Beyond problem identification: valuing methods in a ‘system usability practice’

Historically, usability evaluation methods (UEMs) have been evaluated on their capability for problem identification. However, the relevance of this approach has been questioned for applied usability work. To investigate alternative explanations of what is important for method use a grounded theory of usability practitioners was developed (9 interviews from the website domain and 13 in the safety-critical domain). The analysis proceeded in bottom-up and top-down stages. The bottom-up stages produced insight from the data in an exploratory and inductive manner. This highlighted the importance of contextual factors and the need for system descriptions: UEM adoption and adaptation cannot be fully understood devoid of context. The top-down stages used Distributed Cognition and Resilience Engineering conceptual frameworks as leverage for exploring the data in a deductive manner. These were chosen for their functional descriptions of systems. To illustrate the importance of context we describe three models: 1) where previous research has highlighted the downstream utility of UEMs we expand the metaphor to consider the landscape through which the stream flows, where the landscape represents the project’s context; 2) where information propagation and transformation in a project is influenced by social, information flow, artefact, physical and evolutionary factors; and 3) where the functional couplings between parts of the system of usability practice can be monitored and managed to positively resonate with each other, thereby improving the performance of the system overall. The concept of ‘Positive Resonance’ is introduced to describe how practitioners adapt to the context to maximise their impact under constrained resources. The functional couplings are described in a functional resonance model of HCI practice. This model is validated by interviewees and other practitioners outside of the study. This research shows that problem identification is limited for valuing UEMs. Instead, functional couplings of UEMs should be considered to improve system performance, which influence UEM adoption and adaptation in practice

