In vivo knockdown of the androgen receptor results in growth inhibition and regression of well-established, castration-resistant prostate tumours

Purpose: Progression to the castration-resistant state is the incurable and lethal end stage of prostate cancer, and there is strong evidence that androgen receptor (AR) still plays a central role in this process. We hypothesize that knocking down AR will have a major effect on inhibiting growth of castration-resistant tumors. Experimental Design: Castration-resistant C4-2 human prostate cancer cells stably expressing a tetracycline-inducible AR-targeted short hairpin RNA (shRNA) were generated to directly test the effects of AR knockdown in C4-2 human prostate cancer cells and tumors. Results:In vitro expression of AR shRNA resulted in decreased levels of AR mRNA and protein, decreased expression of prostate-specific antigen (PSA), reduced activation of the PSA-luciferase reporter, and growth inhibition of C4-2 cells. Gene microarray analyses revealed that AR knockdown under hormone-deprived conditions resulted in activation of genes involved in apoptosis, cell cycle regulation, protein synthesis, and tumorigenesis. To ensure that tumors were truly castration-resistant in vivo, inducible AR shRNA expressing C4-2 tumors were grown in castrated mice to an average volume of 450 mm3. In all of the animals, serum PSA decreased, and in 50% of them, there was complete tumor regression and disappearance of serum PSA. Conclusions: Whereas castration is ineffective in castration-resistant prostate tumors, knockdown of AR can decrease serum PSA, inhibit tumor growth, and frequently cause tumor regression. This study is the first direct evidence that knockdown of AR is a viable therapeutic strategy for treatment of prostate tumors that have already progressed to the castration-resistant state.

Empirical investigation of interactive highway safety design model accident prediction algorithm : Rural intersections

One major gap in transportation system safety management is the ability to assess the safety ramifications of design changes for both new road projects and modifications to existing roads. To fulfill this need, FHWA and its many partners are developing a safety forecasting tool, the Interactive Highway Safety Design Model (IHSDM). The tool will be used by roadway design engineers, safety analysts, and planners throughout the United States. As such, the statistical models embedded in IHSDM will need to be able to forecast safety impacts under a wide range of roadway configurations and environmental conditions for a wide range of driver populations and will need to be able to capture elements of driving risk across states. One of the IHSDM algorithms developed by FHWA and its contractors is for forecasting accidents on rural road segments and rural intersections. The methodological approach is to use predictive models for specific base conditions, with traffic volume information as the sole explanatory variable for crashes, and then to apply regional or state calibration factors and accident modification factors (AMFs) to estimate the impact on accidents of geometric characteristics that differ from the base model conditions. In the majority of past approaches, AMFs are derived from parameter estimates associated with the explanatory variables. A recent study for FHWA used a multistate database to examine in detail the use of the algorithm with the base model-AMF approach and explored alternative base model forms as well as the use of full models that included nontraffic-related variables and other approaches to estimate AMFs. That research effort is reported. The results support the IHSDM methodology.

Implementing value management as a decision-making tool in the design stages of design and build construction projects : a methodology for improved cost optimization

Value Management (VM) has been proven to provide a structured framework, together with other supporting tools and techniques, that facilitate effective decision-making in many types of projects, thus achieving ‘best value’ for clients. One of the major success factors of VM in achieving better project objectives for clients is through the provision of beneficial input by multi-disciplinary team members being involved in critical decision-making discussions during the early stage of construction projects. This paper describes a doctoral research proposal based on the application of VM in design and build construction projects, especially focusing on the design stage. The research aims to study the effects of implementing VM in design and build construction projects, in particular how well the methodology addresses issues related to cost overruns resulting from poor coordination and overlooking of critical constructability issues amongst team members in construction projects in Malaysia. It is proposed that through contractors’ early involvement during the design stage, combined with the use of the VM methodology, particularly as a decision-making tool, better optimization of construction cost can be achieved, thus promoting more efficient and effective constructability. The main methods used in this research involve a thorough literature study, semi-structured interviews, and a survey of major stakeholders, a detailed case study and a VM workshop and focus group discussions involving construction professionals in order to explore and possibly develop a framework and a specific methodology for the facilitating successful application of VM within design and build construction projects.

