Functional evaluation of genetic variants associated with endometriosis near GREB1

STUDY QUESTION: Do DNA variants in the growth regulation by estrogen in breast cancer 1 (GREB1) region regulate endometrial GREB1 expression and increase the risk of developing endometriosis in women? SUMMARY ANSWER: We identified new single nucleotide polymorphisms (SNPs) with strong association with endometriosis at the GREB1 locus although we did not detect altered GREB1 expression in endometriosis patients with defined genotypes. WHAT IS ALREADY KNOWN: Genome-wide association studies have identified the GREB1 region on chromosome 2p25.1 for increasing endometriosis risk. The differential expression of GREB1 has also been reported by others in association with endometriosis disease phenotype. STUDY DESIGN, SIZE, DURATION: Fine mapping studies comprehensively evaluated SNPs within the GREB1 region in a large-scale data set (>2500 cases and >4000 controls). Publicly available bioinformatics tools were employed to functionally annotate SNPs showing the strongest association signal with endometriosis risk. Endometrial GREB1 mRNA and protein expression was studied with respect to phases of the menstrual cycle (n = 2-45 per cycle stage) and expression quantitative trait loci (eQTL) analysis for significant SNPs were undertaken for GREB1 [mRNA (n = 94) and protein (n = 44) in endometrium]. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants in this study are females who provided blood and/or endometrial tissue samples in a hospital setting. The key SNPs were genotyped using Sequenom MassARRAY. The functional roles and regulatory annotations for identified SNPs are predicted by various publicly available bioinformatics tools. Endometrial GREB1 expression work employed qRT-PCR, western blotting and immunohistochemistry studies. MAIN RESULTS AND THE ROLE OF CHANCE: Fine mapping results identified a number of SNPs showing stronger association (0.004 < P < 0.032) with endometriosis risk than the original GWAS SNP (rs13394619) (P = 0.034). Some of these SNPs were predicted to have functional roles, for example, interaction with transcription factor motifs. The haplotype (a combination of alleles) formed by the risk alleles from two common SNPs showed significant association (P = 0.026) with endometriosis and epistasis analysis showed no evidence for interaction between the two SNPs, suggesting an additive effect of SNPs on endometriosis risk. In normal human endometrium, GREB1 protein expression was altered depending on the cycle stage (significantly different in late proliferative versus late secretory, P < 0.05) and cell type (glandular epithelium, not stromal cells). However, GREB1 expression in endometriosis cases versus controls and eQTL analyses did not reveal any significant changes. LIMITATIONS, REASONS FOR CAUTION: In silico prediction tools are generally based on cell lines different to our tissue and disease of interest. Functional annotations drawn from these analyses should be considered with this limitation in mind. We identified cell-specific and hormone-specific changes in GREB1 protein expression. The lack of a significant difference observed following our GREB1 expression studies may be the result of moderate power on mixed cell populations in the endometrial tissue samples. WIDER IMPLICATIONS OF THE FINDINGS: This study further implicates the GREB1 region on chromosome 2p25.1 and the GREB1 gene with involvement in endometriosis risk. More detailed functional studies are required to determine the role of the novel GREB1 transcripts in endometriosis pathophysiology. STUDY FUNDING/COMPETING INTERESTS: Funding for this work was provided by NHMRC Project Grants APP1012245, APP1026033, APP1049472 and APP1046880. There are no competing interests.

Identification methods of key contributing factors in crashes with high numbers of fatalities and injuries in China

