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.

Economic growth and suicide rate changes : a case in China from 1982 to 2005

It is to estimate the trend of suicide rate changes during the past three decades in China and try to identify its social and economic correlates. Official data of suicide rates and economic indexes during 1982–2005 from Shandong Province of China were analyzed. The suicide data were categorized for the rural / urban location and gender, and the economic indexes include GDP, GDP per capita, rural income, and urban income, all adjusted for inflation. We found a significant increase of economic development and decrease of suicide rates over the past decades under study. The suicide rate decrease is correlated with the tremendous growth of economy. The unusual decrease of Chinese suicide rates in the past decades is accounted for within the Chinese cultural contexts and maybe by the Strain Theory of Suicide.

Combined time- and space-resolved Raman spectrometer for the non-invasive depth profiling of chemical hazards

A time-resolved inverse spatially offset Raman spectrometer was constructed for depth profiling of Raman-active substances under both the lab and the field environments. The system operating principles and performance are discussed along with its advantages relative to traditional continuous wave spatially offset Raman spectrometer. The developed spectrometer uses a combination of space- and time-resolved detection in order to obtain high-quality Raman spectra from substances hidden behind coloured opaque surface layers, such as plastic and garments, with a single measurement. The time-gated spatially offset Raman spectrometer was successfully used to detect concealed explosives and drug precursors under incandescent and fluorescent background light as well as under daylight. The average screening time was 50 s per measurement. The excitation energy requirements were relatively low (20 mW) which makes the probe safe for screening hazardous substances. The unit has been designed with nanosecond laser excitation and gated detection, making it of lower cost and complexity than previous picosecond-based systems, to provide a functional platform for in-line or in-field sensing of chemical substances.

Non-invasive, quantitative analysis of drug mixtures in containers using spatially offset Raman spectroscopy (SORS) and multivariate statistical analysis

In this paper, spatially offset Raman spectroscopy (SORS) is demonstrated for non-invasively investigating the composition of drug mixtures inside an opaque plastic container. The mixtures consisted of three components including a target drug (acetaminophen or phenylephrine hydrochloride) and two diluents (glucose and caffeine). The target drug concentrations ranged from 5% to 100%. After conducting SORS analysis to ascertain the Raman spectra of the concealed mixtures, principal component analysis (PCA) was performed on the SORS spectra to reveal trends within the data. Partial least squares (PLS) regression was used to construct models that predicted the concentration of each target drug, in the presence of the other two diluents. The PLS models were able to predict the concentration of acetaminophen in the validation samples with a root-mean-square error of prediction (RMSEP) of 3.8% and the concentration of phenylephrine hydrochloride with an RMSEP of 4.6%. This work demonstrates the potential of SORS, used in conjunction with multivariate statistical techniques, to perform non-invasive, quantitative analysis on mixtures inside opaque containers. This has applications for pharmaceutical analysis, such as monitoring the degradation of pharmaceutical products on the shelf, in forensic investigations of counterfeit drugs, and for the analysis of illicit drug mixtures which may contain multiple components.

Deep Raman spectroscopy for the non-invasive standoff detection of concealed chemical threat agents

Deep Raman spectroscopy has been utilized for the standoff detection of concealed chemical threat agents from a distance of 15 meters under real life background illumination conditions. By using combined time and space resolved measurements, various explosive precursors hidden in opaque plastic containers were identified non-invasively. Our results confirm that combined time and space resolved Raman spectroscopy leads to higher selectivity towards the sub-layer over the surface layer as well as enhanced rejection of fluorescence from the container surface when compared to standoff spatially offset Raman spectroscopy. Raman spectra that have minimal interference from the packaging material and good signal-to-noise ratio were acquired within 5 seconds of measurement time. A new combined time and space resolved Raman spectrometer has been designed with nanosecond laser excitation and gated detection, making it of lower cost and complexity than picosecond-based laboratory systems.

Adolescent depression and the family : a paradox

Discusses the role of the family in the development, treatment and prevention of adolescent depression. Studies have demonstrated that between 21–32% of adolescents report mild to severe symptoms of depression. The research points out the need for increased attention to adolescent depression because of its high prevalence, the risk factor for the development of other disorders and suicide, recurrence and tendency to endure into adulthood. Many studies have shown a strong relationship between depressive symptomatology and family factors. Therefore, family interventions should play an important role in the prevention and treatment of adolescent depression. However, there exists a paradox in that the research published to date fails to show that family-intervention programs add to the efficacy of treatments provided to the adolescents. Possible explanations for this paradox are discussed.

When individual child psychotherapy exacerbates family systems problems in child abuse cases : a clinical analysis

Children who have suffered physical or sexual abuse are as vulnerable as adult trauma victims to experience "secondary trauma", in which the reactions of the family or broader system exacerbate the child's difficulties. Three clinical cases (a 7 yr old male, an 8 yr old male, and a 7 yr old female) are presented that suggest that this secondary trauma can be made worse by either excessive or insufficient provision of individual child psychotherapy, and the way the system interprets and reacts to these clinical decisions. Types of secondary trauma and their interactions with clinical decisions are discussed. Ways of framing clinical decisions to minimize the potential secondary trauma are presented.

