To support the free and open dissemination of research findings and information on alcoholism and alcohol-related problems. To encourage open access to peer-reviewed articles free for all to view.

For full versions of posted research articles readers are encouraged to email requests for "electronic reprints" (text file, PDF files, FAX copies) to the corresponding or lead author, who is highlighted in the posting.


Saturday, January 3, 2009

Alcohol Consumption and the Risk of Nasopharyngeal Carcinoma: A Systematic Review

The evidence concerning the influence of alcohol drinking on the risk of nasopharyngeal carcinoma (NPC) has yielded intriguing findings but has lacked a clear-cut interpretation due to inconsistencies.

To unify this body of evidence, we performed a systematic review. With funding and using a protocol developed by the World Cancer Research Fund (WCRF), 15 bibliographic databases were searched for epidemiological studies that reported a measure of association between alcoholic beverage consumption and NPC. Pooled odds ratios (ORs) for highest-vs.-lowest categories of total alcohol intake was obtained by using an inverse-variance weighted random-effects model. A dose-response trend was examined in models using generalized least square estimation.

The search identified 14 case-control studies from 5 countries. For total alcohol intake, the pooled ORs in a comparison of the highest to the lowest category was 1.33 (95% CI: = 1.09-1.62) in 11 studies.

Data from 6 studies indicated a J-shape dose-response trend, with NPC risk decreasing with up to 15 drinks/wk and increasing with higher intake. Fewer data were available to assess the associations between NPC and intake of beer, wine, and spirits. The potential J-shaped dose-response trend suggests a reduced risk of NPC related to the light alcohol drinking, an observation that warrants further study.

Considered in total, the quantitative summaries of the case-control evidence suggest that heavy alcohol consumption is associated with an increased risk of NPC.

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The gene in alcohol dependence and tobacco smoking serotonin 2A receptor
Drug and Alcohol Dependence Article in Press, 25 December 2008

Alcohol and nicotine abuse and dependence are multifactorial traits that frequently co-occur, where 80–90% of alcohol-dependent individuals who seek treatment smoke. Nicotine is the main compound of tobacco and one of its effects is to increase the release of serotonin. Variations in the serotonergic system may influence some aspects of smoking. The serotonin receptor gene HTR2A has been a candidate gene with some evidence for association with alcohol and nicotine dependencies. The polymorphism HTR2A A-1438G is a functional SNP, and the presence of the A allele increases the transcriptional activity of the gene.

The aim of the present study was to test for possible associations between the A-1438G polymorphism in the serotonin receptor gene (HTR2A) with tobacco smoking combined or not with alcohol dependence.

The polymorphic site was genotyped in three groups of European-derived Brazilians: individuals with co-occurrence of alcohol dependence and tobacco smoking (n = 113), non-alcoholic smokers (n = 120) and non-smoking controls (n = 115).

A higher frequency of the A allele was observed in the two groups of smokers than in the non-smoking controls (x2 = 6.53, p = 0.04). Combining these groups in comparison with the control group, the difference is more significant (x2 = 6.45, p = 0.01).

These results support previous evidence for association between HTR2A polymorphisms and substance use disorders.

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Dense Genomewide Linkage Scan for Alcohol Dependence in African Americans: Significant Linkage on Chromosome 10
Biological Psychiatry Volume 65, Issue 2, 15 January 2009, Pages 111-115

Alcohol dependence (AD) is costly to societies worldwide, moderately heritable, and genetically complex. Risk loci in several populations have been identified with genetic linkage analysis. To date, there has been no published linkage study of AD focused on African Americans (AAs).

We identified a genomewide-significant linkage to markers near 117.2 centiMorgans on chromosome 10q23.3-24.1 (logarithm of odds score 3.32; p = 5.0E-05; empirical genomewide p = .033).

These data add to the growing evidence for locations for AD risk loci and provide the first linkage evidence for such a locus in the AA population

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Strain Specific Synaptic Modifications on Ventral Tegmental Area Dopamine Neurons After Ethanol Exposure
Biological Psychiatry Article in Press, 31 December 2008

Genetic factors and previous alcohol experience influence alcohol consumption in both humans and rodents. Specifically, a prior experience with ethanol increases ethanol intake in both ethanol-preferring C57BL/6 (C57) and ethanol non-preferring DBA/2 (DBA) mice.

Whereas the ventral tegmental area (VTA) importantly regulates dopamine levels and ethanol intake, it is unknown whether ethanol experience differentially alters synaptic properties of VTA dopamine neurons in ethanol-preferring and non-preferring mice.

Ethanol exposure increased γ-aminobutyric acid (GABA) release onto VTA dopamine neurons in DBA mice, as previously observed in C57 mice. However, a single ethanol exposure reduced α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) and N-methyl-D-aspartate receptor (NMDAR) function and LTP in VTA dopamine neurons from DBA but not C57 mice.

