Novel PCL-based honeycomb scaffolds as drug delivery systems for rhBMP-2

This study investigated a novel drug delivery system (DDS), consisting of polycaprolactone (PCL) or polycaprolactone 20% tricalcium phosphate (PCL-TCP) biodegradable scaffolds, fibrin Tisseel sealant and recombinant bone morphogenetic protein-2 (rhBMP-2) for bone regeneration. PCL and PCL-TCP-fibrin composites displayed a loading efficiency of 70% and 43%, respectively. Fluorescence and scanning electron microscopy revealed sparse clumps of rhBMP-2 particles, non-uniformly distributed on the rods’ surface of PCL-fibrin composites. In contrast, individual rhBMP-2 particles were evident and uniformly distributed on the rods’ surface of the PCL-TCP-fibrin composites. PCL-fibrin composites loaded with 10 and 20 μg/ml rhBMP-2 demonstrated a triphasic release profile as quantified by an enzyme-linked immunosorbent assay (ELISA). This consisted of burst releases at 2 h, and days 7 and 16. A biphasic release profile was observed for PCL-TCP-fibrin composites loaded with 10 μg/ml rhBMP-2, consisting of burst releases at 2 h and day 14. PCL-TCP-fibrin composites loaded with 20 μg/ml rhBMP-2 showed a tri-phasic release profile, consisting of burst releases at 2 h, and days 10 and 21. We conclude that the addition of TCP caused a delay in rhBMP-2 release. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and alkaline phosphatase assay verified the stability and bioactivity of eluted rhBMP-2 at all time points

The effect of rhBMP-2 on canine osteoblasts seeded onto 3D bioactive polycaprolactone scaffolds

Our strategy entails investigating the influence of varied concentrations (0, 10, 100 and 1000 ng/ml) of human recombinant bone morphogenetic protein-2 (rhBMP-2) on the osteogenic expression of canine osteoblasts, seeded onto poly-caprolactone 20% tricalcium phosphate (PCL-TCP) scaffolds in vitro. Biochemical assay revealed that groups with rhBMP-2 displayed an initial burst in cell growth that was not dose-dependent. However, after 13 days, cell growth declined to a value similar to control. Significantly less cell growth was observed for construct with 1000 ng/ml of rhBMP-2 from 20 days onwards. Confocal microscopy confirmed viability of osteoblasts and at day 20, groups seeded with rhBMP-2 displayed heightened cell death as compared to control. Phase contrast and scanning electron microscopy revealed that osteoblasts heavily colonized surfaces, rods and pores of the PCL-TCP scaffolds. This was consistent for all groups. Finally, Von Kossa and osteocalcin assays demonstrated that cells from all groups maintained their osteogenic phenotype throughout the experiment. Calcification was observed as early as four days after stimulation for groups seeded with rhBMP-2. In conclusion, rhBMP-2 seems to enhance the differentiated function of canine osteoblasts in a non-dose dependent manner. This resulted in accelerated mineralization, followed by death of osteoblasts as they underwent terminal differentiation. Notably, PCL-TCP scaffolds seeded only with canine osteoblasts could sustain excellent osteogenic expression in vitro. Hence, the synergy of PCL with bioactive TCP and rhBMP-2 in a novel composite scaffold, could offer an exciting approach for bone regeneration.

PLGA-based microparticles for the sustained release of BMP-2

The development of growth factor delivery strategies to circumvent the burst release phenomenon prevalent in most current systems has driven research towards encapsulating molecules in resorbable polymer matrices. For these polymer release techniques to be efficacious in a clinical setting, several key points need to be addressed. This present study has investigated the encapsulation of the growth factor, BMP-2 within PLGA/PLGA-PEG-PLGA microparticles. Morphology, size distribution, encapsulation efficiency and release kinetics were investigated and we have demonstrated a sustained release of bioactive BMP-2. Furthermore, biocompatibility of the PLGA microparticles was established and released BMP-2 was shown to promote the differentiation of MC3T3-E1 cells towards the osteogenic lineage to a greater extent than osteogenic supplements (as early as day 10 in culture), as determined using alkaline phosphatase and alizarin red assays. This study showcases a potential BMP-2 delivery system which may now be translated into more complex delivery systems, such as 3D, mechanically robust scaffolds for bone tissue regeneration applications.

