Modelling PK/QT relationships from Phase I dose‐escalation trials for drug combinations and developing quantitative risk assessments of clinically relevant QT prolongations

In current industry practice, it is difficult to assess QT effects at potential therapeutic doses based on Phase I dose‐escalation trials in oncology due to data scarcity, particularly in combinations trials. In this paper, we propose to use dose‐concentration and concentration‐QT models jointly to model the exposures and effects of multiple drugs in combination. The fitted models then can be used to make early predictions for QT prolongation to aid choosing recommended dose combinations for further investigation. The models consider potential correlation between concentrations of test drugs and potential drug–drug interactions at PK and QT levels. In addition, this approach allows for the assessment of the probability of QT prolongation exceeding given thresholds of clinical significance. The performance of this approach was examined via simulation under practical scenarios for dose‐escalation trials for a combination of two drugs. The simulation results show that invaluable information of QT effects at therapeutic dose combinations can be gained by the proposed approaches. Early detection of dose combinations with substantial QT prolongation is evaluated effectively through the CIs of the predicted peak QT prolongation at each dose combination. Furthermore, the probability of QT prolongation exceeding a certain threshold is also computed to support early detection of safety signals while accounting for uncertainty associated with data from Phase I studies. While the prediction of QT effects is sensitive to the dose escalation process, the sensitivity and limited sample size should be considered when providing support to the decision‐making process for further developing certain dose combinations. Copyright © 2016 John Wiley & Sons, Ltd.     

不同震级作用下的设备 结构动力相互作用体系地震反应分析

为研究是否考虑设备 结构动力相互作用在不同地震阶段的差别,对建筑结构中常见的设备 结构相互作用体系进行了小震、中震和大震阶段的地震时程反应分析。分析了不同震级作用下考虑相互作用后给结构与设备的地震反应带来的变化。结果表明：考虑设备 结构动力相互作用与不考虑相互作用相比,结构的地震反应有较明显的区别,设备的地震反应有很大的区别,处于完全失真的状态。大震阶段由于设备和结构均进入了弹塑性阶段,刚度等主要参数发生了变化,导致动力相互作用的影响降低。虽然设备质量占结构总地震质量的比例很小,但仍会对结构位移与内力造成较大的影响。     

Robust Smoothed Rank Estimation Methods for Accelerated Failure Time Model Allowing Clusters

Smoothed Gehan rank estimation methods are widely used in accelerated failure time (AFT) models with/without clusters. However, most methods are sensitive to outliers in the covariates. In order to solve this problem, we propose robust approaches based on the smoothed Gehan rank estimation methods for the AFT model, allowing for clusters by employing two different weight functions. Simulation studies show that the proposed methods outperform existing smoothed rank estimation methods regarding their biases and standard deviations when there are outliers in the covariates. The proposed methods are also applied to a real dataset from the “Major cardiovascular interventions” study.     

教育领域中的国家整合与地方性知识

本文主要讨论了教育领域中的国家整合与地方性知识之间的关系,并对中国民族教育的现状、问题和发展提出了自己的看法.滕星教授提出,民族教育应将国家整合的教育内容与民族地方性知识结合起来,使得民族教育更加切合实际,这有利于民族地区教育"普初"、"普九"目标的实现.     

论违约责任和侵权责任的竞合处理

违约责任与侵权责任是两种性质不同的民事责任,侵权责任保护的是固有利益,在合同签定、履行过程中可能有侵权性违约行为、违约性侵权行为发生,从而会产生违约责任和侵权责任竞合的情形。合理分析和处理违约责任和侵权责任竞合的不同情形,对最大限度地维护当事人的合法权益会起到积极作用。     

Parental Leave Policies and Second Births: A Comparison of Czechia and Slovakia

Population Research and Policy Review - The paper investigates the transition to second births in Czechia and Slovakia in the context of the development of parental leave policies since the...     

Life Satisfaction of Rural Migrant Workers in Urban China: The Roles of Community Service Participation and Identity Integration

Abstract

China is home to approximately 245 million rural-to-urban migrant workers. The influx of migrants into urban areas has posed various challenges for local social service systems. Recently, increasing number of community services have been developed to meet the growing service demands from the migrant population. However, whether increase in community service use results in improved wellbeing among migrant workers remains critically unexplored. As such, this study examines the role of community service use in migrant workers’ life satisfaction and the potential mediating effect of identity integration in Shenzhen, China. Bootstrapped models were adopted to examine relationship among variables. Drawing from a sample of 1,087 rural-to-urban migrant workers, we found that community service use is positively correlated with both identity integration and migrant workers’ life satisfaction. Moreover, identity integration served as a partial mediator between community service use and life satisfaction. The mediating effect of identity integration was found to increase with age. This study highlights that diverse services should be implemented to address divergent needs of migrants in different age groups. Community service can also serve as a vehicle to foster integration among migrant workers in host communities, especially for older age groups. Future studies may further investigate the relationships between community social capital, community social support, quality of community-based organization and frequency of service use so as to optimize the life satisfaction of migrant workers.     

The effect of paid maternity leave on low-income families' welfare use in the US

Despite the critical role that paid maternity leave can assume in the economic lives of low-income families, research to date has paid insufficient attention to whether paid maternity leave reduces welfare use for low-income families. Using the Current Population Survey (CPS) March Supplement 2007–2014 with the difference-in-difference (DiD) technique, this study finds a significant policy effect of paid maternity leave on reducing the probability of using Temporary Assistance for Needy Families (TANF), TANF benefit amounts and TANF participation length. This study confirms that paid maternity leave is likely to prevent low-income families from using welfare during job interruptions stemming from the birth of a child. Given that TANF is often associated with negative political and social connotations, paid maternity leave can be used as an important social policy to improve economic security as well as offer empowerment in overall social standing for low-income mothers. The discussion focuses on the implications of the findings in a broader context of American welfare states.     

制度创新的"亚"形态与可能路径--对我国股份合作制改革的一个历史判断

从宏观的角度看,由于社会经济发展的实质是技术或基本生产函数的不断创新,制度促进经济发展或阻碍经济发展的实质,也就是制度能否使社会的创造力充分释放出来,从而不断推动技术及基本生产函数的创新。制度的价值在于它能为经济活动提供一种稳定的长期服务,凭借它,人们可以对经济活动产生长期的预期。因此,人们选择一种制度并使其在历史过程中延续下去,必然意味着人们不断地对其做长期的利益投入并对其抱以长期的收益预期。     

教养方式对不同性别学前儿童羞怯的影响：基于模糊集定性比较分析（fsQCA）

为探讨父母教养方式对不同性别学前儿童羞怯的组合作用路径,研究采用模糊集定性比较分析（fsQCA）,考察了532名学前儿童的性别和教养方式四个维度（说理、随和、命令、言语攻击）共5个条件变量影响儿童羞怯的条件组态。结果发现：1）单个父母教养方式不是影响学前儿童羞怯的必要条件,教养方式以组态的方式影响学前儿童羞怯;2）影响“儿童羞怯”的三条组合路径分别是“女孩*非说理”、“女孩*命令*言语攻击”、“非说理*命令”;影响“非儿童羞怯”的三条组合路径分别是“男孩*非言语攻击”、“说理*非说理*随和”。