Therapeutic options for metastatic castration resistant prostate cancer : has the situation improved?

Limited treatment options for Castration Resistant Prostate Cancer (CRPC) still remain a major challenge. Despite therapeutic advances, most patients with malignant PCa have a poor prognosis. Since the year 2000, we have rapidly expanded our understanding of the molecular mechanisms underlying CRPC and this has led to an unprecedented number of new drug approvals within a short span of time. Recently, four new agents namely Abiraterone Acetate, Enzalutamide, Cabazitaxel, and Radium-223 have been shown to be effective in the post-chemotherapy setting in CRPC. The continued dependency of CRPC on androgen synthesis has seen the development of a number of new anti-androgen therapies, with abiraterone acetate and Enzalutamide being the most promising discoveries. Immunotherapeutic approaches have also found their niche in PCa with Sipuleucel-T shown to be effective in minimally asymptomatic CRPC. Research focussed on bone-targeting therapies has witnessed the arrival of promising new drugs with Denosumab and Radium-223 displaying improved survival of patients with CRPC. This review briefly discusses the findings and limitations from ongoing and completed clinical trials of novel treatments and regimens. In addition, potential mechanisms of therapy resistance and future challenges are discussed.

Improved fabrication of melt electrospun tissue engineering scaffolds using direct writing and advanced electric field control

Direct writing melt electrospinning is an additive manufacturing technique capable of the layer-by-layer fabrication of highly ordered 3d tissue engineering scaffolds from micron-diameter fibres. The utility of these scaffolds, however, is limited by the maximum achievable height of controlled fibre deposition, beyond which the structure becomes increasingly disordered. A source of this disorder is charge build-up on the deposited polymer producing unwanted coulombic forces. In this study we introduce a novel melt electrospinning platform with dual voltage power supplies to reduce undesirable charge effects and improve fibre deposition control. We produced and characterised several 90° cross-hatched fibre scaffolds using a range of needle/collector plate voltages. Fibre thickness was found to be sensitive only to overall potential and invariant to specific tip/collector voltage. We also produced ordered scaffolds up to 200 layers thick (fibre spacing 1 mm, diameter 40 μm) and characterised structure in terms of three distinct zones; ordered, semi-ordered and disordered. Our in vitro analysis indicates successful cell attachment and distribution throughout the scaffolds, with little evidence of cell death after seven days. This study demonstrates the importance of electrostatic control for reducing destabilising polymer charge effects and enabling the fabrication of morphologically suitable scaffolds for tissue engineering.

Improved Security Analysis of Fugue-256 (Poster)

We present some improved analytical results as part of the ongoing work on the analysis of Fugue-256 hash function, a second round candidate in the NIST’s SHA3 competition. First we improve Aumasson and Phans’ integral distinguisher on the 5.5 rounds of the final transformation of Fugue-256 to 16.5 rounds. Next we improve the designers’ meet-in-the-middle preimage attack on Fugue-256 from 2480 time and memory to 2416. Finally, we comment on possible methods to obtain free-start distinguishers and free-start collisions for Fugue-256.

Simultaneous underwater visibility assessment, enhancement and improved stereo

Vision-based underwater navigation and obstacle avoidance demands robust computer vision algorithms, particularly for operation in turbid water with reduced visibility. This paper describes a novel method for the simultaneous underwater image quality assessment, visibility enhancement and disparity computation to increase stereo range resolution under dynamic, natural lighting and turbid conditions. The technique estimates the visibility properties from a sparse 3D map of the original degraded image using a physical underwater light attenuation model. Firstly, an iterated distance-adaptive image contrast enhancement enables a dense disparity computation and visibility estimation. Secondly, using a light attenuation model for ocean water, a color corrected stereo underwater image is obtained along with a visibility distance estimate. Experimental results in shallow, naturally lit, high-turbidity coastal environments show the proposed technique improves range estimation over the original images as well as image quality and color for habitat classification. Furthermore, the recursiveness and robustness of the technique allows implementation onboard an Autonomous Underwater Vehicle for improving navigation and obstacle avoidance performance.

