Genotype 3 is associated with accelerated fibrosis progression in chronic hepatitis C.

BACKGROUND/AIMS: While several risk factors for the histological progression of chronic hepatitis C have been identified, the contribution of HCV genotypes to liver fibrosis evolution remains controversial. The aim of this study was to assess independent predictors for fibrosis progression. METHODS: We identified 1189 patients from the Swiss Hepatitis C Cohort database with at least one biopsy prior to antiviral treatment and assessable date of infection. Stage-constant fibrosis progression rate was assessed using the ratio of fibrosis Metavir score to duration of infection. Stage-specific fibrosis progression rates were obtained using a Markov model. Risk factors were assessed by univariate and multivariate regression models. RESULTS: Independent risk factors for accelerated stage-constant fibrosis progression (>0.083 fibrosis units/year) included male sex (OR=1.60, [95% CI 1.21-2.12], P<0.001), age at infection (OR=1.08, [1.06-1.09], P<0.001), histological activity (OR=2.03, [1.54-2.68], P<0.001) and genotype 3 (OR=1.89, [1.37-2.61], P<0.001). Slower progression rates were observed in patients infected by blood transfusion (P=0.02) and invasive procedures or needle stick (P=0.03), compared to those infected by intravenous drug use. Maximum likelihood estimates (95% CI) of stage-specific progression rates (fibrosis units/year) for genotype 3 versus the other genotypes were: F0-->F1: 0.126 (0.106-0.145) versus 0.091 (0.083-0.100), F1-->F2: 0.099 (0.080-0.117) versus 0.065 (0.058-0.073), F2-->F3: 0.077 (0.058-0.096) versus 0.068 (0.057-0.080) and F3-->F4: 0.171 (0.106-0.236) versus 0.112 (0.083-0.142, overall P<0.001). CONCLUSIONS: This study shows a significant association of genotype 3 with accelerated fibrosis using both stage-constant and stage-specific estimates of fibrosis progression rates. This observation may have important consequences for the management of patients infected with this genotype.

Glucose and lactate are equally effective in energizing activity-dependent synaptic vesicle turnover in purified cortical neurons.

This study examines the role of glucose and lactate as energy substrates to sustain synaptic vesicle cycling. Synaptic vesicle turnover was assessed in a quantitative manner by fluorescence microscopy in primary cultures of mouse cortical neurons. An electrode-equipped perfusion chamber was used to stimulate cells both by electrical field and potassium depolarization during image acquisition. An image analysis procedure was elaborated to select in an unbiased manner synaptic boutons loaded with the fluorescent dye N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl)pyridinium dibromide (FM1-43). Whereas a minority of the sites fully released their dye content following electrical stimulation, others needed subsequent K(+) depolarization to achieve full release. This functional heterogeneity was not significantly altered by the nature of metabolic substrates. Repetitive stimulation sequences of FM1-43 uptake and release were then performed in the absence of any metabolic substrate and showed that the number of active sites dramatically decreased after the first cycle of loading/unloading. The presence of 1 mM glucose or lactate was sufficient to sustain synaptic vesicle cycling under these conditions. Moreover, both substrates were equivalent for recovery of function after a phase of decreased metabolic substrate availability. Thus, lactate appears to be equivalent to glucose for sustaining synaptic vesicle turnover in cultured cortical neurons during activity.

Node-negative T1-T2 anal cancer: radiotherapy alone or concomitant chemoradiotherapy?

