Timing of androgen-deprivation therapy in patients with prostate cancer with a rising PSA (TROG 03.06 and VCOG PR 01-03 [TOAD]): a randomised, multicentre, non-blinded, phase 3 trial

Background Androgen-deprivation therapy is offered to men with prostate cancer who have a rising prostate-specific antigen after curative therapy (PSA relapse) or who are considered not suitable for curative treatment; however, the optimal timing for its introduction is uncertain. We aimed to assess whether immediate androgen-deprivation therapy improves overall survival compared with delayed therapy. Methods In this randomised, multicentre, phase 3, non-blinded trial, we recruited men through 29 oncology centres in Australia, New Zealand, and Canada. Men with prostate cancer were eligible if they had a PSA relapse after previous attempted curative therapy (radiotherapy or surgery, with or without postoperative radiotherapy) or if they were not considered suitable for curative treatment (because of age, comorbidity, or locally advanced disease). We used a database-embedded, dynamically balanced, randomisation algorithm, coordinated by the Cancer Council Victoria, to randomly assign participants (1:1) to immediate androgen-deprivation therapy (immediate therapy arm) or to delayed androgen-deprivation therapy (delayed therapy arm) with a recommended interval of at least 2 years unless clinically contraindicated. Randomisation for participants with PSA relapse was stratified by type of previous therapy, relapse-free interval, and PSA doubling time; randomisation for those with non-curative disease was stratified by metastatic status; and randomisation in both groups was stratified by planned treatment schedule (continuous or intermittent) and treatment centre. Clinicians could prescribe any form and schedule of androgen-deprivation therapy and group assignment was not masked. The primary outcome was overall survival in the intention-to-treat population. The trial closed to accrual in 2012 after review by the independent data monitoring committee, but data collection continued for 18 months until Feb 26, 2014. It is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12606000301561) and ClinicalTrials.gov (NCT00110162). Findings Between Sept 3, 2004, and July 13, 2012, we recruited 293 men (261 with PSA relapse and 32 with non-curable disease). We randomly assigned 142 men to the immediate therapy arm and 151 to the delayed therapy arm. Median follow-up was 5 years (IQR 3·3–6·2) from the date of randomisation. 16 (11%) men died in the immediate therapy arm and 30 (20%) died in the delayed therapy arm. 5-year overall survival was 86·4% (95% CI 78·5–91·5) in the delayed therapy arm versus 91·2% (84·2–95·2) in the immediate therapy arm (log-rank p=0·047). After Cox regression, the unadjusted HR for overall survival for immediate versus delayed arm assignment was 0·55 (95% CI 0·30–1·00; p=0·050). 23 patients had grade 3 treatment-related adverse events. 105 (36%) men had adverse events requiring hospital admission; none of these events were attributable to treatment or differed between treatment-timing groups. The most common serious adverse events were cardiovascular, which occurred in nine (6%) patients in the delayed therapy arm and 13 (9%) in the immediate therapy arm. Interpretation Immediate receipt of androgen-deprivation therapy significantly improved overall survival compared with delayed intervention in men with PSA-relapsed or non-curable prostate cancer. The results provide benchmark evidence of survival rates and morbidity to discuss with men when considering their treatment options. Funding Australian National Health and Medical Research Council and Cancer Councils, The Royal Australian and New Zealand College of Radiologists, Mayne Pharma Australia.

The appropriateness of default investment options in defined contribution plans : Australian evidence

For participants in defined contribution (DC) plans who refrain from exercising investment choice, plan contributions are invested following the default investment option of their respective plans. Since default investment options of different plans vary widely in terms of their benchmark asset allocation, the most important determinant of investment performance, participants enrolled in these options face significantly different wealth outcomes at retirement. This paper simulates the terminal wealth outcomes under different static asset allocation strategies to evaluate their relative appeal as default investment choice in DC plans. We find that strategies with low or moderate allocation to stocks are consistently outperformed in terms of upside potential of exceeding the participant’s wealth accumulation target at retirement as well as downside risk of falling below that target outcome by aggressive strategies whose allocation to stocks approach 100%. The risk of extremely adverse wealth outcomes for plan participants also does not appear to be very sensitive to asset allocation. Our evidence suggests the appropriateness of strategies heavily tilted towards stocks to be nominated as default investment options in DC plans unless plan providers emphasize predictability of wealth outcomes over adequacy of retirement wealth.

