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.

Infant wrapping as an evidence-based strategy to encourage settling and the utilisation of the supine sleep position

Objective: To identify knowledge, attitudes and practices of child health nurses relating to infant wrapping as an effective settling/sleep strategy. Methods: A pre-test/post-test intervention design was used to explore knowledge, attitudes and practices relating to wrapping in a sample of child health nurses (n=182): a) pre-test survey; b) educational intervention incorporating evidence relating to infant wrapping; SIDS&KIDS endorsed infant wrapping pamphlet; Safe Sleeping recommendations. Emphasis was placed on infant wrapping as an effective settling strategy for parents to use as an alternative to prone positioning; c) post-test survey to evaluate intervention effectiveness. Results: Pretest results identified wide variation in nurses’ knowledge, attitudes and practices of infant wrapping as a settling/sleep strategy. The intervention increased awareness of wrapping guidelines and self-reported practices relating to parent advice. Significant positive changes in nurses’ awareness of wrapping guidelines (p<0.001); to wrap in supine position only (p<0.001); and parental advice to use wrapping as an alternative strategy to prone positioning to assist settling/sleep (p<0.01), were achieved post-test. Conclusions: Managing unsettled infants and promoting safe sleeping practices are issues routinely addressed by child health nurses working with parents of young infants. Queensland has a high incidence of prone sleeping. Infant wrapping is an evidence-based strategy to improve settling and promote supine sleep consistent with public health recommendations. Infant wrapping guidelines are now included in Queensland Health’s state policy and Australian SIDSandKids information relating to safe infant sleeping. In communicating complex health messages to parents, health professionals have a key role in reinforcing safe sleeping recommendations and offering safe, effective settling/sleep strategies to address the non-recommended use of prone positioning for unsettled infants.

The concentric all-polyethylene Exeter acetabular component in primary total hip replacement

We report the long term outcome of the flangeless, cemented all polyethylene Exeter cup at a mean of 14.6 years (range 10-17) after operation. Of the 263 hips in 243 patients, 122 hips are still in situ, 112 patients (119 hips) have died, eighteen hips were revised, and three patients (four hips) had moved abroad and were lost to follow-up (1.5%). Radiographs demonstrated two sockets had migrated and six more had radiolucent lines in all three zones. The Kaplan Meier survivorship at 15 years with endpoint revision for all causes is 89.9% (95% CI 84.6 to 95.2%) and for aseptic cup loosening or lysis 91.7% (CI 86.6 to 96.8%). In 210 hips with a diagnosis of primary osteoarthritis survivorship for all causes is 93.2% (95% CI 88.1 to 98.3%), and for aseptic cup loosening 95.0% (CI 90.3 to 99.7%). The cemented all polyethylene Exeter cup has an excellent long-term survivorship.

Quality of life after total laparoscopic hysterectomy versus total abdominal hysterectomy for stage I endometrial cancer (LACE) : a randomised trial

Background: The two-stage Total Laparoscopic Hysterectomy (TLH) versus Total Abdominal Hysterectomy (TAH) for stage I endometrial cancer (LACE) randomised controlled trial was initiated in 2005. The primary objective of stage 1 was to assess whether TLH results in equivalent or improved QoL up to 6 months after surgery compared to TAH. The primary objective of stage 2 was to test the hypothesis that disease-free survival at 4.5 years is equivalent for TLH and TAH. Results addressing the primary objective of stage 1 of the LACE trial are presented here. Methods: The first 361 LACE participants (TAH n= 142, TLH n=190) were enrolled in the QoL substudy at 19 centres across Australia, New Zealand and Hong Kong, and 332 completed the QoL analysis. Randomisation was performed centrally and independently from other study procedures via a computer generated, web-based system (providing concealment of the next assigned treatment) using stratified permuted blocks of 3 and 6, and assigned patients with histologically confirmed stage 1 endometrioid endometrial adenocarcinoma and ECOG performance status <2 to TLH or TAH stratified by histological grade and study centre. No blinding of patients or study personnel was attempted. QoL was measured at baseline, 1 and 4 weeks (early), and 3 and 6 months (late) after surgery using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. The primary endpoint was the difference between the groups in QoL change from baseline at early and late time points (a 5% difference was considered clinically significant). Analysis was performed according to the intention-to-treat principle using generalized estimating equations on differences from baseline for the early and late QoL recovery. The LACE trial is registered with clinicaltrials.gov (NCT00096408) and the Australian New Zealand Clinical Trials Registry (CTRN12606000261516). Patients for both stages of the trial have now been recruited and are being followed up for disease-specific outcomes. Findings: The proportion of missing values at the 5%, 10% 15% and 20% differences in the FACT-G scale was 6% (12/190) in the TLH and 14% (20/142) in the TAH group. There were 8/332 conversions (2.4%, 7 of which were from TLH to TAH). In the early phase of recovery, patients undergoing TLH reported significantly greater improvement of QoL from baseline compared to TAH in all subscales except the emotional and social well-being subscales. Improvements in QoL up to 6 months post-surgery continued to favour TLH except for the emotional and social well-being of the FACT and the visual analogue scale of the EuroQoL five dimensions (EuroQoL-VAS). Length of operating time was significantly longer in the TLH group (138±43 mins), than in the TAH group at (109±34 mins; p=0.001). While the proportion of intraoperative adverse events was similar between the treatment groups (TAH 8/142, 5.6%; TLH 14/190, 7.4%; p=0.55), postoperatively, twice as many patients in the TAH group experienced adverse events of CTC grade 3+ than in the TLH group (33/142, 23.2% and 22/190, 11.6%, respectively; p=0.004). Postoperative serious adverse events occurred more frequently in patients who had a TAH (27/142, 19.0%) than a TLH (15/190, 7.9%) (p=0.002). Interpretation: QoL improvements from baseline during early and later phases of recovery, and the adverse event profile significantly favour TLH compared to TAH for patients treated for Stage I endometrial cancer.