A single ethanol exposure selectively reduced glutamate receptor function in VTA dopamine neurons from the ethanol non-preferring DBA strain but enhanced GABA signaling in both C57 and DBA strains.

These results support the notion that VTA dopamine neurons are a central target of ethanol-induced neural plasticity, which could contribute to ethanol consumption. Furthermore, these findings highlight the possible need for specialized therapeutic interventions for alcoholism based on individual intrinsic differences.

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Identification of nitroxyl-induced modifications in human platelet proteins using a novel mass spectrometric detection method
MCP Papers in Press. Published on December 31, 2008

Nitroxyl (HNO) exhibits many important pharmacological effects, including inhibition of platelet aggregation, and the HNO donor, Angeli’s salt (AS), has been proposed as a potential therapeutic agent in the treatment of disease including heart failure and alcoholism. Despite this, little is known about HNO’s mechanism of action, and its effects are rarely linked to specific protein targets of HNO or to the actual chemical changes that proteins undergo when in contact with HNO.

Here, we study the presumed major molecular target of HNO within the body: protein thiols.

Cysteine-containing tryptic peptides were reacted with HNO, generating the sulfinamide modification, and to a lesser extent, disulfide linkages. The sulfinamide modification was subjected to a comprehensive analysis including MS/MS by collision induced dissociation (CID) and electron capture dissociation (ECD), and MS3.

These studies revealed a characteristic neutral loss of HS(O)NH2 (65 Da) that is liberated from the modified cysteine upon CID, and can be monitored by mass spectrometry. Upon storage, partial conversion of the sulfinamide to sulfinic acid was observed, leading to coinciding neutral losses of 65 Da and 66 Da (HS(O)OH). Validation of the method was conducted using a targeted study of nitroxylated glyceraldehyde 3-phosphate dehydrogenase (GAPDH) extracted from AS-treated human platelets.

In these ex vivo experiments, the sample preparation process resulted in complete conversion of sulfinamide to sulfinic acid, making this the sole subject of further ex vivo studies.

A global proteomic analysis to discover platelet proteins that carry nitroxyl-induced modifications and a mass spectrometric HNO dose response analysis of the modified proteins was conducted to gain insight into the specificity and selectivity of this modification.

This identified 10 proteins that are modified dose dependently in response to HNO, providing for the first time a possible mechanistic link between HNO-induced modification and the physiological effects of HNO donors in platelets.

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Press Release - Addressing Substance Abuse and Comorbidities among Military Personnel, Veterans, and Their Families: A Research Agenda

There is growing concern that military personnel returning from Iraq and Afghanistan are experiencing a range of difficulties, including traumatic brain injury (TBI), post traumatic stress disorder (PTSD), depression, anxiety, and tobacco, alcohol and drug abuse. The National Institute on Drug Abuse (NIDA) will convene a two-day meeting January 6-7, 2009 to address the issue of substance abuse and associated mental health problems among military personnel and their families, and will produce recommendations for new research directions and priorities.

The goals of the meeting are:
  • Gain an understanding of the intervention needs of military personnel, veterans, and their families regarding substance abuse and associated difficulties;
  • Discuss current prevention and treatment approaches being used with these populations and their evidence base;
  • Review existing efficacious drug abuse prevention and treatments interventions that may be appropriate for adapting and testing for use with military and veteran populations and their families;
  • Understand how to successfully conduct research in military and veteran settings; and
  • Formulate a research agenda for conducting addictions prevention. . . . . . .

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Friday, January 2, 2009

Validation of a DIS-III-R Rescoring Algorithm for DSM-IV Alcohol-Use Disorders.
J. Stud. Alcohol Drugs 70: 143-146, 2009

The aim of this study was to evaluate the validity of the Diagnostic Interview Schedule, Version III, Revised (DIS-IIIR), rescoring algorithm when compared with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), diagnoses established using the Composite International Diagnostic Interview (CIDI).

The research question is "Does our DIS-III-R rescore accurately reflect DSM-IV diagnoses established independently using the CIDI?"

The rescoring algorithm showed good sensitivity for lifetime alcohol abuse (60.4%) and dependence (80.0%) but poor specificity (0.0%). Current alcohol dependence was diagnosed with high sensitivity (100.0%) and moderate specificity (40.2%). Current alcohol abuse was diagnosed with poor sensitivity (18.2%).

Our algorithm can be used to rescore DIS-III-R data to DSM-IV alcohol-use diagnoses, but one must use caution with respect to the timeframe of alcohol-use disorders and the specific diagnosis.

