bluuebunny/crossref_metadata_2025 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

Asthma 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

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.
Thin‐Trading Effects in Beta: Bias v. Estimation Error
Authors: Sercu Piet , Vandebroek Martina , Vinaimont Tom
Published: September 2008

Abstract:  Two regression coefficients often used in Finance, the Scholes‐Williams (1977) quasi‐multiperiod ‘thin‐trading’ beta and the Hansen‐Hodrick (1980) overlapping‐periods regression coefficient, can both be written as instrumental‐variables estimators. Competitors are Dimson's beta and the Hansen‐Hodrick original OLS beta. We check the performance of all these estimators and the validity of the t‐tests in small and medium samples, in and outside their stated assumptions, and we report their performances in a hedge‐fund style portfolio‐management application. In all experiments as well as in the real‐data estimates, less bias comes at the cost of a higher standard error. Our hedge‐portfolio experiment shows that the safest procedure even is to simply match by size and industry; any estimation just adds noise. There is a clear relation between portfolio variance and the variance of the beta estimator used in market‐neutralizing the portfolio, dwarfing the beneficial effect of bias.
Board Independence and Corporate Governance: Evidence From Director Resignations
Authors: Gupta Manu , Fields L. Paige
Published: September 2008

Abstract:  As is evident from recent changes in NYSE and NASDAQ listing requirements, board independence is assumed to be an important and effective governance mechanism. However, the empirical evidence regarding the value of board independence is mixed. We examine board member resignation announcements and their perceived importance in the context of firms' existing governance structures. We find that outside director resignations appear to send negative signals to market participants. However, this market reaction is less negative when the board is more independent before the departure and when institutional ownership is high, but is more negative for higher levels of officer and director ownership and CEO incentive compensation.
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.
Prevalence, seriousness and reporting of work‐related violence in the Danish elderly care
Authors: Sharipova Muborak , Borg Vilhelm , Hogh Annie
Published: September 2008

A survey study (paper and pencil) among staff of elderly care institutions in 36 Danish municipalities (n = 9949) was conducted in 2005 with a response rate of 78%. The majority of the participants of the study were women (96%). The paper presents the prevalence, perpetrators, seriousness (self‐rated seriousness, injuries, sick leave and type of violence) of work‐related physical violence towards care workers in the Danish elderly care and the frequency of reporting the incidents to the safety organization. The findings show that every fourth caregiver was exposed to violence in 2005. Care personnel working in nursing homes and integrated institutions had the highest prevalence of violence (40%) and were also most often (10%) exposed to violence. Clients were most often (>90% of cases) the perpetrators. The most frequent types of violence were hitting (63%) and scratching/pinching (63%). Being held (32%) or kicked (27%) was also mentioned as frequent types of violence; use of weapon, throwing or hitting with a hard objects were more seldom. Nearly 1/3 of the exposed respondents rated at least one incident as very serious. There were significant associations between self‐rated seriousness and type of violence, injuries and sick leave. The incidents were, in particular when perpetrators were clients, often rated as not serious. Only 22% of the victims of violence reported the violent incidents to the safety organizations. Reports of violent incidents were significantly associated with frequency of exposure, type of violence, physical injury, sick leave and perpetrators. The more frequent and most serious cases were reported most often and cases where the perpetrators were clients were reported less often than when perpetrators were others. It has been suggested that underreporting of violence occurs because it is time consuming, lacks supervisory support, because it won’t make any difference, because it is part of the job, and also because there is a tendency to ‘downplay’ the violence in the elderly care. Suggestions for researches and policy makers are made.
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.
Ethanol, Saccharin, and Quinine: Early Ontogeny of Taste Responsiveness and Intake
Authors: Kozlov Andrey P. , Varlinskaya Elena I. , Spear Norman E.
Published: September 2008

Background:  Rat pups demonstrate high levels of immediate acceptance of ethanol during the first 2 weeks of postnatal life. Given that the taste of ethanol is most likely perceived by infant rats as a combination of sweet and bitter, high intake of ethanol early in ontogeny may be associated with age‐related enhanced responsiveness to the sweet component of ethanol taste, as well as with ontogenetic decreases in sensitivity to its bitter component. Therefore, the present study compared responsiveness to ethanol and solutions with bitter (quinine) and sweet (saccharin) taste in terms of intake and palatability across the first 2 weeks of postnatal life.

