Sample size reestimation by Bayesian prediction

We review a Bayesian predictive approach for interim data monitoring and propose its application to interim sample size reestimation for clinical trials. Based on interim data, this approach predicts how the sample size of a clinical trial needs to be adjusted so as to claim a success at the conclusion of the trial with an expected probability. The method is compared with predictive power and conditional power approaches using clinical trial data. Advantages of this approach over the others are discussed.     

Steady-state analysis of metabolic pathways: comparing the double modulation method and the lin-log approach

The increasing interest in studying enzyme kinetics under in vivo conditions requires practical methods to estimate control parameters from experimental data. In contrast to currently established approaches of dynamic modelling, this paper addresses the steady-state analysis of metabolic pathways. Within the framework of metabolic control analysis (MCA), elasticity coefficients are used to describe the control properties of a local enzyme reaction. The double modulation method is one of the first experimental approaches to estimate elasticity coefficients from measurements of steady-state flux rates and metabolite concentrations. We propose a generalized form of the double modulation method and compare it to the recently developed linear-logarithmic approach.     

Biological protection of hardwood logs destined for panel manufacturing using <Emphasis Type="Italic">Gliocladium roseum</Emphasis> against biodegradation

The objective of the present study was to develop a biological technology that would protect logs destined for oriented strand board (OSB) manufacturing from biodegradation. Aspen, red maple, and yellow birch trees were felled in one summer and the logs either debarked or not debarked, and either treated or not treated with a biological product of Gliocladium roseum. The logs were piled in different treatment groups and stored in a yard for 5 months and 1 year before evaluation. The results showed that all untreated logs, with or without bark, were seriously degraded by moulds, stain and decay fungi after a summer storage period of 5 months. The logs with bark were more degraded than the debarked logs, and the log ends were more degraded than the middle sections. After 5 months, 55–83% of the surface area of the wood discs was degraded in untreated logs. The biological treatment was effective, and only 4–16% of the surface area of the wood discs in treated logs was infected by various fungi. Strands cut from untreated logs consisted of 50–75% grey- or blue-stained strands, whereas those cut from biologically treated logs consisted of 10–25% such strands. Panels made using biologically treated logs had a lower thickness swelling and water absorption values compared to panels made using freshly cut logs and untreated stored logs. The other physical and mechanical properties of the various panels made in this test were comparable. In terms of mould resistance, all panels made from fungal-treated logs had a better mould resistance than those made from freshly cut and untreated logs.     

Monitoring succession from space: A case study from the North Carolina Piedmont

Question: Is the successional transition from pine to hardwood, which has been inferred from chronosequence plots in previous studies, validated through a time line of satellite imagery? Location: Durham, North Carolina, USA. Methods: We examined successional trends in a time‐series of winter‐summer pairs of Thematic Mapper imagery from 1986 to 2000. We calculated the normalized difference of vegetation index (NDVI) for winter and summer, as well as the difference between summer and winter NDVI (i.e., summer increment NDVI). A set of approximately 50 forest stands of known age and phenology were used to interpret patterns in winter and summer increment NDVI over successional time, and a continuum was found to exist between pine‐dominance and hardwood‐dominance. We fitted a series of linear regressions that modeled the change in winter and summer increment NDVI as a function of initial winter and summer increment NDVI, and additional explanatory variables. Results: All regressions were highly significant (P < 0.0001, R²= ca. 0.3). Predicted dynamics are in accord with successional theory, with pixels moving from evergreen dominance to deciduous dominance along a line of fairly constant summer NDVI. A large disturbance event that occurred over the course of this study, Hurricane Fran, appeared to slow rates of succession in the short term (1–3 years), but increase the rate of conversion to hardwoods over longer time spans. Conclusions: We conclude that temporal sequences of remote sensing images provide an excellent opportunity for broad‐scale monitoring of successional processes, and that continuous metrics of that change are essential to accurate monitoring.     

Graphical Chain Models and Mental Disorders: An Application to Pathological Gambling

This paper demonstrates that graphical chain models are a suitable statistical tool for investigating the complex structure of a psychiatric disease. The article is motivated by a crucial question arising in psychometric studies on pathological gambling: how are depression and anxiety associated and how do they determine the personality of a pathological gambler? Starting from an initial recursive structure that reduces the complexity of the data, graphical chain models investigate both direct associations and indirect dependencies among the psychometric scales measuring the personality traits. A “behavioral chain” acting in pathological gambling is suggested by the final chain resulted from the Cox and Wermuth variables selection strategy (Cox and Wermuth, 1996). (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Unbiased Confidence Intervals for the Odds Ratio of Two Independent Binomial Samples with Application to Case–Control Data

The problem of confidence interval construction for the odds ratio of two independent binomial samples is considered. Two methods of eliminating the nuisance parameter from the exact likelihood, conditioning and maximization, are described. A conditionally exact tail method exists by putting together upper and lower bounds. A shorter interval can be obtained by simultaneous consideration of both tails. We present here new methods that extend the tail and simultaneous approaches to the maximized likelihood. The methods are unbiased and applicable to case-control data, for which the odds ratio is important. The confidence interval procedures are compared unconditionally for small sample sizes in terms of their expected length and coverage probability. A Bayesian confidence interval method and a large-sample chi2 procedure are included in the comparisons.     

