Cabergoline Decreases Alcohol Drinking and Seeking Behaviors Via Glial Cell Line-Derived Neurotrophic Factor

Background: Cabergoline is an ergotamine derivative that increases the expression of glial cell line-derived neurotrophic factor (GDNF) in vitro. We recently showed that GDNF in the ventral tegmental area (VTA) reduces the motivation to consume alcohol. We therefore set out to determine whether cabergoline administration decreases alcohol-drinking and -seeking behaviors via GDNF. Methods: Reverse transcription polymerase chain reaction (RT-PCR) and Enzyme-Linked ImmunoSorbent Assay (ELISA) were used to measure GDNF levels. Western blot analysis was used for phosphorylation experiments. Operant self-administration in rats and a two-bottle choice procedure in mice were used to assess alcohol-drinking behaviors. Instrumental performance tested during extinction was used to measure alcohol-seeking behavior. The [35S]GTPγS binding assay was used to assess the expression and function of the dopamine D2 receptor (D2R). Results: We found that treatment of the dopaminergic-like cell line SH-SY5Y with cabergoline and systemic administration of cabergoline in rats resulted in an increase in GDNF level and in the activation of the GDNF pathway. Cabergoline treatment decreased alcohol-drinking and -seeking behaviors including relapse, and its action to reduce alcohol consumption was localized to the VTA. Finally, the increase in GDNF expression and the decrease in alcohol consumption by cabergoline were abolished in GDNF heterozygous knockout mice. Conclusions: Together, these findings suggest that cabergoline-mediated upregulation of the GDNF pathway attenuates alcohol-drinking behaviors and relapse. Alcohol abuse and addiction are devastating and costly problems worldwide. This study puts forward the possibility that cabergoline might be an effective treatment for these disorders. © 2009 Society of Biological Psychiatry.

Representational change and strategy use in children's number line estimation during the first years of primary school

Background: The objective of this study was to scrutinize number line estimation behaviors displayed by children in mathematics classrooms during the first three years of schooling. We extend existing research by not only mapping potential logarithmic-linear shifts but also provide a new perspective by studying in detail the estimation strategies of individual target digits within a number range familiar to children. Methods: Typically developing children (n = 67) from Years 1 – 3 completed a number-to-position numerical estimation task (0-20 number line). Estimation behaviors were first analyzed via logarithmic and linear regression modeling. Subsequently, using an analysis of variance we compared the estimation accuracy of each digit, thus identifying target digits that were estimated with the assistance of arithmetic strategy. Results: Our results further confirm a developmental logarithmic-linear shift when utilizing regression modeling; however, uniquely we have identified that children employ variable strategies when completing numerical estimation, with levels of strategy advancing with development. Conclusion: In terms of the existing cognitive research, this strategy factor highlights the limitations of any regression modeling approach, or alternatively, it could underpin the developmental time course of the logarithmic-linear shift. Future studies need to systematically investigate this relationship and also consider the implications for educational practice.

Drawing the line : the legal status and treatment of the 17-year-old accused in Queensland

Seventeen year olds who come into contact with the police in Queensland are classified as adults and are not afforded the protections available under the Youth Justice Act 1992 (Qld) (YJA). As with any other adult, their offences are dealt with under a raft of legislative provisions including the Criminal Code 1889 (Qld) (the Code), the Police Powers and Responsibilities Act 2000 (Qld) (PPRA) and the Penalties and Sentences Act 1992 (Qld) (PSA). This article argues that this situation is unfair and contravenes international human rights agreements which Australia has ratified, in particular the United Nations Convention on the Rights of the Child (CROC). Article 1 of that Convention defines a child as a person under the age of 18. The youth offences legislation in Queensland only applies to those who have not yet turned 17. This article examines the effects of this anomaly in Queensland, focusing in particular on the pre-adjudication treatment of ‘17 year old adults’.