Automatic domain ontology extraction for context-sensitive opinion mining

Automated analysis of the sentiments presented in online consumer feedbacks can facilitate both organizations’ business strategy development and individual consumers’ comparison shopping. Nevertheless, existing opinion mining methods either adopt a context-free sentiment classification approach or rely on a large number of manually annotated training examples to perform context sensitive sentiment classification. Guided by the design science research methodology, we illustrate the design, development, and evaluation of a novel fuzzy domain ontology based contextsensitive opinion mining system. Our novel ontology extraction mechanism underpinned by a variant of Kullback-Leibler divergence can automatically acquire contextual sentiment knowledge across various product domains to improve the sentiment analysis processes. Evaluated based on a benchmark dataset and real consumer reviews collected from Amazon.com, our system shows remarkable performance improvement over the context-free baseline.

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.

Adam Smith's dinner

In 1961, the East German government erected what they claimed was an anti-capitalist barricade. In 1989, this barricade was dismantled by those whom it was supposed to keep apart: the forces it was intended to contain had overwhelmed it. In the aftermath, the victims of Stalinist oppression and the planned economy opted for radical change. Some might have hoped that they would intellectually march resolutely westwards towards the forms of social democracy that had proven so successful in their nearest neighbours – Scandinavia, Germany and Austria – and stop when they had reached a point on the political spectrum with which they felt comfortable, and which worked for them. Unfortunately, they went to the opposite end of political economy. That choice was celebrated by those theorists who wanted our own countries to move in the same direction. Eastern Europe suffered a decline of 50% in its GDP. Much earlier in 1653, Peter Stuyvesant had erected an earth and wooden wall to protect the westernmost settlement of a great commercial nation from those they imagined to be barbarians. In 1699 Stuyvesant’s barrier was dismantled by the British, who replaced it with a street named after the wall. So it came to be that one of the most inconsequential walls in history became one of history’s most famous streets. I am not sure if the Dutch had left some tulip bulbs on either side of the wall, perhaps as a reminder of capitalism’s first bubble, and an inspiration to later bubbles. However, many of the victims of the latest burst bubble are pretty keen to tear down that Wall.1 As in 1989, they want to take action against the guardians of the system that failed them. And the more they suffer, the more likely it is that they will demand radical change, and the more likely that the resulting change will go too far – as seems to have been the case in Eastern Europe after the terminal crisis of communism, and in the majority of democracies that fell in the dozen years following the Great Crash. The current reaction is so strong that some are even wondering what role there will be for markets. I was invited to address a conference in the EU Parliament last November on the topic ‘Capitalism: Quo Vadis?’, where I apologized to the international audience that the topic was posed in a dead European language because the answer to this question is not going to be determined by the west alone. The problems we have been addressing emerged in the west and have affected the rest. However, the answers will not come, solely from the west, and may even come primarily from the south and the east.

Multi-modal summarization of key events and top players in sports tournament videos

To detect and annotate the key events of live sports videos, we need to tackle the semantic gaps of audio-visual information. Previous work has successfully extracted semantic from the time-stamped web match reports, which are synchronized with the video contents. However, web and social media articles with no time-stamps have not been fully leveraged, despite they are increasingly used to complement the coverage of major sporting tournaments. This paper aims to address this limitation using a novel multimodal summarization framework that is based on sentiment analysis and players' popularity. It uses audiovisual contents, web articles, blogs, and commentators' speech to automatically annotate and visualize the key events and key players in a sports tournament coverage. The experimental results demonstrate that the automatically generated video summaries are aligned with the events identified from the official website match reports.

Understanding nonsense : breathing life into shibboleths and killing critical thought in higher education

In this paper, I focus on the growing "nonsense industry" which is most apparent in the writing typical of business, government departments, and the financial press. This writing, like technical writing, is characterised by heavy reliance on grammatical metaphor. It endows shibboleths - for instance, "globalisation"; "efficiencies"; "competition"; "modernisation"; "consumer sentiment"; "reform"; and so on - with anthropomorphic qualities. These anthropomorphic artefacts of technocratised language are then presented as having immutable powers over people. Thus they become banal public excuses for negligent practices in both business and government.

Sequential release of BMP-7 and VEGF from the PLGA/AK-Gelatin Composite Scaffolds

Vascular endothelial growth factor (VEGF) and bone morphogenetic proteins (BMP-7) are key regulators of angiogenesis and osteogenesis during bone regeneration. The aim of this study was to investigate the possibility of realizing sequential release of the two growth factors using a novel composite scaffold. Poly(lactic-co-glycolic acid) (PLGA)-Akermanite (AK) microspheres were used to make the composite scaffold, which was then loaded with BMP-7, followed by embedding in a gelatin hydrogel matrix loaded with VEGF. The release profiles of the growth factors were studied and selected osteogenic related markers of bone marrow stromal cells (BMSCs) were analysed. It was shown that the composite scaffolds exhibited a fast initial burst release of VEGF within the first 3 days and a sustained slow release of BMP-7 over the full period of 20 days. The in vitro proliferation and differentiation of the BMSCs cultured in the osteogenic medium were enhanced by 1 to 2 times, resulting from the additionally and sequentially release of growth factors from the PLGA-AK/gelatin composite scaffolds.

