Endochondral ossification in vitro is influenced by mechanical bending

Bone development is influenced by the local mechanical environment. Experimental evidence suggests that altered loading can change cell proliferation and differentiation in chondro- and osteogenesis during endochondral ossification. This study investigated the effects of three-point bending of murine fetal metatarsal bone anlagen in vitro on cartilage differentiation, matrix mineralization and bone collar formation. This is of special interest because endochondral ossification is also an important process in bone healing and regeneration. Metatarsal preparations of 15 mouse fetuses stage 17.5 dpc were dissected en bloc and cultured for 7 days. After 3 days in culture to allow adherence they were stimulated 4 days for 20 min twice daily by a controlled bending of approximately 1000-1500 microstrain at 1 Hz. The paraffin-embedded bone sections were analyzed using histological and histomorphometrical techniques. The stimulated group showed an elongated periosteal bone collar while the total bone length was not different from controls. The region of interest (ROI), comprising the two hypertrophic zones and the intermediate calcifying diaphyseal zone, was greater in the stimulated group. The mineralized fraction of the ROI was smaller in the stimulated group, while the absolute amount of mineralized area was not different. These results demonstrate that a new device developed to apply three-point bending to a mouse metatarsal bone culture model caused an elongation of the periosteal bone collar, but did not lead to a modification in cartilage differentiation and matrix mineralization. The results corroborate the influence of biophysical stimulation during endochondral bone development in vitro. Further experiments with an altered loading regime may lead to more pronounced effects on the process of endochondral ossification and may provide further insights into the underlying mechanisms of mechanoregulation which also play a role in bone regeneration.

CYR61 (CCN1) protein expression during fracture healing in an ovine tibial model and its relation to the mechanical fixation stability

The formation of new blood vessels is a prerequisite for bone healing. CYR61 (CCN1), an extracellular matrix-associated signaling protein, is a potent stimulator of angiogenesis and mesenchymal stem cell expansion and differentiation. A recent study showed that CYR61 is expressed during fracture healing and suggested that CYR61 plays a significant role in cartilage and bone formation. The hypothesis of the present study was that decreased fixation stability, which leads to a delay in healing, would lead to reduced CYR61 protein expression in fracture callus. The aim of the study was to quantitatively analyze CYR61 protein expression, vascularization, and tissue differentiation in the osteotomy gap and relate to the mechanical fixation stability during the course of healing. A mid-shaft osteotomy of the tibia was performed in two groups of sheep and stabilized with either a rigid or semirigid external fixator, each allowing different amounts of interfragmentary movement. The sheep were sacrificed at 2, 3, 6, and 9 weeks postoperatively. The tibiae were tested biomechanically and histological sections from the callus were analyzed immunohistochemically with regard to CYR61 protein expression and vascularization. Expression of CYR61 protein was upregulated at the early phase of fracture healing (2 weeks), decreasing over the healing time. Decreased fixation stability was associated with a reduced upregulation of the CYR61 protein expression and a reduced vascularization at 2 weeks leading to a slower healing. The maximum cartilage callus fraction in both groups was reached at 3 weeks. However, the semirigid fixator group showed a significantly lower CYR61 immunoreactivity in cartilage than the rigid fixator group at this time point. The fraction of cartilage in the semirigid fixator group was not replaced by bone as quickly as in the rigid fixator group leading to an inferior histological and mechanical callus quality at 6 weeks and therefore to a slower healing. The results supply further evidence that CYR61 may serve as an important regulator of bone healing.

The course of bone healing is influenced by the initial shear fixation stability

Fracture healing is influenced by fixation stability and experimental evidence suggests that the initial mechanical conditions may determine the healing outcome. We hypothesised that mechanical conditions influence not only the healing outcome, but also the early phase of fracture healing. Additionally, it was hypothesised that decreased fixation stability characterised by an increased shear interfragmentary movement results in a delay in healing. Sixty-four sheep underwent a mid-shaft tibial osteotomy which was treated with either a rigid or a semi-rigid external fixator. Animals were sacrificed at 2, 3, 6 and 9 weeks postoperatively and the fracture callus was analysed using radiological, biomechanical and histological techniques. The tibia treated with semi-rigid fixation showed inferior callus stiffness and quality after 6 weeks. At 9 weeks, the calluses were no longer distinguishable in their mechanical competence. The calluses at 9 weeks produced under rigid fixation were smaller and consisted of a reduced fibrous tissue component. These results demonstrate that the callus formation over the course of healing differed both morphologically and in the rate of development. In this study, we provide evidence that the course of healing is influenced by the initial fixation stability. The semi-rigid fixator did not result in delayed healing, but a less optimal healing path was taken. An upper limit of stability required for successful healing remains unknown, however a limit by which healing is less optimal has been determined.