Bone-anchored prosthesis: Evidence that “gains” overcome the “pain”

Most of socket related discomforts leading to a significant decrease in quality of life of individuals with limb amputation can be overcome by surgical techniques enabling bone-anchored prostheses. To date, the OPRA two-stage procedure (i.e., S1, S2) is the most acknowledged treatment. However, surgical implantations of osseointegrated fixations are developing at an unprecedented pace worldwide.[1-18] Clearly, this option is becoming accessible to a wide range of individuals with limb amputations. The team led by Dr Rickard Branemark has published a number of landmark articles each focusing on a particular aspect (e.g., health related quality of life, functional outcomes, bone remodelling, infection rate). [1-3, 19-32] However, evidences presented in this prospective study are remarkable. Functional outcome, health-related quality of life and complications were considered concurrently for a large population (i.e., 51 participants) over an extended period of time (i.e., up to year follow up). Therefore, the “gain” and “pain” of the whole procedure were truly contrasted for the first time. The results confirmed that OPRA surgical and rehabilitation procedures improved significantly prosthetic use, mobility, global situation and fewer problems. Furthermore, the authors reported 47 episodes of infections for 63% (32) participants between post-op S1 and two years follow up. A total of 87% (41) were superficial infections recorded for 28 participants between post-op S2 and two years follow up, while 13% (6) were deep infections occurring for 4 participants during post-op S1 and S2. As expected, post-op S2 phase was the most prone to both infections. More importantly, the vast majority of infections were effectively treated with oral antibiotics. Clearly, this study provided definitive evidence that the benefits of OPRA fixation overcome complications. This article is also establishing reporting standards and benchmark data for future studies focusing on bone-anchored prostheses.

As clear as mud: A critical review of evidence for the ecological roles of Australian dingoes

Top-predators have been reported to have an important role in structuring food webs and maintaining ecological processes for the benefit of biodiversity at lower trophic levels. This is thought to be achieved through their suppressive effects on sympatric mesopredators and prey. Great scientific and public interest surrounds the potential use of top-predators as biodiversity conservation tools, and it can often be difficult to separate what we think we know and what we really know about their ecological utility. Not all the claims made about the ecological roles of top-predators can be substantiated by current evidence. We review the methodology underpinning empirical data on the ecological roles of Australian dingoes (Canis lupus dingo and hybrids) to provide a comprehensive and objective benchmark for knowledge of the ecological roles of Australia's largest terrestrial predator. From a wide variety of methodological flaws, sampling bias, and experimental design constraints inherent to 38 of the 40 field studies we assessed, we demonstrate that there is presently unreliable and inconclusive evidence for dingoes role as a biodiversity regulator. We also discuss the widespread (both taxonomically and geographically) and direct negative effects of dingoes to native fauna, and the few robust studies investigating their positive roles. In light of the highly variable and context-specific impacts of dingoes on faunal biodiversity and the inconclusive state of the literature, we strongly caution against the positive management of dingoes in the absence of a supporting evidence-base for such action.

Evidence for X(5) critical point symmetry in 128Ce

Lifetimes of excited states in 128Ce were measured using the recoil distance Doppler-shift (RDDS) and the Doppler-shift attenuation (DSAM) methods. The experiments were performed at the Wright Nuclear Structure Laboratory of Yale University. Excited states of 128Ce were populated in the 100Mo(32Si,4n) reaction at 120 MeV and the nuclear γ decay was measured with an array of eight Clover detectors positioned at forward and backward angles. The deduced yrast transition strengths together with the energies of the levels within the ground-state (gs) band of 128Ce are in agreement with the predicted values for the X(5) critical point symmetry. Thus, we suggest 128Ce as a benchmark X(5) nucleus in the mass A ≈ 130 region. © World Scientific Publishing Company.

