bluuebunny/crossref_metadata_2025 huggingface dataset:
Petrogenesis of an ultrahigh‐pressure garnet‐bearing ultramafic body from Maowu, Dabie Mountains, east‐central China
Authors: Liou J. G. , Zhang R. Y.
Published: January 2004

The Maowu garnet‐bearing ultramafic body (∼ 250 × > 50 m2) in the Dabie ultrahigh‐pressure (UHP) terrane has several distinct petrologic characteristics: (i) most rocks are layers of garnet‐bearing ultramafics including orthopyroxenite and clinopyroxenite with minor harzburgite and omphacite‐rich layers; these compositional layers range in thickness from 5 cm to 1.6 m; (ii) rutile is ubiquitous and is most abundant in clinopyroxenite (up to 1–2 vol%); (iii) monazite is common as inclusions in silicates and as a matrix phase; (iv) exsolved plates of magnetite occur in olivine (Fo93), and monazite in apatite; (v) chromite occurs as fine‐grained inclusions in enstatite and clinohumite; (vi) hydrous phases including talc, clinochlore and amphibole are common as inclusions in coarse‐grained garnet; and (vii) major silicates are high in Mg/(Mg + Fe) values. Most of the ultramafic rocks are high in rare earth elements (REE), P, Cr and TiO2, and are significantly different from Mg–Cr or Fe–Ti garnet peridotites which are common in the western Alps, Western Gneiss Region, and the Bohemian Massif. Well‐foliated orthopyroxenite is composed of Grt (Prp60–74) + En (En92–96; 0.05–0.14 wt% Al2O3) + Chl (2–3 wt% Cr2O3) ± clinohumite ± magnesite ± Di (Di94–97) + chromite. Omphacitic rocks contain mainly elongated omphacite (> 90 vol%) with rare garnet (Prp45Alm41Gr13), rutile, apatite, and monazite. Omphacites (Jd63–67Ac6–12Aug20–31) display pronounced compositional zoning and contain inclusions of coesite relics and quartz pseudomorphs after coesite. Minor retrograde phases include talc/tremolite after Px, Chl after Grt, Cpx (Jd49Ac13Aug38) and Ab after omphacite. Garnet‐bearing ultramafic and omphacitic rocks have been subjected to UHP metamorphism at pressures of ∼ 35–50 kbar and 750 ± 50 °C under extremely low XCO2 conditions (< 0.001); a minor amphibolite facies overprint took place at P < 15 kbar and 650 °C. The protoliths may be Proterozoic ultramafic crustal cumulates that were subjected to metasomatism prior to Triassic subduction to mantle depths of more than 100 km during the collision of the Sino‐Korean and Yangtze Cratons.
Child and Adolescent Mental Health within Primary Care: A Study of General Practitioners’ Perceptions
Authors: Cockburn Katrina , Bernard Paul
Published: January 2004

Background:  Primary Care teams play an important role in the provision of mental health care to children and young people.

Methods:  We developed and distributed a questionnaire to all General Practitioners within one Health Authority area.

Results:  Many of the respondents rated as less than satisfactory their competence and their knowledge and skills in important areas of child and adolescent mental health practice. A significant minority expressed a high level of interest in child and adolescent mental health and most respondents reported that they would value further training.

Conclusions:  General Practitioners should be provided with more training and support in their role as providers of child and adolescent mental health care.
Evolving scholarly communication
Authors: Marks Jayne , Hannay Timo
Published: January 2004

Nature Publishing Group and the Alliance for Cellular Signaling formed a partnership in 2001 to develop a comprehensive website for researchers in the field of cellular signalling. This website aimed to evolve the traditional form of publication (an article with supplementary information and links) into something that made better use of web and database technologies, and provided more value to scientists. This article gives an overview of the project, some of the thinking behind it, and how it has developed.
The Digital Curation Centre
Authors: Beagrie Neil
Published: January 2004

The JISC and the EPSRCe‐science core programme will shortly establish a Digital Curation Centre to develop key research, services and generic tools needed by institutions and archiving bodies to manage digital collections over the long term. This article sets out its implications for ALPSP members and its relationship to other initiatives in e‐science and digital preservation.
Driving change in the research and HE information market
Authors: Roosendaal Hans E.
Published: January 2004

This paper considers the concept of a federated network of repositories of information for research and higher education, and discusses the main engines for change in that market using availability and use of information as parameters. The value chain is used as an analytical instrument in considering options for, and roles and responsibilities of, the stakeholders. Strategic issues are discussed in the context of a high‐level strategy for this market and its consequences for the different stakeholders in the value chain, and in particular research and higher education institutions.
Between a rock and a hard place: the big squeeze for small publishers
Authors: Prosser David C.
Published: January 2004

The combination of decreased income as a result of the RoweCom collapse, cuts in library budgets internationally, and the success of ‘Big Deal’ bundling arrangements has serious repercussions for smaller and society publishers. This paper argues that the scholarly communications environment is going to become increasingly hostile for these publishers and that their best chance of survival may be to adapt to new business models, in particular open access.
Publishing e‐books: OECD's pay‐per‐view and e‐library services 1998–2003
Authors: Green Toby
Published: January 2004

The OECD's experience in transforming its stagnating book publishing business using the e‐book is described. OECD used e‐books first as a pay‐per‐view system within an online bookshop (1998). It then rejected e‐book aggregators and introduced an online library on a subscription basis (2001). OECD has moved from being a traditional print book publisher to being an online e‐book publisher, supported by print where necessary. It is now developing an e‐book account service inside its online bookshop and has the flexibility to publish a broader range of books to a wider audience than was previously possible.
Metadata for STM journal publishers: a review of the current scene
Authors: Morgan Cliff
Published: January 2004

