Government-Run Liquor Stores The Social Impact of Privatization

A proposal that has circulated in Harrisburg for years is divesting, selling, or privatizing Pennsylvania’s state-owned liquor stores. This discussion is particularly relevant today given the recent drop in Pennsylvania tax collections and long term taxpayer obligations. Geoffrey Segal and Geoffrey Underwood of the Reason Foundation estimate that Pennsylvania could raise $1.7 billion from the sale of its wholesale and retail liquor stores. While such a sale would represent only a onetime cash inflow, Nathan Benefield of the Commonwealth Foundation estimates that Pennsylvania would continue to take in close to $350 million annually in alcohol sales tax.

What gives many pause is the social impact of privatization. Myriad comparisons of privatized markets to state-controlled markets suggest that there are unquestionable advantages to privatization. Of concern are the possible disadvantages. Liquor control proponents maintain that, because the state can directly limit the times and locations at which alcohol can be purchased, and because state stores are not profit driven like private firms, privatization would result in increased alcohol consumption and problems associated with alcohol consumption, such as impaired driving.

A comparison of states with varying degrees of privatization in the retail and wholesale markets for alcohol over the period 1970 through 2006 suggests that privatization is associated neither with increased alcohol consumption nor increased traffic fatalities involving impaired drivers.


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Body mass index and risk of head and neck cancer in a pooled analysis of case–control studies in the International Head and Neck Cancer Epidemiology

Head and neck cancer (HNC) risk is elevated among lean people and reduced among overweight or obese people in some studies; however, it is unknown whether these associations differ for certain subgroups or are influenced by residual confounding from the effects of alcohol and tobacco use or by other sources of biases.

We pooled data from 17 case–control studies including 12 716 cases and the 17 438 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between body mass index (BMI) at different ages and HNC risk, adjusted for age, sex, centre, race, education, tobacco smoking and alcohol consumption.

Adjusted ORs (95% CIs) were elevated for people with BMI at reference (date of diagnosis for cases and date of selection for controls) 18.5 kg/m² (2.13, 1.75–2.58) and reduced for BMI >25.0–30.0 kg/m² (0.52, 0.44–0.60) and BMI 30 kg/m² (0.43, 0.33–0.57), compared with BMI >18.5–25.0 kg/m². These associations did not differ by age, sex, tumour site or control source. Although the increased risk among people with BMI 18.5 kg/m² was not modified by tobacco smoking or alcohol drinking, the inverse association for people with BMI > 25 kg/m² was present only in smokers and drinkers.

In our large pooled analysis, leanness was associated with increased HNC risk regardless of smoking and drinking status, although reverse causality cannot be excluded. The reduced risk among overweight or obese people may indicate body size is a modifier of the risk associated with smoking and drinking. Further clarification may be provided by analyses of prospective cohort and mechanistic studies.

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Request Reprint E-Mail: mia.hashibe@utah.edu

Alcohol-fuelled violence crackdown

Extra cops, bans on troublemakers and designated safe drinking zones will spearhead a Queensland government crackdown on alcohol-fuelled violence.

Premier Anna Bligh has announced three `Drink Safe Precincts' will be set up - in Brisbane's Fortitude Valley, the Gold Coast and Townsville - from December 2010.

Under the $4.2 million plan, police numbers in those precincts will be boosted by 39 per cent and troublemakers will be banned from those areas.

Police numbers will increase during peak times and there will be better supervised taxi zones, Ms Bligh said. > > > >

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The Influence of Adh Function on Ethanol Preference and Tolerance in Adult Drosophila melanogaster

Preference determines behavioral choices such as choosing among food sources and mates. One preference-affecting chemical is ethanol, which guides insects to fermenting fruits or leaves

Here, we show that adult Drosophila melanogaster prefer food containing up to 5% ethanol over food without ethanol and avoid food with high levels (23%) of ethanol. Although female and male flies behaved differently at ethanol-containing food sources, there was no sexual dimorphism in the preference for food containing modest ethanol levels.

We also investigated whether Drosophila preference, sensitivity and tolerance to ethanol was related to the activity of alcohol dehydrogenase (Adh), the primary ethanol-metabolizing enzyme in D. melanogaster.

Impaired Adh function reduced ethanol preference in both D. melanogaster and a related species, D. sechellia.

Adh-impaired flies also displayed reduced aversion to high ethanol concentrations, increased sensitivity to the effects of ethanol on postural control, and negative tolerance/sensitization (i.e., a reduction of the increased resistance to ethanol's effects that normally occurs upon repeated exposure).

These data strongly indicate a linkage between ethanol-induced behavior and ethanol metabolism in adult fruit flies: Adh deficiency resulted in reduced preference to low ethanol concentrations and reduced aversion to high ones, despite recovery from ethanol being strongly impaired.

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Request Reprint E-Mail: henrike.scholz@uni-koeln.de

Alcohol and Violence-Related Injuries Among Emergency Room Patients in an International Perspective

Although alcohol has been found to be more closely associated with violence-related injury than with injury from other causes, few data are available that document heterogeneity in this association across countries or cultures, taking into consideration usual drinking patterns and other sociocultural variables.

