Targeted delivery of a novel group of site-directed transglutaminase inhibitors to the liver using liposomes:a new approach for the potential treatment of liver fibrosis

Liver fibrosis and its end-stage disease cirrhosis are a main cause of mortality and morbidity worldwide. Thus far, there is no efficient pharmaceutical intervention for the treatment of liver fibrosis. Liver fibrosis is characterized by excessive accumulation of the extracellular matrix (ECM) proteins. Transglutaminase (TG)-mediated covalent cross-linking has been implicated in the stabilization and accumulation of ECM in a number of fibrotic diseases. Thus, the use of tissue TG2 inhibitors has potential in the treatment of liver fibrosis. Recently, we introduced a novel group of site-directed irreversible specific inhibitors of TGs. Here, we describe the development of a liposome-based drug-delivery system for the site-specific delivery of these TG inhibitors into the liver. By using anionic or neutral-based DSPC liposomes, the TG inhibitor can be successfully incorporated into these liposomes and delivered specifically to the liver. Liposomes can therefore be used as a potential carrier system for site-specific delivery of the TG2 inhibitors into the liver, opening up a potential new avenue for the treatment of liver fibrosis and its end-stage disease cirrhosis.

Parents’ Preparedness for Their Infants’ Discharge Following First-stage Cardiac Surgery: Development of a Parental Early Warning Tool

Aim The aim of this study was to explore parental preparedness for discharge and their experiences of going home with their infant after the first-stage surgery for a functionally univentricular heart. Background Technological advances worldwide have improved outcomes for infants with a functionally univentricular heart over the last 3 decades; however, concern remains regarding mortality in the period between the first and second stages of surgery. The implementation of home monitoring programmes for this group of infants has improved this initial inter-stage survival; however, little is known about parents’ experiences of going home, their preparedness for discharge, and parents’ recognition of deterioration in their fragile infant. Method This study was conducted in 2011–2013; eight sets of parents were consulted in the research planning stage in September, 2011, and 22 parents with children aged 0–2 years responded to an online survey during November, 2012–March, 2013. Description of categorical data and deductive thematic analysis of the open-ended questions were undertaken. Results Not all parents were taught signs of deterioration or given written information specific to their baby. The following three themes emerged from the qualitative data: mixed emotions about going home, knowledge and preparedness, and support systems. Conclusions Parents are not adequately prepared for discharge and are not well equipped to recognise deterioration in their child. There is a role for greater parental education through development of an early warning tool to address the gap in parents’ understanding of signs of deterioration, enabling appropriate contact and earlier management by clinicians.

Development of gene therapy to deliver the receptor-specific rhTRAIL DHER variant to induce apoptosis in activated hepatic stellate cells for the treatment of liver fibrosis

Dissertação de Mestrado, Engenharia Biológica, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2014

Final report: stage 1 : results

This research project aims to improve economic, social and environmental sustainability of the pre-cast concrete and construction and demolition waste supply chains through the development, trial and evaluation of an innovative supply chain management strategy. The long-term goals are to improve competitive behaviour and market sector performance and improve business process efficiency and effectiveness of public sector program delivery by influencing policy development, changing organisational behaviour and implementation development to achieve more economic, social and environmental sustainable markets.

Safer construction : the development of a guide to best practice

In Australia, an average 49 building and construction workers have been killed at work each year since 1997-98. Building/construction workers are more than twice as likely to be killed at work, than the average worker in all Australian industries. The ‘Safer Construction’ project, funded by the CRC-Construction Innovation and led by a task force comprising representatives of construction clients, designers and constructors, developed a Guide to Best Practice for Safer Construction. The Guide, which was informed by research undertaken at RMIT University, Queensland University of Technology and Curtin University, establishes broad principles for the improvement of safety in the industry and provides a ‘roadmap’ for improvement based upon lifecycle stages of a building/construction project. Within each project stage, best practices for the management of safety are identified. Each best practice is defined in terms of the recommended action, its key benefits, desirable outcomes, performance measures and leadership. ‘Safer Construction’ practices are identified from the planning to commissioning stages of a project. The ‘Safer Construction’ project represents the first time that key stakeholder groups in the Australian building/construction industry have worked together to articulate best practice and establish an appropriate basis for allocating (and sharing) responsibility for project safety performance.

