Androgen receptor (AR) signaling in stromal cells is important in prostate cancer, yet the mechanisms underpinning stromal AR contribution to disease development and progression remain unclear. Using patient-matched benign and malignant prostate samples, we show a significant association between low AR levels in cancer associated stroma and increased prostate cancer-related death at one, three and five years post-diganosis, and in tissue recombination models with primary prostate cancer cells that low stromal AR decreases castration-induced apoptosis. AR-regulation was found to be different in primary human fibroblasts isolated from adjacent to cancerous and non-cancerous prostate epithelia, and to represent altered activation of myofibroblast pathways involved in cell cycle, adhesion, migration, and the extracellular matrix (ECM). Without AR signaling, the fibroblast-derived ECM loses the capacity to promote attachment of both myofibroblasts and cancer cells, is less able to prevent cell-matrix disruption, and is less likely to impede cancer cell invasion. AR signaling in prostate cancer stroma appears therefore to alter patient outcome by maintaining an ECM microenvironment inhibitory to cancer cell invasion. This paper provides comprehensive insight into AR signaling in the non-epithelial prostate microenvironment, and a resource from which the prognostic and therapeutic implications of stromal AR levels can be further explored.

Objectives: A mapping exercise was undertaken to determine how HTA is being described and conducted across the International Network of Agencies for Health Technology Assessment (INAHTA), with the aim of harmonizing terminologies and approaches. Methods: Three progressive surveys were undertaken. In 2010, INAHTA agencies were asked to provide details on all of their HTA products. In 2013, additional information was sought on key methodological characteristics of five of the most common HTA product types. Subsequently, final agreement was sought on three proposed product types. Results: Forty-five HTA agencies responded to at least one of the surveys. In 2010, twenty-one agencies reported publishing over seventy named HTA products. Core domains associated with full HTA reports were reported by a third of agencies but were labeled differently, so products were classified according to product type (n = 17). Agencies producing short, tailored products increased between 2010 and 2013, with the publication of rapid reviews doubling from 33 percent to 66 percent. In 2013, half of the agencies adapted their common HTA products from documents produced by other agencies. A consensus (>70 percent) was achieved on definitions for HTA reports, mini-HTAs, and rapid reviews. Conclusions: The product label for an HTA is not always indicative of its content. Terminology has, therefore, been agreed to make explicit the trade-off between rigor and timeliness in three common HTA product types. An INAHTA Product Type (IPT) Mark has been created to identify each of these. It is hoped this will further facilitate HTA adaptation between agencies and reduce duplication of effort.

Amoxicillin, a new semisynthetic penicillin, was administered in 250-mg doses intravenously and orally to normal men. After intravenous doses, the mean alpha disposition constant was 3.994 hr-1 and the mean beta disposition constant was 0.692 hr-1 with a corresponding beta half-life of 1.05 hr. The serum clearance rate was 0.264 1.kg-1 with a volume of distribution at steady state (Vd,,) of 0.311 1.kg-1 • The mean k. of the oral dose was 1.08 hr-l with a lag time of 0.34 hr. Calculation of areas under individual oral and intravenous serum concentration-time curves indicated an absolute availability of the oral dose of 88.7% (range, 70.9 to 105.5). In comparison with ampiCillin, amoxicillin is absorbed at a faster rate and more completely from the gastro-intestinal tract and has a larger Vd". The beta phase half-life and serum clearance rates of the two antibiotics are similar.

Aims:To describe the clinical and socio-demographic data from a South Australian prostate cancer cohort (PCCOD). Methods: Clinical data for 2329 prostate cancer patients treated at three South Australian teaching hospitals between 1998 and 2007 were analyzed by place of residence, time of diagnosis and socioeconomic status (SES). c 2 tests were used to investigate differences in stage, grade and prostate-specific antigen (PSA) at diagnosis, among subgroups and over time. Logistic regression was used to examine predictors of treatment modalities. Five-year survival was assessed using Kaplan-Meier methods. Results: The distributions of age, SES and place of residence of PCCOD patients closely reflected those of the state-based prostate cancer population, with rural patients slightly underrepresented. Lower SES or rural residence was not associated with higher stage, grade, PSA level or disease-specific survival. Treatment modalities varied with SES (for radical prostatectomy), rural residence (radical prostatectomy, radiotherapy and androgen ablation), age and clinical characteristics. There was a trend over time towards a younger age at diagnosis and more favorable clinical profiles, consistent with earlier diagnosis. However, the current risk profile for this cohort is similar to that reported approximately a decade earlier in a US series. Conclusion: PCCOD patients have a broadly similar socio-demographic profile to prostate cancer patients statewide. Socioeconomic status is not associated with clinical characteristics at diagnosis, but does predict treatment type. The clinical characteristics of the cohort are consistent with a much later stage presentation than reported in current US case series.