Genetic effects on alcohol dependence risk: re-evaluating the importance of psychiatric and other heritable risk factors

Background. Genetic influences have been shown to play a major role in determining the risk of alcohol dependence (AD) in both women and men; however, little attention has been directed to identifying the major sources of genetic variation in AD risk. Method. Diagnostic telephone interview data from young adult Australian twin pairs born between 1964 and 1971 were analyzed. Cox regression models were fitted to interview data from a total of 2708 complete twin pairs (690 MZ female, 485 MZ male, 500 DZ female, 384 DZ male, and 649 DZ female/male pairs). Structural equation models were fitted to determine the extent of residual genetic and environmental influences on AD risk while controlling for effects of sociodemographic and psychiatric predictors on risk. Results. Risk of AD was increased in males, in Roman Catholics, in those reporting a history of major depression, social anxiety problems, and conduct disorder, or (in females only) a history of suicide attempt and childhood sexual abuse; but was decreased in those reporting Baptist, Methodist, or Orthodox religion, in those who reported weekly church attendance, and in university-educated males. After allowing for the effects of sociodemographic and psychiatric predictors, 47 % (95 % CI 28-55) of the residual variance in alcoholism risk was attributable to additive genetic effects, 0 % (95 % CI 0-14) to shared environmental factors, and 53 % (95 % CI 45-63) to non-shared environmental influences. Conclusions. Controlling for other risk factors, substantial residual heritability of AD was observed, suggesting that psychiatric and other risk factors play a minor role in the inheritance of AD.

Population effects on individual systolic blood pressure: A multilevel analysis of the World Health Organization MONICA project

Individuals from the same population share a number of contextual circumstances that may condition a common level of blood pressure over and above individual characteristics. Understanding this population effect is relevant for both etiologic research and prevention strategies. Using multilevel regression analyses, the authors quantified the extent to which individual differences in systolic blood pressure (SBP) could be attributed to the population level. They also investigated possible cross-level interactions between the population in which a person lived and pharmacological (antihypertensive medication) and nonpharmacological (body mass index) effects on individual SBP. They analyzed data on 23,796 men and 24,986 women aged 35-64 years from 39 worldwide Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study populations participating in the final survey of this World Health Organization project (1989-1997). SBP was positively associated with low educational achievement, high body mass index, and use of antihypertensive medication and, for women, was negatively associated with smoking. About 7-8% of all SBP differences between subjects were attributed to the population level. However, this population effect was particularly strong (i.e., 20%) in antihypertensive medication users and overweight women. This empirical evidence of a population effect on individual SBP emphasizes the importance of developing population-wide strategies to reduce individual risk of hypertension.

Appetitive motivation predicts the majority of personality and an ability measure: a comparison of BAS measures and a re-evaluation of the importance of RST

Our first study develops a measure of appetitive motivation and our second study compares several measures of Gray's (1987) behaviour activation system (BAS) in the prediction of the surface scales of personality. In particular, we were interested in determining the utility of the new appetitive motivation scale and Dickman's functional impulsivity scale. In comparison to other well-known measures, both scales were generally good predictors. We conclude that the appetitive motivation scale is a promising measure of BAS based upon construct validation. Contrary to previous studies which have suggested that BAS is a generally poor predictor of the surface scales of personality, we discovered appetitive motivation to be an important predictor of personality in general. Interestingly, the scale was also predictive of scores on the Baddeley reasoning test. (C) 2003 Elsevier Ltd. All rights reserved.

Implications of seasonal climate forecasts on world wheat trade: a stochastic, dynamic analysis

Improvements in seasonal climate forecasts have potential economic implications for international agriculture. A stochastic, dynamic simulation model of the international wheat economy is developed to estimate the potential effects of seasonal climate forecasts for various countries' wheat production, exports and world trade. Previous studies have generally ignored the stochastic and dynamic aspects of the effects associated with the use of climate forecasts. This study shows the importance of these aspects. In particular with free trade, the use of seasonal forecasts results in increased producer surplus across all exporting countries. In fact, producers appear to capture a large share of the economic surplus created by using the forecasts. Further, the stochastic dimensions suggest that while the expected long-run benefits of seasonal forecasts are positive, considerable year-to-year variation in the distribution of benefits between producers and consumers should be expected. The possibility exists for an economic measure to increase or decrease over a 20-year horizon, depending on the particular sequence of years.