Objectives In China, “serious road traffic crashes” (SRTCs) are those in which there are 10-30 fatalities, 50-100 serious injuries or a total cost of 50-100 million RMB ($US8-16m), and “particularly serious road traffic crashes” (PSRTCs) are those which are more severe or costly. Due to the large number of fatalities and injuries as well as the negative public reaction they elicit, SRTCs and PSRTCs have become great concerns to China during recent years. The aim of this study is to identify the main factors contributing to these road traffic crashes and to propose preventive measures to reduce their number. Methods 49 contributing factors of the SRTCs and PSRTCs that occurred from 2007 to 2013 were collected from the database “In-depth Investigation and Analysis System for Major Road traffic crashes” (IIASMRTC) and were analyzed through the integrated use of principal component analysis and hierarchical clustering to determine the primary and secondary groups of contributing factors. Results Speeding and overloading of passengers were the primary contributing factors, featuring in up to 66.3% and 32.6% of accidents respectively. Two secondary contributing factors were road-related: lack of or nonstandard roadside safety infrastructure, and slippery roads due to rain, snow or ice. Conclusions The current approach to SRTCs and PSRTCs is focused on the attribution of responsibility and the enforcement of regulations considered relevant to particular SRTCs and PSRTCs. It would be more effective to investigate contributing factors and characteristics of SRTCs and PSRTCs as a whole, to provide adequate information for safety interventions in regions where SRTCs and PSRTCs are more common. In addition to mandating of a driver training program and publicisation of the hazards associated with traffic violations, implementation of speed cameras, speed signs, markings and vehicle-mounted GPS are suggested to reduce speeding of passenger vehicles, while increasing regular checks by traffic police and passenger station staff, and improving transportation management to increase income of contractors and drivers are feasible measures to prevent overloading of people. Other promising measures include regular inspection of roadside safety infrastructure, and improving skid resistance on dangerous road sections in mountainous areas.

Developing the helping relationship: Engaging with clients in different contexts

"Human service workers need more than just common sense. This book offers a comprehensive introduction to practice skills required across the human service sector. The authors use critical analysis to systematically outline the key stages of interaction with clients."--Libraries Australia "A thorough introduction to the core practice skills needed by social work and welfare professionals. Human service workers need more than just common sense. Practice Skills in Social Work and Welfare offers a comprehensive introduction to practice skills required across the human service sector. The authors use critical analysis to systematically outline the key stages of interaction with clients: engagement, assessment, intervention and evaluation. Drawing on a strengths approach, they examine the skills needed for working with different types of clients: individuals, families and community groups. They also explore the dilemmas faced in daily practice, including the challenges of working with involuntary clients, clients from different cultural backgrounds, and clients in crisis situations. Practice Skills in Social Work and Welfare provides a model of integrated practice which incorporates the key components of ideology, theory, phase, skill and context. Detailed case studies demonstrate how welfare services can be delivered in different contexts. Written by experienced teachers and practitioners from Australia and New Zealand, Practice Skills in Social Work and Welfare is a practical and user friendly text for students and reference for practitioners"--Publisher website

Developing the helping relationship: Engaging with clients in different contexts

"Fully revised edition of this widely used introduction to the core practice skills needed by social work and other human service professionals. 'The main strength of the book is the consistency of its themes throughout the text.I would like to commend the editors of this book for the contribution it should make to practice teaching with social work and welfare' - Karen Heycox in Australian Social Work Human service workers need more than just common sense. Practice Skills in Social Work and Welfare offers a comprehensive introduction to practice skills required across the human service sector. The authors use critical analysis to systematically outline the key stages of interaction with clients: engagement, assessment, intervention and evaluation. Drawing on a strengths approach, they examine the skills needed for working with different types of clients: individuals, families and community groups. They also explore the dilemmas faced in daily practice, including the challenges of working with involuntary clients, clients from different cultural backgrounds, and clients in crisis situations. Practice Skills in Social Work and Welfare provides a model of integrated practice which incorporates the key components of ideology, theory, phase, skill and context. Detailed case studies demonstrate how welfare services can be delivered in different contexts. This second edition has been thoroughly revised and updated and includes new material on online services and strengths-based practice. Written by experienced teachers and practitioners from Australia and New Zealand, Practice Skills in Social Work and Welfare is a practical and user friendly text for students and reference for practitioners."--Publisher website

Airborne particulate matter at a bus station : concentration levels and governing parameters

