An Automatic Test for the Umbrella Alternatives

The paper proposes a new test for detecting the umbrella pattern under a general non‐parametric scheme. The alternative asserts that the umbrella ordering holds while the hypothesis is its complement. The main focus is put on controlling the power function of the test outside the alternative. As a result, the asymptotic error of the first kind of the constructed solution is smaller than or equal to the fixed significance level α on the whole set where the umbrella ordering does not hold. Also, under finite sample sizes, this error is controlled to a satisfactory extent. A simulation study shows, among other things, that the new test improves upon the solution widely recommended in the literature of the subject. A routine, written in R, is attached as the Supporting Information file.     

Meeting summary--cell biology of Parkinson's disease and related neurodegenerative disorders

Parkinsonian disorders (idiopathic Parkinson's disease and clinically similar disorders) are characterized by impaired movements caused by the degeneration of brain centers involved in regulating normal and smooth movements of the body and its extremities. The mechanisms that cause such degeneration are unknown. This Perspective summarizes research described at a meeting held in June 2003, which was organized by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging to provide an update on recent advances in the cell biology of parkinsonian disorders.     

Alzheimer's disease,neuropeptides, neuropeptidase,and amyloid-beta peptide metabolism

Amyloid-beta peptide (Abeta), the pathogenic agent of Alzheimer's disease (AD), is a physiological metabolite in the brain. We have focused our attention and effort on elucidating the unresolved aspect of Abeta metabolism: proteolytic degradation. Among a number of Abeta-degrading enzyme candidates, we used a novel in vivo paradigm to identify a member of the neutral endopeptidase family, neprilysin, as the major Abeta catabolic enzyme. Neprilysin deficiency results in defects in the metabolism of endogenous Abeta 40 and 42 in a gene dose-dependent manner. Our observations suggest that even partial down-regulation of neprilysin activity, which could be caused by aging, can contribute to AD development by promoting Abeta accumulation. Moreover, we discuss the fact that an aging-dependent decline of neprilysin activity, which leads to elevation of Abeta concentrations in the brain, is a natural process that precedes AD pathology. In this Perspective, we hypothesize that neprilysin down-regulation has a role in sporadic AD (SAD) pathogenesis, and we propose that this knowledge be used for developing preventive and therapeutic strategies through use of a G protein-coupled receptor (GPCR).     

Books and Publications Received

Manpower developments should be examined against the population background. Population and manpower structure of post-war Europe is the haphazard result of various trends, war losses and tremendous shifts of population. Conditions have been changing rapidly, so that computations regarding the structural changes of populations prior to 1949 are in many cases not significant.

The major pre-war trends in economic structure appear to have continued after the war with the exception of commerce, which has not maintained its previous upward trend.

The present disturbed situation is not a convenient platform for projections of population or of manpower. Anyhow, any speculation as to future developments should be based on the knowledge of the specific conditions obtaining in the various countries. Differences in the economic and social structure, as well as in legislation between the various parts of Europe, no longer warrant a smooth and uniform development in accordance with the pre-war pattern. There are, on the other hand, some features of a prospective rapprochement in the economic and social field between Western and Eastern Europe.     

Confidence estimation via the parametric bootstrap in logistic joinpoint regression

We consider asymptotic properties of the maximum likelihood and related estimators in a clustered logistic joinpoint model with an unknown joinpoint. Sufficient conditions are given for the consistency of confidence bounds produced by the parametric bootstrap; one of the conditions required is that the true location of the joinpoint is not at one of the observation times. A simulation study is presented to illustrate the lack of consistency of the bootstrap confidence bounds when the joinpoint is an observation time. A removal algorithm is presented which corrects this problem, but at the price of an increased mean square error. Finally, the methods are applied to data on yearly cancer mortality in the US for individuals age 65 and over.     

Drug discovery in neurodegenerative diseases

This meeting report documents the exciting ongoing research aimed at developing new therapeutic agents for neurodegenerative diseases at the interface between academia and industry, and illustrates the direction the NIH "roadmap" for medical research is taking. Some of the projects have resulted in very promising drugs, identified and developed by academic centers, entering clinical trials.     

Data-Driven Tests for Trend

This article proposes a new nonparametric test for the ordered alternatives problem in the k-sample setting for null hypothesis of lack of trend. This article further elaborates upon and extends the results of Ledwina and Wy?upek (2012a Ledwina , T. , Wy?upek , G. ( 2012a ). Two-sample test against one-sided alternatives . Scand. J. Statist. 39 : 358 – 381 .[Crossref], [Web of Science ®] , [Google Scholar]) obtained for k = 2. Simulations show that the new test has high and stable power and is able to control the Type I error to satisfactory extent, thus solving the problem posed in Terpstra and Magel (2003 Terpstra , J. T. , Magel , R. C. ( 2003 ). A new nonparametric test for the ordered alternative problem . J. Nonparametr. Statist. 15 : 289 – 301 .[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]). Our theoretical results say that asymptotic errors of both kinds do not exceed significance level, thus implying that the test is asymptotically unbiased.     

Minimum variance rectangular designs for U-statistics

We consider a certain class of rectangular designs for incomplete U-statistics based on Latin squares and show it to be optimal with respect to the minimal variance criterion. We also show it to be asymptotically efficient when compared with the corresponding complete statistics, as well as uniformly more efficient than the random subset selection. We provide the necessary and sufficient conditions for the existence of our design and give some examples of applications.     

Prediction intervals for time series models with trend via sieve bootstrap

This paper discusses method for constructing the prediction intervals for time series model with trend using the sieve bootstrap procedure. Gasser–Müller type of kernel estimator is used for trend estimation and prediction. The boundary modification of the kernel is applied to control the edge effect and to construct the predictor of a trend.