PURPOSE: To evaluate the influence of concomitant chemotherapy on loco-regional control (LRC) and cancer-specific survival (CSS) in patients with T1-T2 N0 M0 anal cancer treated conservatively by primary radiotherapy (RT). MATERIALS AND METHODS: Between 1976 and 2008, 146 patients with T1 (n=29) or T2 (n=117) N0 M0 anal cancer were treated curatively by RT alone (n=71) or by combined chemoradiotherapy (CRT) (n=75) consisting of mitomycin C±5-fluorouracil. Univariate and multivariate analyses were performed to assess patient-, tumor- and treatment-related factors influencing LRC and CSS. RESULTS: With a median follow-up of 62.5 months (interquartilerange, 26-113 months), 122 (84%) patients were locally controlled. The five-year actuarial LRC, CSS and overall survival for the population were 81.4%±3.6%, 91.9%±2.6%, and 75.4%±3.9%, respectively. The five-year LRC and CSS for patients treated with RT alone and with CRT were 75.5%±6.0% vs. 86.8%±4.1% (p=0.155) and 88.5%±4.5% vs. 94.9%±2.9% (p=0.161), respectively. In the multivariate analysis, no clinical or therapeutic factors were found to significantly influence the LRC and CSS, while the addition of chemotherapy was of borderline significance (p=0.065 and p=0.107, respectively). CONCLUSIONS: In the management of node negative T1-T2 anal cancer, LRC and CSS tend to be superior in patients treated by combined CRT, even though the difference was not significant. Randomized studies are warranted to assess definitively the role of combined treatment in early-stage anal carcinoma.

Perdas de solo e água por erosão hídrica influenciadas por métodos de preparo, classes de declive e níveis de fertilidade do solo

A erosão é a forma mais prejudicial de degradação do solo. Além de reduzir sua capacidade produtiva para as culturas, ela pode causar sérios danos ambientais, como assoreamento e poluição das fontes de água. Contudo, usando adequados sistemas de manejo do solo e bem planejadas práticas conservacionistas de suporte, os problemas de erosão podem ser satisfatoriamente resolvidos. Com o propósito de obter informações quantitativas sobre o assunto, para servirem de guia nos planejamentos conservacionistas de uso da terra, realizou-se um experimento de erosão sob chuva natural, em Latossolo Vermelho distroférrico típico textura muito argilosa, no município de Santo Ângelo, região das Missões (RS), de dezembro de 1994 a maio de 1996, objetivando quantificar as perdas de solo e água causadas por erosão hídrica. Os tratamentos consistiram dos métodos de preparo do solo convencional, reduzido e semeadura direta, avaliados sob as condições "solo com fertilidade corrigida" nas classes de declividade de 0-0,04; 0,04-0,08 e 0,08-0,12 m m-1 (com gradientes médios de, respectivamente, 0,035; 0,065 e 0,095 m m-1) e "solo com fertilidade atual" na classe de declividade de 0,04-0,08 m m-1. As operações de preparo do solo e semeadura foram efetuadas todas transversalmente ao declive, exceto para o tratamento-testemunha (preparo convencional, sem cultivo, continuamente descoberto e sem crosta), no qual as operações de aração e gradagem foram realizadas no sentido do declive. A seqüência de culturas utilizada na avaliação da erosão foi constituída de dois ciclos culturais de soja (Glycine max, L.), no período de primavera-verão de 1994/95 e 1995/96, e um de aveia preta (Avena strigosa, S.), no período de outono-inverno de 1995. O índice de erosividade das chuvas (EI30) calculado no período experimental (1,5 ano) foi de 10.236 MJ mm ha-1 h-1 e concentrou-se, repetidamente, em 1995 e 1996, nos meses de janeiro a março, perfazendo, acumuladamente nestes duplos períodos, 70 % do total. Perdas significativas de solo por erosão hídrica (até 80 Mg ha-1 em um único ciclo cultural) ocorreram somente no preparo convencional sem cultivo e estabelecido no sentido do declive (testemunha), embora o solo na parcela tenha apresentado um valor de erodibilidade muito baixo (fator K igual a 0,0091 Mg ha h MJ-1 mm-1 ha-1 ). Sob cultivo, porém em valores bem mais baixos, as perdas de solo continuaram sendo as maiores no preparo convencional (ao redor de 13,0 Mg ha-1 em 1,5 ano), notadamente nas classes de declividade média e alta, ficando o preparo reduzido com as intermediárias (ao redor de 4,0 Mg ha-1 em 1,5 ano) e a semeadura direta com as menores (ao redor de 1,0 Mg ha-1 em 1,5 ano), enquanto as perdas de água foram todas muito baixas e pouco diferenciadas. A condição "solo com fertilidade corrigida" aumentou muito a quantidade de fitomassa aérea produzida pelas culturas e, conseqüentemente, a massa de resíduos culturais, a percentagem de cobertura morta do solo e as perdas de solo por erosão hídrica, especialmente no preparo convencional; contudo, ela praticamente não influenciou as perdas de água. Apesar das operações de preparo do solo e semeadura em contorno, fertilidade do solo melhorada e alta resistência do solo à erosão, o sistema de produção aveia preta-soja em preparo convencional apresentou, em declives superiores a 0,04 m m-1, perdas anuais de solo por erosão muito próximas ao limite tolerável, já no curto comprimento de rampa de 21 m utilizado nas parcelas experimentais deste estudo.

