bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Bayesian Model for Longitudinal Count Data with Non-Ignorable Dropout
Authors: Kaciroti Niko A. , Raghunathan Trivellore E. , Anthony Schork M. , Clark Noreen M. 
Published: September 2008

SummaryAsthma is an important chronic disease of childhood. An intervention programme for managing asthma was designed on principles of self-regulation and was evaluated by a randomized longitudinal study. The study focused on several outcomes, and, typically, missing data remained a pervasive problem. We develop a pattern–mixture model to evaluate the outcome of intervention on the number of hospitalizations with non-ignorable dropouts. Pattern–mixture models are not generally identifiable as no data may be available to estimate a number of model parameters. Sensitivity analyses are performed by imposing structures on the unidentified parameters. We propose a parameterization which permits sensitivity analyses on clustered longitudinal count data that have missing values due to non-ignorable missing data mechanisms. This parameterization is expressed as ratios between event rates across missing data patterns and the observed data pattern and thus measures departures from an ignorable missing data mechanism. Sensitivity analyses are performed within a Bayesian framework by averaging over different prior distributions on the event ratios. This model has the advantage of providing an intuitive and flexible framework for incorporating the uncertainty of the missing data mechanism in the final analysis.
Semiparametric Two-Sample Changepoint Model with Application to Human Immunodeficiency Virus Studies
Authors: Hu Zonghui , Qin Jing , Follmann Dean 
Published: September 2008

Summary
A two-sample changepoint model is proposed to investigate the difference between two treatments or devices. Under our semiparametric approach, no assumptions are made about the underlying distributions of the measurements from the two treatments or devices, but a parametric link is assumed between the two. The parametric link contains the possible changepoint where the two distributions start to differ. We apply the maximum empirical likelihood for model estimation and show the consistency of the changepoint estimator. An extended changepoint model is studied to handle data censored because of detection limits in viral load assays of human immunodeficiency virus (HIV). Permutation and bootstrap procedures are proposed to test the existence of a changepoint and the goodness of fit of the model. The performance of the semiparametric changepoint model is compared with that of parametric models in a simulation study. We provide two applications in HIV studies: one is a randomized placebo-controlled study to evaluate the effects of a recombinant glycoprotein 120 vaccine on HIV viral load; the other is a study to compare two types of tubes in handling plasma samples for viral load determination.
Exposure to violence in relation to personality traits, coping abilities, and burnout among caregivers in nursing homes: a case–control study
Authors: Isaksson Ulf , Graneheim Ulla Hällgren , Richter Jörg , Eisemann Martin , Åström Sture 
Published: September 2008

Background: Although violence toward caregivers occurs often and caregivers’ ability to interact and deal with difficult situations is relevant in preventing such violence, few studies have been conducted that focus on caregivers’ characteristics.Aim: This study explores the relationship between perceived exposure to violence and demographical factors, parental rearing, personality traits including coping abilities, defence styles, and burnout among caregivers working in nursing homes.Method: A total of 196 caregivers working in nursing homes were included. They were asked to complete questionnaires concerning demographical factors and exposure to violence. One group of female caregivers reporting no exposure to violence (n = 20) was matched with one group of exposed to violence (n = 20). Both groups were asked to complete questionnaires concerning parental rearing, personality traits, coping abilities, and burnout.Result: Around 68.4% of the caregivers had been exposed to violence during the previous year and 22.4% several times a week. Caregivers 50 years of age or younger and employed in geriatric care for more than 3 years were more frequently exposed to violence. Inter‐group differences were found regarding ‘maternal rejection’ and ‘burnout’. No statistical differences could be found concerning defence styles, coping ability, temperament, or character aspects.Conclusion: Violence toward caregivers occurs frequently and appears to be influenced by several factors. ‘Maternal rejection’ and ‘burnout’ among caregivers exposed to violence might influence the communication between caregivers and residents, rendering more violence. However, personality traits among caregivers do not seem to be associated with exposure to violence.
The 3′ Part of the Dopamine Transporter GeneDAT1/SLC6A3Is Associated With Withdrawal Seizures in Patients With Alcohol Dependence
Authors: Le Strat Yann , Ramoz Nicolas , Pickering Paul , Burger Virginie , Boni Claudette , Aubin Henri‐Jean , Adès Jean , Batel Philippe , Gorwood Philip 
Published: September 2008