Electron interaction with gel dosimeters : effective atomic numbers for collisional, radiative and total interaction processes

The effective atomic number is widely employed in radiation studies, particularly for the characterisation of interaction processes in dosimeters, biological tissues and substitute materials. Gel dosimeters are unique in that they comprise both the phantom and dosimeter material. In this work, effective atomic numbers for total and partial electron interaction processes have been calculated for the first time for a Fricke gel dosimeter, five hypoxic and nine normoxic polymer gel dosimeters. A range of biological materials are also presented for comparison. The spectrum of energies studied spans 10 keV to 100 MeV, over which the effective atomic number varies by 30 %. The effective atomic numbers of gels match those of soft tissue closely over the full energy range studied; greater disparities exist at higher energies but are typically within 4 %.

Soil carbon saturation : concept, evidence and evaluation

Current estimates of soil C storage potential are based on models or factors that assume linearity between C input levels and C stocks at steady-state, implying that SOC stocks could increase without limit as C input levels increase. However, some soils show little or no increase in steady-state SOC stock with increasing C input levels suggesting that SOC can become saturated with respect to C input. We used long-term field experiment data to assess alternative hypotheses of soil carbon storage by three simple models: a linear model (no saturation), a one-pool whole-soil C saturation model, and a two-pool mixed model with C saturation of a single C pool, but not the whole soil. The one-pool C saturation model best fit the combined data from 14 sites, four individual sites were best-fit with the linear model, and no sites were best fit by the mixed model. These results indicate that existing agricultural field experiments generally have too small a range in C input levels to show saturation behavior, and verify the accepted linear relationship between soil C and C input used to model SOM dynamics. However, all sites combined and the site with the widest range in C input levels were best fit with the C-saturation model. Nevertheless, the same site produced distinct effective stabilization capacity curves rather than an absolute C saturation level. We conclude that the saturation of soil C does occur and therefore the greatest efficiency in soil C sequestration will be in soils further from C saturation.

Social inclusion through community enterprise? Examining the available evidence

In recent years the concepts of social inclusion and exclusion have become part of the repertoire of third-way policy discourses that seek to respond to complex socioeconomic problems through processes of 'joined-up' and 'integrated' governance. As part of this approach, we are witnessing an increased focus on the role of the third sector in facilitating social inclusion. While the push towards governing through networks has gained moral legitimacy in some areas of social policy, the practical legitimacy - that is, whether these new approaches actually produce demonstrably better outcomes than more traditional policy approaches - remains largely unsubstantiated. This article contributes to the evidence base, by examining the social-inclusion impacts of eleven community enterprises operating in Victoria, and to the wider available evidence on the social, economic and civic effects of social enterprise.

Valuing the impact of the teacher librarian from an evidence base

Evidence-based practice as it applies to the Library and Information (LIS) sector and in particular teacher librarians is the focus of this research investigation. The context for this research is Australian school libraries and teacher librarians. This is a research in progress and the report here will include some very early findings and lessons learned from the initial pilot study. The contributions of this research will be in developing a framework for the library and information sector with a particular application for teacher librarians. Providing meaningful evidence of work practices that demonstrate contributions to the schools goals and mission statements in conjunction with contributions to student academic, social and cultural achievements are crucial for the future of the teacher librarian.

The role of the audit committee and institutional investors in constraining earnings management : evidence from Chinese firms listed in Hong Kong

Using data from 2004 to 2008, we find that an audit committee is an important monitoring mechanism as audit committee independence, expertise and size are associated with reduced levels of abnormal accruals, our measure of earnings management. This study also attempts to discern when the monitoring role of the audit committee is more salient for the firm. We find that ownership concentration and the presence of government officials on the audit committee are important determinants of the negative association between audit committee characteristics and earnings management. In contrast, we find no significant associations between the audit committee and abnormal accruals for Chinese firms listed only on the Chinese domestic Stock Exchanges. The paper contributes to the corporate governance literature in a transitional economy. Identifying the role of audit committees of firms listed on markets other than the domicile market demonstrates the importance of considering the institutional setting in governance research.