Traffic emissions are an important contributor to ambient air pollution, especially in large cities featuring extensive and high density traffic networks. Bus fleets represent a significant part of inner city traffic causing an increase in exposure to general public, passengers and drivers along bus routes and at bus stations. Limited information is available on quantification of the levels, and governing parameters affecting the air pollution exposure at bus stations. The presented study investigated the bus emissions-dominated ambient air in a large, inner city bus station, with a specific focus on submicrometer particles. The study’s objectives were (i) quantification of the concentration levels; (ii) characterisation of the spatio-temporal variation; (iii) identification of the parameters governing the emissions levels at the bus station and (iv) assessment of the relationship between particle concentrations measured at the street level (background) and within the bus station. The results show that up to 90% of the emissions at the station are ultrafine particles (smaller than 100 nm), with the concentration levels up to 10 times the value of urban ambient air background (annual) and up to 4 times the local ambient air background. The governing parameters affecting particle concentration at the station were bus flow rate and meteorological conditions (wind velocity). Particle concentration followed a diurnal trend, with an increase in the morning and evening, associated with traffic rush hours. Passengers’ exposure could be significant compared to the average outdoor and indoor exposure levels.

Leveraging sponsorships on the Internet: Activation, congruence, and articulation

This paper considers how the Internet can be used to leverage commercial sponsorships to enhance audience attitudes toward the sponsor. Definitions are offered that distinguish the terms leverage and activation with respect to sponsorship-linked marketing; leveraging encompasses all marketing communications collateral to the sponsorship investment, whereas activation relates to those communications that encourage interaction with the sponsor. Although activation in many instances may be limited to the immediate event-based audience, leveraging sponsorships via sponsors' Web sites enables activation at the mass-media audience level. Results of a Web site navigation experiment demonstrate that activational sponsor Web sites promote more favorable attitudes than do nonactivational Web sites. It is also shown that sponsorsponsee congruence effects generalize to the online environment, and that the effects of sponsorship articulation on audience attitudes are moderated by the commerciality of the explanation for the sponsor-sponsee relationship. Importantly, the study reveals that attitudinal effects associated with variations in leveraging, congruence, and orientation of articulation may be sustained across time.

Relationships between employees and their nomadic, non-territorial work environment

Recent and current socio-cultural trends are significant factors impacting on how business is conduced and correspondingly, on how work environments are designed. New communication technology is helping to break physical boundaries and change the way and speed of conducting business. One of the main characteristics of these new workplaces is non-permanency wherein the individual employee has no dedicated personally assigned office, work station, or desk. In this non-territorial, nomadic situation, employees undertake their work tasks in a wide variety of work settings inside and outside the office building. Such environments are understood to be must suitable where there is the need for high interaction with others as well as a high level of concentrated, independent work. This thesis reports on a project designed to develop a deeper understanding of the relationships between people (P) and their built environment (E) in the context of everyday work practice in a nomadic and non-territorial work environment. To achieve this, the study focuses on the experiences of employees as they understand them in relation to their work and the designed/ physical work environment. In this sense, the study is qualitative and grounded in nature. It does not assume any previously established theory nor test any presenting hypothesis. Instead it interviews the participants about their situations at work in their workplace, interprets natural interaction and creates a foundation for the development of theory informing workplace design, particularly theory that recognises the human nature of work and the need, as highlighted by several seminal researchers, for a greater understanding of how people manage and adapt in dynamic work environments.

Experience of problem-based learning (PBL) in virtual space : a phenomenographical study

