Towards a molecular epidemiology of alcohol dependence analysing the interplay of genetic and environmental risk factors

Background Progress in identifying genetic factors protective against alcohol dependence (AlcD) requires a paradigm shift in psychiatric epidemiology. Aims To integrate analysis of research into the genetics of alcoholism. Method Data from prospective questionnaire and interview surveys of the Australian twin panel, and from a subsample who underwent alcohol challenge, were analysed. Results In men, effects of alcohol dehydrogenase ADH2*1/*2 genotype or high alcohol sensitivity (risk-decreasing), and of history of childhood conduct disorder, or having monozygotic co-twin or twin sister with AlcD (risk-increasing) were significant and comparable in magnitude. Religious affiliation (Anglican versus other) was associated with the ADH2 genotype, but did not explain the associations with AlcD symptoms. No protective effect of the ADH2*1/*2 genotype was observed in women. Conclusions The early onset and strong familial aggregation of AlcD, and opportunity for within-family tests of genetic association to avoid confounding effects, make epidemiological family studies of adolescents and young adults and their families a priority.

Case fatality after an acute cardiac event: the effect of smoking and alcohol consumption

The objective of this study was to use a population-based register of acute cardiac events to investigate the association between survival after an acute event and history of smoking and alcohol consumption. The population was all residents of the Lower Hunter Region of Australia aged 25 to 69 years who suffered myocardial infarction or sudden cardiac death between 1986 and 1994. Among 10,170 events, 2504 resulted in death within 28 days. After adjusting for sex, age and medical history, current smokers had a similar risk of dying after an acute cardiac event to never-smokers [odds ratio (OR)=1.10, 95% confidence interval (CI) 0.94-1.29]. People who consumed more than 8 alcoholic drinks per day on more than 2 days per week (OR=1.93, 95% CI 1.39-2.69) and former moderate to heavy drinkers (OR=4.59, 95% CI 3.65-5.76) were more likely to die than people who were nondrinkers. The results of this large community study, suggesting no effect of smoking on case fatality and an increased risk of death after an acute cardiac event for heavy drinkers and former moderate to heavy drinkers, highlight the importance of a population view of case fatality. These results can also shed some light on reasons for the paradoxical results from clinical trials. (C) 2001 Elsevier Science Inc. All rights reserved.

An integrative approach for studying the etiology of alcoholism and other addictions

Studies of alcoholism etiology often focus on genetic or psy-chosocial approaches, but not both. Greater understanding of the etiology of alcohol, tobacco and other addictions will come from integration of these research traditions. A research approach is outlined to test three models for the etiology of addictions — behavioral undercontrol, pharmacologic vulnerability, negative affect regulation — addressing key questions including (i) mediators of genetic effects, (ii) genotype-environment correlation effects, (iii) genotype x environment interaction effects, (iv) the developmental unfolding of genetic and environmental effects, (v) subtyping including identification of distinct trajectories of substance involvement, (vi) identification of individual genes that contribute to risk, and (vii) the consequences of excessive use. By using coordinated research designs, including prospective assessment of adolescent twins and their siblings and parents; of adult substance dependent and control twins and their MZ and DZ cotwins, the spouses of these pairs, and their adolescent offspring; and of regular families; by selecting for gene-mapping approaches sibships screened for extreme concordance or discordance on quantitative indices of substance use; and by using experimental (drug challenge) as well as survey approaches, a number of key questions concerning addiction etiology can be addressed. We discuss complementary strengths and weaknesses of different sampling strategies, as well as methods to implement such an integrated approach illustrated for the study of alcoholism etiology. A coordinated program of twin and family studies will allow a comprehensive dissection of the interplay of genetic and environmental risk-factors in the etiology of alcoholism and other addictions.

