A phase II study of irinotecan alternated with five days bolus of 5-fluorouracil and leucovorin in first-line chemotherapy of metastatic colorectal cancer

PURPOSE: This multicenter phase II study was designed to assess the efficacy of the alternating schedule of irinotecan (CPT-11) with bolus 5-fluorouracil (5-FU) and leucovorin (LV) in first-line chemotherapy for metastatic colorectal cancer (CRC). PATIENTS AND METHODS: Patients with histologically proven metastatic colorectal cancer, and at least one bidimensionally measurable lesion, aged 18-70, with performance status < or = 2, normal baseline biological values and no prior chemotherapy (or only adjuvant chemotherapy completed > or = 6 months before study entry) were selected. Treatment was irinotecan 350 mg/m2, i.v., day 1, alternating with leucovorin 20 mg/m2 i.v. and 5-FU 425 mg/m2, i.v. daily for five consecutive days, day 22-26 (Mayo Clinic regimen). One alternating cycle was to be performed every six weeks. Patients were evaluated for efficacy every alternating cycle. Treatment was administered until five alternating cycles, disease progression, unacceptable toxicity or patient refusal. RESULTS: Thirty-three patients (28 chemotherapy-na?ve and five with prior adjuvant treatment completed > 1 year prior to accrual) were enrolled. The objective response rate (RR) was 30% (95% CI: 16-49; 10 patients/33; nine partial response and one complete response). All responses were reviewed by an independent external review committee. An additional 49% of patients had stable disease. The median survival was 16 months, the one year survival amounted to 58% and the median progression free survival was 7.2 months. Relative dose intensity was nearly 90% for both drugs. Grade 3-4 diarrhea and neutropenia were the most frequent severe toxic events, seen in 24% and 64% of patients, respectively. CONCLUSIONS: The alternating schedule of CPT-11 350 mg/m2 with five days bolus of 5-FU and low dose LV is an active and feasible regimen as front-line therapy for metastatic CRC. It is well tolerated, without evidence of overlapping toxicity. The response rate appears promising with regard to that expected with either single agent. This regimen warrants further assessment in randomized trials.     

Upregulation of xanthine oxidase by lipopolysaccharide, interleukin-1, and hypoxia. Role in acute lung injury

LPS and selected cytokines upregulate xanthine dehydrogenase/xanthine oxidase (XDH/XO) in cellular systems. However, the effect of these factors on in vivo XDH/XO expression, and their contribution to lung injury, are poorly understood. Rats were exposed to normoxia or hypoxia for 24 h after treatment with LPS (1 mg/kg) and IL-1beta (100 microg/kg) or sterile saline. Lungs were then harvested for measurement of XDH/XO enzymatic activity and gene expression, and pulmonary edema was assessed by measurement of the wet/dry lung weight ratio (W/D). Although treatment with LPS + IL-1beta or hypoxia independently produced a 2-fold elevation (p < 0. 05 versus exposure to normoxia and treatment with saline) in lung XDH/XO activity and mRNA, the combination of LPS + IL-1beta and hypoxia caused a 4- and 3.5-fold increase in these values, respectively. XDH/XO protein expression was increased 2-fold by hypoxia alone and 1.3-fold by treatment with LPS + IL-1beta alone or combination treatment. Compared with normoxic lungs, W/D was significantly increased by exposure to hypoxia, LPS + IL-1beta, or combination treatment. This increase was prevented by treatment of the animals with tungsten, which abrogated lung XDH/XO activity. In conclusion, LPS, IL-1beta, and hypoxia significantly upregulate lung XDH/XO expression in vivo. The present data support a role for this enzyme in the pathogenesis of acute lung injury.     

