Discovery of VU0467319: an M Positive Allosteric Modulator Candidate That Advanced into Clinical Trials.

Herein we detail the of VU0467319 (VU319), an M Positive Allosteric Modulator (PAM) clinical candidate that successfully completed a Phase I Single Ascending Dose (SAD) clinical trial. VU319 () is a moderately potent M PAM (M PAM EC = 492 nM ± 2.9 nM, 71.

Squeezing the quantum noise of a gravitational-wave detector below the standard quantum limit.

The Heisenberg uncertainty principle dictates that the position and momentum of an object cannot be simultaneously measured with arbitrary precision, giving rise to an apparent limitation known as the standard quantum limit (SQL). Gravitational-wave detectors use photons to continuously measure the positions of freely falling mirrors and so are affected by the SQL. We investigated the performance of the Laser Interferometer Gravitational-Wave Observatory (LIGO) after the experimental realization of frequency-dependent squeezing designed to surpass the SQL.

Cardiac SABR: Image matching techniques for accurate treatment delivery.

Background: Ventricular tachycardia is an irregular heartbeat conventionally treated using invasive cardiac catheter ablation and medication. However, when standard treatments have been exhausted, cardiac SABR provides a final treatment option to this high-mortality condition. Complex diagnostic mapping and planning scans enable multi-disciplinary target delineation for a 25Gy single fraction.

Early vocational rehabilitation and psychological support for trauma patients to improve return to work (the ROWTATE trial): study protocol for an individually randomised controlled multicentre pragmatic trial.

Background: Moderately severe or major trauma (injury severity score (ISS) > 8) is common, often resulting in physical and psychological problems and leading to difficulties in returning to work. Vocational rehabilitation (VR) can improve return to work/education in some injuries (e.g.