Effects of surgical joint destabilization on load sharing between ligamentous structures in the thoracic spine : a finite element investigation

Background: In vitro investigations have demonstrated the importance of the ribcage in stabilising the thoracic spine. Surgical alterations of the ribcage may change load-sharing patterns in the thoracic spine. Computer models are used in this study to explore the effect of surgical disruption of the rib-vertebrae connections on ligament load-sharing in the thoracic spine. Methods: A finite element model of a T7-8 motion segment, including the T8 rib, was developed using CT-derived spinal anatomy for the Visible Woman. Both the intact motion segment and the motion segment with four successive stages of destabilization (discectomy and removal of right costovertebral joint, right costotransverse joint and left costovertebral joint) were analysed for a 2000Nmm moment in flexion/extension, lateral bending and axial rotation. Joint rotational moments were compared with existing in vitro data and a detailed investigation of the load sharing between the posterior ligaments carried out. Findings: The simulated motion segment demonstrated acceptable agreement with in vitro data at all stages of destabilization. Under lateral bending and axial rotation, the costovertebral joints were of critical importance in resisting applied moments. In comparison to the intact joint, anterior destabilization increases the total moment contributed by the posterior ligaments. Interpretation: Surgical removal of the costovertebral joints may lead to excessive rotational motion in a spinal joint, increasing the risk of overload and damage to the remaining ligaments. The findings of this study are particularly relevant for surgical procedures involving rib head resection, such as some techniques for scoliosis deformity correction.

The effect of emotional and attentional load on attentional startle modulation

The interactive effects of emotion and attention on attentional startle modulation were investigated in two experiments. Participants performed a discrimination and counting task with two visual stimuli during which acoustic eyeblink startle-eliciting probes were presented at long lead intervals. In Experiment 1, this task was combined with aversive Pavlovian conditioning. In Group Attend CS+, the attended stimulus was followed by an aversive unconditional stimulus (US) and the ignored stimulus was presented alone whereas the ignored stimulus was paired with the US in Group Attend CS−. In Experiment 2, a non-aversive reaction time task US replaced the aversive US. Regardless of the conditioning manipulation and consistent with a modality non-specific account of attentional startle modulation, startle magnitude was larger during attended than ignored stimuli in both experiments. Blink latency shortening was differentially affected by the conditioning manipulations suggesting additive effects of conditioning and discrimination and counting task on blink startle.

Development of a high-speed sensing and detection system for automatic removal of packages with leaky seals from a high-speed food processing and packaging line

Contamination of packaged foods due to micro-organisms entering through air leaks can cause serious public health issues and cost companies large amounts of money due to product recalls, consumer impact and subsequent loss of market share. The main source of contamination is leaks in packaging which allow air, moisture and microorganisms to enter the package. In the food processing and packaging industry worldwide, there is an increasing demand for cost effective state of the art inspection technologies that are capable of reliably detecting leaky seals and delivering products at six-sigma. The new technology will develop non-destructive testing technology using digital imaging and sensing combined with a differential vacuum technique to assess seal integrity of food packages on a high-speed production line. The cost of leaky packages in Australian food industries is estimated close to AUD $35 Million per year. Contamination of packaged foods due to micro-organisms entering through air leaks can cause serious public health issues and cost companies large sums of money due to product recalls, compensation claims and loss of market share. The main source of contamination is leaks in packaging which allow air, moisture and micro-organisms to enter the package. Flexible plastic packages are widely used, and are the least expensive form of retaining the quality of the product. These packets can be used to seal, and therefore maximise, the shelf life of both dry and moist products. The seals of food packages need to be airtight so that the food content is not contaminated due to contact with microorganisms that enter as a result of air leakage. Airtight seals also extend the shelf life of packaged foods, and manufacturers attempt to prevent food products with leaky seals being sold to consumers. There are many current NDT (non-destructive testing) methods of testing the seal of flexible packages best suited to random sampling, and for laboratory purposes. The three most commonly used methods are vacuum/pressure decay, bubble test, and helium leak detection. Although these methods can detect very fine leaks, they are limited by their high processing time and are not viable in a production line. Two nondestructive in-line packaging inspection machines are currently available and are discussed in the literature review. The detailed design and development of the High-Speed Sensing and Detection System (HSDS) is the fundamental requirement of this project and the future prototype and production unit. Successful laboratory testing was completed and a methodical design procedure was needed for a successful concept. The Mechanical tests confirmed the vacuum hypothesis and seal integrity with good consistent results. Electrically, the testing also provided solid results to enable the researcher to move the project forward with a certain amount of confidence. The laboratory design testing allowed the researcher to confirm theoretical assumptions before moving into the detailed design phase. Discussion on the development of the alternative concepts in both mechanical and electrical disciplines enables the researcher to make an informed decision. Each major mechanical and electrical component is detailed through the research and design process. The design procedure methodically works through the various major functions both from a mechanical and electrical perspective. It opens up alternative ideas for the major components that although are sometimes not practical in this application, show that the researcher has exhausted all engineering and functionality thoughts. Further concepts were then designed and developed for the entire HSDS unit based on previous practice and theory. In the future, it would be envisaged that both the Prototype and Production version of the HSDS would utilise standard industry available components, manufactured and distributed locally. Future research and testing of the prototype unit could result in a successful trial unit being incorporated in a working food processing production environment. Recommendations and future works are discussed, along with options in other food processing and packaging disciplines, and other areas in the non-food processing industry.