Exposing extinction risk analysis to pathogens: Is disease just another form of density dependence?

In the United States and several other countries., the development of population viability analyses (PVA) is a legal requirement of any species survival plan developed for threatened and endangered species. Despite the importance of pathogens in natural populations, little attention has been given to host-pathogen dynamics in PVA. To study the effect of infectious pathogens on extinction risk estimates generated from PVA, we review and synthesize the relevance of host-pathogen dynamics in analyses of extinction risk. We then develop a stochastic, density-dependent host-parasite model to investigate the effects of disease on the persistence of endangered populations. We show that this model converges on a Ricker model of density dependence under a suite of limiting assumptions, including. a high probability that epidemics will arrive and occur. Using this modeling framework, we then quantify: (1) dynamic differences between time series generated by disease and Ricker processes with the same parameters; (2) observed probabilities of quasi-extinction for populations exposed to disease or self-limitation; and (3) bias in probabilities of quasi-extinction estimated by density-independent PVAs when populations experience either form of density dependence. Our results suggest two generalities about the relationships among disease, PVA, and the management of endangered species. First, disease more strongly increases variability in host abundance and, thus, the probability of quasi-extinction, than does self-limitation. This result stems from the fact that the effects and the probability of occurrence of disease are both density dependent. Second, estimates of quasi-extinction are more often overly optimistic for populations experiencing disease than for those subject to self-limitation. Thus, although the results of density-independent PVAs may be relatively robust to some particular assumptions about density dependence, they are less robust when endangered populations are known to be susceptible to disease. If potential management actions involve manipulating pathogens, then it may be useful to. model disease explicitly.

Functional-structural plant modelling using a combination of architectural analysis, L-systems and a canonical model of function

This paper presents a new method for producing a functional-structural plant model that simulates response to different growth conditions, yet does not require detailed knowledge of underlying physiology. The example used to present this method is the modelling of the mountain birch tree. This new functional-structural modelling approach is based on linking an L-system representation of the dynamic structure of the plant with a canonical mathematical model of plant function. Growth indicated by the canonical model is allocated to the structural model according to probabilistic growth rules, such as rules for the placement and length of new shoots, which were derived from an analysis of architectural data. The main advantage of the approach is that it is relatively simple compared to the prevalent process-based functional-structural plant models and does not require a detailed understanding of underlying physiological processes, yet it is able to capture important aspects of plant function and adaptability, unlike simple empirical models. This approach, combining canonical modelling, architectural analysis and L-systems, thus fills the important role of providing an intermediate level of abstraction between the two extremes of deeply mechanistic process-based modelling and purely empirical modelling. We also investigated the relative importance of various aspects of this integrated modelling approach by analysing the sensitivity of the standard birch model to a number of variations in its parameters, functions and algorithms. The results show that using light as the sole factor determining the structural location of new growth gives satisfactory results. Including the influence of additional regulating factors made little difference to global characteristics of the emergent architecture. Changing the form of the probability functions and using alternative methods for choosing the sites of new growth also had little effect. (c) 2004 Elsevier B.V. All rights reserved.

Repeated occurrence of basal cell carcinoma of the skin and multifailure survival analysis: Follow-up data from the nambour skin cancer prevention trial

The aim of this study was to apply multifailure survival methods to analyze time to multiple occurrences of basal cell carcinoma (BCC). Data from 4.5 years of follow-up in a randomized controlled trial, the Nambour Skin Cancer Prevention Trial (1992-1996), to evaluate skin cancer prevention were used to assess the influence of sunscreen application on the time to first BCC and the time to subsequent BCCs. Three different approaches of time to ordered multiple events were applied and compared: the Andersen-Gill, Wei-Lin-Weissfeld, and Prentice-Williams-Peterson models. Robust variance estimation approaches were used for all multifailure survival models. Sunscreen treatment was not associated with time to first occurrence of a BCC (hazard ratio = 1.04, 95% confidence interval: 0.79, 1.45). Time to subsequent BCC tumors using the Andersen-Gill model resulted in a lower estimated hazard among the daily sunscreen application group, although statistical significance was not reached (hazard ratio = 0.82, 95% confidence interval: 0.59, 1.15). Similarly, both the Wei-Lin-Weissfeld marginal-hazards and the Prentice-Williams-Peterson gap-time models revealed trends toward a lower risk of subsequent BCC tumors among the sunscreen intervention group. These results demonstrate the importance of conducting multiple-event analysis for recurring events, as risk factors for a single event may differ from those where repeated events are considered.

