Exploring Extra-Binomial Variation in Teratology Data Using Continuous Mixtures

Discrete data from animal teratology experiments are known to exhibit extra-binomial variation. For example, we discuss a dominant lethal assay experiment in which male mice are exposed to various levels of radiation and are then mated to females. The response of interest is the number of resorptions out of the number of implantations. Most statistical work on analyzing such data has focused on modeling response rates as a function of dose of a suspected teratogen (radiation in this case) while accounting for the extra-binomial variability when calculating standard errors of the regression coefficients. Sometimes, however, when an unobserved genetic or exposure variable is suspected, the shape of the mixing distribution is of interest. We propose a mixture of beta-binomials (MBB) family of distributions that includes the non-parametric mixture of binomials model of Laird (1978) as a special case. The MBB family can accommodate a mixing distribution with one or more modes, and we develop a bootstrap test for multimodality. We apply the method to data from a dominant lethal teratology experiment.     

Nonhuman primates and teratological research

Nonhuman primates were first recognized as models for the study of developmental toxicity (teratology) following the thalidomide tragedy. Since that time they have played important roles in both testing of drugs for human safety and as models for studying specific malformations commonly seen in children. Although in vitro and alternative test systems using lower animal forms or simplified test systems have been incorporated into developmental toxicity studies, whole animal testing will be required for the foreseeable future because of the complex relationship of the maternal/embryofetal/placental unit. The nonhuman primate will be particularly valuable where equivocal results are experienced in other commonly used laboratory species, when the drug/chemical is likely to be used during pregnancy, and for human-derived biotechnical products which often are not bioactive in nonprimate species.     

Four decades of teaching developmental biology in Germany

I have taught developmental biology in Essen for 30 years. Since my department is named Zoophysiologie (Zoophysiology), besides Developmental Biology, I also have to teach General Animal Physiology. This explains why the time for teaching developmental biology is restricted to a lecture course, a laboratory course and several seminar courses. However, I also try to demonstrate in the lecture courses on General Physiology the close relationship between developmental biology, physiology, morphology, anatomy, teratology, carcinogenesis, evolution and ecology (importance of environmental factors on embryogenesis). Students are informed that developmental biology is a core discipline of biology. In the last decade, knowledge about molecular mechanisms in different organisms has exponentially increased. The students are trained to understand the close relationship between conserved gene structure, gene function and signaling pathways, in addition to or as an extension of, classical concepts. Public reports about the human genome project and stem cell research (especially therapeutic and reproductive cloning) have shown that developmental biology, both in traditional view and at the molecular level, is essential for the understanding of these complex topics and for serious and non-emotional debate.     

Morphological and ecological determinants of body temperature of Geukensia demissa, the Atlantic ribbed mussel, and their effects on mussel mortality

Measurements of body temperatures in the field have shown that spatial and temporal patterns are often far more complex than previously anticipated, particularly in intertidal regions, where temperatures are driven by both marine and terrestrial climates. We examined the effects of body size, body position within the sediment, and microhabitat (presence or absence of Spartina alterniflora) on the body temperature of the mussel Geukensia demissa. We then used these data to develop a laboratory study exposing mussels to an artificial "stressful" day, mimicking field conditions as closely as possible. Results suggested that G. demissa mortality increases greatly at average daily peak temperatures of 45 degrees C and higher. When these temperatures were compared to field data collected in South Carolina in the summer of 2004, our data indicated that mussels likely experienced mortality due to high-temperature stress at this site during this period. Our results also showed that body position in the mud is the most important environmental modifier of body temperature. This experiment suggested that the presence of marsh grass leads to increases in body temperature by reducing convection, overwhelming the effects of shading. These data add to a growing body of evidence showing that small-scale thermal variability can surpass large-scale gradients.     

Inter-laboratory comparison of numerical dosimetry for human exposure to 60 Hz electric and magnetic fields

In recent years, with the availability of high resolution models of the human body, numerical computations of induced electric fields and currents have been made in more than one laboratory for various exposure conditions. Despite the verification of computational methods, questions are often asked about the reliability of these data. In this paper, computational results from two laboratories that presented data in compatible formats are compared, supplemented with additional data from the third laboratory. Two exposures to uniform fields at 60 Hz are evaluated. The human body models used in the computations are different and so are the computation al methods and codes. There are some differences in the conductivity values used for some of the tissues, as well. The results of the comparison confirm that these data are reliable, as the overall agreement is reasonably good and the differences can be rationally explained. This comparison also underscores the importance of accurate data on the dielectric properties of tissues.     

