Improved production of industrially relevant recombinant proteins: application of multi-factorial design of experiments and scalable process modelling

The work described in this thesis focuses on the use of a design-of-experiments approach in a multi-well mini-bioreactor to enable the rapid establishments of high yielding production phase conditions in yeast, which is an increasingly popular host system in both academic and industrial laboratories. Using green fluorescent protein secreted from the yeast, Pichia pastoris, a scalable predictive model of protein yield per cell was derived from 13 sets of conditions each with three factors (temperature, pH and dissolved oxygen) at 3 levels and was directly transferable to a 7 L bioreactor. This was in clear contrast to the situation in shake flasks, where the process parameters cannot be tightly controlled. By further optimisating both the accumulation of cell density in batch and improving the fed-batch induction regime, additional yield improvement was found to be additive to the per cell yield of the model. A separate study also demonstrated that improving biomass improved product yield in a second yeast species, Saccharomyces cerevisiae. Investigations of cell wall hydrophobicity in high cell density P. pastoris cultures indicated that cell wall hydrophobin (protein) compositional changes with growth phase becoming more hydrophobic in log growth than in lag or stationary phases. This is possibly due to an increased occurrence of proteins associated with cell division. Finally, the modelling approach was validated in mammalian cells, showing its flexibility and robustness. In summary, the strategy presented in this thesis has the benefit of reducing process development time in recombinant protein production, directly from bench to bioreactor.

Multi-Disciplinary Applications of Oceanographic Geophysical Data Collection

Thesis (Ph.D.)--University of Washington, 2016-08

Expanded scope roles in primary health – what makes them work?

Introduction The demand for better integration between primary and secondary healthcare frequently leads to discussion about expanded scope of practice for nursing, paramedic and allied health professionals and the role these clinicians could play in facilitating improved access to timely and appropriate healthcare. From workforce perspective, expanded scope of practice has also been advocated as a mean of fostering workforce retention. Models of expanded scope roles in nursing and paramedicine have been trialled nationally and internationally in both acute and community care settings. Where they have been successful, trials have resulted in reduction in hospital presentation and admission; improved patient access and timeliness; and patient satisfaction. This paper will examine the characteristics of successful expanded scope programs. Method Exploratory case-study analysis of successful integration of expanded health care roles across primary healthcare settings in rural Australia. Results & Conclusions One size does not fill all. Successful models of integrated expanded health care roles in primary health care settings are built on stakeholder’s capacity and preference; community need; and political will. Collaborative, congruent, multi-disciplinary care teams that prioritise patient-centred care within a dynamic primary care setting have merit and are more likely to foster flexibility and sustainability.

How do Australian podiatrists manage patients with diabetes The Australian diabetic foot management survey

Background Diabetic foot complications are the leading cause of lower extremity amputation and diabetes-related hospitalisation in Australia. Studies demonstrate significant reductions in amputations and hospitalisation when health professionals implement best practice management. Whilst other nations have surveyed health professionals on specific diabetic foot management, to the best of the authors’ knowledge this appears not to have occurred in Australia. The primary aim of this study was to examine Australian podiatrists’ diabetic foot management compared with best practice recommendations by the Australian National Health Medical Research Council. Methods A 36-item Australian Diabetic Foot Management survey, employing seven-point Likert scales (0 = Never; 7 = Always) to measure multiple aspects of best practice diabetic foot management was developed. The survey was briefly tested for face and content validity. The survey was electronically distributed to Australian podiatrists via professional associations. Demographics including sex, years treating patients with diabetes, employment-sector and patient numbers were also collected. Chi-squared and Mann Whitney U tests were used to test differences between sub-groups. Results Three hundred and eleven podiatrists responded; 222 (71%) were female, 158 (51%) from the public sector and 11–15 years median experience. Participants reported treating a median of 21–30 diabetes patients each week, including 1–5 with foot ulcers. Overall, participants registered median scores of at least “very often” (>6) in their use of most items covering best practice diabetic foot management. Notable exceptions were: “never” (1 (1 – 3)) using total contact casting, “sometimes” (4 (2 – 5)) performing an ankle brachial index, “sometimes” (4 (1 – 6)) using University of Texas Wound Classification System, and “sometimes” (4 (3 – 6) referring to specialist multi-disciplinary foot teams. Public sector podiatrists reported higher use or access on all those items compared to private sector podiatrists (p < 0.01). Conclusions This study provides the first baseline information on Australian podiatrists’ adherence to best practice diabetic foot guidelines. It appears podiatrists manage large caseloads of people with diabetes and are generally implementing best practice guidelines recommendations with some notable exceptions. Further studies are required to identify barriers to implementing these recommendations to ensure all Australians with diabetes have access to best practice care to prevent amputations.