Deformation behaviours of coarse-grained and nanocrystalline Mg-5wt% Al alloys

Magnesium alloys have been of growing interest to various engineering applications, such as the automobile, aerospace, communication and computer industries due to their low density, high specific strength, good machineability and availability as compared with other structural materials. However, most Mg alloys suffer from poor plasticity due to their Hexagonal Close Packed structure. Grain refinement has been proved to be an effective method to enhance the strength and alter the ductility of the materials. Several methods have been proposed to produce materials with nanocrystalline grain structures. So far, most of the research work on nanocrystalline materials has been carried out on Face-Centered Cubic and Body-Centered Cubic metals. However, there has been little investigation of nanocrystalline Mg alloys. In this study, bulk coarse-grained and nanocrystalline Mg alloys were fabricated by a mechanical alloying method. The mixed powder of Mg chips and Al powder was mechanically milled under argon atmosphere for different durations of 0 hours (MA0), 10 hours (MA10), 20 hours (MA20), 30 hours (MA30) and 40 hours (MA40), followed by compaction and sintering. Then the sintered billets were hot-extruded into metallic rods with a 7 mm diameter. The obtained Mg alloys have a nominal composition of Mg–5wt% Al, with grain sizes ranging from 13 μm down to 50 nm, depending on the milling durations. The microstructure characterization and evolution after deformation were carried out by means of Optical microscopy, X-Ray Diffraction, Scanning Electron Microscopy, Transmission Electron Microscopy, Scanning Probe Microscopy and Neutron Diffraction techniques. Nanoindentaion, compression and micro-compression tests on micro-pillars were used to study the size effects on the mechanical behaviour of the Mg alloys. Two kinds of size effects on the mechanical behaviours and deformation mechanisms were investigated: grain size effect and sample size effect. The nanoindentation tests were composed of constant strain rate, constant loading rate and indentation creep tests. The normally reported indentation size effect in single crystal and coarse-grained crystals was observed in both the coarse-grained and nanocrystalline Mg alloys. Since the indentation size effect is correlated to the Geometrically Necessary Dislocations under the indenter to accommodate the plastic deformation, the good agreement between the experimental results and the Indentation Size Effect model indicated that, in the current nanocrystalline MA20 and MA30, the dislocation plasticity was still the dominant deformation mechanism. Significant hardness enhancement with decreasing grain size, down to 58 nm, was found in the nanocrystalline Mg alloys. Further reduction of grain size would lead to a drop in the hardness values. The failure of grain refinement strengthening with the relatively high strain rate sensitivity of nanocrystalline Mg alloys suggested a change in the deformation mechanism. Indentation creep tests showed that the stress exponent was dependent on the loading rate during the loading section of the indentation, which was related to the dislocation structures before the creep starts. The influence of grain size on the mechanical behaviour and strength of extruded coarse-grained and nanocrystalline Mg alloys were investigated using uniaxial compression tests. The macroscopic response of the Mg alloys transited from strain hardening to strain softening behaviour, with grain size reduced from 13 ìm to 50 nm. The strain hardening was related to the twinning induced hardening and dislocation hardening effect, while the strain softening was attributed to the localized deformation in the nanocrystalline grains. The tension–compression yield asymmetry was noticed in the nanocrystalline region, demonstrating the twinning effect in the ultra-fine-grained and nanocrystalline region. The relationship k tensions < k compression failed in the nanocrystalline Mg alloys; this was attributed to the twofold effect of grain size on twinning. The nanocrystalline Mg alloys were found to exhibit increased strain rate sensitivity with decreasing grain size, with strain rate ranging from 0.0001/s to 0.01/s. Strain rate sensitivity of coarse-grained MA0 was increased by more than 10 times in MA40. The Hall-Petch relationship broke down at a critical grain size in the nanocrystalline region. The breakdown of the Hall-Petch relationship and the increased strain rate sensitivity were due to the localized dislocation activities (generalization and annihilation at grain boundaries) and the more significant contribution from grain boundary mediated mechanisms. In the micro-compression tests, the sample size effects on the mechanical behaviours were studied on MA0, MA20 and MA40 micro-pillars. In contrast to the bulk samples under compression, the stress-strain curves of MA0 and MA20 micro-pillars were characterized with a number of discrete strain burst events separated by nearly elastic strain segments. Unlike MA0 and MA20, the stress-strain curves of MA40 micro-pillars were smooth, without obvious strain bursts. The deformation mechanisms of the MA0 and MA20 micro-pillars under micro-compression tests were considered to be initially dominated by deformation twinning, followed by dislocation mechanisms. For MA40 pillars, the deformation mechanisms were believed to be localized dislocation activities and grain boundary related mechanisms. The strain hardening behaviours of the micro-pillars suggested that the grain boundaries in the nanocrystalline micro-pillars would reduce the source (nucleation sources for twins/dislocations) starvation hardening effect. The power law relationship of the yield strength on pillar dimensions in MA0, MA20 supported the fact that the twinning mechanism was correlated to the pre-existing defects, which can promote the nucleation of the twins. Then, we provided a latitudinal comparison of the results and conclusions derived from the different techniques used for testing the coarse-grained and nanocrystalline Mg alloy; this helps to better understand the deformation mechanisms of the Mg alloys as a whole. At the end, we summarized the thesis and highlighted the conclusions, contributions, innovations and outcomes of the research. Finally, it outlined recommendations for future work.