Methods:  Characteristic patterns of responsiveness to 10% (v/v) ethanol, 0.1% saccharin, 0.2% quinine, and water in terms of taste reactivity and fluid intake were assessed in rat pups tested on postnatal day (P) 4, 9, or 12 using a new technique of on‐line monitoring of fluid flow through a two‐channel intraoral cannula. Taste reactivity included analysis of ingestive and aversive responses following six intraoral infusions of the test fluids. This taste reactivity probe was followed by the intake test, in which animals were allowed to voluntarily ingest fluids from an intraoral cannula.

Results:  Pups of all ages showed more appetitive responses to saccharin and ethanol than to water or quinine. No age‐related differences were apparent in taste responsiveness to saccharin and ethanol. However, the age‐related pattern of ethanol intake drastically differed from that of saccharin. Intake of saccharin increased from P4 to P9 and decreased substantially by P12, whereas intake of ethanol gradually increased from P4 to P12. Intake of ethanol was significantly lower than intake of saccharin on P9, whereas P12 pups took in more ethanol than saccharin.

Conclusion:  The findings of the present study indicate ontogenetic dissociations between taste reactivity to ethanol and saccharin and intake of these solutions, and suggest that high acceptance of ethanol early in ontogeny may not be associated with its orosensory properties but rather with the pharmacological effects of ethanol.
Impaired Eyeblink Conditioning in Children With Fetal Alcohol Syndrome
Authors: Jacobson Sandra W. , Stanton Mark E. , Molteno Christopher D. , Burden Matthew J. , Fuller Douglas S. , Hoyme H. Eugene , Robinson Luther K. , Khaole Nathaniel , Jacobson Joseph L.
Published: September 2008

Background:  Eyeblink conditioning (EBC) is a Pavlovian paradigm that involves contingent temporal pairing of a conditioned stimulus (e.g., tone) with an unconditioned stimulus (e.g., air puff). Animal studies have shown that binge consumption of alcohol during pregnancy impairs EBC and that this impairment is likely mediated by a loss of neurons in the inferior olive and the cerebellar cortex and deep nuclei, as well as by a reduction in neural plasticity in the cerebellar deep nuclei.

Methods:  Short delay EBC was examined in 98 5‐year‐old children born to women from the Coloured (mixed ancestry) community in Cape Town, South Africa, who were recruited prenatally and are participating in the first prospective longitudinal study of children with fetal alcohol syndrome (FAS). FAS status was assessed at 5 years by expert dysmorphologists. Two sessions of 50 trials each were administered to the children; a third session was administered the following day to those children who did not meet criterion of 40% conditioned responses in session 2.

Results:  Not a single child with FAS met criterion for conditioning as contrasted with 75.0% of the controls. Whereas 86.7% of the controls who were conditioned met criterion by the end of Session 2, a large proportion of the relatively few alcohol‐exposed nonsyndromal children who conditioned did not do so until Session 3. These alcohol effects on EBC persisted after controlling for IQ. Three of 4 microcephalic children who were not exposed to alcohol were successfully conditioned.

