Semantic search and inferencing in health informatics

Consider a person searching electronic health records, a search for the term ‘cracked skull’ should return documents that contain the term ‘cranium fracture’. A information retrieval systems is required that matches concepts, not just keywords. Further more, determining relevance of a query to a document requires inference – its not simply matching concepts. For example a document containing ‘dialysis machine’ should align with a query for ‘kidney disease’. Collectively we describe this problem as the ‘semantic gap’ – the difference between the raw medical data and the way a human interprets it. This paper presents an approach to semantic search of health records by combining two previous approaches: an ontological approach using the SNOMED CT medical ontology; and a distributional approach using semantic space vector space models. Our approach will be applied to a specific problem in health informatics: the matching of electronic patient records to clinical trials.

Enhancing vascularized bone formation using tissue engineered periosteum

Objectives: The periosteum plays an indispensable role in both bone formation and bone defect healing. The aim of this project is to produce tissue engineered periosteum for bone defect treatment. Methods: In this study we constructed an artificial in vitro periosteum by incorporating osteogenic differentiated bone marrow stromal cells (BMSCs) and cobalt chloride (CoCl2)-treated BMSCs. The engineered periostea were implanted both subcutaneously and into skull bone defects in SCID mice to investigate ectopic and orthotopic osteogenesis and vascularisation. After two weeks in subcutaneous and four weeks in bone defect areas, the implanted constructs were assessed for ectopic and orthotopic osteogenesis and vascularisation by micro-CT, histomorphometrical and immunohistochemical methods. Results: The results showed that CoCl2 pre-treated BMSCs induced higher degree of vascularisation and enhanced osteogenesis within the implants in both ectopic and orthotopic areas. Conclusion: This study provided a novel approach using BMSCs sourced from the same patient for both osteogenic and pro-angiogenic purposes in constructing tissue engineered periosteum to enhance vascularized osteogenesis.

Limitations and challenges in MSC delivery for bone regeneration

Objective: Regeneration of osseous defects by tissue-engineering or cell delivery approach provides a novel means of treatment utilizing cell biology, materials sciences, and molecular biology. The concept of in vitro explanted mesenchymal stem cells (MSCs) with an ability to induce new bone formation has been demonstrated in some small animal models. However, contradictory results have been reported regarding the regenerative capacity of MSCs after ex vivo expansion due to the lack of the understanding of microenvironment for MSC differentiation in vivo. ----- ----- Methods: In our laboratory tissue-derived and bone marrow-derived MSCs have been investigated in their osteogenesis. Cell morphology and proliferation were studied by microscopy, confocal microscopy, FACS and cell counting. Cell differentiation and matrix formation were analysed by matrix staining, quantitative PCR, and immunohistochemistry. A SCID skull defect model was used for cell transplantation studies.----- ----- Results: It was noted that tissue-derived and bone marrow-derived MSCs showed similar characteristics in cell surface marker expression, mesenchymal lineage differentiation potential, and cell population doubling. MSCs from both sources could initiate new bone formation in bone defects after delivery into a critical size defects. The bone forming cells were from both transplanted cells and endogenous cells from the host. Interestingly, the majority of in vitro osteogenic differentiated cells did not form new bone directly even though mineralized matrix was synthesized in vitro by MSCs. Furthermore, no new bone formation was detected when MSCs were transplanted subcutaneously.----- ----- Conclusion: This study unveiled the limitations of MSC delivery in bone regeneration and proposed that in vivo microenvironment needs to be optimized for MSC delivery in osteogenesis.

