Androgen-regulated genes differentially modulated by the androgen receptor coactivator L-dopa decarboxylase in human prostate cancer cells

Background The androgen receptor is a ligand-induced transcriptional factor, which plays an important role in normal development of the prostate as well as in the progression of prostate cancer to a hormone refractory state. We previously reported the identification of a novel AR coactivator protein, L-dopa decarboxylase (DDC), which can act at the cytoplasmic level to enhance AR activity. We have also shown that DDC is a neuroendocrine (NE) marker of prostate cancer and that its expression is increased after hormone-ablation therapy and progression to androgen independence. In the present study, we generated tetracycline-inducible LNCaP-DDC prostate cancer stable cells to identify DDC downstream target genes by oligonucleotide microarray analysis. Results Comparison of induced DDC overexpressing cells versus non-induced control cell lines revealed a number of changes in the expression of androgen-regulated transcripts encoding proteins with a variety of molecular functions, including signal transduction, binding and catalytic activities. There were a total of 35 differentially expressed genes, 25 up-regulated and 10 down-regulated, in the DDC overexpressing cell line. In particular, we found a well-known androgen induced gene, TMEPAI, which wasup-regulated in DDC overexpressing cells, supporting its known co-activation function. In addition, DDC also further augmented the transcriptional repression function of AR for a subset of androgen-repressed genes. Changes in cellular gene transcription detected by microarray analysis were confirmed for selected genes by quantitative real-time RT-PCR. Conclusion Taken together, our results provide evidence for linking DDC action with AR signaling, which may be important for orchestrating molecular changes responsible for prostate cancer progression.

A research opportunity : “3D-ROSE” : virtual reality preparation for children having radiotherapy or imaging procedures

Professor Christian Langton is a medical physicist at Queensland University of Technology in Brisbane. He has developed a way of preparing children who are about to have either radiotherapy or MRI imaging procedures and is seeking research partners to develop and test these further. This is a great opportunity for nurses interested in research, and who have access to a children’s hospital, to work with Professor Langton on some truly innovative, multidisciplinary research.

Civic engagement and associationalism : the impact of group membership scope versus intensity of participation

The relationship between participation in civic and political activities and membership of voluntary associations is now well established. What is less clear is the relative impacts of how much time people spend on group activities (associational intensity), and the number and type of groups that individuals are involved with (associational scope). Does it matter in terms of civic engagement, for example, whether one is a member of a quilting-circle or trade union? Does it matter whether association ‘membership’ is simply an annual payment or a major commitment of time and energy? In this article, we use a large survey to explore these questions empirically by focusing on the membership patterns and civic engagement practices of 4,001 citizens drawn from eight suburbs across Greater Melbourne, Australia. Our findings indicate that, while associational intensity is positively related to civic engagement, associational scope (the number of group memberships per person), is a more influential determinant of the level of civic and political participation. The results also suggest that while all forms of associationalism are important in terms of fostering greater levels of civic activity, not all forms have the same impact.

Internet usage, internet marketing intensity and international marketing growth

This paper examines the role of the Internet in international marketing growth. Evidence of a positive relationship between e-mail, website usage, online marketing and advertising with international market growth was found, in terms of increased sales from new customers in new countries, new customers in existing countries, and existing customers.

Prospective, non-randomized phase 2 clinical trial of carboplatin plus paclitaxel with sequential radical pelvic radiotherapy for uterine papillary serous carcinoma

Objective Uterine Papillary Serous Carcinoma (UPSC) is uncommon and accounts for less than 5% of all uterine cancers. Therefore the majority of evidence about the benefits of adjuvant treatment comes from retrospective case series. We conducted a prospective multi-centre non-randomized phase 2 clinical trial using four cycles of adjuvant paclitaxel plus carboplatin chemotherapy followed by pelvic radiotherapy, in order to evaluate the tolerability and safety of this approach. Methods This trial enrolled patients with newly diagnosed, previously untreated patients with stage 1b-4 (FIGO-1988) UPSC with a papillary serous component of at least 30%. Paclitaxel (175 mg/m2) and carboplatin (AUC 6) were administered on day 1 of each 3-week cycle for 4 cycles. Chemotherapy was followed by external beam radiotherapy to the whole pelvis (50.4 Gy over 5.5 weeks). Completion and toxicity of treatment (Common Toxicity Criteria, CTC) and quality of life measures were the primary outcome indicators. Results Twenty-nine of 31 patients completed treatment as planned. Dose reduction was needed in 9 patients (29%), treatment delay in 7 (23%), and treatment cessation in 2 patients (6.5%). Hematologic toxicity, grade 3 or 4 occurred in 19% (6/31) of patients. Patients' self-reported quality of life remained stable throughout treatment. Thirteen of the 29 patients with stages 1–3 disease (44.8%) recurred (average follow up 28.1 months, range 8–60 months). Conclusion This multimodal treatment is feasible, safe and tolerated reasonably well and would be suitable for use in multi-institutional prospective randomized clinical trials incorporating novel therapies in patients with UPSC.

