Causal inference can lead us to modifiable mechanisms and informative archetypes in sepsis.

Medical progress is reflected in the advance from broad clinical syndromes to mechanistically coherent diagnoses. By this metric, research in sepsis is far behind other areas of medicine-the word itself conflates multiple different disease mechanisms, whilst excluding noninfectious syndromes (e.g.

Network and pathway expansion of genetic disease associations identifies successful drug targets.

Genetic evidence of disease association has often been used as a basis for selecting of drug targets for complex common diseases. Likewise, the propagation of genetic evidence through gene or protein interaction networks has been shown to accurately infer novel disease associations at genes for which no direct genetic evidence can be observed. However, an empirical test of the utility of combining these approaches for drug discovery has been lacking.

Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases.

The human proteome is a major source of therapeutic targets. Recent genetic association analyses of the plasma proteome enable systematic evaluation of the causal consequences of variation in plasma protein levels. Here we estimated the effects of 1,002 proteins on 225 phenotypes using two-sample Mendelian randomization (MR) and colocalization.

Redesigning Metal Interference Screws Can Improve Ease of Insertion While Maintaining Fixation of Soft-Tissue Anterior Cruciate Ligament Reconstruction Grafts.

Purpose: To compare the fixation strength and loads on insertion of a titanium alloy interference screw with a modified tip against a conventional titanium interference screw.

Methods: Slippage of bovine digital extensor tendons (as substitutes for human tendon grafts) under cyclic loading and interference fixation strength under a pullout test were recorded in 10 cadaveric knees, with 2 tunnels drilled in each femur and tibia to provide pair-wise comparisons between the modified-tip screw (MS) and conventional screw (CS). To analyze screw insertion, 10 surgeons blindly inserted pairs of the MS and CS into bone-substitute blocks (with polyester shoelaces as graft substitutes), with insertion loads measured using a force/torque sensor.