Total exposure and exposure rate effects for alcohol and smoking and risk of head and neck cancer: a pooled analysis of case-control studies.

Although cigarette smoking and alcohol consumption increase risk for head and neck cancers, there have been few attempts to model risks quantitatively and to formally evaluate cancer site-specific risks. The authors pooled data from 15 case-control studies and modeled the excess odds ratio (EOR) to assess risk by total exposure (pack-years and drink-years) and its modification by exposure rate (cigarettes/day and drinks/day). The smoking analysis included 1,761 laryngeal, 2,453 pharyngeal, and 1,990 oral cavity cancers, and the alcohol analysis included 2,551 laryngeal, 3,693 pharyngeal, and 3,116 oval cavity cancers, with over 8,000 controls. Above 15 cigarettes/day, the EOR/pack-year decreased with increasing cigarettes/day, suggesting that greater cigarettes/day for a shorter duration was less deleterious than fewer cigarettes/day for a longer duration. Estimates of EOR/pack-year were homogeneous across sites, while the effects of cigarettes/day varied, indicating that the greater laryngeal cancer risk derived from differential cigarettes/day effects and not pack-years. EOR/drink-year estimates increased through 10 drinks/day, suggesting that greater drinks/day for a shorter duration was more deleterious than fewer drinks/day for a longer duration. Above 10 drinks/day, data were limited. EOR/drink-year estimates varied by site, while drinks/day effects were homogeneous, indicating that the greater pharyngeal/oral cavity cancer risk with alcohol consumption derived from the differential effects of drink-years and not drinks/day.

Morfometria de Papilioninae (Lepidoptera, Papilionidae) ocorrentes em quatro localidades do Rio Grande do Sul, Brasil. I. Comparações com a massa corporal

A análise da relação entre a asa e partes do corpo em Lepidoptera podem revelar uma conexão entre a estrutura e a função. Este estudo investigou relações entre o tamanho do corpo de papilionídeos e suas partes, importantes para entender como a forma e o tamanho são determinados, e como eles estão adaptados aos ambientes bióticos e abióticos. Fêmeas são mais pesadas que machos (acima de 1,75 g). Em habitat diferentes, o tórax e o abdômen das fêmeas é maior em 100% das 11 espécies analisadas, a massa total 92%, e a massa de asas 75%. Espécies cujas fêmeas tiveram a maior massa também mostraram maior deslocamento e dispersão nas suas áreas de vida. Em habitats mais perturbados pelo homem ou com menor cobertura vegetal, o aumento no tamanho do tórax é significativamente maior que o das asas, tanto para os machos como para as fêmeas. Nos machos, o aumento de abdômen não é significativamente maior que o das asas, em todos os locais investigados. Porém, nas fêmeas o aumento do abdômen é significativo em todas os locais. A análise de agrupamento mostra dois grandes grupos caracterizados por espécies com tamanhos e proporções semelhantes. Um grupo com espécies que ocupam ambientes com umidade alta, e outro (mais heterogêneo) que ocupa habitats alterados pela ação do homem. O primeiro mostra duas subdivisões distinguidas pelo tipo de exibição que machos apresentam às fêmeas.

Molecular and functional characterization of a novel cardiac-specific human tropomyosin isoform.

BACKGROUND: Tropomyosin (TM), an essential actin-binding protein, is central to the control of calcium-regulated striated muscle contraction. Although TPM1alpha (also called alpha-TM) is the predominant TM isoform in human hearts, the precise TM isoform composition remains unclear. METHODS AND RESULTS: In this study, we quantified for the first time the levels of striated muscle TM isoforms in human heart, including a novel isoform called TPM1kappa. By developing a TPM1kappa-specific antibody, we found that the TPM1kappa protein is expressed and incorporated into organized myofibrils in hearts and that its level is increased in human dilated cardiomyopathy and heart failure. To investigate the role of TPM1kappa in sarcomeric function, we generated transgenic mice overexpressing cardiac-specific TPM1kappa. Incorporation of increased levels of TPM1kappa protein in myofilaments leads to dilated cardiomyopathy. Physiological alterations include decreased fractional shortening, systolic and diastolic dysfunction, and decreased myofilament calcium sensitivity with no change in maximum developed tension. Additional biophysical studies demonstrate less structural stability and weaker actin-binding affinity of TPM1kappa compared with TPM1alpha. CONCLUSIONS: This functional analysis of TPM1kappa provides a possible mechanism for the consequences of the TM isoform switch observed in dilated cardiomyopathy and heart failure patients.

Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction.

BACKGROUND: Coronary artery calcification (CAC) detected by computed tomography is a noninvasive measure of coronary atherosclerosis, which underlies most cases of myocardial infarction (MI). We sought to identify common genetic variants associated with CAC and further investigate their associations with MI. METHODS AND RESULTS: Computed tomography was used to assess quantity of CAC. A meta-analysis of genome-wide association studies for CAC was performed in 9961 men and women from 5 independent community-based cohorts, with replication in 3 additional independent cohorts (n=6032). We examined the top single-nucleotide polymorphisms (SNPs) associated with CAC quantity for association with MI in multiple large genome-wide association studies of MI. Genome-wide significant associations with CAC for SNPs on chromosome 9p21 near CDKN2A and CDKN2B (top SNP: rs1333049; P=7.58×10(-19)) and 6p24 (top SNP: rs9349379, within the PHACTR1 gene; P=2.65×10(-11)) replicated for CAC and for MI. Additionally, there is evidence for concordance of SNP associations with both CAC and MI at a number of other loci, including 3q22 (MRAS gene), 13q34 (COL4A1/COL4A2 genes), and 1p13 (SORT1 gene). CONCLUSIONS: SNPs in the 9p21 and PHACTR1 gene loci were strongly associated with CAC and MI, and there are suggestive associations with both CAC and MI of SNPs in additional loci. Multiple genetic loci are associated with development of both underlying coronary atherosclerosis and clinical events.

On the robustness of least-squares Monte Carlo (LSM) for pricing American derivatives

This paper analyses the robustness of Least-Squares Monte Carlo, a techniquerecently proposed by Longstaff and Schwartz (2001) for pricing Americanoptions. This method is based on least-squares regressions in which theexplanatory variables are certain polynomial functions. We analyze theimpact of different basis functions on option prices. Numerical resultsfor American put options provide evidence that a) this approach is veryrobust to the choice of different alternative polynomials and b) few basisfunctions are required. However, these conclusions are not reached whenanalyzing more complex derivatives.

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.

History of diabetes and risk of head and neck cancer: a pooled analysis from the international head and neck cancer epidemiology consortium.

BACKGROUND: A history of diabetes is associated with an increased risk of several types of cancers. Whether diabetes is a risk factor for head and neck cancer (HNC) has received little attention. METHODS: We pooled data from 12 case-control studies including 6,448 cases and 13,747 controls, and estimated odds ratios (OR) and 95% confidence intervals (CI) for the associations between diabetes and HNC, adjusted for age, education level, sex, race/ethnicity, study center, cigarette smoking, alcohol use and body mass index (BMI). RESULTS: We observed a weak association between diabetes and the incidence of HNC overall (OR, 1.09; 95% CI, 0.95-1.24). However, we observed a modest association among never smokers (OR, 1.59; 95% CI, 1.22-2.07), and no association among ever smokers (OR, 0.96; 95% CI, 0.83-1.11); likelihood ratio test for interaction p=0.001. CONCLUSIONS: A history of diabetes was weakly associated with HNC overall, but we observed evidence of effect modification by smoking status, with a positive association among those who never smoked cigarettes. Impact: This study suggests that glucose metabolism abnormalities may be a HNC risk factor in subgroups of the population. Prospective studies incorporating biomarkers are needed to improve our understanding of the relationship between diabetes and HNC risk, possibly providing new strategies in the prevention of HNC.