Comparative analysis of experimental testing procedures for the elicitation of rescue actions in ants

Rescue behavior is observed when 1 individual provides help to another individual in danger. Most reports of rescue behavior concern ants (Formicidae), in which workers rescue each other from various types of entrapment. Many of these entrapment situations can be simulated in the laboratory using an entrapment bioassay, in which ants confront a single endangered nest mate entrapped on a sandy arena by means of an artificial snare. Here, we compared numerous characteristics of rescue actions (contact between individuals, digging around the entrapped individual, pulling at its body parts, transport of the sand covering it, and biting the snare entrapping it) in Formica cinerea ants. We performed entrapment tests in the field and in the laboratory, with the latter under varying conditions in terms of the number of ants potentially engaged in rescue actions and the arena substrate (marked or unmarked by ants’ pheromones). Rescue actions were more probable and pronounced in the field than in the laboratory, regardless of the type of test. Moreover, different test types in the laboratory yielded inconsistent results and showed noteworthy variability depending on the tested characteristic of rescue. Our results illustrate the specifics of ant rescue actions elicited in the natural setting, which is especially important considering the scarcity of field data. Furthermore, our results underline the challenges related to the comparison of results from different types of entrapment tests reported in the available literature. Additionally, our study shows how animal behavior differs in differing experimental setups used to answer the same questions.     

An analysis of allozymic characters of four species of New Zealand Amalda (Gastropoda: Olividae: Ancillinae)

Abstract

This contribution reports the results of an electrophoretic analysis of four species of the molluscan genus Amalda. The results of this analysis confirm that four taxonomically defined species are also biologically distinct, that their often considerable morphological variability is a within-species phenomenon, and that a previously undescribed form of A. depressa, which is genetically and morphologically distinct, occurs in the Bay of Islands. The genetic data were analysed cladistically and the resulting phylogenetic classification supports that based on morphology.     

Wild mouse open field behavior is embedded within the multidimensional data space spanned by laboratory inbred strains

The vast majority of studies on mouse behavior are performed on laboratory mouse strains (Mus laboratorius), while studies of wild-mouse behavior are relatively rare. An interesting question is the relationship between the phenotypes of M. laboratorius and the phenotypes of their wild ancestors. It is commonly believed, often in the absence of hard evidence, that the behavior of wild mice exceeds by far, in terms of repertoire richness, magnitude of variables and variability of behavioral measures, the behavior of the classical inbred strains. Having phenotyped the open field behavior (OF) of eight of the commonly used laboratory inbred strains, two wild-derived strains and a group of first-generation-in-captivity local wild mice (Mus musculus domesticus), we show that contrary to common belief, wild-mouse OF behavior is moderate, both in terms of end-point values and in terms of their variability, being embedded within the multidimensional data space spanned by laboratory inbred strains. The implication could be that whereas natural selection favors moderate locomotor behavior in wild mice, the inbreeding process tends to generate in mice, in some of the features, extreme and more variable behavior.     

Methods for testing hypotheses across studies: applications for teratologists and toxicologists

Methods are presented for analyzing research results across independent studies. These techniques allow researchers to test hypotheses across studies using multiple investigations as data points. The procedures and rationale are developed for purposes of research synthesis and interpretation in teratology and toxicology.     

Competition in variable environments: experiments with planktonic rotifers

1. In a constant environment, competition often tends to reduce species diversity. However, several theories predict that temporal variation in the environment can slow competitive exclusion and allow competing species to coexist. This study reports on laboratory competition experiments in which two pairs of planktonic rotifer species competed for a phytoplankton resource under different conditions of temporal variability in resource supply.
2. For both species pairs, Keratella cochlearis dominated under all conditions of temporal variability, and the other species ( Brachionus calyciflorus or Synchaeta sp.) almost always went extinct. Increasing temporal variation in resource supply slowed competitive exclusion but did not change competitive outcome or allow coexistence.
3. Rotifers show a gleaner–opportunist trade-off, because gleaner species have low threshold resource levels ( R *) and low maximum population growth rates, while opportunist species have the opposite characteristics. In the competition experiments, the gleaner always won and the opportunists always lost. Thus, a gleaner–opportunist trade-off was not sufficient to facilitate coexistence under conditions of resource variability. Instead, the winning species had both the lowest R * and the greatest ability to store resources and ration their use during times of extreme resource scarcity.     

Bioremediation Scaleup Effectiveness: A Review

Bioremediation has been applied in laboratory-scale testing to simulate field-scale bioremediation applications. The simulations have focused on the development of concentration-time profile data in the laboratory to be modeled and used for predicting field-scale performance, particularly the time of treatment and the treatment concentration endpoints. This review reports on more than a dozen examples of bioremediation where both the laboratory-scale and field-scale data are provided. These data have been analyzed to examine how well the laboratory-scale kinetics predict the kinetics at field scale. In most cases, the laboratory-scale kinetics exceed field-scale kinetics and underpredict the time of treatment to a given endpoint in excess of 100% and by as much as 11,900%. In some cases, the laboratory-scale kinetic rate constants fall between ±100% of the field-scale kinetics, leading to predictions within 50 to 200% of the time of treatment to a given concentration level. Not enough examples nor details within the references exist to permit a detailed explanation of why these differences exist. However, several hypotheses are given in this review as to why scaleup is often problematic, and comments from other investigators on this topic are presented.     

