Distribution-free ROC analysis using binary regression techniques

Receiver operating characteristic (ROC) regression methodology is used to identify factors that affect the accuracy of medical diagnostic tests. In this paper, we consider a ROC model for which the ROC curve is a parametric function of covariates but distributions of the diagnostic test results are not specified. Covariates can be either common to all subjects or specific to those with disease. We propose a new estimation procedure based on binary indicators defined by the test result for a diseased subject exceeding various specified quantiles of the distribution of test results from non-diseased subjects with the same covariate values. This procedure is conceptually and computationally simplified relative to existing procedures. Simulation study results indicate that the approach has fairly high statistical efficiency. The new ROC regression methodology is used to evaluate childhood measurements of body mass index as a predictive marker of adult obesity.     

Automated image analysis to improve bead ingestion toxicity test counts in the protozoan Tetrahymena pyriformis

AIMS: To improve bead ingestion counts in Tetrahymena pyriformis by automated image analysis as an alternative to direct-counts. METHODS AND RESULTS: Fluorescent latex beads were added to T. pyriformis cultures for ingestion tests. The number of beads ingested by 25 cells was counted directly by epifluorescence microscopy and compared with similar data from image analysis. anova indicated that counts were not significantly different (P < 0.05). The image analysis particularly provided advantages in terms of speed. CONCLUSIONS: The image analysis is superior to direct beads counting in T. pyriformis particularly in terms of speed of analysis. SIGNIFICANCE AND IMPACT OF THE STUDY: The image analysis method is very rapid and will allow many more toxicological analyses to be undertaken with less operator error.     

Analysis of infant handling and the effects of female rank among Tana River adult female yellow baboons (Papio cynocephalus cynocephalus) using permutation/randomization tests.

Infant handling has been documented in numerous species. Among cercopithecines, interaction motivations are reported to range from aunting to kidnapping; these interactions are often distressful for both mother and infant. Here we examine handling by adult female yellow baboons (Papio cynocephalus cynocephalus) at the Tana River National Primate Reserve, Kenya, using a relatively new, computer-intensive statistical approach of permutation/randomization tests to deal with repeated measures effects and a skewed sample. We hypothesized 1) a tendency for handlers to handle the infants of females ranked similarly or lower than themselves, and 2) more successful infant handling by higher-ranked females, particularly with very young infants. We collected focal data on 23 females (11 mother-infant pairs) over an 11-mo period, with a total of 303 attempted and/or successful "handles" utilized in the permutation analyses. The general patterns apparent in the data seemed to support our hypotheses. However, the permutation tests showed that while females are somewhat more likely to attempt to handle the infants of females ranked "same or lower" than themselves, lower-ranked females are able to prevent more than three-fourths of the attempted interactions, and there is no statistically significant trend for females to successfully handle these infants. Further refinement of the analyses showed no significant tendencies for females to handle those infants ranked "lower" or "immediately lower" than themselves, casting doubt on the significant finding for "same or lower" attempts. Further, there was no significant effect for higher-ranked females to successfully handle an infant during its first month. Thus, rank does not seem to offer any privileges in terms of handling an infant in this population. We believe the permutation tests are an effective way to analyze repeated measures data and offer a more sensitive analysis tool for determining true significance.     

Likelihood analysis of ongoing gene flow and historical association

Abstract.— We develop a Monte Carlo-based likelihood method for estimating migration rates and population divergence times from data at unlinked loci at which mutation rates are sufficiently low that, in the recent past, the effects of mutation can be ignored. The method is applicable to restriction fragment length polymorphisms (RFLPs) and single nucleotide polymorphisms (SNPs) sampled from a subdivided population. The method produces joint maximum-likelihood estimates of the migration rate and the time of population divergence, both scaled by population size, and provides a framework in which to test either for no ongoing gene flow or for population divergence in the distant past. We show the method performs well and provides reasonably accurate estimates of parameters even when the assumptions under which those estimates are obtained are not completely satisfied. Furthermore, we show that, provided that the number of polymorphic loci is sufficiently large, there is some power to distinguish between ongoing gene flow and historical association as causes of genetic similarity between pairs of populations.     