The GDPAL region of the pre-S1 envelope protein is important for morphogenesis of woodchuck hepatitis virus

The pre-S envelope protein of duck hepatitis B virus (DHBV) contains a region, Asp-Asp-Pro-Leu-Leu (DDPLL), that is specifically required for virus assembly and secretion (Lenhoff and Summers, J Virol 1994;68:4565-4571). We found that amino acids 201 to 205 of the pre-S envelope protein of woodchuck hepatitis virus (WHV) form a conserved amino acid cluster, Gly-Asp-Pro-Ala-Leu (GDPAL), which resembles the DDPLL sequence of DHBV. To determine whether the GDPAL region was functionally equivalent to the DDPLL region, we deleted this region from the pre-S protein of WHV or mutated individual amino acids within the region. The mutant DNA was transfected into human hepatoma cell line Huh7, and the medium was assayed for virion production by immunoprecipitation and Southern blot analysis. We found that an in-frame deletion of this small region inhibited virion formation, suggesting that the GDPAL region of the pre-S envelope protein was required for virus assembly and/or secretion of WHV. Individual replacement of alanine 204, leucine 205, or serine 206 with other amino acid residues did not affect virus production. However, substitution of either aspartic acid 202 with valine or proline 203 with leucine dramatically inhibited WHV production. Furthermore, the GDPAL mutants were individually tested for their abilities to complement a pre-S1 defective genome. The results showed that the GDPAL region functioned as part of the pre-S1 protein but was not required to function as part of the pre-S2 protein.     

Modélisation et simulation du séchage en continu des couches minces par rayonnement infrarouge

Basé sur des concepts de transferts simultanés de masse et d'énergie, un modèle différentiel est posé pour le séchage en continu des couches minces par rayonnement infrarouge. Des essais conduits sur le séchage d'une nappe de coton non-mercerisé dans un séchoir semi-industriel d'une capacité maximale de 20 kW ont servi à la calibration du modèle. Les simulations, par intégration numérique des bilans de masse et d'énergie, fournissent les conditions à la sortie du séchoir: température de l'air, température du tissu et degré d'humidité résiduelle dans la nappe. Une étude de sensibilité indique que la température des émetteurs infrarouges est le paramètre qui influence le plus significativement le séchage. Les résultats montrent également que l'air alimenté sert presqu'uniquement à évacuer la vapeur produite, le transfert de chaleur par convection étant faible par rapport au rayonnement.     

Parenting knowledge: Experiential and sociodemographic factors in European American mothers of young children.

Knowledge of child rearing and child development is relevant to parenting and the well-being of children. Using a sociodemographically heterogeneous sample of 268 European American mothers of 2-year-olds, we assessed the state of mothers' parenting knowledge; compared parenting knowledge in groups of mothers who varied in terms of parenthood and social status; and identified principal sources of mothers' parenting knowledge in terms of social factors, parenting supports, and formal classes. On the whole, European American mothers demonstrated fair but less than complete basic parenting knowledge; age, education, and rated helpfulness of written materials each uniquely contributed to mothers' knowledge. Adult mothers scored higher than adolescent mothers, and mothers improved in their knowledge of parenting from their first to their second child (and were stable across time). No differences were found between mothers of girls and boys, mothers who varied in employment status, or birth and adoptive mothers. The implications of variation in parenting knowledge and its sources for parenting education and clinical interactions with parents are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sleep spindles and learning potential.

The number of sleep spindles remains relatively stable within individuals from night to night. However, there is little explanation for the large interindividual differences in spindles. The authors investigated the relationship between spindles and intelligence quotient (IQ) in 3 separate studies. The number of spindles and sigma power were positively correlated with performance IQ (PIQ), but not verbal IQ (VIQ). The perceptual/analytical skills measured by the PIQ Picture Completion subscale accounted for most of the interindividual differences in spindles. Furthermore, there was a relationship between the rapid eye movements (REMs) of REM sleep and VIQ in individuals with higher IQ scores. A similar pattern was observed between spindles and PIQ. It was hypothesized that high-IQ individuals have more spindles that can support more complex cortical networks underlying perceptual/analytical abilities. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An exploration strategy for non-stationary opponents