Conclusions:  This is the first prospective study to demonstrate impaired EBC in children diagnosed with FAS. Successful EBC in a microcephalic group supports the inference that the EBC deficit is specific to prenatal alcohol exposure and a potential biomarker for diagnosis of exposed children lacking the distinctive FAS dysmorphology. Delay EBC has a high sensitivity for identifying individuals with a diagnosis of probable FAS.
Understanding Consumer Attitudes Toward Food Technologies in Canada
Authors: Henson Spencer , Annou Mamane , Cranfield John , Ryks Joanne
Published: September 2008

This article reports a study on consumer attitudes to 21 food and nonfood technologies in Canada. The study involves repertory grid interviews with 36 food consumers, the data from which are analyzed using generalized Procrustes analysis. Results highlight the role of perceived risk and perceived benefit in determining the acceptability of the technologies, with individual technologies lying along a continuum between the two. For technology as a whole and the 21 specific technologies, the perceived risk and perceived benefit constructs were the dominant determinants of consumer acceptability. While perceptions of perceived risk and perceived benefit differed between individual respondents, there were very limited consistent relations with a range of sociodemographic variables.
Exposure Assessment for Pesticide Intake from Multiple Food Products: A Bayesian Latent‐Variable Approach
Authors: Chatterjee Ayona , Horgan Graham , Theobald Chris
Published: September 2008

Pesticide risk assessment for food products involves combining information from consumption and concentration data sets to estimate a distribution for the pesticide intake in a human population. Using this distribution one can obtain probabilities of individuals exceeding specified levels of pesticide intake. In this article, we present a probabilistic, Bayesian approach to modeling the daily consumptions of the pesticide Iprodione though multiple food products. Modeling data on food consumption and pesticide concentration poses a variety of problems, such as the large proportions of consumptions and concentrations that are recorded as zero, and correlation between the consumptions of different foods. We consider daily food consumption data from the Netherlands National Food Consumption Survey and concentration data collected by the Netherlands Ministry of Agriculture. We develop a multivariate latent‐Gaussian model for the consumption data that allows for correlated intakes between products. For the concentration data, we propose a univariate latent‐t model. We then combine predicted consumptions and concentrations from these models to obtain a distribution for individual daily Iprodione exposure. The latent‐variable models allow for both skewness and large numbers of zeros in the consumption and concentration data. The use of a probabilistic approach is intended to yield more robust estimates of high percentiles of the exposure distribution than an empirical approach. Bayesian inference is used to facilitate the treatment of data with a complex structure.
Combustion Synthesis of Titanium Diboride and Zirconia Composite Powders. Part I
Authors: Hayk Khachatryan , Suren Kharatyan , Jan Puszynski
Published: September 2008

A new method of synthesizing titanium diboride‐zirconium oxide composite powders under the combustion mode was investigated. In situ stabilization of formed or added unstabilized zirconia by magnesia and/or yttria, control of TiB2 particle size, as well as the formation of TiB2‐ZrO2 composites in a wide range of concentrations was investigated. Two different synthesis routes were explored, namely: i) from elemental titanium and, boron powders with addition of zirconia or ii) from zirconium, boron, and titania with or without addition of zirconia. Yttrium oxide and/or magnesium present in boron reactant powder were used for zirconia product stabilization. The effect of initial mixture composition, dilution with stabilized or unstabilized zirconia, and other operating conditions, such as inert gas pressure during the combustion and initial mixture density on combustion front propagation velocity and maximum combustion temperature as well as product microstructure and its phase composition was investigated. Products morphology and compositions were examined using XRD, EDX, and SEM analyses.
Verifying an F1 screen for identification and quantification of rare Bacillus thuringiensis resistance alleles in field populations of the sugarcane borer, Diatraea saccharalis
Authors: Yue Bisong , Huang Fangneng , Leonard B. Rogers , Moore Steven , Parker Roy , Andow David A. , Cook Don , Emfinger Karla , Lee Donna R.
Published: September 2008