Delving deeper into maintenance behaviour

Andreasen (2003) argues that there is a ‘starting change’ bias in the social marketing field as much research is centred on inducing initial behavioural change. However, repeat or maintenance behaviour is often critical to achieving social goals across many domains. For instance, the repeat use of professional therapeutic services is vital for improved mental health, although premature discontinuance of service use is common (Wang, 2007). This study contributes to addressing this gap in the social marketing literature by exploring key drivers of maintenance behaviour, in the form of repeat service use, in mental health. This is in line with Andreasen’s (1994) argument that social marketing is an appropriate approach to addressing mental health challenges.

An improved robust field weakening algorithm for direct torque controlled synchronous reluctance motor drives

This paper presents an improved field weakening algorithm for synchronous reluctance motor (RSMs) drives. The proposed algorithm is robust to the variations in the machine d- and q-axes inductances. The transition between the maximum torque per ampere (MTPA), current and voltage limits as well as the maximum torque per flux (MTPF) trajectories is smooth. The proposed technique is combined with the direct torque control method to attain a high performance drive in the field weakening region. Simulation and experimental results are supplemented to verify the effectiveness of the proposed approach.

An improved modal strain energy method for structural damage detection, 2D simulation

Structural damage detection using modal strain energy (MSE) is one of the most efficient and reliable structural health monitoring techniques. However, some of the existing MSE methods have been validated for special types of structures such as beams or steel truss bridges which demands improving the available methods. The purpose of this study is to improve an efficient modal strain energy method to detect and quantify the damage in complex structures at early stage of formation. In this paper, a modal strain energy method was mathematically developed and then numerically applied to a fixed-end beam and a three-story frame including single and multiple damage scenarios in absence and presence of up to five per cent noise. For each damage scenario, all mode shapes and natural frequencies of intact structures and the first five mode shapes of assumed damaged structures were obtained using STRAND7. The derived mode shapes of each intact and damaged structure at any damage scenario were then separately used in the improved formulation using MATLAB to detect the location and quantify the severity of damage as compared to those obtained from previous method. It was found that the improved method is more accurate, efficient and convergent than its predecessors. The outcomes of this study can be safely and inexpensively used for structural health monitoring to minimize the loss of lives and property by identifying the unforeseen structural damages.

Behaviour of LSF floor systems with improved joist sections under fire conditions

Fire safety design of buildings is essential to safeguard lives and minimize the loss of damage to properties. Light-weight cold-formed steel channel sections along with fire resistive plasterboards are used to construct light gauge steel frame floor systems to provide the required fire resistance rating. However, simply adding more plasterboard layers is not an efficient method to increase FRR. Hence this research focuses on using joists with improved joist section profiles such as hollow flange sections to increase the structural capacity of floor systems under fire conditions and thus their FRR. In this research, the structural and thermal behaviour of LSF floor systems made of LiteSteel Beams with different plasterboard and insulation configurations was investigated using four full scale tests under standard fires. Based on the ultimate failure load of the floor joist at ambient temperature, transient state fire tests were conducted for different Load Ratios. These fire tests showed that the new LSF floor system has improved the FRR well above that of those made of lipped channel sections. The joist failure was predominantly due to local buckling of LSB compression flanges near mid-span with severe yielding of tension flanges. Fire tests have provided valuable structural and thermal performance data of tested floor systems that included time-temperature profiles, and failure times and temperatures. Average failure temperatures of LSB joists and reduced yield strengths were used to predict their ultimate moment capacities, which were compared with corresponding test capacities. This allowed an assessment in relation to the accuracy of current design rules for steel joists at elevated temperatures. This paper presents the details of full scale fire tests of LSF floor systems made of LSB joists with different plasterboard and insulation configurations and their results along with some important findings.