This thesis reports the outcomes of an investigation into students’ experience of Problem-based learning (PBL) in virtual space. PBL is increasingly being used in many fields including engineering education. At the same time many engineering education providers are turning to online distance education. Unfortunately there is a dearth of research into what constitutes an effective learning experience for adult learners who undertake PBL instruction through online distance education. Research was therefore focussed on discovering the qualitatively different ways that students experience PBL in virtual space. Data was collected in an electronic environment from a course, which adopted the PBL strategy and was delivered entirely in virtual space. Students in this course were asked to respond to open-ended questions designed to elicit their learning experience in the course. Data was analysed using the phenomenographical approach. This interpretative research method concentrated on mapping the qualitative differences in students’ interpretations of their experience in the course. Five qualitatively different ways of experiencing were discovered: Conception 1: ‘A necessary evil for program progression’; Conception 2: ‘Developing skills to understand, evaluate, and solve technical Engineering and Surveying problems’; Conception 3: ‘Developing skills to work effectively in teams in virtual space’; Conception 4: ‘A unique approach to learning how to learn’; Conception 5: ‘Enhancing personal growth’. Each conception reveals variation in how students attend to learning by PBL in virtual space. Results indicate that the design of students’ online learning experience was responsible for making students aware of deeper ways of experiencing PBL in virtual space. Results also suggest that the quality and quantity of interaction with the team facilitator may have a significant impact on the student experience in virtual PBL courses. The outcomes imply pedagogical strategies can be devised for shifting students’ focus as they engage in the virtual PBL experience to effectively manage the student learning experience and thereby ensure that they gain maximum benefit. The results from this research hold important ramifications for graduates with respect to their ease of transition into professional work as well as their later professional competence in terms of problem solving, ability to transfer basic knowledge to real-life engineering scenarios, ability to adapt to changes and apply knowledge in unusual situations, ability to think critically and creatively, and a commitment to continuous life-long learning and self-improvement.

Implication of 3D culture system for study of prostate cancer (CaP) mediated bone metastasis

Introduction : For the past decade, three dimensional (3D) culture has served as a foundation for regenerative medicine study. With an increasing awareness of the importance of cell-cell and cell-extracellular matrix interactions which are lacking in 2D culture system, 3D culture system has been employed for many other applications namely cancer research. Through development of various biomaterials and utilization of tissue engineering technology, many in vivo physiological responses are now better understood. The cellular and molecular communication of cancer cells and their microenvironment, for instance can be studied in vitro in 3D culture system without relying on animal models alone. Predilection of prostate cancer (CaP) to bone remains obscure due to the complexity of the mechanisms and lack of proper model for the studies. In this study, we aim to investigate the interaction between CaP cells and osteoblasts simulating the natural bone metastasis. We also further investigate the invasiveness of CaP cells and response of androgen sensitve CaP cells, LNCaP to synthetic androgen.----- Method : Human osteoblast (hOB) scaffolds were prepared by seeding hOB on medical grade polycaprolactone-tricalcium phosphate (mPLC-TCP) scaffolds and induced to produce bone matrix. CaP cell lines namely wild type PC3 (PC3-N), overexpressed prostate specific antigen PC3 (PC3k3s5) and LNCaP were seeded on hOB scaffolds as co-cultures. Morphology of cells was examined by Phalloidin-DAPI and SEM imaging. Gelatin zymography was performed on the 48 hours conditioned media (CM) from co-cultures to determine matrix metalloproteinase (MMP) activity. Gene expression of hOB/LNCaP co-cultures which were treated for 48 hours with 1nM synthetic androgen R1881 were analysed by quantitative real time PCR (qRT-PCR).----- Results : Co-culture of PCC/hOB revealed that the morphology of PCCs on the tissue engineered bone matrix varied from homogenous to heterogenous clusters. Enzymatically inactive pro-MMP2 was detected in CM from hOBs and PCCs cultured on scaffolds. Elevation in MMP9 activity was found only in hOB/PC3N co-culture. hOB/LNCaP co-culture showed increase in expression of key enzymes associated with steroid production which also corresponded to an increase in prostate specific antigen (PSA) and MMP9.----- Conclusions : Upregulation of MMP9 indicates involvement of ECM degradation during cancer invasion and bone metastases. Expression of enzymes involved in CaP progression, PSA, which is not expressed in osteoblasts, demonstrates that crosstalk between PCCs and osteoblasts may play a part in the aggressiveness of CaP. The presence of steroidogenic enzymes, particularly, RDH5, in osteoblasts and stimulated expression in co-culture, may indicate osteoblast production of potent androgens, fuelling cancer cell proliferation. Based on these results, this practical 3D culture system may provide greater understanding into CaP mediated bone metastasis. This allows the role of the CaP/hOB interaction with regards to invasive property and steroidogenesis to be further explored.