Dose de nitrogênio associada à produtividade de batata e índices do estado de nitrogênio na folha

O nitrogênio é um dos elementos de grande impacto na produtividade da batata, e seu efeito nas plantas pode ser avaliado por meio de técnicas de diagnóstico do estado nutricional. Este trabalho teve o objetivo de determinar a dose ótima econômica de N para a produção de tubérculos e estimar o nível crítico de índices do estado de N na folha de duas cultivares de batata. O experimento foi conduzido de maio a agosto de 2008, em delineamento em blocos ao acaso em esquema fatorial 4 x 2, sendo quatro doses de N (0, 100, 200 e 400 kg ha-1 de N, aplicadas em pré-plantio como ureia) e duas cultivares de batata (Ágata e Asterix), com quatro repetições. Aos 21 dias após a emergência foram determinadas a leitura SPAD e os teores de N e de clorofila na quarta folha a partir do ápice (QF). A produtividade de tubérculos comerciais aumentou até 45.065 e 46.500 kg ha-1 com o aumento da dose de N até 297 e 250 kg ha-1 para Ágata e Asterix, respectivamente. Para essas cultivares, a dose para obtenção da máxima eficiência econômica foi de 290 e 245 kg ha-1 de N, respectivamente. Nas duas cultivares, houve efeito positivo de doses de N sobre o índice SPAD e teores de N e de clorofila na QF. Os valores críticos foram de 40,5 e 43,7 para o índice SPAD, de 66,7 e 75,2 g kg-1 para o teor foliar de N e de 6,13 e 6,96 mg g-1 para o teor de clorofila total na matéria fresca das folhas, respectivamente, para Ágata e Asterix. Os valores da leitura do índice SPAD correlacionaram-se com os valores de clorofila total extraível na quarta folha e com a produção de tubérculos de batata, indicando a possibilidade de medir o valor SPAD aos 21 DAE para prognosticar a produtividade de tubérculos de batata.

Intervalo hídrico ótimo como indicador de melhoria da qualidade estrutural de latossolo degradado

As pastagens de gramíneas, quando bem formadas e manejadas, representam um componente ambiental importante em razão do papel que exercem na cobertura dos solos, na formação e estabilização dos agregados e na redução do adensamento ou da compactação. Os objetivos deste estudo foram quantificar o intervalo hídrico ótimo (IHO), para um Latossolo Vermelho-Amarelo degradado fisicamente e cultivado com Coastcross (Cynodon spp.), e utilizar o IHO como indicador de alteração da estrutura desse solo. Amostras indeformadas foram coletadas em anéis volumétricos de 0,025 m de altura e 0,065 m de diâmetro, nas profundidades de 0-0,05 e 0,20-0,25 m e no horizonte Bw (0,80-0,85 m), na ausência de tráfego de máquinas agrícolas, durante a estação chuvosa de 2008/2009, nos meses de novembro de 2008, março de 2009 e maio de 2009. Essas amostras foram utilizadas para determinar a curva de retenção de água, a curva de resistência à penetração, a densidade, o IHO e a densidade crítica do solo (Dsc). O IHO revelou-se um adequado indicador da alteração da estrutura de Latossolo. O Coastcross apresenta potencial para melhoria da estrutura, sendo sugerida sua utilização como alternativa ao uso de implementos agrícolas nesse contexto. A Dsc de 1,24 Mg m-3 é limitante ao adequado crescimento e desenvolvimento da forrageira no solo em estudo.

