Mechanistic Models of Anti-HIV Microbicide Drug Delivery

A new modality for preventing HIV transmission is emerging in the form of topical microbicides. Some clinical trials have shown some promising results of these methods of protection while other trials have failed to show efficacy. Due to the relatively novel nature of microbicide drug transport, a rigorous, deterministic analysis of that transport can help improve the design of microbicide vehicles and understand results from clinical trials. This type of analysis can aid microbicide product design by helping understand and organize the determinants of drug transport and the potential efficacies of candidate microbicide products.

Microbicide drug transport is modeled as a diffusion process with convection and reaction effects in appropriate compartments. This is applied here to vaginal gels and rings and a rectal enema, all delivering the microbicide drug Tenofovir. Although the focus here is on Tenofovir, the methods established in this dissertation can readily be adapted to other drugs, given knowledge of their physical and chemical properties, such as the diffusion coefficient, partition coefficient, and reaction kinetics. Other dosage forms such as tablets and fiber meshes can also be modeled using the perspective and methods developed here.

The analyses here include convective details of intravaginal flows by both ambient fluid and spreading gels with different rheological properties and applied volumes. These are input to the overall conservation equations for drug mass transport in different compartments. The results are Tenofovir concentration distributions in time and space for a variety of microbicide products and conditions. The Tenofovir concentrations in the vaginal and rectal mucosal stroma are converted, via a coupled reaction equation, to concentrations of Tenofovir diphosphate, which is the active form of the drug that functions as a reverse transcriptase inhibitor against HIV. Key model outputs are related to concentrations measured in experimental pharmacokinetic (PK) studies, e.g. concentrations in biopsies and blood. A new measure of microbicide prophylactic functionality, the Percent Protected, is calculated. This is the time dependent volume of the entire stroma (and thus fraction of host cells therein) in which Tenofovir diphosphate concentrations equal or exceed a target prophylactic value, e.g. an EC50.

Results show the prophylactic potentials of the studied microbicide vehicles against HIV infections. Key design parameters for each are addressed in application of the models. For a vaginal gel, fast spreading at small volume is more effective than slower spreading at high volume. Vaginal rings are shown to be most effective if inserted and retained as close to the fornix as possible. Because of the long half-life of Tenofovir diphosphate, temporary removal of the vaginal ring (after achieving steady state) for up to 24h does not appreciably diminish Percent Protected. However, full steady state (for the entire stromal volume) is not achieved until several days after ring insertion. Delivery of Tenofovir to the rectal mucosa by an enema is dominated by surface area of coated mucosa and whether the interiors of rectal crypts are filled with the enema fluid. For the enema 100% Percent Protected is achieved much more rapidly than for vaginal products, primarily because of the much thinner epithelial layer of the mucosa. For example, 100% Percent Protected can be achieved with a one minute enema application, and 15 minute wait time.

Results of these models have good agreement with experimental pharmacokinetic data, in animals and clinical trials. They also improve upon traditional, empirical PK modeling, and this is illustrated here. Our deterministic approach can inform design of sampling in clinical trials by indicating time periods during which significant changes in drug concentrations occur in different compartments. More fundamentally, the work here helps delineate the determinants of microbicide drug delivery. This information can be the key to improved, rational design of microbicide products and their dosage regimens.

The PVC Beret

Dip moulded plastic beret. One of a series starting from Jelly Beret 1997.This was made with a UK with the design company Inflate. This 2009 iteration of the PVC beret chosen for Stephen Jones Hat Anthology V&A, the first millinery exhibition of millinery design held at V&A. Whereas traditional millinery is known for its rather staid and bourgeois Stephen Jones selected chose this hat for its edgy sub cultural capital.This is reflected in the choices of materials and beret style with a reference to the Bohemien Parisienne avant garde revisited in 1960s London and made new for 21st century NY "Jelly Beret" the very first prototype of a plastic millinery Reviewed in Vogue UK, this travelling exhibition went from London, New York, Sydney to add exists at the V&A as a touring show. An accompanying catalogue by Oriole Cullen and Stephen Jones discusses the significance of innovative and original millinery design international design culture today.

Exploring problem-framing through behavioural heuristics

Design for behaviour change aims to influence user behaviour, through design, for social or environmental benefit. Understanding and modelling human behaviour has thus come within the scope of designers’work, as in interaction design, service design and user experience design more generally. Diverse approaches to how to model users when seeking to influence behaviour can result in many possible strategies, but a major challenge for the field is matching appropriate design strategies to particular behaviours (Zachrisson & Boks, 2012). In this paper, we introduce and explore behavioural heuristics as a way of framing problem-solution pairs (Dorst & Cross, 2001) in terms of simple rules. These act as a ‘common language’ between insights from user research and design principles and techniques, and draw on ideas from human factors, behavioural economics, and decision research. We introduce the process via a case study on interaction with office heating systems, based on interviews with 16 people. This is followed by worked examples in the ‘other direction’, based on a workshop held at the Interaction ’12 conference, extracting heuristics from existing systems designed to influence user behaviour, to illustrate both ends of a possible design process using heuristics.