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Associations of glutamate decarboxylase genes with initial sensitivity and age-at-onset of alcohol dependence in the Irish Affected Sib Pair Study of Alcohol Dependence
Drug and Alcohol Dependence Article in Press, 25 December 2008

The relation of γ-aminobutyric acid (GABA) to alcohol dependence (AD) has been widely studied. Several previous studies suggest that GABA may be involved in alcohol withdrawal, tolerance, and the symptoms that form an AD diagnosis. The genes coding for glutamate decarboxylase (GAD), the rate-limiting enzyme in GABA synthesis, are of potential interest for their association to ethanol consumption and AD. There are two isoforms of GAD, GAD1 and GAD2, which were reported to be associated with AD in males of Han Taiwanese (GAD1) and Russian (GAD2) ancestry.

The present study examined the association of the two GAD isoforms with AD and relevant alcohol-related traits in the Irish Affected Sib Pair Study of Alcohol Dependence

Nine of 29 markers with minor allele frequencies less than 0.01 were removed from standard analysis; the remaining 20 markers were all in Hardy-Weinberg equilibrium. Three markers in the intronic regions of GAD1 were associated with initial sensitivity to alcohol (P = 0.002); the associations remained significant after a FDR based correction for multiple testing. In addition, one marker located 3 kb upstream of GAD1 exhibited association with age at onset of AD (P = 0.0001). Gender specific effects were observed in results of both single marker and haplotype analyses.

We found no evidence for the association of GAD genes with AD but significant association of GAD1 with initial sensitivity and age at onset of AD. Our findings suggest that the underlying pathophysiology regulated by genes like GAD1 may be more directly related to the component processes that form AD than to the clinical disorder.

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Predictors of Initial AA-Related Helping: Findings From Project MATCH.
J Stud Alcohol Drugs. 2009 Jan;70(1):117-125.

The purpose of this article is to identify the factors that predict initial Alcoholics Anonymous (AA)-related helping following treatment admission.

Demographic characteristics, drinking severity, antisocial personality, and purpose in life were not associated with initial AA-related helping.

Increased self-efficacy, faith-based practices, meeting attendance, number of steps worked, having a sponsor, and length of sobriety predicted initial AA-related helping. Alcoholics reported elevated depressive symptoms before initial AA-related helping, lowered depressive symptoms at the start of AA-related helping, and similarly lowered depressive symptoms in the interval following initial AA-related helping.

The profile of prospective helpers in AA is not limited to alcoholics from certain backgrounds or higher functioning in terms of drinking or clinical severity. To increase participation in AA-related helping, and hence outcomes, results suggest strengthening self-efficacy and progress in other AA programmatic components.

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Binge culture curses 'lost generation'

Erik Jensen
January 3, 2009

A GENERATION of Australian teenagers has been lost to binge drinking and will not be reached by the Federal Government's anti-drinking campaign, one of Australia's leading drug educators warns.

The director of Drug and Alcohol Research and Training Australia, Paul Dillon, said the $53 million national binge-drinking strategy was having little effect on a generation of young drinkers habitually misusing alcohol.
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MSPs vote to reduce drink drive limit to 50mg

The Scottish Parliament has voted in favour of cutting the drink-driving limit to the equivalent of one glass of beer or wine. The move came after doctors urged Scotland's political parties to support reducing the limit from 80mg to 50mg per 100ml of blood. The plan was backed during a debate at Holyrood - although the issue is reserved to Westminster.
. . . . .

Binge drinking in women at risk for developing eating disorders
International Journal of Eating Disorders Published Online: 29 Dec 2008

To determine binge drinking rates in college-age women at risk for eating disorders and to examine factors related to binge drinking over time.

Participants reported high rates of binge drinking and frequent binge drinking throughout college. Binge drinking was positively correlated with dietary restraint, coping using substances, coping using denial, and life events.

The study's findings suggest that binge drinking is highly prevalent in women at high risk for developing eating disorders. Results also indicated that binge drinking was related to dieting and maladaptive coping patterns.
Intervention for women with strong weight and shape concerns should also address problematic alcohol use.

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Thursday, January 1, 2009

Alcohol misuse in the Royal Navy
Occupational Medicine 2009 59(1):25-31

Evidence suggests that military personnel consume considerable amounts of alcohol which may have both medical and occupational implications.

To compare alcohol consumption and misuse within the Royal Navy (RN) to that in the civilian population.

The response rate was 70%. The majority (92%) scored as hazardous drinkers on the AUDIT-C, 40% met the criteria for heavy drinking, 27% for very heavy drinking, 48% reported binge drinking at least once a week and 15% were classed as problem drinkers. Heavy drinking was associated with younger age, lower rank and higher scores for both PCL and GHQ. All results were substantially higher than in age-matched civilian samples.

Excessive alcohol consumption, especially binge drinking, is significantly more prevalent in the RN than in the general population. Such high levels of drinking are likely to impact upon occupational efficiency and have both short-term and long-term health effects. We suggest that more needs to be done to deter excessive levels of consumption in order to avoid long-term health consequences.

