Optimal adaptive designs for acute oral toxicity assessment

Acute oral toxicity studies are used to assess the toxicity to experimental animals of a single dose of the substance under investigation, assigning the substance to one of a number of classes. Animal welfare concerns have led to the development of three adaptive designs as alternatives to the traditional fixed sample design. These lead to reductions in the number of animals required in total and in the number exposed to lethal doses. In this paper, we show how designs can be constructed to optimise utility functions combining the need to classify correctly with the desire to use a small number of animals. Constrained optimal designs are also obtained in which no animal is exposed to a dose higher than that at which a death has been observed. The optimal designs lead to the correct classification with high probability whilst reducing the expected number of animal deaths relative to existing adaptive designs.     

On a redundant repairable system with switching failure: Bayesian approach

System characteristics of a redundant repairable system are studied from a Bayesian viewpoint with different types of priors assumed for the unknown parameters. The system consists of two primary units, one standby unit, and one repair facility which is activated when switching to standby fails. Times to failure and times to repair of the operating units are assumed to follow exponential distributions. When time to failure and time to repair have uncertain parameters, a Bayesian approach is adopted to evaluate system characteristics. Monte Carlo simulation is used to derive the posterior distribution for the mean time to system failure and steady-state availability. Some numerical experiments are performed to illustrate the results derived in this paper.     

我国35个大中城市房价-持久收入比研究

房价收入比是反映居民购房可支付能力的重要指标。为了更真实准确反映我国居民长期承受的购房负担,本文基于持久收入假说,利用我国35个大中城市数据,建立状态空间模型,估计出持久收入意义下的房价收入比,通过情景分析确定其合理上限,并分析主要特征。研究表明：①我国房价-持久收入比的合理上限为7.6,2002-2013年35个大中城市的房价-持久收入比均值是9.2,其中28个城市已超过该上限,比值最高的北京已达到14.9;②城市越发达,则房价-持久收入比越高,居民需要承受的购房压力越大,且在时间趋势上,一线与二三线城市间的差距呈现扩大趋势;③在地理分布上,我国东部、中部、东北地区、西部大中城市的房价-持久收入比呈现从高到低的排列顺序;④相比于传统方法中根据可支配收入测算的房价收入比,房价-持久收入比与其约有10%的差异。当前我国政府应采取有效措施继续限制房价,减轻居民购房负担。     

Get Full Text Research and the Search for Appropriate Copies

Abstract

A group of the largest academic publishers has launched a new service to simplify access to full-text research for users of discovery services and scholarly collaboration platforms. While this service aims to provide easy access to full-text articles using article-level entitlement information linked to institutions through Seamlessaccess.org, it also introduces ambiguity. The service allows for publishers to direct users to alternative versions when a full-text entitlement is not found for the user, though users may already be entitled to full text through providers that do not participate in the service. Depending on specific implementations, this could lead to further confusion and make it more difficult for users to find an appropriate copy.     

On implementing Jeffreys' substitution likelihood for Bayesian inference concerning the medians of unknown distributions

When statisticians are uncertain as to which parametric statistical model to use to analyse experimental data, they will often resort to a non-parametric approach. The purpose of this paper is to provide insight into a simple approach to take when it is unclear as to the appropriate parametric model and plan to conduct a Bayesian analysis. I introduce an approximate, or substitution likelihood, first proposed by Harold Jeffreys in 1939 and show how to implement the approach combined with both a non-informative and an informative prior to provide a random sample from the posterior distribution of the median of the unknown distribution. The first example I use to demonstrate the approach is a within-patient bioequivalence design and then show how to extend the approach to a parallel group design.     

非均衡发展战略与中国城乡收入差距的关系——来自省级面板数据的经验分析

运用非均衡发展战略理论构建中国城乡收入差距成因的理论框架。利用2005—2008年中国省级的数据资料,建立了panel data模型,实证研究中国偏向城市的财政政策、金融政策、就业政策、贸易政策以及偏向城市的社会保障制度和公共产品供给制度对中国城乡收入差距的影响,研究表明：非均衡发展战略所衍生的一系列偏向城市的制度和政策是导致城乡收入差距的原因,逐步改革户籍制度,打破城乡二元体制,统筹城乡发展是缩小城乡收入差距的基础。     

A response to M. Stone: 'How not to measure the efficiency of public services (and how one might)'

Summary.  This is a response to Stone's criticisms of the Spottiswoode report to the UK Treasury which was responding to the Treasury's request for improved methods to evaluate the efficiency and productivity of the 43 police districts in England and Wales. The Spottiswoode report recommended uses of data envelopment analysis (DEA) and stochastic frontier analysis (SFA), which Stone critiqued en route to proposing an alternative approach. Here we note some of the most serious errors in his criticism and inaccurate portrayals of DEA and SFA. Most of our attention is devoted to DEA, and to Stone's recommended alternative approach without much attention to SFA, partly because of his abbreviated discussion of the latter. In our response we attempt to be constructive as well as critical by showing how Stone's proposed approach can be joined to DEA to expand his proposal beyond limitations in his formulations.     

