Continuous intravenous infusion of glucose induces endogenous hyperinsulinaemia and lamellar histopathology in Standardbred horses

Endocrinopathic laminitis is frequently associated with hyperinsulinaemia but the role of glucose in the pathogenesis of the disease has not been fully investigated. This study aimed to determine the endogenous insulin response to a quantity of glucose equivalent to that administered during a laminitis-inducing, euglycaemic, hyperinsulinaemic clamp, over 48. h in insulin-sensitive Standardbred racehorses. In addition, the study investigated whether glucose infusion, in the absence of exogenous insulin administration, would result in the development of clinical and histopathological evidence of laminitis. Glucose (50% dextrose) was infused intravenously at a rate of 0.68 mL/kg/h for 48. h in treated horses (n = 4) and control horses (n = 3) received a balanced electrolyte solution (0.68 mL/kg/h). Lamellar histology was examined at the conclusion of the experiment. Horses in the treatment group were insulin sensitive (M value 0.039 ± 0.0012. mmol/kg/min and M-to-I ratio (100×) 0.014 ± 0.002) as determined by an approximated hyperglycaemic clamp. Treated horses developed glycosuria, hyperglycaemia (10.7 ± 0.78. mmol/L) and hyperinsulinaemia (208 ± 26.1. μIU/mL), whereas control horses did not. None of the horses became lame as a consequence of the experiment but all of the treated horses developed histopathological evidence of laminitis in at least one foot. Combined with earlier studies, the results showed that laminitis may be induced by either insulin alone or a combination of insulin and glucose, but that it is unlikely to be due to a glucose overload mechanism. Based on the histopathological data, the potential threshold for insulin toxicity (i.e. laminitis) in horses may be at or below a serum concentration of ∼200. μIU/mL.

Towards persistent localization and mapping with a continuous appearance-based topology

Appearance-based localization can provide loop closure detection at vast scales regardless of accumulated metric error. However, the computation time and memory requirements of current appearance-based methods scale not only with the size of the environment but also with the operation time of the platform. Additionally, repeated visits to locations will develop multiple competing representations, which will reduce recall performance over time. These properties impose severe restrictions on long-term autonomy for mobile robots, as loop closure performance will inevitably degrade with increased operation time. In this paper we present a graphical extension to CAT-SLAM, a particle filter-based algorithm for appearance-based localization and mapping, to provide constant computation and memory requirements over time and minimal degradation of recall performance during repeated visits to locations. We demonstrate loop closure detection in a large urban environment with capped computation time and memory requirements and performance exceeding previous appearance-based methods by a factor of 2. We discuss the limitations of the algorithm with respect to environment size, appearance change over time and applications in topological planning and navigation for long-term robot operation.

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.

Validation of a new hand-held electronic data capture method for continuous monitoring of subjective appetite sensations

Background When large scale trials are investigating the effects of interventions on appetite, it is paramount to efficiently monitor large amounts of human data. The original hand-held Electronic Appetite Ratings System (EARS) was designed to facilitate the administering and data management of visual analogue scales (VAS) of subjective appetite sensations. The purpose of this study was to validate a novel hand-held method (EARS II (HP® iPAQ)) against the standard Pen and Paper (P&P) method and the previously validated EARS. Methods Twelve participants (5 male, 7 female, aged 18-40) were involved in a fully repeated measures design. Participants were randomly assigned in a crossover design, to either high fat (>48% fat) or low fat (<28% fat) meal days, one week apart and completed ratings using the three data capture methods ordered according to Latin Square. The first set of appetite sensations was completed in a fasted state, immediately before a fixed breakfast. Thereafter, appetite sensations were completed every thirty minutes for 4h. An ad libitum lunch was provided immediately before completing a final set of appetite sensations. Results Repeated measures ANOVAs were conducted for ratings of hunger, fullness and desire to eat. There were no significant differences between P&P compared with either EARS or EARS II (p > 0.05). Correlation coefficients between P&P and EARS II, controlling for age and gender, were performed on Area Under the Curve ratings. R2 for Hunger (0.89), Fullness (0.96) and Desire to Eat (0.95) were statistically significant (p < 0.05). Conclusions EARS II was sensitive to the impact of a meal and recovery of appetite during the postprandial period and is therefore an effective device for monitoring appetite sensations. This study provides evidence and support for further validation of the novel EARS II method for monitoring appetite sensations during large scale studies. The added versatility means that future uses of the system provides the potential to monitor a range of other behavioural and physiological measures often important in clinical and free living trials.

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.

A sequential Monte Carlo approach to the sequential design for discriminating between rival continuous data models

Here we present a sequential Monte Carlo approach to Bayesian sequential design for the incorporation of model uncertainty. The methodology is demonstrated through the development and implementation of two model discrimination utilities; mutual information and total separation, but it can also be applied more generally if one has different experimental aims. A sequential Monte Carlo algorithm is run for each rival model (in parallel), and provides a convenient estimate of the marginal likelihood (of each model) given the data, which can be used for model comparison and in the evaluation of utility functions. A major benefit of this approach is that it requires very little problem specific tuning and is also computationally efficient when compared to full Markov chain Monte Carlo approaches. This research is motivated by applications in drug development and chemical engineering.

