Bayesian adaptive dose‐escalation designs for simultaneously estimating the optimal and maximum safe dose based on safety and efficacy

The main purpose of dose‐escalation trials is to identify the dose(s) that is/are safe and efficacious for further investigations in later studies. In this paper, we introduce dose‐escalation designs that incorporate both the dose‐limiting events and dose‐limiting toxicities (DLTs) and indicative responses of efficacy into the procedure. A flexible nonparametric model is used for modelling the continuous efficacy responses while a logistic model is used for the binary DLTs. Escalation decisions are based on the combination of the probabilities of DLTs and expected efficacy through a gain function. On the basis of this setup, we then introduce 2 types of Bayesian adaptive dose‐escalation strategies. The first type of procedures, called “single objective,” aims to identify and recommend a single dose, either the maximum tolerated dose, the highest dose that is considered as safe, or the optimal dose, a safe dose that gives optimum benefit risk. The second type, called “dual objective,” aims to jointly estimate both the maximum tolerated dose and the optimal dose accurately. The recommended doses obtained under these dose‐escalation procedures provide information about the safety and efficacy profile of the novel drug to facilitate later studies. We evaluate different strategies via simulations based on an example constructed from a real trial on patients with type 2 diabetes, and the use of stopping rules is assessed. We find that the nonparametric model estimates the efficacy responses well for different underlying true shapes. The dual‐objective designs give better results in terms of identifying the 2 real target doses compared to the single‐objective designs.     

“重陆轻海”与“通洋裕国”之海洋观刍议

明清两朝正处于世界性海洋历史发展的"千古变局"时代,但统治者沿袭传统模式,在立国思想上"重农抑商"、"重陆轻海",在国防战略上以"禁海"代替海防,禁海迁界、"守土防御",反映其海洋观念的淡薄;而东南沿海地方官员,尤其郑成功"通洋裕国"思想的提出和实践,显露出"以商立国",向海洋空间发展的意涵;传统时代"重陆轻海"与"通洋裕国"所反映的海洋观念,对国家民族发展的影响在某种程度上可以忽略不计,但大航海时代,海洋作为人类的第二生存空间影响到世界历史走向和发展格局时,"重陆轻海"观念所带来的深层影响会因此而改变国家和民族的命运。     

20世纪20年代的乡土文学状况

20世纪20年代的乡土文学作为乡土文学流派的源头，对乡土文学的发展、流变具有重要的启悟意义。对此一时期的乡土文学研究，概念研究、思想主题研究以及艺术美学研究是研究的中心和重点，对后起的乡土文学创作和评论产生了决定性的影响。     

Using Work Values to Predict Post‐Retirement Work Intentions

Work values might be proximal predictors of individuals' late‐career intentions because they serve as guiding principles for the selection, evaluation, and justification of vocational behavior. The purpose of this study was to examine the relationship between work values and post‐retirement work intentions. The authors investigated individual work values within the structure of 4 higher order values elaborated on by Schwartz et al. ( 2012 ). Relationships between work values and 4 types of post‐retirement work intentions were examined. Data from 1,071 employees of a German logistics company were used to test the hypotheses. The results of a structural equation model indicated that work values were differentially related to the 4 types of post‐retirement work intentions. The identified work value–work type combinations add to the literature on post‐retirement work. Practice implications for promoting positive individual and organizational outcomes are drawn from the results.     

Micro‐investment perspective and the potential of the universal basic income

The article evaluates prospects of the Basic Income (BI) as a development policy tool. While BI is a relatively new initiative within development policy, the article argues that it should be seen as a serious option in the future, given the changing geography of poverty and the findings from existing cash transfer schemes. The analysis is carried out as a synthesis of existing findings on BI pilot programmes, along with cash transfer instruments more generally. While not including new empirical data, the synthesis allows preliminary estimates on the likely impacts of abolishing conditioning and targeting in cash transfer schemes. Particular attention is paid to the notion of micro‐investment and the psychological conditions of micro‐investment.     

Nonparametric Shrinkage Estimation for Aalen's Additive Hazards Model

Aalen's nonparametric additive model in which the regression coefficients are assumed to be unspecified functions of time is a flexible alternative to Cox's proportional hazards model when the proportionality assumption is in doubt. In this paper, we incorporate a general linear hypothesis into the estimation of the time‐varying regression coefficients. We combine unrestricted least squares estimators and estimators that are restricted by the linear hypothesis and produce James‐Stein‐type shrinkage estimators of the regression coefficients. We develop the asymptotic joint distribution of such restricted and unrestricted estimators and use this to study the relative performance of the proposed estimators via their integrated asymptotic distributional risks. We conduct Monte Carlo simulations to examine the relative performance of the estimators in terms of their integrated mean square errors. We also compare the performance of the proposed estimators with a recently devised LASSO estimator as well as with ridge‐type estimators both via simulations and data on the survival of primary billiary cirhosis patients.     

Who is a Distracted Driver? Associations between Mobile Phone Use while Driving,Domain‐Specific Risk Taking,and Personality

Mobile phone use while driving (MPUWD) is an increasingly common form of distracted driving. Given its widespread prevalence, it is important for researchers to identify factors that may predict who is more likely to engage in this risky behavior. The current study investigates associations between MPUWD risk behaviors, domain‐specific risk perceptions, and broad personality dimensions. An Italian community sample (n = 804) completed a survey regarding MPUWD risk perceptions and engagement in MPUWD, in addition to the HEXACO‐PI‐R, a broad six‐factor personality inventory (honesty‐humility, emotionality, extraversion, agreeableness, conscientiousness, openness to experience), and the DOSPERT, a six‐factor domain‐specific self‐report risk‐taking measure (health/safety, recreational, social, ethical, gambling, and investment). With respect to domain‐specific risk taking, greater frequency of SMS use while driving most strongly was associated with greater risk taking for the health/safety, gambling, and ethical risk domains. Further, greater honesty‐humility and conscientiousness, two traits related to cognitive control and risk behaviors, and to a lesser extent openness to experience, were associated with less frequent MPUWD, and positively associated with MPUWD risk perceptions. With growing public safety concern surrounding MPUWD, understanding associated personality factors is not only important for identifying psychological mechanisms underlying risk behavior, but also for more effective prevention and intervention programs.     

And I Still Love Them: On Touching Loss

In this article, the author performs a re‐membering practice that incorporates a relational materialist theory. It traces the disturbances that follow in the wake of three deaths in her family. Written in an autoethnographic voice, the article is a polyphonic composition of the narrative therapy approach of re‐membering entangled with the spacetimematter of silence, speaking, sitting, staying, presence, absence, loss of momentum, dreams, trees, books, cardiac pace‐makers, writing, breath, ashes, murmuring, suffering. Thus, the dispersed agencies of bodies, human and non‐human, reinvigorate a linguistic practice and the author's personal and professional life.     

唐宋书法观念研究

唐代、宋代的书法观念是中国古代封建社会书法观念的典型代表,二者之间又有颇为明显的异同之处。正如常人所说的＂唐书法＂就是说唐代书法对于字体规范、风格法度有着严密的内在要求,其实由于科举进仕的需要以及宋人文化素养的普通提升,宋代文人对＂法＂也有着自觉地遵循。同时,在宋代还大量出现了＂游与艺＂、＂以书为乐＂等更为轻松的书法观念。