城市能源效率的PS-kNN分类综合评价

为了对区域能源效率做出客观评价,提出一种新的基于不可控因素的地级城市分类的能源效率分类比较方法,旨在研究能源效率的地区可比性问题。分类问题的讨论包括类别个数的确定和分类方法的选取;分类个数和分类原则的确定采用预测强度和基础因子相结合的办法,进一步采用k最近邻分类方法对其余不可控因子进行分类预测,以避免所谓的自评判问题;运用文中所给出的综合分类结果对一些城市的能源效率进行评价,便于相关城市找到提高能源效率的有效措施。"     

Waiting time to exhaust lottery numbers

Questions related to lotteries are usually of interest to the public since people think there is a magic formula which will help them to win lottery draws. This note shows how to compute the expected waiting time to observe specific numbers in a sequence of lottery draws and show that surprising facts are expected to occur.     

A Bayesian model for estimating the malaria transition probabilities considering individuals lost to follow-up

It is known that patients may cease participating in a longitudinal study and become lost to follow-up. The objective of this article is to present a Bayesian model to estimate the malaria transition probabilities considering individuals lost to follow-up. We consider a homogeneous population, and it is assumed that the considered period of time is small enough to avoid two or more transitions from one state of health to another. The proposed model is based on a Gibbs sampling algorithm that uses information of lost to follow-up at the end of the longitudinal study. To simulate the unknown number of individuals with positive and negative states of malaria at the end of the study and lost to follow-up, two latent variables were introduced in the model. We used a real data set and a simulated data to illustrate the application of the methodology. The proposed model showed a good fit to these data sets, and the algorithm did not show problems of convergence or lack of identifiability. We conclude that the proposed model is a good alternative to estimate probabilities of transitions from one state of health to the other in studies with low adherence to follow-up.     

SIMEX method for censored quantile regression with measurement error

Censored quantile regression serves as an important supplement to the Cox proportional hazards model in survival analysis. In addition to being exposed to censoring, some covariates may subject to measurement error. This leads to substantially biased estimate without taking this error into account. The SIMulation-EXtrapolation (SIMEX) method is an effective tool to handle the measurement error issue. We extend the SIMEX approach to the censored quantile regression with covariate measurement error. The algorithm is assessed via extensive simulations. A lung cancer study is analyzed to verify the validation of the proposed method.     

Preserving the Scholarly Collection: An Examination of the Perpetual Access Clauses in the Texas A&M University Libraries' Major E-Journal Licenses

Librarians are urged to lobby for the inclusion of perpetual access clauses during license negotiations and to examine existing contracts to ensure that perpetual access provisions are clearly understood and achievable. The authors analyzed the perpetual access clauses in nineteen of the Texas A&M University Libraries' licenses for electronic journal packages to determine the exact provisions granted, and found that the Libraries do not really know what access to previously subscribed content will entail. This raises profound concerns about the Libraries' ability to provide meaningful perpetual access to previously subscribed content to its users in the current environment.     

Prediction for generalized linear models

Regression models are often used to make predictions. All the information needed is contained in the predictive distribution. However, this cannot be evaluated explicitly for most generalized linear models. We construct two approximations to this distribution and demonstrate their use on two sets of survival data, corresponding to the outcome of patients admitted to intensive care units and the survival times of leukaemia patients.Regression models are often used to make predictions. All the information needed is contained in the predictive distribution. However, this cannot be evaluated explicitly for most generalized linear models. We construct two approximations to this distribution and demonstrate their use on two sets of survival data, corresponding to the outcome of patients admitted to intensive care units and the survival times of leukaemia patients.Regression models are often used to make predictions. All the information needed is contained in the predictive distribution. However, this cannot be evaluated explicitly for most generalized linear models. We construct two approximations to this distribution and demonstrate their use on two sets of survival data, corresponding to the outcome of patients admitted to intensive care units and the survival times of leukaemia patients.Regression models are often used to make predictions. All the information needed is contained in the predictive distribution. However, this cannot be evaluated explicitly for most generalized linear models. We construct two approximations to this distribution and demonstrate their use on two sets of survival data, corresponding to the outcome of patients admitted to intensive care units and the survival times of leukaemia patients.     