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.

The critical competences needed for innovative organizational inter-firm and intra-firm integration

In today's highly challenging business environment, an innovative and systemic approach is imperative to survival and growth. Organisational integration and technological integration, are often seen as a catalyst of change that could lead to significant improvements in organisations. The levels of improvement in inter and intra firm integration should arise from a detailed understanding and development of competences within and between organisations. Preliminary findings suggest that lack of trust across organisational cultures within the firms has a negative influence on the development of the capabilities to integrate and align technological innovations and hinders implementation and the effectiveness of the operations. Additionally, poor communication and conflict effects customer satisfaction. Firms need to transfer the competences that support cooperative integration, developed through interaction with supply chain partners, to their relationship arrangements with other supply chain partners, as these are key to ensuring low operational costs.

Development of a particle number and particle mass vehicle emissions inventory for an urban fleet

Motor vehicles are major emitters of gaseous and particulate pollution in urban areas, and exposure to particulate pollution can have serious health effects, ranging from respiratory and cardiovascular disease to mortality. Motor vehicle tailpipe particle emissions span a broad size range from 0.003-10µm, and are measured as different subsets of particle mass concentrations or particle number count. However, no comprehensive inventories currently exist in the international published literature covering this wide size range. This paper presents the first published comprehensive inventory of motor vehicle tailpipe particle emissions covering the full size range of particles emitted. The inventory was developed for urban South-East Queensland by combining two techniques from distinctly different disciplines, from aerosol science and transport modelling. A comprehensive set of particle emission factors were combined with traffic modelling, and tailpipe particle emissions were quantified for particle number (ultrafine particles), PM1, PM2.5 and PM10 for light and heavy duty vehicles and buses. A second aim of the paper involved using the data derived in this inventory for scenario analyses, to model the particle emission implications of different proportions of passengers travelling in light duty vehicles and buses in the study region, and to derive an estimate of fleet particle emissions in 2026. It was found that heavy duty vehicles (HDVs) in the study region were major emitters of particulate matter pollution, and although they contributed only around 6% of total regional vehicle kilometres travelled, they contributed more than 50% of the region’s particle number (ultrafine particles) and PM1 emissions. With the freight task in the region predicted to double over the next 20 years, this suggests that HDVs need to be a major focus of mitigation efforts. HDVs dominated particle number (ultrafine particles) and PM1 emissions; and LDV PM2.5 and PM10 emissions. Buses contributed approximately 1-2% of regional particle emissions.

How do other people influence your driving speed? Exploring the 'who' and the 'how' of social influences on speeding from a qualitative perspective

Using only legal sanctions to manage the speed at which people drive ignores the potential benefits of harnessing social factors such as the influence of others. Social influences on driver speeds were explored in this qualitative examination of 67 Australian drivers. Focus group interviews with 8 driver types (young, mid-age and older males and females, and self-identified Excessive and Rare speeders) were guided by Akers’ social learning theory (Akers, 1998). Findings revealed two types of influential others: people known to the driver (passengers and parents), and unknown other drivers. Passengers were generally described as having a slowing influence on drivers: responsibility for the safety of people in the car and consideration for passenger comfort were key themes. In contrast, all but the Rare speeders reported increasing their speed when driving alone. Parental role modelling was also described. In relation to other drivers, key themes included speeding to keep up with traffic flow and perceived pressure to drive faster. This ‘pressure’ from others to ‘speed up’ was expressed in all groups and reported strategies for managing this varied. Encouragingly, examples of actual or anticipated social rewards for speeding were less common than examples of social punishments. Three main themes relating to social punishments were embarrassment, breaching the trust of others, and presenting an image of a responsible driver. Impression management and self-presentation are discussed in light of these findings. Overall, our findings indicate scope to exploit the use of social sanctions for speeding and social praise for speed limit compliance to enhance speed management strategies.