The influence of genetic and environmental factors in estimations of current body size, desired body size, and body dissatisfaction

The objective was to investigate the genetic epidemiology of figural stimuli. Standard figural stimuli were available from 5,325 complete twin pairs: 1,751 (32.9%) were monozygotic females, 1,068 (20.1%) were dizygotic females, 752 (14.1%) were monozygotic males, 495 (9.3%) were dizygotic males, and 1,259 (23.6%) were dizygotic male-female pairs. Univariate twin analyses were used to examine the influences on the individual variation in current body size and ideal body size. These data were analysed separately for men and women in each of five age groups. A factorial analysis of variance, with polychoric correlations between twin pairs as the dependent variable, and age, sex, zygosity, and the three interaction terms (age x sex, age x zygosity, sex x zygosity) as independent variables, was used to examine trends across the whole data set. Results showed genetic influences had the largest impact on the individual variation in current body size measures, whereas non-shared environmental influences were associated with the majority of individual variation in ideal body size. There was a significant main effect of zygosity (heritability) in predicting polychoric correlations for current body size and body dissatisfaction. There was a significant main effect of gender and zygosity in predicting ideal body size, with a gender x zygosity interaction. In common with BMI, heritability is important in influencing the estimation of current body size. Selection of desired body size for both men and women is more strongly influenced by environmental factors.

A review of the impact of education and prior experience on new venture performance

The importance of education and experience to the successful performance of new firms is well recognized both by management practitioners and academics. Yet empirical research to support the significance of this relationship is inconclusive. This paper discusses theories describing the relationship between education and experience and firm performance. It also analyses and classifies the differing measures of performance, education and experience, and compares the results of multiple studies undertaken between 1977 and 2000. Possible reasons for conflicting results are identified, such as lack of sound theoretical bases that relate education and experience to performance, varying definitions of the key variables and the diversity of measures used. Finally, a framework is developed that incorporates variables that interact with experience and education to influence new venture performance.

Advanced precursors in marine biosynthetic study. Part 2: The biosynthesis of isocyanides and isothiocyanates in the tropical marine sponge Axinyssa n.sp.

The biosynthetic origins of the isocyanide and isothiocyanate groups in 9-isocyanop upukeanane (2) and 9-isothiocyanato-pupukeanane (3) are investigated by incorporation of [C-14]-labelled advanced precursors into the sponge Axinyssa n.sp. (C) 2001 Elsevier Science Ltd. All rights reserved.

Assessing the effects of attention and emotion on startle eyeblink modulation

Two experiments were conducted to assess simultaneously the effects of attentional and emotional processes on startle eyeblink modulation. In each experiment, participants were presented with a pleasant and an unpleasant picture. Half the participants were asked to attend to the pleasant picture and to ignore the unpleasant picture, whereas the reverse was the case for the other participants. Startle probes were presented at 3500 and 4500 ins after stimulus onset in Experiment I and at 250, 750, and 4450 ms after stimulus onset and 950 ms after stimulus offset in Experiment 2. Attentional processing affected startle eyeblink modulation and electrodermal responses in both experiments, However, effects of picture valence on startle eyeblink modulation were found only in Experiment 2. The results confirm the utility of startle eyeblink modulation as an index of attentional and emotional processing. They also illustrate that procedural characteristics, such as the nature of the lead intervals and how attention and emotion are operationalized, can determine whether emotional or attentional processes will be reflected in startle eyeblink.

Effect of tissue Doppler on the accuracy of novice and expert interpreters of Dobutamine echocardiography