Multinomial Selection for Comparison with a Standard

The multinomial selection problem is considered under the formulation of comparison with a standard, where each system is required to be compared to a single system, referred to as a “standard,” as well as to other alternative systems. The goal is to identify systems that are better than the standard, or to retain the standard when it is equal to or better than the other alternatives in terms of the probability to generate the largest or smallest performance measure. We derive new multinomial selection procedures for comparison with a standard to be applied in different scenarios, including exact small-sample procedure and approximate large-sample procedure. Empirical results and the proof are presented to demonstrate the statistical validity of our procedures. The tables of the procedure parameters and the corresponding exact probability of correct selection are also provided.     

Bayesian local influence for survival models

The aim of this paper is to develop a Bayesian local influence method (Zhu et al. 2009, submitted) for assessing minor perturbations to the prior, the sampling distribution, and individual observations in survival analysis. We introduce a perturbation model to characterize simultaneous (or individual) perturbations to the data, the prior distribution, and the sampling distribution. We construct a Bayesian perturbation manifold to the perturbation model and calculate its associated geometric quantities including the metric tensor to characterize the intrinsic structure of the perturbation model (or perturbation scheme). We develop local influence measures based on several objective functions to quantify the degree of various perturbations to statistical models. We carry out several simulation studies and analyze two real data sets to illustrate our Bayesian local influence method in detecting influential observations, and for characterizing the sensitivity to the prior distribution and hazard function.     

How many ways can you look at a proportion?: cross-community vote transfers in Northern Ireland after the Belfast Agreement

Summary.  The single transferable vote is a method of election that allows voters to mark candidates in order of preference. Votes that are not required to elect a candidate are passed to the next candidate in the voter's order of preference. Results of this kind of election give us data about the degree to which voters of a given persuasion are willing to pass their vote to a candidate of a different persuasion. Measures of voters' willingness to pass a vote to a candidate of a different persuasion are of particular interest in places such as Northern Ireland, where communities differ by religion and national aspiration, and agreed new political institutions are based on cross-community power-sharing. How we quantify this voting data may depend on the questions that we want to answer, of course. But, to understand changes in how the voter orders her or his preference, one may need to ask several questions, and to quantify the results of the election in more than one way.     

Markov Chains and De-initializing Processes

We define a notion of de-initializing Markov chains. We prove that to analyse convergence of Markov chains to stationarity, it suffices to analyse convergence of a de-initializing chain. Applications are given to Markov chain Monte Carlo algorithms and to convergence diagnostics.     

Sample size calculation for logrank test and prediction of number of events over time

We review and compare existing methods for sample size calculation based on the logrank statistic and recommend the method of Lakatos for its accuracy and flexibility in allowing time-dependent rates of event, loss to follow-up, and noncompliance. We extend the Lakatos method to allow a general follow-up scheme, to handle non-inferiority tests, and to predict the number of events over calendar time. We apply the Lakatos method to the simple nonproportional hazard situation of delayed treatment effect to facilitate the comparison of different weighting methods and to evaluate the performance of the maximum combination tests. We use simulation studies to confirm the validity of the Lakatos method and its extensions.     

A new approximation for the distribution of the difference of two t-variables

A mixture representation for the distribution of the difference of two independent t-varlables is provided to approximate the probabilities and percentiles The mixture of normal and standardized t is found to be quite suitable in terms of the accuracy and simplicity as it compares favorably to the best known approximation namelyt that due to Ghosh (1975). The idea of the mixture distribution is also extended to provide an approximation to the distribution of a linear combination of independent t-variables which provides an approximation to the Behrens-Fisher distribution in particular.     

Implementation of a Bayesian adaptive design in a proof of concept study

With increased costs of drug development the need for efficient studies has become critical. A key decision point on the development pathway has become the proof of concept study. These studies must provide clear information to the project teams to enable decision making about further developing a drug candidate but also to gain evidence that any effect size is sufficient to warrant this development given the current market environment. Our case study outlines one such proof of concept trial where a new candidate therapy for neuropathic pain was investigated to assess dose-response and to evaluate the magnitude of its effect compared to placebo. A Normal Dynamic Linear Model was used to estimate the dose-response--enforcing some smoothness in the dose-response, but allowing for the fact that the dose-response may be non-monotonic. A pragmatic, parallel group study design was used with interim analyses scheduled to allow the sponsor to drop ineffective doses or to stop the study. Simulations were performed to assess the operating characteristics of the study design. The study results are presented. Significant cost savings were made when it transpired that the new candidate drug did not show superior efficacy when compared placebo and the study was stopped.