This article provides an overview of those metadata schemes that are of most relevance to STM journal publishers. The current status of each scheme is discussed, and references given for detailed specifications.
Print on‐demand is boosting availability of books and journal issues — and that's good for sales!
Authors: Higgins Suzanne Wilson
Published: January 2004

An account is given of the advantages of print‐on‐demand to the learned publishing sector. The need for appropriate administrative arrangements for it is stressed and some examples of the issues that should be addressed are given.
The role of academic journal publications in the UK Research Assessment Exercise
Authors: Bence Valerie , Oppenheim Charles
Published: January 2004

This article explores the evolution of the role of academic journal articles submitted to the UK's Research Assessment Exercise (RAE). By reviewing their role, it is possible to see how the changes from quantitative to qualitative assessment (and the resulting problems surrounding the definition of ‘quality’ journals) has impacted both on the journals selected by academics for publishing their research and the assessment of them. Although only one part of RAE submissions, the listing of published research outputs provides the primary evidence for research quality to most RAE panels, and is a significant driver of the final grade awarded, and thus the funding received by submitting institutions. The RAE, being a peer‐reviewed assessment exercise, mirrors in some ways the peer‐review process immured within scholarly publication. The developing role of journal publications as a vehicle for academic research output is examined via the chronology of the RAE, before assessing the current situation in which published journal output formed almost 70% of all output assessed by RAE panels in the latest exercise. The impact of this increased importance of academic journals in the assessment process is considered not only for academics but also for the wider community, i.e. publishers and libraries.
Liver Disease in Heavy Drinkers With and Without Alcohol Withdrawal Syndrome
Authors: Barrio E. , Tomé S. , Rodríguez I. , Gude F. , Sánchez‐Leira J. , Pérez‐Becerra E. , González‐Quintela A.
Published: January 2004

Abstract: Background: Withdrawal syndrome is a hallmark of alcohol dependence. The characteristics of alcohol consumption, closely related to dependence, could influence the development of alcoholic liver disease. The study aimed to investigate if patients with severe alcohol withdrawal syndrome have a peculiar profile of liver disease.

Methods: The study included 256 heavy drinkers (aged 19–75 years, 70.3% males) admitted to an Internal Medicine Department. Patients admitted for complications of liver disease were not included. Severe alcohol withdrawal syndrome (seizures, disordered perceptions, or delirium) developed in 150 patients (58.6%). Alcohol consumption (daily quantity, duration, and pattern [regular or irregular]) was assessed by questionnaire. Liver biopsy was performed in all cases.

Results: Patients with alcohol withdrawal syndrome showed a lower prevalence of liver cirrhosis and a higher prevalence of alcoholic hepatitis than patients without it. The negative association of alcohol withdrawal syndrome with liver cirrhosis persisted after we adjusted for sex, daily intake, duration, and pattern of alcohol consumption. Alcoholic hepatitis was independently associated with the irregular pattern of alcohol consumption, which was closely associated with severe alcohol withdrawal syndrome.

Conclusions: The profile of liver injury is different in heavy drinkers who develop and who do not develop a severe alcohol withdrawal syndrome when admitted to the hospital.
Endogenous Opioid Receptor Genes and Alcohol Dependence Among Taiwanese Han
Authors: Loh El Wui , Fann Cathy S. J. , Chang Yuh Terng , Chang Ching Jui , Cheng Andrew T. A.
Published: January 2004

Abstract: Background: Nonselective opioid antagonists reduce alcohol consumption under various experimental situations, and several association studies have examined possible roles of opioid receptor mu (OPRM), delta (OPRD), and kappa (OPRK) genes in the development of alcohol dependence.

Methods: We examined 20 single nucleotide polymorphisms (SNPs) across the OPRM, OPRD, and OPRK genes in 158 alcohol‐dependent subjects and 149 controls. Differences in allele frequency and genotype distribution between case subjects and controls, as well as the deviation from Hardy‐Weinberg equilibrium, were examined using Fisher's exact tests.

Results: No significant difference in either allele or genotype frequency was found between case subjects and controls for each of the SNPs.

Conclusions: Our findings do not support a possible role of the opioid receptor genes for the proclivity to alcohol dependence in the Taiwanese Han.
Survival of AA and ANA Rats During Lifelong Ethanol Exposure
Authors: Sarviharju Maija , Riikonen Jarno , Jaatinen Pia , Sinclair David , Hervonen Antti , Kiianmaa Kalervo
Published: January 2004

Abstract: Background: Study of the long‐term effects of chronic alcohol consumption in human populations is confounded by genetic and environmental factors.

Methods: The study was intended to investigate the effects on morbidity and survival of lifetime forced ethanol consumption in male and female AA (Alko, Alcohol) and ANA (Alko, Non‐Alcohol) rats. The ethanol‐exposed rats had 12% ethanol as the only available fluid from 3 to 24 months of age. The control groups had water. Rats that died during the experiment and those that were killed at 24 months of age were all autopsied, and the pathologic findings were recorded.