The subjective interpretation of dobutamine echocardiography (DBE) makes the accuracy of this technique dependent on the experience of the observer, and also poses problems of concordance between observers. Myocardial tissue Doppler velocity (MDV) may offer a quantitative technique for identification of coronary artery disease, but it is unclear whether this parameter could improve the results of less expert readers and in segments with low interobserver concordance. The aim of this study was to find whether MDV improved the accuracy of wall motion scoring in novice readers, experienced echocardiographers, and experts in stress echocardiography, and to identify the optimal means of integrating these tissue Doppler data in 77 patients who underwent DBE and angiography. New or worsening abnormalities were identified as ischemia and abnormalities seen at rest as scarring. Segmental MDV was measured independently and previously derived cutoffs were applied to categorize segments as normal or ab normal. Five strategies were used to combine MDV and wall motion score, and the results of each reader using each strategy were compared with quantitative coronary angiography. The accuracy of wall motion scoring by novice (68 +/- 3%) and experienced echocardiographers (71 +/- 3%) was less than experts in stress echocardiography (88 +/- 3%, p < 0.001). Various strategies for integration with MDV significantly improved the accuracy of wall motion scoring by novices from 75 +/- 2% to 77 +/- 5% (p < 0.01). Among the experienced group, accuracy improved from 74 +/- 2% to 77 +/- 5% (p < 0.05), but in the experts, no improvement was seen from their baseline accuracy. Integration with MDV also improved discordance related to the basal segments. Thus, use of MDV in all segments or MDV in all segments with wall motion scoring in the apex offers an improvement in sensitivity and accuracy with minimal compromise in specificity. (C) 2001 by Excerpta Medica, Inc.

The influence of diet and exercise on muscle and plasma glutamine concentrations

Purpose: This study examined the relationship between muscle glutamine, muscle glycogen, and plasma glutamine concentrations over 3 d of high-intensity exercise during which dietary carbohydrate (CHO) intake varied. Methods: Five endurance-trained men completed two exercise trials in randomized order, over a 14-d period. Each trial required subjects to perform 50 min of high-intensity continuous and interval exercise on three consecutive days while consuming a diet that provided 45% of the energy as CHO or a diet in which CHO provided 70% of the total energy. Four days of inactivity and consumption of a 55% CHO diet separated the two randomized trials. Menus and food were provided for the subjects and all food and drink consumed were weighed and recorded for later analysis. Before exercise on the first day of each trial, at the start of exercise on day 3 and on completion of exercise on day 3, muscle was biopsied from the vastus lateralis for the analysis of glutamine and glycogen concentrations. Venous blood was sampled before and twice after exercise on each day for the analysis of plasma glutamine and cortisol concentrations. Results: Mean plasma glutamine concentration was significantly higher during the 70% CHO exercise trial when compared with the 45% CHO trial (P < 0.05). Glycogen decreased by the same magnitude during both trials and there was no relationship between changes in plasma glutamine and changes in muscle glycogen concentration. Muscle glutamine concentration did not change in either trial. Conclusions: These data suggest that the influence of carbohydrate intake upon the concentration of plasma glutamine is not mediated through the concentration of intramuscular glycogen.

The future of cognitive and behavioral therapies in the prevention and early management of psychosis: Opportunities and risks

Behavioral and cognitive interventions for people with psychosis have a long and distinguished history, although the evidence for their application to young people remains limited. We anticipate that the next decades will show substantial research into psychological intervention for this population. Important targets will include the management of environmental stressors, reduction of substance misuse, and promotion of early treatment. Psychological management of positive symptoms, depression, and suicidal behavior will continue to be critical objectives. Important secondary prevention goals will be the retention of cognitive functioning, vocational options, social skills, and social network support, including appropriate family support. We expect primary prevention to include both universal programs and interventions for adolescents at particularly high risk. Technical innovations will include increasing use of Internet-based intervention and behavior cueing devices. Pressures for intervention brevity will continue, as will problems with the systematic delivery of effective procedures.

The mechanisms of combustion and continuous reactions during mechanical alloying

Some materials exhibit a combustion event during mechanical alloying, which results in the rapid transformation of reactants into products, while others show a slow transformation of reactants into products, In this paper, the continuous W + C --> WC reaction is compared to the Ti + C --> TiC combustion reaction. Rietveld refinement of X-ray diffraction patterns is used to show that these particular reactions proceed through different pathways, determined by crystallographic factors of the reactants. When a crystallographic relationship exists between the reactants and the products, such as that between W and WC, the product forms slowly over a period of time. In contrast, insertion of C into the Ti structure is associated with atomic rearrangements within the crowded lattice planes and the subsequent catastrophic failure of the reactant lattices results in combustion to form TiC. (C) 2001 Academic Press.