An adaptive model switching approach for phase I dose‐finding trials

Model‐based phase I dose‐finding designs rely on a single model throughout the study for estimating the maximum tolerated dose (MTD). Thus, one major concern is about the choice of the most suitable model to be used. This is important because the dose allocation process and the MTD estimation depend on whether or not the model is reliable, or whether or not it gives a better fit to toxicity data. The aim of our work was to propose a method that would remove the need for a model choice prior to the trial onset and then allow it sequentially at each patient's inclusion. In this paper, we described model checking approach based on the posterior predictive check and model comparison approach based on the deviance information criterion, in order to identify a more reliable or better model during the course of a trial and to support clinical decision making. Further, we presented two model switching designs for a phase I cancer trial that were based on the aforementioned approaches, and performed a comparison between designs with or without model switching, through a simulation study. The results showed that the proposed designs had the advantage of decreasing certain risks, such as those of poor dose allocation and failure to find the MTD, which could occur if the model is misspecified. Copyright © 2013 John Wiley & Sons, Ltd.     

冷战遗留视角下的当代朝美关系跟踪分析

朝鲜半岛是冷战的焦点地区之一。两极格局瓦解后,冷战阴影在朝鲜半岛仍然挥之不去。两极格局瓦解后的朝鲜半岛冷战现象更多地具有不对称性和不平衡性,体现了美国东北亚外交的主导性。美国继续并强化在朝鲜半岛的冷战外交是美国东北亚战略利益的需要。当代关朝关系发展体现了冷战在亚洲结束的独特性。     

建国初期朝鲜文报语言词汇与社会变迁

通过对1949-1951年朝鲜文报语言词汇的Han Maru统计,从社会语言学角度探讨了朝鲜文报语言词汇与社会变迁的关联。以语种和应用领域分析了语言词汇与社会变迁的关联,并分别从政治、经济、文化教育、社会生活等四个领域统计出各领域前五位高频率词汇,通过对这些高频词汇的分析,探讨了新中国成立初期政治、经济、文化及朝鲜族社会的一系列急剧变化。     

扩散与聚合：基督教在我国朝鲜族中的发展历程

基督教传入我国朝鲜族聚居地区已近150年,期间经历了两个不同的发展阶段。基督教在朝鲜族社会早期形成了一种以传教士为中心的小群体扩散性传播发展,部分朝鲜族民众与传教士的日常生活交往形成了对外来宗教的尝试性体验、简单仪式参与及所属基督徒群体自身的身份认同。此后随着众多小群体的发展,更多政治权力涉入逐渐发展起来的基督教教会组织中,基督教在朝鲜族地方性社会进入了以教会组织为依托的聚合性发展阶段。此阶段伴随政治权力的涉入,先后经历了委身发展及非自觉发展阶段到至今已显现出理性化信仰的发展趋势。     

朝核危机析论

20世纪90年代朝核危机爆发以来,各方围绕朝鲜核政治的博弈动机一直扑朔迷离。笔者认为,朝鲜追求和发展核武器的动因是复杂多重的,朝鲜核政治的本质乃是各方现实利益的杯葛和较量。以解决朝核问题为主旨的六方会谈,由于其本身的功能缺陷及受到诸多因素掣肘,在实现朝鲜弃核和半岛重归和平方面还有很长路程要走。     

Some Problems in Determining Risks from Cancer

Age-adjusted cancer mortality data (1964) were examined for evidence of independence. Indications were found that substitution of one cancer for another is a common occurrence. The data were interpreted as supportive of the view that natural selection for resistance to cancer in general has occurred with many resistance-related genes common to prevention of cancer of several sites. Consequently, the comparison of age-adjusted incidence or mortality rates of cancer of single sites alone does not provide a satisfactory estimate of the magnitude of an "environmentally induced" cancer risk. It is necessary to examine all causes of death to find indications of a real life-shortening episode.     

Comparison of cancer slope factors using different statistical approaches.

