Caloric restriction minimizes aging effects on the femoral medial condyle

This study aimed to analyze the effects of caloric restriction on aged femoral articular cartilage of Wistar rats. Three groups of eight animals each were considered: young (YC) and old (OC) control groups fed with a normal diet and old caloric restriction group (OCR) composed of 18-month-old animals fed with a 31% less caloric diet from 6-months of age. Articular cartilage was studied through morphometry and immunohistochemistry. Body mass was 12% less in the OCR group than in the OC group. The articular cartilage from OC rats show thinner medial condyles, fewer chondrocytes, smaller chondrocytes nuclear volume and, in both condyles, a predominance of collagen type II and less collagen density compared to both YC and OCR groups (p?p?相似文献   

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.     

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.     

Production and changeover control policies of a class of failure prone buffered flow-shops

This article deals with a stochastic optimal control problem for a class of buffered multi-parts flow-shops manufacturing system. The involved machines are subject to random breakdowns and repairs. The flow-shop under consideration is not completely flexible and hence requires setup time and cost in order to switch the production from a part type to another, this changeover is carried on the whole line. Our objective is to find the production plan and the sequence of setups that minimise the cost function, which penalises inventories/backlogs and setups. A continuous dynamic programming formulation of the problem is presented. Then, a numerical scheme is adopted to solve the obtained optimality conditions equations for a two buffered serial machines two parts case. A complete heuristic policy, based on the numerical observations which describe the optimal policies in system states, is developed. It will be shown that the obtained policy is a combination of a KANBAN/CONWIP and a modified hedging corridor policy. Moreover, based on our observations and existent research studies extension to cover more complex flow-shops is henceforth possible. The robustness of such a policy is illustrated through sensitivity analysis.     

Graphical and Numerical Methods for Detecting Influential Observations in Complex Bingham Data

We describe methods to detect influential observations in a sample of pre-shapes when the underlying distribution is assumed to be complex Bingham. One of these methods is based on Cook's distance, which is derived from the likelihood of the complex Bingham distribution. Other method is related to the tangent space, which is based on the local influence for the multivariate normal distribution. A method to detect outliers is also explained. The application of the methods is illustrated in both a real dataset and a simulated sample.     

The Multi-dimensional Characteristics of Wellbeing: How Different Aspects of Wellbeing Interact and Do Not Interact with Each Other

Because wellbeing is a multi-varied and dynamic phenomenon, social scientists need to better understand how different aspects of people’s wellbeing are tied together and how these ties differ between individuals at one point in time and within individuals over time. The paper outlines a general model that considers the multidimensional structure of wellbeing. We utilize the potential of latent variable modelling on a unique Swedish database: the Panel Survey of Ageing and the Elderly (PSAE). An inclusive and flexible model that considers the interactions between semi-autonomous domains (material resources, health, psychosocial factors, lifestyle, etc.) is developed. Our empirical study is based on cross-sectional PSAE data and focuses on people 55 years or older (N = 5,374). The analysis takes advantage of recent developments in statistical theory in the field of latent variable modelling to bring about a more dynamic and theory confirming analysis of a multifaceted phenomenon such as wellbeing.     

Testing the Granger Noncausality Hypothesis in Stationary Nonlinear Models of Unknown Functional Form

In this article, we propose a general method for testing the Granger noncausality hypothesis in stationary nonlinear models of unknown functional form. These tests are based on a Taylor expansion of the nonlinear model around a given point in the sample space. We study the performance of our tests by a Monte Carlo experiment and compare these to the most widely used linear test. Our tests appear to be well-sized and have reasonably good power properties.     

The Political Economy of Moral Conflict: An Empirical Study of Learning and Law Enforcement Under Prohibition

The U.S. Prohibition experience shows a remarkable policy reversal. In only 14 years, a drastic shift in public opinion required two constitutional amendments. I develop and estimate a model of endogenous law enforcement, determined by beliefs about the Prohibition‐crime nexus and alcohol‐related moral views. In turn, the policy outcomes shape subsequent learning about Prohibition enforcement costs. I estimate the model through maximum likelihood on Prohibition Era city‐level data on police enforcement, crime, and alcohol‐related legislation. The model can account for the variation in public opinion changes, and the heterogeneous responses of law enforcement and violence across cities. Results show that a 15% increase in the homicide rate can be attributed to Prohibition enforcement. The subsequent learning‐driven adjustment of local law enforcement allowed for the alcohol market to rebound to 60% of its pre‐Prohibition size. I conclude with counterfactual exercises exploring the welfare implications of policy learning, prior beliefs, preference polarization, and alternative political environments. Results illustrate the importance of incorporating the endogenous nature of law enforcement into our understanding of policy failure and policy success.     

Central quantile subspace

Quantile regression (QR) is becoming increasingly popular due to its relevance in many scientific investigations. There is a great amount of work about linear and nonlinear QR models. Specifically, nonparametric estimation of the conditional quantiles received particular attention, due to its model flexibility. However, nonparametric QR techniques are limited in the number of covariates. Dimension reduction offers a solution to this problem by considering low-dimensional smoothing without specifying any parametric or nonparametric regression relation. The existing dimension reduction techniques focus on the entire conditional distribution. We, on the other hand, turn our attention to dimension reduction techniques for conditional quantiles and introduce a new method for reducing the dimension of the predictor $$\mathbf {X}$$. The novelty of this paper is threefold. We start by considering a single index quantile regression model, which assumes that the conditional quantile depends on $$\mathbf {X}$$ through a single linear combination of the predictors, then extend to a multi-index quantile regression model, and finally, generalize the proposed methodology to any statistical functional of the conditional distribution. The performance of the methodology is demonstrated through simulation examples and real data applications. Our results suggest that this method has a good finite sample performance and often outperforms the existing methods.