Really really

In “Really Really”, a series of words float through animated star constellations. While apparently drifting aimlessly, the words can be rearranged in numerous ways to recount roughly the same sappy avowal of long-distance love. The many combinations of words, and their predictable associations, call attention to the thresholds of verbal expression. When some sincere words are needed most it seems as if they’ve all been said before. And so, this declaration of love is both enabled and haunted by the tension between sentiment and formula. “Really Really” continues my interests in how meaning is constructed and circulated, and in particular, how common models of communication continue to frame and yet fall short of our personal experiences.

A longitudinal assessment of chronic wound fluid to detect biochemical indicators of healing

Chronic venous leg ulcers are a detrimental health issue plaguing our society, resulting in long term pain, immobility and decreased quality of life for a large proportion of sufferers. The frequency of these chronic wounds has led current research to focus on the wound environment to provide important information regarding the prolonged, fluctuated or static healing patterns of these wounds. Disruption to the normal wound healing process results in release of multiple factors in the wound environment that could correlate to wound chronicity. These biochemical factors can often be detected through non-invasively sampling chronic wound fluid (CWF) from the site of injury. Of note, whilst there are numerous studies comparing acute and chronic wound fluids, there have not been any reports in the literature employing a longitudinal study in order to track biochemical changes in wound fluid as patients transition from a non-healing to healed state. Initially the objective of this study was to identify biochemical changes in CWF associated with wound healing using a proteomic approach. The proteomic approach incorporated a multi-dimensional liquid chromatography fractionation technique coupled with mass spectrometry (MS) to enable identification of proteins present in lower concentrations in CWF. Not surprisingly, many of the proteins identified in wound fluid were acute phase proteins normally expressed during the inflammatory phase of healing. However, the number of proteins positively identified by MS was quite low. This was attributed to the diverse range in concentration of protein species in CWF making it challenging to detect the diagnostically relevant low molecular weight proteins. In view of this, SELDI-TOF MS was also explored as a means to target low molecular weight proteins in sequential patient CWF samples during the course of healing. Unfortunately, the results generated did not yield any peaks of interest that were altered as wounds transitioned to a healed state. During the course of proteomic assessment of CWF, it became evident that a fraction of non-proteinaceous compounds strongly absorbed at 280 nm. Subsequent analyses confirmed that most of these compounds were in fact part of the purine catabolic pathway, possessing distinctive aromatic rings and which results in high absorbance at 254 nm. The accumulation of these purinogenic compounds in CWF suggests that the wound bed is poorly oxygenated resulting in a switch to anaerobic metabolism and consequently ATP breakdown. In addition, the presence of the terminal purine catabolite, uric acid (UA), indicates that the enzyme xanthine oxidoreductase (XOR) catalyses the reaction of hypoxanthine to xanthine and finally to UA. More importantly, the studies provide evidence for the first time of the exogenous presence of XOR in CWF. XOR is the only enzyme in humans capable of catalysing the production of UA in conjunction with a burst of the highly reactive superoxide radical and other oxidants like H2O2. Excessive release of these free radicals in the wound environment can cause cellular damage disrupting the normal wound healing process. In view of this, a sensitive and specific assay was established for monitoring low concentrations of these catabolites in CWF. This procedure involved combining high performance liquid chromatography (HPLC) with tandem mass spectrometry and multiple reaction monitoring (MRM). This application was selective, using specific MRM transitions and HPLC separations for each analyte, making it ideal for the detection and quantitation of purine catabolites in CWF. The results demonstrated that elevated levels of UA were detected in wound fluid obtained from patients with clinically worse ulcers. This suggests that XOR is active in the wound site generating significant amounts of reactive oxygen species (ROS). In addition, analysis of the amount of purine precursors in wound fluid revealed elevated levels of purine precursors in wound fluid from patients with less severe ulcers. Taken together, the results generated in this thesis suggest that monitoring changes of purine catabolites in CWF is likely to provide valuable information regarding the healing patterns of chronic venous leg ulcers. XOR catalysis of purine precursors not only provides a method for monitoring the onset, prognosis and progress of chronic venous leg ulcers, but also provides a potential therapeutic target by inhibiting XOR, thus blocking UA and ROS production. Targeting a combination of these purinogenic compounds and XOR could lead to the development of novel point of care diagnostic tests. Therefore, further investigation of these processes during wound healing will be worthwhile and may assist in elucidating the pathogenesis of this disease state, which in turn may lead to the development of new diagnostics and therapies that target these processes.