Background: Some studies have reported that the A9 allele of the variable nucleotide tandem repeat (VNTR) of the gene which encodes the dopamine transporter (DAT1/SLC6A3) is associated with alcoholism withdrawal symptoms such as alcohol withdrawal seizures (WSs), whereas others did not. We investigated whether polymorphisms within theDAT1gene are associated with WS taking into account some of the confounding factors such as the severity of alcohol dependence.Methods: To further assess the role of this gene in WS, we genotyped the VNTR and 7 single nucleotide polymorphisms (SNPs) encompassing theDAT1gene in a sample of 250 alcohol‐dependent subjects (175 men and 75 women), of whom 24% exhibited WSs, taking into account the severity of alcohol dependence.Results: The VNTR is associated with an increased risk of WSs (odd ratio = 3.5;p = 0.019), even when controlling for confounding factors (p = 0.031). As 2 SNPs, in roughly the same location of the gene (namely rs27072 and rs27048), are also associated with WSs, it is possible that the initial association of the VNTR polymorphism was tagging a specific haplotype of this gene. Indeed, in our sample of alcohol‐dependent patients, 2 haplotypes were associated with a significantly different risk of WSs.Conclusions: The present study adds evidence for a significant role of the 3′ part of the DAT1 gene in WS of alcohol‐dependent patients, not only because it is in accordance with previous work, but also because of larger statistical power (as relying on a sample over sampled with the studied phenotype), as it gives a more precise analysis of different SNPs within theDAT1gene, and as it confirms the association when major potentially confounding factors are taken into account in a logistical regression analysis.
Differential Modulation of Ethanol‐Induced Sedation and Hypnosis by Metabotropic Glutamate Receptor Antagonists in C57BL/6J Mice
Authors: Sharko Amanda C. , Hodge Clyde W. 
Published: September 2008

Background:  Emerging evidence implicates metabotropic glutamate receptor (mGluR) function in the neurobiological effects of ethanol. The recent development of subtype specific mGluR antagonists has made it possible to examine the roles of specific mGluRs in biochemical and behavioral responses to ethanol. The purpose of the present study was to determine if mGluRs modulate the acute sedative‐hypnotic properties of ethanol in mice.Methods:  C57BL/6J mice were tested for locomotor activity (sedation) and duration of loss of the righting reflex (hypnosis) following acute systemic administration of ethanol alone or in combination with the mGluR5‐selective antagonist, 2‐methyl‐6‐(phenylethynyl)pyridine (MPEP), the mGluR1‐selective antagonist, 7‐(hydroxyimino)cyclopropa[b]chromen‐1a‐carboxylate ethyl ester (CPCCOEt), or the mGluR2/3‐selective antagonist (2S)‐2‐Amino‐2‐[(1S,2S)‐2‐carboxycycloprop‐1‐yl]‐3‐(xanth‐9‐yl) propanoic acid (LY341495)).Results:  MPEP (10 and 30 mg/kg) significantly enhanced both the sedative and hypnotic effects of ethanol, while LY341495 (10 and 30 mg/kg) significantly reduced the sedative‐hypnotic effects of ethanol. CPCCOEt had no effect at any concentration tested. Further loss of righting reflex experiments revealed that LY341495 (30 mg/kg) significantly reduced hypnosis induced by the gamma‐aminobutyric acid type A (GABAA) positive modulators, pentobarbital (50 mg/kg) and midazolam (60 mg/kg), and the N‐methyl‐d‐aspartate (NMDA) receptor antagonist, ketamine (150 mg/kg), while MPEP (30 mg/kg) only significantly enhanced the hypnotic properties of ketamine (150 mg/kg).Conclusions:  These findings suggest that specific subtypes of the metabotropic glutamate receptor differentially modulate the sedative‐hypnotic properties of ethanol through separate mechanisms of action, potentially involving GABAA and NMDA receptors.
The Impact of Depressive Symptoms on Alcohol and Cigarette Consumption Following Treatment for Alcohol and Nicotine Dependence
Authors: Kodl Molly M. , Fu Steven S. , Willenbring Mark L. , Gravely Amy , Nelson David B. , Joseph Anne Marie 
Published: September 2008