Models of the user: designers’ perspectives on influencing sustainable behaviour

Influencing more environmentally friendly and sustainable behaviour is a current focus of many projects, ranging from government social marketing campaigns, education and tax structures to designers’ work on interactive products, services and environments. There is a wide variety of techniques and methods used, intended to work via different sets of cognitive and environmental principles. These approaches make different assumptions about ‘what people are like’: how users will respond to behavioural interventions, and why, and in the process reveal some of the assumptions that designers and other stakeholders, such as clients commissioning a project, make about human nature. This paper discusses three simple models of user behaviour – the pinball, the shortcut and the thoughtful – which emerge from user experience designers’ statements about users while focused on designing for behaviour change. The models are characterised using systems terminology and the application of each model to design for sustainable behaviour is examined via a series of examples.

Making instructions for others: exploring mental models through a simple exercise

This article introduces the idea of asking people to create instructions for others, as a way of exploring their mental models of designed systems. An example exercise run at the 2012 Brighton Maker Faire provides context. Article part of the 'On Modelling' forum edited by Hugh Dubberly.

Research in practice: Bringing behavioural change from lab to studio

Design influences behaviour, whether it's planned or not. Service Design has a great opportunity to lead the emerging field of design for behavioural change, helping guide and shape experiences to benefit users, service providers and wider society. In this article, presented as an evolving conversation between research and practice, Nick Marsh (EMC Consulting) and Dan Lockton (Brunel University) discuss and explore design patterns for influencing behaviour through Service Design, and how Service Designers and academics can work together for social benefit.

Ambulance Treatment Space Ergonomic Layout

This is the first time a multidisciplinary team has employed an iterative co-design method to determine the ergonomic layout of an emergency ambulance treatment space. This process allowed the research team to understand how treatment protocols were performed and developed analytical tools to reach an optimum configuration towards ambulance design standardisation. Fusari conducted participatory observations during 12-hour shifts with front-line ambulance clinicians, hospital staff and patients to understand the details of their working environments whilst on response to urgent and emergency calls. A simple yet accurate 1:1 mock-up of the existing ambulance was built for detailed analysis of these procedures through simulations. Paramedics were called in to participate in interviews and role-playing inside the model to recreate tasks, how they are performed, the equipment used and to understand the limitations of the current ambulance. The use of Link Analysis distilled 5 modes of use. In parallel, an exhaustive audit of all equipment and consumables used in ambulances was performed (logging and photography) to define space use. These developed 12 layout options for refinement and CAD modelling and presented back to paramedics. The preferred options and features were then developed into a full size test rig and appearance model. Two key studies informed the process. The 2005 National Patient Safety Agency funded study “Future Ambulances” outlined 9 design challenges for future standardisation of emergency vehicles and equipment. Secondly, the 2007 EPSRC funded “Smart Pods” project investigated a new system of mobile urgent and emergency medicine to treat patients in the community. A full-size mobile demonstrator unit featuring the evidence-based ergonomic layout was built for clinical tests through simulated emergency scenarios. Results from clinical trials clearly show that the new layout improves infection control, speeds up treatment, and makes it easier for ambulance crews to follow correct clinical protocols.

“Medical bag for General Practice” Just in Case: redesigning the doctor’s bag (2012)

This research addressed practice related problems from a medico-legal perspective and aims to provide a working tool that aids GPs to comply with best practice protocols. The resulting bag was developed in collaboration with General Practitioners, clinicians and members of the Medical Defense Union. Using proven methods developed within the Healthcare & Patient Safety Lab (e.g. DOME, Ambulance) to establish an evidence-based brief, this research used task, equipment and consumables analysis to determine minimum requirements and preferred layouts for task optimisation. The research established that clinicians require three distinct functions in their workspace: laying out, organisation and information retrieval. Feedback from clinicians indicates that this working tool allows them to access information and equipment wherever they may be and suggests an improvement from current practice. The research is now into a second year where the design of the bag will be refined and tested. Lifestyle and demographic changes such as the ageing population and increased prevalence of chronic diseases require more consistent standards of primary care, and care that is well coordinated and integrated (Imison, et al., 2011). Many guidelines exist relating to general practice and the doctor’s bag (NSLMC, 2008, RACGP, 2010, RCGP, 2008 and Hiramanek, 2004), however there is no standard in the UK that regulates the shape and materials of the bag or its contents. Doctors may use any sort of vessel to transport their equipment and consumables to a patient’s location. Furthermore, treating a patient in their own home, outside an ideal clinical environment, presents its own complications. A looks-like, works-like bag prototype and information system that will be used in clinical trials, the results of which will determine the manufacturing of a new, standardised bag for clinical treatment used by members of the Medical Defence Union.

