Combined efficacy of acamprosate and disulfiram in the treatment of alcoholism: a controlled study.

This study presents the results of a multicenter investigation of the efficacy of acamprosate in the treatment of patients with chronic or episodic alcohol dependence. One hundred eighteen patients were randomly assigned to either placebo or acamprosate, and both groups were stratified for concomitant voluntary use of disulfiram. Treatment lasted for 360 days, with an additional 360-day follow-up period. The primary efficacy parameters evaluated were: relapse rate and cumulative abstinence duration (CAD). Results were analyzed according to Intention-To-Treat principles using chi2, t, and multiple regression analyses where appropriate. After 30 days on study medication, 40 of 55 (73%) acamprosate-treated patients were abstinent, compared with 26 of 55 (43%) placebo-treated patients (p = 0.019). The treatment advantage remained throughout the study medication period and was statistically significant until day 270 (p = 0.028). Twenty-seven percent of patients on acamprosate and 53% of patients on placebo had a first drink within the first 30 days of the study. The mean CAD was 137 days (40% abstinent days) for the patients treated with acamprosate and 75 days (21% abstinent days) for the placebo group (p = 0.013). No adverse interaction between acamprosate and disulfiram occurred, and the subgroup who received both medications had a better outcome on CAD than the those on only one or no medication. Acamprosate was well tolerated. Diarrhea was the only significant treatment-induced effect. It was concluded that acamprosate was a useful and safe pharmacotherapy in the long-term treatment of alcoholism. Concomitant administration of disulfiram improved the effectiveness of acamprosate.

Distribuição de 137Cs em três solos representativos do estado de pernambuco

O 137Cs tem sido usado para quantificar perdas ou deposição de solo, com base em valores das concentrações em áreas de referência que tiveram pouca perturbação nas últimas décadas. Determinações em áreas assim ainda não foram feitas na região Nordeste do Brasil. Em Pernambuco, foram selecionadas três áreas com topografia plana, vegetação nativa e solos não perturbados, em Goiana, Sertânia e Araripina. Em cada área, foram marcados quatro pontos, distantes 20 a 50 m um do outro, e em cada um retiradas amostras de solo, em camadas consecutivas de 3 cm de espessura, até 30 cm. As atividades de 137Cs foram determinadas usando espectrometria gama com detector de germânio hiperpuro (HPGe). Os estoques médios de 137Cs (Bq m-2) foram de 71,6 ± 6,3 em Goiana, 64,0 ± 13,8 em Araripina e 95,5 ± 9,8 em Sertânia. Valores nessa faixa têm sido relatados na Paraíba e na Bahia e, mais altos, na região Sudeste, confirmando a diminuição dos estoques em áreas mais próximas do Equador. As maiores atividades ocorreram nas camadas superficiais, variando de 0,5 a 1,6 Bq kg-1, e decresceram linearmente com a profundidade, até os limites de detecção: 18 cm em Araripina, 15 cm em Goiana e 9 cm em Sertânia. Em Goiana, acima dos horizontes inorgânicos havia um horizonte orgânico, com a mais alta atividade (2,06 Bq kg-1). Atividades e estoque altos e menor aprofundamento em Sertânia poderiam ser explicados pela predominância de argilominerais 2:1, em contraposição à de argilominerais 1:1 nos outros locais. Houve correlações positivas entre a atividade de 137Cs e os valores de pH em água e KCl e correlação negativa com as concentrações de Al3+. Confirma-se que, em áreas de referência, a maior atividade do 137Cs está na camada superior, com decréscimos regulares ao longo do perfil do solo.

The daily energy expenditure in stable chronic obstructive pulmonary disease.