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Press Release - Study Shows that the Societal, Economic Burden of Insomnia is High
American Academy of Sleep Medicine12/24/2008

Westchester, Ill. — A study in the Jan. 1 issue of the journal Sleep indicates that the indirect costs of untreated insomnia are significantly greater than the direct costs associated with its treatment. The study estimates that the total annual cost of insomnia in the province of Quebec is 6.5 billion Canadian dollars, representing about one percent of the province’s $228.5 billion in gross domestic product for 2002.

Annual indirect costs of insomnia related to lost hours of productivity are estimated to be $5 billion, representing the largest proportion (76 percent) of all insomnia costs. The annual estimate of insomnia-related lost productivity is 27.6 days per year for individuals with insomnia syndrome, and 6.2 days per year for people with insomnia symptoms. The second-highest cost of insomnia is attributed to job absenteeism, with $970.6 million – 14.7 percent of the total economic burden of insomnia - estimated to be lost annually due to insomnia-related absences. Individuals with insomnia syndrome are absent from work an estimated 4.36 days per year because of insomnia.

Lead author of the study, Meagan Daley, PhD, professor of psychology and business, in Quebec City, Canada, stated that costs associated with the use of alcohol as a sleep aid exceed those associated with consultations and the use of medications and over-the-counter products.
. . . . . .

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Optimization of Small Molecule Probes for the Nervous System (R21)
Request for Applications (RFA) Number: RFA-NS-09-003

The aim of this FOA issued by the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the National Institute on Drug Abuse (NIDA) is to facilitate the discovery of new small molecule probes for investigating biological function in the nervous system by providing funding for advanced medicinal chemistry and the biological testing of compounds.

Eligible Investigators will have identified probe candidates via screening of small molecule collections, using in vitro assays of biological activity developed to interrogate these collections, and be able to show that the structural features of these small molecules are related to their biological activity.

Project proposals should nominate small molecule probe candidates from distinct structural series for the further, iterative design and testing of analogues in structure-activity relationship studies, using in vitro assays of biological function adapted to the medium throughput screening requirements of this work.

These studies should have the goal of developing a small molecule probe possessing the attributes (eg: affinity, selectivity, activity) required for its use in future pharmacological studies proposed by the investigator.

Applicants are strongly encouraged to utilize publicly available cheminformatic capabilities for the acquisition of compounds, and semi-custom synthesis of analogues, which is required of these studies.


Wednesday, December 31, 2008

Raising a Glass, Perhaps Labeled

By Cindy Skrzycki
Wednesday, December 31, 2008; Page D01

Consumer advocates are toasting the arrival of Timothy Geithner as President-elect Barack Obama's choice to be the new Treasury secretary by urging him to fix -- along with the economy -- labels on alcoholic drinks.

In a Dec. 11 letter, four groups told Geithner that while they recognize the challenges he faces, nutritional details on the ingredients in libations, especially the alcohol content per serving, have gone unaddressed for too long.
. . . . . .

Monday, December 29, 2008

Does Low to Moderate Alcohol Intake Protect Against Cognitive Decline in Older People?
Journal of the American Geriatrics Society Volume 56 Issue 12, Pages 2217 - 2224

To determine whether low to moderate alcohol intake is protective against cognitive decline in older people.

Alcohol consumption was determined at study baseline. Serial measures of cognitive function over 3.2 years mean follow-up included Mini-Mental-State-Examination (MMSE), speed of information processing (Stroop and Letter-Digit Coding tests), and immediate and delayed memory (Picture-Word Learning test).

Forty-two percent of women and 71% of men were alcohol drinkers. Cognitive performance was better for female drinkers than nondrinkers for all cognitive domains over the 3.2-year follow-up; no significant effects were seen for men (linear mixed model, including adjusting for possible confounders). The rate of cognitive decline was similar for drinkers and nondrinkers for all cognitive domains, except for MMSE, which declined significantly less in female drinkers than nondrinkers (linear mixed model attenuated rate of decline=0.05 MMSE units per annum, P=.001).