Sugarcane trash management assessed by the interaction of yield with soil properties

Currently, sugarcane plays an important global role, particularly with a view to alternative energy sources. Thus, in a sugarcane field of the mill Vale do Paraná S/A Álcool e Açúcar, Rubineia, São Paulo State, managed under two green cane harvest systems (cane trash left on and cane trash removed from the soil), Pearson and spatial correlations between the sugarcane yield (variety RB855035 in the third cut) and soil physical and chemical properties were studied to identify the property best correlated with stalk yield and the best harvest method. For this purpose, two geostatistical grids (121 sampling points on 1.30 ha) were installed on a eutrophic Red Argisol (homogeneous slope of 0.065 m m-1), in 2011, to determine the properties: stalk yield and sugarcane plant population, and soil resistance to penetration, gravimetric moisture, bulk density, and carbon stock, in the layers 0-0.20 and 0.20-0.40 m. The data were analyzed by descriptive, linear correlation and geostatistical analysis. In both treatments, the property stand density was best correlated with sugarcane yield (r = 0.725 in the trash mulching treatment - TM and r = 0.769 in the trash removal treatment - TR). However, in relation to the soil properties, bulk density (0-0.20 m) was best correlated (r = 0.305 in TM, r = 0.211 in TR). Similarly, from the spatial point of view, stand density was the property that best explained the sugarcane yield. However, in the TM treatment the density (0.20-0.40 m) was the only soil property spatially correlated with stalk yield. The carbon stock in the soil of the TM was 11.5 % higher than in the TR treatment. Results of the TM treatment were best, also with regard to soil management and conservation.

Special Sentence Revocations High, Data Download, Iowa Department of Corrections, May 2010

In addition to their original sentence, persons convicted of sexual abuse, incest or sexual exploitation of a minor also receive a “special sentence” of ten years, or in some cases, life. In its prison population forecast, the Iowa Division of Criminal and Juvenile Justice Planning noted “an unexpectedly high rate of revocation among those released to the special sentence, particularly given past research that has shown Iowa sex offenders having very low rates of re-arrest and/or return to prison.”

Comparaison des performances des systèmes CR à aiguilles et à poudre en mammographie.

Objectifs: Comparaison des performances en qualité d'image des deux types de systèmes CR. Matériels et méthodes: Les performances ont été mesurées au moyen de la fonction de transfert de modulation (FTM), du spectre de bruit, de l'efficacité quantique de détection (DQE),le seuil de détection du contraste en épaisseur d'or et la dose glandulaire moyenne. Les systèmes CR à aiguilles Agfa HM5.0 et Carestream SNP-M1 ont étécomparés aux systèmes à poudre Agfa MM3.0, Fuji ProfectCS et Carestream EHR-M3. Résultats: La FTM à 5mm-1 de Agfa HM5,0 et Carestream SNP-M1 est 0,21 et 0,27, et entre 0,14 et 0,16 pour les systèmes à poudre. Un DQE maximal de 0,51 et 0,5 a étéobtenu pour Agfa HM5,0 et Carestream SNP-M1, et 0,35, 0,50 et 0,34 pour Agfa MM3,0, Fuji Profect et Carestream EHR-M3. Des valeurs de DQE à 5mm-1 de0,18 et 0,13 ont été obtenues pour Agfa HM5,0 et Carestream SNP-M1, et entre 0,04 et 0,065 pour les systèmes à poudre. Les seuils de détection du contrastede Agfa HM5,0 et Carestream SNP-M1 étaient 1,33im et 1,29im, et 1,45im et 1,63im pour Agfa MM3,0 et Fuji Profect. Conclusion: Les systèmes à aiguilles offrent des meilleures FTM et DQE et un seuil de visibilité du contraste plus bas que les systèmes à poudre .

Temporal variation of the biomass and structure of Caulerpa prolifera (Forsskal) Lamouroux meadows in the Mar Menor lagoon (SE Spain).

The temporal changes in the structure, biomass and C, N and P content of meadows of Caulerpa prolifera (Forsskal) Lamouroux in the Mar Menor coastal lagoon (SE Spain) are described over the period from November 1986 to March 1989. C. prolifera meadows showed a unimodal pattern of vegetative development with maximum biomass values (168-173 g d.w. m-2) reached in summer and maintained during autumn, and minimum biomass values (0-57 g d.w. m-2) during late winter and early spring. Leaf area index values changed between 0.37-0.40 m2 m-2 in January-February and 2.60-7.06 m2 m-2 in July. The seasonality in the biomass and structure of the meadow was mainly related to the vegetative development of the secondary fronds. Carbon and phosphorus content of the thallus (32.5-34.8% d.w. and 0.065-0.069% d.w., respectively) had no seasonality, but nitrogen content showed a bimodal annual pattern with higher values in spring and fall (>2.5% d.w.) than in summer and winter (<2.5% d.w.).