ART-EMAP: A Neural Network Architecture for Learning and Prediction by Evidence Accumulation

This paper introduces ART-EMAP, a neural architecture that uses spatial and temporal evidence accumulation to extend the capabilities of fuzzy ARTMAP. ART-EMAP combines supervised and unsupervised learning and a medium-term memory process to accomplish stable pattern category recognition in a noisy input environment. The ART-EMAP system features (i) distributed pattern registration at a view category field; (ii) a decision criterion for mapping between view and object categories which can delay categorization of ambiguous objects and trigger an evidence accumulation process when faced with a low confidence prediction; (iii) a process that accumulates evidence at a medium-term memory (MTM) field; and (iv) an unsupervised learning algorithm to fine-tune performance after a limited initial period of supervised network training. ART-EMAP dynamics are illustrated with a benchmark simulation example. Applications include 3-D object recognition from a series of ambiguous 2-D views.

ART-EMAP: A Neural Network Architecture for Object Recognition by Evidence Accumulation

A new neural network architecture is introduced for the recognition of pattern classes after supervised and unsupervised learning. Applications include spatio-temporal image understanding and prediction and 3-D object recognition from a series of ambiguous 2-D views. The architecture, called ART-EMAP, achieves a synthesis of adaptive resonance theory (ART) and spatial and temporal evidence integration for dynamic predictive mapping (EMAP). ART-EMAP extends the capabilities of fuzzy ARTMAP in four incremental stages. Stage 1 introduces distributed pattern representation at a view category field. Stage 2 adds a decision criterion to the mapping between view and object categories, delaying identification of ambiguous objects when faced with a low confidence prediction. Stage 3 augments the system with a field where evidence accumulates in medium-term memory (MTM). Stage 4 adds an unsupervised learning process to fine-tune performance after the limited initial period of supervised network training. Each ART-EMAP stage is illustrated with a benchmark simulation example, using both noisy and noise-free data. A concluding set of simulations demonstrate ART-EMAP performance on a difficult 3-D object recognition problem.

Tracking error of exchange-traded funds: Evidence from the UK

This paper is mainly concerned with the tracking accuracy of Exchange Traded Funds (ETFs) listed on the London Stock Exchange (LSE) but also evaluates their performance and pricing efficiency. The findings show that ETFs offer virtually the same return but exhibit higher volatility than their benchmark. It seems that the pricing efficiency, which should come from the creation and redemption process, does not fully hold as equity ETFs show consistent price premiums. The tracking error of the funds is generally small and is decreasing over time. The risk of the ETF, daily price volatility and the total expense ratio explain a large part of the tracking error. Trading volume, fund size, bid-ask spread and average price premium or discount did not have an impact on the tracking error. Finally, it is concluded that market volatility and the tracking error are positively correlated.

Development of an evidence-based scoring system (HF-IS) to assess the quality of heart failure programmes for patients postdischarge from hospital

Aim.  The aim of this study was to develop a potential scoring algorithm for interventions in a chronic heart failure management programme – the Heart Failure Intervention Score – to facilitate quality improvement and programme auditing.

Background.  The overall efficacy of chronic heart failure management programmes has been demonstrated in several meta-analyses. However, meta-analyses did not determine individual interventions in a programme that resulted in beneficial patient outcomes.

Design.  A prospective cross-sectional survey design.

Method.  All chronic heart failure management programmes in Australia (n = 62), identified by a national register, were surveyed to determine programme characteristics and interventions.

Results.  Of the 62 national chronic heart failure management programmes, 48 (77%) completed the survey and 27 individual interventions were identified. Variability in the use of the key interventions was common among the programmes. Each intervention was given an arbitrary weighted score according to the level of supportive evidence available and a total score calculated. Programmes were then categorised into low or high complexity based on several interventions implemented and their weighted score. A total score of ≥190 (median = 178, interquartile range 176–195) was used to divide programmes into two groups. Nine programmes were categorised into high Heart Failure Intervention Score group and majority of these were based in the acute hospital setting (78%). In the low Heart Failure Intervention Score group, there were 39 programmes of which there were a higher proportion of community-based programmes (38%) and programmes in small community hospitals (10%).

Conclusion.  The Heart Failure Intervention Score provides a potential evidence-based quality improvement tool through which a set of minimum standards can be developed. Implementation of the Heart Failure Intervention Score provides guidance to programme coordinators to enable monitoring of standards of heart failure programmes, which may potentially result in better patient outcomes.

