IGF2 increases de novo steroidogenesis in prostate cancer cells

Androgen-dependent pathways regulate maintenance and growth of normal and malignant prostate tissues. Androgen deprivation therapy (ADT) exploits this dependence and is used to treat metastatic prostate cancer; however, regression initially seen with ADT gives way to development of incurable castration-resistant prostate cancer (CRPC). Although ADT generates a therapeutic response, it is also associated with a pattern of metabolic alterations consistent with metabolic syndrome including elevated circulating insulin. Because CRPC cells are capable of synthesizing androgens de novo, we hypothesized that insulin may also influence steroidogenesis in CRPC. In this study, we examined this hypothesis by evaluating the effect of insulin on steroid synthesis in prostate cancer cell lines. Treatment with 10 nmol/L insulin increased mRNA and protein expression of steroidogenesis enzymes and upregulated the insulin receptor substrate insulin receptor substrate 2 (IRS-2). Similarly, insulin treatment upregulated intracellular testosterone levels and secreted androgens, with the concentrations of steroids observed similar to the levels reported in prostate cancer patients. With similar potency to dihydrotestosterone, insulin treatment resulted in increased mRNA expression of prostate-specific antigen. CRPC progression also correlated with increased expression of IRS-2 and insulin receptor in vivo. Taken together, our findings support the hypothesis that the elevated insulin levels associated with therapeutic castration may exacerbate progression of prostate cancer to incurable CRPC in part by enhancing steroidogenesis.

A flexible asset maintenance decision-making process model

Optimal Asset Maintenance decisions are imperative for efficient asset management. Decision Support Systems are often used to help asset managers make maintenance decisions, but high quality decision support must be based on sound decision-making principles. For long-lived assets, a successful Asset Maintenance decision-making process must effectively handle multiple time scales. For example, high-level strategic plans are normally made for periods of years, while daily operational decisions may need to be made within a space of mere minutes. When making strategic decisions, one usually has the luxury of time to explore alternatives, whereas routine operational decisions must often be made with no time for contemplation. In this paper, we present an innovative, flexible decision-making process model which distinguishes meta-level decision making, i.e., deciding how to make decisions, from the information gathering and analysis steps required to make the decisions themselves. The new model can accommodate various decision types. Three industrial case studies are given to demonstrate its applicability.

Optimising preventive maintenance strategy for production Lines

Preventive Maintenance (PM) is often applied to improve the reliability of production lines. A Split System Approach (SSA) based methodology is presented to assist in making optimal PM decisions for serial production lines. The methodology treats a production line as a complex series system with multiple (imperfect) PM actions over multiple intervals. The conditional and overall reliability of the entire production line over these multiple PM intervals are hierarchically calculated using SSA, and provide a foundation for cost analysis. Both risk-related cost and maintenance-related cost are factored into the methodology as either deterministic or random variables. This SSA based methodology enables Asset Management (AM) decisions to be optimised considering a variety of factors including failure probability, failure cost, maintenance cost, PM performance, and the type of PM strategy. The application of this new methodology and an evaluation of the effects of these factors on PM decisions are demonstrated using an example. The results of this work show that the performance of a PM strategy can be measured by its Total Expected Cost Index (TECI). The optimal PM interval is dependent on TECI, PM performance and types of PM strategies. These factors are interrelated. Generally, it was found that a trade-off between reliability and the number of PM actions needs to be made so that one can minimise Total Expected Cost (TEC) for asset maintenance.

Study protocol : Screening and treatment of alcohol-related trauma (START): a randomised controlled trial

Background: The incidence of mandibular fractures in the Northern Territory of Australia is very high, especially among Indigenous people. Alcohol intoxication is implicated in the majority of facial injuries, and substance use is therefore an important target for secondary prevention. The current study tests the efficacy of a brief therapy, Motivational Care Planning, in improving wellbeing and substance misuse in youth and adults hospitalised with alcohol-related facial trauma. Methods and design: The study is a randomised controlled trial with 6 months of follow-up, to examine the effectiveness of a brief and culturally adapted intervention in improving outcomes for trauma patients with at-risk drinking admitted to the Royal Darwin Hospital maxillofacial surgery unit. Potential participants are identified using AUDIT-C questionnaire. Eligible participants are randomised to either Motivational Care Planning (MCP) or Treatment as Usual (TAU). The outcome measures will include quantity and frequency of alcohol and other substance use by Timeline Followback. The recruitment target is 154 participants, which with 20% dropout, is hoped to provide 124 people receiving treatment and follow-up. Discussion: This project introduces screening and brief interventions for high-risk drinkers admitted to the hospital with facial trauma. It introduces a practical approach to integrating brief interventions in the hospital setting, and has potential to demonstrate significant benefits for at-risk drinkers with facial trauma.

