SNP technologies for drug discovery : a current review

Single nucleotide polymorphisms (SNPs) are unique genetic differences between individuals that contribute in significant ways to the determination of human variation including physical characteristics like height and appearance as well as less obvious traits such as personality, behaviour and disease susceptibility. SNPs can also significantly influence responses to pharmacotherapy and whether drugs will produce adverse reactions. The development of new drugs can be made far cheaper and more rapid by selecting participants in drug trials based on their genetically determined response to drugs. Technology that can rapidly and inexpensively genotype thousands of samples for thousands of SNPs at a time is therefore in high demand. With the completion of the human genome project, about 12 million true SNPs have been identified to date. However, most have not yet been associated with disease susceptibility or drug response. Testing for the appropriate drug response SNPs in a patient requiring treatment would enable individualised therapy with the right drug and dose administered correctly the first time. Many pharmaceutical companies are also interested in identifying SNPs associated with polygenic traits so novel therapeutic targets can be discovered. This review focuses on technologies that can be used for genotyping known SNPs as well as for the discovery of novel SNPs associated with drug response.

Life cycle modelling and design knowledge development in 3D virtual environments : final report

Experience plays an important role in building management. “How often will this asset need repair?” or “How much time is this repair going to take?” are types of questions that project and facility managers face daily in planning activities. Failure or success in developing good schedules, budgets and other project management tasks depend on the project manager's ability to obtain reliable information to be able to answer these types of questions. Young practitioners tend to rely on information that is based on regional averages and provided by publishing companies. This is in contrast to experienced project managers who tend to rely heavily on personal experience. Another aspect of building management is that many practitioners are seeking to improve available scheduling algorithms, estimating spreadsheets and other project management tools. Such “micro-scale” levels of research are important in providing the required tools for the project manager's tasks. However, even with such tools, low quality input information will produce inaccurate schedules and budgets as output. Thus, it is also important to have a broad approach to research at a more “macro-scale.” Recent trends show that the Architectural, Engineering, Construction (AEC) industry is experiencing explosive growth in its capabilities to generate and collect data. There is a great deal of valuable knowledge that can be obtained from the appropriate use of this data and therefore the need has arisen to analyse this increasing amount of available data. Data Mining can be applied as a powerful tool to extract relevant and useful information from this sea of data. Knowledge Discovery in Databases (KDD) and Data Mining (DM) are tools that allow identification of valid, useful, and previously unknown patterns so large amounts of project data may be analysed. These technologies combine techniques from machine learning, artificial intelligence, pattern recognition, statistics, databases, and visualization to automatically extract concepts, interrelationships, and patterns of interest from large databases. The project involves the development of a prototype tool to support facility managers, building owners and designers. This final report presents the AIMMTM prototype system and documents how and what data mining techniques can be applied, the results of their application and the benefits gained from the system. The AIMMTM system is capable of searching for useful patterns of knowledge and correlations within the existing building maintenance data to support decision making about future maintenance operations. The application of the AIMMTM prototype system on building models and their maintenance data (supplied by industry partners) utilises various data mining algorithms and the maintenance data is analysed using interactive visual tools. The application of the AIMMTM prototype system to help in improving maintenance management and building life cycle includes: (i) data preparation and cleaning, (ii) integrating meaningful domain attributes, (iii) performing extensive data mining experiments in which visual analysis (using stacked histograms), classification and clustering techniques, associative rule mining algorithm such as “Apriori” and (iv) filtering and refining data mining results, including the potential implications of these results for improving maintenance management. Maintenance data of a variety of asset types were selected for demonstration with the aim of discovering meaningful patterns to assist facility managers in strategic planning and provide a knowledge base to help shape future requirements and design briefing. Utilising the prototype system developed here, positive and interesting results regarding patterns and structures of data have been obtained.