Patterns, heuristics for architectural design support: making use of evolutionary modelling in design

Software used by architectural and industrial designers – has moved from becoming a tool for drafting, towards use in verification, simulation, project management and project sharing remotely. In more advanced models, parameters for the designed object can be adjusted so a family of variations can be produced rapidly. With advances in computer aided design technology, numerous design options can now be generated and analyzed in real time. However the use of digital tools to support design as an activity is still at an early stage and has largely been limited in functionality with regard to the design process. To date, major CAD vendors have not developed an integrated tool that is able to both leverage specialized design knowledge from various discipline domains (known as expert knowledge systems) and support the creation of design alternatives that satisfy different forms of constraints. We propose that evolutionary computing and machine learning be linked with parametric design techniques to record and respond to a designer’s own way of working and design history. It is expected that this will lead to results that impact on future work on design support systems-(ergonomics and interface) as well as implicit constraint and problem definition for problems that are difficult to quantify.

Positive design and construction of mechanisms for the sustainable development in microenterprises in Africa

Enterprise development and its contribution to societal and economic outcomes are well known. However, limited research into microenterprises and the practices of microfinance and microcredit in developing countries has been carried out. This chapter presents the findings of research based on six years of engagement with the microentrepreneurs of Beira in Mozambique and suggests a model for responsible and sustainable support for enterprise development in developing economies. Building on semistructured interviews, observation, and participatory action research, this research project articulates a new approach supportive of enterprise development, as a process of cocreation with local people and based on sustainability principles. These findings are part of a longitudinal study of the successes and failures of small enterprises and their impact on social and economic activity.

Perceptions of the psychological well-being and care of older home care clients : clients and their carers

Aim. To explore and compare older home care clients’ (65+) and their professionals’ perceptions of the clients’ psychological well-being and care and to identify possible differences in these perceptions. Background. Psychological well-being is considered an important dimension of quality of life. With advancing age, older people require home care support to be able to remain in their own home. The main goal of care is to maximise their independence and quality of life. Design. Descriptive, survey design with questionnaire. Methods. A postal questionnaire was distributed to 200 older home care clients and 570 social and health care professionals in 2007. The total response rate was 63%. The questionnaire consisted of questions about clients’ psychological well-being and the provision of care by home care professionals. The differences in responses between clients and professionals were analysed using cross-tabulations, the Pearson Chi-Square Test and Fisher’s Exact Tests. Results. The professional group believed that their clients did not have plans for the future. They believed that their clients felt themselves depressed and suffering from loneliness significantly more often than the client group did. The client group were also significantly more critical of the care (motivating independent actions, physical, psychological and social care) they got from the professional group than how the professionals evaluated the care they gave. Conclusions. To be able to support older clients to continue living at home, professionals need to provide a service that meets client’s own perceptions and complex social and health care needs as well as personal sense of well-being. Relevance to clinical practice. The findings offer useful insights for the professional in planning and delivering appropriate home care services. A better understanding of differences between clients’ and professionals’ perceptions could lead to a better individualised care outcome.

Smart Grid Test Bed Design and Implementation

Given there is currently a migration trend from traditional electrical supervisory control and data acquisition (SCADA) systems towards a smart grid based approach to critical infrastructure management. This project provides an evaluation of existing and proposed implementations for both traditional electrical SCADA and smart grid based architectures, and proposals a set of reference requirements which test bed implementations should implement. A high-level design for smart grid test beds is proposed and initial implementation performed, based on the proposed design, using open source and freely available software tools. The project examines the move towards smart grid based critical infrastructure management and illustrates the increased security requirements. The implemented test bed provides a basic framework for testing network requirements in a smart grid environment, as well as a platform for further research and development. Particularly to develop, implement and test network security related disturbances such as intrusion detection and network forensics. The project undertaken proposes and develops an architecture of the emulation of some smart grid functionality. The Common Open Research Emulator (CORE) platform was used to emulate the communication network of the smart grid. Specifically CORE was used to virtualise and emulate the TCP/IP networking stack. This is intended to be used for further evaluation and analysis, for example the analysis of application protocol messages, etc. As a proof of concept, software libraries were designed, developed and documented to enable and support the design and development of further smart grid emulated components, such as reclosers, switches, smart meters, etc. As part of the testing and evaluation a Modbus based smart meter emulator was developed to provide basic functionality of a smart meter. Further code was developed to send Modbus request messages to the emulated smart meter and receive Modbus responses from it. Although the functionality of the emulated components were limited, it does provide a starting point for further research and development. The design is extensible to enable the design and implementation of additional SCADA protocols. The project also defines an evaluation criteria for the evaluation of the implemented test bed, and experiments are designed to evaluate the test bed according to the defined criteria. The results of the experiments are collated and presented, and conclusions drawn from the results to facilitate discussion on the test bed implementation. The discussion undertaken also present possible future work.