Data are reported from 15 countries comprising the Emergency Room Collaborative Alcohol Analysis Project and the WHO Collaborative Study on Alcohol and Injury.

Case-crossover analysis was used to analyze the risk of injury (among current drinkers) from drinking 6 hours prior to the event, based on frequency of usual drinking, for violence-related injuries and separately for non-violence-related injuries.

Relative risk (RR) for a violence-related injury was significantly greater than for injuries from other causes across all countries (pooled RR = 22.22 vs. 4.33), but the magnitude of risk varied considerably (ranging from 4.68 in Spain to 942 in Canada).

Pooled effect size was found to be heterogeneous across countries, and was explained, in part, by the level of detrimental drinking pattern in a country.

Risk for a violence-related injury was not significantly different by age (<30 and 30+ years), reporting five or more drinks on at least one occasion during the last year, or reporting symptoms of alcohol dependence.

A number of methodological concerns suggest that risk of a violence-related injury compared with injuries from other causes may be inflated, and such variables as context of drinking should be taken into consideration in establishing relative risk and alcohol attributable fraction of violence-related injury across countries and cultures.


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ccherpitel@arg.org

Nursing Knowledge About Alcohol Use and Alcohol Problems in Women: A Review of the Literature

In this article, the authors review the nursing empirical literature on alcohol and women’s health published over the past 5 years (2005-2010).

A total of 36 data-based articles authored by nurse investigators met eligibility criteria and were included in this review. Most were single studies by individual nurse investigators; few studies reflected ongoing programs of research related to alcohol and women’s health.

Studies were categorized into four main groups, including (a) determinants of alcohol use and alcohol problems; (b) patterns of use, assessment of alcohol use, and comorbidity; (c) consequences of alcohol use; and (d) the effects of treatment or specific interventions and the contributions of nursing research to the knowledge base of each group are summarized.

The authors then propose a research agenda for nursing that addresses the most pressing issues related to alcohol use and alcohol problems in women.


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ccorte@uic.edu

Early Drinking and Its Association With Adolescents’ Participation in Risky Behaviors

Adolescent alcohol use is a significant public health problem. Drinking before 13 years of age is correlated to the use of illicit drugs and other risky behaviors, such as cigarette smoking.

The purpose of this research was to examine the elationship between adolescents’ early alcohol use and participation in risky behaviors such as smoking marijuana and cigarettes, as well as risky sexual behaviors.

Respondents for this cross-sectional secondary analysis came from a sample of 809 racially diverse adolescents in a community-based study examining familial influences on offspring outcomes.

Early-onset drinking, compared with nondrinking, was significantly related to participating in many of the risky behaviors. Many of the relationships persisted in the multivariable models that adjusted for demographic characteristics.

Early drinking was associated with participation in various risky behaviors (e.g., multiple sexual partners, unprotected intercourse), which may negatively alter an adolescent’s future. Screening should focus on the co-occurrence of such behaviors.


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Request Reprint E-Mail: calvert@umsl.edu

Antisocial Behavioral Syndromes in Adulthood and Alcohol Use Disorder Treatment Over Three-Year Follow-Up: Results From Wave 2 of the National Epidemi

Antisocial personality disorder (ASPD) is associated with poorer treatment outcomes, but more help seeking, for alcohol use disorders (AUDs); however, associations of ASPD with AUD treatment in the general population have not been studied prospectively.

To examine prediction of treatment over 3-year follow-up among adults with AUDs by baseline ASPD and syndromal adult antisocial behavior without conduct disorder before age 15 (AABS).

Face-to-face interviews with 34,653 respondents to the National Epidemiologic Survey on Alcohol and Related Conditions, of whom 3,875 had prevalent AUDs between Waves 1 and 2 and ASPD, AABS, or no antisocial syndrome at Wave 1.

In unadjusted analyses, baseline ASPD predicted AUD treatment but AABS did not. After adjustment for additional need, predisposing, and enabling factors, antisocial syndromes did not predict treatment. Baseline predictors of treatment included more past-year AUD symptoms and past-year nicotine dependence and AUD treatment.

That baseline antisocial syndrome did not predict AUD treatment may reflect strong associations of antisociality with previously identified predictors of help seeking.


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goldster@mail.nih.gov

Evidence-based practices in addiction treatment: Review and recommendations for public policy

The movement in recent years towards evidence-based practice (EBP) in health care systems and policy has permeated the substance abuse treatment system, leading to a growing number of federal and statewide initiatives to mandate EBP implementation.

Nevertheless, due to a lack of consensus in the addiction field regarding procedures or criteria to identify EBPs, the optimal processes for disseminating empirically based interventions into real-world clinical settings have not been identified.

Although working lists of interventions considered to be evidence-based have been developed by a number of constituencies advocating EBP dissemination in addiction treatment settings, the use of EBP lists to form policy-driven mandates has been controversial.

This article examines the concept of EBP, critically reviews criteria used to evaluate the evidence basis of interventions, and highlights the manner in which such criteria have been applied in the addictions field.

