Packing polymorphism of dapivirine and its impact on the performance of a dapivirine-releasing silicone elastomer vaginal ring

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Postcode Lotteries in Public Health - The NHS Health Checks Programme in North West London

<p>Abstract</p> <p>Background</p> <p>Postcode lotteries in health refer to differences in health care between different geographic areas. These have been previously associated with clinical services. However there has been little documentation of postcode lotteries relating to preventative health care services. This paper describes a postcode lottery effect in relation to the NHS Health Checks Programme (a national cardiovascular screening programme in England) in eight PCTs in the North West sector of London.</p> <p>Methods</p> <p>A descriptive cross-sectional analysis of the Health Checks Programme was carried out in eight PCTs in North West London using a structured data-collecting instrument.</p> <p>Results</p> <p>The analysis found variation in the implementation of the national Health Checks Programme in terms of: the screening approach taken; the allocated budget (which varied from £69,000 to £1.4 million per 100,000 eligible population); payment rates made to providers of Health Checks; tools used to identify and measure risk of cardiovascular disease and diabetes; monitoring and evaluation; and preventative services available following the health check.</p> <p>Conclusions</p> <p>This study identifies a postcode lottery effect related to a national public health programme. Although it is important to allow enough flexibility in the design of the Health Checks Programme so that it fits in with local factors, aspects of the programme may benefit from greater standardisation or stronger national guidance.</p

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Uncoupled activation and cyclization in catmint reductive terpenoid biosynthesis

Terpene synthases typically form complex molecular scaffolds by concerted activation and cyclization of linear starting materials in a single enzyme active site. Here we show that iridoid synthase, an atypical reductive terpene synthase, catalyzes the activation of its substrate 8-oxogeranial into a reactive enol intermediate, but does not catalyze the subsequent cyclization into nepetalactol. This discovery led us to identify a class of nepetalactol-related short-chain dehydrogenase enzymes (NEPS) from catmint (Nepeta mussinii) that capture this reactive intermediate and catalyze the stereoselective cyclisation into distinct nepetalactol stereoisomers. Subsequent oxidation of nepetalactols by NEPS1 provides nepetalactones, metabolites that are well known for both insect-repellent activity and euphoric effect in cats. Structural characterization of the NEPS3 cyclase reveals that it binds to NAD+ yet does not utilize it chemically for a non-oxidoreductive formal [4 + 2] cyclization. These discoveries will complement metabolic reconstructions of iridoid and monoterpene indole alkaloid biosynthesis

Vaginal rings for delivery of HIV microbicides

Following the successful development of long-acting steroid-releasing vaginal ring devices for the treatment of menopausal symptoms and contraception, there is now considerable interest in applying similar devices to the controlled release of microbicides against HIV. In this review article, the vaginal ring concept is first considered within the wider context of the early advances in controlled-release technology, before describing the various types of ring device available today. The remainder of the article highlights the key developments in HIV microbicide-releasing vaginal rings, with a particular focus on the dapivirine ring that is presently in late-stage clinical testing