Conduct, Oversight, and Ethical Considerations of Clinical Trials in Companion Animals with Cancer: Report of a Workshop on Best Practice Recommendations.

Development of effective and safe treatments for companion animals with cancer requires the collaboration of numerous animal health professionals and the full engagement of animal owners. Establishing 'Best Practice Recommendations' for clinical trials in veterinary oncology represents an important step toward meeting the goal of rigorous clinical trial design and conduct that is required to establish valid evidence. Likewise, optimizing patient welfare and owner education and advocacy is crucial to meet the unique ethical obligations to both owners and animals enrolled in these clinical trials and to ensure trust in the team conducting the research. To date, 'Best Practice Recommendations' for clinical trial conduct have not been reported for veterinary oncology. This document summarizes the consensus of a workshop held in November, 2014 to identify relevant ethical principles and to ensure responsible conduct of clinical research in companion animals with cancer. It is intended as a working document that will be updated as advances in science and ethical considerations require. To the extent possible, existing guidelines for the conduct and oversight of clinical trials in humans have been adapted for veterinary trials to avoid duplicative effort and to facilitate integration of clinical trials such that translational research with benefits for both companion animals and humans are encouraged.

Breeds of dogs involved in fatal human attacks in the United States between 1979 and 1998.

OBJECTIVE: To summarize breeds of dogs involved in fatal human attacks during a 20-year period and to assess policy implications. ANIMALS: Dogs for which breed was reported involved in attacks on humans between 1979 and 1998 that resulted in human dog bite-related fatalities (DBRF). PROCEDURE: Data for human DBRF identified previously for the period of 1979 through 1996 were combined with human DBRF newly identified for 1997 and 1998. Human DBRF were identified by searching news accounts and by use of The Humane Society of the United States' registry databank. RESULTS: During 1997 and 1998, at least 27 people died of dog bite attacks (18 in 1997 and 9 in 1998). At least 25 breeds of dogs have been involved in 238 human DBRF during the past 20 years. Pit bull-type dogs and Rottweilers were involved in more than half of these deaths. Of 227 reports with relevant data, 55 (24%) human deaths involved unrestrained dogs off their owners' property, 133 (58%) involved unrestrained dogs on their owners' property, 38 (17%) involved restrained dogs on their owners' property, and 1 (< 1%) involved a restrained dog off its owner's property. CONCLUSIONS: Although fatal attacks on humans appear to be a breed-specific problem (pit bull-type dogs and Rottweilers), other breeds may bite and cause fatalities at higher rates. Because of difficulties inherent in determining a dog's breed with certainty, enforcement of breed-specific ordinances raises constitutional and practical issues. Fatal attacks represent a small proportion of dog bite injuries to humans and, therefore, should not be the primary factor driving public policy concerning dangerous dogs. Many practical alternatives to breed-specific ordinances exist and hold promise for prevention of dog bites.

Development of a teaching model for coronal access to the canine dentition.

A dolichocephalic canine skull was utilized to develop a teaching and study model for coronal access cavity preparation of the dentition. The teeth from the right side of the skull were extracted. Each tooth was radiographed in two planes to localize the "ideal" endodontic access point. Barium markers were placed over these points and each tooth was radiographed again to confirm the appropriate location of the marker. Access was created by drilling through the barium marker. Then, K-files were inserted through the access preparation into the root canal system. The teeth were radiographed with the K-files in place to verify straight pathways to the apices. Straight line access to the apex was obtained in all teeth. Creation of this model provides an opportunity for the veterinary dental student to develop and refine skills used in performing endodontic therapy. The model can be utilized by the veterinary dental practitioner in clinical practice.

Dynamic properties of the first enzymatic reaction steps of porcine pancreatic elastase. How rigid is the active site of the native enzyme? Molecular dynamics simulation.

Two molecular dynamics simulations (100 and 50 ps) of native porcine pancreatic elastase i.e., without bound substrate and with the active site hydrated by a dome of water (630 molecules) have been performed. Dynamical properties of the catalytic tetrad have been examined. While relative conformations of the Asp 102, His 57, and Ser 214 are rather stable in time, the side chain of Ser 195 undergoes several conformational changes. No preferences are observed for the formation of a hydrogen bond between the O gamma-H group (Ser 195) and nitrogen N, (His 57). A cluster of ordered water molecules effectively competes with the H-O gamma group (Ser 195) and thereby prevents the formation of this H bond, which is generally agreed to be crucial for catalysis.