Drinking low to moderate amounts of alcohol may delay age-associated cognitive decline in older women (including slowing deterioration in global cognitive function), but these apparent benefits were not clearly seen in older men

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A selective Gβγ-linked intracellular mechanism for modulation of a ligand-gated ion channel by ethanol
PNAS December 23, 2008 vol. 105 no. 51 20523-20528

The current understanding about ethanol effects on the ligand-gated ion channel (LGIC) superfamily has been restricted to identify potential binding sites within transmembrane (TM) domains in the Cys-loop family.
Here, we demonstrate a key role of the TM3–4 intracellular loop and Gβγ signaling for potentiation of glycine receptors (GlyRs) by ethanol. We discovered 2 motifs within the large intracellular loop of the GlyR α1 subunit that are critical for the actions of pharmacological concentrations of ethanol. Significantly, the sites were ethanol-specific because they did not alter the sensitivity to general anesthetics, neurosteroids, or longer n-alcohols. Furthermore, Gβγ scavengers selectively attenuated the ethanol effects on recombinant and native neuronal GlyRs.
These results show a selective mechanism for low-ethanol concentration effects on the GlyR and provide a mechanism on ethanol pharmacology, which may be applicable to other LGIC members.
Moreover, these data provide an opportunity to develop new genetically modified animal models and novel drugs to treat alcohol-related medical concerns.
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Similarities in Drinking Behavior of Twin’s Friends: Moderation of Heritability of Alcohol Use
Behavior Genetics Online First December 28, 2008

Previous research has indicated that friends’ drinking may influence alcohol use in adolescents and young adults.
We explored whether similarities in the drinking behavior of friends of twins influence the genetic architecture of alcohol use in adolescence and young adulthood.
Survey data from The Netherlands Twin Register were available for 1,526 twin pairs aged 16–25 years. We categorized the twin pairs as concordant (both report similar alcohol use in their friends) or discordant for the alcohol use of their friends. Genetic moderator models were tested by carrying out multi-group analyzes in Mplus.
Findings showed a significant moderation effect. Genetic factors were more and common environment less important in the explanation of variation in alcohol use in twins discordant for alcohol use of friends than in twins concordant for alcohol use of friends.
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Three-Year Changes in Adult Risk Drinking Behavior in Relation to the Course of Alcohol-Use Disorders
J. Stud. Alcohol Drugs 69: 866-877, 2008)

This study examines the associations between the course of alcohol-use disorder (AUD) and changes in average daily volume of ethanol intake, frequency of risk drinking, and maximum quantity of drinks consumed per day over a 3-year follow-up interval in a sample of U.S. adults.

There were positive changes in all consumption measures associated with developing an AUD and negative changes associated with remission of an AUD, even among individuals who continued to drink. Increases and decreases associated with onset and offset of dependence exceeded those associated with onset/offset of abuse only, and the decreases associated with full remission from dependence exceeded those associated with partial remission. There were few changes in consumption among individuals whose AUD status did not change.
Interactions of AUD transitions with other factors indicate that development of an AUD is associated with a greater increase in consumption among men, possibly reflecting their greater total body water and lower blood alcohol concentration in response to a given dose of ethanol, and among individuals with high baseline levels of consumption.

Changes in consumption associated with onset and offset of AUD are substantial enough to have important implications for the risk of associated physical and psychological harm.

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Health campaigns to curb binge brinking seen as 'unrealistic', say researchers

By Ben Leach
28 Dec 2008

Health campaigns warning of the dangers of alcohol are being ignored by many young people because they are seen as "unrealistic", a study shows.

Researchers at Birmingham and Bath universities said the Government must stop "demonising" young people in its attempts to promote safe drinking.

The study found that adverts such as this year's Home Office £4m anti-binge-drinking campaign, were viewed as "laughably unrealistic" in the way they portrayed binge drinking.
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Wine and health: state of proofs and research needs
Inflammopharmacology 16 (2008) 265–271

Regular moderate wine consumption is often associated with reduced morbidity and mortality from to a variety of chronic diseases in which inflammation is a root cause. Wine comes in a wide variety of styles that contain quite different ethanol and polyphenol contents.

Controversy remains as to whether the alcohol or polyphenols contribute more to the health benefits of regular moderate wine consumption. The variety of wines available to consumers can be expected to affect health differently in accordance with a particular wine’s total polyphenolic content and spectrum of individual polyphenols.

The overall effect of wine consumption on health depends upon the total amounts consumed, the style and possibly the pattern of consumption. The apparent effect of wine consumption may be modified by the non-wine diet composition of the consumer in that alcohol may appear as the primary component in consumers with high fruit, vegetable and whole grain intakes while phytochemical benefit may become significant in diets where wine is the primary dietary source of phytochemical.

In this review, wine polyphenol mechanisms of action will be reviewed in connection with the mechanism the development of atherosclerotic cardiovascular disease (ASCVD). Selected clinical studies published in 2004–2008 were reviewed.

Experimental requirements for valid clinical studies, translation of in vitro to in vivo application and areas where additional evidence needs to be developed were identified.

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Comparison of 3 Data Collection Methods for Gathering Sensitive and Less Sensitive Information
Ambulatory Pediatrics Volume 8, Issue 4, Pages 255-260

When gathering sensitive information about personal experiences such as child abuse, drug and alcohol use, and intimate partner violence (IPV), it is especially important for both research and clinical purposes to use optimal methods to limit socially desirable responses.