A practical approach for cross-functional vehicle body weight optimization

The goal of optimization in vehicle design is often blurred by the myriads of requirements belonging to attributes that may not be quite related. If solutions are sought by optimizing attribute performance-related objectives separately starting with a common baseline design configuration as in a traditional design environment, it becomes an arduous task to integrate the potentially conflicting solutions into one satisfactory design. It may be thus more desirable to carry out a combined multi-disciplinary design optimization (MDO) with vehicle weight as an objective function and cross-functional attribute performance targets as constraints. For the particular case of vehicle body structure design, the initial design is likely to be arrived at taking into account styling, packaging and market-driven requirements. The problem with performing a combined cross-functional optimization is the time associated with running such CAE algorithms that can provide a single optimal solution for heterogeneous areas such as NVH and crash safety. In the present paper, a practical MDO methodology is suggested that can be applied to weight optimization of automotive body structures by specifying constraints on frequency and crash performance. Because of the reduced number of cases to be analyzed for crash safety in comparison with other MDO approaches, the present methodology can generate a single size-optimized solution without having to take recourse to empirical techniques such as response surface-based prediction of crash performance and associated successive response surface updating for convergence. An example of weight optimization of spaceframe-based BIW of an aluminum-intensive vehicle is given to illustrate the steps involved in the current optimization process.

Value management in infrastructure project design : unlocking the project team’s creativity

Value Management (VM) is a proven methodology that provides a structured framework using supporting tools and techniques that facilitate effective decision-making in many types of projects, thus achieving ‘best value’ for clients. It offers an exceptionally robust approach to exploring the need and function of projects to be aligned with client’s objectives. The functional analysis and creativity phases of VM are crucial as it focused on utilising innovative thinking to understand the objectives of clients’ projects and provide value-adding solutions at the early discovery stages of projects. There is however a perception of VM as just being another cost-cutting tool, which has overshadowed the fundamental benefits of the method, therefore negating both influence and wider use in the construction industry. This paper describes findings from a series of case studies conducted at project and corporate levels of a current public funded infrastructure projects in Malaysia. The study aims to investigate VM processes practised by the project client organisation and evaluate the effects of project team involvement in VM workshops during the design-stage of these projects. The focus of the study is on how issues related to ‘upstream’ infrastructure design aimed at improving ‘downstream’ construction process on-site, are being resolved through multi-disciplinary team consideration and decision-making. Findings from the case studies indicate that the mix of disciplines of project team members at a design-stage of a VM workshop has minimal influence on improving construction processes. However, the degree of interaction, institutionalized thinking, cultural dimensions and visualization aids adopted, have a significant impact in maximizing creativity amongst project team members during VM workshop. The case studies conducted for this research have focused on infrastructure projects that utilise traditional VM workshop as client’s chosen VM methodology to review and develop designs. Documents review and semi-structured interview with project teams are used as data collection techniques for the case study. The significant outcomes of this research are expected to offer alternative perspectives for construction professionals and clients to minimise the constraints and strengthen strategies for implementing VM on future projects.

The subtropical residential tower: An investigation by Design Charrette

QUT's Centre for Subtropical Design (CSD) partnered with a major developer to bring together some of Brisbane’s most experienced and creative architects and designers in a two-day intensive design charrette to propose innovative design strategies for naturally-ventilated high rise residential buildings. An inner-urban renewal site in Queensland’s capital city Brisbane gave four multi-disciplinary teams the opportunity to address a raft of issues that developers and consultants will confront more and more in the future in warm humid climates. The quest to release apartment dwellers from dependence on energy-hungry air-conditioning and artificial lighting was central to the design brief for the towers. Mentored by Richard Hassell of WOHA, the creative teams focussed on climate-responsive design principles for passive climate control including orientation, cross-ventilation and outdoor living in order to reduce greenhouse gas emissions and offset occupants’ rising energy costs. This article discusses how outcomes of the charrette take their cue from the city’s subtropical climate and demonstrate how high-density high-rise living can be attractive, affordable and sustainable through positive engagement with the subtropical climate’s natural attributes.

