oriented (0001) Cr2O3 were grown onto Al2O3(0001) substrates. Films display a sharp magnetic transition at 375 K and a saturation magnetization of 1.92 mu(B)/f.u., close to the bulk value of 2 mu(B)/f.u. for the CrO2.