Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial.

Based on previous findings, we hypothesised that radiotherapy to the prostate would improve overall survival in men with metastatic prostate cancer, and that the benefit would be greatest in patients with a low metastatic burden. We aimed to compare standard of care for metastatic prostate cancer, with and without radiotherapy.This article is freely available via Open Access

Assessing UK Drug Policy from a Crime Control Perspective.

Over the entire last quarter of the 20th century the British drug problem worsened, despite the implementation of a variety of approaches and commitment of substantial criminal justice and other resources. The link between chronic use of expensive drugs and property crime makes this experience important for understanding trends in crime and justice in Britain. The worsening of the problem can be seen in the growing number of new heroin users each year over almost the entire period 1975–2000, on top of which was layered, starting in the late 1990s, the first major outbreak of chronic cocaine use. This was not the common pattern in Western Europe over that time and by 2000 the UK had Western Europe’s most serious drug problem. The response initially took the form of increasing enforcement against drug markets; in just the decade 1994–2005 the number of prison cell years handed out in annual sentences has tripled. Even with this expansion we estimate that the annual probability of incarceration for a class A drug dealer is only approximately 6 per cent. Since 2000 there has also been a massive increase in treatment resources linked to the criminal justice system. The number of treatment assessments in recent years has been as large as 58 per cent of the number of persons estimated to be problematic users of Class A drugs. The government believes that drug policy has contributed to the decline in crime in the UK since 2000. Using what is known about treatment outcomes, we argue that despite impressive evidence of effect on individual level offending, the effect of treatment expansion in reducing overall crime rates is likely to have been limited

Allosteric mechanism controls traffic in the chaperone/usher pathway

Many virulence organelles of Gram-negative bacterial pathogens are assembled via the chaperone/ usher pathway. The chaperone transports organelle subunits across the periplasm to the outer membrane usher, where they are released and incorporated into growing fibers. Here, we elucidate the mechanism of the usher-targeting step in assembly of the Yersinia pestis F1 capsule at the atomic level. The usher interacts almost exclusively with the chaperone in the chaperone:subunit complex. In free chaperone, a pair of conserved proline residues at the beginning of the subunit-binding loop form a ‘‘proline lock’’ that occludes the usher-binding surface and blocks usher binding. Binding of the subunit to the chaperone rotates the proline lock away from the usher-binding surface, allowing the chaperone-subunit complex to bind to the usher. We show that the proline lock exists in other chaperone/usher systems and represents a general allosteric mechanism for selective targeting of chaperone:subunit complexes to the usher and for release and recycling of the free chaperone