Enabling robust assessment of QTc prolongation in early phase clinical trials

Since the implementation of the International Conference on Harmonization (ICH) E14 guideline in 2005, regulators have required a “thorough QTc” (TQT) study for evaluating the effects of investigational drugs on delayed cardiac repolarization as manifested by a prolonged QTc interval. However, TQT studies have increasingly been viewed unfavorably because of their low cost effectiveness. Several researchers have noted that a robust drug concentration‐QTc (conc‐QTc) modeling assessment in early phase development should, in most cases, obviate the need for a subsequent TQT study. In December 2015, ICH released an “E14 Q&As (R3)” document supporting the use of conc‐QTc modeling for regulatory decisions. In this article, we propose a simple improvement of two popular conc‐QTc assessment methods for typical first‐in‐human crossover‐like single ascending dose clinical pharmacology trials. The improvement is achieved, in part, by leveraging routinely encountered (and expected) intrasubject correlation patterns encountered in such trials. A real example involving a single ascending dose and corresponding TQT trial, along with results from a simulation study, illustrate the strong performance of the proposed method. The improved conc‐QTc assessment will further enable highly reliable go/no‐go decisions in early phase clinical development and deliver results that support subsequent TQT study waivers by regulators.     

模糊变权组合预测方法研究

在不确定环境组合预测中,用模糊权重系数更能体现各单项预测方法的客观表现.文章提出一种新的权重系数为三角模糊数的组合预测方法.首先建立以组合预测精确度指数最小为准则的模糊加权组合预测模型,为了避免样本数据中极端值对模型的影响,对模型进行改进,提出带有0-1变量的模糊加权组合预测模型.进一步考虑到单项预测方法在不同时刻的表现有所差异,建立基于诱导有序模糊加权平均(IOFWA)算子的模糊变权组合预测模型,该模型不仅能克服极端值的影响,而且具有更高的预测精确度.并实证验证了该方法的适用性和灵活性.     

Quantile regression for robust estimation and variable selection in partially linear varying-coefficient models

In this paper, we develop a new estimation procedure based on quantile regression for semiparametric partially linear varying-coefficient models. The proposed estimation approach is empirically shown to be much more efficient than the popular least squares estimation method for non-normal error distributions, and almost not lose any efficiency for normal errors. Asymptotic normalities of the proposed estimators for both the parametric and nonparametric parts are established. To achieve sparsity when there exist irrelevant variables in the model, two variable selection procedures based on adaptive penalty are developed to select important parametric covariates as well as significant nonparametric functions. Moreover, both these two variable selection procedures are demonstrated to enjoy the oracle property under some regularity conditions. Some Monte Carlo simulations are conducted to assess the finite sample performance of the proposed estimators, and a real-data example is used to illustrate the application of the proposed methods.     

经济状况、社会保障对居民养老意愿的影响及城乡差异

基于中国综合社会调查(CGSS,2013)数据,分析了经济状况和社会保障对居民养老意愿的影响及城乡差异.研究发现:我国居民养老意愿以自助型及半自助型为主,家庭型次之,社会型最低,农村居民更倾向于家庭型模式;多项Logistic模型的结果显示,经济状况和社会保障因素对居民养老意愿均有显著影响,经济状况和社会保障越好,居民家庭型养老的意愿显著性越低,社会型养老的意愿相对地较高,并且,经济状况和社会保障对城镇居民养老意愿的影响更为显著,对农村居民的影响相对较小.     

表演性视角下民族节日旅游“主-客”展演互动研究——以广西三江侗族多耶节为例

民族节日作为重要的旅游吸引物,在民族地区旅游中发挥重要作用.在节日旅游中,东道主往往用表演的形式将本民族的文化进行呈现.而游客在凝视表演文化的过程中,也通过参与表演来获得身体化的表演体验.文章以广西三江侗族多耶节为研究案例,以节日活动中的表演行为为切入点,以节日空间中东道主和游客为研究对象,探讨在民族节日旅游展演的背景下,东道主和游客的表演性是如何在“客-我”的互动中进行建构的.研究发现,在民族节日旅游中,东道主作为节日旅游的“主人”,为了更好地展示本民族的文化,发挥其旅游经济及社会功能,往往通过编排或排练使民族文化富于表演性,从而使其更好地在旅游舞台上进行呈现,发挥交流媒介的功能;另一方面,游客作为节日旅游场域中的“客人”,其在通过视觉的凝视对东道主所表演的文化进行消费的过程中,已不单纯地满足于视觉感官的体验,更多的在于追求身体的多感官体验,进行旅游的身体化实践和表演性参与.     

山西省城乡居民收入差距问题研究

文章利用改革开放以来山西省的统计数据,通过对山西省城乡居民收入差距进行历史的、全方位的、多角度的分析,可以看出这一差距从总体上来说是扩大趋势,这种趋势必然会影响改革、发展、稳定的大局。城乡居民收入差距扩大既有我国长期实行的＂二元＂经济结构和现阶段分配制度的影响,又有公共产品供给不平衡和社会保障体系不完善等原因。缩小这种差距,需要采取科学推进新农村建设、完善社会保障体系、进一步减轻农民负担、促进劳动力要素合理流动、进一步加大对农村教育的投入等措施。     

The use of affective interaction design in car user interfaces

Recent developments in the car industry have put Human Machine Interfaces under the spotlight. Developing gratifying human-car interactions has become one of the more prominent areas that car manufacturers want to invest in. However, concepts like emotional design remain foreign to the industry. In this study 12 experts on the field of automobile HMI design were interviewed in order to investigate their needs and opinions of emotional design. Results show that emotional design has yet to be introduced for this context of use. Designers need a tool customized for the intricacies of the car HMI field that can provide them with support and guidance so that they can create emotionally attractive experiences for drivers and passengers alike.     

Using naturalistic driving films as a design tool for investigating driver requirements in HMI design for ADAS

In recent years, there are many naturalistic driving projects have been conducted, such as the 100-Car Project (Naturalistic Driving study in United State), EuroFOT(European Large-Scale Field Operational Tests on Vehicle Systems), SeMi- FOT(Sweden Michigan Naturalistic Field Operational Test and etc. However, those valuable naturalistic driving data hasn't been applied into Human-machine Interaction (HMI) design for Advanced Driver Assistance Systems (ADAS), a good HMI design for ADAS requires a deep understanding of drive environment and the interactions between the driving car and other road users in different situations. The results demonstrated the benefits of using naturalistic driving films as a mean for enhancing focus group discussion for better understanding driver's needs and traffic environment constraints. It provided an efficient tool for designers to have inside knowledge about drive and the needs for information presentation; The recommendations for how to apply this method is discussed in the paper.     

对等理论与进口商标的翻译

好的商标翻译不仅可以为企业带来好的第一印象,而且可以对产品的销售起到很大的推动作用。尤金奈达的对等翻译理论在进口商标的翻译中有可应用性及可操作性。在该理论指导下翻译进口商标时应采取不同的策略。不仅要达到语言功能上的对等,也要具有对等的经济效益。     

中国城市“居住分异”模式的问题与对策

当前,我国城市化进程逐渐加快,导致城市发展出现一系列城市病问题,城市居住区呈现出越来越明显的"居住分异"现象,整个城市形成一种居住空间分化甚至相互隔离的状况,给社会健康发展带来一系列负面影响。混合居住是目前解决居住分异的一种重要途径。混合居住模式以消除居民的社会差异为住宅建设的社会意义和目标,是解决不同社会阶层隔离、促进不同居民交往的有效方法,有利于营造和谐的居住模式。