Numerical modelling of non-load bearing light gauge cold-formed steel frame walls under fire conditions

Recently an innovative composite panel system was developed, where a thin insulation layer was used externally between two plasterboards to improve the fire performance of light gauge cold-formed steel frame walls. In this research, finite-element thermal models of both the traditional light gauge cold-formed steel frame wall panels with cavity insulation and the new light gauge cold-formed steel frame composite wall panels were developed to simulate their thermal behaviour under standard and realistic fire conditions. Suitable apparent thermal properties of gypsum plasterboard, insulation materials and steel were proposed and used. The developed models were then validated by comparing their results with available fire test results. This article presents the details of the developed finite-element models of small-scale non-load-bearing light gauge cold-formed steel frame wall panels and the results of the thermal analysis. It has been shown that accurate finite-element models can be used to simulate the thermal behaviour of small-scale light gauge cold-formed steel frame walls with varying configurations of insulations and plasterboards. The numerical results show that the use of cavity insulation was detrimental to the fire rating of light gauge cold-formed steel frame walls, while the use of external insulation offered superior thermal protection to them. The effects of real fire conditions are also presented.

Termination fees in a ‘bright line’ jurisdiction

We seek to statistically inform the debate regarding the Australian Takeovers Panel’s ‘bright line’ policy towards break fees. Based on 313 takeovers from 2002 to 2006, 85 involving break fees, we find post-bid competition to be unrelated to break fee usage and inversely related to bid success. We also find that break fee usage has a detrimental effect on shareholder wealth as measured by both the final bid premium and abnormal returns. Therefore, although break fees appear to be neither anticompetitive nor coercive within the Australian context, they do appear to have had a deleterious effect on shareholder wealth.

On-line film distribution : Its history and global complexion

‘Nobody knows anything’, said William Goldman of studio filmmaking. The rule is ever more apt as we survey the radical changes that digital distribution, along with the digitisation of production and exhibition, is wreaking on global film circulation. Digital Disruption: Cinema Moves On-line helps to make sense of what has happened in the short but turbulent history of on-line distribution. It provides a realistic assessment of the genuine and not-so-promising methods that have been tried to address the disruptions that moving from ‘analogue dollars’ to ‘digital cents’ has provoked in the film industry. Paying close attention to how the Majors have dealt with the challenges – often unsuccessfully – it focuses as much attention on innovations and practices outside the mainstream. Throughout, it is alive to, and showcases, important entrepreneurial innovations such as Mubi, Jaman, Withoutabox and IMDb. Written by leading academic commentators that have followed the fortunes of world cinema closely and passionately, as well as experienced hands close to the fluctuating fortunes of the industry, Digital Disruption: Cinema Moves On-line is an indispensable guide to great changes in film and its audiences.

The effect of exercise intensity on fat oxidation and non-exercise activity thermogenesis in overweight/obese men