Application of hyperbaric oxygen in bone tissue engineering : effect of hyperbaric oxygen treatment on bone marrow stem cells

and non-union of bony fractures has been proposed since 1966, little has been known about the effect of HBOT on bone marrow stem cells (BMSC). The aim of this study is to investigate the effect of HBO treatment on osteogenetic differentiation of BMSC and potential application in bone tissue engineering. Adhesive stromal cells harvested from bone marrow were characterized by mesenchymal differentiation potential, cell surface markers and their proliferation capacity. Mesenchymal stem cells, which demonstrated osteogenic, chondrogenic and adipogenic differentiation potential and expressed positively for CD 29, CD 44, CD 73, CD 90, CD 105, CD 166 and negatively for CD34 and CD 45, were selected and treated in a laboratory-scale HBO chamber using different oxygen pressures and exposure times. No obvious effect of HBO treatment on BMSC proliferation was noticed. However, cytotoxic effects of HBO were considerably less pronounced when cells were cultured in medium supplemented with 10% FBS in comparison to medium supplemented with 2% FCS, as was evaluated by WST-1 assay. Under HBO treatment, bone nodules were formed in three days, which was clearly revealed by Von Kossa staining. In contrasts, without HBO treatment, bone nodules were not detected until 9-12 days using the same inducing culture media. Calcium deposition was also significantly increased after three days of HBO treatments compared to no HBO treatment. In addition it was also found that oxygen played a direct role in the enhancement of BMSC osteogenic differentiation, which was independent of the effect of air pressure.

In vitro and in vivo evaluation of adenovirus combined silk fibroin scaffolds for BMP-7 gene delivery

Introduction and aims: For a scaffold material to be considered effective and efficient for tissue engineering it must be biocompatible as well as bioinductive. Silk fiber is a natural biocompatible material suitable for scaffold fabrication; however, silk is tissue-conductive and lacks tissue-inductive properties. One proposed method to make the scaffold tissue-inductive is to introduce plasmids or viruses encoding a specific growth factor into the scaffold. In this study, we constructed adenoviruses encoding bone morphogenetic protein-7 (BMP-7) and incorporated these into silk scaffolds. The osteo-inductive and new bone formation properties of these constructs were assessed in vivo in a critical-sized skull defect animal model. Materials and methods: Silk fibroin scaffolds containing adenovirus particles coding BMP-7 were prepared. The release of the adenovirus particles from the scaffolds was quantified by tissue-culture infective dose (TCID50) and the bioactivity of the released viruses was evaluated on human bone marrow mesenchymal stromal cells (BMSCs). To demonstrate the in vivo bone forming ability of the virus-carrying silk fibroin scaffold, the scaffold constructs were implanted into calvarial defects in SCID mice. Results: In vitro studies demonstrated that the virus-carrying silk fibroin scaffold released virus particles over a 3 week period while preserving their bioactivity. In vivo test of the scaffold constructs in critical-sized skull defect areas revealed that silk scaffolds were capable of delivering the adenovirus encoding BMP-7, resulting significantly enhanced new bone formation. Conclusions: Silk scaffolds carrying BMP-7 encoding adenoviruses can effectively transfect cells and enhance both in vitro and in vivo osteogenesis. The findings of this study indicate silk fibroin is a promising biomaterial for gene delivery to repair critical-sized bone defects.

Is there a difference between narrowing of the spinal canal and neurological deficits comparing Denis and Magerl classifications?

We have read with great interest the retrospective study by Caffaro and Avanzi1 evaluating the relation between narrowing of the spinal canal and neurological deficits in patients with burst-type fractures of the spine. The authors are to be commended for obtaining detailed neurological and radiological data in a large cohort of 227 patients. The authors conclude: “The percentage of narrowing of the spinal canal proved to be a pre-disposing factor for the severity of the neurological status in thoracolumbar and lumbar burst-type fractures according to the classifications of Denis and Magerl.” Although this conclusion is mainly in accordance with previous findings, we would like to comment on the methodological approach applied in the current study.