Razão de Perdas de Solo sob cultivo de três leguminosas

Um experimento sobre perdas de água e solo por erosão foi desenvolvido, durante seis anos agrícolas (1973/74 a 1978/79), no Centro Experimental de Campinas do Instituto Agronômico do estado de São Paulo, Brasil, em um Typic Haplortox, com vistas em avaliar a Razão de Perdas de Solo (RPS) para três leguminosas utilizadas como adubos verdes. As leguminosas estudadas foram a Crotalaria juncea L. (crotalária); Stizolobium Aterrinum Piper et Tracy (mucuna-preta) e Dolichos lablab L. (labelabe). Para determinar a razão de perdas de solo, foram estabelecidos quatro períodos das culturas isolados de 0-30, 30-60, 60-90 e 60-120 dias após a semeadura e períodos cumulativos de 0-30, 0-60, 0-90 e 0-120 dias após a semeadura. Os resultados obtidos mostraram maior proteção oferecida pela mucuna-preta à erosão, com valores de RPS de 0,28; 0,37; 0,17; e 0,09 para os períodos isolados de 0-30, 30-60; 60-90 e 60-120 dias após a semeadura. O labelabe apresentou, para a mesma situação, os valores de 0,50; 0,45; 0,27 e 0,19; enquanto, para a crotalária, os valores foram de 0,30; 0,42; 0,26 e 0,24. Os resultados mostraram proteção mais efetiva do solo à erosão a partir dos 60 dias após a semeadura, por parte das espécies avaliadas. A mucuna-preta apresentou maior efetividade na proteção do solo, seguida da crotalária, especialmente no primeiro período, e do labelabe, no estádio mais próximo ao florescimento.

Absorção de N, P e K por espécies de adubos verdes cultivadas em diferentes épocas e densidades num latossolo vermelho-escuro argiloso sob cerrados

Populações específicas de plantas e a época de semeadura podem promover interferências na absorção dos nutrientes. Assim, um experimento foi realizado, no ano agrícola de 1991/92, num Latossolo Vermelho-Escuro argiloso no Centro Nacional de Pesquisa de Solos/Embrapa, em Senador Canedo (GO), com o objetivo de determinar os teores e as quantidades absorvidas de nitrogênio, fósforo e potássio na parte aérea da Crotalaria juncea: l., Crotalaria ochroleuca: G. Don, mucuna preta ( Mucuna aterrima (Piper & Tracy) Merr.) e guandu cv. Kaki (Cajanus cajan (L.) Millsp.), em três épocas de semeadura (início, meados e final da estação chuvosa) e em dois espaçamentos entrelinhas (0,5 e 0,4 m). O delineamento experimental, dentro de cada época, foi o de blocos ao acaso em parcelas subdivididas, com três repetições. As espécies diferiram entre si quanto aos teores e quantidades absorvidas de N, P e K. Ao contrário das épocas de semeadura, não houve efeito significativo dos espaçamentos nos teores e quantidades absorvidas de N, P e K. A interação de espécies e épocas de semeadura foi significativa apenas para o nitrogênio e fósforo.

Marqueurs de la filtration glomérulaire en pédiatrie [Glomerular filtration markers in pediatrics]

The assessment of glomerular filtration rate (GFR) is critical for the diagnosis and management of renal diseases in pediatric nephrology. Ideally, it requires the measurement of the renal clearance of a filtration marker. Inulin, an exogenous marker, is the only compound the excretion of which occurs exclusively by glomerular filtration, with no tubular handling. Therefore, inulin clearance provides the most accurate method to measure GFR and is considered as the "gold standard", at all ages including very premature neonates. However, inulin dearance is cumbersome and alternative methods are used in clinical practice. If urine is available, endogenous creatinine clearance is the most reliable method. When urine collection is difficult to obtain, GFR can be estimated by the plasma concentration of endogenous markers mainly eliminated by glomerular filtration, such as creatinine, or the more recently described cystatin C and beta 2-microglobulin. When the endogenous production of these markers is constant, their plasma concentration reflects glomerular filtration; it increases with decreasing renal function. However, in pediatric patients creatinine production depends on muscle mass, which significantly increases with linear growth, as well as age and gender. Mathematical formulas taking these parameters into account have thus been developed. Among these, the so-called "Schwartz formula" is often used and is a reliable estimate of GFR in children. Finally, radionuclide renal scans can be used to evaluate the separate glomerular function of each kidney.

