Impact of physical activity on activity of daily living in moderate to severe dementia: a critical review

The objectives of this study were to describe the different modalities of physical activity programs designed for moderate to severe dementia and to identify their impact on functional independence in activities of daily living (ADL). A critical review of randomized controlled trials related to the impact of physical activity programs in moderately to severely demented persons on ADL performance and meta-analysis of the identified studies were performed. Among the 303 identified articles, five responded to the selection criteria. Four out of the five studies demonstrated limited methodological quality. In one high-quality study, physical activity programs significantly delayed deterioration of ADL performance. The program components and ADL assessment tools vary widely across studies. Although the proposed treatments have not proven their efficiency in improving the ADL status of the patients, they were able to limit the decline in ADL functioning. Future research is warranted in order to identify clinically relevant modalities for physical activity programs for people with moderate to severe dementia.     

FDR control of detected regions by multiscale matched filtering

Feature extraction from observed noisy samples is a common important problem in statistics and engineering. This paper presents a novel general statistical approach to the region detection problem in long data sequences. The proposed technique is a multiscale kernel regression in conjunction with statistical multiple testing for region detection while controlling the false discovery rate (FDR) and maximizing the signal-to-noise ratio via matched filtering. This is achieved by considering a one-dimensional region detection problem as its equivalent zero-dimensional peak detection problem. The detection method does not require a priori knowledge of the shape of the nonzero regions. However, if the shape of the nonzero regions is known a priori, e.g., rectangular pulse, the signal regions can also be reconstructed from the detected peaks, seen as their topological point representatives. Simulations show that the method can effectively perform signal detection and reconstruction in the simulated data under high noise conditions, while controlling the FDR of detected regions and their reconstructed length.     

Empirical evaluation of the implementation of the EMA guideline on missing data in confirmatory clinical trials: Specification of mixed models for longitudinal data in study protocols

In confirmatory clinical trials, the prespecification of the primary analysis model is a universally accepted scientific principle to allow strict control of the type I error. Consequently, both the ICH E9 guideline and the European Medicines Agency (EMA) guideline on missing data in confirmatory clinical trials require that the primary analysis model is defined unambiguously. This requirement applies to mixed models for longitudinal data handling missing data implicitly. To evaluate the compliance with the EMA guideline, we evaluated the model specifications in those clinical study protocols from development phases II and III submitted between 2015 and 2018 to the Ethics Committee at Hannover Medical School under the German Medicinal Products Act, which planned to use a mixed model for longitudinal data in the confirmatory testing strategy. Overall, 39 trials from different types of sponsors and a wide range of therapeutic areas were evaluated. While nearly all protocols specify the fixed and random effects of the analysis model (95%), only 77% give the structure of the covariance matrix used for modeling the repeated measurements. Moreover, the testing method (36%), the estimation method (28%), the computation method (3%), and the fallback strategy (18%) are given by less than half the study protocols. Subgroup analyses indicate that these findings are universal and not specific to clinical trial phases or size of company. Altogether, our results show that guideline compliance is to various degrees poor and consequently, strict type I error rate control at the intended level is not guaranteed.     

Mathematische aspekte zu einer methode zur numerischen bestimmung individueller thermodynamischer aktivitätskoeffizienten einzelner ionensorten in konzentrierten elektrolytlösungen

The mathematical problems of the – in an communication [3] described – principle for the calculation of individual thermodynamic activity coefficients of single ionic species in concentrated electrolyte solutions are specified. It is the Newtonian approximation method that makes possible the evaluation of the constants b ₁,…b ₄ in the concentration function (0.1) for the product of the activity coefficients.

The efficiency of the method is represented by the example of the activity coefficients of pure and of – with other electrolytes – mixed solutions of NaCIO₄. The individual activity coefficients of the single ionic species are evaluated for several electrolytes of the concentration range from m = 0 to m = 10 mole/kg and published at another place [3, 17, 18].     

Tukey-Type Distributions in the Context of Financial Data

Abstract

In one-parameter (θ) families, we were not aware of explicit hypothesis testing scenarios where maximal invariant statistics failed to distinguish the models. We start with a concrete example (Sec. 2.2) to highlight such a hypothesis testing problem involving markedly different models. In this problem, because of the absence of a nontrivial uniformly most powerful invariant (UMPI) test, we briefly suggest two approaches to test the hypothesis. The first resolution (Sec. 3.1) is frequentist in nature. It utilizes a weight function on the parameter space and compares “average” distributions obtained under the null and alternative models in the sense of Wald (1947 Wald , A. ( 1947 ). Sequential Analysis . New York : Wiley . [Google Scholar] 1950 Wald , A. ( 1950 ). Statistical Decision Functions . New York : Wiley . [Google Scholar]). In contrast, a fully Bayesian resolution (Sec. 3.2) is also included. The note ends with a series of other interesting examples involving one-parameter families where maximal invariant statistics fail to distinguish the hypothesized models. The examples include easy-to-construct families of probability models involving only a single location or scale parameter θ.     

A Method for Computing the Fraction of Attributable Risk Related to Climate Damages

The recent decision of the U.S. Supreme Court on the regulation of CO₂ emissions from new motor vehicles^{( 1 )} shows the need for a robust methodology to evaluate the fraction of attributable risk from such emissions. The methodology must enable decisionmakers to reach practically relevant conclusions on the basis of expert assessments the decisionmakers see as an expression of research in progress, rather than as knowledge consolidated beyond any reasonable doubt.^{( 2,3,4 )} This article presents such a methodology and demonstrates its use for the Alpine heat wave of 2003. In a Bayesian setting, different expert assessments on temperature trends and volatility can be formalized as probability distributions, with initial weights (priors) attached to them. By Bayesian learning, these weights can be adjusted in the light of data. The fraction of heat wave risk attributable to anthropogenic climate change can then be computed from the posterior distribution. We show that very different priors consistently lead to the result that anthropogenic climate change has contributed more than 90% to the probability of the Alpine summer heat wave in 2003. The present method can be extended to a wide range of applications where conclusions must be drawn from divergent assessments under uncertainty.     

COMPETITION AND RELATIONAL CONTRACTS: THE ROLE OF UNEMPLOYMENT AS A DISCIPLINARY DEVICE

Abstract When workers are faced with the threat of unemployment, their relationship with a particular firm becomes valuable. As a result, a worker may comply with the terms of a relational contract that demands high effort even when performance is not enforceable by a third party. But can relational contracts motivate high effort when workers can easily find alternative jobs? We examine how competition for labor affects the emergence of relational contracts and their effectiveness in overcoming moral hazard in the labor market. We show that effective relational contracts do emerge in a market with excess demand for labor. Long‐term relationships turn out to be less frequent when there is excess demand for labor than they are in a market characterized by exogenous unemployment. However, stronger competition for labor does not impair labor market efficiency: higher wages induced by competition lead to higher effort out of concerns for reciprocity.