Large animal models of heart failure are essential in preclinical device testing. In sheep, catheter-based coil embolization of the left anterior descending and diagonal artery provides a minimally invasive and reproducible model of myocardial infarction (MI). Although widely used, this model has historically been plagued with a 30% mortality rate, both in the literature and in our own experience. Our study endeavored to decrease the mortality rate by targeting the most common cause of death, intractable arrhythmias, during creation of the ovine MI model. To this end, we evaluated 2 methods of managing perioperative antiarrhythmic therapy and cardiopulmonary resuscitation during model creation. The first group of sheep was managed at the discretion of the individual operator, whereas the second group was treated according to a standardized protocol that included mandatory pretreatment with amiodarone. Sheep experiencing life-threatening arrhythmias, most commonly ventricular fibrillation, were either resuscitated according to operator-driven instructions or the standardized protocol. By comparing these 2 treatment groups, we have shown that using a standardized protocol is advantageous in reducing mortality associated with the ovine MI model. Since implementing the standardized protocol, our laboratory has lowered the expected mortality rate to 10% during catheter-based induction of ovine MI and has greatly reduced the number of animals required for study needs. In addition, the standardized protocol has proven beneficial in training new staff members. By implementing this standardized method of model management, the outcomes of model creation have been optimized.
Arms races between brood parasites and their hosts provide model systems for studying the evolutionary repercussions of species interactions. However, how naive hosts identify brood parasites as enemies remains poorly understood, despite its ecological and evolutionary significance. Here, we investigate whether young, cuckoo-naive superb fairy-wrens, Malurus cyaneus, can learn to recognize cuckoos as a threat through social transmission of information. Naive individuals were initially unresponsive to a cuckoo specimen, but after observing conspecifics mob a cuckoo, they made more whining and mobbing alarm calls, and spent more time physically mobbing the cuckoo. This is the first direct evidence that naive hosts can learn to identify brood parasites as enemies via social learning.
A novel class of 1,3,5-pyrazoles has been discovered as potent human glucagon receptor antagonists. Notably, compound 26 is orally bioavailable in several preclinical species and shows selectivity towards cardiac ion channels, other family B receptors such hGIP and hGLP1, and a large panel of enzymes and additional receptors. When dosed orally, compound 26 is efficacious in suppressing glucagon induced plasma glucose excursion in rhesus monkey and transgenic murine pharmacodynamic models at 1 and 10 mpk, respectively.
Tissue distribution, bioavailability, and efficacy of alendronate in preventing progression of resorption of teeth were evaluated in cats. [Butyl-4-14C-]-alendronate accumulates on subgingival tooth and alveolar bone surfaces adjacent to vascularized tissue resulting in concentration of the drug around tooth roots. Three cats were treated with a 0.03 mg/kg i.v. bolus of [butyl-4-14C-]-alendronate followed by blood, urine, and feces collection and euthanasia 24-hours later. Drug tissue distribution was accessed by autoradiography and sample combustion. To assess bioavailability, 12 cats were administered alendronate orally (3.0 or 9.0 mg/kg in water or 9.0 mg/kg in tuna water) and urine was collected for 24-hours. In these formulations, alendronate oral bioavailability in cats was approximately 3%. In addition, 10 cats with radiographic evidence of pre-existing tooth resorption (14 affected teeth) were treated with vehicle or 3.0 mg/kg alendronate per os once weekly for 22-weeks and, then, 9.0 mg/kg per os twice weekly for 27-weeks in a random, masked study. Radiographic area of resorption was measured and progression scored every 3 to 4-months. In placebo-treated cats, resorption progressed in five of six teeth (+ 97% average increase in area of resorption), whereas progression of resorption was seen in only three of eight affected teeth in alendronate-treated cats with a -22% average change (decrease) in area (P < 0.01 difference in number of teeth showing progression; P < 0.001 difference in area of resorption). Alendronate accumulated preferentially on subgingival tooth surfaces and adjacent alveolar bone and, at a dose of 9 mg/kg twice weekly, effectively slowed or arrested the progression of resorption.
The discovery that an individual may be constrained, and even behave sub-optimally, because of its personality type has fundamental implications for understanding individual- to group-level processes. Despite recent interest in the study of animal personalities within behavioural ecology, the field is fraught with conceptual and methodological difficulties inherent in any young discipline. We review the current agreement of definitions and methods used in personality studies across taxa and systems, and find that current methods risk misclassifying traits. Fortunately, these problems have been faced before by other similar fields during their infancy, affording important opportunities to learn from past mistakes. We review the tools that were developed to overcome similar methodological problems in psychology. These tools emphasise the importance of attempting to measure animal personality traits using multiple tests and the care that needs to be taken when interpreting correlations between personality traits or their tests. Accordingly, we suggest an integrative theoretical framework that incorporates these tools to facilitate a robust and unified approach in the study of animal personality.
Animal personality, repeatable behaviour through time and across contexts, is ecologically and evolutionarily important as it can account for the exhibition of sub-optimal behaviours. Interspecific comparisons have been suggested as important for understanding the evolution of animal personality; however, these are seldom accomplished due, in part, to the lack of statistical tools for quantifying differences and similarities in behaviour between groups of individuals. We used nine species of closely-related coral reef fishes to investigate the usefulness of ecological community analyses for the analysis of between-species behavioural differences and behavioural heterogeneity. We first documented behavioural carryover across species by observing the fishes behaviour and measuring their response to a threatening stimulus to quantify boldness. Bold fish spent more time away from the reef and fed more than shy fish. We then used ecological community analysis tools (canonical variate analysis, multi-response permutation procedure, and permutational analysis of multivariate dispersion) and identified four clusters of behaviourally similar fishes, and found that the species differ in the behavioural variation expressed; some species are more behaviourally heterogeneous than others. We found that ecological community analysis tools are easily and fruitfully applied to comparative studies of personality and encourage their use by future studies.
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