Managing player load in professional rugby union: a review of current knowledge and practices.

BACKGROUND: The loads to which professional rugby players are subjected has been identified as a concern by coaches, players and administrators. In November 2014, World Rugby commissioned an expert group to identify the physical demands and non-physical load issues associated with participation in professional rugby. OBJECTIVE: To describe the current state of knowledge about the loads encountered by professional rugby players and the implications for their physical and mental health. FINDINGS: The group defined 'load' as it relates to professional rugby players as the total stressors and demands applied to the players. In the 2013-2014 seasons, 40% of professional players appeared in 20 matches or more, and 5% of players appeared in 30 matches or more. Matches account for ∼5-11% of exposure to rugby-related activities (matches, team and individual training sessions) during professional competitions. The match injury rate is about 27 times higher than that in training. The working group surmised that players entering a new level of play, players with unresolved previous injuries, players who are relatively older and players who are subjected to rapid increases in load are probably at increased risk of injury. A mix of 'objective' and 'subjective' measures in conjunction with effective communication among team staff and between staff and players was held to be the best approach to monitoring and managing player loads. While comprehensive monitoring holds promise for individually addressing player loads, it brings with it ethical and legal responsibilities that rugby organisations need to address to ensure that players' personal information is adequately protected. CONCLUSIONS: Administrators, broadcasters, team owners, team staff and the players themselves have important roles in balancing the desire to have the 'best players' on the field with the ongoing health of players. In contrast, the coaching, fitness and medical staff exert significant control over the activities, duration and intensity of training sessions. If load is a major risk factor for injury, then managing training loads should be an important element in enabling players to perform in a fit state as often as possible.

Discovery of potent & selective inhibitors of activated thrombin-activatable fibrinolysis inhibitor for the treatment of thrombosis.

Thrombin-activatable fibrinolysis inhibitor (TAFI) has emerged as a key link between the coagulation and fibrinolysis cascades and represents a promising new target for the treatment of thrombosis. A novel series of imidazolepropionic acids has been designed that exhibit high potency against activated TAFI (TAFIa) and excellent selectivity over plasma carboxypeptidase N (CPN). Structure activity relationships suggest that the imidazole moiety plays a key role in binding to the catalytic zinc of TAFIa, and this has been supported by crystallographic studies using porcine pancreatic carboxypeptidase B as a surrogate for TAFIa. The SAR program led to the identification of 21 (TAFIa Ki = 10 nM, selectivity TAFIa/CPN > 1000) as a candidate for clinical development. Compound 21 exhibited antithrombotic efficacy in a rabbit model of venous thrombosis, yet had no effect on surgical bleeding in the rabbit. In addition, 21 exhibited an excellent preclinical and clinical pharmacokinetic profile, characterized by paracellular absorption, low clearance, and a low volume of distribution, fully consistent with its physicochemical properties of low molecular weight (MW = 239) and high hydrophilicity (log D = -2.8). These data indicate 21 (UK-396,082) has potential as a novel TAFIa inhibitor for the treatment of thrombosis and other fibrin-dependent diseases in humans.

Murine mesenchymal and embryonic stem cells express a similar Hox gene profile.

Using degenerate oligonucleotide primers targeting the homeobox domain, we amplified by PCR and sequenced 723 clones from five murine cell populations and lines derived from embryonic mesoderm and adult bone marrow. Transcripts from all four vertebrate Hox clusters were expressed by the different populations. Hierarchical clustering of the data revealed that mesenchymal stem cells (MSCs) and the embryonic stem (ES) cell line D3 shared a similar Hox expression profile. These populations exclusively expressed Hoxb2, Hoxb5, Hoxb7, and Hoxc4, transcripts regulating self-renewal and differentiation of other stem cells. Additionally, Hoxa7 transcript quantified by real-time PCR strongly correlated (r2=0.89) with the number of Hoxa7 clones identified by sequencing, validating that data from the PCR screen reflects differences in Hox mRNA abundance between populations. This is the first study to catalogue Hox transcripts in murine MSCs and by comparative analyses identify specific Hox genes that may contribute to their stem cell character.