The success or failure of any learning algorithm is partially due to the exploration strategy it exerts. However, most exploration strategies assume that the environment is stationary and non-strategic. In this work we shed light on how to design exploration strategies in non-stationary and adversarial environments. Our proposed adversarial drift exploration (DE) is able to efficiently explore the state space while keeping track of regions of the environment that have changed. This proposed exploration is general enough to be applied in single agent non-stationary environments as well as in multiagent settings where the opponent changes its strategy in time. We use a two agent strategic interaction setting to test this new type of exploration, where the opponent switches between different behavioral patterns to emulate a non-deterministic, stochastic and adversarial environment. The agent’s objective is to learn a model of the opponent’s strategy to act optimally. Our contribution is twofold. First, we present DE as a strategy for switch detection. Second, we propose a new algorithm called R-max# for learning and planning against non-stationary opponent. To handle such opponents, R-max# reasons and acts in terms of two objectives: (1) to maximize utilities in the short term while learning and (2) eventually explore opponent behavioral changes. We provide theoretical results showing that R-max# is guaranteed to detect the opponent’s switch and learn a new model in terms of finite sample complexity. R-max# makes efficient use of exploration experiences, which results in rapid adaptation and efficient DE, to deal with the non-stationary nature of the opponent. We show experimentally how using DE outperforms the state of the art algorithms that were explicitly designed for modeling opponents (in terms average rewards) in two complimentary domains.     

Comparative study of antigen retrieval heating methods: microwave, microwave and pressure cooker, autoclave, and steamer

We present a study comparing the most popular heating methods currently used for antigen retrieval (AR) immunostaining: the microwave oven, microwave with pressure cooker, autoclave, and steamer heating. A panel of 21 antibodies was tested on formalin fixed, paraffin embedded sections using these heating methods and Tris-HC1 buffer, pH 9.5, plus 5% urea as the AR solution. Three observers independently evaluated the intensity of AR immunostaining. All heating methods yielded good results for AR immunostaining. There were only minor differences among the heating methods for AR when the optimal concentration of primary antibody for normal immunostaining was used; however, background staining may occasionally be troublesome if antibodies are not retitrated and diluted further for use on tissues after AR. Significant differences were observed only after further dilution of the primary antibodies: the microwave pressure cooker, extended microwave heating (5 min x 4) and autoclave heating then showed a similar intensity of staining that was stronger than results obtained with the steamer (20 min) or regular microwave heating (5 min x 2). Extension of the steamer heating time, however, yielded equivalent results. This study indicates that different heating methods can yield similar intensities of AR immunostaining if the heating times are adjusted appropriately. It is noteworthy that, in general, the adjusted conditions for maximal retrieval differ from those most widely cited in the literature, or recommended by manufacturers. That several heating devices may provide similar results permits the use of different AR heating methods according to the equipment available. This study also is an early step in standardizing the AR immunostaining protocol by providing uniform conditions for "maximal retrieval" as a common end point for all laboratories.     

Parenting beliefs and behaviors in northern and southern groups of Italian mothers of young infants.

Similarities and differences in northern and southern Italian mothers' social and didactic parenting beliefs and behaviors, and relations between their beliefs and behaviors, are reported. Both groups of mothers reported that they engaged more in social than didactic interactions with their infants, whereas in actuality both groups engaged in didactic behaviors with their infants for longer periods of time than they engaged in social behaviors. In addition, northern mothers engaged in more social interactions with their infants than did southern mothers. No correlations between beliefs and behaviors emerged in either group. These data speak to issues of intracultural variation and cross-cultural similarities in family psychology and parenting, belief-behavior relations in parenting, and the importance of methodology (parental report or observation) in the study of parenting and family functioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

向生产价值的30nm光刻协合渐进

提出了对现代光刻设备性能数据和系统预先筹划和配置 ,并在此基础上讨论了对关键性能方面进一步开发的方法和模式 ,同时还讨论了关于这些模式性能的支持分析结果。