A novel SNP in COMT is associated with alcohol dependence but not opiate or nicotine dependence: a case control study

Background It is well established that COMT is a strong candidate gene for substance use disorder and schizophrenia. Recently we identified two SNPs in COMT (rs4680 and rs165774) that are associated with schizophrenia in an Australian cohort. Individuals with schizophrenia were more than twice as likely to carry the GG genotype compared to the AA genotype for both the rs165774 and rs4680 SNPs. Association of both rs4680 and rs165774 with substance dependence, a common comorbidity of schizophrenia has not been investigated. Methods To determine whether COMT is important in substance dependence, rs165774 and rs4680 were genotyped and haplotyped in patients with nicotine, alcohol and opiate dependence. Results The rs165774 SNP was associated with alcohol dependence. However, it was not associated with nicotine or opiate dependence. Individuals with alcohol dependence were more than twice as likely to carry the GG or AG genotypes compared to the AA genotype, indicating a dominant mode of inheritance. The rs4680 SNP showed a weak association with alcohol dependence at the allele level that did not reach significance at the genotype level but it was not associated with nicotine or opiate dependence. Analysis of rs165774/rs4680 haplotypes also revealed association with alcohol dependence with the G/G haplotype being almost 1.5 times more common in alcohol-dependent cases. Conclusions Our study provides further support for the importance of the COMT in alcohol dependence in addition to schizophrenia. It is possible that the rs165774 SNP, in combination with rs4680, results in a common molecular variant of COMT that contributes to schizophrenia and alcohol dependence susceptibility. This is potentially important for future studies of comorbidity. As our participant numbers are limited our observations should be viewed with caution until they are independently replicated.

A DRD2 and ANKK1 haplotype is associated with nicotine dependence

To test the importance of the dopamine D2 receptor (DRD2) region in nicotine dependence, 150 smokers and 228 controls were genotyped for the DRD2 C957T, -141delC and ANKK1 TaqIA polymorphisms (rs6277, rs1799732 and rs1800497, respectively). The -141delC SNP did not show any association but both the C957T and TaqIA SNPs showed association at the allele, genotype, haplotype and combined genotype levels. The 957C/TaqI A1 haplotype was more than 3.5 times as likely to be associated with nicotine dependence compared with the 957T/TaqI A1 haplotype (P = 0.003). Analysis of the combined genotypes of both SNPs revealed that individuals who were homozygous for the 957C-allele (CC) and had either one or two copies of the TaqI A1-allele were 3.3 times as likely to have nicotine dependence compared to all other genotype combinations (P = 0.0003) and that these genotypes accounted for approximately 13% of the susceptibility to nicotine addiction in our population. Our findings suggest that the DRD2 C957T polymorphism and the ANKK1 TaqIA polymorphism are key contributors to the genetic susceptibility to nicotine dependence.

DRD2 C957T and TaqIA genotyping reveals gender effects and unique low-risk and high-risk genotypes in alcohol dependence

AIMS: As recent conflicting reports describe a genetic association between both the C- and the T-alleles of the dopamine D2 receptor (DRD2) C957T polymorphism (rs6277) in alcohol-dependent subjects, our aim was to examine this polymorphism and TaqIA (rs1800497) in Australian alcohol-dependent subjects. METHODS: The C957T polymorphism was genotyped in 228 patients with alcohol dependence (72 females and 156 males) and 228 healthy controls. RESULTS: The C-allele and C/C genotype of C957T was associated with alcohol dependence, whereas the TaqIA polymorphism was not. When analysed separately for C957T, males showed an even stronger association with the C-allele and females showed no association. The C957T and TaqIA haplotyping revealed a strong association with alcohol dependence and a double-genotype analysis (combining C957T and TaqIA genotypes) revealed that the relative risk of different genotypes varied by up to 27-fold with the TT/A1A2 having an 8.5-fold lower risk of alcohol dependence than other genotypes. CONCLUSION: Decreased DRD2 binding associated with the C-allele of the DRD2 C957T polymorphism is likely to be important in the underlying pathophysiology of at least some forms of alcohol dependence, and this effect appears to be limited to males only.