Results: Lifelong ethanol consumption did not change the survival rate of the rats, and had no significant effect on the rates of any of the pathologic measures in either the AA or ANA line of rats, suggesting that this may not be a good animal model for studying the detrimental effects of chronic alcohol. An unexpected, highly significant finding was observed: the AA rats, bred for high voluntary ethanol drinking, lived much longer than the ANA rats, bred for ethanol avoidance. The death rate by 24 months in the AA line was less than one‐third of that in the ANA line. This difference was found regardless of whether the animals were maintained on alcohol or water, and in both genders. The AA rats had significantly lower rates of kidney disease, benign tumors, and cardiovascular disease than the ANA animals.

Conclusions: Lifelong ethanol consumption increased neither the mortality nor the morbidity of AA and ANA line of rats. Genes selected in the development of the high drinking AA line have additional effects producing rats that are healthier and living longer than the ANA rats possessing genes resulting in alcohol avoidance.
Ethanol Withdrawal Influences Survival and Morphology of Developing Rat Hippocampal Neurons In Vitro
Authors: Lindsley Tara A. , Clarke Shannon
Published: January 2004

Abstract: Background: Previous studies in this laboratory have shown that, like their counterparts in vivo, fetal rat hippocampal pyramidal neurons in culture develop abnormally small dendritic arbors when exposed to ethanol. This study asked whether ethanol's inhibitory effects on dendritic development differ when the duration of ethanol exposure and timing of withdrawal are varied to correspond with early versus later stages of development and whether ethanol withdrawal influences survival of these neurons.

Methods: We compared neurons exposed continuously for 6 or 14 days to ethanol (70 mM) with neurons transferred from ethanol‐containing medium to control medium either 1 day after adding ethanol (before dendrites elongated) or 6 days after adding ethanol (after dendrites began elongating). We then performed morphometric and cell density analyses at 6 and 14 days using digital images of neurons immunostained with microtubule‐associated protein 2 (MAP2) to visualize dendrites.

Results: Continuous exposure to ethanol decreased the length and number of dendrites formed but had no effect on neuron survival compared with controls without ethanol. Dendritic length was less inhibited when ethanol was withdrawn after 1 day, but the number of dendrites per cell was unchanged compared with neurons continuously exposed to ethanol. Withdrawal from ethanol at 1 day slightly enhanced the survival of neurons assessed at 14 days compared with neurons in control medium and with neurons exposed continuously to ethanol. In contrast, withdrawal from ethanol at 6 days severely decreased the number of neurons at 14 days.

Conclusions: These results suggest that dendrites can achieve normal length when ethanol exposure is limited to only 1 day and withdrawal occurs before dendrites begin elongating. However, a persistent reduction in dendrite number results in smaller overall dendritic arbor size. Although continuous exposure to ethanol has little effect on neuron survival in these cultures, and exposure limited to 1 day followed by withdrawal can be neuroprotective against cell death associated with increased time in culture, longer exposure before withdrawal can trigger cell death.
Fetal Alcohol Exposure Alters GAP‐43 Phosphorylation and Protein Kinase C Responses to Contextual Fear Conditioning in the Hippocampus of Adult Rat Offspring
Authors: Tanner Daniel C. , Githinji Ann W. , Young Elizabeth A. , Meiri Karina , Savage Daniel D. , Perrone‐Bizzozero Nora I.
Published: January 2004

Abstract:Background:The growth‐ and plasticity‐associated protein GAP‐43 plays a significant role in the establishment and remodeling of neuronal connections. We have previously shown that GAP‐43 levels, protein kinase C (PKC) activity, and GAP‐43 phosphorylation increase during contextual fear conditioning and that fetal alcohol exposure (FAE) decreases PKC activity and GAP‐43 phosphorylation in the hippocampus of adult offspring. Drawing on these observations, we hypothesized that FAE manifests its cognitive impairment by disrupting PKC activation and membrane translocation, thereby decreasing GAP‐43 phosphorylation and function.

Methods:Three groups of pregnant rat dams (FAE and two control diet groups) were placed on different diet regimens. Offspring from each of these groups were placed into each of four test groups, a contextual fear conditioned (CFC) group, a naïve unhandled group, and two nonlearning stress control groups. Hippocampi were dissected, homogenized, and used to prepare a cytosolic and a membrane fraction. These fractions were probed for total GAP‐43, PKC‐phosphorylated GAP‐43, and several PKC subtypes. PKC activity also was measured in total homogenates.

Results:Compared with both control diet groups, FAE animals showed a deficit in the activation of PKC in the hippocampus at 24 hr but not at 1.5 hr after CFC. Likewise, we found that the amount of GAP‐43 and its phosphorylation were decreased 24 hr after CFC in FAE rats but not at early times after training. Analysis of the translocation of various PKC isoforms revealed that FAE animals had decreased levels of membrane‐bound PKC β2and PKC ε 24 hr after CFC.

Conclusions:Considering the role of PKC activation and GAP‐43 phosphorylation in synaptic plasticity, our results suggest that deficient translocation of PKC β2and PKC ε in the hippocampus may mediate the electrophysiological and behavioral deficits observed in fetal alcohol exposed animals.
NMDA Receptor Subunit Expression After Combined Prenatal and Postnatal Exposure to Ethanol
Authors: Nixon Kimberly , Hughes Peter D. , Amsel Abram , Leslie Steven W.
Published: January 2004

Abstract: Background: The N‐methyl‐d‐aspartate receptor (NMDAR), a subtype of glutamate receptor, is essential for normal neurodevelopment. The brain growth spurt, which is both prenatal and postnatal in the rat, is a time when the brain is especially sensitive to the effects of a teratogen, such as alcohol. Changes in NMDAR function after early perinatal exposure to ethanol (EtOH) may be related to alterations in the expression of secondary subunits. Thus, we investigated the expression of the NR1, NR2A, and NR2B subunits after combined prenatal and postnatal exposure to EtOH.