Subchondral bone osteoblasts can induce chondrocyte mineralization during osteoarthritis and this process is relevant to cartilage degradation

Pathological mineralization of articular cartilage is a characteristic feature of osteoarthritis (OA); however, the underlying mechanisms, and their relevance to cartilage degeneration, are not clear. The involvement of subchondral bone changes in OA have been reported previously with the characterization of abnormal subchondral bone mineral density (BMD), osteiod volume, altered bone mechanical parameters and an increase in bone turnover markers. A number of osteoarthritic animal models have demonstrated that subchondral bone changes often precede cartilage degeneration. In this study site specific localization of mineralization markers were detected in the OA cartilage. Chondrocytes and osteoblasts derived from OA cartilage and subchondral bone showed a significant increase in the mRNA expressions of mineralization markers. Interestingly, osteoblasts from OA subchondral bone could significantly decrease cartilage matrix expression; whereas, increase mineralization of chondrocytes (Figure 1). Osteogenic factors, such as CBFA1, ALP, and type X collagen (Col-X), were detected in chondrocytes under mineralization conditions (Figure 2). Furthermore, chondrocyte mineralization was followed by increased mRNA and protein levels of MMP-2, MMP-9 and MMP-13, all of which are detrimental to cartilage integrity in vivo. The data reported here suggests that the upregulation of subchondral bone-mineralization, typical of OA progression, causes cartilage mineralization, and that the mineralization of chondrocytes induce increased MMP levels with a subsequent degradation of the articular cartilage.

Gender influences on the work-related stress-coping process

The increasing incidence of occupational stress is recognized as a global phenomenon that is having a detrimental impact on both individuals and organizations. This study aims to identify whether men and women adopt different stress and coping processes when subjected to stress in a work context. A total of 258 workers of various professions (males = 106, females = 152) participated in the study. Results indicated that men and women differ in their stress and coping processes, forming two very distinct groups and adopting specific process models when encountering a stressful situation at work. Limitations and implications from this study are discussed.

Call for action : investigating the role of business process management in green IS

Sustainable practices are more than ever on the radar screen of organizations, triggered by a growing demand of the wider population towards approaches and practices that can be considered "green" or "sustainable". Our specific intent with this call for action is to immerse deeper into the role of business processes, and specifically the contributions that the management of these processes can play in leveraging the transformative power of information systems (IS) in order to create environmentally sustainable organizations. Our key premise is that business and information technology (IT) managers need to engage in a process-focused discussion to enable a common, comprehensive understanding of process, and the process-centered opportunities for making these processes, and ultimately the organization as a process-centric entity, "green". Based on a business process lifecycle model, we propose possible avenues for future research.

Preclinical animal models for segmental bone defect research and tissue engineering

Currently, well-established clinical therapeutic approaches for bone reconstruction are restricted to the transplantation of autografts and allografts, and the implantation of metal devices or ceramic-based implants to assist bone regeneration. Bone grafts possess osteoconductive and osteoinductive properties, however they are limited in access and availability and associated with donor site morbidity, haemorrhage, risk of infection, insufficient transplant integration, graft devitalisation, and subsequent resorption resulting in decreased mechanical stability. As a result, recent research focuses on the development of alternative therapeutic concepts. Analysing the tissue engineering literature it can be concluded that bone regeneration has become a focus area in the field. Hence, a considerable number of research groups and commercial entities work on the development of tissue engineered constructs for bone regeneration. However, bench to bedside translations are still infrequent as the process towards approval by regulatory bodies is protracted and costly, requiring both comprehensive in vitro and in vivo studies. In translational orthopaedic research, the utilisation of large preclinical animal models is a conditio sine qua non. Consequently, to allow comparison between different studies and their outcomes, it is essential that animal models, fixation devices, surgical procedures and methods of taking measurements are well standardized to produce reliable data pools as a base for further research directions. The following chapter reviews animal models of the weight-bearing lower extremity utilized in the field which include representations of fracture-healing, segmental bone defects, and fracture non-unions.