Low intensity CBT by mail

Introduction: There are many low intensity (LI) cognitive behavoural therapy (CBT) solutions to the problem of limited service access. In this chapter, we aim to discuss a relatively low-technology approach to access using standard postal services-CBT by mail, or M-CBT. Bibliotherapies including M-CBT teach key concepts and self-management techniques, together with screening tools and forms to structure home practice. M-CBT differs from other bibliotherapies by segmenting interventions and mailing them at regular intervals. Most involve participants returning copies of monitoring forms or completed handouts. Therapist feedback is provided, often in personal letters that accompany the printed materials. Participants may also be given access to telephone or email support. ----- ----- M-CBT clearly fulfills criteria for an LI CBT (see Bennett-Levy et al., Chapter 1, for a definition of LI interventions). Once written, they involve little therapist time and rely heavily on self-management. However, content and overall treatment duration need not be compromised. Long-term interventions with multiple components can be delivered via this method, provided their content can be communicated in letters and engagement is maintained.

Implementing low intensity CBT in case management of clients with severe mental illness

In a previous chapter (Dean and Kavanagh, Chapter 37), the authors made a case for applying low intensity (LI) cognitive behaviour therapy (CBT) to people with serious mental illness (SMI). As in other populations, LI CBT interventions typically deal with circumscribed problems or behaviours. LI CBT retains an emphasis on self-management, has restricted content and segment length, and does not necessarily require extensive CBT training. In applying these interventions to SMI, adjustments may be needed to address cognitive and symptomatic difficulties often faced by these groups. What may take a single session in a less affected population may require several sessions or a thematic application of the strategy within case management. In some cases, the LI CBT may begin to appear more like a high-intensity (HI) intervention, albeit simple and with many LI CBT characteristics still retained. So, if goal setting were introduced in one or two sessions, it could clearly be seen as an LI intervention. When applied to several different situations and across many sessions, it may be indistinguishable from a simple HI treatment, even if it retains the same format and is effectively applied by a practitioner with limited CBT training. ----- ----- In some ways, LI CBT should be well suited to case management of patients with SMI. treating staff typically have heavy workloads, and find it difficult to apply time-consuming treatments (Singh et al. 2003). LI CBT may allow provision of support to greater numbers of service users, and allow staff to spend more time on those who need intensive and sustained support. However, the introduction of any change in practice has to address significant challenges, and LI CBT is no exception. ----- ----- Many of the issues that we face in applying LI CBT to routine case management in a mnetal health service and their potential solutions are essentially the same as in a range of other problem domains (Turner and Sanders 2006)- and, indeed, are similar to those in any adoption of innovation (Rogers 2003). Over the last 20 years, several commentators have described barriers to implementing evidence-based innovations in mental health services (Corrigan et al. 1992; Deane et al. 2006; Kavanagh et al. 1993). The aim of the current chapter is to present a cognitive behavioural conceptualisation of problems and potential solutions for dissemination of LI CBT.