Facilitating needs based cancer care for people with a chronic disease : evaluation of an intervention using a multi-centre interrupted time series design

Background: Palliative care should be provided according to the individual needs of the patient, caregiver and family, so that the type and level of care provided, as well as the setting in which it is delivered, are dependent on the complexity and severity of individual needs, rather than prognosis or diagnosis. This paper presents a study designed to assess the feasibility and efficacy of an intervention to assist in the allocation of palliative care resources according to need, within the context of a population of people with advanced cancer. ---------- Methods/design: People with advanced cancer and their caregivers completed bi-monthly telephone interviews over a period of up to 18 months to assess unmet needs, anxiety and depression, quality of life, satisfaction with care and service utilisation. The intervention, introduced after at least two baseline phone interviews, involved a) training medical, nursing and allied health professionals at each recruitment site on the use of the Palliative Care Needs Assessment Guidelines and the Needs Assessment Tool: Progressive Disease - Cancer (NAT: PD-C); b) health professionals completing the NAT: PD-C with participating patients approximately monthly for the rest of the study period. Changes in outcomes will be compared pre-and post-intervention.---------- Discussion: The study will determine whether the routine, systematic and regular use of the Guidelines and NAT: PD-C in a range of clinical settings is a feasible and effective strategy for facilitating the timely provision of needs based care.

Longitudinal modelling of the influence of individual differences and the workplace on well-being and work engagement

A set of non-nested longitudinal models tested the relationships between personal and workplace resources, well-being and work engagement. The reciprocal model, trimmed of trivial paths had the best fit and parsimony. The model showed the strong influences of concurrent functioning, stability of variables over time and weaker reciprocal relationships between variables across time. Individuals with greater confidence in themselves and the future experience better work conditions and have greater well-being and work engagement. These day-to-day influences are equalled by the long term strength and stability of Individual Factors, Positive Workplace Factors, and Overall Well-Being. Whilst the reciprocal paths had only weak to mild effects, there was mutual reinforcement of Individual Factors and Overall Well-Being, with Positive Workplace Factors and Work Engagement counterbalancing each other, indicating a more complex relationship. Well-being, particularly, is anchored in the immediate and distant past and provides a robust stability to functioning into the future.

Assessing the leanness in product design : a model for planned design reuse

Shrinking product lifecycles, tough international competition, swiftly changing technologies, ever increasing customer quality expectation and demanding high variety options are some of the forces that drive next generation of development processes. To overcome these challenges, design cost and development time of product has to be reduced as well as quality to be improved. Design reuse is considered one of the lean strategies to win the race in this competitive environment. design reuse can reduce the product development time, product development cost as well as number of defects which will ultimately influence the product performance in cost, time and quality. However, it has been found that no or little work has been carried out for quantifying the effectiveness of design reuse in product development performance such as design cost, development time and quality. Therefore, in this study we propose a systematic design reuse based product design framework and developed a design leanness index (DLI) as a measure of effectiveness of design reuse. The DLI is a representative measure of reuse effectiveness in cost, development time and quality. Through this index, a clear relationship between reuse measure and product development performance metrics has been established. Finally, a cost based model has been developed to maximise the design leanness index for a product within the given set of constraints achieving leanness in design process.

A synthesizable hardware evolutionary algorithm design for unmanned aerial system real-time path planning

The main objective of this paper is to detail the development of a feasible hardware design based on Evolutionary Algorithms (EAs) to determine flight path planning for Unmanned Aerial Vehicles (UAVs) navigating terrain with obstacle boundaries. The design architecture includes the hardware implementation of Light Detection And Ranging (LiDAR) terrain and EA population memories within the hardware, as well as the EA search and evaluation algorithms used in the optimizing stage of path planning. A synthesisable Very-high-speed integrated circuit Hardware Description Language (VHDL) implementation of the design was developed, for realisation on a Field Programmable Gate Array (FPGA) platform. Simulation results show significant speedup compared with an equivalent software implementation written in C++, suggesting that the present approach is well suited for UAV real-time path planning applications.