Genetic characterisation of dough rheological properties in a wheat doubled haploid population: additive genetic effects and epistatic interactions

Doubled haploid lines (n=160) from a cross between wheat cultivars Cranbrook (high dough extensibility) and Halberd (low dough extensibility) were grown at three Australian locations. The parents differ at all high- and low-molecular-weight glutenin loci. Dough rheological parameters were measured using small-scale testing procedures, and quantitative trait locus (QTL) mapping procedures were carried out using an existing well-saturated genetic linkage map for this cross. Genetic parameters were estimated using three software packages: QTLCartographer, Epistat and Genstat. Results indicated that environmental factors are a major determinant of dough extensibility across the three trial sites, whereas genotypic factors are the major determinants of dough strength. Composite interval mapping analysis across the 21 linkage groups revealed that as expected, the main additive QTLs for dough rheological properties are located at the high- and low-molecular-weight glutenin loci. A new QTL on chromosome 5A for M-extensibility (a mixograph-estimated measure of extensibility) was detected. Analysis of epistatic interactions revealed that there were significant conditional epistatic interactions related with the additive effects of glutenin loci on dough rheological properties. Therefore, the additive genetic effects of glutenins on dough rheological properties are conditional upon the genetic background of the wheat line. The molecular basis of the interactions with the glutenin loci may be via proteins that modify or alter the gluten protein matrix or variations in the expression level of the glutenin genes. Reverse-phase high performance liquid chromatography analysis of the molar number of individual glutenin subunits across the population showed that certain conditional epistases resulted in increased expression of the affected glutenin. The epistatic interactions detected in this study provide a possible explanation of the variable genetic effects of some glutenins on quality attributes in different genetic backgrounds and provide essential information for the accurate prediction of glutenin related variance in marker-assisted wheat breeding.     

Notch1 is essential for postnatal hair follicle development and homeostasis

Notch genes encode evolutionarily conserved large, single transmembrane receptors, which regulate many cell fate decisions and differentiation processes during fetal and postnatal life. Multiple Notch receptors and ligands are expressed in both developing and adult epidermis and hair follicles. Proliferation and differentiation of these two ectodermal-derived structures have been proposed to be controlled in part by the Notch pathway. Whether Notch signaling is involved in postnatal hair homeostasis is currently unknown. Here, we investigate and compare the role of the Notch1 receptor during embryonic hair follicle development and postnatal hair homeostasis using Cre-loxP based tissue specific and inducible loss-of-function approaches. During embryonic development, tissue-specific ablation of Notch1 does not perturb formation and patterning of hair follicle placodes. However, Notch1 deficient hair follicles invaginate prematurely into the dermis. Embryonic as well as postnatal inactivation of Notch1 shortly after birth or in adult mice results in almost complete hair loss followed by cyst formation. The first hair cycle of Notch1 deficient mice is characterized by shortened anagen and a premature entry into catagen. These data show that Notch1 is essential for late stages of hair follicle development during embryogenesis as well as for post-natal hair follicle development and hair homeostasis.     

Conditional likelihood score functions for mixed models in linkage analysis

In this paper, we develop a general strategy for linkage analysis, applicable for arbitrary pedigree structures and genetic models with one major gene, polygenes and shared environmental effects. Extending work of Whittemore (1996), McPeek (1999) and Hossjer (2003d), the efficient score statistic is computed from a conditional likelihood of marker data given phenotypes. The resulting semiparametric linkage analysis is very similar to nonparametric linkage based on affected individuals. The efficient score S depends not only on identical-by-descent sharing and phenotypes, but also on a few parameters chosen by the user. We focus on (1) weak penetrance models, where the major gene has a small effect and (2) rare disease models, where the major gene has a possibly strong effect but the disease causing allele is rare. We illustrate our results for a large class of genetic models with a multivariate Gaussian liability. This class incorporates one major gene, polygenes and shared environmental effects in the liability, and allows e.g. binary, Gaussian, Poisson distributed and life-length phenotypes. A detailed simulation study is conducted for Gaussian phenotypes. The performance of the two optimal score functions S(wpairs) and S(normdom) are investigated. The conclusion is that (i) inclusion of polygenic effects into the score function increases overall performance for a wide range of genetic models and (ii) score functions based on the rare disease assumption are slightly more powerful.