9,707 research outputs found

    The Extent of Drug Use among High School Seniors in Tennessee, April 1985

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    The purpose of this study was to obtain information relative to the extent of drug use by high school seniors in Tennessee. Patterns of drug use were obtained by using a questionnaire/opinionnaire developed by Bachman, Johnston, and O\u27Malley of the Institute for Social Research, Ann Arbor, Michigan. The review of literature focused on patterns of drug use by seniors throughout the nation using the same questionnaire/opinionnaire. The results of the national survey were compared with the findings in Tennessee. The questionnaire was administered to a stratified random sample of 450 seniors in 15 randomly selected high schools in West, Middle, and East Tennessee. The State Department of Education was utilized to select the 15 participating schools. Thirty students, 15 males and 15 females from each school, were selected by using a table of random numbers. A guidance counselor or other designated individual in each school was responsible for administering the questionnaire. The data obtained provided information regarding the extent of drug use by high school seniors in Tennessee. The study revealed that seniors in Tennessee use alcohol less on a lifetime and yearly basis compared with seniors throughout the nation. Monthly rates of alcohol utilization were practically the same. The study further showed that high school seniors in Tennessee were less likely to use marijuana on a lifetime, yearly and monthly basis than seniors in other high schools in the nation and less likely to use stimulants on a lifetime basis. The use of barbiturates, LSD, cocaine and heroin could not be statistically analyzed because of a lack of responses to the survey questions. Additional conclusions drawn as a result of the study are summarized as follows: (1) The main reasons seniors in Tennessee used drugs were: to experiment, to relieve tension, to get high, and to have a good time with friends. (2) The situations in which seniors in Tennessee used drugs were: at home, or at a party, on a date, with one or two other people, and in a car. (3) The drugs most abused in Tennessee were alcohol and marijuana. (Abstract shortened with permission of author.

    Energy dissipation and ion heating at the heliospheric termination shock

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    The Los Alamos hybrid simulation code is used to examine heating and the partition of dissipation energy at the perpendicular heliospheric termination shock in the presence of pickup ions. The simulations are one-dimensional in space but three-dimensional in field and velocity components, and are carried out for a range of values of pickup ion relative density. Results from the simulations show that because the solar wind ions are relatively cold upstream, the temperature of these ions is raised by a relatively larger factor than the temperature of the pickup ions. An analytic model for energy partition is developed on the basis of the Rankine-Hugoniot relations and a polytropic energy equation. The polytropic index gamma used in the Rankine-Hugoniot relations is varied to improve agreement between the model and the simulations concerning the fraction of downstream heating in the pickup ions as well as the compression ratio at the shock. When the pickup ion density is less than 20%, the polytropic index is about 5/3, whereas for pickup ion densities greater than 20%, the polytropic index tends toward 2.2, suggesting a fundamental change in the character of the shock, as seen in the simulations, when the pickup ion density is large. The model and the simulations both indicate for the upstream parameters chosen for Voyager 2 conditions that the pickup ion density is about 25% and the pickup ions gain the larger share ( approximately 90%) of the downstream thermal pressure, consistent with Voyager 2 observations near the shock

    The nature of CuA in cytochrome c oxidase

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    The isolation and purification of yeast cytochrome c oxidase is described. Characterization of the purified protein indicates that it is spectroscopically identical with cytochrome c oxidase isolated from beef heart. Preparations of isotopically substituted yeast cytochrome c oxidase are obtained incorporating [1,3-15N2]histidine or [beta,beta- 2H2]cysteine. Electron paramagnetic resonance and electron nuclear double resonance spectra of the isotopically substituted proteins identify unambiguously at least 1 cysteine and 1 histidine as ligands to CuA and suggest that substantial spin density is delocalized onto a cysteine sulfur in the oxidized protein to render the site Cu(I)-S

    The Primordial Helium Abundance: Toward Understanding and Removing the Cosmic Scatter in the \u3cem\u3eDY/DZ\u3c/em\u3e Relation