Improving the management of building life cycle : a data mining approach

The construction industry has adapted information technology in its processes in terms of computer aided design and drafting, construction documentation and maintenance. The data generated within the construction industry has become increasingly overwhelming. Data mining is a sophisticated data search capability that uses classification algorithms to discover patterns and correlations within a large volume of data. This paper presents the selection and application of data mining techniques on maintenance data of buildings. The results of applying such techniques and potential benefits of utilising their results to identify useful patterns of knowledge and correlations to support decision making of improving the management of building life cycle are presented and discussed.

Life Cycle Modelling and Design Knowledge Development in 3D Virtual Environments

Experience plays an important role in building management. “How often will this asset need repair?” or “How much time is this repair going to take?” are types of questions that project and facility managers face daily in planning activities. Failure or success in developing good schedules, budgets and other project management tasks depend on the project manager's ability to obtain reliable information to be able to answer these types of questions. Young practitioners tend to rely on information that is based on regional averages and provided by publishing companies. This is in contrast to experienced project managers who tend to rely heavily on personal experience. Another aspect of building management is that many practitioners are seeking to improve available scheduling algorithms, estimating spreadsheets and other project management tools. Such “micro-scale” levels of research are important in providing the required tools for the project manager's tasks. However, even with such tools, low quality input information will produce inaccurate schedules and budgets as output. Thus, it is also important to have a broad approach to research at a more “macro-scale.” Recent trends show that the Architectural, Engineering, Construction (AEC) industry is experiencing explosive growth in its capabilities to generate and collect data. There is a great deal of valuable knowledge that can be obtained from the appropriate use of this data and therefore the need has arisen to analyse this increasing amount of available data. Data Mining can be applied as a powerful tool to extract relevant and useful information from this sea of data. Knowledge Discovery in Databases (KDD) and Data Mining (DM) are tools that allow identification of valid, useful, and previously unknown patterns so large amounts of project data may be analysed. These technologies combine techniques from machine learning, artificial intelligence, pattern recognition, statistics, databases, and visualization to automatically extract concepts, interrelationships, and patterns of interest from large databases. The project involves the development of a prototype tool to support facility managers, building owners and designers. This Industry focused report presents the AIMMTM prototype system and documents how and what data mining techniques can be applied, the results of their application and the benefits gained from the system. The AIMMTM system is capable of searching for useful patterns of knowledge and correlations within the existing building maintenance data to support decision making about future maintenance operations. The application of the AIMMTM prototype system on building models and their maintenance data (supplied by industry partners) utilises various data mining algorithms and the maintenance data is analysed using interactive visual tools. The application of the AIMMTM prototype system to help in improving maintenance management and building life cycle includes: (i) data preparation and cleaning, (ii) integrating meaningful domain attributes, (iii) performing extensive data mining experiments in which visual analysis (using stacked histograms), classification and clustering techniques, associative rule mining algorithm such as “Apriori” and (iv) filtering and refining data mining results, including the potential implications of these results for improving maintenance management. Maintenance data of a variety of asset types were selected for demonstration with the aim of discovering meaningful patterns to assist facility managers in strategic planning and provide a knowledge base to help shape future requirements and design briefing. Utilising the prototype system developed here, positive and interesting results regarding patterns and structures of data have been obtained.

Accounting : building business skills, 3rd ed.

The new edition of this widely used and respected introductory accounting textbook continues to provide students and academics with a well written and accessible resource, with ample illustrations and applications to business for a first study of accounting. The text effectively maintains the balance between a 'user' and 'preparer' perspective by integrating real financial information and business decisions throughout. Through the use of real company information and financial statements students will quickly appreciate the use and users of accounting information. The textbook clearly outlines to students how a financial statement - such as a balance sheet, income statement, cash flow statement - communicates the financing, operating, and investing activities of a business. The text builds a strong conceptual understanding and develops skills in the application of accounting principles and techniques, providing students with a solid foundation for further studies in accounting. The integral role of financial statements for decision making is also emphasised in this text and is reinforced throughout by the Decision Toolkit in each chapter. Students are provided with an extensive set of tools necessary to make business decisions based on financial information.