Controversies regarding EBP implementation policies and practices in addiction treatment are described, and suggestions are made to shift the focus of dissemination efforts from manualized psychosocial interventions to specific skill sets that are broadly applicable and easily learned by clinicians.

Organizational and workforce barriers to EBP implementation are delineated, with corresponding recommendations to facilitate successful dissemination of evidence-based skills.



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Request Reprint E-Mail: sglasner@ucla.edu

Survival analysis of head and neck squamous cell carcinoma: Influence of smoking and drinking

Head and neck squamous cell carcinomas (HNSCCs) are associated with tobacco and alcohol; however, the prognostic relevance of these substances is unclear.

Univariate and multivariate survival analyses were performed for patients with (n = 1829) and without (n = 183) substance use.

HNSCC-specific survival (death due to primary-HNSCC or recurrent HNSCC) and HNSCC/second primary tumor–specific survival (death due to primary-HNSCC or recurrent HNSCC or second primary tumor) were not significantly different for patients who smoked and drank alcohol (hazard ratio [HR], 1.26; 95% confidence interval [CI], 0.86–1.85) and those who did not (HR, 1.34; 95% CI, 0.96–1.88). Overall survival was significantly affected; HR for patients who smoked and drank alcohol was 1.50 (95% CI, 1.16–1.93).

Although tobacco and alcohol use are the main risk factors for development of HNSCC, disease outcome was comparable in patients who did or did not use these substances. Tobacco and alcohol use affected overall survival, which emphasizes the importance of substance use cessation.

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Request Reprint E-Mail: F.Farshadpour@umcutrecht.nl

Deficiency of insulin-like growth factor 1 reduces vulnerability to chronic alcohol intake-induced cardiomyocyte mechanical dysfunction: Role of AMPK

Circulating insulin-like growth factor I (IGF-1) levels are closely associated with cardiac performance although the role of IGF-1 in alcoholic cardiac dysfunction is unknown.

This study was designed to evaluate the impact of severe liver IGF-1 deficiency (LID) on chronic alcohol-induced cardiomyocyte contractile and intracellular Ca²⁺²⁺ properties were evaluated including peak shortening (PS), maximal velocity of shortening/relengthening (± dL/dt), time-to-relengthening (TR₉₀), change in fura-fluorescence intensity (ΔFFI) and intracellular Ca²⁺ decay.

Levels of apoptotic regulators Caspase-3, Bcl-2 and JNK, the ethanol metabolizing enzyme mitochondrial aldehyde dehydrogenase (ALDH2), as well as the cellular fuel gauge AMPK were evaluated.

Chronic alcohol intake enlarged myocyte cross-sectional area, reduced PS, ± dL/dt and ΔFFI as well as prolonged TR₉₀ and intracellular Ca²⁺ decay, the effect of which was greatly attenuated by IGF-1 deficiency.

The beneficial effect of LID against alcoholic cardiac mechanical defect was ablated by IGF-1 replenishment. Alcohol intake increased Caspase-3 activity/expression while downregulated Bcl-2, ALDH2 and pAMPK without affecting JNK and AMPK. IGF-1 deficiency attenuated alcoholism-induced responses in all these proteins with the exception of Bcl-2.

In addition, the AMPK agonist 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) abrogated short-term ethanol incubation-elicited cardiac mechanical dysfunction.

Taken together, these data suggested that IGF-1 deficiency may reduce the sensitivity to ethanol-induced myocardial mechanical dysfunction.

Our data further depicted a likely role of Caspase-3, ALDH2 and AMPK activation in IGF-1 deficiency-induced “desensitization” of alcoholic cardiomyopathy.


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Request Reprint E-Mail: jren@uwyo.edu

Editorial - Let’s broaden debate on alcohol problems

It is unfortunate that in the last few months, dozens of Kenyans have died after consuming illicit, contaminated liquor.

Predictably the Provincial Administration has responded by mounting frequent raids. However, the huge number of brewers and patrons still being netted indicates that neither the threat of death nor arrests are enough to check the production and consumption of these products.

The reported deaths, loss of sight and other medical problems caused by the suspect drinks coincided with the passing of the Alcoholic Drinks Control Bill 2009 by Parliament.

This coincidence may have robbed the Bill of its wider significance, with public debate being mainly confined to views about the killer brews.

However, the Bill covers all types of alcoholic drinks including those that are legal. It is far broader than traditional or illicit brews. > > > >

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Zimbabwe: Alcohol Consumption Increases Dramatically

Zimbabwe is likely to join the top 10 African drinking nations after the country's leading beer producer - Delta Beverages recorded a 50 percent jump in beer sales in the current reporting period.

According to the 2004 Global Status Report on Alcohol, Zimbabwe was ranked number 12 in Africa with per capita consumption of alcohol pegged at 5,08 litres per year compared to an average 4 litres in other African countries. Uganda still leads in the consumption of alcohol in Africa and the world with a per capita consumption of alcohol of 19,47 litres per year according to a 2005 World Health Organisation report. > > > >

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ER-targeted Bcl-2 and inhibition of ER-associated caspase-12 rescue cultured immortalized cells from ethanol toxicity

Alcohol abuse, known for promoting apoptosis in the liver and nervous system, is a major public health concern.