Methods: A binge model was used to administer EtOH (5 g/kg) or isocaloric vehicle to pregnant female rats followed by EtOH (6.2 g/kg) or isocaloric control diet from postnatal days 4 through 9 via an artificial rearing method. Proteins from crude membrane homogenates isolated from cortex and hippocampus at postnatal day 10, 14, or 21 were separated in a standard Western blot procedure.

Results: The expression of the NR2A subunit of EtOH‐exposed pups showed a significant increase at postnatal day 10 in hippocampus compared with diet controls. No significant changes were seen for any other subunit in either region.

Conclusions: The up‐regulation of NR2A during EtOH withdrawal is consistent with compensatory changes to prolonged inhibition of the NMDAR. These results indicate that postnatal exposure to ethanol produces distinct effects on the NMDAR, which may underlie deficits associated with alcohol‐related neurodevelopmental disorder.
Mismatch Negativity: No Difference Between Controls and Abstinent Alcoholics
Authors: Fein George , Whitlow Bridget , Finn Peter
Published: January 2004

Abstract: Background: A number of studies have examined the amplitude of the mismatch negativity (MMN) evoked potential as a measure of a brain inhibitory deficit in alcoholics or those at risk for alcoholism. The current study examined MMN in alcoholics abstinent an average of 6.7 years (with a minimum of six months abstinence) compared to controls. This study examined the association of MMN with alcoholism family history density, with indices of the presence and severity of externalizing disorders (a risk‐factor for alcoholism), and with alcohol use variables.

Methods: Electroencephalograms were gathered on 76 subjects (38 controls, 38 abstinent alcoholics) during a nonattending mismatch negativity experiment. Measures of alcoholism family history density, disinhibited personality traits, and antisocial symptoms served as measures of risk‐factors known to be associated with a genetic liability to alcoholism. Alcohol use variables were used as measures of alcoholism severity.

Results: There were no differences in MMN amplitude or latency between controls and abstinent alcoholics. There also were no significant associations between MMN measures and the measures of risk for alcoholism or with the severity of alcohol use or duration of abstinence.

Conclusions: The results suggest that MMN is neither affected in chronic alcoholics nor associated with alcoholism vulnerability, and thus does not reflect a trait marker of alcoholism or alcoholism risk. The current results do not address effects on MMN of acute alcohol ingestion or withdrawal from alcohol.
Effective Strategies for Recruiting Families Ascertained Through Alcoholic Probands
Authors: Seaton Kimberly L. , Cornell Jodi L. , Wilhelmsen Kirk C. , Vieten Cassandra
Published: January 2004

Abstract: Background: Recruiting a large number of participants meeting strict inclusion criteria can be challenging, particularly when selecting for a condition associated with a social stigma such as alcoholism, when participation involves collection of medical specimens and sensitive information, and when the participation of family members or other collaterals is required. Developing and implementing a successful recruitment plan depends upon identifying the most effective recruitment strategies given the available resources.

Methods: Several strategies for recruiting subjects for a large family study on the genetics of alcoholism were evaluated over a two‐year period with regard to participant yield, time and cost expenditure.

Results: Overall effectiveness of a recruitment strategy was determined based on a composite of yield, cost and time expenditure. The most effective recruitment strategies were direct mail, press release, the Internet and treatment center collaborations.

Conclusion:: Results provide insight into successful strategies for recruiting large numbers of participants and their family members selected for a condition associated with a social stigma.
Determination of an Estradiol Dose‐Response Relationship in the Modulation of Ethanol Intake
Authors: Ford Matthew M. , Eldridge J. C. , Samson Herman H.
Published: January 2004

Abstract: Background: Estradiol (E2) potentiates the self‐administration of numerous psychoactive drugs in female rodents. An analogous modulatory role of E2 on ethanol consumption remains unresolved because of examination of limited doses. The purpose of this study was to delineate a dose‐response relationship for E2 on ethanol intake with an extended range and number of E2 doses.

Methods: Female Long‐Evans rats had continuous access (22 hr/day) to both 10% ethanol (10E) solution and water. After the establishment of stable 10E intake baselines, rats were assigned to one of seven dose groups balanced for 10E intake [sham‐operated (Shm) or ovariectomized (Ovx) plus E2 (μg/kg)]: Shm + 0, Ovx + 0, Ovx + 0.05, Ovx + 0.15, Ovx + 0.5, Ovx + 1.5, and Ovx + 5. Ethanol preference drinking was evaluated during 25 consecutive days of E2 replacement treatment, and trunk blood was collected for the determination of plasma E2 and progesterone concentrations.

Results: Chronic E2 replacement regimens (0.05–1.5 μg/kg) dose‐dependently augmented 10E intakes and ethanol preference ratios without concomitantly altering water consumption. Despite the maintenance of 2‐ to 3‐fold greater plasma E2 levels, a supraphysiologic E2 dose (5 μg/kg) failed to precipitate ethanol intakes in excess of levels observed after treatment with a high physiologic E2 dose (1.5 μg/kg). Plasma progesterone concentrations were significantly increased in treatment groups (1.5 and 5 μg/kg E2) that exhibited corresponding significant increases in ethanol consumption.