Resting energy expenditure is frequently increased in chronic obstructive pulmonary disease (COPD), but it is unknown if this hypermetabolism holds true over 24 h. The aim of this study was to measure the actual 24-h energy expenditure (24-h EE) in patients with stable COPD. Energy expenditure was measured by indirect calorimetry, using a metabolic chamber for 24-h EE and a canopy for basal metabolic rate (BMR). Physical activity was detected in the chamber by a radar system, and its duration was quantified. Two groups matched for age and height were studied: 16 male ambulatory patients with stable COPD and 12 male normal subjects. Body weight was 92 +/- 12% of ideal body weight in the group with COPD and 108 +/- 11% in the control group (p = 0.01). BMR was 120 +/- 7% of predicted in the group with COPD and 108 +/- 12% in the control group (p < 0.01). However, 24-h EE was similar in the two groups, amounting to 1,935 +/- 259 kcal in patients with COPD and 2,046 +/- 253 kcal in the control group (NS). This corresponded to 145% and 137% of predicted BMR, and to 121% and 126% of measured BMR in patients with COPD and the control group, respectively (NS). Patients were allowed to pursue their usual treatment within the chamber, and a positive correlation existed between 24-h EE and the daily dose of inhaled beta 2-agonists (p < 0.03). During daytime, physical activity was lower in patients with COPD. This study shows that patients with stable COPD are characterized by a normal daily energy expenditure in controlled conditions in spite of an increased basal metabolic rate. They appear to save energy by reducing their spontaneous level of physical activity.

Valores de referência de qualidade para metais pesados em solos no Estado do Espírito Santo

Valores de referência de qualidade (VRQ) para metais pesados em solos, em âmbito mundial, são bastante heterogêneos. No Brasil, poucos estudos para estabelecer esses valores foram concluídos. Na ausência de VRQ para metais pesados em solos, estabelecidos para as condições do Estado do Espírito Santo, utilizam-se valores genéricos internacionais ou desenvolvidos para outros Estados. Entretanto, deve-se ressaltar que o uso desses valores pode levar a avaliações inadequadas, já que existem diferenças nas condições técnicas e variáveis ambientais de cada região, em especial das condições geológicas, hídricas e pedológicas. Essas diferenças justificam o desenvolvimento de uma tabela própria com VRQ para metais pesados em solos, adequada às condições do Estado do Espírito Santo. Nesse sentido, o presente estudo buscou obter os teores naturais de 10 metais pesados e verificar a distribuição desses elementos nos solos das bacias hidrográficas Riacho, Reis Magos e Santa Maria da Vitória, no Estado do Espírito Santo, tendo em vista o estabelecimento de Valores de Referência de Qualidade (VRQ). Para isso, foram determinados os teores totais por ataque ácido, com digestão em forno micro-ondas, conforme o método SW-846 3052 da Environmental Protection Agency (USEPA) e dosagem por espectrofotometria de emissão óptica com plasma induzido (ICP- OES). Os teores totais extraídos nos solos dessas bacias hidrográficas são relativamente baixos e inferiores aos reportados para solos de regiões brasileiras e de outros países. Os teores de cádmio ficaram abaixo do limite de detecção (LD) do método para todas as amostras. Em consequência, os VRQ obtidos para 12 metais pesados no Estado do Espírito Santo foram semelhantes ou inferiores aos obtidos para outras regiões do Brasil e do mundo. Os VRQ obtidos a partir do percentil 75 (quartil superior) para As (< 12,83), Cd (< 0,13), Co (10,21), Cr (54,13), Cu (5,91), Mn (137,80), Mo (1,74), Ni (9,17), Pb (< 4,54), V (109,96) e Zn (29,87), em mg kg-1; encontram-se próximos ou abaixo daqueles obtidos para o Estado de São Paulo e para solos brasileiros, de modo geral.

Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits.

Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5×10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.