Despite significant morbidity and mortality resulting from ethanol consumption, the precise cellular mechanism of its toxicity remains unknown. Previous work has shown that wild-type Bcl-2 is protective against ethanol.

The present study investigated whether protection from ethanol toxicity involves mitochondrial Bcl-2 or endoplasmic reticulum (ER) Bcl-2, and whether mitochondria-associated or ER-associated caspases are involved in ethanol toxicity.

Chinese hamster ovary (CHO695) cells were transiently transfected with cDNA constructs encoding wild-type Bcl-2, mitochondria-targeted Bcl-2, or ER-targeted Bcl-2.

MTT assay was used to measure cell viability in response to ethanol. Ethanol treatments of 1 and 2.5M reduced cell viability at 5, 10, and 24h. Wild-type Bcl-2, localized both to mitochondria and ER, provided significant rescue for CHO695 cells treated with 1M ethanol for 24h, but did not rescue toxicity at 2.5M. ER-targeted Bcl-2, however, provided significant and robust rescue following 24h of 1 and 2.5M ethanol.

Mitochondria-targeted Bcl-2 offered no protection at any ethanol concentration and generally reduced cell viability.

To follow up these experiments, we used a peptide inhibitor approach to investigate which caspases were responsible for ethanol-induced apoptosis.

Caspase-9 and caspase-12 are known to be downstream of mitochondria and the ER, respectively. CHO695 cells were treated with a pan-caspase inhibitor, a caspase-9 or caspase-12 inhibitor along with 1.5M ethanol, followed by MTT cell viability assay.

Treatment with the pan-caspase inhibitor provided significant rescue from ethanol, whereas inhibition of caspase-9 did not. Inhibition of ER-associated caspase-12, however, conferred significant protection from ethanol toxicity, similar to the pan inhibitor.

These findings are consistent with our transfection data and, taken together, suggest a significant role for the ER in ethanol toxicity.


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Request Reprint E-Mail: bmoore@kzoo.edu

An improved method for rapidly quantifying fatty acid ethyl esters in meconium suitable for prenatal alcohol screening

Fatty acid ethyl esters (FAEEs) are nonoxidative metabolites of ethanol, and elevated levels of FAEE in meconium are a useful biomarker for heavy prenatal alcohol exposure.

FAEE in meconium has been recommended as useful and cost-effective for universal screening for prenatal alcohol exposure. To support an efficient universal screening program, an analytical method to detect and quantify FAEE in meconium needs to be accurate, inexpensive, and rapid.

The purpose of this study was to develop an analytical method that would satisfy these criteria and to validate this method using established laboratory guidelines.

A method was developed and validated to detect and quantify four FAEEs (ethyl palmitate, ethyl linoleate, ethyl oleate, and ethyl stearate) from 0.5g of meconium using d5-ethyl esters as internal standards. The sample undergoes liquid–liquid extraction with heptane:acetone, the heptane layer is isolated and evaporated, and then, the resulting residue undergoes headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry.

The detection limits of the four FAEEs ranged from 0.020 to 0.042nmol/g and are 6- to 25-fold lower than the individual FAEE threshold concentrations (0.5nmol/g).

This method also has good precision with the coefficient of variation ranging from 2.6 to 19.4% for concentrations of individual FAEE between 0.5 and 2.62nmol/g meconium (n=4).

Calculated concentrations of FAEE that underwent extraction from meconium were 100–101% of the expected concentration, demonstrating the accuracy of the method. The peak shape and retention time of each FAEE were unaffected by the presence of the matrix, and there is no carryover at clinically relevant concentrations.

This method was also able to produce clean chromatograms from meconium samples that could not be quantified using a previous method because of high chromatographic background.

This method provides an optimal approach to detecting and quantifying FAEE in meconium that could be used in a universal screening program for prenatal alcohol exposure.


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Request Reprint E-Mail: gkoren@sickkids.ca

Subtle decreases in DNA methylation and gene expression at the mouse Igf2 locus following prenatal alcohol exposure: effects of a methyl-supplemented

C57BL/6J (B6) mice are susceptible to in utero growth retardation and a number of morphological malformations following prenatal alcohol exposure, while DBA/2J (D2) mice are relatively resistant. We have previously shown that genomic imprinting may play a role in differential sensitivity between B6 and D2. The best-characterized mechanism mediating genomic imprinting is differential DNA methylation.

In the present study we examined DNA methylation and gene expression, in both embryonic and placental tissue, at the mouse Igf2 locus following in utero ethanol exposure.

We also examined the effects of a methyl-supplemented diet on methylation and ethanol teratogenesis.

In embryos from susceptible B6 mice, we found small decreases in DNA methylation at four CpG sites in one of the differentially methylated regions of the Igf2 locus; only one of the four sites showed a statistically significant decrease.