Conclusions: A positive dose‐response relationship between E2 and ethanol intake (incremental increases in E2 dose corresponded to incremental increases in intake) was apparently limited to a physiologic concentration range, because a supraphysiologic dose failed to elicit an additional stepwise increase in ethanol intake. These findings stipulate a modulatory role for E2 in the regulation of moderate ethanol intake and suggest that endogenous fluctuations of E2 may alter the propensity toward consumption in women and in female animal models of ethanol self‐administration.
Postnatal Binge Ethanol Exposure Affects Habituation of the Cardiac Orienting Response to an Olfactory Stimulus in Preweanling Rats
Authors: Hunt Pamela S. , Phillips Jessicah S.
Published: January 2004

Abstract:Background:Prenatal exposure to alcohol can result in intellectual impairments, reduced habituation and distractibility, visual‐spatial deficits, and problems in attention. Dysfunction in attention, including habituation of responses to nonsignal stimuli, can have devastating consequences for cognitive development. This research examined whether binge exposure to ethanol on postnatal days (PD) 4 to 9 would affect cardiac orienting or response habituation to an olfactory stimulus in preweanling rats.

Methods:Ethanol‐exposed subjects were given ethanol 5.25 g/kg/day on PD4 to 9. Controls were either sham intubated or unhandled during this time. To assess baseline and phasic cardiac function, PD16 subjects were tested under differential pharmacological blockade of the sympathetic or parasympathetic nervous systems by administration of the peripherally acting antagonists atenolol or atropine methyl nitrate. In a second experiment, separate groups of subjects were tested for habituation of the cardiac orienting response to an olfactory stimulus.

Results:Results indicate that postnatal ethanol had no observable effect on the functional development of autonomic control over heart rate. Similarly, ethanol exposure had no effect on the form or magnitude of the cardiac orienting response. However, neonatal ethanol exposure did result in a deficit in orienting response habituation; ethanol‐exposed subjects continued to respond to the stimulus with a large‐magnitude bradycardia after control subjects exhibited complete response habituation. In addition, ethanol‐exposed subjects had longer orienting response latencies than controls.

Conclusions:The results indicate that this animal model has the potential to contribute to investigations designed to understand basic forms of memory impairments observed in humans with a history of prenatal alcohol exposure. The postnatal binge ethanol model of fetal alcohol effects produces deficits in nonassociative memory that are similar to those observed in human infants exposed prenatally to ethanol. Deficits in response habituation have important implications for cognitive development.
Improvement in Quality of Life After Treatment for Alcohol Dependence With Acamprosate and Psychosocial Support
Authors: Morgan Marsha Y. , Landron Frédéric , Lehert Philippe ,   for the New European Alcoholism Treatment Study Group
Published: January 2004

Abstract: Background: The impact of disease on health‐related quality of life is now well recognized, as is the importance of this variable as a measure of treatment efficacy.

Methods: Patients from five European countries were enrolled in an open, multicenter, prospective study designed to observe outcome in dependent drinkers treated for 6 months with acamprosate and psychosocial support. Version 1 of the 36‐item Short Form Health Profile (SF‐36v1) questionnaire was administered at inclusion and at 3 and 6 months. Responses were described as handicaps compared with an appropriately matched, healthy reference population. One‐way fixed ANOVA and simultaneous stepwise linear regression analysis were used to identify potential predictors of quality of life at baseline and after treatment.

Results: Baseline SF‐36v1 data were obtained from 1216 patients (mean age, 43 ± 9 years; 77% male). Mean values for all SF‐36v1 dimensions were significantly lower in the patient population than in the normative reference population; the most important deficits were observed in physical and emotional role limitations and in social functioning. The most important predictors of baseline quality of life were severity of alcohol dependence, employment status, psychiatric history, quantity and frequency of alcohol consumption, attendance at Alcoholics Anonymous, global alcohol health status, age, gender, and education. SF‐36v1 data were obtained from 686 patients at 3 months and from 497 at 6 months. Significant improvements were observed in all SF‐36v1 dimensional and summary scores after 3 months of treatment (p < 0.001); further marginal improvements were observed between 3 and 6 months. The most important predictors of quality of life following treatment were the SF‐36v1 profile at baseline, followed by abstinence duration; patients who completed the trial and remained abstinent throughout showed the greatest improvement.

Conclusions: Health‐related quality of life is severly impaired in dependent drinkers. Treatment with acamprosate and psychosocial support, by promoting abstinence, improves the quality of life profile to levels comparable to those observed in healthy individuals.
Abnormal Hepatic Methionine and Glutathione Metabolism in Patients With Alcoholic Hepatitis
Authors: Lee Taunia D. , Sadda Mamatha R. , Mendler Michel H. , Bottiglieri Teodoro , Kanel Gary , Mato José M. , Lu Shelly C.
Published: January 2004

Abstract: Background: Abnormal methionine metabolism occurs in animals fed ethanol and in end‐stage cirrhotic patients. Expected consequences of these abnormalities include reduced hepatic S‐adenosylmethionine and glutathione (GSH) levels, impaired transmethylation, and reduced homocysteine catabolism, resulting in the often‐observed hyperhomocystinemia in cirrhotic patients. These parameters have not been examined simultaneously in patients with less advanced alcoholic liver disease.

Methods: Six patients hospitalized for alcoholic hepatitis were studied. Plasma was analyzed for homocysteine, methionine, and GSH levels. Liver biopsies diagnosed acute alcoholic hepatitis and underlying fibrosis. Liver specimens were processed for messenger RNA (mRNA) levels and various metabolites and were compared with those of six normal controls.