Building Information Modelling for FM at Sydney Opera House

“SOH see significant benefit in digitising its drawings and operation and maintenance manuals. Since SOH do not currently have digital models of the Opera House structure or other components, there is an opportunity for this national case study to promote the application of Digital Facility Modelling using standardized Building Information Models (BIM)”. The digital modelling element of this project examined the potential of building information models for Facility Management focusing on the following areas: • The re-usability of building information for FM purposes • BIM as an Integrated information model for facility management • Extendibility of the BIM to cope with business specific requirements • Commercial facility management software using standardised building information models • The ability to add (organisation specific) intelligence to the model • A roadmap for SOH to adopt BIM for FM The project has established that BIM – building information modelling - is an appropriate and potentially beneficial technology for the storage of integrated building, maintenance and management data for SOH. Based on the attributes of a BIM, several advantages can be envisioned: consistency in the data, intelligence in the model, multiple representations, source of information for intelligent programs and intelligent queries. The IFC – open building exchange standard – specification provides comprehensive support for asset and facility management functions, and offers new management, collaboration and procurement relationships based on sharing of intelligent building data. The major advantages of using an open standard are: information can be read and manipulated by any compliant software, reduced user “lock in” to proprietary solutions, third party software can be the “best of breed” to suit the process and scope at hand, standardised BIM solutions consider the wider implications of information exchange outside the scope of any particular vendor, information can be archived as ASCII files for archival purposes, and data quality can be enhanced as the now single source of users’ information has improved accuracy, correctness, currency, completeness and relevance. SOH current building standards have been successfully drafted for a BIM environment and are confidently expected to be fully developed when BIM is adopted operationally by SOH. There have been remarkably few technical difficulties in converting the House’s existing conventions and standards to the new model based environment. This demonstrates that the IFC model represents world practice for building data representation and management (see Sydney Opera House – FM Exemplar Project Report Number 2005-001-C-3, Open Specification for BIM: Sydney Opera House Case Study). Availability of FM applications based on BIM is in its infancy but focussed systems are already in operation internationally and show excellent prospects for implementation systems at SOH. In addition to the generic benefits of standardised BIM described above, the following FM specific advantages can be expected from this new integrated facilities management environment: faster and more effective processes, controlled whole life costs and environmental data, better customer service, common operational picture for current and strategic planning, visual decision-making and a total ownership cost model. Tests with partial BIM data – provided by several of SOH’s current consultants – show that the creation of a SOH complete model is realistic, but subject to resolution of compliance and detailed functional support by participating software applications. The showcase has demonstrated successfully that IFC based exchange is possible with several common BIM based applications through the creation of a new partial model of the building. Data exchanged has been geometrically accurate (the SOH building structure represents some of the most complex building elements) and supports rich information describing the types of objects, with their properties and relationships.

Capital Works Procurement: The Selection of a Building Procurement Method

The determination of the most appropriate procurement method for capital works projects is a challenging task for the Department of Housing and Works (DHW) and other Western Australian State Government Agencies because of the array of assessment criteria that are considered and the procurement methods that are available. A number of different procurement systems can be used to deliver capital works projects such a traditional, design and construct and management. Sub-classifications of these systems have proliferated and continue to emerge in response to market demands. The selection of an inappropriate procurement method may lead to undesirable project outcomes. To facilitate DHW in selecting an appropriate procurement method for its capital works projects, a six step procurement method selection process is presented. The characteristics of the most common forms of procurement method used in Australia are presented. Case studies where procurement methods have been used for specific types of capital works in Western Australia are offered to provide a reference point and learning opportunity for procurement method selection.

Building procurement methods

A plethora of methods for procuring building projects are available to meet the needs of clients. Deciding what method to use for a given project is a difficult and challenging task as a client’s objectives and priorities need to marry with the selected method so as to improve the likelihood of the project being procured successfully. The decision as to what procurement system to use should be made as early as possible and underpinned by the client’s business case for the project. The risks and how they can potentially affect the client’s business should also be considered. In this report, the need for client’s to develop a procurement strategy, which outlines the key means by which the objectives of the project are to be achieved is emphasised. Once a client has established a business case for a project, appointed a principal advisor, determined their requirements and brief, then consideration as to which procurement method to be adopted should be made. An understanding of the characteristics of various procurement options is required before a recommendation can be made to a client. Procurement systems can be categorised as traditional, design and construct, management and collaborative. The characteristics of these systems along with the procurement methods commonly used are described. The main advantages and disadvantages, and circumstances under which a system could be considered applicable for a given project are also identified.