Interoperable Standards Development : Final Report

Since 1995 the buildingSMART International Alliance for Interoperability (buildingSMART)has developed a robust standard called the Industry Foundation Classes (IFC). IFC is an object oriented data model with related file format that has facilitated the efficient exchange of data in the development of building information models (BIM). The Cooperative Research Centre for Construction Innovation has contributed to the international effort in the development of the IFC standard and specifically the reinforced concrete part of the latest IFC 2x3 release. Industry Foundation Classes have been endorsed by the International Standards Organisation as a Publicly Available Specification (PAS) under the ISO label ISO/PAS 16739. For more details, go to http://www.tc184- sc4.org/About_TC184-SC4/About_SC4_Standards/ The current IFC model covers the building itself to a useful level of detail. The next stage of development for the IFC standard is where the building meets the ground (terrain) and with civil and external works like pavements, retaining walls, bridges, tunnels etc. With the current focus in Australia on infrastructure projects over the next 20 years a logical extension to this standard was in the area of site and civil works. This proposal recognises that there is an existing body of work on the specification of road representation data. In particular, LandXML is recognised as also is TransXML in the broader context of transportation and CityGML in the common interfacing of city maps, buildings and roads. Examination of interfaces between IFC and these specifications is therefore within the scope of this project. That such interfaces can be developed has already been demonstrated in principle within the IFC for Geographic Information Systems (GIS) project. National road standards that are already in use should be carefully analysed and contacts established in order to gain from this knowledge. The Object Catalogue for the Road Transport Sector (OKSTRA) should be noted as an example. It is also noted that buildingSMART Norway has submitted a proposal

The quality of interface design for educational courseware development in Malaysian educational context

Interactive educational courseware has been adopted in diverse education sectors such as primary, secondary, tertiary education, vocational and professional training. In Malaysian educational context, the ministry of education has implemented Smart School Project that aims to increase high level of academic achievement in primary and secondary schools by using interactive educational courseware. However, many researchers have reported that many coursewares fail to accommodate the learner and teacher needs. In particular, the interface design is not appropriately designed in terms of quality of learning. This paper reviews educational courseware development process in terms of defining quality of interface design and suggests a conceptual model of interface design through the integration of design components and interactive learning experience into the development process. As a result, it defines the concept of interactive learning experience in a more practical approach in order to implement each stage of the development process in a seamless and integrated way.

Simulation and development of a mock circulation loop with variable compliance

Heart disease is attributed as the highest cause of death in the world. Although this could be alleviated by heart transplantation, there is a chronic shortage of donor hearts and so mechanical solutions are being considered. Currently, many Ventricular Assist Devices (VADs) are being developed worldwide in an effort to increase life expectancy and quality of life for end stage heart failure patients. Current pre-clinical testing methods for VADs involve laboratory testing using Mock Circulation Loops (MCLs), and in vivo testing in animal models. The research and development of highly accurate MCLs is vital to the continuous improvement of VAD performance. The first objective of this study was to develop and validate a mathematical model of a MCL. This model could then be used in the design and construction of a variable compliance chamber to improve the performance of an existing MCL as well as form the basis for a new miniaturised MCL. An extensive review of literature was carried out on MCLs and mathematical modelling of their function. A mathematical model of a MCL was then created in the MATLAB/SIMULINK environment. This model included variable features such as resistance, fluid inertia and volumes (resulting from the pipe lengths and diameters); compliance of Windkessel chambers, atria and ventricles; density of both fluid and compressed air applied to the system; gravitational effects on vertical columns of fluid; and accurately modelled actuators controlling the ventricle contraction. This model was then validated using the physical properties and pressure and flow traces produced from a previously developed MCL. A variable compliance chamber was designed to reproduce parameters determined by the mathematical model. The function of the variability was achieved by controlling the transmural pressure across a diaphragm to alter the compliance of the system. An initial prototype was tested in a previously developed MCL, and a variable level of arterial compliance was successfully produced; however, the complete range of compliance values required for accurate physiological representation was not able to be produced with this initial design. The mathematical model was then used to design a smaller physical mock circulation loop, with the tubing sizes adjusted to produce accurate pressure and flow traces whilst having an appropriate frequency response characteristic. The development of the mathematical model greatly assisted the general design of an in vitro cardiovascular device test rig, while the variable compliance chamber allowed simple and real-time manipulation of MCL compliance to allow accurate transition between a variety of physiological conditions. The newly developed MCL produced an accurate design of a mechanical representation of the human circulatory system for in vitro cardiovascular device testing and education purposes. The continued improvement of VAD test rigs is essential if VAD design is to improve, and hence improve quality of life and life expectancy for heart failure patients.