Adapting low intensity CBT interventions for clients with severe mental illness

Many people with severe mental illness (SMI) such as schizophrenia, whose psychotic symptoms are effectively managed, continue to experience significant functional problems. This chapter argues that low intensity (LI) cognitive behaviour therapy (CBT; e.g. for depression, anxiety, or other issues) is applicable to these clients, and that LI CBT can be consistent with long-term case management. However, adjustments to LI CBT strategies are often necessary and boundaries between LI CBT and high intensity (HI) CBT (with more extensive practitioner contact and complexity) may become blurred. Our focus is on LI CBT's self-management emphasis, its restricted content and segment length, and potential use after limited training. In addition to exploring these issues, it draws on the authors' Collaborative Recovery (CR; Oades et al. 2005) and 'Start Over and Survive' programs (Kavanagh et al. 2004) as examples. ----- ----- Evidence for the effectiveness of LI CBT with severe mental illness is often embedded within multicomponent programs. For example, goal setting and therapeutic homework are common components of such programs, but they can also be used as discrete LI CBT interventions. A review of 40 randomised controlled trials involving recipients with schizophrenia or other sever mental illnesses has identified key components of illness management programs (Mueser et al. 2002). However, it is relatively rare for specific components of these complex interventions to be assessed in isolation. Given these constraints, the evidence for specific LI CBT interventions with severe mental ilnness is relatively limited.

A hybrid radiation detector for simultaneous spatial and temporal dosimetry

In this feasibility study an organic plastic scintillator is calibrated against ionisation chamber measurements and then embedded in a polymer gel dosimeter to obtain a quasi-4D experimental measurement of a radiation field. This hybrid dosimeter was irradiated with a linear accelerator, with temporal measurements of the dose rate being acquired by the scintillator and spatial measurements acquired with the gel dosimeter. The detectors employed in this work are radiologically equivalent; and we show that neither detector perturbs the intensity of the radiation field of the other. By employing these detectors in concert, spatial and temporal variations in the radiation intensity can now be detected and gel dosimeters can be calibrated for absolute dose from a single irradiation.

Investigation of stereotactic radiotherapy dose using dosimetry film and Monte Carlo simulations

This study uses dosimetry film measurements and Monte Carlo simulations to investigate the accuracy of type-a (pencil-beam) dose calculations for predicting the radiation doses delivered during stereotactic radiotherapy treatments of the brain. It is shown that when evaluating doses in a water phantom, the type-a algorithm provides dose predictions which are accurate to within clinically relevant criteria, gamma(3%,3mm), but these predictions are nonetheless subtly different from the results of evaluating doses from the same fields using radiochromic film and Monte Carlo simulations. An analysis of a clinical meningioma treatment suggests that when predicting stereotactic radiotherapy doses to the brain, the inaccuracies of the type-a algorithm can be exacerbated by inadequate evaluation of the effects of nearby bone or air, resulting in dose differences of up to 10% for individual fields. The results of this study indicate the possible advantage of using Monte Carlo calculations, as well as measurements with high-spatial resolution media, to verify type-a predictions of dose delivered in cranial treatments.

Realisation of ternary sigma-delta modulated arithmetic processing modules

Sigma-delta modulated systems have a number of very appealing properties and are, therefore, heavily used in analog to digital converters, amplifiers, and modulators. This paper presents new results which indicate that they may also have significant potential for general purpose arithmetic processing.

Negative Mood Regulation (NMR) expectancies, mood, and affect intensity among clients in substance disorder treatment facilities

Negative mood regulation (NMR) expectancies, stress, anxiety, depression and affect intensity were examined by means of self-report questionnaires in 158 volunteers, including 99 clients enrolled in addiction treatment programs. As expected, addicts reported significantly higher levels of stress, anxiety, depression and affect intensity and lower levels of NMR compared to non-addict controls. NMR was negatively correlated with stress, anxiety, depression and affect intensity. The findings indicate that mood self-regulation is impaired in addicts. Low NMR and high affect intensity may predispose to substance abuse and addiction, or alternatively may reflect chronic drug-induced affective dysregulation.

Relationships between rainfall intensity, duration and suspended particle washoff from an urban road surface

A basic understanding of the relationships between rainfall intensity, duration of rainfall and the amount of suspended particles in stormwater runoff generated from road surfaces has been gained mainly from past washoff experiments using rainfall simulators. Simulated rainfall was generally applied at constant intensities, whereas rainfall temporal patterns during actual storms are typically highly variable. This paper discusses a rationale for the application of the constant-intensity washoff concepts to actual storm event runoff. The rationale is tested using suspended particle load data collected at a road site located in Toowoomba, Australia. Agreement between the washoff concepts and measured data is most consistent for intermediate-duration storms (duration <5 h and >1 h). Particle loads resulting from these storm events increase linearly with average rainfall intensity. Above a threshold intensity, there is evidence to suggest a constant or plateau particle load is reached. The inclusion of a peak discharge factor (maximum 6 min rainfall intensity) enhances the ability to predict particle loads.