It is frequently reported that the actual weight loss achieved through exercise interventions is less than theoretically expected. Amongst other compensatory adjustments that accompany exercise training (e.g., increases in resting metabolic rate and energy intake), a possible cause of the less than expected weight loss is a failure to produce a marked increase in total daily energy expenditure due to a compensatory reduction in non-exercise activity thermogenesis (NEAT). Therefore, there is a need to understand how behaviour is modified in response to exercise interventions. The proposed benefits of exercise training are numerous, including changes to fat oxidation. Given that a diminished capacity to oxidise fat could be a factor in the aetiology of obesity, an exercise training intensity that optimises fat oxidation in overweight/obese individuals would improve impaired fat oxidation, and potentially reduce health risks that are associated with obesity. To improve our understanding of the effectiveness of exercise for weight management, it is important to ensure exercise intensity is appropriately prescribed, and to identify and monitor potential compensatory behavioural changes consequent to exercise training. In line with the gaps in the literature, three studies were performed. The aim of Study 1 was to determine the effect of acute bouts of moderate- and high-intensity walking exercise on NEAT in overweight and obese men. Sixteen participants performed a single bout of either moderate-intensity walking exercise (MIE) or high-intensity walking exercise (HIE) on two separate occasions. The MIE consisted of walking for 60-min on a motorised treadmill at 6 km.h-1. The 60-min HIE session consisted of walking in 5-min intervals at 6 km.h-1 and 10% grade followed by 5-min at 0% grade. NEAT was assessed by accelerometer three days before, on the day of, and three days after the exercise sessions. There was no significant difference in NEAT vector magnitude (counts.min-1) between the pre-exercise period (days 1-3) and the exercise day (day 4) for either protocol. In addition, there was no change in NEAT during the three days following the MIE session, however NEAT increased by 16% on day 7 (post-exercise) compared with the exercise day (P = 0.32). During the post-exercise period following the HIE session, NEAT was increased by 25% on day 7 compared with the exercise day (P = 0.08), and by 30-33% compared with the pre-exercise period (day 1, day 2 and day 3); P = 0.03, 0.03, 0.02, respectively. To conclude, a single bout of either MIE or HIE did not alter NEAT on the exercise day or on the first two days following the exercise session. However, extending the monitoring of NEAT allowed the detection of a 48 hour delay in increased NEAT after performing HIE. A longer-term intervention is needed to determine the effect of accumulated exercise sessions over a week on NEAT. In Study 2, there were two primary aims. The first aim was to test the reliability of a discontinuous incremental exercise protocol (DISCON-FATmax) to identify the workload at which fat oxidation is maximised (FATmax). Ten overweight and obese sedentary male men (mean BMI of 29.5 ¡Ó 4.5 kg/m2 and mean age of 28.0 ¡Ó 5.3 y) participated in this study and performed two identical DISCON-FATmax tests one week apart. Each test consisted of alternate 4-min exercise and 2-min rest intervals on a cycle ergometer. The starting work load of 28 W was increased every 4-min using 14 W increments followed by 2-min rest intervals. When the respiratory exchange ratio was consistently >1.0, the workload was increased by 14 W every 2-min until volitional exhaustion. Fat oxidation was measured by indirect calorimetry. The mean FATmax, ƒtV O2peak, %ƒtV O2peak and %Wmax at which FATmax occurred during the two tests were 0.23 ¡Ó 0.09 and 0.18 ¡Ó 0.08 (g.min-1); 29.7 ¡Ó 7.8 and 28.3 ¡Ó 7.5 (ml.kg-1.min-1); 42.3 ¡Ó 7.2 and 42.6 ¡Ó 10.2 (%ƒtV O2max) and 36.4 ¡Ó 8.5 and 35.4 ¡Ó 10.9 (%), respectively. A paired-samples T-test revealed a significant difference in FATmax (g.min-1) between the tests (t = 2.65, P = 0.03). The mean difference in FATmax was 0.05 (g.min-1) with the 95% confidence interval ranging from 0.01 to 0.18. Paired-samples T-test, however, revealed no significant difference in the workloads (i.e. W) between the tests, t (9) = 0.70, P = 0.4. The intra-class correlation coefficient for FATmax (g.min-1) between the tests was 0.84 (95% confidence interval: 0.36-0.96, P < 0.01). However, Bland-Altman analysis revealed a large disagreement in FATmax (g.min-1) related to W between the two tests; 11 ¡Ó 14 (W) (4.1 ¡Ó 5.3 ƒtV O2peak (%)).These data demonstrate two important phenomena associated with exercise-induced substrate oxidation; firstly, that