Maintenance optimisation of a multi-state series-parallel system considering economic dependence and state-dependent inspection intervals

This paper presents a maintenance optimisation method for a multi-state series-parallel system considering economic dependence and state-dependent inspection intervals. The objective function considered in the paper is the average revenue per unit time calculated based on the semi-regenerative theory and the universal generating function (UGF). A new algorithm using the stochastic ordering is also developed in this paper to reduce the search space of maintenance strategies and to enhance the efficiency of optimisation algorithms. A numerical simulation is presented in the study to evaluate the efficiency of the proposed maintenance strategy and optimisation algorithms. The simulation result reveals that maintenance strategies with opportunistic maintenance and state-dependent inspection intervals are more cost-effective when the influence of economic dependence and inspection cost is significant. The study further demonstrates that the optimisation algorithm proposed in this paper has higher computational efficiency than the commonly employed heuristic algorithms.

KPNA3 variation is associated with schizophrenia, major depression, opiate dependence and alcohol dependence

KPNA3 is a gene that has been linked to schizophrenia susceptibility. In this study we investigated the possible association between KPNA3 variation and schizophrenia. To investigate a wider role of KPNA3 across psychiatric disorders we also analysed major depression, PTSD, nicotine dependent, alcohol dependent and opiate dependent cohorts. Using a haplotype block-based gene-tagging approach we genotyped six KPNA3 single nucleotide polymorphisms (SNPs) in 157 schizophrenia patients, 121 post-traumatic stress disorder patients, 120 opiate dependent patients, 231 alcohol dependent patients, 147 nicotine dependent patients and 266 major depression patients. One SNP rs2273816 was found to be significantly associated with schizophrenia, opiate dependence and alcohol dependence at the genotype and allele level. Major depression was also associated with rs2273816 but only at the allele level. Our study suggests that KPNA3 may contribute to the genetic susceptibility to schizophrenia as well as other psychiatric disorders.

Planar radial spots in a three-component FitzHugh-Nagumo system

Localized planar patterns arise in many reaction-diffusion models. Most of the paradigm equations that have been studied so far are two-component models. While stationary localized structures are often found to be stable in such systems, travelling patterns either do not exist or are found to be unstable. In contrast, numerical simulations indicate that localized travelling structures can be stable in three-component systems. As a first step towards explaining this phenomenon, a planar singularly perturbed three-component reaction-diffusion system that arises in the context of gas-discharge systems is analysed in this paper. Using geometric singular perturbation theory, the existence and stability regions of radially symmetric stationary spot solutions are delineated and, in particular, stable spots are shown to exist in appropriate parameter regimes. This result opens up the possibility of identifying and analysing drift and Hopf bifurcations, and their criticality, from the stationary spots described here.

Preliminary Design and Performance Estimation of Radial Inflow Turbines: An Automated Approach

A comprehensive one-dimensional meanline design approach for radial inflow turbines is described in the present work. An original code was developed in Python that takes a novel approach to the automatic selection of feasible machines based on pre-defined performance or geometry characteristics for a given application. It comprises a brute-force search algorithm that traverses the entire search space based on key non-dimensional parameters and rotational speed. In this study, an in-depth analysis and subsequent implementation of relevant loss models as well as selection criteria for radial inflow turbines is addressed. Comparison with previously published designs, as well as other available codes, showed good agreement. Sample (real and theoretical) test cases were trialed and results showed good agreement when compared to other available codes. The presented approach was found to be valid and the model was found to be a useful tool with regards to the preliminary design and performance estimation of radial inflow turbines, enabling its integration with other thermodynamic cycle analysis and three-dimensional blade design codes.