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    We present results from photoionization models of low-metallicity H II regions. These nebulae form the basis for measuring the primordial helium abundance. Our models show that the helium ionization correction factor (ICF) can be nonnegligible for nebulae excited by stars with effective temperatures larger than 40,000 K. Furthermore, we find that when the effective temperature rises to above 45,000 K, the ICF can be significantly negative. This result is independent of the choice of stellar atmosphere. However, if an H II region has an [O III] λ5007/[O I] λ6300 ratio greater than 300, then our models show that, regardless of its metallicity, it will have a negligibly small ICF. A similar, but metallicity-dependent, result was found using the [O III] λ5007/Hβ ratio. These two results can be used as selection criteria to remove nebulae with potentially nonnegligible ICFs. Use of our metallicity-independent criterion on the data of Izotov & Thuan results in a 20% reduction of the rms scatter about the best-fit Y-Z line. A fit to the selected data results in a slight increase of the value of the primordial helium abundance

    Stereochemical studies on protonated bridgehead amines. ^1H NMR determination of cis and trans B-C ring-fused structures for salts of hexahydropyrrolo [2,1-a] isoquinolines and related C ring homologs. Capture of unstable ring-fused structures in the solid state

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    Acid-addition salts of tricyclic isoquinolines 2a/b, 3a/b, 4a-4c, 5, 6a/b, 7, 8a/b, 9a/b, and 17a/b were studied by high-field ^1H NMR in CDCl_3 solution. Cis (e.g., 14 and 15 in Figure 1) and trans (e.g., 13)B-C ring-fused structures were identified by using the vicinal ^3J(CH-NH) coupling constants, which demonstrate a Karplus-like behavior. In some cases, we initially observed a trans form, which converted to a cis A form by N H proton exchange. For 4c.HBr, the exchange process was slowed by addition of trifluoroacetic acid. In many cases, cis A and cis B structures were preferred in solution. The pendant phenyl group exerted a strong influence on the preferred solution structure. Observation of the initial, unstable trans-fused structures was related to their capture in the solid state and release intact on dissolution. X-ray diffraction was performed on the HBr salts of 2a (B-C cis), 2b (B-C cis), and 4c (B-C trans). The result for 4c.HBr confirmed the connection between the initial trans form in solution and the solid state. For 17b.HCI two conformers, associated with hindered rotation about the bond connecting the 2,6-disubstituted phenyl group to the tricyclic array, were detected at ambient probe temperature; however, rotamers were not observed for either of the two forms (trans and cis A) of 17a.HBr. Two conformers were also found for 16b.HBr. Temperature-dependent behavior was recorded in the ^1H NMR spectra of 17b.HBr and 16b.HBr; the activation free energy for interconversion of conformers was estimated to be in the vicinity of 17 kcal/mol for the former and 14-15 kcal/mol for the latter. The ^1H NMR spectrum of butaclamol hydrochloride (20.HC1), a potent neuroleptic agent, in Me_2SO-d_6 revealed two species in a ratio of 81:19, which were assigned as trans and cis A forms, respectively. ^1H NMR data for various free bases are also presented and discussed. Empirical force field calculations on three model hydrocarbons are discussed from a perspective of finding an explanation for the configurational/conformational behavior of the bridgehead ammonium salts. Diverse literature examples of structures for protonated bridgehead amines are also discussed. A tentative rationale is suggested for the preference of cis A forms in some protonated tetrahydroisoquinoline derivatives

    Targeted validation: validating clinical prediction models in their intended population and setting

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    Clinical prediction models must be appropriately validated before they can be used. While validation studies are sometimes carefully designed to match an intended population/setting of the model, it is common for validation studies to take place with arbitrary datasets, chosen for convenience rather than relevance. We call estimating how well a model performs within the intended population/setting "targeted validation". Use of this term sharpens the focus on the intended use of a model, which may increase the applicability of developed models, avoid misleading conclusions, and reduce research waste. It also exposes that external validation may not be required when the intended population for the model matches the population used to develop the model; here, a robust internal validation may be sufficient, especially if the development dataset was large

    In vivo pharmacological activity and biodistribution of S-nitrosophytochelatins after intravenous and intranasal administration in mice