Efeito de leguminosas nos atributos físicos e carbono orgânico de um Luvissolo

A degradação de um solo sob cultivo é resultante, principalmente, de seu manejo inadequado, com reflexos nas baixas produtividades das culturas. Com a finalidade de avaliar o efeito de leguminosas nos atributos físicos e carbono orgânico (CO) de um Luvissolo, realizou-se, no município de Alagoinha (PB), um experimento entre 1997 e 1999, com as seguintes espécies: crotalária (Crotalaria juncea, L), guandu (Cajanus cajan,L), guandu anão (Cajanus cajan (L) Millsp), calopogônio (Calopogonium mucunoides, L), feijão-de-porco (Canavalia ensiforme, L), lab-lab (Dolichos lab lab, L), kudzu tropical (Pueraria phaseoloides, L), siratro (Macroptilium atropurpureum, L), leucena (Leucaena leucocephala, L), cunhã (Clitoria ternatea, L), mucuna preta (Styzolobium aterrimum, L), mucuna cinza (Styzolobium cinereum Piper e Tracy), e uma parcela com vegetação espontânea, como testemunha. O delineamento experimental utilizado foi o de blocos ao acaso em esquema de parcela subdividida, com distribuição de treze tratamentos principais na parcela (12 leguminosas + 1 testemunha) e três tratamentos secundários, representados pelas profundidades de coleta de amostras de solo (0,00-0,10; 0,10-0,20; e 0,20-0,30 m), na subparcela, com três repetições. Na condição edafoclimática deste experimento, durante os três anos de trabalho, constatou-se que o emprego das leguminosas em relação à testemunha manteve inalterados o CO do solo, a densidade do solo, a porosidade total, a argila dispersa em água e a estabilidade dos agregados do solo.

Glomerular filtration rate: measure creatinine and height rather than cystatin C!

AIM: Inulin clearance (Cin) is the gold standard for assessing glomerular filtration rate (GFR). Other methods are based on the plasma creatinine concentration (Pcreat), creatinine clearance (Ccreat), the Haycock-Schwartz formula and the plasma concentration of cystatin C (PcysC), a 13 kDa basic protein produced at a constant rate by all nucleated cells. The present prospective study was thus designed to evaluate the reliability of PcysC as a marker of GFR in comparison with that of Pcreat, Ccreat and the Haycock-Schwartz formula, using Cin as the gold standard. METHODS: Ninety-nine children (51 m/48 f), with a median age of 8.3 y (1.0-17.9) were studied. Using a cut-off for Cin of 100 ml/min per 1.73 m2, 54 children (54.5%) had impaired GFR. Those with normal GFR were comparable for age, height, weight and body mass index. RESULTS: Logistic regression, ROC analysis and linear regression all showed that Ccreat was the best parameter to discriminate between impaired and normal GFR, followed by the Haycock-Schwartz formula, PcysC, and finally Pcreat, each one being significantly more predictive than the next. CONCLUSION: GFR is better assessed by the Haycock-Schwartz formula than by PcysC or Pcreat alone. It is therefore concluded that when urine collection is not possible, simply measuring the child's Pcreat and height is the best, easiest and cheapest way to assess GFR.

New combined serum creatinine and cystatin C quadratic formula for GFR assessment in children.