Biotribological assessment for artificial synovial joints : the role of boundary lubrication

Biotribology, the study of lubrication, wear and friction within the body, has become a topic of high importance in recent times as we continue to encounter debilitating diseases and trauma that destroy function of the joints. A highly successful surgical procedure to replace the joint with an artificial equivalent alleviates dysfunction and pain. However, the wear of the bearing surfaces in prosthetic joints is a significant clinical problem and more patients are surviving longer than the life expectancy of the joint replacement. Revision surgery is associated with increased morbidity and mortality and has a far less successful outcome than primary joint replacement. As such, it is essential to ensure that everything possible is done to limit the rate of revision surgery. Past experience indicates that the survival rate of the implant will be influenced by many parameters, of primary importance, the material properties of the implant, the composition of the synovial fluid and the method of lubrication. In prosthetic joints, effective boundary lubrication is known to take place. The interaction of the boundary lubricant and the bearing material is of utmost importance. The identity of the vital active ingredient within synovial fluid (SF) to which we owe the near frictionless performance of our articulating joints has been the quest of researchers for many years. Once identified, tribo tests can determine what materials and more importantly what surfaces this fraction of SF can function most optimally with. Surface-Active Phospholipids (SAPL) have been implicated as the body’s natural load bearing lubricant. Studies in this thesis are the first to fully characterise the adsorbed SAPL detected on the surface of retrieved prostheses and the first to verify the presence of SAPL on knee prostheses. Rinsings from the bearing surfaces of both hip and knee prostheses removed from revision operations were analysed using High Performance Liquid Chromatography (HPLC) to determine the presence and profile of SAPL. Several common prosthetic materials along with a novel biomaterial were investigated to determine their tribological interaction with various SAPLs. A pin-on-flat tribometer was used to make comparative friction measurements between the various tribo-pairs. A novel material, Pyrolytic Carbon (PyC) was screened as a potential candidate as a load bearing prosthetic material. Friction measurements were also performed on explanted prostheses. SAPL was detected on all retrieved implant bearing surfaces. As a result of the study eight different species of phosphatidylcholines were identified. The relative concentrations of each species were also determined indicating that the unsaturated species are dominant. Initial tribo tests employed a saturated phosphatidylcholine (SPC) and the subsequent tests adopted the addition of the newly identified major constituents of SAPL, unsaturated phosphatidylcholine (USPC), as the test lubricant. All tribo tests showed a dramatic reduction in friction when synthetic SAPL was used as the lubricant under boundary lubrication conditions. Some tribopairs showed more of an affinity to SAPL than others. PyC performed superior to the other prosthetic materials. Friction measurements with explanted prostheses verified the presence and performance of SAPL. SAPL, in particular phosphatidylcholine, plays an essential role in the lubrication of prosthetic joints. Of particular interest was the ability of SAPLs to reduce friction and ultimately wear of the bearing materials. The identification and knowledge of the lubricating constituents of SF is invaluable for not only the future development of artificial joints but also in developing effective cures for several disease processes where lubrication may play a role. The tribological interaction of the various tribo-pairs and SAPL is extremely favourable in the context of reducing friction at the bearing interface. PyC is highly recommended as a future candidate material for use in load bearing prosthetic joints considering its impressive tribological performance.

Improving the Traversal of Large Hierarchical Process Repositories

Business Process Management (BPM) has increased in popularity and maturity in recent years. Large enterprises engage use process management approaches to model, manage and refine repositories of process models that detail the whole enterprise. These process models can run to the thousands in number, and may contain large hierarchies of tasks and control structures that become cumbersome to maintain. Tools are therefore needed to effectively traverse this process model space in an efficient manner, otherwise the repositories remain hard to use, and thus are lowered in their effectiveness. In this paper we analyse a range of BPM tools for their effectiveness in handling large process models. We establish that the present set of commercial tools is lacking in key areas regarding visualisation of, and interaction with, large process models. We then present six tool functionalities for the development of advanced business process visualisation and interaction, presenting a design for a tool that will exploit the latest advances in 2D and 3D computer graphics to enable fast and efficient search, traversal and modification of process models.