Daylighting performance of subtropical multi-residential towers : simulations tools for design decisions

During an intensive design-led workshop multidisciplinary design teams examined options for a sustainable multi-residential tower on an inner urban site in Brisbane (Australia). The main aim was to demonstrate the key principles of daylight to every habitable room and cross-ventilation to every apartment in the subtropical climate while responding to acceptable yield and price points. The four conceptual design proposals demonstrated a wide range of outcomes, with buildings ranging from 15 to 30 storeys. Daylight Factor (DF), view to the outside, and the avoidance of direct sunlight were the only quantitative and qualitative performance metrics used to implement daylighting to the proposed buildings during the charrette. This paper further assesses the daylighting performance of the four conceptual designs by utilizing Climate-based daylight modeling (CBDM), specifically Daylight Autonomy (DA) and Useful Daylight Illuminance (UDI). Results show that UDI 100-2000lux calculations provide more useful information on the daylighting design than DF. The percentage of the space with a UDI <100-2000lux larger than 50% ranged from 77% to 86% of the time for active occupant behaviour (occupancy from 6am to 6pm). The paper also highlights the architectural features that mostly affect daylighting design in subtropical climates.

The InstaBooth: Making common ground for media architectural design

Media architecture has emerged from and relies upon a range of different disciplinary traditions and areas of expertise. As this field develops, it is timely to reflect upon the ways in which designers of different disciplinary stripes can be brought together to collaborate in a design process. What are the means by which design teams can establish a ‘common ground’ where design work can take place while recognizing the diversity of ways of working those different disciplines bring to the process? A co-design approach has been the fundamental backbone of the InstaBooth project, which has brought together a multidisciplinary design team of academics and practitioners. The intention of this project has been to explore the combination of digital and physical interactions within a small media architecture installation to intervene with urban environments and public places for the purposes of community engagement. It is by exploring the design process of the InstaBooth project that we highlight the value of multi-disciplinary collaborations, the lessons that can be learned, and the struggles and hurdles along the way. This paper highlights the iterative process of design, the materials and physical prototypes that were employed to ultimately create a working version of the InstaBooth, a media architecture that evolves as users push its boundaries and take ownership of the installation. The concept of the InstaBooth continues to develop not only as more data are collected on its mechanics and potentials through observations, interviews and workshops, but also as more and more users engage with the installation in their individual ways.

A multidisciplinary reference framework to support innovative design, implementation and assessment of chronic care models