A multiple account framework for cost-benefit analysis

The paper presents a spreadsheet-based multiple account framework for cost-benefit analysis which incorporates all the usual concerns of cost-benefit analysts such as shadow-pricing to account for market failure. distribution of net benefits. sensitivity and risk analysis, cost of public funds, and environmental effects. The approach is generalizable to a wide range of projects and situations and offers a number of advantages to both analysts and decision-makers, including transparency, a check on internal consistency, and a detailed summary of project net benefits disaggregated by stakeholder group. Of particular importance is the ease with which this framework allows for a project to be evaluated from alternative decision-making perspectives and under alternative policy scenarios where the trade-offs among the project's stakeholders can readily be identified and quantified. (C) 2004 Elsevier Ltd. All rights reserved.

The importance of modelling heterogeneity in complex disease: application to NIMH Schizophrenia Genetics Initiative data

As for other complex diseases, linkage analyses of schizophrenia (SZ) have produced evidence for numerous chromosomal regions, with inconsistent results reported across studies. The presence of locus heterogeneity appears likely and may reduce the power of linkage analyses if homogeneity is assumed. In addition, when multiple heterogeneous datasets are pooled, intersample variation in the proportion of linked families ( a) may diminish the power of the pooled sample to detect susceptibility loci, in spite of the larger sample size obtained. We compare the significance of linkage. findings obtained using allele- sharing LOD scores ( LODexp) - which assume homogeneity - and heterogeneity LOD scores ( HLOD) in European American and African American NIMH SZ families. We also pool these two samples and evaluate the relative power of the LODexp and two different heterogeneity statistics. One of these ( HLOD- P) estimates the heterogeneity parameter a only in aggregate data, while the second ( HLOD- S) determines a separately for each sample. In separate and combined data, we show consistently improved performance of HLOD scores over LODexp. Notably, genome-wide significant evidence for linkage is obtained at chromosome 10p in the European American sample using a recessive HLOD score. When the two samples are combined, linkage at the 10p locus also achieves genome-wide significance under HLOD- S, but not HLOD- P. Using HLOD- S, improved evidence for linkage was also obtained for a previously reported region on chromosome 15q. In linkage analyses of complex disease, power may be maximised by routinely modelling locus heterogeneity within individual datasets, even when multiple datasets are combined to form larger samples.

The importance of the relevance of the issue to the group in voting intentions: The case of the Australian republic referendum

A questionnaire was distributed on the Australian republic issue to examine the interplay between norms and relevance of the issue to the group on voting intentions. Supporters of an Australian republic (N = 188) indicated the level of support for a republic within their peer Group, the relevance of the republic issue to the group, and measures designed to assess voting intentions and other attitude outcomes. Analysis revealed an interaction between normative support and relevance of the issue to the group. On the measure of intention, increasing normative support was associated with increased intention to vote in an attitude-consistent way at both relevance levels, but the effect was heightened when the issue was highly relevant to the group. On the outcomes of willingness to express opinion and perceived personal importance of the republic issue, normative support had a positive effect only when the issue was highly relevant to the group. Mediation analyses revealed that the impact of normative support and group relevance on intention were mediated through perceived personal importance of the republic issue.

Views of general practitioners and benzodiazepine users on benzodiazepines: A qualitative analysis

Effectively assisting benzodiazepine users to cease use requires a greater understanding of general practitioners' (GPs) and benzodiazepine users' views on using and ceasing benzodiazepines. This paper reports the findings from a qualitative study that examined the views of 28 GPs and 23 benzodiazepine users (BUs) in Cairns, Australia. A semi-structured interview was conducted with all participants and the information gained was analysed using the Consensual Qualitative Research Approach, which allowed comparisons to be made between the views of the two groups of interviewees. There was commonality between GPs and BUs on reasons for commencing benzodiazepines, the role of dependence in continued use, and the importance of lifestyle change in its cessation. However, several differences emerged regarding commencement of use and processes of cessation. In particular, users felt there was greater need for GPs to routinely advise patients about non-pharmacological management of their problems and potential adverse consequences of long-term use before commencing benzodiazepines. Cessation could be discussed with all patients who use benzodiazepines for longer than 3 months, strategies offered to assist in management of withdrawal and anxiety, and referral to other health service providers for additional support. Lifestyle change could receive greater focus at all stages of treatment. (c) 2005 Elsevier Ltd. All rights reserved.

