Can bone tissue engineering contribute to therapy concepts after resection of musculoskeletal sarcoma?

Resection of musculoskeletal sarcoma can result in large bone defects where regeneration is needed in a quantity far beyond the normal potential of self-healing. In many cases, these defects exhibit a limited intrinsic regenerative potential due to an adjuvant therapeutic regimen, seroma, or infection. Therefore, reconstruction of these defects is still one of the most demanding procedures in orthopaedic surgery. The constraints of common treatment strategies have triggered a need for new therapeutic concepts to design and engineer unparalleled structural and functioning bone grafts. To satisfy the need for long-term repair and good clinical outcome, a paradigm shift is needed from methods to replace tissues with inert medical devices to more biological approaches that focus on the repair and reconstruction of tissue structure and function. It is within this context that the field of bone tissue engineering can offer solutions to be implemented into surgical therapy concepts after resection of bone and soft tissue sarcoma. In this paper we will discuss the implementation of tissue engineering concepts into the clinical field of orthopaedic oncology.

Characterization of the tail-specific protease (Tsp) from Legionella

Bacterial tail-specific proteases (Tsps) have been attributed a wide variety of functions including intracellular virulence, cell wall morphology, proteolytic signal cascades and stress response. This study tested the hypothesis that Tsp has a key function for the transmissive form of Legionella pneumophila. A tsp mutant was generated in Legionella pneumophila 130b and the characteristics of this strain and the isogenic wild-type were examined using a range of growth and proteomic analyses. Recombinant Tsp protein was also produced and analyzed. The L. pneumophila tsp mutant showed no defect in growth on rich media or during thermo-osmotic stress conditions. In addition, no defects in cellular morphology were observed when the cells were examined using transmission electron microscopy. Purified recombinant Tsp was found to be an active protease with a narrow substrate range. Proteome analysis using iTRAQ (5% coverage of the proteome) found that, of those proteins detected, only 5 had different levels in the tsp mutant compared to the wild type. ACP (Acyl Carrier Protein), which has a key role for Legionella differentiation to the infectious form, was reduced in the tsp mutant; however, tsp(-) was able to infect and replicate inside macrophages to the same extent as the wild type. Combined, these data demonstrate that Tsp is a protease but is not essential for Legionella growth or cell infection. Thus, Tsp may have functional redundancy in Legionella.

H2AX phosphorylation screen of cells from radiosensitive cancer patients reveals a novel DNA double-strand break repair cellular phenotype

BACKGROUND: About 1-5% of cancer patients suffer from significant normal tissue reactions as a result of radiotherapy (RT). It is not possible at this time to predict how most patients' normal tissues will respond to RT. DNA repair dysfunction is implicated in sensitivity to RT particularly in genes that mediate the repair of DNA double-strand breaks (DSBs). Phosphorylation of histone H2AX (phosphorylated molecules are known as gammaH2AX) occurs rapidly in response to DNA DSBs, and, among its other roles, contributes to repair protein recruitment to these damaged sites. Mammalian cell lines have also been crucial in facilitating the successful cloning of many DNA DSB repair genes; yet, very few mutant cell lines exist for non-syndromic clinical radiosensitivity (RS). METHODS: Here, we survey DNA DSB induction and repair in whole cells from RS patients, as revealed by gammaH2AX foci assays, as potential predictive markers of clinical radiation response. RESULTS: With one exception, both DNA focus induction and repair in cell lines from RS patients were comparable with controls. Using gammaH2AX foci assays, we identified a RS cancer patient cell line with a novel ionising radiation-induced DNA DSB repair defect; these data were confirmed by an independent DNA DSB repair assay. CONCLUSION: gammaH2AX focus measurement has limited scope as a pre-RT predictive assay in lymphoblast cell lines from RT patients; however, the assay can successfully identify novel DNA DSB repair-defective patient cell lines, thus potentially facilitating the discovery of novel constitutional contributions to clinical RS.

Caribbean schooling and the social divide – what will it take to change neo-colonial education systems?

When Professor N’Dri Assie-Lumumba asked me to reflect on what ‘ubuntu’ might mean in the context of education in the Caribbean, the first thing that came to mind was an image of pit latrines in impoverished primary schools in poor countries. In this essay, I argue that the continuing problem of pit latrines in these schools symbolizes the failure to solve the problem of poverty, neglect and inadequate provision of education services for people at the bottom rungs of Caribbean and other decolonising societies. I ask what implications the ‘ubuntu’ concept chosen for the 2015 CIES conference would have for reforming education in a direction that combines global reform, ethics and good sense. Educators rarely consider toilets when they are thinking about what is needed to reform the system. But talking about toilets draws attention to the entrenched inequity that persists in education systems across the globe – an inequity that forces many schools and young people to remain at the base of the social pyramid, and that perpetuates a dysfunctional model of education holding back many societies. Starting from the twin images of social pyramids and toilets, we can ask some pointed questions about education reform.