Autonomous underwater vehicle trajectory design coupled with predictive ocean models : a case study

Data collection using Autonomous Underwater Vehicles (AUVs) is increasing in importance within the oceano- graphic research community. Contrary to traditional moored or static platforms, mobile sensors require intelligent planning strategies to manoeuvre through the ocean. However, the ability to navigate to high-value locations and collect data with specific scientific merit is worth the planning efforts. In this study, we examine the use of ocean model predictions to determine the locations to be visited by an AUV, and aid in planning the trajectory that the vehicle executes during the sampling mission. The objectives are: a) to provide near-real time, in situ measurements to a large-scale ocean model to increase the skill of future predictions, and b) to utilize ocean model predictions as a component in an end-to-end autonomous prediction and tasking system for aquatic, mobile sensor networks. We present an algorithm designed to generate paths for AUVs to track a dynamically evolving ocean feature utilizing ocean model predictions. This builds on previous work in this area by incorporating the predicted current velocities into the path planning to assist in solving the 3-D motion planning problem of steering an AUV between two selected locations. We present simulation results for tracking a fresh water plume by use of our algorithm. Additionally, we present experimental results from field trials that test the skill of the model used as well as the incorporation of the model predictions into an AUV trajectory planner. These results indicate a modest, but measurable, improvement in surfacing error when the model predictions are incorporated into the planner.

Design and implementation of sensor networks for the observation and research of harmful algal blooms in southern California coastal waters

Harmful Algal Blooms (HABs) have become an important environmental concern along the western coast of the United States. Toxic and noxious blooms adversely impact the economies of coastal communities in the region, pose risks to human health, and cause mortality events that have resulted in the deaths of thousands of fish, marine mammals and seabirds. One goal of field-based research efforts on this topic is the development of predictive models of HABs that would enable rapid response, mitigation and ultimately prevention of these events. In turn, these objectives are predicated on understanding the environmental conditions that stimulate these transient phenomena. An embedded sensor network (Fig. 1), under development in the San Pedro Shelf region off the Southern California coast, is providing tools for acquiring chemical, physical and biological data at high temporal and spatial resolution to help document the emergence and persistence of HAB events, supporting the design and testing of predictive models, and providing contextual information for experimental studies designed to reveal the environmental conditions promoting HABs. The sensor platforms contained within this network include pier-based sensor arrays, ocean moorings, HF radar stations, along with mobile sensor nodes in the form of surface and subsurface autonomous vehicles. FreewaveTM radio modems facilitate network communication and form a minimally-intrusive, wireless communication infrastructure throughout the Southern California coastal region, allowing rapid and cost-effective data transfer. An emerging focus of this project is the incorporation of a predictive ocean model that assimilates near-real time, in situ data from deployed Autonomous Underwater Vehicles (AUVs). The model then assimilates the data to increase the skill of both nowcasts and forecasts, thus providing insight into bloom initiation as well as the movement of blooms or other oceanic features of interest (e.g., thermoclines, fronts, river discharge, etc.). From these predictions, deployed mobile sensors can be tasked to track a designated feature. This focus has led to the creation of a technology chain in which algorithms are being implemented for the innovative trajectory design for AUVs. Such intelligent mission planning is required to maneuver a vehicle to precise depths and locations that are the sites of active blooms, or physical/chemical features that might be sources of bloom initiation or persistence. The embedded network yields high-resolution, temporal and spatial measurements of pertinent environmental parameters and resulting biology (see Fig. 1). Supplementing this with ocean current information and remotely sensed imagery and meteorological data, we obtain a comprehensive foundation for developing a fundamental understanding of HAB events. This then directs labor- intensive and costly sampling efforts and analyses. Additionally, we provide coastal municipalities, managers and state agencies with detailed information to aid their efforts in providing responsible environmental stewardship of their coastal waters.

Research report. A subtropical urban community. Investigating medium to high density residential typologies. Findings and recommendations from the Design Charrette

In June 2009 the Centre for Subtropical Design at the Queensland University of Technology conducted a design charrette to research design concepts for liveable subtropical neighbourhoods characterised by higher-density, mixed-use, family orientated housing. Subsequent analysis of the proposed designs evaluated how well these typologies support economic, environmental and social sustainability. The study was led by Ms Rosemary Kennedy, Director of the Centre for Subtropical Design and QUT School of Design Adjunct Professor Peter Richards, Chair of the Centre for Subtropical Design Board and director of Deicke Richards Architects and Urban Designers.

A subtropical urban community. Investigating medium to high density residential typologies. Recommendations from the design charrette

In June 2009 the Centre for Subtropical Design at the Queensland University of Technology conducted a design charrette to research design concepts for liveable subtropical neighbourhoods characterised by higher-density, mixed-use, family orientated housing. Subsequent analysis of the proposed designs evaluated how well these typologies support economic, environmental and social sustainability. The study was led by Ms Rosemary Kennedy, Director of the Centre for Subtropical Design and QUT School of Design Adjunct Professor Peter Richards, Chair of the Centre for Subtropical Design Board and director of Deicke Richards Architects and Urban Designers.