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    AbstractS-nitrosophytochelatins (SNOPCs) are novel analogues of S-nitrosoglutathione (GSNO) with the advantage of carrying varying ratios of S-nitrosothiol (SNO) moieties per molecule. Our aim was to investigate the in vivo pharmacological potency and biodistribution of these new GSNO analogues after intravenous (i.v.) and intranasal (i.n.) administration in mice. SNOPCs with either two or six SNO groups and GSNO were synthesized and characterized for purity. Compounds were administered i.v. or i.n. at 1 μmol NO/kg body weight to CD-1 mice. Blood pressure was measured and biodistribution studies of total nitrate and nitrite species (NOx) and phytochelatins were performed after i.v. administration. At equivalent doses of NO, it was observed that SNOPC-6 generated a rapid and significantly greater reduction in blood pressure (∼60% reduction compared to saline) whereas GSNO and SNOPC-2 only achieved a 30–35% decrease. The reduction in blood pressure was transient and recovered to baseline levels within ∼2 min for all compounds. NOx species were transiently elevated (over 5 min) in the plasma, lung, heart and liver. Interestingly, a size-dependent phytochelatin accumulation was observed in several tissues including the heart, lungs, kidney, brain and liver. Biodistribution profiles of NOx were also obtained after i.n. administration, showing significant lung retention of NOx over 15 min with minor systemic increases observed from 5 to 15 min. In summary, this study has revealed interesting in vivo pharmacological properties of SNOPCs, with regard to their dramatic hypotensive effects and differing biodistribution patterns following two different routes of administration

    Climate Change and the Residential Development Industry in Ottawa, Canada.

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    This paper is intended to inform discussions between industry and government policymakers in and beyond Ottawa, Canada about climate change and potential impacts on residential development regulations and corresponding industry practices. Ultimately, both private and public stakeholders must acknowledge the impacts of urban form on greenhouse gas (GHG) emissions, and, conversely, the impacts of climate change on cities, for any meaningful progress on urban sustainability to ensue. Section 1 introduces the basic relationships between urban development and climate change. Urban form is directly tied to energy consump

    Variability in the α and β anomer content of commercially available lactose

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    Lactose, a disaccharide is a ubiquitous excipient in many pharmaceutical formulations which exists in two anomeric forms; either as - or -lactose. The anomers have different properties which can affect their application. Nevertheless, batches of lactose products are widely produced by many manufacturers, and is available in many grades. However, the anomeric content of these batches has not been accurately characterized and reported previously. Therefore, the aim of this study was to analyse a set of 19 commercially available samples of lactose using a novel H⁠1-NMR technique to establish a library showing the anomeric content of a large range of lactose products. The lactose samples were also analysed by DSC. The anomeric content of the -lactose monohydrate samples were found to vary by more than 10%, which might in_uence bioavailability from ^nal formulations. The data showed that there is a need to determine and monitor the anomeric content of lactose and this should be a priority to both manufacturers and formulators of medicines

    Establishing the importance of oil-membrane interactions on the transmembrane diffusion of physicochemically diverse compounds

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    © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This is a pre-copyedited, author produced PDF of an article accepted for publication in International Journal of Phrmaceutics following peer review. The final, definitive version of this paper Vol 56 (1-2): 429-437 , first published online March 21, 2016, is available on line at doi: 10.1016/j.ijpharm.2016.03.020The diffusion process through a non-porous barrier membrane depends on the properties of the drug, vehicle and membrane. The aim of the current study was to investigate whether a series of oily vehicles might have the potential to interact to varying degrees with synthetic membranes and to determine whether any such interaction might affect the permeation of co-formulated permeants: methylparaben (MP); butylparaben (BP) or caffeine (CF). The oils (isopropyl myristate (IPM), isohexadecane (IHD), hexadecane (HD), oleic acid (OA) and liquid paraffin (LP)) and membranes (silicone, high density polyethylene and polyurethane) employed in the study were selected such that they displayed a range of different structural, and physicochemical properties. Diffusion studies showed that many of the vehicles were not inert and did interact with the membranes resulting in a modification of the permeants’ flux when corrected for membrane thickness (e.g. normalized flux of MP increased from 1.25 ± 0.13 μg cm−1 h−1 in LP to 17.94 ± 0.25 μg cm−1 h−1in IPM). The oils were sorbed differently to membranes (range of weight gain: 2.2 ± 0.2% for polyurethane with LP to 105.6 ± 1.1% for silicone with IHD). Membrane interaction was apparently dependent upon the physicochemical properties including; size, shape, flexibility and the Hansen solubility parameter values of both the membranes and oils. Sorbed oils resulted in modified permeant diffusion through the membranes. No simple correlation was found to exist between the Hansen solubility parameters of the oils or swelling of the membrane and the normalized fluxes of the three compounds investigated. More sophisticated modelling would appear to be required to delineate and quantify the key molecular parameters of membrane, permeant and vehicle compatibility and their interactions of relevance to membrane permeation.Peer reviewe
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