Jet and flash imprint defectivity - Assessment and reduction for semiconductor applications

Defectivity has been historically identified as a leading technical roadblock to the implementation of nanoimprint lithography for semiconductor high volume manufacturing. The lack of confidence in nanoimprint's ability to meet defect requirements originates in part from the industry's past experiences with 1 × lithography and the shortage in enduser generated defect data. SEMATECH has therefore initiated a defect assessment aimed at addressing these concerns. The goal is to determine whether nanoimprint, specifically Jet and Flash Imprint Lithography from Molecular Imprints, is capable of meeting semiconductor industry defect requirements. At this time, several cycles of learning have been completed in SEMATECH's defect assessment, with promising results. J-FIL process random defectivity of < 0.1 def/cm2 has been demonstrated using a 120nm half-pitch template, providing proof of concept that a low defect nanoimprint process is possible. Template defectivity has also improved significantly as shown by a pre-production grade template at 80nm pitch. Cycles of learning continue on feature sizes down to 22nm. © 2011 SPIE.

Do twins differ from single-born children on rates of behavioral difficulty in early childhood? A study of sibling relationship risk factors

The hypothesis that twinning raises risk for behavioral difficulties in childhood is persistent, yet there is limited and inconsistent empirical evidence. Simple mean comparison without control for confounders provides data on prevalence rates but cannot provide knowledge about risk or etiology. To assess the effect of twin relationship on behavior, comparison of patterns of association with single-born siblings may be informative. Analyses of data from an Australian sample of twins and single-born children (N = 305, mean age 4 years 9 months, and a follow-up 12 months later) were undertaken. The outcome measure was the Strengths and Difficulties Questionnaire. Predictor and control measures were obtained from parent report on the sibling/co-twin relationship behavior, family demographics, and obstetric history. We assessed difference between twins and single-born children in two respects: (a) mean behavioral difficulties, and (b) patterns of association between sibling relationship and behavioral difficulties, controlling for confounders. Results showed no differences in mean levels of behavioral difficulties between twins and single-born siblings identifying the importance of statistical control for family and obstetric adversity. Differences in patterns of association were found; for twin children, conflict in their co-twin relationship predicted externalizing behaviors, while for single-born children conflict predicted internalizing behaviors. The findings of mean differences between twin and single-born children in social background, but not in behavioral difficulties, underscore the necessity of statistical control to identify risk associated with twinning compared with risk associated with family and obstetric background factors.

Activation of the canonical Wnt signaling pathway induces cementum regeneration

Canonical Wnt signaling is important in tooth development but it is unclear whether it can induce cementogenesis and promote the regeneration of periodontal tissues lost due to disease. Therefore, the aim of this study is to investigate the influence of canonical Wnt signaling enhancers on human periodontal ligament cell (hPDLCs) cementogenic differentiation in vitro and cementum repair in a rat periodontal defect model. Canonical Wnt signaling was induced by (i) local injection of lithium chloride; (ii) local injection of sclerostin antibody; and (iii) local injection of a lentiviral construct overexpressing β-catenin. The results showed that the local activation of canonical Wnt signaling resulted in significant new cellular cementum deposition and the formation of well-organized periodontal ligament fibers, which was absent in the control group. In vitro experiments using hPDLCs showed that the Wnt signaling pathway activators significantly increased mineralization, alkaline phosphatase (ALP) activity, and gene and protein expression of the bone and cementum markers osteocalcin (OCN), osteopontin (OPN), cementum protein 1 (CEMP1), and cementum attachment protein (CAP). Our results show that the activation of the canonical Wnt signaling pathway can induce in vivo cementum regeneration and in vitro cementogenic differentiation of hPDLCs.

The whole world shook : shifts in ethnic, national and heroic identities in children's fiction about 9/11