A decision support system for sustainable urban development : the integrated land use and transportation indexing model

The broad definition of sustainable development at the early stage of its introduction has caused confusion and hesitation among local authorities and planning professionals. The main difficulties are experience in employing loosely-defined principles of sustainable development in setting policies and goals. The question of how this theory/rhetoric-practice gap could be filled will be the theme of this study. One of the widely employed sustainability accounting approaches by governmental organisations, triple bottom line, and applicability of this approach to sustainable urban development policies will be examined. When incorporating triple bottom line considerations with the environmental impact assessment techniques, the framework of GIS-based decision support system that helps decision-makers in selecting policy option according to the economic, environmental and social impacts will be introduced. In order to embrace sustainable urban development policy considerations, the relationship between urban form, travel pattern and socio-economic attributes should be clarified. This clarification associated with other input decision support systems will picture the holistic state of the urban settings in terms of sustainability. In this study, grid-based indexing methodology will be employed to visualise the degree of compatibility of selected scenarios with the designated sustainable urban future. In addition, this tool will provide valuable knowledge about the spatial dimension of the sustainable development. It will also give fine details about the possible impacts of urban development proposals by employing disaggregated spatial data analysis (e.g. land-use, transportation, urban services, population density, pollution, etc.). The visualisation capacity of this tool will help decision makers and other stakeholders compare and select alternative of future urban developments.

The Quality of Interface Design for Educational Courseware Development in Malaysian Educational Context

Interactive educational courseware has been adopted in diverse education sectors such as primary, secondary, tertiary education, vocational and professional training. In Malaysian educational context, the ministry of education has implemented Smart School Project that aims to increase high level of academic achievement in primary and secondary schools by using interactive educational courseware. However, many researchers have reported that many coursewares fail to accommodate the learner and teacher needs. In particular, the interface design is not appropriately designed in terms of quality of learning. This paper reviews educational courseware development process in terms of defining quality of interface design and suggests a conceptual model of interface design through the integration of design components and interactive learning experience into the development process. As a result, it defines the concept of interactive learning experience in a more practical approach in order to implement each stage of the development process in a seamless and integrated way.

User-designer collaboration during the early stage of the design process

As user involvement becomes a necessary part of the product development process, various ways of accessing users' latent needs have been developed and studied. Reviews of literatures in user involvement and product development have revealed that accessing users' latent needs and transferring them into design process could be facilitated by effectively implementing user-designer collaboration during the early stage of the design process. In this paper, various types of user-designer collaboration were observed and then distinct characteristics of user-designer collaboration were classified into three categories. 1) Passive objectivity, 2) workplace democratisation, and 3) shared contexts were observed as strategies for better user-designer collaboration, which have been employed in the area of user-centred design, user participatory design and design for experiencing. Based on the literature review, this paper proposed a basic collaboration mechanism between the users and the designers during the early stage of the design process and then discussed how its mechanism will help to describe the interactions between the users and the designers during the user involvement sessions.

Practising inspired leadership : the use of applied theatre 'prophetical' in the Executive Leadership Development Program for Queensland Health

The Executive Leadership Development Program embarked upon by Queensland Health as a part of the major reform program is discussed. The second stage of the program has begun and the main aim is to ensure leadership development across the organization.