Candidate radial-inflow turbines and high-density working fluids for geothermal power systems

Optimisation of Organic Rankine Cycle (ORCs) for binary-cycle geothermal applications could play a major role in determining the competitiveness of low to moderate temperature geothermal resources. Part of this optimisation process is matching cycles to a given resource such that power output can be maximised. Two major and largely interrelated components of the cycle are the working fluid and the turbine. Both components need careful consideration: the selection of working fluid and appropriate operating conditions as well as optimisation of the turbine design for those conditions will determine the amount of power that can be extracted from a resource. In this paper, we present the rationale for the use of radial-inflow turbines for ORC applications and the preliminary design of several radial-inflow machines based on a number of promising ORC systems that use five different working fluids: R134a, R143a, R236fa, R245fa and n-Pentane. Preliminary meanline analysis lead to the generation of turbine designs for the various cycles with similar efficiencies (77%) but large differences in dimensions (139–289 mm rotor diameter). The highest performing cycle, based on R134a, was found to produce 33% more net power from a 150 °C resource flowing at 10 kg/s than the lowest performing cycle, based on n-Pentane.

Open design of high pressure ratio radial-inflow turbine for academic validation

Computational Fluid Dynamics (CFD) simulations are widely used in mechanical engineering. Although achieving a high level of confidence in numerical modelling is of crucial importance in the field of turbomachinery, verification and validation of CFD simulations are very tricky especially for complex flows encountered in radial turbines. Comprehensive studies of radial machines are available in the literature. Unfortunately, none of them include enough detailed geometric data to be properly reproduced and so cannot be considered for academic research and validation purposes. As a consequence, design improvements of such configurations are difficult. Moreover, it seems that well-developed analyses of radial turbines are used in commercial software but are not available in the open literature especially at high pressure ratios. It is the purpose of this paper to provide a fully open set of data to reproduce the exact geometry of the high pressure ratio single stage radial-inflow turbine used in the Sundstrand Power Systems T-100 Multipurpose Small Power Unit. First, preliminary one-dimensional meanline design and analysis are performed using the commercial software RITAL from Concepts-NREC in order to establish a complete reference test case available for turbomachinery code validation. The proposed design of the existing turbine is then carefully and successfully checked against the geometrical and experimental data partially published in the literature. Then, three-dimensional Reynolds-Averaged Navier-Stokes simulations are conducted by means of the Axcent-PushButton CFDR CFD software. The effect of the tip clearance gap is investigated in detail for a wide range of operating conditions. The results confirm that the 3D geometry is correctly reproduced. It also reveals that the turbine is shocked while designed to give a high-subsonic flow and highlight the importance of the diffuser.

Candidate radial-inflow turbines and high-density working fluids for geothermal power systems

Optimisation of Organic Rankine Cycles (ORCs) for binary-cycle geothermal applications could play a major role in the competitiveness of low to moderate temperature geothermal resources. Part of this optimisation process is matching cycles to a given resource such that power output can be maximised. Two major and largely interrelated components of the cycle are the working fluid and the turbine. Both components need careful consideration. Due to the temperature differences in geothermal resources a one-size-fits-all approach to surface power infrastructure is not appropriate. Furthermore, the traditional use of steam as a working fluid does not seem practical due to the low temperatures of many resources. A variety of organic fluids with low boiling points may be utilised as ORC working fluids in binary power cycle loops. Due to differences in thermodynamic properties, certain fluids are able to extract more heat from a given resource than others over certain temperature and pressure ranges. This enables the tailoring of power cycle infrastructure to best match the geothermal resource through careful selection of the working fluid and turbine design optimisation to yield the optimum overall cycle performance. This paper presents the rationale for the use of radial-inflow turbines for ORC applications and the preliminary design of several radial-inflow turbines based on a selection of promising ORC cycles using five different high-density working fluids: R134a, R143a, R236fa, R245fa and n-Pentane at sub- or trans-critical conditions. Numerous studies published compare a variety of working fluids for various ORC configurations. However, there is little information specifically pertaining to the design and implementation of ORCs using realistic radial turbine designs in terms of pressure ratios, inlet pressure, rotor size and rotational speed. Preliminary 1D analysis leads to the generation of turbine designs for the various cycles with similar efficiencies (77%) but large differences in dimensions (139289 mm rotor diameter). The highest performing cycle (R134a) was found to produce 33% more net power from a 150°C resource flowing at 10 kg/s than the lowest performing cycle (n-Pentane).