Internet interventions for treatment of alcohol related problems

This is the protocol for a review and there is no abstract. The objectives are as follows: The primary objective of this review will be to assess the effect of internet and mobile phone alcohol-related interventions on reducing participants' alcohol consumption. Secondary objectives will include assessing the impact of the interventions on symptoms of alcohol-related disorders and degree of alcohol dependence, the effects on functioning, and patient acceptability. The review will also assess whether there are different outcomes for different diagnostic groups, and which intervention approaches or components (including therapeutic support) may be contributing to any positive effects.

Craving as a predictor of treatment outcomes in heavy drinkers with comorbid depressed mood

Alcohol and depression comorbidity is high and is associated with poorer outcomes following treatment. The ability to predict likely treatment response would be advantageous for treatment planning. Craving has been widely studied as a potential predictor, but has performed inconsistently. The effect of comorbid depression on craving's predictive performance however, has been largely neglected, despite demonstrated associations between negative affect and craving. The current study examined the performance of craving, measured pretreatment using the Obsessive subscale of the Obsessive Compulsive Drinking Scale, in predicting 18-week and 12-month post-treatment alcohol use outcomes in a sample of depressed drinkers. Data for the current study were collected during a randomized controlled trial (Baker, Kavanagh, Kay-Lambkin, Hunt, Lewin, Carr, & Connolly, 2010) comparing treatments for comorbid alcohol and depression. A subset of 260 participants from that trial with a Timeline Followback measure of alcohol consumption was analyzed. Pre-treatment craving was a significant predictor of average weekly alcohol consumption at 18 weeks and of frequency of alcohol binges at 18 weeks and 12months, but pre-treatment depressive mood was not predictive, and effects of Baseline craving were independent of depressive mood. Results suggest a greater ongoing risk from craving than from depressive mood at Baseline.

Response to “Topical agent therapy for prevention and treatment of radiodermatitis : a meta-analysis”

To the Editor; It was with interest that I read the recent article by Zhang et al. published in Supportive Care in Cancer [1]. This paper highlighted the importance of radiodermatitis (RD) being an unresolved and distressing clinical issue in patients with cancer undergoing radiation therapy. However, I am concerned with a number of clinical and methodological issues within this paper: (i) the clinical and operational definition of prophylaxis and treatment of RD; (ii) the accuracy of the identification of trials; and (iii) the appropriateness of the conduct of the meta-analyses...

Treatment of cannabis use among people with psychotic disorders : critical review of randomised controlled trials

There is growing and converging evidence that cannabis may be a major risk factor in people with psychotic disorders and prodromal psychotic symptoms. The lack of available pharmacological treatments for cannabis use indicates that psychological interventions should be a high priority, especially among people with psychotic disorders. However, there have been few randomised controlled trials (RCTs) of psychological interventions among this group. In the present study we critically overview RCTs of psychological and pharmacologic interventions among people with psychotic disorders, giving particular attention to those studies which report cannabis use outcomes. We then review data regarding treatment preferences among this group. RCTs of interventions within "real world" mental health systems among adults with severe mental disorders suggest that cannabis use is amenable to treatment in real world settings among people with psychotic disorders. RCTs of manual guided interventions among cannabis users indicate that while brief interventions are associated with reductions in cannabis use, longer interventions may be more effective. Additionally, RCTs reviewed suggest treatment with antipsychotic medication is not associated with a worsening of cannabis cravings or use and may be beneficial. The development of cannabinoid agonist medication may be an effective strategy for cannabis dependence and suitable for people with psychotic disorders. The development of cannabis use interventions for people with psychotic disorders should also consider patients' treatment preferences. Initial results indicate face-to-face interventions focussed on cannabis use may be preferred. Further research investigating the treatment preferences of people with psychotic disorders using cannabis is needed.

A confirmatory factor analysis of the Observer Alexithymia Scale in treatment seeking alcohol-dependent patients

Confirmatory factor analyses evaluated the factorial validity of the Observer Alexithymia Scale (OAS) in an alcohol-dependent sample. Observation was conducted by clinical psychologists. All models examined were rejected, given their poor fit. Given the psychometric limitations of the OAS shown in this study, the OAS may not be the most appropriate measure to use early in treatment among alcohol-dependent individuals.

An assessment for cost effective maintenance and operation of the Callide Power Station electrical system, using reliability evaluation

The reliable operation of the electrical system at Callide Power Station is of extreme importance to the normal everyday running of the Station. This study applied the principles of reliability to do an analysis on the electrical system at Callide Power Station. It was found that the level of expected outage cost increased exponentially with a declining level of maintenance. Concluding that even in a harsh economic electricity market where CS Energy tries and push their plants to the limit, maintenance must not be neglected. A number of system configurations were found to increase the reliability of the system and reduce the expected outage costs. A number of other advantages were identified as a result of using reliability principles to do this study on the Callide electrical system configuration.