Comparação de modelos não-lineares para descrever o crescimento de fêmeas da raça Guzerá

Dados de crescimento e reprodução de 573 vacas da raça Guzerá, nascidas entre 1961 e 1985, na Fazenda Canoas, em Curvelo, MG, foram analisados com o objetivo de estabelecer um padrão médio de crescimento, mediante o uso de um modelo matemático que se ajuste adequadamente aos dados. Os modelos Brody, Bertalanffy, Logístico, Gompertz e Richards foram ajustados aos dados de peso/idade, coletados até 1992, e comparados quanto à qualidade de ajustamento. Os pesos assintóticos e as taxas de maturidade estimadas foram, respectivamente: para o modelo Brody, 464,49 e 0,046; para o Bertalanffy, 453,18 e 0,065; para o Logístico, 447,05 e 0,085; para o Gompertz, 449,89 e 0,075, e para o Richards, 458,26 e 0,055. O modelo Richards apresentou dificuldades computacionais para ajustamento aos dados. Os outros modelos se revelaram adequados para descrever o crescimento nesses animais, apresentando pequenas variações na qualidade de ajustamento, de acordo com os critérios utilizados. O modelo Bertalanffy foi escolhido para representar a curva média de crescimento dos animais, por apresentar um ajustamento superior no conjunto dos critérios.

High precision anatomy for MEG.

Precise MEG estimates of neuronal current flow are undermined by uncertain knowledge of the head location with respect to the MEG sensors. This is either due to head movements within the scanning session or systematic errors in co-registration to anatomy. Here we show how such errors can be minimized using subject-specific head-casts produced using 3D printing technology. The casts fit the scalp of the subject internally and the inside of the MEG dewar externally, reducing within session and between session head movements. Systematic errors in matching to MRI coordinate system are also reduced through the use of MRI-visible fiducial markers placed on the same cast. Bootstrap estimates of absolute co-registration error were of the order of 1mm. Estimates of relative co-registration error were <1.5mm between sessions. We corroborated these scalp based estimates by looking at the MEG data recorded over a 6month period. We found that the between session sensor variability of the subject's evoked response was of the order of the within session noise, showing no appreciable noise due to between-session movement. Simulations suggest that the between-session sensor level amplitude SNR improved by a factor of 5 over conventional strategies. We show that at this level of coregistration accuracy there is strong evidence for anatomical models based on the individual rather than canonical anatomy; but that this advantage disappears for errors of greater than 5mm. This work paves the way for source reconstruction methods which can exploit very high SNR signals and accurate anatomical models; and also significantly increases the sensitivity of longitudinal studies with MEG.

Contribution of electrostatic interactions, compactness and quaternary structure to protein thermostability: lessons from structural genomics of Thermotoga maritima.

Studies of the structural basis of protein thermostability have produced a confusing picture. Small sets of proteins have been analyzed from a variety of thermophilic species, suggesting different structural features as responsible for protein thermostability. Taking advantage of the recent advances in structural genomics, we have compiled a relatively large protein structure dataset, which was constructed very carefully and selectively; that is, the dataset contains only experimentally determined structures of proteins from one specific organism, the hyperthermophilic bacterium Thermotoga maritima, and those of close homologs from mesophilic bacteria. In contrast to the conclusions of previous studies, our analyses show that oligomerization order, hydrogen bonds, and secondary structure play minor roles in adaptation to hyperthermophily in bacteria. On the other hand, the data exhibit very significant increases in the density of salt-bridges and in compactness for proteins from T.maritima. The latter effect can be measured by contact order or solvent accessibility, and network analysis shows a specific increase in highly connected residues in this thermophile. These features account for changes in 96% of the protein pairs studied. Our results provide a clear picture of protein thermostability in one species, and a framework for future studies of thermal adaptation.