Hoy en día, por primera vez en la historia, la mayor parte de la población podrá vivir hasta los sesenta años y más (United Nations, 2015). Sin embargo, todavía existe poca evidencia que demuestre que las personas mayores, estén viviendo con mejor salud que sus padres, a la misma edad, ya que la mayoría de los problemas de salud en edades avanzadas están asociados a las enfermedades crónicas (WHO, 2015). Los sistemas sanitarios de los países desarrollados funcionan adecuadamente cuando se trata del cuidado de enfermedades agudas, pero no son lo suficientemente eficaces en la gestión de las enfermedades crónicas. Durante la última década, se han realizado esfuerzos para mejorar esta gestión, por medio de la utilización de estrategias de prevención y de reenfoque de la provisión de los servicios de atención para la salud (Kane et al. 2005). Según una revisión sistemática de modelos de cuidado de salud, comisionada por el sistema nacional de salud Británico, pocos modelos han conceptualizado cuáles son los componentes que hay que utilizar para proporcionar un cuidado crónico efectivo, y estos componentes no han sido suficientemente estructurados y articulados. Por lo tanto, no hay suficiente evidencia sobre el impacto real de cualquier modelo existente en la actualidad (Ham, 2006). Las innovaciones podrían ayudar a conseguir mejores diagnósticos, tratamientos y gestión de pacientes crónicos, así como a dar soporte a los profesionales y a los pacientes en el cuidado. Sin embargo, la forma en las que estas innovaciones se proporcionan no es lo suficientemente eficiente, efectiva y amigable para el usuario. Para mejorar esto, hace falta crear equipos de trabajo y estrategias multidisciplinares. En conclusión, hacen falta actividades que permitan conseguir que las innovaciones sean utilizadas en los sistemas de salud que quieren mejorar la gestión del cuidado crónico, para que sea posible: 1) traducir la “atención sanitaria basada en la evidencia” en “conocimiento factible”; 2) hacer frente a la complejidad de la atención sanitaria a través de una investigación multidisciplinaria; 3) identificar una aproximación sistemática para que se establezcan intervenciones innovadoras en el cuidado de salud. El marco de referencia desarrollado en este trabajo de investigación es un intento de aportar estas mejoras. Las siguientes hipótesis han sido propuestas: Hipótesis 1: es posible definir un proceso de traducción que convierta un modelo de cuidado crónico en una descripción estructurada de objetivos, requisitos e indicadores clave de rendimiento. Hipótesis 2: el proceso de traducción, si se ejecuta a través de elementos basados en la evidencia, multidisciplinares y de orientación económica, puede convertir un modelo de cuidado crónico en un marco descriptivo, que define el ciclo de vida de soluciones innovadoras para el cuidado de enfermedades crónicas. Hipótesis 3: es posible definir un método para evaluar procesos, resultados y capacidad de desarrollar habilidades, y asistir equipos multidisciplinares en la creación de soluciones innovadoras para el cuidado crónico. Hipótesis 4: es posible dar soporte al desarrollo de soluciones innovadoras para el cuidado crónico a través de un marco de referencia y conseguir efectos positivos, medidos en indicadores clave de rendimiento. Para verificar las hipótesis, se ha definido una aproximación metodológica compuesta de cuatro Fases, cada una asociada a una hipótesis. Antes de esto, se ha llevado a cabo una “Fase 0”, donde se han analizado los antecedentes sobre el problema (i.e. adopción sistemática de la innovación en el cuidado crónico) desde una perspectiva multi-dominio y multi-disciplinar. Durante la fase 1, se ha desarrollado un Proceso de Traducción del Conocimiento, elaborado a partir del JBI Joanna Briggs Institute (JBI) model of evidence-based healthcare (Pearson, 2005), y sobre el cual se han definido cuatro Bloques de Innovación. Estos bloques consisten en una descripción de elementos innovadores, definidos en la fase 0, que han sido añadidos a los cuatros elementos que componen el modelo JBI. El trabajo llevado a cabo en esta fase ha servido también para definir los materiales que el proceso de traducción tiene que ejecutar. La traducción que se ha llevado a cabo en la fase 2, y que traduce la mejor evidencia disponible de cuidado crónico en acción: resultado de este proceso de traducción es la parte descriptiva del marco de referencia, que consiste en una descripción de un modelo de cuidado crónico (se ha elegido el Chronic Care Model, Wagner, 1996) en términos de objetivos, especificaciones e indicadores clave de rendimiento y organizada en tres ciclos de innovación (diseño, implementación y evaluación). Este resultado ha permitido verificar la segunda hipótesis. Durante la fase 3, para demostrar la tercera hipótesis, se ha desarrollado un método-mixto de evaluación de equipos multidisciplinares que trabajan en innovaciones para el cuidado crónico. Este método se ha creado a partir del método mixto usado para la evaluación de equipo multidisciplinares translacionales (Wooden, 2013). El método creado añade una dimensión procedural al marco. El resultado de esta fase consiste, por lo tanto, en una primera versión del marco de referencia, lista para ser experimentada. En la fase 4, se ha validado el marco a través de un caso de estudio multinivel y con técnicas de observación-participante como método de recolección de datos. Como caso de estudio se han elegido las actividades de investigación que el grupo de investigación LifeStech ha desarrollado desde el 2008 para mejorar la gestión de la diabetes, actividades realizadas en un contexto internacional. Los resultados demuestran que el marco ha permitido mejorar las actividades de trabajo en distintos niveles: 1) la calidad y cantidad de las publicaciones; 2) se han conseguido dos contratos de investigación sobre diabetes: el primero es un proyecto de investigación aplicada, el segundo es un proyecto financiado para acelerar las innovaciones en el mercado; 3) a través de los indicadores claves de rendimiento propuestos en el marco, una prueba de concepto de un prototipo desarrollado en un proyecto de investigación ha sido transformada en una evaluación temprana de una intervención eHealth para el manejo de la diabetes, que ha sido recientemente incluida en Repositorio de prácticas innovadoras del Partenariado de Innovación Europeo en Envejecimiento saludable y activo. La verificación de