The purpose of this paper is to determine which of the following 3 methods is optimal for gathering data: 1) face-to-face interviews, 2) self-administered paper and pencil questionnaires, or 3) audio computer-assisted self-interviews (ACASI).

In general, ACASI yielded the highest rates for sensitive problems such as social isolation and parental stress, with face-to-face interviews occupying an intermediate position. The differences between ACASI and self-administered paper and pencil questionnaires were significant for many items. The differences between ACASI and face-to-face interviews, however, were modest. There were no significant group differences among the 3 methods in the prevalence rates of the neutral, less sensitive items.

ACASI resulted in greater disclosure of sensitive information than did a paper and pencil approach. No significant differences were observed between the computer-assisted interview and the face-to-face interview, both done in a research setting. The 3 methods appeared similar when gathering less sensitive data.

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Press Release - 'Tis the season to be jolly?

As the party season approaches, a timely reminder of the issues surrounding the binge drinking culture are again highlighted by research into 'young people and alcohol' a team led by Professor Christine Griffin, at the University of Bath. The research, funded by the Economic and Social Research Council (ESRC) suggests several considerations for future policy.

Focusing on the role of marketing practices in shaping young people's attitudes to alcohol consumption, the research included analysis of 216 alcohol adverts, both in print and broadcast. While extreme drinking and determined drunkenness may be perceived as the norm amongst young people, there is some positive news from the research. Evidence suggests that increases in young people's alcohol consumption is levelling off.

Previously, representations of binge drinking as a source of entertainment, coupled with pervasive coverage of drunken celebrities has increased the social acceptance of binge drinking. Advertising representing the 'coolness' of excessive drinking, along with the increasing use of internet based social networking sites that are used to share images of drunken nights out,, also enable the linkage between alcohol and 'having fun'.

Looking at what steps society may need to take to tackle the scourge of binge drinking, Professor Griffin says, "Top of my list would have to be to stop demonizing and making generalisations about young people and their drinking. We also need to listen and incorporate their views and perspectives."
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Branded Consumption and Social Identification: Young People and Alcohol

In most British towns and cities, young people drinking alcohol is now a central part of the night-time economy. For young people themselves, drinking to excess has become a normal part of a ‘good night out’ for many, and they are the target of extensive advertising and marketing campaigns by drinks manufacturers. All this has led to concern about risks to young people’s health and social problems related to their drinking.

This study (the Young People and Alcohol project) aimed to present a systematic and in-depth examination of young people’s own accounts of alcohol consumption and the part it plays in their lives. Interviews, focus groups and study visits to drinking venues were carried out in three different UK locations. The researchers analysed the results to assess the views of young people aged 18–25 on alcohol. The researchers also analysed a selected sample of 216 alcohol adverts aimed at young people to assess the influence of advertising and marketing. Finally, the project considered the implications for future policy and practice

Key Findings
  • Drinking alcohol is socially important in young people’s lives

  • Practices differ across gender, and less so across class, ethnicity and place

  • Advertising reflects the idea of drinking as ‘fun’

  • Overall, government policy needs to change to reflect how young people use alcohol

  • Future applications and research

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Regular binge drinking can cause long-term brain damage - study

Denis Campbell, health correspondent
The Guardian, Monday 29 December 2008

• High alcohol intake can affect mental abilities

• Researchers say findings should be a wake-up call

Just a few sessions of heavy drinking can damage someone's ability to pay attention, remember things and make good judgments, research shows

Binge drinkers are known to be at increased risk of accidents, violence and engaging in unprotected sex. But the study is the first to identify brain damage as a danger of consuming more alcohol than official safe limits.

The research, to be published in the journal Alcohol and Alcoholism, is significant because binge drinking is so widespread in the UK. Twenty-three per cent of men and 15% of women drink more than twice the government's recommended daily limit. For men this means consuming more than eight units a day and for women more than six, according to the Office for National Statistics.
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The Overlap in Predicting Alcohol Outcome for Two Measures of the Level of Response to Alcohol
Alcoholism: Clinical and Experimental Research Published Online: 22 Dec 2008

Two different measures have been used to establish a person's level of response (LR) to alcohol as a risk factor for alcohol use disorders. LR values established by the alcohol challenge protocol and the Self-Report of the Effects of Ethanol (SRE) questionnaire usually correlate at 0.3 to 0.4, up to 0.6. However, it is not clear how this correlation relates to the ability of each measure to predict alcohol outcomes. This paper evaluates that overlap.

Sixty-six Caucasian males (mean age = 22 years) from 2 protocols participated in alcohol challenges with 0.75 ml/kg of ethanol, filled out the SRE, and were followed with a structured interview ∼5 years later. The relationship between the subjective feelings of intoxication at the time of peak breath alcohol levels from the alcohol challenge and the SRE score for a time early in the drinking career were evaluated regarding predicting the drinks per occasion in the 6 months prior to follow-up.