Roadway Lighting and Safety: Phase II – Monitoring Quality, Durability and Efficiency, November 2011

This Phase II project follows a previous project titled Strategies to Address Nighttime Crashes at Rural, Unsignalized Intersections. Based on the results of the previous study, the Iowa Highway Research Board (IHRB) indicated interest in pursuing further research to address the quality of lighting, rather than just the presence of light, with respect to safety. The research team supplemented the literature review from the previous study, specifically addressing lighting level in terms of measurement, the relationship between light levels and safety, and lamp durability and efficiency. The Center for Transportation Research and Education (CTRE) teamed with a national research leader in roadway lighting, Virginia Tech Transportation Institute (VTTI) to collect the data. An integral instrument to the data collection efforts was the creation of the Roadway Monitoring System (RMS). The RMS allowed the research team to collect lighting data and approach information for each rural intersection identified in the previous phase. After data cleanup, the final data set contained illuminance data for 101 lighted intersections (of 137 lighted intersections in the first study). Data analysis included a robust statistical analysis based on Bayesian techniques. Average illuminance, average glare, and average uniformity ratio values were used to classify quality of lighting at the intersections.

Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer.

BACKGROUND: A 70-gene signature was previously shown to have prognostic value in patients with node-negative breast cancer. Our goal was to validate the signature in an independent group of patients. METHODS: Patients (n = 307, with 137 events after a median follow-up of 13.6 years) from five European centers were divided into high- and low-risk groups based on the gene signature classification and on clinical risk classifications. Patients were assigned to the gene signature low-risk group if their 5-year distant metastasis-free survival probability as estimated by the gene signature was greater than 90%. Patients were assigned to the clinicopathologic low-risk group if their 10-year survival probability, as estimated by Adjuvant! software, was greater than 88% (for estrogen receptor [ER]-positive patients) or 92% (for ER-negative patients). Hazard ratios (HRs) were estimated to compare time to distant metastases, disease-free survival, and overall survival in high- versus low-risk groups. RESULTS: The 70-gene signature outperformed the clinicopathologic risk assessment in predicting all endpoints. For time to distant metastases, the gene signature yielded HR = 2.32 (95% confidence interval [CI] = 1.35 to 4.00) without adjustment for clinical risk and hazard ratios ranging from 2.13 to 2.15 after adjustment for various estimates of clinical risk; clinicopathologic risk using Adjuvant! software yielded an unadjusted HR = 1.68 (95% CI = 0.92 to 3.07). For overall survival, the gene signature yielded an unadjusted HR = 2.79 (95% CI = 1.60 to 4.87) and adjusted hazard ratios ranging from 2.63 to 2.89; clinicopathologic risk yielded an unadjusted HR = 1.67 (95% CI = 0.93 to 2.98). For patients in the gene signature high-risk group, 10-year overall survival was 0.69 for patients in both the low- and high-clinical risk groups; for patients in the gene signature low-risk group, the 10-year survival rates were 0.88 and 0.89, respectively. CONCLUSIONS: The 70-gene signature adds independent prognostic information to clinicopathologic risk assessment for patients with early breast cancer.

Anthropogenic radionuclides in atmospheric air over Switzerland during the last few decades.

The atmospheric nuclear testing in the 1950s and early 1960s and the burn-up of the SNAP-9A satellite led to large injections of radionuclides into the stratosphere. It is generally accepted that current levels of plutonium and caesium radionuclides in the stratosphere are negligible. Here we show that those radionuclides are present in the stratosphere at higher levels than in the troposphere. The lower content in the troposphere reveals that dry and wet deposition efficiently removes radionuclides within a period of a few weeks to months. Since the stratosphere is thermally stratified and separated from the troposphere by the tropopause, radioactive aerosols remain longer. We estimate a mean residence time for plutonium and caesium radionuclides in the stratosphere of 2.5-5 years. Our results also reveal that strong volcanic eruptions like Eyjafjallajökull in 2010 have an important role in redistributing anthropogenic radionuclides from the stratosphere to the troposphere.