Designing Creative Destruction

This research aims to make a contribution in the context of design thinking at a global cultural scale and specifically how design methods are a feature of the homogenising and heterogenising forces of globalisation via creative destruction. Since Schumpeter’s description of economic innovation destroying the old and creating the new, a number of other interpretations of creative destruction have developed including those driving cultural evolution. However a design model showing the impact of different types of design method on cultural evolution can develop an understanding on a more systemic level from the medium to longer term impact of new designs that homogenise or increase the differences between various cultures. This research explores the theoretical terrain between creative destruction, design thinking and cybernetics in the context of exchanging cultural influences for collaborative creativity and concludes with an experiment that proposes a feedback loop between ubiquitising and differentiating design methods mediating cultural variety in creative ecosystems.

Makespaces: From Redistributed Manufacturing to a Circular Economy

Redistributed manufacturing is an emerging concept which captures the anticipated reshoring and localisation of production from large scale manufacturing plants to smaller-scale localised, customisable production units, largely driven by new additive digital production technologies. Critically, community based digital fabrication workshops, or makespaces, are anticipated to be the hothouse for this new era of localised production and as such are key to future sustainable design and manufacturing practices. In parallel, the concept of the circular economy (CE) conceptualises the move from a linear economy of take-make-waste to a closed loop system, through repair, remanufacturing, refurbishment and recycling which maintains the value of materials and resources. Despite the clear interplay between RdM and CE, there is limited research exploring this relationship. In light of these interconnected developments, the aim of this paper is to explore the role of makespaces in contributing to a circular economy through RdM activities. This is achieved through six semi-structured interviews with thought leaders on these topics. The research findings identify barriers and opportunities to both CE and RdM, uncover key overlaps between CE and RdM, and identify a range of future research directions that can support the coming together of these areas. The research contributes to a wider conversation on embedding circular practices within makespaces and their role in RdM.

Designing Creative Destruction

This research aims to make a contribution in the context of design thinking at a global cultural scale and specifically how design methods are a feature of the homogenising and heterogenising forces of globalisation via creative destruction. Since Schumpeter’s description of economic innovation destroying the old and creating the new, a number of other interpretations of creative destruction have developed including those driving cultural evolution. However a design model showing the impact of different types of design method on cultural evolution can develop an understanding on a more systemic level from the medium to longer term impact of new designs that homogenise or increase the differences between various cultures. This research explores the theoretical terrain between creative destruction, design thinking and cybernetics in the context of exchanging cultural influences for collaborative creativity and concludes with an experiment that proposes a feedback loop between ubiquitising and differentiating design methods mediating cultural variety in creative ecosystems.

Desenho do real : análise, representação e consciência crítica

O presente relatório reflete sobre o processo de representação pelo desenho de uma forma tridimensional num suporte bidimensional. A intenção deste relatório é analisar e compreender a relação entre o que é analisado pelo cérebro, o que é representado no papel e a consciência crítica do erro praticado no desenho de observação, bem como conhecer como poderá ser desenvolvida esta triangulação (análise, representação e consciência crítica do erro) de modo a melhorar a qualidade da representação do real. A investigação empírica foi realizada na disciplina de Desenho A, no ano letivo de 2012/2013, com duas turmas do 11º ano do Curso de Design de Produto na Escola Artística Soares dos Reis, no Porto. Os resultados obtidos sugerem que a perspetiva, enquanto estratégia, poderá melhorar significativamente a qualidade da representação do real. Todavia, relativamente ao estímulo da consciência crítica do erro através das estratégias abordadas dentro de sala de aula, não ficou comprovada relevância na qualidade das representações.

Uma cidade para pessoas: funcionalidade, racionalidade e emotividade nas relações mobiliário urbano, espaço público e cidadãos