Cross-sectional correlations between alcohol challenge and SRE LR's ranged from −0.25 (p < 0.05) to −0.32 (p = 0.02) for the full sample, and the 2 LR measures correlated with drinking at follow-up (−0.26 and 0.41, respectively). The SRE measure was more robust than the challenge in a regression analysis predicting the outcome in the context of other baseline predictors (e.g., drinking at baseline). As much as 60% of the ability of the more well established (gold standard) alcohol challenge LR to predict outcome was shared with the SRE. The alcohol challenge accounted for as much as 44% of the ability of the SRE to predict outcome.

The SRE-generated LR overlapped considerably with the alcohol challenge LR in the ability to predict future heavier drinking.

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Alcohol and Colorectal Cancer: The Role of Alcohol Dehydrogenase 1C Polymorphism
Alcoholism: Clinical and Experimental Research Published Online: 22 Dec 2008

Chronic alcohol consumption is a risk factor for colorectal cancer. Animal experiments as well as genetic linkage studies in Japanese individuals with inactive acetaldehyde dehydrogenase leading to elevated acetaldehyde concentrations following ethanol ingestion support the hypothesis that acetaldehyde may be responsible for this carcinogenic effect of alcohol. In Caucasians, a polymorphism of alcohol dehydrogenase 1C (ADH1C) exists resulting in different acetaldehyde concentrations following ethanol oxidation.

Genotype ADH1C*1/1 was more frequent in patients with alcohol-associated colorectal neoplasia compared to patients without cancers in the multivariate model controlling for age, gender, and alcohol intake (odds ratio = 1.674, 95% confidence interval = 1.110–2.524, 2-sided p from Wald test = 0.0139). In addition, the joint test of the genetic effect and interaction between ADH1C genotype and alcohol intake (2-sided p = 0.0007) indicated that the difference in ADH1C*1 polymorphisms between controls and colorectal neoplasia is strongly influenced by the alcohol consumption and that only individuals drinking more than 30 g ethanol per day with the genotype ADH1C*1/1 had an increased risk for colorectal tumors.

These data identify ADH1C homozygosity as a genetic risk marker for colorectal tumors in individuals consuming more than 30 g alcohol per day and emphasize the role of acetaldehyde as a carcinogenic agent in alcohol-related colorectal carcinogenesis.

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Long-Term Ethanol Exposure Impairs Neuronal Differentiation of Human Neuroblastoma Cells Involving Neurotrophin-Mediated Intracellular Signaling and in Particular Protein Kinase C
Alcoholism: Clinical and Experimental Research Published Online: 22 Dec 2008

Revealing the molecular changes in chronic ethanol-impaired neuronal differentiation may be of great importance for understanding ethanol-related pathology in embryonic development but also in the adult brain. In this study, both acute and long-term effects of ethanol on neuronal differentiation of human neuroblastoma cells were investigated. We focused on several aspects of brain-derived neurotrophic factor (BDNF) signaling because BDNF activates the extracellular signal-regulated kinase (ERK) cascade, promoting neuronal differentiation including neurite outgrowth.

Chronic ethanol interfered with the development of a neuronal network consisting of cell clusters and neuritic bundles. Furthermore, neuronal and synaptic markers were reduced, indicating impaired neuronal differentiation. BDNF-mediated activation of the ERK cascade was found to be continuously impaired by ethanol. This could not be explained by expressional changes monitored for TrkB, Raf-1, MEK, and ERK. However, BDNF also activates PKC signaling which involves RKIP, which finally leads to ERK activation as well. Therefore, we hypothesized that ethanol impairs this branch of BDNF signaling. Indeed, both PKC and RKIP were significantly down-regulated.

Chronic ethanol exposure impaired neuronal differentiation of neuroblastoma cells and BDNF signaling, particularly the PKC-dependent branch. RKIP, acting as a signaling switch at the merge of the PKC cascade and the Raf/MEK/ERK cascade, was associated with neuronal differentiation and significantly reduced in ethanol treatment. Moreover, PKC expression itself was even more strongly reduced. In contrast, members of the Raf-1/MEK/ERK cascade were less affected and the observed changes were not associated with impaired differentiation.

Thus, reduced RKIP and PKC levels and subsequently reduced positive feedback on ERK activation provide an explanation for the striking effects of long-term ethanol exposure on BDNF signal transduction and neuronal differentiation, respectively.