Results: Three patients had cirrhosis, and three had only portal fibrosis. Plasma levels of homocysteine and methionine were increased in two of the three patients with cirrhosis but not in the patients with fibrosis. All patients had markedly lower plasma GSH levels (mean ± SD: 0.27 ± 0.19 μM, which is at least 10‐fold lower than the normal range). Hepatic S‐adenosylmethionine levels were reduced by 50%, whereas methionine, GSH, and cysteine levels were reduced by 70–80%. The mRNA levels of most enzymes involved in methionine metabolism and GSH synthesis were decreased, whereas albumin expression was unchanged. Despite the well known induction of cytochrome P450 2E1 in chronic alcoholics, its mRNA levels were nearly 70% lower in these patients.

Conclusions: In alcoholic hepatitis, abnormal hepatic gene expression in methionine and GSH metabolism occurs and often contributes to decreased hepatic methionine, S‐adenosylmethionine, cysteine, and GSH levels. It may be important to replenish these thiols in patients hospitalized with alcoholic hepatitis.
Acute Ethanol Withdrawal (Hangover) and Social Behavior in Adolescent and Adult Male and Female Sprague‐Dawley Rats
Authors: Varlinskaya Elena I. , Spear Linda P.
Published: January 2004

Abstract: Background: The extensive use of alcohol during adolescence may be facilitated by an age‐specific attenuation in sensitivity to adverse effects of ethanol. Adolescent rats are less sensitive than adults to some delayed effects of acute ethanol, including hangover‐related anxiety on an elevated plus maze. The purpose of this study was to determine whether adolescent rats are also less sensitive than adults to hangover‐related anxiogenesis when indexed in terms of social inhibition.

Methods: Anxiety during ethanol hangover was indexed in adolescent and adult Sprague‐Dawley rats of both genders by assessing the suppression in social behavior during a social interaction test. Animals were tested 18 hr after intraperitoneal administration of 0 g/kg (saline) or 4 g/kg ethanol (experiment 1) or at test intervals chosen on the basis of assessments of ethanol clearance time (experiment 2) to equate clearance‐to‐test intervals across age and gender (experiments 3–5).

Results: Adults showed more hangover‐related social suppression and slower postclearance recovery than adolescents. Sex differences were more pronounced in adults than adolescents, with males being more affected than females. Ethanol clearance time was considerably longer in adult males than in adolescent animals and adult females. In contrast to the modest decreases in social activity observed in adolescent animals shortly after ethanol clearance, adolescents showed a surprising increase in play fighting later in the recovery period— a hangover‐related social facilitation that was not evident in adults.

Conclusions: The attenuated anxiety and increase in social interactions seen in adolescents during hangover are less likely to serve as deterrents for further drinking than the aversive increase in anxiety seen in adults. A facilitation of social interactions not only during a drinking episode, but also during the postalcohol recovery period, could help to establish a persisting cycle of drinking in at‐risk adolescents, leading to dependency and a lifelong history of alcohol‐related problems.
The Efficacy of Acamprosate in the Maintenance of Abstinence in Alcohol‐Dependent Individuals: Results of a Meta‐Analysis
Authors: Mann Karl , Lehert Philippe , Morgan Marsha Y.
Published: January 2004

Abstract: Background: A number of clinical trials have been undertaken to determine the efficacy of acamprosate in the maintenance of abstinence in alcohol‐dependent individuals. However, the reported differences in patient populations, treatment duration, and study endpoints make comparisons difficult. An assessment of the efficacy of treatment with acamprosate was, therefore, undertaken using meta‐analytical techniques.

Methods: All randomized, placebo‐controlled trials (RCTs) that fulfilled predetermined criteria were identified using (1) a language unrestricted search of 10 electronic databases; (2) a manual search of relevant journals, symposia, and conference proceedings; (3) cross‐referencing of all identified publications; (4) personal communications with investigators; and (5) scrutiny of Merck‐Santé's internal reports of all European trials. Study quality was assessed, independently, by three blinded workers. Key outcome data were identified; some outcome variables were recalculated to ensure consistency across trials. The primary outcome measure was continuous abstinence at 6 months; abstinence rates were determined by estimating Relative Benefit (RB).

Results: A total of 19 published 1 unpublished RCTs were identified that fulfilled the selection criteria; 3 were excluded because the documentation available was insufficient to allow adequate assessment. The remaining 17 studies, which included 4087 individuals, 53% of whom received active drug, were of good quality and were otherwise reasonably comparable. There was no evidence of publication bias. Continuous abstinence rates at 6 months were significantly higher in the acamprosate‐treated patients (acamprosate, 36.1%; placebo, 23.4%; RB, 1.47; [95% confidence intervals (CI): 1.29–1.69]; p < 0.001). This effect was observed independently of the method used for assigning missing data. The effect sizes in abstinent rates at 3, 6, and 12 months were 1.33, 1.50, and 1.95, respectively. At 12 months, the overall pooled difference in success rates between acamprosate and placebo was 13.3% (95% CI, 7.8–18.7%; number needed to treat, 7.5). Acamprosate also had a modest but significant beneficial effect on retention (6.01%; [95% CI, 2.90–8.82]; p= 0.0106).