文昌鱼的实验室繁育及子二代获得

文昌鱼特殊的进化地位、简单的器官系统和终生透明的躯体等特征,使其很有希望成为一个新型实验室模式动物。要实现文昌鱼的模式动物化,实验室内全人工条件下繁殖是关键的第一步。为此,我们于2003年9月和2004年4月两次采集产于厦门海域的2种文昌鱼,开展实验室内养殖研究。经过3年多的持续实验室养殖,继2005年夏季于实验室内繁殖出子一代文昌鱼后,又在2006年夏季成功获得了这两种文昌鱼的子二代,初步实现文昌鱼在实验室内的全人工养殖。对子代文昌鱼养殖的初步观察发现,不同水温对生长发育速度有一定影响,提示有可能通过水温控制实现文昌鱼一年多次产卵的目的。目前这两种文昌鱼子二代幼体已完成变态,进入亚成体生长发育阶段,其体长分别已达14.6mm(日本文昌鱼Branchiostomajaponicum)和6.5mm(白氏文昌鱼B.belcheri)。     

On a likelihood-based goodness-of-fit test of the beta-binomial model

When faced with proportion data that exhibit extra-binomial variation, data analysts often consider the beta-binomial distribution as an alternative model to the more common binomial distribution. A typical example occurs in toxicological experiments with laboratory animals, where binary observations on fetuses within a litter are often correlated with each other. In such instances, it may be of interest to test for the goodness of fit of the beta-binomial model; this effort is complicated, however, when there is large variability among the litter sizes. We investigate a recent goodness-of-fit test proposed by Brooks et al. (1997, Biometrics 53, 1097-1115) but find that it lacks the ability to distinguish between the beta-binomial model and some severely non-beta-binomial models. Other tests and models developed in their article are quite useful and interesting but are not examined herein.     

New approach to the statistical analysis of cardiovascular data.

Fourier-based approaches to analysis of variability of R-R intervals or blood pressure typically compute power in a given frequency band (e.g., 0.01-0.07 Hz) by aggregating the power at each constituent frequency within that band. This paper describes a new approach to the analysis of these data. We propose to partition the blood pressure variability spectrum into more narrow components by computing power in 0.01-Hz-wide bands. Therefore, instead of a single measure of variability in a specific frequency interval, we obtain several measurements. The approach generates a more complex data structure that requires a careful account of the nested repeated measures. We briefly describe a statistical methodology based on generalized estimating equations that suitably handles this more complex data structure. To illustrate the methods, we consider systolic blood pressure data collected during psychological and orthostatic challenge. We compare the results with those obtained using the conventional methods to compute blood pressure variability, and we show that our approach yields more efficient results and more powerful statistical tests. We conclude that this approach may allow a more thorough analysis of cardiovascular parameters that are measured under different experimental conditions, such as blood pressure or heart rate variability.     

Control of variability

Genetic variability is an important component of the phenotypic variation within populations; however, there are often many other contributing factors, which receive little attention. Randomization techniques or grouping factors known to contribute to variability can do much to isolate, or at least accommodate, this variability. The European Centre for the Validation of Alternative Methods addressed some of these approaches in 1998, and others are considered in this article. However, laboratory animals are living beings that respond to scientific procedures, or indeed to subtle variations in husbandry conditions, which our senses do not equip us to comprehend readily. These variations may either bias our experimental results or introduce sufficient background noise to mask differences arising from the scientific procedures. In planning an experiment, it is important to devote adequate time considering such factors and developing appropriate strategies to handle them.     

Variation in the transition from inside to outside work in the red harvester ant Pogonomyrmex barbatus

Summary. In laboratory colonies of the red harvester ant, Pogonomyrmex barbatus, we observed the sequence of tasks performed by marked individuals. Observations of about 760 ants in three laboratory colonies indicate that ants often move from inside to outside work. However, there was a great deal of variation in the sequence. If trends in sequence were weak because ants do move from inside to outside work but the duration of our observations was too short to see the transition, ants should be observed to stay either inside or outside. There was no significant tendency for ants to persist in inside or outside work, indicating the variability in sequence is real. Ants tended to perform midden work before they died. Foraging activity is low in laboratory colonies, and it may be that ants that would be foragers in the field end up as midden workers in the laboratory. High variability in task sequence, in uniform laboratory conditions, contrasts with the apparently more consistent sequence from inside to outside work in the field. This suggests that requirements imposed by variable external conditions and colony needs in the field have a strong influence on task sequence.Received 7 May 2004; revised 11 November 2004; accepted 18 November 2004.     

