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Objectives The objective of this clinical trial was to evaluate the long-term effect of endothelin receptor antagonism with bosentan on the morbidity and mortality of patients with severe chronic heart failure. Background Endothelin may play a role in heart failure, but short-term clinical trials with endothelin receptor antagonists have reported disappointing results. Long-term trials are lacking. Methods In 2 identical double-blind trials, we randomly assigned 1,613 patients with New York Heart Association functional class IIIb to IV heart failure and an ejection fraction Results Bosentan did not influence clinical status at 9 months in either trial (p = 0.928 and p = 0.263). In addition, 321 patients in the placebo group and 312 patients in the bosentan group died or were hospitalized for heart failure (hazard ratio [HR]: 1.01; 95% confidence interval [CI]: 0.86 to 1.18; p = 0.90). The bosentan group experienced fluid retention within the first 2 to 4 weeks, as evidenced by increased peripheral edema, weight gain, decreases in hemoglobin, and an increased risk of hospitalization for heart failure, despite intensification of background diuretics. During follow-up, 173 patients died in the placebo group and 160 patients died in the bosentan group (HR: 0.94; 95% CI: 0.75 to 1.16). About 10% of the bosentan group showed meaningful increases in hepatic transaminases, but none had acute or chronic liver failure. Conclusions Bosentan did not improve the clinical course or natural history of patients with severe chronic heart failure and but caused early and important fluid retention.

In this study, patina layers on artefacts composed of different rock types were examined, with all specimens originating from arid and semi-arid environments of South Africa. Microscopic observations showed a continuous mineralogical change from the unaltered core to the rim, suggesting that the patina layer is the result of weathering and/or chemical leaching of the rock surface. Elemental mapping by micro-PIXE and SEM showed depletion in leachable elements such as Mg, K, Ca, Fe and to a lesser extent Al, Si and Mn towards the surface for all artefacts analysed. This kind of distribution suggests the possibility that a leaching and exudation process through fluid activity might be responsible for the gradual, and in some cases extensive removal of the elements towards the patina surface.

The synthesis and 5-HT3 receptor antagonist activity of indolizidin-7-yl and 8-oxaquinolizidin-2-yl benzamides related to the quinolizidine, BRL 20627 (2), are described. High potency is restricted to axial isomers and both the indolizidines and oxa-quinolizidines are much more potent than (2), an effect which appears to be unrelated to basicity.

The South American Suckermouth Armored Catfish, Pterygoplichthys anisitsi (Pisces: Loricaridae), in Texas, with Comments on Foreign Fish Introductions in the American Southwest Author(s): Leo G. Nico and R. Trent Martin Source: The Southwestern Naturalist, Vol. 46, No. 1 (Mar., 2001), pp. 98-104 Published by: Southwestern Association of Naturalists Stable URL: http://www.jstor.org/stable/3672381 . Accessed: 10/09/2014 17:50

Systematic knowledge of the mechanical properties of ice is a fundamental requirement for the solution of a wide range of problems in the earth sciences and engineering. Past research has been characterized by specialized studies, involving a variety of motivations and scientific disciplines, without much overall coordination. When the results of this research are synthesized, a reasonably coherent picture emerges, but there are major gaps in knowledge. From the deduced behavior of ice, and from informed speculation where data are lacking, a coherent plan for future research can be developed. This report summarizes existing knowledge and proposes experiments and test programs for a new research thrust. The studies that are proposed can be expected to yield significant benefits in glacier studies, ice engineering, and the mechanics of frozen ground.

A nove one-step synthesis of N-(3-butenyl) imides (1) from dicarboxylic acids, and the sodium borohydride reduction/formic acid cyclisation of the N-(3-butenyl)-morpholin- and thiomorpholin-2,6-diones are described.