Using technology to improve peer review and collaborative conversations to benchmark academic standards

In 2010 the Australian government commissioned the Australian Learning and Teaching Council (ALTC) to undertake a national project to facilitate disciplinary development of threshold learning standards. The aim was to lay the foundation for all higher education providers to demonstrate to the new national higher education regulator, the Tertiary Education Quality and Standards Agency (TEQSA), that graduates achieved or exceeded minimum academic standards. Through a yearlong consultative process, representatives of employers, professional bodies, academics and students, developed learning standards applying to any Australian higher education provider. Willey and Gardner reported using a software tool, SPARKPLUS, in calibrating academic standards amongst teaching staff in large classes. In this paper, we investigate the effectiveness of this technology to promote calibrated understandings with the national accounting learning standards. We found that integrating the software with a purposely designed activity provided significant efficiencies in calibrating understandings about learning standards, developed expertise and a better understanding of what is required to meet these standards and how best to demonstrate them. The software and supporting calibration and assessment process can be adopted by other disciplines, including engineering, seeking to provide direct evidence about performance against learning standards. © 2012 IEEE.

Empirical evidence on real convergence across brazilian states

This paper examines the real convergence hypothesis across Brazilian states. In order to test for the existence of income convergence the or- der of integration of real Gross State Product (GSP) per capita series is examined as well as their di¤erences with respect to the São Paulo state which is used as a benchmark state. Both parametric and semiparametric methods are used and the results show that convergence is achieved in the cases of Alagoas, Amazonas, Bahia, Goiás, Mato Grosso, Minas Gerais, Pernambuco, Piauí, Rio Grande do Sul, Rio de Janeiro and Santa Cata- rina and convergence is weakly achieved in the cases of Ceará, Maranhao, Pará, Paraná and Sergipe .The states of Espírito Santo, Paraíba and Rio Grande do Norte show no convergence. O artigo examina a hipótese de convergência real entre os estados brasileiros. Para testar a existência ou não da convergência da renda a ordem da integração da série do produto real bruto do estado per capita é examinada assim como suas diferenças com respeito ao estado de São Paulo que é usado como base. Foram utilizados métodos paramétricos e semiparametric e os resultados mostram que ocorre convergência nos estados: Alagoas, Amazonas, Baía, Goiás, Mato Grosso, Minas Gerais, Pernambuco, Piauí, Rio Grande do Sul, Rio de Janeiro e Santa Catarina e ocorre convergência fraca nos estados: Ceará, de Maranhão, Pará, Paraná e Sergipe. Nos estado

Exchange rate policies, patterns of specialization and economic development: theory and evidence in developing countries

The objectives of this paper are twofold. First, it intends to provide theoretical elements to analyze the relation between real exchange rates and economic development. Our main hypothesis is very much in line with the Dutch disease literature, and states that competitive currencies contribute to the existence and maintenance of the anufacturing sector in the economy. This, in turn, brings about higher growth rates in the long run, given the existence of increasing returns in the industrial sector, and its importance in generating echnological change and increasing productivity in the overall economy. The second objective of this paper is empirical. It intends to analyze examples of successful exchange rate policies, such as Chile and Indonesia in the eighties, as a benchmark for comparison with countries where currency overvaluation has taken place, such as Brazil. In the latter case, the local currency is being inflated by large capital inflows, due to high domestic interest rates and to a boom in demand and prices of commodities in the international markets. It will be argued that the industrial sector bears most of the burden when the currency appreciates, and that Brazil risks at deindustrialization if there are no changes in the exchange rate regime

Relationships between company size, types of production system and supply chain management: evidence from electro-electronics sector in Brazil

Purpose – The purpose of this paper is to investigate how company size and the type of production system affect the adoption of supply chain management (SCM) practices in companies in the electro‐electronics sector in Brazil. Design/methodology/approach – An e‐mail survey of 107 companies associated with the Brazilian Electrical and Electronics Industry Association (ABINEE) was conducted. Statistical techniques were employed to verify the adoption of SCM practices according to the size of the company and its production system. Findings – The major results indicate that the larger the size of the company, the higher the level of adoption of SCM practices, and that the choice of SCM practices depends upon the type of production system implemented. Practical implications – The implications of this study are useful to top management leaders of small and medium‐sized enterprises since the findings enable them to identify the most common practices adopted by either large‐, medium‐ or small‐sized companies in order to benchmark the level of adoption of SCM practices. Production managers can also benefit from this study by identifying the SCM practices that may support certain production systems.