Uncertainty in Calculations of Net Primary Production for Grasslands

Net primary production (NPP) is a fundamental characteristic of all ecosystems and foundational to understanding the fluxes of energy and nutrients. Because NPP cannot be measured directly, researchers use field-measured surrogates as input variables in various equations designed to estimate ‘true NPP’. This has led to considerable debate concerning which equations most accurately estimate ‘true NPP’. This debate has influenced efforts to assess NPP in grasslands, with researchers often advocating more complex equations to avoid underestimation. However, this approach ignores the increase in statistical error associated with NPP estimates as a greater number of parameters and more complex mathematical functions are introduced into the equation. Using published grassland data and Monte Carlo simulation techniques, we assessed the relative variability in NPP estimates obtained using six different NPP estimation equations that varied in both the number of parameters and intricacy of mathematical operations. Our results indicated that more complex equations may result in greater uncertainty without reducing the probability of underestimation. The amount of uncertainty associated with estimates of NPP was influenced by the number of parameters as well as the variability in the data and the nature of the mathematical operations. For example, due to greater variability in the field-measured belowground data than aboveground data, estimates of belowground NPP tended to have more uncertainty than estimates of aboveground NPP. An analysis in which the input data were standardized allowed us to isolate the details of the calculations from the variability in the data in assessing the propagation of uncertainty. This analysis made clear that equations with product terms have the potential to magnify the uncertainty of the inputs in the estimates of NPP although this relationship was complicated by interactions with data variability and number of parameters. Our results suggest that more complex NPP estimation equations can increase uncertainty without necessarily reducing risk of underestimation. Because estimates can never be tested by comparison to “true NPP”, we recommend that researchers include an assessment of propagation of statistical error when evaluating the ‘best’ estimation method.     

Ecological realism and mechanisms by which diversity begets stability

We investigated how ecological realism might impact the outcome of three experimental manipulations of species richness to determine whether the patterns and the mechanisms underlying richness–variability relationships differ as ecological communities are increasingly exposed to external forces that may drive richness–variability patterns in nature. To test for such an effect, we conducted experiments using rock pool meio‐invertebrate communities housed in three experimental venues: controlled laboratory microcosms, artificially constructed rock pools in the field, and naturally occurring rock pools in the field. Our results showed that experimental venue can have a strong effect on the outcome of richness manipulation experiments. As ecological realism increased, the strength of the relationship between species richness and community variability declined from 32.9% in the laboratory microcosms to 16.8% in the artificial pools to no effect of species richness on community variability in the natural rock pools. The determinants of community variability also differed as ecological realism increased. In laboratory microcosms, community variability was driven solely by mechanisms related to increasing species richness. In artificial rock pools, community variability was driven by a combination of direct and indirect environmental factors as well as mechanisms related to increasing species richness. In the natural rock pools community variability was independent of species richness and was only related to environmental factors. In summary, we found that stabilizing mechanisms associated with species interactions were influential in establishing species richness–variability relations only in the less realistic experimental venues (the laboratory microcosms and the artificial rock pools in the field), and that these mechanisms diminished in importance as ecological realism and complexity of the experimental venue increased. Our results suggest that the effects of diversity might be more difficult to detect in natural systems due to the combined effects of biotic and abiotic forcing, which can mask our ability to detect richness effects.     

Circular dichroism reveals sensitivity of glucagon solution structure to fluoroalcohols, pH and ionic strength

Circular dichroism reports that glucagon in solution becomes increasingly helical with the addition of fluoroalcohol (which also decreases solution pH), and with changes in pH and ionic strength. Given the variability of structure observed, these data indicate that care must be taken when comparing results obtained under different solution conditions.     

Genetic diversity in yeast assessed with whole-genome oligonucleotide arrays

The availability of a complete genome sequence allows the detailed study of intraspecies variability. Here we use high-density oligonucleotide arrays to discover 11,115 single-feature polymorphisms (SFPs) existing in one or more of 14 different yeast strains. We use these SFPs to define regions of genetic identity between common laboratory strains of yeast. We assess the genome-wide distribution of genetic variation on the basis of this yeast population. We find that genome variability is biased toward the ends of chromosomes and is more likely to be found in genes with roles in fermentation or in transport. This subtelomeric bias may arise through recombination between nonhomologous sequences because full-gene deletions are more common in these regions than in more central regions of the chromosome.