Application of an optimisation algorithm to configure an internal fixation device

Fractures of long bones are sometimes treated using various types of fracture fixation devices including internal plate fixators. These are specialised plates which are used to bridge the fracture gap(s) whilst anatomically aligning the bone fragments. The plate is secured in position by screws. The aim of such a device is to support and promote the natural healing of the bone. When using an internal fixation device, it is necessary for the clinician to decide upon many parameters, for example, the type of plate and where to position it; how many and where to position the screws. While there have been a number of experimental and computational studies conducted regarding the configuration of screws in the literature, there is still inadequate information available concerning the influence of screw configuration on fracture healing. Because screw configuration influences the amount of flexibility at the area of fracture, it has a direct influence on the fracture healing process. Therefore, it is important that the chosen screw configuration does not inhibit the healing process. In addition to the impact on the fracture healing process, screw configuration plays an important role in the distribution of stresses in the plate due to the applied loads. A plate that experiences high stresses is prone to early failure. Hence, the screw configuration used should not encourage the occurrence of high stresses. This project develops a computational program in Fortran programming language to perform mathematical optimisation to determine the screw configuration of an internal fixation device within constraints of interfragmentary movement by minimising the corresponding stress in the plate. Thus, the optimal solution suggests the positioning and number of screws which satisfies the predefined constraints of interfragmentary movements. For a set of screw configurations the interfragmentary displacement and the stress occurring in the plate were calculated by the Finite Element Method. The screw configurations were iteratively changed and each time the corresponding interfragmentary displacements were compared with predefined constraints. Additionally, the corresponding stress was compared with the previously calculated stress value to determine if there was a reduction. These processes were continued until an optimal solution was achieved. The optimisation program has been shown to successfully predict the optimal screw configuration in two cases. The first case was a simplified bone construct whereby the screw configuration solution was comparable with those recommended in biomechanical literature. The second case was a femoral construct, of which the resultant screw configuration was shown to be similar to those used in clinical cases. The optimisation method and programming developed in this study has shown that it has potential to be used for further investigations with the improvement of optimisation criteria and the efficiency of the program.

Glycosaminoglycan and growth factor mediated murine calvarial cell proliferation

Understanding the complex mechanisms underlying bone remodeling is crucial to the development of novel therapeutics. Glycosaminoglycans (GAGs) localised to the extracellular matrix (ECM) of bone are thought to play a key role in mediating aspects of bone development. The influence of isolated GAGs was studied by utilising in vitro murine calvarial monolayer and organ culture model systems. Addition of GAG preparations extracted from the cell surface of human osteoblasts at high concentrations (5 microg/ml) resulted in decreased proliferation of cells and decreased suture width and number of bone lining cells in calvarial sections. When we investigated potential interactions between the growth factors fibroblast growth factor-2 (FGF2), bone morphogenic protein-2 (BMP2) and transforming growth factor-beta1 (TGFbeta1) and the isolated cell surface GAGs, differences between the two model systems emerged. The cell culture system demonstrated a potentiating role for the isolated GAGs in the inhibition of FGF2 and TGFbeta1 actions. In contrast, the organ culture system demonstrated an enhanced stimulation of TFGbeta1 effects. These results emphasise the role of the ECM in mediating the interactions between GAGs and growth factors during bone development and suggest the GAG preparations contain potent inhibitory or stimulatory components able to mediate growth factor activity.

Prospective association between physical activity and falls in community-dwelling older women

Abstract Objective: To explore associations between physical activity and risk of falls and broken or fractured bones in community-dwelling older women. Design, setting and participants: This was a prospective observational survey with 3- and 6-year follow-ups. The sample included 8562 healthy, community-dwelling women, aged 70-75 years in 1996, who completed surveys as participants in the Australian Longitudinal Study on Women’s Health. Outcomes were reports of a fall to the ground, injury from a fall, and broken or fractured bones in 1999 and 2002. The main predictor variable was physical activity level in 1996, categorized based on weekly frequency as none/very low, low, moderate, high, and very high. Covariates were demographic and health-related variables. Logistic regression models were computed separately for each outcome in 1999 and 2002. Main results: In multivariable models, very high physical activity was associated with decreased risk of a fall in 1999 (odds ratio 0.67, 95% CI 0.48 to 0.93) and in 2002 (odds ratio 0.62, 95% CI 0.42 to 0.92). High/very high physical activity was associated with decreased risk of broken or fractured bones in 2002 (odds ratio 0.64, 95% CI 0.42 to 0.96). No significant association was found between physical activity and injury from a fall. Conclusions: The results suggest that at least daily moderate to vigorous physical activity is required for the primary prevention of falls to the ground and broken or fractured bones in women aged 70-75 years.

