Recently, researchers in several areas of ecology and evolution have begun to change the way in which they analyze data and make biological inferences. Rather than the traditional null hypothesis testing approach, they have adopted an approach called model selection, in which several competing hypotheses are simultaneously confronted with data. Model selection can be used to identify a single best model, thus lending support to one particular hypothesis, or it can be used to make inferences based on weighted support from a complete set of competing models. Model selection is widely accepted and well developed in certain fields, most notably in molecular systematics and markrecapture analysis. However, it is now gaining support in several other areas, from molecular evolution to landscape ecology. Here, we outline the steps of model selection and highlight several ways that it is now being implemented. By adopting this approach, researchers in ecology and evolution will find a valuable alternative to traditional null hypothesis testing, especially when more than one hypothesis is plausible.Science is a process for learning about nature in which competing ideas about how the world works are evaluated against observations [1]. These ideas are usually expressed first as verbal hypotheses, and then as mathematical equations, or models. Models depict biological processes in simplified and general ways that provide insight into factors that are responsible for observed patterns. Hence, the degree to which observed data support a model also reflects the relative support for the associated hypothesis.Two basic approaches have been used to draw biological inferences. The dominant paradigm is to generate a null hypothesis (typically one with little biological meaning [2]) and ask whether the hypothesis can be rejected in light of observed data. Rejection occurs when a test statistic generated from observed data falls beyond an arbitrary probability threshold (usually P , 0.05), which is interpreted as tacit support for a biologically more meaningful alternative hypothesis. Hence, the actual hypothesis of interest (the alternative hypothesis) is accepted only in the sense that the null hypothesis is rejected. By contrast, model selection offers a way to draw inferences from a set of multiple competing hypotheses. Model selection is grounded in likelihood theory, a robust framework that supports most modern statistical approaches. Moreover, this approach is rapidly gaining support across several fields in ecology and evolution as a preferred alternative to null hypothesis testing [1,3,4]. Advocates of model selection argue that it has three primary advantages. First, practitioners are not restricted to evaluating a single model where significance is measured against some arbitrary probability threshold. Instead, competing models are compared to one another by evaluating the relative support in the observed data for each model. Second, models can be ranked and weighted, thereby providing a quantitative measure of relative sup...

No abstract

The anthrax lethal toxin neutralization assay (TNA) will likely be used to correlate the protection offered by new anthrax vaccines in animal models to the immunogenicity that will be provided in humans. TNA data are being generated in several different laboratories to measure the immune responses in rabbits, nonhuman primates, and humans. In order to compare data among species and laboratories, a collaborative study was conducted in which 108 samples from the three species were analyzed in seven independent laboratories. Six of the seven laboratories had participated in an interlaboratory technology transfer of the TNA. Analysis of the titration curves generated by samples from each species indicated that the behaviors of the samples from all species were similar; the upper and lower asymptotes and the slopes of the curves were less than 30% divergent from those for human reference material. Dilutional linearity was consistent among samples from each species, with spike to effective dilution at 50% inhibition (ED 50 ) slopes of less than 1.2 for all species. Agreement among the laboratories with consensus values was within 10% of the ED 50 s for all samples and within 7.5% of the quotients of the test sample ED 50 and the reference standard ED 50 (NF 50 s) for all samples. The relative standard deviations obtained when data from all laboratories and for all species were combined were 45% for the ED 50 s and 35% for the NF 50 s. These precision data suggest that the NF 50 readout may normalize the values generated by different laboratories. This study demonstrates that the TNA is a panspecies assay that can be performed in several different laboratories with a high degree of quantitative agreement and precision.

Francisella tularensis is a highly infectious Gram-negative bacterium that is the etiologic agent of tularemia in animals and humans and a Tier 1 select agent. The natural incidence of pneumonic tularemia worldwide is very low; therefore, it is not feasible to conduct clinical efficacy testing of tularemia medical countermeasures (MCM) in human populations. Development and licensure of tularemia therapeutics and vaccines need to occur under the Food and Drug Administration's (FDA's) Animal Rule under which efficacy studies are conducted in well-characterized animal models that reflect the pathophysiology of human disease. The Tularemia Animal Model Qualification (AMQ) Working Group is seeking qualification of the cynomolgus macaque (Macaca fascicularis) model of pneumonic tularemia under Drug Development Tools Qualification Programs with the FDA based upon the results of studies described in this manuscript. Analysis of data on survival, average time to death, average time to fever onset, average interval between fever and death, and bacteremia; together with summaries of clinical signs, necropsy findings, and histopathology from the animals exposed to aerosolized F. tularensis Schu S4 in five natural history studies and one antibiotic efficacy study form the basis for the proposed cynomolgus macaque model. Results support the conclusion that signs of pneumonic tularemia in cynomolgus macaques exposed to 300–3,000 colony forming units (cfu) aerosolized F. tularensis Schu S4, under the conditions described herein, and human pneumonic tularemia cases are highly similar. Animal age, weight, and sex of animals challenged with 300–3,000 cfu Schu S4 did not impact fever onset in studies described herein. This study summarizes critical parameters and endpoints of a well-characterized cynomolgus macaque model of pneumonic tularemia and demonstrates this model is appropriate for qualification, and for testing efficacy of tularemia therapeutics under Animal Rule.

No abstract

No abstract

No abstract

Red-spotted newts migrate between breeding sites in ponds and upland habitats. I tested the use and importance of slope as an orientation cue among adult male newts that I had removed from ponds. Newts reliably oriented downhill upon being released in a sloped orientation arena and in enclosures on the forest floor. By contrast, juvenile newts, which are wholly terrestrial animals, oriented randomly with respect to slope. Adult newts oriented downhill after having spent five days in pens at the test sites even though they presumably had access to information about the location of their pond during that time. Newts kept on land for 10 or 20 days prior to testing still oriented downhill in the orientation arenas but oriented randomly with respect to both slope and the homeward direction in the forest enclosures. I trained newts to exhibit shoreward orientation in aquaria, then tested their response in orientation arenas. Newts oriented toward shore in a flat arena and when the downhill direction coincided with the trained shoreward direction, but they oriented downhill rather than toward shore when the two directions conflicted. These results show that slope is an important cue to adult red-spotted newts returning to ponds and suggest that orientation based on ambient directional information is one of the mechanisms red-spotted newts employ when migrating to their breeding sites.