均衡独立样本设计的研究

均衡独立样本设计是一种把独立样本设计与差异显著性检验相结合的试验设计．它基本上可以保证参试的优劣个体在所分样本（或组）间的分布相对均匀一致,使所分样本既具有独立性又具有均衡性,以增强对处理效果反应的灵敏度,提高试验的准确度．     

The Use of Multiple Outcomes Analysis in Neurotoxicity: An Example from the New Zealand Study of Offspring of Mothers Exposed to Methyl Mercury

Neurotoxicity has become an important area in the study of the risk to children of noncarcinogens. Many of the tests used to evaluate neurotoxic effects in neurotoxic studies are psychometric tests to assess cognitive, motor, and perceptual performance in individuals in order to determine the presence of psychological problems, impaired educational achievement, or neurological abnormalities. The underlying assumption of these procedures are that a test performance deficit is indicative of a neurological disability, and that such disability derives from the prenatal exposure to an offending substance. The usual analytic paradigm for discerning environmental impacts is to analyze the scores of a particular subtest in a battery taken separately as the dependent variable with regression analysis, which adjusts for cultural background, educational level, and socioeconomic status. The impact of this analysis is to determine the correlation of each of the psychometric test results to exposure. We show a statistical method to simultaneously analyze the multiple outcomes of many tests using General Estimating Equations (GEE) to determine if a correlation exists between the global measure of all these tests and exposure adjusted for covariates of interest and the correlation among the dependent psychometric variables. We show the application of this method to the results of children whose mothers were exposed to mercury during pregnancy.     

Variation in sclerophylly among Iberian populations of Quercus coccifera L. is associated with genetic differentiation across contrasting environments

Evergreen oaks are an emblematic element of the Mediterranean vegetation and have a leaf phenotype that seems to have remained unchanged since the Miocene. We hypothesise that variation of the sclerophyll phenotype among Iberian populations of Quercus coccifera is partly due to an ulterior process of ecotypic differentiation. We analysed the genetic structure of nine Iberian populations using ISSR fingerprints, and their leaf phenotypes using mean and intracanopy plasticity values of eight morphological (leaf angle, area, spinescence, lobation and specific area) and biochemical traits (VAZ pool, chlorophyll and β-carotene content). Climate and soil were also characterised at the population sites. Significant genetic and phenotypic differences were found among populations and between NE Iberia and the rest of the populations of the peninsula. Mean phenotypes showed a strong and independent correlation with both genetic and geographic distances. Northeastern plants were smaller, less plastic, with smaller, spinier and thicker leaves, a phenotype consistent with the stressful conditions that prevailed in the steppe environments of the refugia within this geographic area during glaciations. These genetic, phenotypic, geographic and environmental patterns are consistent with previously reported palaeoecological and common evidence. Such consistency leads us to conclude that there has been a Quaternary divergence within the sclerophyllous syndrome that was at least partially driven by ecological factors.     

Phenotyping Mouse Pulmonary Function In Vivo with the Lung Diffusing Capacity

The mouse is now the primary animal used to model a variety of lung diseases. To study the mechanisms that underlie such pathologies, phenotypic methods are needed that can quantify the pathologic changes. Furthermore, to provide translational relevance to the mouse models, such measurements should be tests that can easily be done in both humans and mice. Unfortunately, in the present literature few phenotypic measurements of lung function have direct application to humans. One exception is the diffusing capacity for carbon monoxide, which is a measurement that is routinely done in humans. In the present report, we describe a means to quickly and simply measure this diffusing capacity in mice. The procedure involves brief lung inflation with tracer gases in an anesthetized mouse, followed by a 1 min gas analysis time. We have tested the ability of this method to detect several lung pathologies, including emphysema, fibrosis, acute lung injury, and influenza and fungal lung infections, as well as monitoring lung maturation in young pups. Results show significant decreases in all the lung pathologies, as well as an increase in the diffusing capacity with lung maturation. This measurement of lung diffusing capacity thus provides a pulmonary function test that has broad application with its ability to detect phenotypic structural changes with most of the existing pathologic lung models.     

Improved Logrank-Type Tests for Survival Data Using Adaptive Weights

Summary .  For testing for treatment effects with time-to-event data, the logrank test is the most popular choice and has some optimality properties under proportional hazards alternatives. It may also be combined with other tests when a range of nonproportional alternatives are entertained. We introduce some versatile tests that use adaptively weighted logrank statistics. The adaptive weights utilize the hazard ratio obtained by fitting the model of Yang and Prentice (2005,  Biometrika   92 , 1–17). Extensive numerical studies have been performed under proportional and nonproportional alternatives, with a wide range of hazard ratios patterns. These studies show that these new tests typically improve the tests they are designed to modify. In particular, the adaptively weighted logrank test maintains optimality at the proportional alternatives, while improving the power over a wide range of nonproportional alternatives. The new tests are illustrated in several real data examples.