Blinded continuous monitoring in clinical trials with recurrent event endpoints

In studies with recurrent event endpoints, misspecified assumptions of event rates or dispersion can lead to underpowered trials or overexposure of patients. Specification of overdispersion is often a particular problem as it is usually not reported in clinical trial publications. Changing event rates over the years have been described for some diseases, adding to the uncertainty in planning. To mitigate the risks of inadequate sample sizes, internal pilot study designs have been proposed with a preference for blinded sample size reestimation procedures, as they generally do not affect the type I error rate and maintain trial integrity. Blinded sample size reestimation procedures are available for trials with recurrent events as endpoints. However, the variance in the reestimated sample size can be considerable in particular with early sample size reviews. Motivated by a randomized controlled trial in paediatric multiple sclerosis, a rare neurological condition in children, we apply the concept of blinded continuous monitoring of information, which is known to reduce the variance in the resulting sample size. Assuming negative binomial distributions for the counts of recurrent relapses, we derive information criteria and propose blinded continuous monitoring procedures. The operating characteristics of these are assessed in Monte Carlo trial simulations demonstrating favourable properties with regard to type I error rate, power, and stopping time, ie, sample size.     

Estimating household structure in ancient China by using historical data: a latent class analysis of partially missing patterns

Summary.  Social data often contain missing information. The problem is inevitably severe when analysing historical data. Conventionally, researchers analyse complete records only. Listwise deletion not only reduces the effective sample size but also may result in biased estimation, depending on the missingness mechanism. We analyse household types by using population registers from ancient China (618–907 AD) by comparing a simple classification, a latent class model of the complete data and a latent class model of the complete and partially missing data assuming four types of ignorable and non-ignorable missingness mechanisms. The findings show that either a frequency classification or a latent class analysis using the complete records only yielded biased estimates and incorrect conclusions in the presence of partially missing data of a non-ignorable mechanism. Although simply assuming ignorable or non-ignorable missing data produced consistently similarly higher estimates of the proportion of complex households, a specification of the relationship between the latent variable and the degree of missingness by a row effect uniform association model helped to capture the missingness mechanism better and improved the model fit.     

Quasi-maximum likelihood estimation and inference in dynamic models with time-varying covariances

We study the properties of the quasi-maximum likelihood estimator (QMLE) and related test statistics in dynamic models that jointly parameterize conditional means and conditional covariances, when a normal log-likelihood os maximized but the assumption of normality is violated. Because the score of the normal log-likelihood has the martingale difference property when the forst two conditional moments are correctly specified, the QMLE is generally Consistent and has a limiting normal destribution. We provide easily computable formulas for asymptotic standard errors that are valid under nonnormality. Further, we show how robust LM tests for the adequacy of the jointly parameterized mean and variance can be computed from simple auxiliary regressions. An appealing feature of these robyst inference procedures is that only first derivatives of the conditional mean and variance functions are needed. A monte Carlo study indicates that the asymptotic results carry over to finite samples. Estimation of several AR and AR-GARCH time series models reveals that in most sotuations the robust test statistics compare favorably to the two standard (nonrobust) formulations of the Wald and IM tests. Also, for the GARCH models and the sample sizes analyzed here, the bias in the QMLE appears to be relatively small. An empirical application to stock return volatility illustrates the potential imprtance of computing robust statistics in practice.     

语境对语义的作用探析

语境是语义学中一个重要的范畴。以丰富的例句从以下四个方面:使语言中的多义和歧义现象获得明确的单一性;影响语义的感情色彩;语义的语体色彩及填补或丰富语言本身的意义探讨了语境对语义的作用,旨在唤起读者学会在不同的语境中择取语义的自觉意识。     

Rural/Urban Differences in Child Growth and Survival in Bolivia

Abstract Using data from a national survey in Bolivia and from a regional sample of poor communities in two regions of Bolivia, we model the effects of community conditions, household characteristics, and social relations on child health as measured by child mortality and stunted growth. Based on national data, children in rural areas are twice as likely to die before the age of two than are children in large cities, and about one‐third of the children in rural areas are stunted. Including measures of community, household, and maternal characteristics accounts for at least two‐thirds of the urban/rural difference in child health. We conclude that expansion of health services, improvements in household and community sanitation, and socioeco‐nomic development are all needed to overcome the rural disadvantage in child health.     

连续时延神经网络的Hopf分岔现象研究

讨论了带连续时延神经网络的Hopf分岔现象。对于强核和弱核的情况,利用平均时延作为分岔参数,证明了模型经历了Hopf分岔过程。在带弱核的神经网络模型中,得到了分岔周期解稳定性准则。给出了一些数值例子,通过计算机仿真验证了所得结论的正确性。     

历史演义小说:中国小说家的一大发明

世界诸国均无历史演义小说这一品种 ,只有中国才有历史演义小说。中国的正史 ,历来就有神话、传说、虚构的成份 ,以史为本 ,并敷演其大义 ,达到以史为鉴 ,教育和娱乐民众的目的 ,于是乃有历史演义小说的出现 ,历史演义小说经历了衍变过程。中国历史演义小说 ,具有其鲜明艺术特点。     

谈古代散文的语言艺术

本文从长于说理、富于哲理 ;以简驭繁、言简意赅 ;清朴自然、情真意切 ;音韵和谐 ,语调铿锵四个方面探讨了古代散文的语言艺术     

高校图书馆阅览室藏书布局分析及问题研究

当今社会,科学技术的迅猛发展导致图书文献出版量急剧增长。知识更新的周期在明显缩短,读者对文献需求的程度在不断增长和提高,合理的藏书布局越显重要。通过对我馆阅览室藏书布局的分析,指出了阅览室在藏书布局上存在的问题以及对这些问题的4点建议。     

论理工科院校人文教育与科学教育的融合

从重理工、轻人文 ,重职业选择、轻素质教育到以文化素质为切入点的全面素质教育 ,这是改革开放以来教育思想的一次重大飞跃。今天我国的素质教育工作者正在热烈地讨论高等教育中人文教育与科学教育的融合 ,这是对文化素质教育认识上的又一次重大飞跃。以人文教育与科学教育的融合为切入点的全面素质教育有其历史的必然性 ,也符合在新时期全面贯彻国家教育方针的现实需要。但是 ,因为我国生产力水平较低 ,教育相对滞后 ,所以必须充分认识这种融合的长期性和艰巨性。在当前 ,努力探讨人文教育与科学教育融合的途径 ,消除人文教育与科学教育在历史上形成的壁垒观念 ,必将推动素质教育向纵深发展