We observed no significant decreases in methylation in placentae. All Igf2 transcripts showed approximately 1.5-fold decreases following intrauterine alcohol exposure.

Placing dams on a methyl-supplemented diet before pregnancy and throughout gestation brought methylation back up to control levels. Methyl supplementation also resulted in lower prenatal mortality, greater prenatal growth, and decreased digit malformations; it dramatically reduced vertebral malformations.

Thus, although prenatal alcohol had only small effects on DNA methylation at the Igf2 locus, placing dams on a methyl-supplemented diet partially ameliorated ethanol teratogenesis.


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Request Reprint E-Mail: cdowning@pharmacy.isu.edu

Prevalence of the metabolic syndrome in men and women with alcohol dependence: results from a cross-sectional study during behavioural treatment in a

Prevalence of metabolic syndrome (MetS) in men and women who use alcohol has been inconsistent in the literature.

The aim of this study is to compare the prevalence of MetS in patients with a diagnosis of alcohol dependence who are currently abstinent in a controlled environment, and in control subjects followed in primary care from a similar region in Northern Germany.

Cross-sectional study.

In-patient cognitive behavioural therapy.

One hundred and ninety-seven men and women with alcohol dependence during behavioural treatment in a controlled environment were compared to 1158 subjects from primary care from a similar region in northern Germany.

We used the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHBLI) criteria to determine the rate of MetS and each single criterion of MetS in both groups.

The prevalence of MetS was almost twice as high in men and women with alcohol dependence compared to control subjects (30.6% versus 17.0%). With respect to the single criteria, elevations were found for fasting glucose and blood pressure in both genders and for triglycerides in women only. High density lipoprotein (HDL)-cholesterol was higher in men and women with alcohol dependence.

Our results demonstrate an increased rate of MetS, increased blood pressure and dysregulation of glucose and lipid metabolism in alcohol-dependent patients. Whether high HDL-cholesterol has cardioprotective effects in this context remain doubtful.

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Kahl.Kai@mh-hannover.de

The Impact of Alcohol Marketing on Youth Drinking Behaviour: A Two-stage Cohort Study

To examine whether awareness of, and involvement with alcohol marketing at age 13 is predictive of initiation of drinking, frequency of drinking and units of alcohol consumed at age 15.

A two-stage cohort study, involving a questionnaire survey, combining interview and self-completion, was administered in respondents’ homes. Respondents were drawn from secondary schools in three adjoining local authority areas in the West of Scotland, UK. From a baseline sample of 920 teenagers (aged 12–14, mean age 13), in 2006, a cohort of 552 was followed up 2 years later (aged 14–16, mean age 15). Data were gathered on multiple forms of alcohol marketing and measures of drinking initiation, frequency and consumption.

At follow-up, logistic regression demonstrated that, after controlling for confounding variables, involvement with alcohol marketing at baseline was predictive of both uptake of drinking and increased frequency of drinking. Awareness of marketing at baseline was also associated with an increased frequency of drinking at follow-up.

Our findings demonstrate an association between involvement with, and awareness of, alcohol marketing and drinking uptake or increased drinking frequency, and we consider whether the current regulatory environment affords youth sufficient protection from alcohol marketing.

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Request Reprint E-Mail: r.gordon@open.ac.uk

Changes in Alcohol Availability, Price and Alcohol-related Problems and the Collectivity of Drinking Cultures: What Happened in Southern and Northern

The aims of this study were to study whether alcohol-related self-reported problems follow the same pattern of changes in alcohol consumption in southern Sweden, assumed to be affected by a decrease in Danish spirits tax and by an increase in Swedish travellers’ import quotas, and to study whether the results obtained for southern and northern Sweden follow the predictions of Skog's theory of collectivity of drinking cultures.

Analysis was carried out on a sample from the Swedish general population from southern and northern Sweden separately. Two indices such as impaired self-control/dependent behaviour and extrinsic problems for alcohol-related problems were computed and analysed in terms of sex, age, income and alcohol consumption level.

Although there were no huge changes in the number of persons reporting alcohol-related problems, the general trend in data for various subpopulations was a decrease in the southern site and an increase in the northern site. In the northern site, the increase in alcohol consumption among men also showed an increase in alcohol-related problems. However, various population subgroups changed in different directions and did not move in concert over the population distribution.

Confirmed that alcohol-related problems, according to the two indices used, followed a similar pattern to alcohol consumption, but less divergent. A version of Skog's theory applied on alcohol-related problems could not confirm that alcohol-related problems did not change collectively within the population.


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Request Reprint E-Mail: nina-katri.gustafsson@sorad.su.se

Signatures of founder effects, admixture, and selection in the Ashkenazi Jewish population

The Ashkenazi Jewish (AJ) population has long been viewed as a genetic isolate, yet it is still unclear how population bottlenecks, admixture, or positive selection contribute to its genetic structure.

Here we analyzed a large AJ cohort and found higher linkage disequilibrium (LD) and identity-by-descent relative to Europeans, as expected for an isolate.