Building mentoring capacities in experienced teachers

While teacher education equips beginning teachers with critical knowledge and skills about teaching and fosters an understanding of learning in and from teaching some of the most critical elements of teaching are only learned in the workplace when beginning teachers commence their professional teaching careers. This transition to professional practice may be facilitated by mentoring from a more experienced teacher. Expert mentoring assists beginning teachers to build their teaching capacities more quickly and also lays the foundation for innovative professional practice. However, the presence of a mentor alone is not sufficient with the success of mentoring reliant on the skills and knowledge of mentors. Mentoring relationships are most effective when mentors are trained for their roles. While mentor preparation is the single most important factor in contributing to mentoring success, few teachers receive formal training to prepare them adequately for mentoring roles. The purpose of this paper is to report on the implementation of a mentoring development program designed to build mentoring capacities in experienced teachers. The program was trialled in a school in rural Australia. A range of qualitative data was collected from participants over the duration of the mentoring program and follow up data collected six months subsequent to the conclusion of the program.

Review on Australian and international practices for asset management in building infrastructure

Both in developed and developing economies, major public funding is invested in civil infrastructure assets. Efficiency and comfort level of expected and demanded living standards are largely dependant on the management strategies of these assets. Buildings are one of the major & vital assets, which need to be maintained primarily to ensure its functionality by effective & efficient delivery of services and to optimize economic benefits. Not withstanding, public building infrastructure is not considered in Infrastructure report card published by Australian Infrastructure Report Card Alliance Partners (2001). The reason appears to be not having enough data to rate public building infrastructure. American Infrastructure Report Card (2001) gave “School Buildings” ‘d-’ rating, which is below ‘poor’. For effective asset management of building infrastructure, a need emerged to optimise the budget for managing assets, to cope up with increased user expectations, to response effectively to possible asset failures, to deal with ageing of assets and aging populations and to treat other scenarios including technology advancement and non-asset solutions. John (Asset Management, 2001) suggests that in the area of asset management worldwide, UK, Australia and New Zealand are leading.

Sustainability and the building code of Australia

This report is the culmination of a two-stage research project to inform the Australian property and construction industry generally, in addition to providing the Australian Building Codes Board (ABCB) with information to allow it to determine whether or not sustainability requirements are necessary in the Future Building Code of Australia (BCA21). The Australian Building Codes Board is a joint initiative of all levels of government in Australia. The Board’s mission is to provide for efficiency and cost effectiveness in meeting community expectations for health, safety and amenity in the design, construction and use of buildings through the creation of nationally consistent building codes, standards, regulatory requirements and regulatory systems. The Stage 1 (literature review) and Stage 2 (workshops) reports are intended to be read in conjunction with one another. These reports and the Database are provided as appendices. The Conclusions of this, the final report, are the result of the overall program of work.

Parametric building development during early design stage

Objectives The objectives of this project were two-fold: • Assess the ease with which current architectural CAD systems supported the use ofparametric descriptions in defining building shape, engineering system performance and cost at the early stages of building design; • Assess the feasibility of implementing a software decision support system that allowed designers to trade-off the characteristics and configuration of various engineering systems to move towards a “global optimum” rather than considering each system in isolation and expecting humans to weigh up all of the costs and benefits. The first stage of the project consisted of using four different CAD systems to define building shells (envelopes) with different usages. These models were then exported into a shared database using the IFC information exchange specifications. The second stage involved the implementation of small computer programs that were able to estimate relevant system parameters based on performance requirements and the constraints imposed by the other systems. These are presented in a unified user interface that extracts the appropriate building shape parameters from the shared database Note that the term parametric in this context refers to the relationships among and between all elements of the building model - not just geometric associations - which will enable the desired coordination.