This research investigates how functionality, rationality, and emotionality applied to urban furniture design contribute to the organization, legibility, and qualification of public spaces, according to different layouts, physical and visual qualities of the urban furniture as well as the quality of urban infrastructure that may influence the uses and appropriation of urban spaces by pedestrians, turning those spaces into socially centripetal or centrifugal places. The work consists of two parts. First refers to a bibliographical review concerning two main issues of the investigation: product design and legibility of public space, defining the conceptual and theoretical bases, linked to methodological strategies aimed at systemic planning and integrated management of urban furniture design and legibility of public spaces (sidewalks), that are necessary to define the existing relationships among the user s interface (pedestrians); product (urban artifacts); built environment (sidewalks). The second part refers to the achievement of empirical approach throughout visual analysis of public spaces and the functional and qualitative evaluation of the existing urban furniture in the central neighborhood of Cidade Alta, Natal, RN, according to the theoretical researched concepts and methodological procedures. The results expose the weaknesses and levels of intensity arising from the relations among public space, urban furniture, and users, revealing the need for theoretical and practical approaches which would help the decision-making in planning, designing and integrating innovative, sustainable, and ethical solutions in order to design attractive public spaces that could provide sociability and citizenship throughout integrated public management, city systemic thinking and urban identity. The suggested guidelines at the end of this research will provide the necessary strategies to design suitable urban furniture systems according to aesthetic and practical urban infrastructure and city context, aiming to ease visual and physical conflicts that may negatively interfere with the appropriation of public spaces by the citizens

An investigation of environmental conditions experienced during the life of high-value wood components and products

Australian forest industries have a long history of export trade of a wide range of products from woodchips (for paper manufacturing), sandalwood (essential oils, carving and incense) to high value musical instruments, flooring and outdoor furniture. For the high value group, fluctuating environmental conditions brought on by changes in temperature and relative humidity, can lead to performance problems due to consequential swelling, shrinkage and/or distortion of the wood elements. A survey determined the types of value-added products exported, including species and dimensions packaging used and export markets. Data loggers were installed with shipments to monitor temperature and relative humidity conditions. These data were converted to timber equilibrium moisture content values to provide an indication of the environment that the wood elements would be acclimatising to. The results of the initial survey indicated that primary high value wood export products included guitars, flooring, decking and outdoor furniture. The destination markets were mainly located in the northern hemisphere, particularly the United States of America, China, Hong Kong, Europe (including the United Kingdom), Japan, Korea and the Middle East. Other regions importing Australian-made wooden articles were south-east Asia, New Zealand and South Africa. Different timber species have differing rates of swelling and shrinkage, so the types of timber were also recorded during the survey. Results from this work determined that the major species were ash-type eucalypts from south-eastern Australia (commonly referred to in the market as Tasmanian oak), jarrah from Western Australia, spotted gum, hoop pine, white cypress, black butt, brush box and Sydney blue gum from Queensland and New South Wales. The environmental conditions data indicated that microclimates in shipping containers can fluctuate extensively during shipping. Conditions at the time of manufacturing were usually between 10 and 12% equilibrium moisture content, however conditions during shipping could range from 5 (very dry) to 20% (very humid). The packaging systems incorporated were reported to be efficient at protecting the wooden articles from damage during transit. The research highlighted the potential risk for wood components to ‘move’ in response to periods of drier or more humid conditions than those at the time of manufacturing, and the importance of engineering a packaging system that can account for the environmental conditions experienced in shipping containers. Examples of potential dimensional changes in wooden components were calculated based on published unit shrinkage data for key species and the climatic data returned from the logging equipment. The information highlighted the importance of good design to account for possible timber movement during shipping. A timber movement calculator was developed to allow designers to input component species, dimensions, site of manufacture and destination, to see validate their product design.

Desenvolvimento de um flotador industrial

A presente dissertação apresenta uma investigação teórica e prática na área de Engenharia e Design de Produto com o objetivo principal de desenvolver um Flotador Industrial para a Adventech, procurando indicadores inovadores, competitivos e focando a necessidade de encontrar uma solução que reflita numa relação entre necessidade, utilizador, performance e design. Desta forma, no presente trabalho cruzam-se temas como a Engenharia e o Design de Produto, Tratamentos de Efluentes Líquidos e Flotação de modo a introduzir e compreender o desenvolvimento deste equipamento. Foi efetuada uma pesquisa sobre o tema para compreender, as suas características e limitações, bem como as formas e mecanismos utilizados para dar resposta aos requisitos e produzir um produto eficiente e eficaz. Paralelamente realizou-se uma abordagem teórica sobre Design de Produto e Processo de Flotação, de modo a conhecer o seu desenvolvimento e as suas restrições, preocupações e objetivos. Complementou-se o trabalho desenvolvido com pesquisa e analisaram-se os produtos existentes na concorrência com o objetivo de conhecer características técnicas, funcionais e físicas. Desta forma, o estudo desenvolvido nesta dissertação serviu e auxiliou o projeto no resultado final, incluindo a materialização do conceito para proporcionar uma boa relação entre utilizador, performance e design. Obtendo assim, um resultado final com características adequadas nas diversas aplicações deste produto nas Estações de Águas Residuais, reduzindo custos de operação e manutenção, eficiência do processo de flotação e vida útil do produto. Paralelamente o design proporciona uma apresentação estética do produto que transmite fiabilidade e profissionalismo.