BACKGROUND AND OBJECTIVES: The estimated GFR (eGFR) is important in clinical practice. To find the best formula for eGFR, this study assessed the best model of correlation between sinistrin clearance (iGFR) and the solely or combined cystatin C (CysC)- and serum creatinine (SCreat)-derived models. It also evaluated the accuracy of the combined Schwartz formula across all GFR levels. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Two hundred thirty-eight iGFRs performed between January 2012 and April 2013 for 238 children were analyzed. Regression techniques were used to fit the different equations used for eGFR (i.e., logarithmic, inverse, linear, and quadratic). The performance of each model was evaluated using the Cohen κ correlation coefficient and the percentage reaching 30% accuracy was calculated. RESULTS: The best model of correlation between iGFRs and CysC is linear; however, it presents a low κ coefficient (0.24) and is far below the Kidney Disease Outcomes Quality Initiative targets to be validated, with only 84% of eGFRs reaching accuracy of 30%. SCreat and iGFRs showed the best correlation in a fitted quadratic model with a κ coefficient of 0.53 and 93% accuracy. Adding CysC significantly (P<0.001) increased the κ coefficient to 0.56 and the quadratic model accuracy to 97%. Therefore, a combined SCreat and CysC quadratic formula was derived and internally validated using the cross-validation technique. This quadratic formula significantly outperformed the combined Schwartz formula, which was biased for an iGFR≥91 ml/min per 1.73 m(2). CONCLUSIONS: This study allowed deriving a new combined SCreat and CysC quadratic formula that could replace the combined Schwartz formula, which is accurate only for children with moderate chronic kidney disease.

Moesin interacts with the cytoplasmic region of intercellular adhesion molecule-3 and is redistributed to the uropod of T Lymphocytes during cell polarization

During activation, T lymphocytes become motile cells, switching from a spherical to a polarized shape. Chemokines and other chemotactic cytokines induce lymphocyte polarization with the formation of a uropod in the rear pole, where the adhesion receptors intercellular adhesion molecule-1 (ICAM-1), ICAM-3, and CD44 redistribute. We have investigated membrane-cytoskeleton interactions that play a key role in the redistribution of adhesion receptors to the uropod. Immunofluorescence analysis showed that the ERM proteins radixin and moesin localized to the uropod of human T lymphoblasts treated with the chemokine RANTES (regulated on activation, normal T cell expressed, and secreted), a polarization-inducing agent; radixin colocalized with arrays of myosin II at the neck of the uropods, whereas moesin decorated the most distal part of the uropod and colocalized with ICAM-1, ICAM-3, and CD44 molecules. Two other cytoskeletal proteins, ß-actin and ¿-tubulin, clustered at the cell leading edge and uropod, respectively, of polarized lymphocytes. Biochemical analysis showed that moesin coimmunoprecipitates with ICAM-3 in T lymphoblasts stimulated with either RANTES or the polarization- inducing anti-ICAM-3 HP2/19 mAb, as well as in the constitutively polarized T cell line HSB-2. In addition, moesin is associated with CD44, but not with ICAM-1, in polarized T lymphocytes. A correlation between the degree of moesin-ICAM-3 interaction and cell polarization was found as determined by immunofluorescence and immunoprecipitation analysis done in parallel. The moesin-ICAM-3 interaction was specifically mediated by the cytoplasmic domain of ICAM-3 as revealed by precipitation of moesin with a GST fusion protein containing the ICAM-3 cytoplasmic tail from metabolically labeled Jurkat T cell lysates. The interaction of moesin with ICAM-3 was greatly diminished when RANTES-stimulated T lymphoblasts were pretreated with the myosin-disrupting drug butanedione monoxime, which prevents lymphocyte polarization. Altogether, these data indicate that moesin interacts with ICAM-3 and CD44 adhesion molecules in uropods of polarized T cells; these data also suggest that these interactions participate in the formation of links between membrane receptors and the cytoskeleton, thereby regulating morphological changes during cell locomotion.