Like many other cataclysmic events September 11, a day now popularly believed to have 'changed the world', has become a topic taken up by children's writers. This thesis, titled The Whole World Shook: Ethnic, National and Heroic Identities in Children's Fiction About 9/11, examines how cultural identities are constructed within fictional texts for young people written about the attacks on the Twin Towers. It identifies three significant identity categories encoded in 9/11 books for children: ethnic identities, national identities, and heroic identities. The thesis argues that the identities formed within the selected children's texts are in flux, privileging performances of identities that are contingent on post-9/11 politics. This study is located within the field of children's literature criticism, which supports the understanding that children's books, like all texts, play a role in the production of identities. Children's literature is highly significant both in its pedagogical intent (to instruct and induct children into cultural practices and beliefs) and in its obscurity (in making the complex simple enough for children, and from sometimes intentionally shying away from difficult things). This literary criticism informed the study that the texts, if they were to be written at all, would be complex, varied and most likely as ambiguous and contradictory as the responses to the attacks on New York themselves. The theoretical framework for this thesis draws on a range of critical theories including literary theory, cultural studies, studies of performativity and postmodernism. This critical framework informs the approach by providing ways for: (i) understanding how political and ideological work is performed in children's literature; (ii) interrogating the constructed nature of cultural identities; (iii) developing a nuanced methodology for carrying out a close textual analysis. The textual analysis examines a representative sample of children's texts about 9/11, including picture books, young adult fiction, and a selection of DC Comics. Each chapter focuses on a different though related identity category. Chapter Four examines the performance of ethnic identities and race politics within a sample of picture books and young adult fiction; Chapter Five analyses the construction of collective, national identities in another set of texts; and Chapter Six does analytic work on a third set of texts, demonstrating the strategic performance of particular kinds of heroic identities. I argue that performances of cultural identities constructed in these texts draw on familiar versions of identities as well as contribute to new ones. These textual constructions can be seen as offering some certainties in increasingly uncertain times. The study finds, in its sample of books a co-mingling of xenophobia and tolerance; a binaried competition between good and evil and global harmony and national insularity; and a lauding of both the commonplace hero and the super-human. Being a recent corpus of texts about 9/11, these texts provide information on the kinds of 'selves' that appear to be privileged in the West since 2001. The thesis concludes that the shifting identities evident in texts that are being produced for children about 9/11 offer implicit and explicit accounts of what constitute good citizenship, loyalty to nation and community, and desirable attributes in a Western post-9/11 context. This thesis makes an original contribution to the field of children's literature by providing a focussed and sustained analysis of how texts for children about 9/11 contribute to formations of identity in these complex times of cultural unease and global unrest.

Utilizing micropellets as building blocks in cartilage tissue engineering

Osteoarthritis is the most common cause of pain and disability in Australia. This project describes a method where hundreds of cartilage microtissues are generated as tiny building blocks for assembly into larger tissues suitable for cartilage defect repair. Tissue engineering applications has the potential to overcome natural barriers and effectively repair damaged cartilage tissue. However, engineering few-millimeter thick cartilage, similar to human cartilage in the knee, remains a challenge. Utilizing micropellets as building blocks has the potential to overcome some of the challenges in cartilage tissue engineering.

A lightweight, modular robotic vehicle for the sustainable intensification of agriculture

This paper describes a lightweight, modular and energy efficient robotic vehicle platform designed for broadacre agriculture - the Small Robotic Farm Vehicle (SRFV). The current trend in farming is towards increasingly large machines that optimise the individual farmer’s productivity. Instead, the SRFV is designed to promote the sustainable intensification of agriculture by allowing farmers to concentrate on more important farm management tasks. The robot has been designed with a user-centred approach which focuses the outcomes of the project on the needs of the key project stakeholders. In this way user and environmental considerations for broadacre farming have informed the vehicle platform configuration, locomotion, power requirements and chassis construction. The resultant design is a lightweight, modular four-wheeled differential steer vehicle incorporating custom twin in-hub electric drives with emergency brakes. The vehicle is designed for a balance between low soil impact, stability, energy efficiency and traction. The paper includes modelling of the robot’s dynamics during an emergency brake in order to determine the potential for tipping. The vehicle is powered by a selection of energy sources including rechargeable lithium batteries and petrol-electric generators.

Wonder and method

In this paper, my aim is to address the twin concerns raised in this session - models of practice and geographies or spaces of practice - through regarding a selection of works and processes that have arisen from my recent research. Setting up this discussion, I first present a short critique of the idea of models of creative practice, recognising possible problems with the attempt to generalise or abstract its complexities. Working through a series of portraits of my working environment, I will draw from Lefebvre’s Rhythmanalysis as a way of understanding an art practice both spatially and temporally, suggesting that changes and adjustments can occur through attending to both intuitions and observations of the complex of rhythmic layers constantly at play in any event. Reflecting on my recent studio practice I explore these rhythms through the evocation of a twin axis: the horizontal and the vertical and the arcs of difference or change that occur between them, in both spatial and temporal senses. What this analysis suggests is the idea that understanding does not only emerge from the construction of general principles, derived from observation of the particular, but that the study of rhythms allows us to maintain the primacy of the particular. This makes it well suited to a study of creative methods and objects, since it is to the encounter with and expression of the particular that art practices, most certainly my own, are frequently directed.