Prophylaxis of disease caused by bacterial pathogens of man

This thesis reports research undertaken which will lead to improved pretreatments and therapies for disease caused by Clostridium perfringens, Francisella tularensis, Yersinia pestis and Burkholderia pseudomallei. C. perfringens is thought to be the most widely distributed bacterial pathogen and is the most important Clostridial species associated with enteric disease in domesticated animals. During warfare C. perfringens has been a significant causes of mortality. Between 1 and 10% of wounded personnel developed gas gangrene during the 1st and 2nd world wars. The ability of the bacterium to cause a range of diseases is due largely to the differential production of toxins. The first reported cloning and nucleotide sequencing of three of the four major toxins (α, β and ε-toxins) is documented in this thesis. The regulation of expression of α-toxin in C. perfringens has been investigated and methods for the expression of recombinant proteins in E. coli have been devised This information has been used to develop improved PCR-based diagnostic tests, and to investigate structure-function relationships. A high resolution crystal structure of a-toxin (phospholipase C) is reported. Using molecular and biophysical techniques, the functions of the two domains of the protein have been determined. Residues that play roles in the interaction of the toxin with host cell membranes have been identified using site-directed mutagenesis. This work has also provided a major insight into the structures and functions of related phospholipases C (the zincmetallophospholipases C) from other bacterial pathogens. This pioneering work with α-toxin is recognised by invitations to write reviews and book chapters on this subject and on bacterial phospholipases C. C. perfringens β-toxin has been shown to be related to pore forming toxins such as Staphylococcus aureus α-toxin. This finding suggests, for the first time, the mode of action of β-toxin. The interaction of C. perfringens ε-toxin with host cells has been investigated and progress made in identifying the cell-surface receptor for the toxin. Genetically engineered toxoids have been devised which induce high-level protection against α and ε-toxins. These vaccines are currently being developed by industry for veterinary use. Similar approaches have been used to devise a recombinant vaccine against Clostridium botulinum toxin F. The wider applications of toxins as therapeutics have also been investigated, and a novel cancer drug delivery system based on targeted lysis of drug-containing liposomes by α-toxin has been devised and patented. F. tularensis is the etiological agent of tularemia, a disease of man that is found in most countries in the Northern hemisphere and most frequently in Scandinavia, N. America, Japan and N. Russia. In this thesis the efficacy of antibiotics for the prevention and treatment of experimental tularemia is documented. Two surface antigens (lipopolysaccharide and FopA) have been evaluated as sub-unit vaccines. Of these, lipopolysaccharide shows potential as a protective antigen. However, because of the paucity of information available on this bacterium, a wider approach to vaccine development, involving the determination of the genome sequence of a fully virulent strain of F. tularensis has been undertaken. A preliminary analysis of the genome sequence is reported here, which has allowed the identification of targets for the development of a rationally attenuated mutant for use as a live vaccine. Y. pestis is generally recognised to have caused three major pandemics of disease, and credible estimates indicate that together these resulted in 200 million deaths. WHO figures indicate that there is a continuing public health problem from plague, especially in Africa, Asia and South America. In this thesis existing vaccines and antibiotics have been evaluated for the prevention and treatment of plague and found to have limitations. A number of approaches to the development of an improved vaccine have been investigated including rationally attenuated strains of the bacterium and isolated surface antigens. A sub-unit vaccine against plague has been devised based on recombinant forms of the F1- and V-antigens. This vaccine provides high level protection against both bubonic and pneumonic plague. This recombinant sub-unit vaccine has been patented and is currently in phase I clinical trials in man. This vaccine has been formulated for single oral or intranasal delivery, using microencapsulated or Salmonella-based delivery systems. Methods for enhancing the stability and efficacy of these vaccines have been investigated. Reviews on plague and plague vaccines have been written, confirming the status of the author as a world leader in this field. The work to devise an improved vaccine has also provided insight into the molecular basis of pathogencity of Y. pestis. A phoP / phoQ regulatory system has been discovered in the bacterium, which plays a key role in survival of the bacterium within macrophages. The V-antigen has been shown to be surface located to play a key role in the translocation of effector proteins into host cells. The biogenesis of the F1-capsular antigen has been investigated at a genetic and biophysical level. In order to underpin future work with this pathogen, the genome sequence is currently being determined. This work has already provided major new insights into the evolution of this pathogen. B. pseudomallei (formerly Pseudomonas pseudomallei) is found primarily in S. E. Asia, N. Australia and other tropical areas of the world. Melioidosis has recently appeared in temperate zones, including mainland France and the UK possible as a consequence of increased international travel. Acute disease can be treated with antibiotics but the bacterium can persist in the host and subsequent disease episodes can occur. In this thesis ciprofloxacin and doxycyline have been are evaluated and shown to have significant limitations for the treatment of melioidodis. In the longer term there is a requirement for an effective vaccine against melioidosis, and work is reported here to devise the genetic tools which will be necessary for the genetic manipulation of the bacterium, with a view towards the identification of virulence determinants

Proceedings of the First International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics

1st International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Kruger Park, 8-10 April 2002.This lecture is a principle-based review of a growing body of fundamental work stimulated by multiple opportunities to optimize geometric form (shape, structure, configuration, rhythm, topology, architecture, geography) in systems for heat and fluid flow. Currents flow against resistances, and by generating entropy (irreversibility) they force the system global performance to levels lower than the theoretical limit. The system design is destined to remain imperfect because of constraints (finite sizes, costs, times). Improvements can be achieved by properly balancing the resistances, i.e., by spreading the imperfections through the system. Optimal spreading means to endow the system with geometric form. The system construction springs out of the constrained maximization of global performance. This 'constructal' design principle is reviewed by highlighting applications from heat transfer engineering. Several examples illustrate the optimized internal structure of convection cooled packages of electronics. The origin of optimal geometric features lies in the global effort to use every volume element to the maximum, i.e., to pack the element not only with the most heat generating components, but also with the most flow, in such a way that every fluid packet is effectively engaged in cooling. In flows that connect a point to a volume or an area, the resulting structure is a tree with high conductivity branches and low-conductivity interstices.tm201