However, paradoxically we also found higher genetic diversity, a sign of an older or more admixed population but not of a long-term isolate.

Recent reports have reaffirmed that the AJ population has a common Middle Eastern origin with other Jewish Diaspora populations, but also suggest that the AJ population, compared with other Jews, has had the most European admixture.

Our analysis indeed revealed higher European admixture than predicted from previous Y-chromosome analyses.

Moreover, we also show that admixture directly correlates with high LD, suggesting that admixture has increased both genetic diversity and LD in the AJ population.

Additionally, we applied extended haplotype tests to determine whether positive selection can account for the level of AJ-prevalent diseases.

We identified genomic regions under selection that account for lactose and alcohol tolerance, and although we found evidence for positive selection at some AJ-prevalent disease loci, the higher incidence of the majority of these diseases is likely the result of genetic drift following a bottleneck.

Thus, the AJ population shows evidence of past founding events; however, admixture and selection have also strongly influenced its current genetic makeup.


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BK channels play a counter-adaptive role in drug tolerance and dependence

Disturbance of neural activity by sedative drugs has been proposed to trigger a homeostatic response that resists unfavorable changes in net cellular excitability, leading to tolerance and dependence. The Drosophila slo gene encodes a BK-type Ca²⁺-activated K⁺ channel implicated in functional tolerance to alcohol and volatile anesthetics.

We hypothesized that increased expression of BK channels induced by these drugs constitutes the homeostatic adaptation conferring resistance to sedative drugs.

In contrast to the dogmatic view that BK channels act as neural depressants, we show that drug-induced slo expression enhances excitability by reducing the neuronal refractory period.

Although this neuroadaptation directly counters some effects of anesthetics, it also causes long-lasting enhancement of seizure susceptibility, a common symptom of drug withdrawal.

These data provide a possible mechanism for the long-standing counter-adaptive theory for drug tolerance in which homeostatic adaptations triggered by drug exposure to produce drug tolerance become counter-adaptive after drug clearance and result in symptoms of dependence


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Request Reprint E-Mail: nigela@mail.utexas.edu.

Increased Risk of Esophageal Varices, Liver Cancer, and Death in Patients With Alcoholic Liver Disease

During the last decades, a multitude of different treatments for chronic liver disease have been introduced. New surveillance programs have been established to detect esophageal varices and liver cancer.

The aims of our study were to assess whether the prognosis for patients hospitalized with liver diseases between 1969 and 2006 had improved and to study the differences in mortality and complications between patients with alcoholic liver disease and nonalcoholic liver diseases.

We used the Swedish Hospital Discharge Register and Cause of Death Register at the National Board of Health and Welfare in Sweden between 1969 and 2006 to identify and follow-up a cohort of patients with liver disease according to the International Classification of Diseases-8, -9, and -10.

There were 36,462 patients hospitalized with alcoholic and 95,842 with nonalcoholic liver diseases. The main finding was that patients hospitalized with alcoholic liver disease had an increased mortality risk, compared to patient with nonalcoholic liver disease, 1.89 (1.85 to 1.92). In addition, the patients with alcoholic liver disease had an increased risk for esophageal varices and liver cancer. There was a reduced risk for hospitalization with esophageal varices for patients with nonalcoholic liver disease up to 1998.

We found that the prognosis for patients hospitalized with chronic liver diseases had not improved. Patients with alcoholic liver disease have an increased risk of complications, which suggest that the disease is more aggressive and are in need of closer follow-up than other chronic liver diseases.

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Request Reprint E-Mail: knut.stokkeland@gotland.se

Study of Metamemory in Patients With Chronic Alcoholism Using a Feeling-of-Knowing Episodic Memory Task

Alcoholism affects various cognitive processes, including components of memory. Metamemory, though of particular interest for patient treatment, has not yet been extensively investigated.

A feeling-of-knowing (FOK) measure of metamemory was administered to 28 alcoholic patients and 28 healthy controls during an episodic memory task including the learning of 20 pairs of items, followed by a 20-minute delayed recall and a recognition task. Prior to recognition, participants rated their ability to recognize each nonrecalled word among 4 items. This episodic FOK measure served to compare predictions of future recognition performance and actual recognition performance. Furthermore, a subjective measure of metamemory, the Metamemory In Adulthood (MIA) questionnaire, was completed by patients and controls. This assessment of alcoholic patients’ metamemory profile was accompanied by an evaluation of episodic memory and executive functioning.

FOK results revealed deficits in accuracy, with the alcoholic patients providing overestimations. There were also links between FOK inaccuracy, executive decline, and episodic memory impairment in patients. MIA results showed that although alcoholics did display memory difficulties, they did not differ from controls on questions about memory capacity.

Chronic alcoholism affects both episodic memory and metamemory for novel information. Patients were relatively unaware of their memory deficits and believed that their memory was as good as that of the healthy controls. The monitoring measure (FOK) and the subjective measure of metamemory (MIA) showed that patients with chronic alcoholism overestimated their memory capacities. Episodic memory deficit and executive dysfunction would explain metamemory decline in this clinical population.