Influence of internal fixator stiffness on murine fracture healing : two types of fracture healing lead to two distinct cellular events and FGF-2 expressions

This study aimed to clarify the relationship between the mechanical environment at the fracture site and endogenous fibroblast growth factor-2 (FGF-2). We compared two types of fracture healing with different callus formations and cellular events using MouseFix(TM) plate fixation systems for murine fracture models. Left femoral fractures were induced in 72 ten-week-old mice and then fixed with a flexible (Group F) or rigid (Group R) Mouse Fix(TM) plate. Mice were sacrificed on days 3, 5, 7, 10, 14, and 21. The callus volumes were measured by 3D micro-CT and tissues were histologically stained with hematoxylin & eosin or safranin-O. Sections from days 3, 5, and 7 were immunostained for FGF-2 and Proliferating Cell Nuclear Antigen (PCNA). The callus in Group F was significantly larger than that in Group R. The rigid plate allowed bone union without a marked external callus or chondrogenesis. The flexible plate formed a large external callus as a result of endochondral ossification. Fibroblastic cells in the granulation tissue on days 5 and 7 in Group F showed marked FGF-2 expression compared with Group R. Fibroblastic cells showed ongoing proliferation in granulation tissue in group F, as indicated by PCNA expression, which explained the relative granulation tissue increase in group F. There were major differences in early phase endogenous FGF-2 expression between these two fracture healing processes, due to different mechanical environments.

Journeys with friends

Journeys with Friends Truna aka J. Turner, Giselle Rosman and Matt Ditton Panel Session description: We are no longer an industry (alone) we are a sector. Where the model once consisted of industry making games, we now see the rise of a cultural sector playing in the game space – industry, indies (for whatever that distinction implies) artists (another odd distinction), individuals and well … everyone and their mums. This evolution has an affect – on audiences and who they are, what they expect and want, and how they understand the purpose and language of these “digital game forms’; how we talk about our worlds and the kinds of issues that are raised; on what we create and how we create it and on our communities and who we are. This evolution has an affect on how these works are understood within the wider social context and how we present this understanding to the next generation of makers and players. We can see the potential of this evolution from industry to sector in the rise of the Australian indie. We can see the potential fractures created by this evolution in the new voices that ask questions about diversity and social justice. And yet, we still see a ‘solution’ type reaction to the current changing state of our sector which announces the monolithic, Fordist model as desirable (albeit in smaller form) – with the subsequent ramifications for ‘training’ and production of local talent. Experts talk about a mismatch of graduate skills and industry needs, insufficient linkages between industry and education providers and the need to explore opportunity for the now passing model in new spaces such as adver-games and serious games. Head counts of Australian industry don’t recognise trans media producers as being part of their purview or opportunity, they don’t count the rise of the cultural playful game inspired creative works as one of thier team. Such perspectives are indeed relevant to the Australian Games Industry, but what about the emerging Australian Games Sector? How do we enable a future in such a space? This emerging sector is perhaps best represented by Melbourne’s Freeplay audience: a heady mix of indie developers, players, artists, critical thinkers and industry. Such audiences are no longer content with an ‘industry’ alone; they are the community who already see themselves as an important, vibrant cultural sector. Part of the discussion presented here seeks to identify and understand the resources, primarily in the context of community and educational opportunities, available to the evolving sector now relying more on the creative processes. This creative process and community building is already visibly growing within the context of smaller development studios, often involving more multiskilling production methodologies where the definition of ‘game’ clearly evolves beyond the traditional one.