Background:  Although depression is common among alcohol and tobacco dependent patients, its impact on treatment outcomes is not well established. The purpose of this study was to examine the impact of depressive symptoms on abstinence from tobacco and alcohol after treatment for alcohol dependence and nicotine dependence.Methods:  The Timing of Alcohol and Smoking Cessation Study (TASC) randomized adults receiving intensive alcohol dependence treatment, who were also smokers, to concurrent or delayed smoking cessation treatment. The sample consisted of 462 adults who completed depression and substance use (alcohol and smoking) assessments at treatment entry and 6, 12, and 18 months posttreatment. Longitudinal regression models were used to examine the relationships between depression and subsequent abstinence from alcohol and tobacco after baseline characteristics, including alcohol and smoking histories, were considered.Results:  Depressive symptoms were prospectively related to nonabstinence from alcohol. Depressive symptoms at the previous assessment increased the odds of drinking at the subsequent time point by a factor of 1.67 (95% CI 1.14, 2.43), p < 0.01. Depressive symptoms were not significantly related to subsequent abstinence from cigarettes.Conclusions:  Depression is an important negative predictor of the ability to maintain abstinence from alcohol within the context of intensive alcoholism and smoking treatment. It may be important to include depression‐specific interventions for alcohol and tobacco dependent individuals to facilitate successful drinking treatment outcomes.
Functional Consequences of GABAAReceptor α4 Subunit Deletion on Synaptic and Extrasynaptic Currents in Mouse Dentate Granule Cells
Authors: Liang Jing , Suryanarayanan Asha , Chandra Dev , Homanics Gregg E. , Olsen Richard W. , Spigelman Igor 
Published: September 2008

Background: The α4 subunit‐containing γ‐aminobutyric acid (A) receptors (GABAARs) are highly expressed primarily at extrasynaptic sites in the dentate gyrus (DG) and thalamus and are suspected to contribute to tonic inhibition that is sensitive to potentiation by gaboxadol and ethanol (EtOH). Global α4 subunit knockout (KO) mice exhibit greatly reduced tonic currents and insensitivity to ataxic, sedative and analgesic effects of gaboxadol compared to wild type (WT) controls. The α4 KO mice were also significantly more sensitive to pentylenetetrazol‐induced seizures. However, no differences were observed between α4 KO and WT mice in other baseline behaviors or in the effects of EtOH on these behaviors. To examine possible functional and pharmacological GABAAR alterations, and search for causes for the lack of differences in EtOH behaviors we studied the effects of acute EtOH application on GABAAR‐currents of DG cells from α4 KO and WT control mice complemented by Western blot measurements.Methods: We studied the consequences of α4 subunit deletion using Western immunoblotting and whole cell patch recordings from DG cells in brain slices from α4 KO and WT mice.Results: The magnitude of tonic current and its potentiation by EtOH (10 to 100 mM), alphaxalone (3 μM), and Ro15‐4513 (0.3 μM) was greatly attenuated in α4 KO mice. The kinetics of miniature inhibitory postsynaptic currents (mIPSCs) in α4 KO mice were significantly slower compared to WT mice. Potentiation of mIPSCs by alphaxalone was greatly reduced in α4 KO mice. Ro15‐4513 had no effect on mIPSCs from WT or KO mice. However, mIPSCs of α4 KO mice were significantly more sensitive to EtOH than those from WT mice. The γ2 subunit protein levels were selectively increased in hippocampus and thalamus, but not cortex of α4 KO mice.Conclusions: These data suggest that the global loss of α4 subunits leads to region‐ and cell location‐specific compensatory increases in γ2 subunits, which in turn alter the pharmacological sensitivity of synaptic and extrasynaptic GABAAR‐currents. Our data also suggests that while enhancement of tonic inhibitory currents by gaboxadol, alphaxalone, and EtOH are reduced, and behavioral sensitivity to gaboxadol and alphaxalone may be reduced, compensatory changes in synaptic GABAAR subunits may prevent similar reductions in behavioral sensitivity to EtOH.
Children’s Introduction to Alcohol Use: Sips and Tastes
Authors: Donovan John E. , Molina Brooke S. G. 
Published: September 2008