Análise de sensibilidade dos parâmetros do modelo SWAT e simulação dos processos hidrossedimentológicos em uma bacia no agreste nordestino

O processo erosivo constitui-se na principal causa de degradação dos solos e é acelerado por intervenções humanas nas bacias hidrográficas, resultando em prejuízos ao setor agrícola e ao meio ambiente. Para a previsão dos impactos de ações antrópicas ou de mudanças climáticas sobre os processos hidrossedimentológicos, os modelos distribuídos e de base física têm sido bastante eficazes. Neste estudo, aplicou-se o modelo SWAT à sub-bacia do Rio Japaratuba Mirim, em Sergipe, nas seções de medição das estações Fazenda Pão de Açúcar (PA) e Fazenda Cajueiro (CJ), com áreas de contribuição respectivamente de 137,3 e 277,8 km², visando à parametrização das duas bacias aninhadas por meio dos processos de calibração e de validação. Foram realizadas simulações do escoamento na bacia menor (PA), a partir dos parâmetros calibrados na bacia maior (CJ), e, reciprocamente, do escoamento na bacia maior (CJ). Em seguida, foram também realizadas simulações do escoamento e da produção de sedimentos para o período de dados de vazão disponíveis (1985 a 2000), para a seção CJ. Os resultados evidenciaram que o modelo calibrado simulou bem o escoamento superficial e conseguiu prever, de forma coerente, a produção de sedimentos com base nos 12 parâmetros mais sensíveis do modelo. A transposição dos parâmetros da bacia maior para a menor e, vice-versa, resultou em índices de Eficiência de Nash-Sutcliffe (NSE) e de Tendência Percentual (PBIAS), considerados satisfatórios para o primeiro caso e insatisfatório para o segundo.

Sleep deprivation (SD) on focal brain ischemia in the rat : effects of different SD protocols

Sleep-wake disturbances are frequently observed in stroke patients and are associated with poorer functional outcome. Until now the effects of sleep on stroke evolution are unknown. The purpose of the present study was to evaluate the effects of three sleep deprivation (SD) protocols on brain damages after focal cerebral ischemia in a rat model. Permanent occlusion of distal branches of the middle cerebral artery was induced in adult rats. The animals were then subjected to 6h SD, 12h SD or sleep disturbances (SDis) in which 3 x 12h sleep deprivation were performed by gentle handling. Infarct size and brain swelling were assessed by Cresyl violet staining, and the number of damaged cells was measured by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining. Behavioral tests, namely tape removal and cylinder tests, were performed for assessing sensorimotor function. In the 6h SD protocol, no significant difference (P > 0.05) was found either in infarct size (42.5 ± 30.4 mm3 in sleep deprived animals vs. 44.5 ± 20.5 mm3 in controls, mean ± s.d.), in brain swelling (10.2 ± 3.8 % in sleep deprived animals vs. 11.3 ± 2.0 % in controls) or in number of TUNEL-positive cells (21.7 ± 2.0/mm2 in sleep deprived animals vs. 23.0 ± 1.1/mm2 in controls). In contrast, 12h sleep deprivation increased infarct size by 40 % (82.8 ± 10.9 mm3 in SD group vs. 59.2 ± 13.9 mm3 in control group, P = 0.008) and number of TUNEL-positive cells by 137 % (46.8 ± 15/mm in SD group vs. 19.7 ± 7.7/mm2 in control group, P = 0.003). There was no significant difference (P > 0.05) in brain swelling (12.9 ± 6.3 % in sleep deprived animals vs. 11.6 ± 6.0 % in controls). The SDis protocol also increased infarct size by 76 % (3 x 12h SD 58.8 ± 20.4 mm3 vs. no SD 33.8 ± 6.3 mm3, P = 0.017) and number of TUNEL-positive cells by 219 % (32.9 ± 13.2/mm2 vs. 10.3 ± 2.5/mm2, P = 0.008). Brain swelling did not show any difference between the two groups (24.5 ± 8.4 % in SD group vs. 16.7 ± 8.9 % in control group, p > 0.05). Both behavioral tests did not show any concluding results. In summary, we demonstrate that sleep deprivation aggravates brain damages in a rat model of stroke. Further experiments are needed to unveil the mechanisms underlying these effects.