Conclusion:: Acamprosate has a significant beneficial effect in enhancing abstinence in recently detoxified, alcohol‐dependent individuals.
Chronic Ethanol Consumption Reduces δ‐and μ‐Opioid Receptor–Stimulated G‐Protein Coupling in Rat Brain
Authors: Saland L. C. , Abeyta A. , Frausto S. , Raymond‐Stintz M. , Hastings C. M. , Carta M. , Valenzuela C. F. , Savage D. D.
Published: January 2004

Abstract: Background: Ethanol consumption is thought to enhance the release of endogenous opioids acting at opioid receptors (ORs) in the central nervous system. Prior studies have shown that chronic ethanol consumption in alcohol‐preferring rats uncouples μ‐ORs from Gi proteins. The purpose of this study was to investigate the potential for uncoupling of the δ‐ and the μ‐OR after chronic ethanol consumption in a nonpreferring rat strain.

Methods: We used radiohistochemical methods to study μ‐ and δ‐OR‐stimulated G‐protein coupling in brain tissue of rats ingesting liquid diets containing 6.7% ethanol (v/v) for 16 days, as compared with 0% ethanol pair‐fed control rats. Sections of brain from pair‐fed and ethanol‐treated rats were incubated with guanylyl 5′‐[gamma‐[35S]‐thio]‐triphosphate ([35S]‐GTPγS) in the absence and presence of d‐Pen2,d‐Pen5 enkephalin (DPDPE), a δ‐OR agonist, or Tyr‐d‐Ala‐Gly‐N (me)Phe‐Gly‐ol‐enkephalin (DAMGO), a μ‐OR agonist.

Results: DPDPE significantly stimulated [35S]‐GTPγS binding in the hippocampal dentate gyrus (DG), CA1, cerebellum, and inferior colliculus of untreated pair‐fed controls. By contrast, DPDPE‐stimulated [35S]‐GTPγS binding was reduced significantly in those brain regions in the ethanol‐consuming group. DAMGO stimulated [35S]‐GTPγS binding in cortex, caudate, nucleus accumbens, DG, CA1, and superior and inferior colliculi, whereas the DG, CA1, and colliculi showed a significant reduction of binding after chronic ethanol. Basal [35S]‐GTPγS binding was not different between the two diet groups.

Conclusions: These data are the first to demonstrate functional uncoupling of δ‐ORs from G proteins after chronic ethanol consumption. Uncoupling may result from modulation of receptors, possibly by internalization or phosphorylation. Alterations in functional coupling of both δ‐ and μ‐ORs and subsequent effects may contribute to continued ethanol consumption.
The Effects of Binge Alcohol Exposure on Bone Resorption and Biomechanical and Structural Properties are Offset by Concurrent Bisphosphonate Treatment
Authors: Callaci John J. , Juknelis Dainius , Patwardhan Avinash , Sartori Mark , Frost Nathan , Wezeman Frederick H.
Published: January 2004

Abstract: Background: Chronic alcohol consumption reduces bone mass and strength, increasing fracture risk for alcohol abusers. Mechanisms underlying this vulnerability involve modulation of bone remodeling. Direct effects of alcohol on bone formation have been documented; those on bone resorption are less well studied. Skeletal effects of exposure to high blood alcohol concentrations (BAC's) attained during binge drinking have not been studied. We examined the effects of repeated binge‐like alcohol treatment on bone resorption, bone mineral density and vertebral compressive strength in adult male rats treated with the aminobisphosphonate, risedronate.

Methods: A binge alcohol exposure model was developed using intraperitoneal (IP) injection to administer a 20% (vol/vol) alcohol/saline solution (3 g/kg, 1X/day) on four consecutive days for 1, 2 or 3 weeks in 400 g rats, with and without weekly risedronate treatment (0.5 mg/kg, 1X/week). Total serum deoxypyridinoline (Dpd) a crosslink of bone type collagen released during resorption was measured by ELISA. Bone mineral density (BMD) was measured using peripheral quantitative computed tomography (pQCT). Vertebral compressive strength was determined using an Instron materials testing machine. Trabecular integrity was analyzed by computer‐aided trabecular analysis system (TAS).

Results: Peak BAC's averaged 308.5 ± 12 mg/dL; average BAC was 258.6 ± 28.7 mg/dL at time of euthanasia. No significant effects of treatment were observed after 1 or 2 weeks of binge alcohol exposure. At 3 weeks of alcohol treatment serum Dpd was significantly increased (205%, p < 0.05) over controls. Bone mineral density (BMD) in cancellous bone of distal femur and lumbar spine were significantly decreased (34% and 21% respectively, p < 0.01) after 3 weeks of binge treatment. Vertebral (L4) compressive strength (maximum load sustained before failure) also decreased (27%, p < 0.05) after 3 binge alcohol cycles. Risedronate maintained the Dpd level (p < 0.01), BMD (p < 0.001) and vertebral structural biomechanical properties (p < 0.01) of binge‐treated rats at control levels (E vs ER). Indices of trabecular architectural integrity [Trabecular bone volume/tissue volume (BV/TV), bone area (BAR) and trabecular separation (Tb.Sp)] analyzed at week 3 showed (BV/TV) and (BAR) were significantly reduced in alcohol‐binged rats (p < 0.01), while (Tb.Sp) was significantly increased (p < 0.01). Risedronate also maintained the trabecular architectural indices of binge‐treated rats at control levels (E versus ER, p < 0.01).