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Request Reprint E-Mail: helene.beaunieux@unicaen.fr

Reduced Expression of Circadian Clock Genes in Male Alcoholic Patients

There are clear interactions between chronic alcohol consumption and circadian rhythmicity that is regulated by several circadian clock genes. The altered expressions of these genes have been mainly described in animals. The mammalian master clock in the suprachiasmatic nuclei orchestrates the biological rhythms in peripheral tissues. As peripheral blood mononuclear cells (PBMCs) are the most accessible tissue clinically, we assessed the mRNA levels of these genes in patients with alcohol dependence (AD) undergoing alcohol-withdrawal (AW) treatment.

Twenty-two male patients fulfilled the DSM-IV diagnostic criteria of AD, and 12 comparison healthy control subjects were recruited. The patients with AD were further divided by the presence of delirium tremens (DTs), the most severe form of AW syndrome, into DT group and non-DT group. All the participants received blood withdrawal at 9 am, while the patients with AD had blood collection twice: on the next morning of admission (baseline) and on the seventh day. PBMCs were isolated from whole blood, and the mRNA expression profiles of hClock1, hBmal1, hPer1, hPer2, hCry1, and hCry2 were determined by quantitative real-time PCR.

The baseline mRNA levels of the target circadian clock genes were markedly lower in patients with AD than in control subjects. After 1 week of alcohol detoxification, there were very limited restorations of discrete circadian gene expressions. DT group did not differ in the expression patterns of circadian clock genes from non-DT group.

This is the first study demonstrating the overall lowering of circadian clock genes among patients with AD. The expression pattern is comparable between patients with and without DTs. Although preliminary with data at only one single time point, the observation of strikingly reduced mRNA levels supports the association between circadian clock gene dysregulation and chronic alcohol intake.

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Request Reprint E-Mail: cmbsycl@tmu.edu.tw

Effect of 24-h alcohol licensing on emergency departments: the South Yorkshire experience

The alcohol Licensing Act (2003) was introduced to England and Wales on 23 November 2005. A single-centre study in 2007 from St Thomas's Hospital concluded that their alcohol-related attendances had significantly increased after the implementation of this new Act.

This study aimed to assess whether this finding was reproduced in other hospitals.

A retrospective cohort study, reviewing anonymised routine data from four emergency departments (ED) in South Yorkshire, was undertaken. The study population was adults (over the age of 18 years) attending the ED with injuries or illnesses directly related to alcohol in the 12 months before and after the implementation of the Licensing Act (2003). The primary outcome was the number of these alcohol-related attendances. Secondary outcomes assessed whether there was any change in the timing of these presentations.

Alcohol-related attendances, as detected by clinical coding, increased from 0.6% to 0.7% as a proportion of all attendances.

Trends in alcohol-related attendances after the implementation of the Licensing Act (2003) varied across South Yorkshire hospitals and probably reflect local factors rather than any consistent impact from the Act.

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National Survey of Drinking and Driving attitudes and Behaviors

Twenty percent of the public 16 and older had in the past year driven a motor vehicle within two hours of drinking alcohol. About two-thirds of these, or 13% of the total population 16 and older had done so in the past 30 days.

The survey produced an estimate of 85.5 million past-month drinking-driving trips, up from 73.7 million trips in 2004 and reversing a declining trend in such trips since 1995. More than three-fourths (78%) of the trips were made by males.

Those who reported driving within two hours of drinking in the past year tended to be more frequent drinkers than did other drivers who drink but do not drive afterwards.

More than one in four (28%) drinking drivers usually consumed alcoholic beverages 3 or more days a week, compared to 10% of drivers who drink but do not drink and drive.

While few 16- to 20-year-olds reported drinking and driving, those that did averaged 5.7 drinks per sitting during the times they drink alcohol (inclusive of all drinking occasions, not just drinking and driving). For 21- to 24-year-old drinking drivers, their average alcohol intake was 4.2 drinks per sitting. The average number of drinks dropped sharply again for 25- to 34-year-old drinking drivers (3.0), then declined more slowly across ensuing age groups.

The survey also produced an estimate of 17.2 million drivers (or 8% of all drivers) having driven one or more times in the preceding 12 months when they thought they were over the legal limit for alcohol and driving. These were mostly males, by a more than two-to-one ratio.

Several questions in the survey were used to classify a segment of the sample as problem drinkers. Problem drinkers composed 22% of past-month drinking drivers, but 36% (or 31 million) of past-month drinking and driving trips. Drinking drivers who were problem drinkers were almost twice as likely as other drinker-drivers to report driving at least once in the past year when they thought they were over the legal limit for alcohol and driving (56% compared to 24%).


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Personality-Targeted Interventions Delay Uptake of Drinking and Decrease Risk of Alcohol-Related Problems When Delivered by Teachers

This trial examined the efficacy of teacher-delivered personality-targeted interventions for alcohol-misuse over a 6-month period.