Conference report: Lights, Camera, Action : Spotlight on Tourism in the New Millennium. 31st Annual Travel and Tourism Research Association Conference.

The 31st TTRA conference was held in California’s San Fernando Valley, home of Hollywood and Burbank’s movie and television studios. The twin themes of Hollywood and the new Millennium promised and delivered “something old, yet something new”. The meeting offered a historical summary, not only of the year in review but also of many features of travel research since the first literature in the field appeared in the 1970s. Also, the millennium theme set the scene for some stimulating and forward thinking discussions. The Hollywood location offered an opportunity to ponder on the value of the movie-induced tourism for Los Angeles, at a time when Hollywood Boulevard was in the midst of a much needed redevelopment programme. Hollywood Chamber of Commerce speaker Oscar Arslanian acknowledged that the face of the famous district had become tired, and that its ability to continue to attract visitors in the future lay in redeveloping its past heritage. In line with the Hollywood theme a feature of the conference was a series of six special sessions with “Stars of Travel Research”. These sessions featured: Clare Gunn, Stanley Plog, Charles Gouldner, John Hunt, Brent Ritchie, Geoffrey Crouch, Peter Williams, Douglas Frechtling, Turgut Var, Robert Christie-Mill, and John Crotts. Delegates were indeed privileged to hear from many of the pioneers of tourism research. Clare Gunn, Charles Goeldner, Turgut Var and Stanley Plog, for example, traced the history of different aspects of the tourism literature, and in line with the millennium theme, offered some thought provoking discussion on the future challenges facing tourism. These included; the commodotisation of airlines and destinations, airport and traffic congestion, environment sustainability responsibility and the looming burst of the baby-boomer bubble. Included in the conference proceedings are four papers presented by five of the “Stars”. Brent Ritchie and Geoffrey Crouch discuss the critical success factors for destinations, Clare Gunn shares his concerns about tourism being a smokestack industry, Doug Frechtling provides forecasts of outbound travel from 20 countries, and Charles Gouldner, who has attended all 31 TTRA conferences, reflects on the changes that have taken place in tourism research over 35 years...

Review of "Violence, Prejudice and Sexuality" by Stephen Tomsen (Routledge, New York and London, 2009)

Tomsen’s book Violence, Prejudice and Sexuality engages with important questions about sexuality and anti homosexual sentiment that criminologists have grappled with for some time. Tomsen’s work refines these questions in the context of essentialism, and notes how this concept has enabled only very specific ways of thinking about and analysing violence, prejudice, and sexuality. Indeed, thinking about the nexus between these three concepts are now almost taken for granted. As Tomsen demonstrates in his discussion of historical understandings of sexual desire, although social constructionism and queer perspectives have challenged essentialist notions of sexuality, research has in many respects upheld a binary understanding of heterosexuality as normal and homosexuality as abnormal. Interestingly, essentialist binaries like this have been conveniently employed in more recent times when activists align with minority status to gain basic human rights. While no one could deny the importance of access to rights and justice, Tomsen notes the danger inherent in arguments like this that draw on essentialism. He argues we are working through similar dichotomies of heterosexuality as normal and homosexuality as abnormal set up in very early research on sexual desire. The key difference now is that, in the rush towards public and political citizenship, ‘heterosexuals are recast as “perpetrators” and homosexuals as “victims”’ (Tomsen 2009: 16). Violence, Prejudice and Sexuality importantly notes this is no less an essentialist dichotomy and no less divisive....