Sugammadex hypersensitivity and underlying mechanisms: a randomised study of healthy non-anaesthetised volunteers.

BACKGROUND: We investigated potential for hypersensitivity reactions after repeated sugammadex administration and explored the mechanism of hypersensitivity. METHODS: In this double-blind, placebo-controlled study (NCT00988065), 448 healthy volunteers were randomised to one of three arms to receive three repeat i.v. administrations of either sugammadex 4 mg kg-1, 16 mg kg-1, or placebo. Primary endpoint was percentage of subjects with hypersensitivity (assessed by an independent adjudication committee). Secondary endpoint of anaphylaxis was classified per Sampson and Brighton criteria. Exploratory endpoints included skin testing, serum tryptase, anti-sugammadex antibodies [immunoglobulin (Ig) E/IgG], and other immunologic parameters. RESULTS: Hypersensitivity was adjudicated for 1/148 (0.7%), 7/150 (4.7%), and 0/150 (0.0%) subjects after sugammadex 4 mg kg-1, 16 mg kg-1, and placebo, respectively. After sugammadex 16 mg kg-1, one subject met Sampson criterion 1 and Brighton level 1 (highest certainty) anaphylaxis criteria; two met Brighton level 2 criteria. After database lock it was determined that certain protocol deviations could have introduced bias in the reporting of hypersensitivity signs/symptoms in a subject subset. Objective laboratory investigations indicated that potential underlying hypersensitivity mechanisms were unlikely to have been activated; the results suggest that most of the observed hypersensitivity reactions were unlikely IgE/IgG-mediated. CONCLUSION: Dose-dependent hypersensitivity or anaphylaxis reactions to sugammadex were observed when administered without prior neuromuscular blocking agent. Laboratory investigations do not suggest prevalent allergen-specific IgE/IgG-mediated immunologic hypersensitivity. Because it could not be fully excluded that estimates of hypersensitivity/anaphylaxis incidence were unbiased, an additional study was conducted to characterise the potential for hypersensitivity reactions and is described in a companion report. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov NCT00988065; Protocol number P06042.

Process Design and Costing of Bioethanol Technology: A Tool for Determining the Status and Direction of Research and Development.

Bioethanol is a fuel-grade ethanol made from trees, grasses, and waste materials. It represents a sustainable substitute for gasoline in today's passenger cars. Modeling and design of processes for making bioethanol are critical tools used in the U.S. Department of Energy's bioethanol research and development program. We use such analysis to guide new directions for research and to help us understand the level at which and the time when bioethanol will achieve commercial success. This paper provides an update on our latest estimates for current and projected costs of bioethanol. These estimates are the result of very sophisticated modeling and costing efforts undertaken in the program over the past few years. Bioethanol could cost anywhere from $1.16 to $1.44 per gallon, depending on the technology and the availability of low cost feedstocks for conversion to ethanol. While this cost range opens the door to fuel blending opportunities, in which ethanol can be used, for example, to improve the octane rating of gasoline, it is not currently competitive with gasoline as a bulk fuel. Research strategies and goals described in this paper have been translated into cost savings for ethanol. Our analysis of these goals shows that the cost of ethanol could drop by 40 cents per gallon over the next ten years by taking advantage of exciting new tools in biotechnology that will improve yield and performance in the conversion process.

Low-intensity degenerate four-wave mixing at the cesium D1 resonance in thin cells.

We observed low-intensity cw degenerate four-wave mixing at the D1 resonance in a 10-microm-thick cesium-vapor cell. Normal population depletion caused by optical pumping is alleviated by frequent atom-wall collisions. The reflectivity at the D1 resonance is approximately equal in magnitude to that observed at the D2 cycling transition under similar conditions.