Stimulation of osteogenesis and angiogenesis of hBMSCs by delivering Si ions and functional drug from mesoporous silica nanospheres

Multifunctional bioactive materials with the ability to stimulate osteogenesis and angiogenesis of stem cells play an important role in the regeneration of bone defects. However, how to develop such biomaterials remains a significant challenge. In this study, we prepared mesoporous silica nanospheres (MSNs) with uniform sphere size (∼90 nm) and mesopores (∼2.7 nm), which could release silicon ions (Si) to stimulate the osteogenic differentiation of human bone marrow stromal cells (hBMSCs) via activating their ALP activity, bone-related gene and protein (OCN, RUNX2 and OPN) expression. Hypoxia-inducing therapeutic drug, dimethyloxaloylglycine (DMOG), was effectively loaded in the mesopores of MSNs (D-MSNs). The sustained release of DMOG from D-MSNs could stabilize HIF-1α and further stimulated the angiogenic differentiation of hBMSCs as indicated by the enhanced VEGF secretion and protein expression. Our study revealed that D-MSNs could combine the stimulatory effect on both osteogenic and angiogenic activity of hBMSCs. The potential mechanism of D-MSN-stimulated osteogenesis and angiogenesis was further elucidated by the supplementation of cell culture medium with pure Si ions and DMOG. Considering the easy handling characteristics of nanospheres, the prepared D-MSNs may be applied in the forms of injectable spheres for minimally invasive surgery, or MSNs/polymer composite scaffolds for bone defect repair. The concept of delivering both stimulatory ions and functional drugs may offer a new strategy to construct a multifunctional biomaterial system for bone tissue regeneration.

A robot application to marine vessel inspection

Seagoing vessels have to undergo regular inspections, which are currently performed manually by ship surveyors. The main cost factor in a ship inspection is to provide access to the different areas of the ship, since the surveyor has to be close to the inspected parts, usually within arm's reach, either to perform a visual analysis or to take thickness measurements. The access to the structural elements in cargo holds, e.g., bulkheads, is normally provided by staging or by 'cherry-picking' cranes. To make ship inspections safer and more cost-efficient, we have introduced new inspection methods, tools, and systems, which have been evaluated in field trials, particularly focusing on cargo holds. More precisely, two magnetic climbing robots and a micro-aerial vehicle, which are able to assist the surveyor during the inspection, are introduced. Since localization of inspection data is mandatory for the surveyor, we also introduce an external localization system that has been verified in field trials, using a climbing inspection robot. Furthermore, the inspection data collected by the robotic systems are organized and handled by a spatial content management system that enables us to compare the inspection data of one survey with those from another, as well as to document the ship inspection when the robot team is used. Image-based defect detection is addressed by proposing an integrated solution for detecting corrosion and cracks. The systems' performance is reported, as well as conclusions on their usability, all in accordance with the output of field trials performed onboard two different vessels under real inspection conditions.

Process quality indicators targeting cognitive impairment to support quality of care for older people with cognitive impairment in emergency departments

Objectives The objective of this study was to develop process quality indicators (PQIs) to support the improvement of care services for older people with cognitive impairment in emergency departments (ED). Methods A structured research approach was taken for the development of PQIs for the care of older people with cognitive impairment in EDs, including combining available evidence with expert opinion (phase 1), a field study (phase 2), and formal voting (phase 3). A systematic review of the literature identified ED processes targeting the specific care needs of older people with cognitive impairment. Existing relevant PQIs were also included. By integrating the scientific evidence and clinical expertise, new PQIs were drafted and, along with the existing PQIs, extensively discussed by an advisory panel. These indicators were field tested in eight hospitals using a cohort of older persons aged 70 years and older. After analysis of the field study data (indicator prevalence, variability across sites), in a second meeting, the advisory panel further defined the PQIs. The advisory panel formally voted for selection of those PQIs that were most appropriate for care evaluation. Results In addition to seven previously published PQIs relevant to the care of older persons, 15 new indicators were created. These 22 PQIs were then field tested. PQIs designed specifically for the older ED population with cognitive impairment were only scored for patients with identified cognitive impairment. Following formal voting, a total of 11 PQIs were included in the set. These PQIs targeted cognitive screening, delirium screening, delirium risk assessment, evaluation of acute change in mental status, delirium etiology, proxy notification, collateral history, involvement of a nominated support person, pain assessment, postdischarge follow-up, and ED length of stay. Conclusions This article presents a set of PQIs for the evaluation of the care for older people with cognitive impairment in EDs. The variation in indicator triggering across different ED sites suggests that there are opportunities for quality improvement in care for this vulnerable group. Applied PQIs will identify an emergency services' implementation of care strategies for cognitively impaired older ED patients. Awareness of the PQI triggers at an ED level enables implementation of targeted interventions to improve any suboptimal processes of care. Further validation and utility of the indicators in a wider population is now indicated.