Metacognitive therapy for alcohol abuse and dependence

While the consumption of alcohol has been part of the collective psyche of Australians since colonisation, the overconsumption of alcohol has been and continues to be a significant problem for the Australian community. Currently motivational interviewing and cognitive behaviour therapy are seen as the two standard psychological interventions for alcohol abuse and dependence. While these two approaches have shown significant impact on reducing alcohol abuse and dependence, they are not without their limitations. As such there is a need to continue to explore the application of newer developments in psychotherapy to the treatment problematic drinking behaviours. In this chapter we propose that Metacognitive Therapy is one such psychotherapy that is likely to provide a promising new approach to the treatment of alcohol abuse and dependence. In this chapter we will first briefly outline the history and significance of problematic drinking behaviours in Australia. Following this, we will quickly summarise the literature regarding motivational interviewing and cognitive behaviour therapy. Next we will provide an outline of the theoretical framework of Metacognitive Therapy and then describe two brief case studies illustrating the application of Metacognitive Therapy to the treatment of alcohol abuse and dependence. From this discussion we propose that the combination of Motivational Interviewing and Metacognitive Therapy is a promising new approach that can provide great assistance for the treatment of alcohol abuse or dependence.

Does legal heritage affect obesity? The channel of motor vehicle dependence

We find a robust relationship between motor vehicle ownership, its interaction with legal heritage and obesity in OECD countries. Our estimates indicate that an increase of 100 motor vehicles per thousand residents is associated with about a 6% point increase in obesity in common law countries, whereas it has a much smaller or insignificant impact in civil law countries. These relations hold whether we examine trend data and simple correlations, or conduct cross-section or panel data regression analysis. Our results suggest that obesity rises with motor vehicle ownership in countries following a common law tradition where individual liberty is encouraged, whereas the link is small or statistically non-existent in countries with a civil law background where the rights of the individual tend to be circumscribed by the power of the state.

Determinants of place identity and dependence : the case of international tourism in Tanzania

This research examines the effects of expectation (perceived attractiveness) on satisfaction, place identity, and place dependence. Place identity and place dependence are viewed as relational components of choice and relate to deeper needs. This study proposes that these two relational components depend on transactional expectations, which are emergent and determined by past experiences and visitor goals. In a theoretically elaborated and tested Structural Equation Model (SEM) this study assumes that these relationships vary according to intentions to return. The study addresses the conditions under which loyalty intentions influence the deeper place attachments (place identity and place dependence) that visitors associate with attractive cultural and natural destinations. The model is tested on a sample of 504 international tourists visiting Tanzania during fall 2010, and explains 59% of variance in the predicted dependent variables. The results are linked to a discussion on loyalty programs.

Integrating agency and resource dependence theory : firm profitability, industry regulation, and board task performance

Boards of directors are key governancemechanisms in organizations and fulfill twomain tasks:monitoringmanagers and firm performance, and providing advice and access to resources. In spite of a wealth of researchmuch remains unknown about how boards attend to the two tasks. This study investigates whether organizational (firm profitability) and environmental factors (industry regulation) affect board task performance. The data combine CEOs' responses to a questionnaire, and archival data from a sample of large Italian firms. Findings show that past firm performance is negatively associatedwith board monitoring and advice tasks; greater industry regulation enhances perceived board task performance; board monitoring and advice tasks tend to reinforce each other, despite their theoretical and practical distinction.