An examination of the dynamic relationship between self-efficacy and performance across levels of analysis and levels of specificity

This research used resource allocation theory to generate predictions regarding dynamic relationships between self-efficacy and task performance from 2 levels of analysis and specificity. Participants were given multiple trials of practice on an air traffic control task. Measures of task-specific self-efficacy and performance were taken at repeated intervals. The authors used multilevel analysis to demonstrate differential and dynamic effects. As predicted, task-specific self-efficacy was negatively associated with task performance at the within-person level. On the other hand, average levels of task-specific self-efficacy were positively related to performance at the between-persons level and mediated the effect of general self-efficacy. The key findings from this research relate to dynamic effects - these results show that self-efficacy effects can change over time, but it depends on the level of analysis and specificity at which self-efficacy is conceptualized. These novel findings emphasize the importance of conceptualizing self-efficacy within a multilevel and multispecificity framework and make a significant contribution to understanding the way this construct relates to task performance.

Analysis of the effect of different NKT cell subpopulations on the activation of CD4 and CD8 T cells, NK cells, and B cells

Objective. NKT cells have diverse immune regulatory functions including activation of cells involved in Th1- and Th2-type immune activities. Most previous studies have investigated the functions of NKT cells as a single family but more recent evidence indicates the distinct functional properties of NKT cell subpopulation. This study aims to determine whether NKT cell subpopulations have different stimulatory activities on other immune cells that may affect the outcome of NKT cell-based immunotherapy. Methods. NKT cells and NKT cell subpopulations (CD4(+)CD8(-), CD4(-)CD8(+), CD4(-)CD8(+)) were cocultured with PBMC and their activities on immune cells including CD4(+) and CD8(+) T cells, NK cells, and B cells were assessed by flow cytometry. The production of cytokines in culture was measured by enzyme-linked immunsorbent assay. Results. The CD4(+)CD8(-) NKT cells demonstrated substantially greater stimulatory activities on CD4(+) T cells, NK cells, and B cells than other NKT cell subsets. The CD4(-)CD8(+) NKT cells showed the greatest activity on CD8(+) T cells, and were the only NKT cell subset that activated these immune cells. The CD4(-)CD8(-) NKT cells showed moderate stimulatory activity on CD4(+) T cells and the least activity on other immune cells. Conclusion. The results here suggest that NKT cell subpopulations differ in their abilities to stimulate other immune cells. This highlights the potential importance of manipulating specific NKT cell subpopulations for particular therapeutic situations and of evaluating subpopulations, rather than NKT cells as a group, during investigation of a possible role of NKT cells in various disease settings. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc.

Applying network analysis to the conservation of habitat trees in urban environments: a case study from Brisbane, Australia

In Australia more than 300 vertebrates, including 43 insectivorous bat species, depend on hollows in habitat trees for shelter, with many species using a network of multiple trees as roosts, We used roost-switching data on white-striped freetail bats (Tadarida australis; Microchiroptera: Molossidae) to construct a network representation of day roosts in suburban Brisbane, Australia. Bats were caught from a communal roost tree with a roosting group of several hundred individuals and released with transmitters. Each roost used by the bats represented a node in the network, and the movements of bats between roosts formed the links between nodes. Despite differences in gender and reproductive stages, the bats exhibited the same behavior throughout three radiotelemetry periods and over 500 bat days of radio tracking: each roosted in separate roosts, switched roosts very infrequently, and associated with other bats only at the communal roost This network resembled a scale-free network in which the distribution of the number of links from each roost followed a power law. Despite being spread over a large geographic area (> 200 km(2)), each roost was connected to others by less than three links. One roost (the hub or communal roost) defined the architecture of the network because it had the most links. That the network showed scale-free properties has profound implications for the management of the habitat trees of this roosting group. Scale-free networks provide high tolerance against stochastic events such as random roost removals but are susceptible to the selective removal of hub nodes. Network analysis is a useful tool for understanding the structural organization of habitat tree usage and allows the informed judgment of the relative importance of individual trees and hence the derivation of appropriate management decisions, Conservation planners and managers should emphasize the differential importance of habitat trees and think of them as being analogous to vital service centers in human societies.