maximal fat oxidation derived from a discontinuous FATmax protocol differed statistically between repeated tests, and secondly, there was large variability in the workload corresponding with FATmax. The second aim of Study 2 was to test the validity of a DISCON-FATmax protocol by comparing maximal fat oxidation (g.min-1) determined by DISCON-FATmax with fat oxidation (g.min-1) during a continuous exercise protocol using a constant load (CONEX). Ten overweight and obese sedentary males (BMI = 29.5 ¡Ó 4.5 kg/m2; age = 28.0 ¡Ó 4.5 y) with a ƒtV O2max of 29.1 ¡Ó 7.5 ml.kg-1.min-1 performed a DISCON-FATmax test consisting of alternate 4-min exercise and 2-min rest intervals on a cycle ergometer. The 1-h CONEX protocol used the workload from the DISCON-FATmax to determine FATmax. The mean FATmax, ƒtV O2max, %ƒtV O2max and workload at which FATmax occurred during the DISCON-FATmax were 0.23 ¡Ó 0.09 (g.min-1); 29.1 ¡Ó 7.5 (ml.kg-1.min-1); 43.8 ¡Ó 7.3 (%ƒtV O2max) and 58.8 ¡Ó 19.6 (W), respectively. The mean fat oxidation during the 1-h CONEX protocol was 0.19 ¡Ó 0.07 (g.min-1). A paired-samples T-test revealed no significant difference in fat oxidation (g.min-1) between DISCON-FATmax and CONEX, t (9) = 1.85, P = 0.097 (two-tailed). There was also no significant correlation in fat oxidation between the DISCON-FATmax and CONEX (R=0.51, P = 0.14). Bland- Altman analysis revealed a large disagreement in fat oxidation between the DISCONFATmax and CONEX; the upper limit of agreement was 0.13 (g.min-1) and the lower limit of agreement was ¡V0.03 (g.min-1). These data suggest that the CONEX and DISCONFATmax protocols did not elicit different rates of fat oxidation (g.min-1). However, the individual variability in fat oxidation was large, particularly in the DISCON-FATmax test. Further research is needed to ascertain the validity of graded exercise tests for predicting fat oxidation during constant load exercise sessions. The aim of Study 3 was to compare the impact of two different intensities of four weeks of exercise training on fat oxidation, NEAT, and appetite in overweight and obese men. Using a cross-over design 11 participants (BMI = 29 ¡Ó 4 kg/m2; age = 27 ¡Ó 4 y) participated in a training study and were randomly assigned initially to: [1] a lowintensity (45%ƒtV O2max) exercise (LIT) or [2] a high-intensity interval (alternate 30 s at 90%ƒtV O2max followed by 30 s rest) exercise (HIIT) 40-min duration, three times a week. Participants completed four weeks of supervised training and between cross-over had a two week washout period. At baseline and the end of each exercise intervention,ƒtV O2max, fat oxidation, and NEAT were measured. Fat oxidation was determined during a standard 30-min continuous exercise bout at 45%ƒtV O2max. During the steady state exercise expired gases were measured intermittently for 5-min periods and HR was monitored continuously. In each training period, NEAT was measured for seven consecutive days using an accelerometer (RT3) the week before, at week 3 and the week after training. Subjective appetite sensations and food preferences were measured immediately before and after the first exercise session every week for four weeks during both LIT and HIIT. The mean fat oxidation rate during the standard continuous exercise bout at baseline for both LIT and HIIT was 0.14 ¡Ó 0.08 (g.min-1). After four weeks of exercise training, the mean fat oxidation was 0.178 ¡Ó 0.04 and 0.183 ¡Ó 0.04 g.min-1 for LIT and HIIT, respectively. The mean NEAT (counts.min-1) was 45 ¡Ó 18 at baseline, 55 ¡Ó 22 and 44 ¡Ó 16 during training, and 51 ¡Ó 14 and 50 ¡Ó 21 after training for LIT and HIIT, respectively. There was no significant difference in fat oxidation between LIT and HIIT. Moreover, although not statistically significant, there was some evidence to suggest that LIT and HIIT tend to increase fat oxidation during exercise at 45% ƒtV O2max (P = 0.14 and 0.08, respectively). The order of training treatment did not significantly influence changes in fat oxidation, NEAT, and appetite. NEAT (counts.min-1) was not significantly different in the week following training for either LIT or HIIT. Although not statistically significant (P = 0.08), NEAT was 20% lower during week 3 of exercise training in HIIT compared with LIT. Examination of appetite sensations revealed differences in the intensity of hunger, with higher ratings after LIT compared with HIIT. No differences were found in preferences for high-fat sweet foods between LIT and HIIT. In conclusion, the results of this thesis suggest that while fat oxidation during steady state exercise was not affected by the level of exercise intensity, there is strong evidence to suggest that intense exercise could have a debilitative effect on NEAT.

