大学科研不端行为的成因剖析

当代中国大学日益严重的科研不端行为的产生既存在科研价值认识模糊、科研规范意识淡薄、科研荣辱之情缺乏和科研追求集体偏向等主观原因,也与高校管理体制的政学合一、学术职称评定集权操作、科研评价数量化、科研纠错机制被动无力等客观原因密切相关。而这些原因为我们探讨科研不端行为之防治模式提供了基本思路。     

Dose intra-subject escalation to an event (DIETE): A new method for phase 1 dose-finding utilizing systematic intra-subject dose escalation with application to T-cell engagers

T-cell engagers are a class of oncology drugs which engage T-cells to initiate immune response against malignant cells. T-cell engagers have features that are unlike prior classes of oncology drugs (e.g., chemotherapies or targeted therapies), because (1) starting dose level often must be conservative due to immune-related side effects such as cytokine release syndrome (CRS); (2) dose level can usually be safely titrated higher as a result of subject's immune system adaptation after first exposure to lower dose; and (3) due to preventive management of CRS, these safety events rarely worsen to become dose limiting toxicities (DLTs). It is generally believed that for T-cell engagers the dose intensity of the starting dose and the peak dose intensity both correlate with improved efficacy. Existing dose finding methodologies are not designed to efficiently identify both the initial starting dose and peak dose intensity in a single trial. In this study, we propose a new trial design, dose intra-subject escalation to an event (DIETE) design, that can (1) estimate the maximum tolerated initial dose level (MTD1); and (2) incorporate systematic intra-subject dose-escalation to estimate the maximum tolerated dose level subsequent to adaptation induced by the initial dose level (MTD2) with a survival analysis approach. We compare our framework to similar methodologies and evaluate their key operating characteristics.     

内心确信的外在制约

内心确信这一主观性判断是形成心证的关键,保障心证客观化必然要以遏制内心确信的恣意为前提。从内心确信的主体、标准、监督和救济角度出发,以期探索预防和阻断法官滥用司法权力、枉法裁判的规制路径,进而外在化、明示化裁判者确信的心素,实现对主观确信客观性标准的规制。明确和实现内心确信的外在制约设置,能够有效提高司法公信力,顺应新时代下司法改革的新要求。     

Patient-specific dose finding in phase I clinical trials

This article proposes an extension of the continual reassessment method to determine the maximum tolerated dose (MTD) in the presence of patients' heterogeneity in phase I clinical trials. To start with a simple case, we consider the covariate as a binary variable representing two groups of patients. A logistic regression model is used to establish the dose–response relationship and the design is based on the Bayesian framework. Simulation studies for six plausible dose–response scenarios show that the proposed design is likely to determine the MTD more accurately than the design that does not take covariate into consideration.     

SPIRIT: A seamless phase I/II randomized design for immunotherapy trials

Immunotherapy—treatments that enlist the immune system to battle tumors—has received widespread attention in cancer research. Due to its unique features and mechanisms for treating cancer, immunotherapy requires novel clinical trial designs. We propose a Bayesian seamless phase I/II randomized design for immunotherapy trials (SPIRIT) to find the optimal biological dose (OBD) defined in terms of the restricted mean survival time. We jointly model progression‐free survival and the immune response. Progression‐free survival is used as the primary endpoint to determine the OBD, and the immune response is used as an ancillary endpoint to quickly screen out futile doses. Toxicity is monitored throughout the trial. The design consists of two seamlessly connected stages. The first stage identifies a set of safe doses. The second stage adaptively randomizes patients to the safe doses identified and uses their progression‐free survival and immune response to find the OBD. The simulation study shows that the SPIRIT has desirable operating characteristics and outperforms the conventional design.     

基于LD分解的空间谱估计技术

提出了一种基于对阵列协方差矩阵进行 LD 分解的空间谱估计算法。对一大类阵列来说,该算法对空间谱估计方法的工程实现问题具有十分重要的实际意义。文中证明了特殊Hernitian 矩阵 LD 分解的原理,给出了求分解因式的递推公式,然后,由 LD 分解找出的信号子空间,得出了估计信号源方向的空间谱计算公式。理论分析和模拟结果表明,LD 分解和原有的特征分解法相比,更易于用专用数字信号处理片实现,有更小的计算量,需更少的存储单元。     

改善高校图书馆外文文献采访工作的思考

采访工作是图书馆工作的重点.文章就如何改进外文文献采访工作提出若干对策建议.     

A Bayesian dose‐finding design for drug combination clinical trials based on the logistic model

In early phase dose‐finding cancer studies, the objective is to determine the maximum tolerated dose, defined as the highest dose with an acceptable dose‐limiting toxicity rate. Finding this dose for drug‐combination trials is complicated because of drug–drug interactions, and many trial designs have been proposed to address this issue. These designs rely on complicated statistical models that typically are not familiar to clinicians, and are rarely used in practice. The aim of this paper is to propose a Bayesian dose‐finding design for drug combination trials based on standard logistic regression. Under the proposed design, we continuously update the posterior estimates of the model parameters to make the decisions of dose assignment and early stopping. Simulation studies show that the proposed design is competitive and outperforms some existing designs. We also extend our design to handle delayed toxicities. Copyright © 2014 John Wiley & Sons, Ltd.     

Specifications of a continual reassessment method design for phase I trials of combined drugs

In studies of combinations of agents in phase I oncology trials, the dose–toxicity relationship may not be monotone for all combinations, in which case the toxicity probabilities follow a partial order. The continual reassessment method for partial orders (PO‐CRM) is a design for phase I trials of combinations that leans upon identifying possible complete orders associated with the partial order. This article addresses some practical design considerations not previously undertaken when describing the PO‐CRM. We describe an approach in choosing a proper subset of possible orderings, formulated according to the known toxicity relationships within a matrix of combination therapies. Other design issues, such as working model selection and stopping rules, are also discussed. We demonstrate the practical ability of PO‐CRM as a phase I design for combinations through its use in a recent trial designed at the University of Virginia Cancer Center. Copyright © 2013 John Wiley & Sons, Ltd.     

Academic parenthood: Navigating structure and culture in an elite occupation

Many contemporary workers struggle to manage paid work and family responsibilities, leading scholars to explore mechanisms contributing to conflict between these two domains. Such examinations often center on pinpointing specific factors that explain variation in work-family conflict, but these studies have less to say about how some occupational contexts create overwhelming demands for workers. In this article, I advocate for an approach that details the cultural and structural components of specific occupations. Building on scholarship about demanding jobs, I use academic parenthood as an illustrative case to demonstrate how certain occupational contexts are organized in ways that introduce challenges for caregiving. I then analyze how culture and structure jointly influence family-friendly policies in the university setting, along with comparative experiences across discipline, gender, and race/ethnicity. Next, I describe how academic parents in the face of constraints, make choices, show agency, and demonstrate resistance. I conclude by identifying promising areas for future research.