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  • 1
    Publication Date: 2008-02-16
    Description: Alcohol dependence is a major public health challenge in need of new treatments. As alcoholism evolves, stress systems in the brain play an increasing role in motivating continued alcohol use and relapse. We investigated the role of the neurokinin 1 receptor (NK1R), a mediator of behavioral stress responses, in alcohol dependence and treatment. In preclinical studies, mice genetically deficient in NK1R showed a marked decrease in voluntary alcohol consumption and had an increased sensitivity to the sedative effects of alcohol. In a randomized controlled experimental study, we treated recently detoxified alcoholic inpatients with an NK1R antagonist (LY686017; n = 25) or placebo (n = 25). LY686017 suppressed spontaneous alcohol cravings, improved overall well-being, blunted cravings induced by a challenge procedure, and attenuated concomitant cortisol responses. Brain functional magnetic resonance imaging responses to affective stimuli likewise suggested beneficial LY686017 effects. Thus, as assessed by these surrogate markers of efficacy, NK1R antagonism warrants further investigation as a treatment in alcoholism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉George, David T -- Gilman, Jodi -- Hersh, Jacqueline -- Thorsell, Annika -- Herion, David -- Geyer, Christopher -- Peng, Xiaomei -- Kielbasa, William -- Rawlings, Robert -- Brandt, John E -- Gehlert, Donald R -- Tauscher, Johannes T -- Hunt, Stephen P -- Hommer, Daniel -- Heilig, Markus -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2008 Mar 14;319(5869):1536-9. doi: 10.1126/science.1153813. Epub 2008 Feb 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18276852" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged ; *Alcohol Drinking/drug therapy ; Alcoholism/*drug therapy ; Animals ; Behavior, Addictive/drug therapy ; Brain/drug effects/physiology ; Emotions/drug effects ; Ethanol/administration & dosage/pharmacology ; Female ; Humans ; Hydrocortisone/blood ; Magnetic Resonance Imaging ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; *Neurokinin-1 Receptor Antagonists ; Pyridines/administration & dosage/pharmacology/*therapeutic use ; Receptors, Neurokinin-1/deficiency/genetics/*physiology ; Triazoles/administration & dosage/pharmacology/*therapeutic use
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2022-05-25
    Description: © 2008 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial License. The definitive version was published in Environmental Fluid Mechanics 8 (2008): 495-509, doi:10.1007/s10652-008-9107-2.
    Description: Estuarine turbulence is notable in that both the dissipation rate and the buoyancy frequency extend to much higher values than in other natural environments. The high dissipation rates lead to a distinct inertial subrange in the velocity and scalar spectra, which can be exploited for quantifying the turbulence quantities. However, high buoyancy frequencies lead to small Ozmidov scales, which require high sampling rates and small spatial aperture to resolve the turbulent fluxes. A set of observations in a highly stratified estuary demonstrate the effectiveness of a vessel-mounted turbulence array for resolving turbulent processes, and for relating the turbulence to the forcing by the Reynolds-averaged flow. The observations focus on the ebb, when most of the buoyancy flux occurs. Three stages of mixing are observed: (1) intermittent and localized but intense shear instability during the early ebb; (2) continuous and relatively homogeneous shear-induced mixing during the mid-ebb, and weakly stratified, boundary-layer mixing during the late ebb. The mixing efficiency as quantified by the flux Richardson number Rf was frequently observed to be higher than the canonical value of 0.15 from Osborn (J Phys Oceanogr 10:83–89, 1980). The high efficiency may be linked to the temporal–spatial evolution of shear instabilities.
    Description: The funding for this research was obtained from ONR Grant N00014-06-1-0292 and NSF Grant OCE-0729547.
    Keywords: Turbulence ; Estuaries ; Shear instability ; Buoyancy flux
    Repository Name: Woods Hole Open Access Server
    Type: Article
    Format: application/pdf
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