TIMI and GRACE are the risk scores that up until now have been most extensively investigated, with GRACE performing better. There are other potentially useful ACS risk scores available however these have not undergone rigorous validation. This study suggests that these other scores may be potentially useful and should be further researched.

Consider the problem of finding the dose that is as high as possible subject to having a controlled rate of toxicity. The problem is commonplace in oncology Phase I clinical trials. Such a dose is often called the maximum tolerated dose (MTD) since it represents a necessary trade-off between efficacy and toxicity. The continual reassessment method (CRM) is an improvement over traditional up-and-down schemes for estimating the MTD. It is based on a Bayesian approach and on the assumption that the dose-toxicity relationship follows a specific response curve, e.g., the logistic or power curve. The purpose of this paper is to illustrate how the assumption of a specific curve used in the CRM is not necessary and can actually hinder the efficient use of prior inputs. An alternative curve-free method in which the probabilities of toxicity are modeled directly as an unknown multidimensional parameter is presented. To that purpose, a product-of-beta prior (PBP) is introduced and shown to bring about logical improvements. Practical improvements are illustrated by simulation results.

Our data confirm previous studies suggesting that the HCRTR2 gene or a linked locus significantly modulates the risk for CH. In addition, we suggest that the V308I substitution of the HCRTR2 may interfere with the dimerization process of the receptor, thereby influencing its functional activity.

BackgroundThere is a substantial paucity of studies concerning musculoskeletal injuries in harness Standardbred racehorses. Specifically, little is known about the epidemiology of exercise-related musculoskeletal injuries. Most studies on this subject involve Thoroughbred racehorses, whose biomechanics and racing speed differ from Standardbred, making comparisons difficult. Here, a population of Standardbred racehorses trained at the same racecourse was studied over four years and a classification system for exercise-related musculoskeletal injuries was designed. The incidence rates of musculoskeletal injuries causing horses’ withdrawal from training for 15 days or longer were investigated. A mixed-effects Poisson regression model was used to estimate musculoskeletal injury rates and to describe significance of selected risk factors for exercise-related injuries in this population.ResultsA total of 356 trotter racehorses from 10 different stables contributed 8961 months at risk of musculoskeletal injuries. Four-hundred-and-twenty-nine injuries were reported and classified into 16 categories, based on their aetiology and anatomical localisation. The overall exercise-related injury rate was 4.79 per 100 horse months. When considering risk factors one by one in separate univariable analyses, we obtained the following results: rates did not differ significantly between genders and classes of age, whereas one driver seemed to cause fewer injuries than the others. Racing speed and racing intensity, as well as recent medical history, seemed to be significant risk factors (p < 0.001), while being shod or unshod during racing was not. On the other hand, when pooling several risk factors in a multivariable approach, only racing intensity turned out to be significant (p < 0.001), since racing speed and the racing intensity were partially confounded, being strongly correlated to one another.ConclusionCharacterizing epidemiology of exercise-related musculoskeletal injuries in trotter racehorses provides baseline incidence rate values. Incidence rates of stress fracture are lower in Standardbreds compared to Thoroughbreds, whereas the opposite is true for tendon and suspensory ligament injuries. In addition to identification of risk factors for musculoskeletal injuries among Standardbred racehorses, results suggest that racing intensity seems to be a protective predictor of risk and recent medical history could be used to identify horses at risk of injury.

Pharmacokinetics of valsartan are unchanged after multiple once-daily dosing, with little (expected) accumulation in plasma. Effects of 200 mg valsartan on blood pressure in healthy subjects on a normal sodium intake are small and become more prominent after repeated dosing. Indirect evidence of AT1 blockade by valsartan is demonstrated by an increase of plasma Ang II and by a blunted DBP response to passive tilting. The decrease in blood pressure at steady state enhances the increase in plasma Ang II. Valsartan is well tolerated and is devoid of effects on water, electrolyte and uric acid excretion at 200 mg per day in healthy normotensive volunteers.