Discretionary use of open briefings in the Australian continuous reporting environment

The Australian Securities Exchange (ASX) listing rule 3.1 requires listed companies to immediately disclose price sensitive information to the market via the ASX’s Company Announcements Platform (CAP) prior to release through other disclosure channels. Since 1999, to improve the communication process, the ASX has permitted third-party mediation in the disclosure process that leads to the release of an Open Briefing (OB) through CAP. An OB is an interview between senior executives of the firm and an Open Briefing analyst employed by Orient Capital Pty Ltd (broaching topics such as current profit and outlook). Motivated by an absence of research on factors that influence firms to use OBs as a discretionary disclosure channel, this study examines (1) Why do firms choose to release information to the market via OBs?, (2) What are the firm characteristics that explain the discretionary use of OBs as a disclosure channel?, and (3) What are the disclosure attributes that influence firms’ decisions to regularly use OBs as a disclosure channel? Based on agency and information economics theories, a theoretical framework is developed to address research questions. This theoretical framework comprises disclosure environments such as firm characteristics and external factors, disclosure attributes and disclosure consequences. In order to address the first research question, the study investigates (i) the purpose of using OBs, (2) whether firms use OBs to provide information relating to previous public announcements, and (3) whether firms use OBs to provide routine or non-routine disclosures. In relation to the second and third research questions, hypotheses are developed to test factors expected to explain the discretionary use of OBs and firms’ decisions to regularly use OBs, and to explore the factors influencing the nature of OB disclosure. Content analysis and logistic regression models are used to investigate the research questions and test the hypotheses. Data are drawn from a hand-collected population of 1863 OB announcements issued by 239 listed firms between 2000 and 2010. The results show that types of information disclosed via an OB announcement are principally on matters relating to corporate strategies and performance and outlook. Most OB announcements are linked with a previous related announcement, with the lag between announcements significantly longer for loss-making firms than profitmaking firms. The main results show that firms which tend to be larger, have an analyst following, and have higher growth opportunities, are more likely to release OBs. Further, older firms and firms that release OB announcements containing good news, historical information and less complex information tend to be regular OB users. Lastly, firms more likely to disclose strategic information via OBs tend to operate in industries facing greater uncertainty, do not have analysts following, and have higher growth opportunities are less likely to disclose good news, historical information and complex information via OBs. This study is expected to contribute to disclosure literature in terms of disclosure attributes and firm characteristics that influence behaviour in this unique (OB) disclosure channel. With regard to practical significance, regulators can gain an understanding of how OBs are disclosed which can assist them in monitoring the use of OBs and improving the effectiveness of communications with stakeholders. In addition, investors can have a better comprehension of information contained in OB announcements, which may in turn better facilitate their investment decisions.

An examination of keystroke dynamics for continuous user authentication

Most current computer systems authorise the user at the start of a session and do not detect whether the current user is still the initial authorised user, a substitute user, or an intruder pretending to be a valid user. Therefore, a system that continuously checks the identity of the user throughout the session is necessary without being intrusive to end-user and/or effectively doing this. Such a system is called a continuous authentication system (CAS). Researchers have applied several approaches for CAS and most of these techniques are based on biometrics. These continuous biometric authentication systems (CBAS) are supplied by user traits and characteristics. One of the main types of biometric is keystroke dynamics which has been widely tried and accepted for providing continuous user authentication. Keystroke dynamics is appealing for many reasons. First, it is less obtrusive, since users will be typing on the computer keyboard anyway. Second, it does not require extra hardware. Finally, keystroke dynamics will be available after the authentication step at the start of the computer session. Currently, there is insufficient research in the CBAS with keystroke dynamics field. To date, most of the existing schemes ignore the continuous authentication scenarios which might affect their practicality in different real world applications. Also, the contemporary CBAS with keystroke dynamics approaches use characters sequences as features that are representative of user typing behavior but their selected features criteria do not guarantee features with strong statistical significance which may cause less accurate statistical user-representation. Furthermore, their selected features do not inherently incorporate user typing behavior. Finally, the existing CBAS that are based on keystroke dynamics are typically dependent on pre-defined user-typing models for continuous authentication. This dependency restricts the systems to authenticate only known users whose typing samples are modelled. This research addresses the previous limitations associated with the existing CBAS schemes by developing a generic model to better identify and understand the characteristics and requirements of each type of CBAS and continuous authentication scenario. Also, the research proposes four statistical-based feature selection techniques that have highest statistical significance and encompasses different user typing behaviors which represent user typing patterns effectively. Finally, the research proposes the user-independent threshold approach that is able to authenticate a user accurately without needing any predefined user typing model a-priori. Also, we enhance the technique to detect the impostor or intruder who may take over during the entire computer session.

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.

Use of the piggyBac transposon to create HIV-1 gag transgenic insect cell lines for continuous VLP production

Background Insect baculovirus-produced Human immunodeficiency virus type 1 (HIV-1) Gag virus-like-particles (VLPs) stimulate good humoral and cell-mediated immune responses in animals and are thought to be suitable as a vaccine candidate. Drawbacks to this production system include contamination of VLP preparations with baculovirus and the necessity for routine maintenance of infectious baculovirus stock. We used piggyBac transposition as a novel method to create transgenic insect cell lines for continuous VLP production as an alternative to the baculovirus system. Results Transgenic cell lines maintained stable gag transgene integration and expression up to 100 cell passages, and although the level of VLPs produced was low compared to baculovirus-produced VLPs, they appeared similar in size and morphology to baculovirus-expressed VLPs. In a murine immunogenicity study, whereas baculovirus-produced VLPs elicited good CD4 immune responses in mice when used to boost a prime with a DNA vaccine, no boost response was elicited by transgenically produced VLPs. Conclusion Transgenic insect cells are stable and can produce HIV Pr55 Gag VLPs for over 100 passages: this novel result may simplify strategies aimed at making protein subunit vaccines for HIV. Immunogenicity of the Gag VLPs in mice was less than that of baculovirus-produced VLPs, which may be due to lack of baculovirus glycoprotein incorporation in the transgenic cell VLPs. Improved yield and immunogenicity of transgenic cell-produced VLPs may be achieved with the addition of further genetic elements into the piggyBac integron.

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.

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.