Passive control of a bi-ventricular assist device : an experimental and numerical investigation

For the last two decades heart disease has been the highest single cause of death for the human population. With an alarming number of patients requiring heart transplant, and donations not able to satisfy the demand, treatment looks to mechanical alternatives. Rotary Ventricular Assist Devices, VADs, are miniature pumps which can be implanted alongside the heart to assist its pumping function. These constant flow devices are smaller, more efficient and promise a longer operational life than more traditional pulsatile VADs. The development of rotary VADs has focused on single pumps assisting the left ventricle only to supply blood for the body. In many patients however, failure of both ventricles demands that an additional pulsatile device be used to support the failing right ventricle. This condition renders them hospital bound while they wait for an unlikely heart donation. Reported attempts to use two rotary pumps to support both ventricles concurrently have warned of inherent haemodynamic instability. Poor balancing of the pumps’ flow rates quickly leads to vascular congestion increasing the risk of oedema and ventricular ‘suckdown’ occluding the inlet to the pump. This thesis introduces a novel Bi-Ventricular Assist Device (BiVAD) configuration where the pump outputs are passively balanced by vascular pressure. The BiVAD consists of two rotary pumps straddling the mechanical passive controller. Fluctuations in vascular pressure induce small deflections within both pumps adjusting their outputs allowing them to maintain arterial pressure. To optimise the passive controller’s interaction with the circulation, the controller’s dynamic response is optimised with a spring, mass, damper arrangement. This two part study presents a comprehensive assessment of the prototype’s ‘viability’ as a support device. Its ‘viability’ was considered based on its sensitivity to pathogenic haemodynamics and the ability of the passive response to maintain healthy circulation. The first part of the study is an experimental investigation where a prototype device was designed and built, and then tested in a pulsatile mock circulation loop. The BiVAD was subjected to a range of haemodynamic imbalances as well as a dynamic analysis to assess the functionality of the mechanical damper. The second part introduces the development of a numerical program to simulate human circulation supported by the passively controlled BiVAD. Both investigations showed that the prototype was able to mimic the native baroreceptor response. Simulating hypertension, poor flow balancing and subsequent ventricular failure during BiVAD support allowed the passive controller’s response to be assessed. Triggered by the resulting pressure imbalance, the controller responded by passively adjusting the VAD outputs in order to maintain healthy arterial pressures. This baroreceptor-like response demonstrated the inherent stability of the auto regulating BiVAD prototype. Simulating pulmonary hypertension in the more observable numerical model, however, revealed a serious issue with the passive response. The subsequent decrease in venous return into the left heart went unnoticed by the passive controller. Meanwhile the coupled nature of the passive response not only decreased RVAD output to reduce pulmonary arterial pressure, but it also increased LVAD output. Consequently, the LVAD increased fluid evacuation from the left ventricle, LV, and so actually accelerated the onset of LV collapse. It was concluded that despite the inherently stable baroreceptor-like response of the passive controller, its lack of sensitivity to venous return made it unviable in its present configuration. The study revealed a number of other important findings. Perhaps the most significant was that the reduced pulse experienced during constant flow support unbalanced the ratio of effective resistances of both vascular circuits. Even during steady rotary support therefore, the resulting ventricle volume imbalance increased the likelihood of suckdown. Additionally, mechanical damping of the passive controller’s response successfully filtered out pressure fluctuations from residual ventricular function. Finally, the importance of recognising inertial contributions to blood flow in the atria and ventricles in a numerical simulation were highlighted. This thesis documents the first attempt to create a fully auto regulated rotary cardiac assist device. Initial results encourage development of an inlet configuration sensitive to low flow such as collapsible inlet cannulae. Combining this with the existing baroreceptor-like response of the passive controller will render a highly stable passively controlled BiVAD configuration. The prototype controller’s passive interaction with the vasculature is a significant step towards a highly stable new generation of artificial heart.