Background:  Sipping or tasting alcohol is one of the earliest alcohol use behaviors in which young children engage, yet there is relatively little research on this behavior. The present research describes the prevalence of sipping or tasting in a community sample of children, examines the sociodemographic correlates and social contexts of this behavior, and tests whether variables reflecting psychosocial problem‐behavior proneness, that predict adolescent drinking, account for this behavior.Methods:  A sample of 452 children (238 girls) aged 8 or 10 and their families was drawn from Allegheny County PA using targeted‐age directory sampling and random digit dialing procedures. Children were interviewed using computer‐assisted interviews. Logistic regression analyses were used to examine the univariate and multivariate correlates of sipping/tasting.Results:  Thirty‐nine percent of the sample had only sipped or tasted alcohol (35% of 8 year olds and 48% of 10 year olds), while 6% reported having had a drink of alcohol (5% and 7%, respectively). African‐American children were less likely than White children to be sippers. Neither gender nor mother’s education related to sipping status. Most sipping was done in a family context. Sipping/tasting did not generally relate to variables reflecting psychosocial proneness for problem behavior. Instead, the variables most predictive of sipping/tasting were perceived parents’ drinking status, perceived parents’ approval for child sipping, mother’s drinking frequency, and children’s attitudes toward sipping/tasting alcohol.Conclusions:  Young children’s sipping/tasting of alcohol reflects parental modeling of alcohol use and increased opportunities to try alcohol in the home rather than deliberate family socialization of alcohol use, and appears not to be a precocious manifestation of a psychosocial proneness to engage in problem behavior.
Ethanol Increases Fetal Human Neurosphere Size and Alters Adhesion Molecule Gene Expression
Authors: Vangipuram Sharada D. , Grever William E. , Parker Graham C. , Lyman William D. 
Published: September 2008

Background:  Ethanol (ETOH) consumption by pregnant women can result in Fetal Alcohol Spectrum Disorder (FASD). To date, the cellular targets and mechanisms responsible for FASD are not fully characterized. Our aim was to determine if ETOH can affect fetal human brain‐derived neural progenitor cells (NPC).Methods:  Neural progenitor cells were isolated by positive selection from normal second trimester fetal human brains (n = 4) and cultured, for up to 72 hours, in mitogenic media containing 0, 1, 10, or 100 mM ETOH. From 48 to 72 hours in culture, neurospheres generated in these conditions were filmed using time‐lapse video microscopy. At the end of 72 hours, neurosphere diameter and roundness were measured using videographic software. Mitotic phase analysis of cell‐cycle activity and apoptotic cell count were also performed at this time, by flow cytometry using propidium iodide (PI) staining. Real‐time PCR was used to estimate expression of genes associated with cell adhesion pathways.Results:  Neurosphere diameter correlated positively (r = 0.87) with increasing ETOH concentrations. There was no significant difference in cell‐cycle activity and no significant increase in apoptosis with increasing ETOH concentrations. Time‐lapse video microscopy showed that ETOH (100 mM) reduced the time for neurosphere coalescence. Real‐time PCR analysis showed that ETOH significantly altered the expression of genes involved in cell adhesion. There was an increase in the expression of α and β Laminins 1, β Integrins 3 and 5, Secreted phosphoprotein1 and Sarcoglycan ε. No change in the expression of β Actin was observed while the expression of β Integrin 2 was significantly suppressed.Conclusions:  ETOH had no effect on NPC apoptosis but, resulted in more rapid coalescence and increased volume of neurospheres. Additionally, the expression of genes associated with cell adhesion was significantly altered. ETOH induced changes in NPC surface adhesion interactions may underlie aspects of neurodevelopmental abnormalities in FASD.
Effects of Acamprosate on Neuronal Receptors and Ion Channels Expressed inXenopusOocytes
Authors: Reilly Matthew T. , Lobo Ingrid A. , McCracken Lindsay M. , Borghese Cecilia M. , Gong Diane , Horishita Takafumi , Adron Harris R. 
Published: September 2008