This randomized controlled trial randomly allocated participating schools to intervention (n = 11) or control (n = 7) conditions. A total of 2,506 (mean age, 13.7 years) were assessed for elevated levels of personality risk factors for substance misuse: sensation-seeking, impulsivity, anxiety sensitivity, and hopelessness. Six hundred ninety-six adolescents were invited to participate in teacher-delivered personality-targeted interventions, and 463 were assigned to the nontreatment condition. Primary outcomes were drinking, binge-drinking status, quantity by frequency of alcohol use, and drinking-related problems.

School delivery of the personality-targeted intervention program was associated with significantly lower drinking rates in high-risk students at 6-month follow-up (odds ratio, 0.6), indicating a 40% decreased risk of alcohol consumption in the intervention group. Receiving an intervention also predicted significantly lower binge-drinking rates in students who reported alcohol use at baseline (odds ratio, 0.45), indicating a 55% decreased risk of binge-drinking in this group compared with controls. In addition, high-risk intervention-school students reported lower quantity by frequency of alcohol use (β = −.18) and drinking-related problems (β = −.15) compared with the nontreatment group at follow-up.

This trial replicates previous studies reporting the efficacy of personality-targeted interventions and demonstrates that targeted interventions can be successfully delivered by teachers, suggesting potential for this approach as a sustainable school-based prevention model.

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Is it simply British to 'get smashed'?

The land that gave the world the 20-ounce pint of beer is in the throes of a loaded debate: Should government act to curb a dangerous culture of binge drinking, or is it simply British to get smashed?

It is no secret the residents of these isles like a drink, or three. An inebriated King James I once fell to the royal floor while greeting the King of Denmark, and a room at the Priory - the London rehabilitation clinic - is something of a rite of passage for British celebrities. But even here, the national outcry is reaching a fevered pitch over lager lad hooligans and increasingly, their female counterparts, ladettes, turning British cities and towns into what the new Conservative Prime Minister David Cameron denounced this month as "the wild west."

Concern over "boozy Britain" has been mounting for years, with attempts to curb binge drinking either backfiring or having little effect. But with late-night crime and alcohol-related hospitalizations surging, a fresh push is afoot for stronger local and national laws. A ban on ladies' nights and all-you-can-drink specials went into effect in April, as did a law forcing pubs and bars in England and Wales to offer smaller glass sizes to patrons. > > > > >

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Heritabilities of Alcohol Use Disorders Identification Test (AUDIT) scores and alcohol biomarkers in Koreans: The KoGES and Healthy Twin Study

Both the Alcohol Use Disorders Identification Test (AUDIT) and alcohol biomarkers are used to screen for alcohol problems. The purpose of this study was to examine the genetic and environmental contributions to the AUDIT score and alcohol biomarkers in Koreans.

The study included 1678 current alcohol drinkers: 818 Korean twins and 860 their families. The Korean version of AUDIT and alcohol biomarkers, i.e., gamma glutamyltransferase (GGT), alanine aminotransferase (ALT), mean corpuscular volume (MCV), and triglycerides (TG), were studied. The analyses were conducted using variance components method to estimate heritability and common environmental effects, and bivariate analyses for genetic and environmental correlations between the AUDIT score and the biomarkers after adjustment for age, gender, interaction of age and gender, smoking status, the amount of consumed alcohol, body mass index, and education.

Heritabilities for the AUDIT score were 0.35 and 0.40–0.71 for biomarkers. The risk of alcohol problems using AUDIT score was positively associated with the levels of biomarkers (GGT, MCV, and TG) in men, while the relationship was significant only for MCV in women. Genetic or environmental correlations between the AUDIT score and some of the biomarkers (GGT and MCV) were significant in men, but not significant in women.

We found a significant genetic contribution to the AUDIT score and the alcohol biomarkers.

As there were significant genetic and environmental relationships between the AUDIT score and the alcohol biomarkers in men, future studies are warranted to identify common genes and environmental effects affecting the relationships.

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Onset and course of alcoholism over 25 years in middle class men

Patterns of drinking and alcohol problems change with age. However, few studies use multiple data points and detailed history spanning early adulthood to middle age. This study reports such data from 373 men in the San Diego Prospective Study.

Data were generated at baseline (T1) at age 20, and through face-to-face followup interviews every 5 years in >90% of these eligible Caucasian and relatively higher educated men. Subjects were placed into 4 groups regarding their course: 62.5% with no alcohol use disorder (AUD); 17.2% with AUD onset 5 years before the 25-year followup.

On a univariate level, low level of response (LR) to alcohol, family history of AUDs, and higher Novelty Seeking at age 20 predicted AUDs with onset before age 30 (mean age 25), but among these only LR predicted later onset (mean age 38) as well. Additional predictors of AUDs included demography (lower education), and greater involvement with alcohol, drugs, and nicotine prior to T1. Sustained remission from AUDs among alcoholics was predicted by lower T1 and T10 drinking frequencies, and being separated or divorced at T10, along with a trend for higher Reward Dependence.

These data indicate that information available in ages of the late teens to early twenties can help predict the future onset and course of AUDs, and underscore the importance of longitudinal studies in substance use disorders.

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