Using an F1 screen, 352 feral individuals of the sugarcane borer, Diatraea saccharalis (F.) (Lepidoptera: Crambidae), were examined for the presence of Bacillus thuringiensis (Bt)‐resistance alleles. These insects represented four geographical populations collected in central and northeastern Louisiana, USA, and one field population from the Gulf Coast area of Texas, USA, during 2006. The F1 screen used various crosses between field‐collected insects and a laboratory strain of Cry1Ab‐resistant D. saccharalis, including both reciprocal crosses and group mating. F1 neonates of the crosses were screened for Bt resistance on Bt maize leaf tissue. One field‐collected individual of D. saccharalis was shown to have a Bt‐resistance allele. Based on Bayesian analysis procedures, the Bt‐resistance allele frequency in the five populations of D. saccharalis was 0.0028 with a 95% confidence interval of 0.0003–0.0079. The successful identification of a resistance allele in a field collection of insects suggests that the F1 screening technique could be an effective tool for detecting and monitoring rare Bt‐resistance alleles in field populations of D. saccharalis.
Quantitative assessment of WT1 gene expression after allogeneic stem cell transplantation is a useful tool for monitoring minimal residual disease in acute myeloid leukemia
Authors: Candoni Anna , Tiribelli Mario , Toffoletti Eleonora , Cilloni Daniela , Chiarvesio Alexia , Michelutti Angela , Simeone Erica , Pipan Corrado , Saglio Giuseppe , Fanin Renato
Published: September 2008

Introduction:  WT1 overexpression is described in several oncological diseases including acute myeloid leukemia (AML). Quantification of WT1 in bone marrow samples may be useful as a marker of minimal residual disease (MRD) and may predict the relapse of AML after allogeneic hematopoietic stem cell transplant (HSCT).

Methods and results:  The quantitative expression of WT1 was measured in 38 AML patients (16 males and 22 females) at diagnosis, at the time of transplant and after the allogeneic HSCT (at precise time points). All cases showed high WT1 expression levels at diagnosis with a mean of 4189 (SD 3325) and a median of 3495 (range 454–13923) copies WT1/104Abl. At transplant, 25 patients (66%) were in complete cytologic remission (CcR) and 13 (34%) had refractory or relapsed AML. Bone marrow samples from patients transplanted in CcR showed significantly lower WT1 expression levels during HSCT compared with the samples from patients with a relapsed or refractory AML (P = 0.004). After HSCT, a rapid decline in WT1 expression levels was observed in all patients who attained or maintained a condition of CcR. Six of 38 patients (13%) relapsed after HSCT and all of them had an increase in WT1 expression at/or before relapse. Five of these six patients died of leukemia and one was successfully reinduced with donor lymphocyte infusion (DLI) + chemotherapy with a rapid reduction of WT1 levels. Besides, we found a complete concordance between WT1 expression levels and other disease markers (when available).

Conclusions:  In our experience, there was a complete concordance between WT1 expression levels (measured by quantitative RT‐PCR at precise time points) and status of AML before and after allogeneic HSCT. WT1 may be useful as a non‐specific leukemia marker for monitoring MRD and as a predictor of AML clinical relapse. Based on these results, cases with increase of WT1 levels after HSCT and without graft vs. host disease may be candidate to discontinuation of immunosuppression and/or DLI therapy.
Poor correlations between measurements of bone quality by quantitative ultrasound sonography and dual energy X‐ray absorptiometry in patients with β‐thalassaemia major
Authors: Christoforidis Athanasios , Perifanis Vassilios , Papadopoulou Eleni , Dimitriadou Meropi , Kazantzidou Eirini , Vlachaki Efthimia , Tsatra Ioanna
Published: September 2008

Objectives:  Osteopenia/osteoporosis is a major component of morbidity even in young patients with β‐thalassaemia major. Dual energy X‐ray absorptiometry (DXA) is the reference method for determining bone mineral density (BMD). Quantitative ultrasound sonography (QUS) for bone measurement is a relatively new, inexpensive and radiation‐free method that could serve as an alternative to DXA. Our aim was to assess bone status in thalassaemic patients both with QUS and DXA and, consequently, to investigate the degree of correlation between the two methods.