An improved computational method in structural dynamics

Purpose – In structural, earthquake and aeronautical engineering and mechanical vibration, the solution of dynamic equations for a structure subjected to dynamic loading leads to a high order system of differential equations. The numerical methods are usually used for integration when either there is dealing with discrete data or there is no analytical solution for the equations. Since the numerical methods with more accuracy and stability give more accurate results in structural responses, there is a need to improve the existing methods or develop new ones. The paper aims to discuss these issues. Design/methodology/approach – In this paper, a new time integration method is proposed mathematically and numerically, which is accordingly applied to single-degree-of-freedom (SDOF) and multi-degree-of-freedom (MDOF) systems. Finally, the results are compared to the existing methods such as Newmark’s method and closed form solution. Findings – It is concluded that, in the proposed method, the data variance of each set of structural responses such as displacement, velocity, or acceleration in different time steps is less than those in Newmark’s method, and the proposed method is more accurate and stable than Newmark’s method and is capable of analyzing the structure at fewer numbers of iteration or computation cycles, hence less time-consuming. Originality/value – A new mathematical and numerical time integration method is proposed for the computation of structural responses with higher accuracy and stability, lower data variance, and fewer numbers of iterations for computational cycles.

Renewable energy distribution in public spaces: Analyzing the case of Ballast Point Park in Sydney, using a triple bottom line approach

As cities are rapidly developing new interventions against climate change, embedding renewable energy in public spaces is an important strategy. However, most interventions primarily include environmental sustainability while neglecting the social and economic interrelationships of electricity production. Although there is a growing interest in sustainability within environmental design and landscape architecture, public spaces are still awaiting viable energy-conscious design and assessment interventions. The purpose of this paper is to investigate this issue in a renowned public space—Ballast Point Park in Sydney—using a triple bottom line (TBL) case study approach. The emerging factors and relationships of each component of TBL, within the context of public open space, are identified and discussed. With specific focus on renewable energy distribution in and around Ballast Point Park, the paper concludes with a general design framework, which conceptualizes an optimal distribution of onsite electricity produced from renewable sources embedded in public open spaces.

Book Review: "Below the Line: Producers and Production Studies in the New Television Economy by Vicki Mayer", Duke University Press, 2012

Vicki Mayer’s book is unusual in that, despite its title, it is not about television producers at all, or at least not in the sense that scholars and the television industry itself have traditionally understood the role. Rather than referring to those in creative, managerial or financial control, or those with substantial intellectual input into a program, Mayer uses the term in a deliberately broad sense to mean, essentially, anyone ‘whose labor, however small, contributes to [television] production’ (179).

Improved Kalman filter initialisation using neurofuzzy estimation

It is traditional to initialise Kalman filters and extended Kalman filters with estimates of the states calculated directly from the observed (raw) noisy inputs, but unfortunately their performance is extremely sensitive to state initialisation accuracy: good initial state estimates ensure fast convergence whereas poor estimates may give rise to slow convergence or even filter divergence. Divergence is generally due to excessive observation noise and leads to error magnitudes that quickly become unbounded (R.J. Fitzgerald, 1971). When a filter diverges, it must be re initialised but because the observations are extremely poor, re initialised states will have poor estimates. The paper proposes that if neurofuzzy estimators produce more accurate state estimates than those calculated from the observed noisy inputs (using the known state model), then neurofuzzy estimates can be used to initialise the states of Kalman and extended Kalman filters. Filters whose states have been initialised with neurofuzzy estimates should give improved performance by way of faster convergence when the filter is initialised, and when a filter is re started after divergence

Case study: Dragline swing to dump automation

Dragline Swing to Dump Automation By Peter Corke, CSIRO Manufacturing Technology/CRC for Mining Technology and Equipment (CMTE) Peter Corke presented a case study of a project to automate the dragline swing to dump operation. The project is funded by ACARP, BHP Coal, Pacific Coal and the CMTE and is being carried out on a dragline at Pacific Coal's Meandu mine near Brisbane. Corke began by highlighting that the minerals industry makes extensive use of large, mechanised machines. However, unlike other industries, mining has not adopted automation and most machines are controlled by human operators on board the machine itself. Choosing an automation target The dragline automation was chosen because: ò draglines are one of the biggest capital assets in a mine; ò performance between operators vary significantly, so improved capital utilisation is possible; ò the dragline is often the bottleneck in production; ò a large part of the operation cycle is spent swinging from dig to dump; and ò it is technically feasible. There has been a history of drag line automation projects, none with great success.