Ecosystem resilience, specialized adaptation and population decline: A modern Malthusian theory

The purpose of this article is to construct a theoretical framework characterizing the interactions among economic development, ecosystem equilibrium and possible population decline, and to discuss the population dynamics in the very long run. In our framework, economic activities bridge population and environment. On the one hand, human beings reform the environment through economic activities; on the other hand, economic activities decrease environmental resilience and increase the possibility of an environmental change in a discontinuous and irreversible pattern, as described in Arrow et al. (1995). Furthermore, a highly developed economy also causes over-specialization of human adaptation, which tends to exaggerate the impact of an environmental change on human population size. Received: 19 January 1999/Accepted: 3 July 1999     

青海厄鲁特蒙古与清朝之早期关系述略

清定鼎之初 ,因忙于镇压中原地区的各种反抗势力 ,对于西陲各地只能采取安抚稳定的策略 ,即羁縻政策。清康熙帝之时 ,则逐步加强了对青海地区的统治和管辖 ,将青海诸部纳入中央势力范围之内。     

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.     

Some alternative bivariate Kumaraswamy models

In this article we discuss various strategies for constructing bivariate Kumaraswamy distributions. As alternatives to the Nadarajah et al. (2011) bivariate model, four different models are introduced utilizing a conditional specification approach, a conditional survival function approach, and an Arnold–Ng bivariate beta distribution construction approach. Distributional properties for such bivariate distributions are investigated. Parameter estimation strategies for the models are discussed, as are the consequences of fitting two of the models to a particular data set involving the proportion of foggy days at two different airports in Colombia.     

Threshold Estimation for Stochastic Processes with Small Noise

Consider a process satisfying a stochastic differential equation with unknown drift parameter, and suppose that discrete observations are given. It is known that a simple least squares estimator (LSE) can be consistent but numerically unstable in the sense of large standard deviations under finite samples when the noise process has jumps. We propose a filter to cut large shocks from data and construct the same LSE from data selected by the filter. The proposed estimator can be asymptotically equivalent to the usual LSE, whose asymptotic distribution strongly depends on the noise process. However, in numerical study, it looked asymptotically normal in an example where filter was chosen suitably, and the noise was a Lévy process. We will try to justify this phenomenon mathematically, under certain restricted assumptions.