las 4 hipótesis ha permitido demonstrar la hipótesis principal de este trabajo de investigación: es posible contribuir a crear un puente entre la atención sanitaria y la innovación y, por lo tanto, mejorar la manera en que el cuidado crónico sea procurado en los sistemas sanitarios. ABSTRACT Nowadays, for the first time in history, most people can expect to live into their sixties and beyond (United Nations, 2015). However, little evidence suggests that older people are experiencing better health than their parents, and most of the health problems of older age are linked to Chronic Diseases (WHO, 2015). The established health care systems in developed countries are well suited to the treatment of acute diseases but are mostly inadequate for dealing with CDs. Healthcare systems are challenging the burden of chronic diseases by putting more emphasis on the prevention of disease and by looking for new ways to reorient the provision of care (Kane et al., 2005). According to an evidence-based review commissioned by the British NHS Institute, few models have conceptualized effective components of care for CDs and these components have been not structured and articulated. “Consequently, there is limited evidence about the real impact of any of the existing models” (Ham, 2006). Innovations could support to achieve better diagnosis, treatment and management for patients across the continuum of care, by supporting health professionals and empowering patients to take responsibility. However, the way they are delivered is not sufficiently efficient, effective and consumer friendly. The improvement of innovation delivery, involves the creation of multidisciplinary research teams and taskforces, rather than just working teams. There are several actions to improve the adoption of innovations from healthcare systems that are tackling the epidemics of CDs: 1) Translate Evidence-Based Healthcare (EBH) into actionable knowledge; 2) Face the complexity of healthcare through multidisciplinary research; 3) Identify a systematic approach to support effective implementation of healthcare interventions through innovation. The framework proposed in this research work is an attempt to provide these improvements. The following hypotheses have been drafted: Hypothesis 1: it is possible to define a translation process to convert a model of chronic care into a structured description of goals, requirements and key performance indicators. Hypothesis 2: a translation process, if executed through evidence-based, multidisciplinary, holistic and business-oriented elements, can convert a model of chronic care in a descriptive framework, which defines the whole development cycle of innovative solutions for chronic disease management. Hypothesis 3: it is possible to design a method to evaluate processes, outcomes and skill acquisition capacities, and assist multidisciplinary research teams in the creation of innovative solutions for chronic disease management. Hypothesis 4: it is possible to assist the development of innovative solutions for chronic disease management through a reference framework and produce positive effects, measured through key performance indicators. In order to verify the hypotheses, a methodological approach, composed of four Phases that correspond to each one of the stated hypothesis, was defined. Prior to this, a “Phase 0”, consisting in a multi-domain and multi-disciplinary background analysis of the problem (i.e.: systematic adoption of innovation to chronic care), was carried out. During phase 1, in order to verify the first hypothesis, a Knowledge Translation Process (KTP) was developed, starting from the JBI Joanna Briggs Institute (JBI) model of evidence-based healthcare was used (Pearson, 2005) and adding Four Innovation Blocks. These blocks represent an enriched description, added to the JBI model, to accelerate the transformation of evidence-healthcare through innovation; the innovation blocks are built on top of the conclusions drawn after Phase 0. The background analysis gave also indication on the materials and methods to be used for the execution of the KTP, carried out during phase 2, that translates the actual best available evidence for chronic care into action: this resulted in a descriptive Framework, which is a description of a model of chronic care (the Chronic Care Model was chosen, Wagner, 1996) in terms of goals, specified requirements and Key Performance Indicators, and articulated in the three development cycles of innovation (i.e. design, implementation and evaluation). Thanks to this result the second hypothesis was verified. During phase 3, in order to verify the third hypothesis, a mixed-method to evaluate multidisciplinary teams working on innovations for chronic care, was created, based on a mixed-method used for the evaluation of Multidisciplinary Translational Teams (Wooden, 2013). This method adds a procedural dimension to the descriptive component of the Framework, The result of this phase consisted in a draft version of the framework, ready to be tested in a real scenario. During phase 4, a single and multilevel case study, with participant-observation data collection, was carried out, in order to have a complete but at the same time multi-sectorial evaluation of the framework. The activities that the LifeStech research group carried out since 2008 to improve the management of diabetes have been selected as case study. The results achieved showed that the framework allowed to improve the research activities in different directions: the quality and quantity of the research publications that LifeStech has issued, have increased substantially; 2 project grants to improve the management of diabetes, have been assigned: the first is a grant funding applied research while the second is about accelerating innovations into the market; by using the assessment KPIs of the framework, the proof of concept validation of a prototype developed in a research project was transformed into an early stage assessment of innovative eHealth intervention for Diabetes Management, which has been recently included in the repository of innovative practice of the European Innovation Partnership on Active and Health Ageing initiative. The verification of the 4 hypotheses lead to verify the main hypothesis of this research work: it is possible to contribute to bridge the gap between healthcare and innovation and, in turn, improve the way chronic care is delivered by healthcare systems.