Field portable time resolved SORS sensor for the identification of concealed hazards

Raman spectroscopy, when used in spatially offset mode, has become a potential tool for the identification of explosives and other hazardous substances concealed in opaque containers. The molecular fingerprinting capability of Raman spectroscopy makes it an attractive tool for the unambiguous identification of hazardous substances in the field. Additionally, minimal sample preparation is required compared with other techniques. We report a field portable time resolved Raman sensor for the detection of concealed chemical hazards in opaque containers. The new sensor uses a pulsed nanosecond laser source in conjunction with an intensified CCD detector. The new sensor employs a combination of time and space resolved Raman spectroscopy to enhance the detection capability. The new sensor can identify concealed hazards by a single measurement without any chemometric data treatments.

Toward non-invasive detection of concealed energetic materials in-field under ambient-light conditions

Spatially offset Raman spectroscopy (SORS) is demonstrated for the non-contact detection of energetic materials concealed within non-transparent, diffusely scattering containers. A modified design of an inverse SORS probe has been developed and tested. The SORS probe has been successfully used for the detection of various energetic substances inside different types of plastic containers. The tests have been successfully conducted under incandescent and fluorescent background lights as well as under daylight conditions, using a non-contact working distance of 6 cm. The interrogation times for the detection of the substances were less than 1 minute in each case, highlighting the suitability of the device for near real-time detection of concealed hazards in the field. The device has potential applications in forensic analysis and homeland security investigations.

Real-time detection of concealed chemical hazards under ambient light conditions using Raman spectroscopy

Current concerns regarding terrorism and international crime highlight the need for new techniques for detecting unknown and hazardous substances. A novel Raman spectroscopy-based technique, spatially offset Raman spectroscopy (SORS), was recently devised for non-invasively probing the contents of diffusely scattering and opaque containers. Here, we demonstrate a modified portable SORS sensor for detecting concealed substances in-field under different background lighting conditions. Samples including explosive precursors, drugs and an organophosphate insecticide (chemical warfare agent surrogate) were concealed inside diffusely scattering packaging including plastic, paper and cloth. Measurements were carried out under incandescent and fluorescent light as well as under daylight to assess the suitability of the probe for different real-life conditions. In each case, it was possible to identify the substances against their reference Raman spectra in less than one minute. The developed sensor has potential for rapid detection of concealed hazardous substances in airports, mail distribution centers and customs checkpoints.

Corporate governance and misappropriation

This study examines the occurrence of misappropriation-type fraud within Australian listed firms and the relation between the incidence of this type of fraud and a firm's governance strength. We measure governance strength using factors relating to traditional corporate governance, such as board composition, CEO duality, and audit committee composition, as well as factors relating to information technology governance. In our study, we use actual dollar amount of fraud reported by listed companies responding to the 2004 KPMG Fraud Survey as one of three different misappropriation measures and publicly available firm-specific data to measure the other variables in the model. Our study found that where the chief executive officer (CEO) also holds the position of chairperson of the board of directors, the likelihood of fraud increases. We also find that the greater the number of independent directors on the audit committee, the lower the level of fraud. Taken together, these results are particularly encouraging as they provide support for regulatory bodies such as the Australian Stock Exchange (ASX) and the Australian Securities and Investment Commission (ASIC), which place considerable emphasis on the importance of establishing good corporate governance practices. The study provides empirical evidence that employing good corporate governance reduces the risk of the misappropriation of assets.

Implications of lipid biology for the pathogenesis of schizophrenia

Objective: Preclinical and clinical data suggest that lipid biology is integral to brain development and neurodegeneration. Both aspects are proposed as being important in the pathogenesis of schizophrenia. The purpose of this paper is to examine the implications of lipid biology, in particular the role of essential fatty acids (EFA), for schizophrenia. Methods: Medline databases were searched from 1966 to 2001 followed by the crosschecking of references. Results: Most studies investigating lipids in schizophrenia described reduced EFA, altered glycerophospholipids and an increased activity of a calcium-independent phospholipase A2 in blood cells and in post-mortem brain tissue. Additionally, in vivo brain phosphorus-31 Magnetic Resonance Spectroscopy (31P-MRS) demonstrated lower phosphomonoesters (implying reduced membrane precursors) in first- and multi-episode patients. In contrast, phosphodiesters were elevated mainly in first-episode patients (implying increased membrane breakdown products), whereas inconclusive results were found in chronic patients. EFA supplementation trials in chronic patient populations with residual symptoms have demonstrated conflicting results. More consistent results were observed in the early and symptomatic stages of illness, especially if EFA with a high proportion of eicosapentaenoic acid was used. Conclusion: Peripheral blood cell, brain necropsy and 31P-MRS analysis reveal a disturbed lipid biology, suggesting generalized membrane alterations in schizophrenia. 31P-MRS data suggest increased membrane turnover at illness onset and persisting membrane abnormalities in established schizophrenia. Cellular processes regulating membrane lipid metabolism are potential new targets for antipsychotic drugs and might explain the mechanism of action of treatments such as eicosapentaenoic acid.

Non-party disclosure - UCPR r 242(2)

In TSPD Pty Ltd v Resortrez Pty Ltd [2008] QSC 001 Fryberg J made an order permitting the applicant to inspect and copy documents which had been produced to the court under a subpoena, but had remained in the registry. Though not essential to the decision the judgment contains some interesting discussion about the construction of r 242 of the Uniform Civil Procedure Rules 1999 (Qld) (UCPR).