Investigating the process of teaching and learning principles through practice : a case study on collegiate action by media practitioners and teachers, designing a skills-based learning program

This paper in the journalism education field reports on the construction of a new subject as part of a postgraduate coursework degree. The subject, or unit1 will offer both Journalism students and other students an introductory experience of creating media, using common ‘new media’ tools, with exercises that will model the learning of communication principles through practice. It has been named ‘Fundamental Media Skills for the Workplace’. The conceptualisation and teaching of it will be characteristic of the Journalism academic discipline that uses the ‘inside perspective’—understanding mass media by observing from within. Proposers for the unit within the Journalism discipline have sought to extend the common teaching approach, based on training to produce start-ready recruits for media jobs, backed by a study of contexts, e.g. journalistic ethics, or media audiences. In this proposal, students would then examine the process to elicit additional knowledge about their learning. The paper draws on literature of journalism and its pedagogy, and on communication generally. It also documents a ‘community of practice’ exercise conducted among practitioners as teachers for the subject, developing exercises and models of media work. A preliminary conclusion from that exercise is that it has taken a step towards enhancing skills-based learning for media work, as a portal to more generalised knowledge.

Fragment-based version management for repositories of business process models

As organizations reach higher levels of Business Process Management maturity, they tend to accumulate large collections of process models. These repositories may contain thousands of activities and be managed by different stakeholders with varying skills and responsibilities. However, while being of great value, these repositories induce high management costs. Thus, it becomes essential to keep track of the various model versions as they may mutually overlap, supersede one another and evolve over time. We propose an innovative versioning model, and associated storage structure, specifically designed to maximize sharing across process models and process model versions, reduce conflicts in concurrent edits and automatically handle controlled change propagation. The focal point of this technique is to version single process model fragments, rather than entire process models. Indeed empirical evidence shows that real-life process model repositories have numerous duplicate fragments. Experiments on two industrial datasets confirm the usefulness of our technique.

Translating competency statements into desired outcomes : a representational model for conceptualising the competency acquisition process

The need to develop effective and efficient training programs has been recognised by all sectors engaged in training. In responding to the above need, focus has been directed to developing good competency statements and performance indicators to measure the outcomes. Very little has been done to understand how the competency statements get translated into good performance. To conceptualise this translation process, a representational model based on an information processing paradigm is proposed and discussed. It is argued that learners’ prior knowledge and the effectiveness of the instructional material are two variables that have significant bearing on how effectively the competency knowledge is translated into outcomes. To contextualise the model examples from apprentice training are used.

Deliberation and collaboration in the policy process : a Web 2.0 approach

This paper is a summary of a PhD thesis proposal. It will explore how the Web 2.0 platform could be applied to enable and facilitate the large-scale participation, deliberation and collaboration of both governmental and non-governmental actors in an ICT supported policy process. The paper will introduce a new democratic theory and a Web 2.0 based e-democracy platform, and demonstrate how different actors would use the platform to develop and justify policy issues.

Exploring the impact of entrepreneur optimism on the new venture process

By integrating two theoretical foundations of entrepreneurship research, behaviour and process, this conceptual paper proposes a new model to examine the behaviour of the entrepreneur across the new venture development process. Existing macro level research on the new venture creation process recognises the entrepreneur as a central agent in the process yet generally avoids, at each stage of the process, an examination of the micro level psychological experiences of the individual entrepreneur. Similarly, behavioural research examining entrepreneur individual differences has failed to systematically explore the emotion and behaviour of the entrepreneur across the cycle of the new venture creation process. We propose a conceptual framework to integrate the new venture creation process of opportunity discovery, evaluation and exploitation, with the psychological capital (efficacy, hope, resilience and optimism) of the individual entrepreneur. Propositions for future research to facilitate deeper insight into the impact of entrepreneur behaviour on the new venture creation process and ultimately the success or failure of the new venture are provided.