Maintenance considerations in applied substation reliability assessment

This paper presents a reliability assessment of a substation, part of the Queensland transmission network in Australia. As part of a maintenance considerations, this study utilises the substation reliability assessment package STAREL to quantitatively compare the reliability improvement achieved by two circuit breaker reinforcement alternatives for Swanbank circuit breaker replacement or refurbishment. Substation reliability is interpreted on the basis of outage frequency and outage duration indices for each individual transmission line terminated in Swanbank 'B' substation. By considering the reliability indices in this paper with the cost associated conducted by POWERLINK Queensland, a Swanbank 'B' reinforcement alternative can be selected that optimises both transmission line security and the costs incurred in achieving it.

Impact of a novel nurse-led prechemotherapy education intervention (ChemoEd) on patient distress, symptom burden, and treatment-related information and support needs : results from a randomised, controlled trial

Background: High levels of distress and need for self-care information by patients commencing chemotherapy suggest that current prechemotherapy education is suboptimal. We conducted a randomised, controlled trial of a prechemotherapy education intervention (ChemoEd) to assess impact on patient distress, treatment-related concerns, and the prevalence and severity of and bother caused by six chemotherapy side-effects. Patients and methods: One hundred and ninety-two breast, gastrointestinal, and haematologic cancer patients were recruited before the trial closing prematurely (original target 352). ChemoEd patients received a DVD, question-prompt list, self-care information, an education consultation ≥24 h before first treatment (intervention 1), telephone follow-up 48 h after first treatment (intervention 2), and a face-to-face review immediately before second treatment (intervention 3). Patient outcomes were measured at baseline (T1: pre-education) and immediately preceding treatment cycles 1 (T2) and 3 (T3). Results: ChemoEd did not significantly reduce patient distress. However, a significant decrease in sensory/psychological (P = 0.027) and procedural (P = 0.03) concerns, as well as prevalence and severity of and bother due to vomiting (all P = 0.001), were observed at T3. In addition, subgroup analysis of patients with elevated distress at T1 indicated a significant decrease (P = 0.035) at T2 but not at T3 (P = 0.055) in ChemoEd patients. Conclusions: ChemoEd holds promise to improve patient treatment-related concerns and some physical/psychological outcomes; however, further research is required on more diverse patient populations to ensure generalisability.

Efficient route update and maintenance processes for multipath routing in large-scale industrial wireless sensor networks

Reliable communications is one of the major concerns in wireless sensor networks (WSNs). Multipath routing is an effective way to improve communication reliability in WSNs. However, most of existing multipath routing protocols for sensor networks are reactive and require dynamic route discovery. If there are many sensor nodes from a source to a destination, the route discovery process will create a long end-to-end transmission delay, which causes difficulties in some time-critical applications. To overcome this difficulty, the efficient route update and maintenance processes are proposed in this paper. It aims to limit the amount of routing overhead with two-tier routing architecture and introduce the combination of piggyback and trigger update to replace the periodic update process, which is the main source of unnecessary routing overhead. Simulations are carried out to demonstrate the effectiveness of the proposed processes in improvement of total amount of routing overhead over existing popular routing protocols.

The development of a Monte Carlo system to verify radiotherapy treatment dose calculations

Recent advances in the planning and delivery of radiotherapy treatments have resulted in improvements in the accuracy and precision with which therapeutic radiation can be administered. As the complexity of the treatments increases it becomes more difficult to predict the dose distribution in the patient accurately. Monte Carlo methods have the potential to improve the accuracy of the dose calculations and are increasingly being recognised as the “gold standard” for predicting dose deposition in the patient. In this study, software has been developed that enables the transfer of treatment plan information from the treatment planning system to a Monte Carlo dose calculation engine. A database of commissioned linear accelerator models (Elekta Precise and Varian 2100CD at various energies) has been developed using the EGSnrc/BEAMnrc Monte Carlo suite. Planned beam descriptions and CT images can be exported from the treatment planning system using the DICOM framework. The information in these files is combined with an appropriate linear accelerator model to allow the accurate calculation of the radiation field incident on a modelled patient geometry. The Monte Carlo dose calculation results are combined according to the monitor units specified in the exported plan. The result is a 3D dose distribution that could be used to verify treatment planning system calculations. The software, MCDTK (Monte Carlo Dicom ToolKit), has been developed in the Java programming language and produces BEAMnrc and DOSXYZnrc input files, ready for submission on a high-performance computing cluster. The code has been tested with the Eclipse (Varian Medical Systems), Oncentra MasterPlan (Nucletron B.V.) and Pinnacle3 (Philips Medical Systems) planning systems. In this study the software was validated against measurements in homogenous and heterogeneous phantoms. Monte Carlo models are commissioned through comparison with quality assurance measurements made using a large square field incident on a homogenous volume of water. This study aims to provide a valuable confirmation that Monte Carlo calculations match experimental measurements for complex fields and heterogeneous media.