Generalized phase I-II designs to increase long term therapeutic success rate

Designs for early phase dose finding clinical trials typically are either phase I based on toxicity, or phase I-II based on toxicity and efficacy. These designs rely on the implicit assumption that the dose of an experimental agent chosen using these short-term outcomes will maximize the agent's long-term therapeutic success rate. In many clinical settings, this assumption is not true. A dose selected in an early phase oncology trial may give suboptimal progression-free survival or overall survival time, often due to a high rate of relapse following response. To address this problem, a new family of Bayesian generalized phase I-II designs is proposed. First, a conventional phase I-II design based on short-term outcomes is used to identify a set of candidate doses, rather than selecting one dose. Additional patients then are randomized among the candidates, patients are followed for a predefined longer time period, and a final dose is selected to maximize the long-term therapeutic success rate, defined in terms of duration of response. Dose-specific sample sizes in the randomization are determined adaptively to obtain a desired level of selection reliability. The design was motivated by a phase I-II trial to find an optimal dose of natural killer cells as targeted immunotherapy for recurrent or treatment-resistant B-cell hematologic malignancies. A simulation study shows that, under a range of scenarios in the context of this trial, the proposed design has much better performance than two conventional phase I-II designs.     

现代汉语时相之系统功能视角研究

以往对现代汉语时相的研究集中在动词本身,着眼于动词本身的时间意义,并且缺乏系统的理论指导。文章以系统功能语言学为研究视角,对不同过程类型小句的时相特征进行分析和讨论。研究表明:谓体为小句时相的表达提供了基本的可能性,如果没有其他成分的影响,谓体表达的时间意义则决定小句的时相特征;小句其他句法成分有时对时相起着重要的影响作用。      

对拉美国家现代化几个阶段的认识

拉美国家从19世纪下半叶步入现代化的历史进程以来,先后经历了现代化的初始阶段、自主发展阶段、快速发展阶段和调整阶段。探索这一现代化的演进过程,有助于我们从整体上把握拉美国家现代化的进程和发展脉络,从中吸取对发展中国家现代化建设一些有益启示。     

Two-stage phase II trials with early stopping for effectiveness and safety as well as ineffectiveness or harm

This article proposes new optimal and minimax designs, which allow early stopping not only for ineffectiveness or toxicity but also for sufficient effectiveness and safety. These designs may facilitate effective drug development by detecting sufficient effectiveness and safety at an early stage or by detecting ineffectiveness or excessive toxicity at an early stage. The proposed design has advantage over other designs in the sense that it can control the type I error rate and is robust against the real association parameter. Comparing to Jin's design, it is always advantageous in terms of expected sample size.     

Prediction of accrual closure date in multi-center clinical trials with discrete-time Poisson process models

In a phase III multi‐center cancer clinical trial or a large public health study, sample size is predetermined to achieve desired power, and study participants are enrolled from tens or hundreds of participating institutions. As the accrual is closing to the target size, the coordinating data center needs to project the accrual closure date on the basis of the observed accrual pattern and notify the participating sites several weeks in advance. In the past, projections were simply based on some crude assessment, and conservative measures were incorporated in order to achieve the target accrual size. This approach often resulted in excessive accrual size and subsequently unnecessary financial burden on the study sponsors. Here we proposed a discrete‐time Poisson process‐based method to estimate the accrual rate at time of projection and subsequently the trial closure date. To ensure that target size would be reached with high confidence, we also proposed a conservative method for the closure date projection. The proposed method was illustrated through the analysis of the accrual data of the National Surgical Adjuvant Breast and Bowel Project trial B‐38. The results showed that application of the proposed method could help to save considerable amount of expenditure in patient management without compromising the accrual goal in multi‐center clinical trials. Copyright © 2012 John Wiley & Sons, Ltd.     

相位旋转的速率为2的空时分组码

速率为2的空时分组码(R2-STBC)能达到全速率全分集,然而其译码复杂度与调制阶数的平方成正比。为了降低译码复杂度,提出了一种基于相位旋转的、速率为2的空时分组码(PR-R2-STBC),发送端根据反馈信息将部分发送信号旋转一定的角度,实现了信号在传输过程中两两正交,从而使得其译码复杂度与调制阶数成正比。仿真结果显示,与R2-STBC相比,该编码仅需反馈7 bit就极大地降低了译码复杂度。     

《庚道集》中“定”的语法化等级考察

谓语动词"定"在《庚道集》中通过语法化,主要作述补式结果补语以及表完成态的动相补语。在"V定"和"V定O"格式中,当V是造成"稳紧"义的动作动词时,"定"的语义特征更倾向于表示结果补语。"定"作动相补语可与动词和形容词结合,但与动词的组合能力不强,对所黏附的动词具有选择性。     

临床X射线相衬成像研究进展

X射线相衬成像在提高人体软组织成像的衬度分辨率及空间分辨率研究中具有潜在优势,是一项有着广阔发展前景的技术。它利用空间相干X射线投过物体后携带的相位信息进行成像,在临床上适用于软组织物体,可以减少吸收剂量,进而减轻病人的辐射损伤。本文详述了当今几种典型的X射线相衬成像方法,包括X射线干涉相衬,衍射增强相衬以及类同轴相衬的成像原理以及发展历程。通过对比表明了几种成像方法的优缺点。最后对临床X射线相衬成像有待解决的问题作了分析。     

民国成渝铁路土地征收问题考察

1936年成渝铁路征地工作开始,为了顺利实施土地征收,四川省政府特别设立铁路征地机关,并制定了组织章程、征地程序和土地补偿标准等,至1937年底征地工作基本完成.从征地的行政补偿与实际行政程序来看,存在着严重失衡与失位,造成被征地人的利益受损.