Human herpesvirus 8 load and progression of AIDS-related Kaposi sarcoma lesions

Introduction—Human herpesvirus 8 (HHV8) is necessary for Kaposi sarcoma (KS) to develop, but whether peripheral blood viral load is a marker of KS burden (total number of KS lesions), KS progression (the rate of eruption of new KS lesions), or both is unclear. We investigated these relationships in persons with AIDS. Methods—Newly diagnosed patients with AIDS-related KS attending Mulago Hospital, in Kampala, Uganda, were assessed for KS burden and progression by questionnaire and medical examination. Venous blood samples were taken for HHV8 load measurements by PCR. Associations were examined with odds ratio (OR) and 95% confidence intervals (CI) from logistic regression models and with t-tests. Results—Among 74 patients (59% men), median age was 34.5 years (interquartile range [IQR], 28.5-41). HHV8 DNA was detected in 93% and quantified in 77% patients. Median virus load was 3.8 logs10/106 peripheral blood cells (IQR 3.4-5.0) and was higher in men than women (4.4 vs. 3.8 logs; p=0.04), in patients with faster (>20 lesions per year) than slower rate of KS lesion eruption (4.5 vs. 3.6 logs; p<0.001), and higher, but not significantly, among patients with more (>median [20] KS lesions) than fewer KS lesions (4.4 vs. 4.0 logs; p=0.16). HHV8 load was unrelated to CD4 lymphocyte count (p=0.23). Conclusions—We show significant association of HHV8 load in peripheral blood with rate of eruption of KS lesions, but not with total lesion count. Our results suggest that viral load increases concurrently with development of new KS lesions.

ACE research vignette 014 : how does networking contribute to the bottom line? - The value of purpose-driven networking

This series of research vignettes is aimed at sharing current and interesting research findings from our team and other international researchers. In this vignette, Dr Martie-Louise Verreynne from the University of Queensland Business School summaries the findings from a paper written in conjunction with Sarel Gronum and Tim Kastelle from the UQ Business School that examined if networking really contributes to small firms' bottom line. Their findings show that unless networks are used for productive means, efforts to cultivate and maintain them may be wasteful.

Emergency medicine in China

With the world’s largest population of 1.3 billion, China is a rapidly developing country. In line with this development, China’s enormous health system is experiencing an unprecedented series of reforms. According to a recent official government report, China has 300, 000 health organizations, which include 60, 000 hospitals and a total number of 3.07 million beds (China NBoSoP 2006). To provide health services for the national population, as well as the substantial number of visitors, China has 1.93 million doctors and 1.34 million registered nurses (China NBoSoP 2006). From 1984 to 2004, the number of inpatients grew from about 25 to 50 million, with outpatient figures increasing from 1.1 to 1.3 billion (China MoH 2006). The scale of the health system is likely bigger than in any other countries in the world, but the quality of medical services is still among the levels of developing countries. In 2005, approximately 3.8% of inpatients (about 1.5 million)(China NBoSoP 2006) were admitted because of injury and poisoning, which created significant load for the acute health system. These increased figures are at least partly because of the development of the health system and technological health-care advances but, even with such advances, this rapid change in emergency health-care demand has created a very significant burden on existing systems...

An example of cognitive obstacles in advanced integration: the case of scalar line integrals

Cognitive obstacles that arise in the teaching and learning of scalar line integrals, derived from cognitive aids provided to students when first learning about integration of single variable functions are described. A discussion of how and why the obstacles cause students problems is presented and possible strategies to overcome the obstacles are outlined.

Induction motor load impact on power system eigenvalue sensitivity analysis

Load modelling plays an important role in power system dynamic stability assessment. One of the widely used methods in assessing load model impact on system dynamic response is parametric sensitivity analysis. A composite load model-based load sensitivity analysis framework is proposed. It enables comprehensive investigation into load modelling impacts on system stability considering the dynamic interactions between load and system dynamics. The effect of the location of individual as well as patches of composite loads in the vicinity on the sensitivity of the oscillatory modes is investigated. The impact of load composition on the overall sensitivity of the load is also investigated.