Methods:  Thirty‐three patients (15 male and 18 female) with β‐thalassaemia major, regularly transfused and systematically iron‐chelated, participated in the study. Mean age was 22.0 ± 8.0 yr (range: 6.5–41.0 yr). All patients were evaluated with QUS at radius and tibia and had DXA scan at lumbar spine vertebrae (L2–L4), whereas 20 patients were additionally assessed with DXA at the left hip (femoral neck, trochanter region and Ward’s triangle).

Results:  Results were expressed as Z‐scores compared with sex‐ and age‐matched population. Lowest mean Z‐scores measured with DXA were recorded at lumbar spine and Ward’s triangle (−1.1 ± 1.13 and −0.95 ± 1.07, respectively). Lowest mean QUS‐derived Z‐scores were measured at radius, statistically significant compared with Z‐scores measured at tibia (−0.6 ± 1.1 vs. 0.4 ± 1.1, P < 0.001). QUS measurements at radius were significantly correlated to QUS measurements at tibia (r = 0.51, P = 0.002). The latter were correlated to BMD measured at lumbar spine (r = 0.516, P = 0.002) and at trochanter region (r = 0.646, P = 0.003). All BMD measurements at hip were significantly correlated to each other. Lumbar spine BMD was correlated to BMD at femoral neck (r = 0.607, P = 0.003) and to BMD at Ward’s triangle (r = 0.438, P = 0.027). Finally, no agreement was recorded between the two methods in identifying thalassaemic patients at risk for osteoporosis (κ = 0.203, P = 0.04).

Conclusion:  Quantitative ultrasound sonography could not serve as an alternate to DXA.
ORIGINAL ARTICLE: Poly‐Immunoglobulin Receptor‐Mediated Transport of IgA into the Male Genital Tract is Important for Clearance of Chlamydia muridarum Infection
Authors: Cunningham Kelly A. , Carey Alison J. , Finnie Jane M. , Bao Shisan , Coon Charmere , Jones Russell , Wijburg Odilia , Strugnell Richard A. , Timms Peter , Beagley Kenneth W.
Published: September 2008

Problem  Chlamydia trachomatis is the most common sexually transmitted infection worldwide. While infection in females requires a Th1 response for clearance, such a response in males may disrupt the immune privileged nature of the male reproductive tract, potentially contributing to infertility.

Method of study  We investigated the role of IgA in protection against an intrapenile Chlamydia muridarum infection of C57BL/6 and pIgR−/− mice.

Results  Here, we show that the poly immunoglobulin receptor is the main pathway for IgA transport into the male reproductive tract. The high levels of IgA seen in prostatic fluid of wild‐type mice correlate with reduction in chlamydial infection both in vitro and in vivo.

Conclusion  These findings indicate that a Chlamydia vaccine that induces neutralizing IgA in the prostate will aid in the protection against infection in males.
ORIGINAL ARTICLE: Comparison of Thrombophilic Gene Mutations Among Patients Experiencing Recurrent Miscarriage and Deep Vein Thrombosis
Authors: Coulam Carolyn B. , Wallis Diane , Weinstein Jordan , DasGupta Dipankar S. , Jeyendran Rajasingam S.
Published: September 2008

Problem  Inherited thrombophilia has been shown to be a risk factor for cardiovascular disease including deep venous thrombosis as well as reproductive disorders including recurrent pregnancy loss. We have previously reported three out of the 10 thrombophilic mutations studied, plasminogen activator inhibitor‐1 (PAI‐1) 4G/5G, factor XIII V34L, and homozygous MTHFR C667T, correlated significantly with recurrent pregnancy loss compared with controls. This study was undertaken to compare the frequencies of nine inherited thrombophilias among women with a history of recurrent pregnancy loss with individuals experiencing deep venous thrombosis and fertile controls.

Method of study  Six hundred thirty‐four participants including 550 women with a history of recurrent pregnancy loss, 43 individuals with deep vein thrombosis and 41 fertile women without a history of recurrent miscarriage. All participants had buccal swabs taken for DNA analyses of nine gene polymorphisms including factor V G1691A, factor V H1299R (R2), factor II Prothrombin G20210A, factor XIII V34L, β‐fibrinogen −455G>A, PAI‐1 4G/5G, human platelet antigen 1 a/b (L33P), MTHFR C677T, MTHFR A1298C. Frequencies of thrombophilic gene polymorphisms were compared among the three populations studied.

