The impact of period effects on dose level contrasts in alternating cross‐over designs for first‐time‐in‐human studies

For first‐time‐in‐human studies with small molecules alternating cross‐over designs are often employed and at study end are analyzed using linear models. We discuss the impact of including a period effect in the model on the precision with which dose level contrasts can be estimated and quantify the bias of least squares estimators if a period effect is inherent in the data that is not accounted for in the model. We also propose two alternative designs that allow a more precise estimation of dose level contrasts compared with the standard design when period effects are included in the model. Copyright © 2010 John Wiley & Sons, Ltd.     

Aging and inactivity—capitalizing on the protective effect of planned physical activity in old age

The paper discusses two parallel biocultural trends—aging and inactivity. The principle of economy in movement in modern society versus the dependency of human beings on movement for their development and health is described. The results of inactivity are sometimes mistakenly considered irreversible losses caused by aging, but in actual fact, inactivity accelerates the irreversible losses caused by the aging process. The paper then describes the contribution of physical activity in terms of increasing positive aspects or decreasing risks: increasing life expectancy or decreasing risk of mortality, increasing cardiovascular fitness or decreasing risk of cardiovascular disease, increasing muscle mass or decreasing falls and instability, improving cognitive performance or reducing cognitive decline and neurological disorders, and improving well-being or reducing depression. The optimal dose of physical activity is then described, followed by recommendations for further research on mechanisms determining physical activity behavior.     

Some statistical properties of Hadamard products of random matrices

The mean of the Hadamard product of two linear combinations of a random matrix is presented in terms of the mean and variance of the random matrix for any distribution. The variance is given for the normal distribution. Further, the means of four Hadamard products of matrix bilinear forms in a normally distributed random matrix are given. Finally, the mean of a quadruple Hadamard product of linear combinations is derived under normality. Received: January 5, 2000; revised version: April 3, 2000     

Parametric scalp mapping and inference via spatially smooth linear models for mismatch negativity studies

Mismatch negativity (MMN) is a neurophysiological tool that can be used to investigate various facets of comprehension. Subjects are presented with different stimuli to elicit the MMN response, which is derived from electroencephalography (EEG) signals recorded at electrodes across the brain. We propose a methodology to extend single electrode analyses of MMN data by generating smooth scalp maps of estimated experimental effects. It is shown that penalized least squares estimates of effect maps can be produced using a two step procedure involving (a) ANOVA at each electrode and (b) spatial smoothing across electrodes. A Fisher von-Mises kernel is used for smoothing scalp maps with cross-validated bandwidth selection. The methodology is applied to a case control study involving aphasics (language disordered individuals). Analysis of residuals shows possible heteroscedasticity and non-Gaussian tail behavior. For robust inference, a semiparametric multivariate approach is proposed to determine the significance of parametric maps. A variety of global and regional test statistics are developed to investigate the significance of spatial patterns in treatment effects. The methodology is seen to confirm previous findings from single electrode analysis and identifies some new significant spatial patterns of difference between controls and aphasics.     

The role of mitochondria in conserved mechanisms of aging

The European research project MiMage, supported by the European Community's Sixth Framework for Research and Technological Development, focuses on elucidating the role of mitochondria in conserved mechanisms of aging. This Perspective summarizes a selection of talks presented in April 2006 at the second MiMage symposium by members from participating laboratories and invited speakers.     

The net asset value and stock prices of European real estate companies

The frequently large divergences between share price and net asset value (NAV) of listed real estate companies have been a key topic in real estate research for many years. However, previous research has mainly focused on the U.S. market, concentrating on companies’ performance ratios related to information from balance sheet statements and/or income statements as well as information from the stock market, and its results are not satisfying. This study, on the other hand, focuses on the European real estate market and presents a semi-rational model for explaining NAV spreads, taking into account performance ratios and market sentiment simultaneously. It appears that market sentiment in particular substantially improves the model, which explains more than 76% of the NAV spread. Thus, the developed model constitutes a significant improvement over previous studies on the explanation of NAV spreads.     

Classroom learning environments and the mental health of first grade children

Sociological research focuses on how poverty, family, and neighborhood dynamics shape children's problems, but knowledge about how school is related to children's mental health is underdeveloped, despite its central presence in children's lives. Using a social structure and personality-stress contagion perspective, the authors use a nationally representative sample of first graders (N = 10,700) to assess how the classroom learning environment affects children's emotional and behavior problems. Children in more negative environments-such as classrooms with fewer material resources and whose teachers receive less respect from colleagues-have more learning, externalizing, interpersonal, and internalizing problems. Moreover, children in classrooms with low academic standards, excessive administrative paperwork, rowdy behavior, and low skill level of peers have more problems across one or more outcomes. Some school effects vary across race and ethnicity.     

Perceptions of variation and change in German and Swedish address1

German and Swedish speakers diverge in contemporary address practice. The Swedish T form has become unmarked, with V limited to very specific situations. Apart from some specific T or V contexts, German now has coexistent systems, one with T, the other with V as the unmarked form, with different speakers or networks preferring one or the other. In an ongoing project, focus groups and participant observation in Austria, (eastern and western) Germany and Sweden and with Swedish speakers in Finland have identified factors and contexts determining degree of social distance and hence address choice. First name use is more marked than T use in Swedish but the two are closely linked in German. National variation is more substantial in Swedish than in German. In both languages there is some reversal of liberalization and distaste for imposition of the address form.