Background: Acamprosate (calcium acetylhomotaurinate) has proven to be a moderately effective pharmacological adjunct for the treatment of alcoholism. However, the central nervous system mechanism by which acamprosate reduces alcohol relapse remains unclear. Here we survey a number of metabotropic receptors, ligand‐gated ion channels, and voltage‐gated ion channels, to determine if acamprosate has actions at these sites in the central nervous system.Methods: Xenopusoocytes were injected with cDNAs or cRNAs encoding metabotropic glutamate receptors 1 and 5, M1 muscarinic receptors, glycine α1 homomeric and α1β1 heteromeric receptors, γ‐aminobutyric acid A (GABAAα4β3δ, α4β3γ2s, and α1β2γ2s) receptors, vanilloid receptor 1, and various combinations of α and β subunits of voltage‐gated Na+channels. Electrophysiological responses were measured using two‐electrode voltage clamp parameters after activation with agonists or voltage steps (for the voltage‐gated channels). Acamprosate (0.1 to 100 μM) was pre‐applied for 1 minute, followed by co‐application with agonist. Acamprosate was also applied with ethanol to determine if it altered ethanol responses at some of these receptors and channels.Results: None of the receptors or ion channels responded to acamprosate alone. Acamprosate also failed to alter the activation of receptors or channels by agonists or after activation of voltage‐gated channels. There was no effect of acamprosate on ethanol responses at GABAAα1β2γ2s receptors or Na+channels.Conclusions: Acamprosate does not significantly modulate the function of these receptors and ion channels at clinically relevant concentrations. Thus, the clinical effectiveness of acamprosate in the treatment of alcoholism is not likely due to direct effects on these receptors or ion channels.
Ethanol Increases the Activity of Rat Excitatory Amino Acid Transporter Type 4 Expressed inXenopusOocytes: Role of Protein Kinase C and Phosphatidylinositol 3‐Kinase
Authors: Park Hee‐Yeon , Kim Jin‐Hee , Zuo Zhiyi , Do Sang‐Hwan 
Published: September 2008

Background: Glutamate is the major excitatory neurotransmitter in the central nervous system and is critical for essentially all physiological processes, such as learning, memory, central pain transduction, and control of motor function. Excitatory amino acid transporters (EAATs) play a key role in regulating glutamate neurotransmission by uptake of glutamate into cells. EAAT4 is the major EAAT in the cerebellar Purkinje cells. The authors investigated the effects of ethanol on EAAT4 and the mediatory effects of protein kinase C (PKC) and phosphatidylinositol 3‐kinase (PI3K) in this context.Methods: Excitatory amino acid transporter 4 was expressed inXenopusoocytes by injecting EAAT4 mRNA.l‐aspartate‐induced membrane currents were measured using a two‐electrode voltage clamp. Responses were quantified by integrating current traces and are represented in microCoulombs (μC).Results: Ethanol increased EAAT4 activity in a dose‐dependent manner. At ethanol concentrations of 25, 50, 100, and 200 mM, the responses were significantly higher than untreated control values. Ethanol (25 mM) significantly increased theVmax(1.5 ± 0.1 μC for control vs. 2.0 ± 0.1 μC for ethanol,p < 0.05), but did not affectKm(2.3 ± 0.6 μM for control vs. 1.7 ± 0.7 μM for ethanol,p > 0.05) of EAAT4 forl‐aspartate. Preincubation of oocytes with phorbol‐12‐myristate‐13‐acetate (PMA, a PKC activator) significantly increased EAAT4 activity. However, combinations of PMA and ethanol versus PMA or ethanol alone did not increase responses further. Two PKC inhibitors, chelerythrine and staurosporine did not reduce basal EAAT4 activity but abolished ethanol‐enhanced EAAT4 activity. Pretreatment with wortmannin (a PI3K inhibitor) also abolished ethanol‐enhanced EAAT4 activity.Conclusions: These results demonstrate that acute ethanol exposure increases EAAT4 activity at clinically relevant concentrations and that PKC and PI3K may mediate this. The effects of ethanol on EAAT4 may play a role in the cerebellar dysfunction caused by ethanol intoxication.