Results  Individuals with a history of DVT had a significantly higher frequency of all of the polymorphisms studied compared with women experiencing a history of recurrent pregnancy loss and the fertile controls. The frequencies of mutations for V34L and PAI‐1 4G/5G were significantly increased among women experiencing recurrent pregnancy loss compared with controls. The most prevalent polymorphisms were factor XIII V34L and PAI‐1 4G/4G for both individuals with a history of deep vein thrombosis and recurrent pregnancy loss compared with controls.

Conclusion  Screening for risk factors for inherited thrombophilia with only polymorphisms for factor V von Leiden, factor II prothrombin and MTHFR may be missing the more prevalent identifiers of jeopardy.
Microgravity and the implications for wound healing
Authors: Farahani Ramin Mostofizadeh , DiPietro Luisa A
Published: September 2008

Wound healing is a sophisticated response ubiquitous to various traumatic stimuli leading to an anatomical/functional disruption. The aim of present article was to review the current evidence regarding the effects of microgravity on wound healing dynamics. Modulation of haemostatic phase because of alteration of platelet quantity and function seems probable. Furthermore, production of growth factors that are released from activated platelets and infiltration/function of inflammatory cells seem to be impaired by microgravity. Proliferation of damaged structures is dependent on orchestrated function of various growth factors, for example transforming growth factors, platelet‐derived growth factor and epidermal growth factor, all of which are affected by microgravitational status. Moreover, gravity‐induced alterations of gap junction, neural inputs, and cell populations have been reported. It may be concluded that different cellular and extracellular element involved in the healing response are modified through effect of microgravity which may lead to impairment in healing dynamics.
Mapping Quantitative Trait Loci Associated with Aluminum Toxin Tolerance in NJRIKY Recombinant Inbred Line Population of Soybean (Glycine max)
Authors: Qi Bo , Korir Paul , Zhao Tuanjie , Yu Deyue , Chen Shouyi , Gai Junyi
Published: September 2008

To investigate the genetic mechanism of Al‐tolerance in soybean, a recombinant inbred line population (RIL) with 184 F2:7:11 lines derived from the cross of Kefeng No.1 × Nannong 1138‐2 (Al‐tolerant × Al‐sensitive) were tested in pot experiment with sand culture medium in net room in Nanjing. Four traits, i.e. plant height, number of leaves, shoot dry weight and root dry weight at seedling stage, were evaluated and used to calculate the average membership index (FAi) as the indicator of Al‐tolerance. The composite interval mapping (CIM) under WinQTL Cartographer v. 2.5 detected five QTLs (i.e. qFAi‐1, qFAi‐2, qFAi‐3, qFAi‐4 and qFAi‐5), explaining 5.20%–9.07% of the total phenotypic variation individually. While with the multiple interval mapping (MIM) of the same software, five QTLs (qFAi‐1, qFAi‐5, qFAi‐6, qFAi‐7, and qFAi‐8) explaining 5.7%–24.60% of the total phenotypic variation individually were mapped. Here qFAi‐1 and qFAi‐5 were detected by both CIM and MIM with the locations in a same flanking marker region, GMKF046‐GMKF080 on B1 and satt278‐sat_95 on L, respectively. While qFAi‐2 under CIM and qFAi‐6 under MIM both on D1b2 were located in neighboring regions with their confidence intervals overlapped and might be the same locus. Segregation analysis under major gene plus polygene inheritance model showed that Al‐tolerance was controlled by two major genes (h2mg = 33.05%) plus polygenes (h2pg = 52.73%). Both QTL mapping and segregation analysis confirmed two QTLs responsible for Al‐tolerance with relatively low heritability, and there might be a third QTL, confounded with the polygenes in segregation analysis.