Follow-up definitions in clinical orthopaedic research : a systematic review.

Aims: The follow-up interval of a study represents an important aspect that is frequently mentioned in the title of the manuscript. Authors arbitrarily define whether the follow-up of their study is short-, mid-, or long-term. There is no clear consensus in that regard and definitions show a large range of variation.

Fisheries management in the face of uncertainty: Designing time-area closures that are effective under multiple spatial patterns of fishing effort displacement in an estuarine gill net fishery.

A commonly cited reason for the failure of time-area closures to achieve fisheries management goals is the displacement of fishing effort from inside the closure into the surrounding area still open to fishing. Designing time-area closures that are predicted to achieve management goals under multiple spatial patterns of effort redistribution will increase chances of success. Using data from an estuarine gill net fishery, we tested if there are time-area closures predicted to reduce bycatch of two protected species groups while maintaining target catch under four simulated effort redistribution patterns.

Factor XII full and partial null in rat confers robust antithrombotic efficacy with no bleeding.

This report aims at exploring quantitatively the relationship between FXII inhibition and thromboprotection. FXII full and partial null in rats were established via zinc finger nuclease-mediated knockout and siRNA-mediated knockdown, respectively. The rats were subsequently characterized in thrombosis and hemostasis models.

Improved Stability of Proline-Derived Direct Thrombin Inhibitors through Hydroxyl to Heterocycle Replacement.

Modification of the previously disclosed (S)-N-(2-(aminomethyl)-5-chlorobenzyl)-1-((R)-2-hydroxy-3,3-dimethylbutanoyl)pyrrolidine-2-carboxamide 2 by optimization of the P3 group afforded novel, low molecular weight thrombin inhibitors. Heterocycle replacement of the hydroxyl functional group helped maintain thrombin in vitro potency while improving the chemical stability and pharmacokinetic profile. These modifications led to the identification of compound 10, which showed excellent selectivity over related serine proteases as well as in vivo efficacy in the rat arteriovenous shunt.

Titrating haemophilia B phenotypes using siRNA strategy: evidence that antithrombotic activity is separated from bleeding liability.

Haemophilia A and B are characterised by a life-long bleeding predisposition, and several lines of evidence suggest that risks of atherothrombotic events may also be reduced. Establishing a direct correlation between coagulation factor levels, thrombotic risks and bleeding propensity has long been hampered by an inability to selectively and specifically inhibit coagulation factor levels. Here, the exquisite selectivity of gene silencing combined with a gene knockout (KO) approach was used to define the relative contribution of factor IX (fIX) to thrombosis and primary haemostasis in the rat.