Investigation of electrophoretic loading and enhanced mechanical properties of hydrogels for delivery of therapeutic proteins

Hydrogels, which are three-dimensional crosslinked hydrophilic polymers, have been used and studied widely as vehicles for drug delivery due to their good biocompatibility. Traditional methods to load therapeutic proteins into hydrogels have some disadvantages. Biological activity of drugs or proteins can be compromised during polymerization process or the process of loading protein can be really timeconsuming. Therefore, different loading methods have been investigated. Based on the theory of electrophoresis, an electrochemical gradient can be used to transport proteins into hydrogels. Therefore, an electrophoretic method was used to load protein in this study. Chemically and radiation crosslinked polyacrylamide was used to set up the model to load protein electrophoretically into hydrogels. Different methods to prepare the polymers have been studied and have shown the effect of the crosslinker (bisacrylamide) concentration on the protein loading and release behaviour. The mechanism of protein release from the hydrogels was anomalous diffusion (i.e. the process was non-Fickian). The UV-Vis spectra of proteins before and after reduction show that the bioactivities of proteins after release from hydrogel were maintained. Due to the concern of cytotoxicity of residual monomer in polyacrylamide, poly(2-hydroxyethyl- methacrylate) (pHEMA) was used as the second tested material. In order to control the pore size, a polyethylene glycol (PEG) porogen was introduced to the pHEMA. The hydrogel disintegrated after immersion in water indicating that the swelling forces exceeded the strength of the material. In order to understand the cause of the disintegration, several different conditions of crosslinker concentration and preparation method were studied. However, the disintegration of the hydrogel still occurred after immersion in water principally due to osmotic forces. A hydrogel suitable for drug delivery needs to be biocompatible and also robust. Therefore, an approach to improving the mechanical properties of the porogen-containing pHEMA hydrogel by introduction of an inter-penetrating network (IPN) into the hydrogel system has been researched. A double network was formed by the introduction of further HEMA solution into the system by both electrophoresis and slow diffusion. Raman spectroscopy was used to observe the diffusion of HEMA into the hydrogel prior to further crosslinking by ã-irradiation. The protein loading and release behaviour from the hydrogel showing enhanced mechanical property was also studied. Biocompatibility is a very important factor for the biomedical application of hydrogels. Different hydrogels have been studied on both a three-dimensional HSE model and a HSE wound model for their biocompatibilities. They did not show any detrimental effect to the keratinocyte cells. From the results reported above, these hydrogels show good biocompatibility in both models. Due to the advantage of the hydrogels such as the ability to absorb and deliver protein or drugs, they have potential to be used as topical materials for wound healing or other biomedical applications.

Optimization of container process at seaport terminals

Seaport container terminals are an important part of the logistics systems in international trades. This paper investigates the relationship between quay cranes, yard machines and container storage locations in a multi-berth and multi-ship environment. The aims are to develop a model for improving the operation efficiency of the seaports and to develop an analytical tool for yard operation planning. Due to the fact that the container transfer times are sequence-dependent and with the large number of variables involve, the proposed model cannot be solved in a reasonable time interval for realistically sized problems. For this reason, List Scheduling and Tabu Search algorithms have been developed to solve this formidable and NP-hard scheduling problem. Numerical implementations have been analysed and promising results have been achieved.

Using virtual worlds for collaborative business process modeling

Purpose Process modeling is a complex organizational task that requires many iterations and communication between the business analysts and the domain specialists. The challenge of process modeling is exacerbated, when the process of modeling has to be performed in a cross-organizational, distributed environment. In this paper we suggest a 3D environment for collaborative process modeling, using Virtual World technology. Design/methodology/approach We suggest a new collaborative process modeling approach based on Virtual World technology. We describe the design of an innovative prototype collaborative process modeling approach, implemented as a 3D BPMN modeling environment in Second Life. We use a case study to evaluate the suggested approach. Findings Based on our case study application, we show that our approach increases user empowerment and adds significantly to the collaboration and consensual development of process models even when the relevant stakeholders are geographically dispersed. Research limitations implications – We present design work and a case study. More research is needed to more thoroughly evaluate the presented approach in a variety of real-life process modeling settings. Practical implications Our research outcomes as design artifacts are directly available and applicable by business process management professionals and can be used by business, system and process analysts in real-world practice. Originality/value Our research is the first reported attempt to develop a process modeling approach on the basis of virtual world technology. We describe a novel and innovative 3D BPMN modeling environment in Second Life.