Irbesartan in Marfan syndrome (AIMS): a double-blind, placebo-controlled randomised trial

BACKGROUND: Irbesartan, a long acting selective angiotensin-1 receptor inhibitor, in Marfan syndrome might reduce aortic dilatation, which is associated with dissection and rupture. We aimed to determine the effects of irbesartan on the rate of aortic dilatation in children and adults with Marfan syndrome. METHODS: We did a placebo-controlled, double-blind randomised trial at 22 centres in the UK. Individuals aged 6-40 years with clinically confirmed Marfan syndrome were eligible for inclusion. Study participants were all given 75 mg open label irbesartan once daily, then randomly assigned to 150 mg of irbesartan (increased to 300 mg as tolerated) or matching placebo. Aortic diameter was measured by echocardiography at baseline and then annually. All images were analysed by a core laboratory blinded to treatment allocation. The primary endpoint was the rate of aortic root dilatation. This trial is registered with ISRCTN, number ISRCTN90011794. FINDINGS: Between March 14, 2012, and May 1, 2015, 192 participants were recruited and randomly assigned to irbesartan (n=104) or placebo (n=88), and all were followed for up to 5 years. Median age at recruitment was 18 years (IQR 12-28), 99 (52%) were female, mean blood pressure was 110/65 mm Hg (SDs 16 and 12), and 108 (56%) were taking β blockers. Mean baseline aortic root diameter was 34·4 mm in the irbesartan group (SD 5·8) and placebo group (5·5). The mean rate of aortic root dilatation was 0·53 mm per year (95% CI 0·39 to 0·67) in the irbesartan group compared with 0·74 mm per year (0·60 to 0·89) in the placebo group, with a difference in means of -0·22 mm per year (-0·41 to -0·02, p=0·030). The rate of change in aortic Z score was also reduced by irbesartan (difference in means -0·10 per year, 95% CI -0·19 to -0·01, p=0·035). Irbesartan was well tolerated with no observed differences in rates of serious adverse events. INTERPRETATION: Irbesartan is associated with a reduction in the rate of aortic dilatation in children and young adults with Marfan syndrome and could reduce the incidence of aortic complications

Graduate recital in horn

Includes recorded audio files in WAV and MP3 formats, 70:47 in length.Telemann???s D Major Concerto, composed between 1712 and 1721, is a good example of the baroque horn concerto style. The three movement form includes a lively opening movement of signaling style followed by the high, floating, melodic line of the second movement. The third movement is a Minuet (without Trio) in two parts. In performance, authentic baroque ornamentation is used at the plyers discretion giving the piece spontaneity.\ud Thea Musgrave???s Music for horn and piano (1967) is an example of contemporary horn writing. Both rhythmic and arrhythmic sections are included along with the various tonal effects of natural, stopped and echo tones. Although, it may be less understandable to some in the audience, its positioning as the second work performed gives it a good listening since audience attention tends to be at its peak during second pieces on recitals. \ud Alec Wilder???s Suite for Horn and Piano is first and foremost a happy, fun piece. Its practicality for use on a recital of serious music is self-evident. It is musically rewarding work requiring a virtuoso technique of the performer. Wilder???s musical ideas are drawn from his own experience in popular idioms and helps make the piece an appropriate finish for the first half of the recital.\ud The Brahms Horn Trop Op. 40 is a favorite of romantic period horn compositions. The Trio???s individual musical personality combines rich melody and harmonic enterprise with the blended colors possible from horn, violin, and piano. The adoption of multi-subject schemes permitted expansion of traditional sonata style. It is the logical closing piece on this recital.\ud The varied repertoire is the major strong point of this recital program. The recital???s emphasis on a wide range of technique, versatility, and musical styles is not only good from a programming standpoint but also sheds favorable light on the accomplishments of the performer

Growth and abundance of O-group herrings, Clupea harengus L., in the Severn Estuary

Collections made from the cooling water intake screens of Power Stations in the Severn Estuary and the Bristol Channel have been used to investigate the biology of O-group herrings in this region. The abundance of herrings at Oldbury, the principal sampling site, was low in most years and in five successive seasons between July 1972 and December 1976, large numbers were caught only between the summer of 1975 and the spring of 1976. The herrings were first observed in July, when many had still not completed metamorphosis, and reached peak numbers in September and October during which period they were clearly growing. Numbers declined in December before rising dramatically in January at which time the length-frequency curves displayed a pronounced bimodality. On the basis of data from other parts of the Bristol Channel and Severn Estuary, it is suggested that this bimodality is due to the influx of some animals from other regions where the growth rate was greater. Although movement is apparently taking place at this time and the numbers decline markedly in subsequent months, the last remnants of the population do not leave the estuary until early May. Post-pelvic scute (K2) and vertebral counts (VS) of 13.82 and 55.24 respectively, indicate that the Severn Estuary herrings are the product of a spring spawning stock, a view entirely consistent with length and field data

Comprehensive expression atlas of fibroblast growth factors and their receptors generated by a novel robotic in situ hybridization platform.

A recently developed robotic platform termed "Genepaint" can carry out large-scale nonradioactive in situ hybridization (ISH) on tissue sections. We report a series of experiments that validate this novel platform. Signal-to-noise ratio and mRNA detection limits were comparable to traditional ISH procedures, and hybridization was transcript-specific, even in cases in which probes could have hybridized to several transcripts of a multigene family. We established an atlas of expression patterns of fibroblast growth factors (Fgfs) and their receptors (Fgfrs) for the embryonic day 14.5 mouse embryo. This atlas provides a comprehensive overview of previously known as well as novel sites of expression for this important family of signaling molecules. The Fgf/Fgfr atlas was integrated into the transcriptome database (www.genepaint.org), where individual Fgf and Fgfr expression patterns can be interactively viewed at cellular resolution and where sites of expressions can be retrieved using an anatomy-based search

The Citizen’s New Clothes: care in a Welsh community

The government has launched a sustained attack upon the concept of society, championing the individual. However, in certain arenas they are now providing contradictory messages. For example, health service restructuring is calling for greater citizen involvement, appealing to a simplistic mixture of individualistic and communitarian identities. Located within that arena, this article explores the discourses of 'everyday citizens'. It is demonstrated that there is a greater diversity of citizen and community identities than is recognized in government rhetoric, and it is suggested that this diversity needs to be addressed if citizenship and community are to be useful tools upon which to base policy