Conclusions: In adult male rats, BAC's reflective of those attained during alcoholic binge drinking may affect the skeleton in part by stimulating bone resorption, an effect mitigated by risedronate.
Alcohol Dehydrogenase Polymorphisms Influence Alcohol‐Elimination Rates in a Male Jewish Population
Authors: Neumark Yehuda D. , Friedlander Yechiel , Durst Ronen , Leitersdorf Eran , Jaffe Dena , Ramchandani Vijay A. , O'Connor Sean , Carr Lucinda G. , Li T.‐K.
Published: January 2004

Abstract: Background: Genetic variation in the alcohol dehydrogenase (ADH) enzyme is associated with an aversion to alcohol and a lower risk of alcoholism among Asians. There is growing evidence of a functional role of the ADH2*2 allele in alcohol‐drinking patterns among Jews, who have traditionally exhibited low rates of alcoholism and alcohol‐related problems. The mechanism by which this allelic effect is mediated is not yet clearly understood. This study examined the effect of ADH2*2 on alcohol‐elimination rates (AER) under experimental conditions.

Methods: Young adult male Jews (N= 109) received an intravenous alcohol infusion; metabolism was measured by using standard breath alcohol concentration tests. A clamping technique was used to achieve and maintain a target breath alcohol concentration of 50 mg/100 ml for a defined time period. The AER at steady state was calculated. The alcohol disappearance rate was also calculated from the descending limb slope. Polymerase chain reaction was used for allelic determination of the ADH2 and ADH3 loci.

Results: The mean AER among ADH2*2 carriers was significantly higher (8.09 ± 1.4 g/hr) than among ADH2*1 homozygotes (7.14 ± 1.5 g/hr; p= 0.003). Significance was retained on adjustment for potential confounding covariates. The ADH2 allele explains 8.5% of the AER variance in this population. Little AER difference was observed across ADH3 genotype groups. The slope of the descending limb increased with increasing copies of the ADH2*2 allele.

Conclusions: The rate of alcohol elimination is significantly associated with the ADH2 genotype of Jewish males. Evidence for variation in alcohol metabolism across ADH genotypic groups provides support for the role of physiologic protective factors in alcohol drinking and suggests that reduced drinking among Jews may be genetically as well as environmentally determined. We believe that application of the novel “Indiana clamp” enhances AER measurement accuracy, allowing for detection of hitherto undetectable differences.
Methods to reduce direct maintenance costs for commercial aircraft
Authors: Wu Haiqiao , Liu Yi , Ding Yunliang , Liu Jia
Published: January 2004

Direct maintenance costs (DMC) of commercial aircraft make a significant contribution to an aircraft's cost of ownership. The aim of our research is to find out some methods to reduce DMC. The paper first points out that design and fault diagnosis are the key factors to influence DMC, disregarding factors unique to a particular airline. A new concept of R&M design – maintenance free operating period and fault diagnosis expert system are discussed in this paper, in order to reduce DMC.
Dynamic and impact response of damaged laminated composite plates
Authors: Ghosh Anup , Sinha P.K.
Published: January 2004

In the present investigation, a finite element analysis procedure is developed to predict the initiation and propagation of damages as well as to analyse damaged laminated composite plates under forced vibration and impact loads. Isoparametric quadratic plate bending element (nine‐noded rectangular) based on Mindlin plate theory is used to develop the FE codes for the present analysis. A phenomenological damage model assuming the effective stress concept is used to represent the damage of a lamina. The initiation and progress of damage due to forced vibration and low velocity impact are studied for different impactor velocities.
RKF‐based fault tolerant integrated INS/radar altimeter
Authors: Hajiyev Chingiz , Saltoglu Remzi
Published: January 2004

In this study, the integrated navigation system, consisting of radio and inertial navigation system (INS) altimeters, is presented. INS and the radio altimeter have different benefits and drawbacks. The integration is achieved by using an indirect Kalman filter. Hereby, the error models of the navigators are used by the Kalman filter to estimate vertical channel parameters of the navigation system. In the open loop system, INS is the main source of information, and radio altimeter provides discrete aiding data to support the estimations. At the next step of the study, in case of abrupt faults, the performance of the integrated system is examined. The optimal Kalman filter reacts with abnormal estimates to this situation as expected. To recover such a possible malfunctioning, the robust Kalman filter algorithm is suggested.
Anticorrosive spinel‐type pigments of the mixed metal oxides compared to metal polyphosphates
Authors: Kalendová A. , Veselý D. , Brodinová J.
Published: January 2004

The spinel‐type pigments of a general formula corresponding to AB2O4 containing as A the Mg2+ or Zn2+ ions and as B the Fe3+ or Al3+ ions or combinations of both the A and B were prepared and investigated with respect to their anticorrosive action as pigments in organic coatings. For the same purposes, comparative pigments, known for their efficiency as the metal‐corrosion inhibiting ingredients in similar formulations, were used. Further evaluation was carried out on the properties of condensed phosphates as anticorrosion pigments. The results obtained showed the high anticorrosion action of the spinel‐type pigments.
An evaluation of rust conversion coatings in simulated reinforced concrete pore solutions
Authors: Guidoni Griselda , Vázquez Marcela
Published: January 2004

The performance of reinforcing steel bars (rebars) coated with two different rust conversion coatings was analysed by means of electrochemical methods. Two exposure conditions were investigated, immersion in a pH 14 solution simulating pores in standard concrete, and immersion in a pH 9 solution simulating pore environments in carbonated concrete. The rebar corrosion potential (Ecorr), the corrosion rate (CR) and the electrochemical impedance (Z) were measured over 3 weeks. None of the products investigated helped to improve the resistance of steel against corrosion. Some parameters even indicated a detrimental action, particularly as the alkalinity of the solutions increased. Therefore, the application of this type of coating cannot be recommended during repair procedures of reinforced concrete structures due to the extremely alkaline environment provided by concrete.