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.

Design and Ethics: Reflections on Practice

This book is an multi disciplinary approach to design thinking across the fields of Architecture, Communication Design, Fashion, Graphic Design, Urban Design and Philosophy.

A hierarchical evolutionary algorithmic design (HEAD) system for generating and evolving building design models

This thesis develops a detailed conceptual design method and a system software architecture defined with a parametric and generative evolutionary design system to support an integrated interdisciplinary building design approach. The research recognises the need to shift design efforts toward the earliest phases of the design process to support crucial design decisions that have a substantial cost implication on the overall project budget. The overall motivation of the research is to improve the quality of designs produced at the author's employer, the General Directorate of Major Works (GDMW) of the Saudi Arabian Armed Forces. GDMW produces many buildings that have standard requirements, across a wide range of environmental and social circumstances. A rapid means of customising designs for local circumstances would have significant benefits. The research considers the use of evolutionary genetic algorithms in the design process and the ability to generate and assess a wider range of potential design solutions than a human could manage. This wider ranging assessment, during the early stages of the design process, means that the generated solutions will be more appropriate for the defined design problem. The research work proposes a design method and system that promotes a collaborative relationship between human creativity and the computer capability. The tectonic design approach is adopted as a process oriented design that values the process of design as much as the product. The aim is to connect the evolutionary systems to performance assessment applications, which are used as prioritised fitness functions. This will produce design solutions that respond to their environmental and function requirements. This integrated, interdisciplinary approach to design will produce solutions through a design process that considers and balances the requirements of all aspects of the design. Since this thesis covers a wide area of research material, 'methodological pluralism' approach was used, incorporating both prescriptive and descriptive research methods. Multiple models of research were combined and the overall research was undertaken following three main stages, conceptualisation, developmental and evaluation. The first two stages lay the foundations for the specification of the proposed system where key aspects of the system that have not previously been proven in the literature, were implemented to test the feasibility of the system. As a result of combining the existing knowledge in the area with the newlyverified key aspects of the proposed system, this research can form the base for a future software development project. The evaluation stage, which includes building the prototype system to test and evaluate the system performance based on the criteria defined in the earlier stage, is not within the scope this thesis. The research results in a conceptual design method and a proposed system software architecture. The proposed system is called the 'Hierarchical Evolutionary Algorithmic Design (HEAD) System'. The HEAD system has shown to be feasible through the initial illustrative paper-based simulation. The HEAD system consists of the two main components - 'Design Schema' and the 'Synthesis Algorithms'. The HEAD system reflects the major research contribution in the way it is conceptualised, while secondary contributions are achieved within the system components. The design schema provides constraints on the generation of designs, thus enabling the designer to create a wide range of potential designs that can then be analysed for desirable characteristics. The design schema supports the digital representation of the human creativity of designers into a dynamic design framework that can be encoded and then executed through the use of evolutionary genetic algorithms. The design schema incorporates 2D and 3D geometry and graph theory for space layout planning and building formation using the Lowest Common Design Denominator (LCDD) of a parameterised 2D module and a 3D structural module. This provides a bridge between the standard adjacency requirements and the evolutionary system. The use of graphs as an input to the evolutionary algorithm supports the introduction of constraints in a way that is not supported by standard evolutionary techniques. The process of design synthesis is guided as a higher level description of the building that supports geometrical constraints. The Synthesis Algorithms component analyses designs at four levels, 'Room', 'Layout', 'Building' and 'Optimisation'. At each level multiple fitness functions are embedded into the genetic algorithm to target the specific requirements of the relevant decomposed part of the design problem. Decomposing the design problem to allow for the design requirements of each level to be dealt with separately and then reassembling them in a bottom up approach reduces the generation of non-viable solutions through constraining the options available at the next higher level. The iterative approach, in exploring the range of design solutions through modification of the design schema as the understanding of the design problem improves, assists in identifying conflicts in the design requirements. Additionally, the hierarchical set-up allows the embedding of multiple fitness functions into the genetic algorithm, each relevant to a specific level. This supports an integrated multi-level, multi-disciplinary approach. The HEAD system promotes a collaborative relationship between human creativity and the computer capability. The design schema component, as the input to the procedural algorithms, enables the encoding of certain aspects of the designer's subjective creativity. By focusing on finding solutions for the relevant sub-problems at the appropriate levels of detail, the hierarchical nature of the system assist in the design decision-making process.