Abstract: Measurement of peak vertical ground reaction force (GRFz) from multiple limbs simultaneously during high-speed, over-ground locomotion would enhance our understanding of the locomotor mechanics of cursorial animals. Here, we evaluate the accuracy of predicting peak GRFz from duty factor (the proportion of the stride for which the limb is in contact with the ground). Foot-mounted uniaxial accelerometers, combined with UHF FM telemetry, are shown to be practical and accurate for the field measurement of stride timing variables, including duty factor. Direct comparison with the force plate produces a mean error of 2.3 ms and 3.5 ms for the timing of foot on and foot off, respectively, across all gaits. Predictions of peak GRFz from duty factor show mean errors (with positive values indicating an overestimate) of 0.8+/-0.04 N kg(-1) (13%; N=42; mean +/- S.E.M.) at walk, -0.3+/-0.06 N kg(-1) (3%; N=75) at trot, -2.3+/-0.27 N kg(-1) (16%; N=18) for the non-lead limb at canter and +2.1+/-0.7 N kg(-1) (19%; N=9) for the lead limb at canter. The substantial over- and underestimate seen at canter, in the lead and non-lead limbs, respectively, is attributed to the different functions performed by the two limbs in the asymmetrical gaits. The difference in load experienced by the lead and non-lead limbs decreased with increasing speed.

Abstract: The pregnane X receptor (PXR) is a ligand-activated transcription factor and member of the nuclear receptor superfamily. Activation of PXR represents an important mechanism for the induction of cytochrome P450 3A (CYP3A) enzymes that can convert acetaminophen (APAP) to its toxic intermediate metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Therefore, it was hypothesized that activation of PXR plays a major role in APAP-induced hepatotoxicity. Pretreatment with the PXR activator, pregnenolone 16alpha-carbonitrile (PCN), markedly enhanced APAP-induced hepatic injury, as revealed by increased serum ALT levels and hepatic centrilobular necrosis, in wild-type but not in PXR-null mice. Further analysis showed that following PCN treatment, PXR-null mice had lower CYP3A11 expression, decreased NAPQI formation, and increased maintenance of hepatic glutathione content compared to wild-type mice. Thus, these results suggest that PXR plays a critical role in APAP-induced hepatic toxicity, probably by inducing CYP3A11 expression and hence increasing bioactivation.

Abstract: REASONS FOR PERFORMING STUDY: Fractures below the level of the radius or tibia (distal limb fractures) are the most common cause of equine fatality on UK racecourses; however, little is known about their epidemiology or aetiology. Identification of risk factors could enable intervention strategies to be designed to reduce the number of fatalities. OBJECTIVES: To identify horse-level risk factors for fatal distal limb fracture in Thoroughbreds on UK racecourses. METHODS: A case-control study design was used. Fractures in case horses were confirmed by post mortem examination and 3 matched uninjured controls were selected from the race in which the case horse was running. One hundred and nine cases were included and information was collected about previous racing history, horse characteristics and training schedules. Conditional logistic regression was used to identify the relationship between a number of independent variables and the likelihood of fracture. RESULTS: Horses doing no gallop work during training and those in their first year of racing were at significantly increased risk of fracture on the racecourse. Case horses were also more likely to have trained on a sand gallop, i.e. a gallop described by trainers as being primarily composed of sand. CONCLUSIONS: Modifications to training schedules, specifically within the first year of racing, may have a large impact on the risk of fatal distal limb fracture on the racecourse. Horses should do some gallop work in training and our results suggest that the minimum distance galloped should be between 805-2012 m (4-10 furlongs)/week. POTENTIAL RELEVANCE: The information from this study can be used to alter training schedules in an attempt to reduce the incidence of fatal distal limb fracture in Thoroughbred racehorses. Training should include some gallop work, and further studies, recording the exact level of work, will help to identify an optimum range of training speeds and distances which will reduce the liklihood of catastrophic fracture on the racecourse.

Abstract: Eight crows were taught to discriminate overlapping pairs of visual stimuli (A+ B-, B+ C-, C+ D-, and D+ E-). For 4 birds, the stimuli were colored cards with a circle of the same color on the reverse side whose diameter decreased from A to E (ordered feedback group). These circles were made available for comparison to potentially help the crows order the stimuli along a physical dimension. For the other 4 birds, the circles corresponding to the colored cards had the same diameter (constant feedback group). In later testing, a novel choice pair (BD) was presented. Reinforcement history involving stimuli B and D was controlled so that the reinforcement/nonreinforcement ratios for the latter would be greater than for the former. If, during the BD test, the crows chose between stimuli according to these reinforcement/nonreinforcement ratios, then they should prefer D; if they chose according to the diameter of the feedback stimuli, then they should prefer B. In the ordered feedback group, the crows strongly preferred B over D; in the constant feedback group, the crows' choice did not differ significantly from chance. These results, plus simulations using associative models, suggest that the orderability of the postchoice feedback stimuli is important for crows' transitive responding.

Abstract: In a recent paper, Kaminski, Call and Fischer report pioneering research on word-learning in a dog. In this commentary we suggest ways of distinguishing referential word use from mere association. We question whether the dog is reasoning by exclusion and, if so, compare three explanations – learned heuristics, default assumptions, and pragmatic reasoning – as they apply to children and might apply to dogs. Kaminski et al.'s work clearly raises important questions about the origins and basis of word learning and social cognition.