A new model to analyze metaphyseal bone healing in mice

Background: Despite the increasing clinical problems with metaphyseal fractures, most experimental studies investigate the healing of diaphyseal fractures. Although the mouse would be the preferable species to study the molecular and genetic aspects of metaphyseal fracture healing, a murine model does not exist yet. Using a special locking plate system, we herein introduce a new model, which allows the analysis of metaphyseal bone healing in mice. Methods: In 24 CD-1 mice the distal metaphysis of the femur was osteotomized. After stabilization with the locking plate, bone repair was analyzed radiologically, biomechanically, and histologically after 2 (n = 12) and 5 wk (n = 12). Additionally, the stiffness of the bone-implant construct was tested biomechanically ex vivo. Results: The torsional stiffness of the bone-implant construct was low compared with nonfractured control femora (0.23 ± 0.1 Nmm/°versus 1.78 ± 0.15 Nmm/°, P < 0.05). The cause of failure was a pullout of the distal screw. At 2 wk after stabilization, radiological analysis showed that most bones were partly bridged. At 5 wk, all bones showed radiological union. Accordingly, biomechanical analyses revealed a significantly higher torsional stiffness after 5 wk compared with that after 2 wk. Successful healing was indicated by a torsional stiffness of 90% of the contralateral control femora. Histological analyses showed new woven bone bridging the osteotomy without external callus formation and in absence of any cartilaginous tissue, indicating intramembranous healing. Conclusion: With the model introduced herein we report, for the first time, successful metaphyseal bone repair in mice. The model may be used to obtain deeper insights into the molecular mechanisms of metaphyseal fracture healing. © 2012 Elsevier Inc. All rights reserved.

Prevention of pelvic sepsis in major open pelviperineal injury

Compound pelvic fractures are deemed to be one of the most severe orthopaedic injuries with an extremely high morbidity and mortality. After the initial resuscitation phase the prevention of pelvic sepsis is one of the main treatment goals for patients with an open pelvic fracture. If there is a suspicion of a rectal injury or if the wounds are in the perineal area, The Princess Alexandra Hospital's management plan includes early faecal diversion combined with vigorous soft tissue debridement, VAC(®) therapy and (if indicated) external fixation of the pelvic fracture. We present our flowchart for the treatment of trauma patients with compound pelvic fractures illustrated by a case report describing a 32 year old patient who sustained an open pelvic ring injury in a workplace accident. The aim of this paper is to underline the importance of a safe, straightforward approach to compound pelvic fractures.

Mechanical considerations in fracture fixation

Bone’s capacity to repair following trauma is both unique and astounding. However, fractures sometimes fail to heal. Hence, the goal of fracture treatment is the restoration of bone’s structure, composition and function. Fracture fixation devices should provide a favourable mechanical and biological environment for healing to occur. The use of internal fixation is increasing as these devices may be applied with less invasive techniques. Recent studies suggest however that, internal fixation devices may be overly stiff and suppresses callus formation. The degree of mechanical stability influences the healing outcome. This is determined by the stiffness of the fixation device and the degree of limb loading. This project aims to characterise the fixation stability of an internal plate fixation device and the influence of modifications to its configuration on implant stability. As there are no standardised methods for the determination of fixation stiffness, the first part of this project aims to compares different methodologies and determines the most appropriate method to characterise the stiffness of internal plate fixators. The stiffness of a fixation device also influences the physiological loads experienced by the healing bone. Since bone adapts to this applied load by undergoing changes through a remodelling process, undesirable changes could occur during the period of treatment with an implant. The second part of this project aims to develop a methodology to quantify remodelling changes. This quantification is expected to aid our understanding of the changes in pattern due to implant related remodelling and on the factors driving the remodelling process. Knowledge gained in this project is useful to understand how the configuration of internal fixation devices can promote timely healing and prevent undesirable bone loss.