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  • American Geophysical Union  (4)
  • American Association for the Advancement of Science (AAAS)
  • Berlin: Deutsches Institut für Wirtschaftsforschung (DIW)
  • American Geophysical Union (AGU)
  • American Meteorological Society (AMS)
  • 2005-2009  (4)
  • 1980-1984  (1)
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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: 1982-01-01
    Print ISSN: 0148-0227
    Electronic ISSN: 2156-2202
    Topics: Geosciences
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  • 3
    Publication Date: 2008-07-18
    Print ISSN: 0148-0227
    Electronic ISSN: 2156-2202
    Topics: Geosciences
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  • 4
    Publication Date: 2006-12-23
    Print ISSN: 0148-0227
    Electronic ISSN: 2156-2202
    Topics: Geosciences
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  • 5
    Publication Date: 2022-05-25
    Description: Author Posting. © American Geophysical Union, 2005. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 110 (2005): C05001, doi:10.1029/2004JC002691.
    Description: Numerical simulations of the Hudson River estuary using a terrain-following, three-dimensional model (Regional Ocean Modeling System, ROMS) are compared with an extensive set of timeseries and spatially resolved measurements over a 43-day period with large variations in tidal forcing and river discharge. The model is particularly effective at reproducing the observed temporal variations in both the salinity and current structure, including tidal, spring-neap, and river discharge induced variability. Large observed variations in stratification between neap and spring tides are captured qualitatively and quantitatively by the model. The observed structure and variations of the longitudinal salinity gradient are also well reproduced. The most notable discrepancy between the model and the data is in the vertical salinity structure. While the surface-to-bottom salinity difference is well reproduced, the stratification in the model tends to extend all the way to the water surface, whereas the observations indicate a distinct pycnocline and a surface mixed layer. Because the southern boundary condition is located near the mouth the estuary, the salinity within the domain is particularly sensitive to the specification of salinity at the boundary. A boundary condition for the horizontal salinity gradient, based on the local value of salinity, is developed to incorporate physical processes beyond the open boundary not resolved by the model. Model results are sensitive to the specification of the bottom roughness length and vertical stability functions, insofar as they influence the intensity of vertical mixing. The results only varied slightly between different turbulence closure methods of k-ε, k-ω, and k-kl.
    Description: We gratefully acknowledge support from the U.S. Geological Survey Mendenhall Post-doctoral Research Program for support of J. C. Warner. J. A. Lerczak and W. R. Geyer were supported by the Hudson River Foundation.
    Keywords: Estuary ; Model skill assessment ; Hudson River
    Repository Name: Woods Hole Open Access Server
    Type: Article
    Format: application/pdf
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