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Ethanol-Induced Conditioned Taste Avoidance: Reward or Aversion?
Alcoholism: Clinical and Experimental Research Published Online: 22 Dec 2008

Rats avoid intake of a palatable taste cue when paired with all drugs of abuse tested. Evidence suggests that, at least for morphine and cocaine, rats avoid the taste cue because they are anticipating the rewarding properties of the drug. Thus, the suppressive effects of a rewarding sucrose solution and cocaine, but not those of the putatively aversive agent, lithium chloride (LiCl), are exaggerated in drug-sensitive Lewis rats. Likewise, the suppressive effects of sucrose and morphine, but not those of LiCl, are eliminated by bilateral lesions of the gustatory thalamus. Unlike morphine and cocaine, it is less clear whether rewarding or aversive drug properties are responsible for ethanol-induced suppression of intake of a taste cue.

The present set of studies tests whether, like cocaine, ethanol-induced suppression of intake of a taste cue also is greater in the drug-sensitive Lewis rats and whether the suppressive effects of the drug are prevented by bilateral lesions of the taste thalamus.

Ethanol-induced suppression of intake of the saccharin conditioned stimulus (CS) did not differ between the drug-sensitive Lewis rats relative to the less-sensitive Fischer rats. Lesions of the taste thalamus, however, prevented the suppressive effect of the 0.75 g/kg dose of the drug, but had no impact on the suppressive effect of the 1.5 g/kg dose of ethanol.

The results suggest that the suppressive effects of ethanol on CS intake are mediated by both rewarding and aversive consequences, varying as a function of dose.

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Genomewide SNP Screen to Detect Quantitative Trait Loci for Alcohol Preference in the High Alcohol Preferring and Low Alcohol Preferring Mice
Alcoholism: Clinical and Experimental Research Published Online: 22 Dec 2008

The high and low alcohol preferring (HAP1 and LAP1) mouse lines were selectively bred for differences in alcohol intake. The HAP1 and LAP1 mice are essentially noninbred lines that originated from the outbred colony of HS/Ibg mice, a heterogeneous stock developed from intercrossing 8 inbred strains of mice.

QTL analysis detected significant evidence of association on 4 chromosomes: 1, 3, 5, and 9. The region on chromosome 9 was previously found linked in a subset of these F2 animals using a whole genome microsatellite screen.

We have detected strong evidence of association to multiple chromosomal regions in the mouse. Several of these regions include candidate genes previously associated with alcohol dependence in humans or other animal models.

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Sunday, December 28, 2008

Press Release - New power and guidance to tackle alcohol-related crime

23 December 2008

A new power targeting offenders who commit crime under the influence of alcohol was unveiled today.

From next summer, drinking banning orders will allow police and local authorities to stop a person entering certain premises if they have been involved in criminal or disorderly conduct under the influence of alcohol. Breach of a drinking banning order, which can last up to two years, could lead to a fine of up to £2,500. The orders are focused on people whose drinking has been identified as a factor in their irresponsible and disorderly behaviour.

To add to the range of tools and powers to tackle alcohol-related crime and disorder, the government also published new guidance on obtaining designated public place orders and establishing alcohol disorder zones.

. . . . .

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News Release - “A drink or two may be good for baby?”

We are alarmed to learn of many recent news articles reporting the results of a recent epidemiological study entitled “Light drinking in pregnancy, a risk for behavioral problems and cognitive deficits at 3 years of age?” published by Dr. Yvonne Kelly and colleagues in the International Journal of Epidemiology (2008).
A few of the lay press reports include:

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FASDSG assembled a panel of Clinical and Basic Science Investigators who are currently conducting research in the field to discuss the impact of light drinking during pregnancy.

The following statement has been sent to the editors of several lay press reports.
. . . . .
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Alcohol and drugs in fatally and non-fatally injured motor vehicle drivers in northern Sweden
Analysis & PreventionVolume 41, Issue 1, January 2009, Pages 129-136 Accident

Alcohol and drugs are important risk factors for traffic injuries, a major health problm worldwide. This prospective study investigated the epidemiology and the presence of alcohol and drugs in fatally and hospitalized non-fatally injured drivers of motor vehicles in northern Sweden.

During a 2-year study period, blood from fatally and hospitalized non-fatally injured drivers was tested for alcohol and drugs. The study subjects were recruited from well-defined geographical areas with known demographics. Autopsy reports, medical journals, police reports, and toxicological analyses were evaluated.

Of the fatally injured, 38% tested positive for alcohol and of the non-fatally 21% tested positive; 7% and 13%, respectively, tested positive for pharmaceuticals with a warning for impaired driving; 9% and 4%, respectively, tested positive for illicit drugs. The most frequently detected pharmaceuticals were benzodiazepines, opiates, and antidepressants. Tetrahydrocannabiol was the most frequently detected illicit substance. No fatally injured women had illegal blood alcohol concentration.

The relative proportion of positively tested drivers has increased and was higher than in a similar study 14 years earlier.

This finding indicates that alcohol and drugs merit more attention in future traffic safety work

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