The U.S. Environmental Protection Agency's cancer guidelines ( USEPA, 2005 ) present the default approach for the cancer slope factor (denoted here as s*) as the slope of the linear extrapolation to the origin, generally drawn from the 95% lower confidence limit on dose at the lowest prescribed risk level supported by the data. In the past, the cancer slope factor has been calculated as the upper 95% confidence limit on the coefficient (q*₁) of the linear term of the multistage model for the extra cancer risk over background. To what extent do the two approaches differ in practice? We addressed this issue by calculating s* and q*₁ for 102 data sets for 60 carcinogens using the constrained multistage model to fit the dose‐response data. We also examined how frequently the fitted dose‐response curves departed appreciably from linearity at low dose by comparing q₁, the coefficient of the linear term in the multistage polynomial, with a slope factor, s_c, derived from a point of departure based on the maximum liklihood estimate of the dose‐response. Another question we addressed is the extent to which s* exceeded s_c for various levels of extra risk. For the vast majority of chemicals, the prescribed default EPA methodology for the cancer slope factor provides values very similar to that obtained with the traditionally estimated q*₁. At 10% extra risk, q*₁/s* is greater than 0.3 for all except one data set; for 82% of the data sets, q*₁ is within 0.9 to 1.1 of s*. At the 10% response level, the interquartile range of the ratio, s*/s_c, is 1.4 to 2.0.     

朝鲜义勇队与中国抗日战争

朝鲜义勇队是活跃在中国战场上朝鲜众多抗日力量中最突出的一支 ,它不仅是朝鲜民族解放运动的先锋队 ,而且是中国战场上的国际纵队。在 1937年到 194 5年间 ,它从成立到合并到分化 ,与中国人民并肩作战 ,为中国抗日战争的胜利作出了杰出的贡献。     

Physical injury risks associated with drinking water arsenic treatment.

We estimated the number of transportation deaths that would be associated with water treatment in Albuquerque to meet the EPA's recently proposed revisions of the Maximum Contaminant Level (MCL) for arsenic. Vehicle mileage was estimated for ion exchange, activated alumina, and iron coagulation/microfiltration water treatment processes to meet an MCL of 0.020 mg/L, 0.010 mg/L, 0.005 mg/L, and 0.003 mg/L. Local crash, injury, and death rates per million vehicle miles were used to estimate the number of injuries and deaths. Depending on the water treatment options chosen, we estimate that meeting an arsenic MCL of 0.005 mg/L will result in 143 to 237 crashes, 58 to 98 injuries, and 0.6 to 2.6 deaths in Albuquerque over a 70-year period, resulting in 26 to 113 years of life lost. The anticipated health benefits for Albuquerque residents from a 0.005 mg/L arsenic MCL, estimated using either a multistage Weibull or Poisson model, ranged from 3 to 80 arsenic-related bladder and lung cancer deaths prevented over a 70-year period, adding between 43 and 1,123 years of life. Whether a revised arsenic MCL increases or reduces overall loss of life in Albuquerque depends on the accuracy of EPA's cancer risk assessment. If the multistage Weibull model accurately estimates the benefits, the years of life added is comparable or lower than the anticipated years lost due to transportation associated with the delivery of chemicals, disposal of treatment waste, and operation of the water treatment system. Coagulation/microfiltration treatment will result in substantially fewer transportation deaths than either ion exchange or activated alumina.     

Cell Proliferation and Formaldehyde-Induced Respiratory Carcinogenesis

Formaldehyde is a nasal carcinogen in the rat but the cancer risk this chemical poses for humans remains to be determined. Formaldehyde induces nonlinear, concentration-dependent increases in nasal epithelial cell proliferation and DNA-protein cross-link formation following short-term exposure. Presented in this review are results from a mechanistically based formaldehyde inhalation study in which an important endpoint was the measurement of cell proliferation indices in target sites for nasal tumor induction. Male Fischer 344 rats were exposed to 0, 0.7, 2, 6, 10, or 15 ppm formaldehyde for up to 2 years (6 hr/day, 5 day/week). Statistically significant increases in cell proliferation were confined to the 10 and 15 ppm groups, which remained elevated throughout the study. The concentration-dependent increases in cell proliferation correlated strongly with the tumor response curve, supporting the proposal that sustained increases in cell proliferation are an important component of formaldehyde carcinogenesis. The nonlinearity observed in formaldehyde-induced rodent nasal cancer is consistent with a high-concentration effect of regenerative cell proliferation of the target organ coupled with the genotoxic effects of formaldehyde. Cell kinetic data from these studies provide important information that may be utilized in the assessment of risk for humans exposed to formaldehyde.